Global Systematic Review of the Cost-Effectiveness of Indigenous Health Interventions

Background

Indigenous populations around the world have consistently been shown to bear a greater burden of disease, death and disability than their non-Indigenous counterparts. Despite this, little is known about what constitutes cost-effective interventions in these groups. The objective of this paper was to assess the global cost-effectiveness literature in Indigenous health to identify characteristics of successful and unsuccessful interventions and highlight areas for further research.

Methods and Findings

A systematic review of the published literature was carried out. MEDLINE, PSYCINFO, ECONLIT, EMBASE and CINAHL were searched with terms to identify cost-effectiveness evaluations of interventions in Indigenous populations around the world. The WHO definition was followed in identifying Indigenous populations. 19 studies reporting on 27 interventions were included in the review. The majority of studies came from high-income nations with only two studies of interventions in low and middle-income nations. 22 of the 27 interventions included in the analysis were found to be cost-effective or cost-saving by the respective studies. There were only two studies that focused on Indigenous communities in urban areas, neither of which was found to be cost-effective. There was little attention paid to Indigenous conceptions of health in included studies. Of the 27 included studies, 23 were interventions that specifically targeted Indigenous populations. Outreach programs were shown to be consistently cost-effective.

Conclusion

The comprehensive review found only a small number of studies examining the cost-effectiveness of interventions into Indigenous communities around the world. Given the persistent disparities in health outcomes faced by these populations and commitments from governments around the world to improving these outcomes, it is an area where the health economics and public health fields can play an important role in improving the health of millions of people.     

Highly automated nano-LC/MS-based approach for thousand cell-scale quantification of side chain-hydroxylated oxysterols

Iso-octyl chain-hydroxylated oxysterols were determined in attomoles per 10,000 cells concentrations in 10,000–80,000 cultured pancreatic adenocarcinoma cells, using a sensitive, highly automated nano-LC-ESI-MS-based method. Identified oxysterols included 24S hydroxycholesterol (24S-OHC), 25 hydroxycholesterol (25-OHC), and 27 hydroxycholesterol (27-OHC), while 20S hydroxycholesterol and 22S hydroxycholesterol were not detected. Lower mass limit of quantification was 23 fg (65 amol) for 25-OHC and 27-OHC (100 times lower than our previous method) and 54 fg (135 amol) for 24S-OHC, after derivatization into Girard T hydrazones and online sample cleanup using simplified and robust automatic filtration and filter back flushing solid phase extraction LC/MS/MS. The instrument configuration was easily installed using a commercial nano-LC/MS system. Recoveries in spiked sample were 96, 97, and 77% for 24S-OHC, 25-OHC, and 27-OHC, with within- and between-day repeatabilities of 1–21% and 2–20% relative SD, respectively. The study demonstrates the potential of nano-LC in lipidomics/sterolomics.     

Graminivory and Fallback Foods: Annual Diet Profile of Geladas (<Emphasis Type="Italic">Theropithecus gelada</Emphasis>) Living in the Simien Mountains National Park,Ethiopia

All primates show some dietary flexibility, particularly during food shortages. Foods consumed during times of scarcity (i.e., fallback foods) strongly influence the ecology and evolution of a species. Geladas (Theropithecus gelada) eat primarily graminoid leaves (i.e., grasses and sedges), but also consume other diet items (e.g., underground storage organs), especially in the dry season. We investigated the feeding ecology of wild geladas in the Sankaber region of the Simien Mountains National Park, Ethiopia across 12 mo. We asked how the gelada diet in this region, which is disturbed by livestock and agriculture, correlated with food availability and whether underground foods are fallback foods. We quantified the monthly diets of adults from eight reproductive units using instantaneous scan sampling, and seasonal aboveground and underground food availability using point-intercept transects and soil core sampling. Geladas primarily consumed graminoid leaves year-round (76.3% of the annual diet, 36.2–93.2% of the monthly diet) but spent considerable time consuming underground foods in the dry season (14.0% of the annual diet, 11.1–49.7% of the diet across dry season months). Graminoid consumption increased with graminoid availability, and underground food consumption decreased with graminoid availability. Underground food availability did not vary significantly between the dry and wet season sampling months, supporting the hypothesis that underground foods are fallback foods for geladas. We then compiled data from gelada feeding studies and found that underground foods are an important dry season diet item across study sites, but geladas rely more heavily on underground foods in habitats more heavily influenced by humans. Understanding the range and effects of primate dietary flexibility in human-modified habitats will contribute to a better understanding of how changing environments shape primate ecology and evolution.     

TIP,a novel host factor linking callose degradation with the cell-to-cell movement of Potato virus X

The cell-to-cell movement of Potato virus X (PVX) requires four virus-encoded proteins, the triple gene block (TGB) proteins (TGB25K, TGB12K, and TGB8K) and the coat protein. TGB12K increases the plasmodesmal size exclusion limit (SEL) and may, therefore, interact directly with components of the cell wall or with plant proteins associated with bringing about this change. A yeast two-hybrid screen using TGB12K as bait identified three TGB12K-interacting proteins (TIP1, TIP2, and TIP3). All three TIPs interacted specifically with TGB12K but not with TGB25K or TGB8K. Similarly, all three TIPs interacted with beta-1,3-glucanase, the enzyme that may regulate plasmodesmal SEL through callose degradation. Sequence analyses revealed that the TIPs encode very similar proteins and that TIP1 corresponds to the tobacco ankyrin repeat-containing protein HBP1. A TIP1::GFP fusion protein localized to the cytoplasm. Coexpression of this fusion protein with TGB12K induced cellular changes manifested as deposits of additional cytoplasm at the cell periphery. This work reports a direct link between a viral movement protein required to increase plasmodesmal SEL and a host factor that has been implicated as a key regulator of plasmodesmal SEL. We propose that the TIPs are susceptibility factors that modulate the plasmodesmal SEL.     

Enhancer trapping identifies TRI, an Arabidopsis gene up-regulated by pathogen infection

Enhancer trap Arabidopsis thaliana plants were screened for genes up-regulated by virus infection. The plants carried T-DNA insertions comprising a minimal -60-bp Cauliflower mosaic virus 35S promoter fused to the beta-glucuronidase (GUS) reporter gene. Approximately 12,000 plants were assayed for GUS activity before and after rub-inoculation with Tobacco rattle virus (TRV) tagged with the green fluorescent protein (GFP). One plant and its progeny consistently showed upregulation of GUS activity in response to TRV-GFP infection, indicating that a virus-responsive enhancer element was "tagged" by the T-DNA in this line. Other viruses, bacteria, and oomycetes, but not wounding, up-regulated GUS activity in the enhancer trap line, indicating that the response was not specific to TRV-GFP infection. A pathogen-inducible, alternatively spliced gene was identified, which we have termed TRI for TRV-induced gene. A pathogen-responsive element was localized to a 1.1-kb region upstream of the T-DNA insertion, and two different cis-acting elements, both implicated in defense responses, were found in the sequence upstream of TRI. Sequence analyses revealed that TRI is similar to ACRE169, a gene that is up-regulated in Cf-9-expressing tobacco when treated with Avr-9, the Cladosporium fulvum elicitor of the Cf-9 resistance response.     

Glucose repression in Streptomyces coelicolor A3(2): a likely regulatory role for glucose kinase

The glucose kinase gene (glkA-ORF3) of Streptomyces coelicolor A3(2) plays an essential role in glucose utilisation and in glucose repression of a variety of genes involved in the utilisation of alternative carbon sources. These genes include dagA, which encodes an extracellular agarase that permits agar utilisation. Suppressor mutants of glkA-ORF3 deletion strains capable of utilising glucose (Glc⁺) arise at a frequency of about 10^–5 on prolonged incubation. The Glc⁺ phenotype of the mutants is reversible (at a frequency of about 10^–3) and reflects either the activation of a normally silent glucose kinase gene or the modification of an existing sugar kinase. Although the level of glucose kinase activity in the Glc⁺ supressor mutants is similar to that in the glkA ⁺ parental strain, glucose repression of dagA remains defective. Expression of the glucose kinase gene of Zymomonas mobilis in glkA-ORF3 mutants restored glucose utilisation, but not glucose repression of dagA. Over-expression of glkA-ORF3 on a high-copy-number plasmid failed to restore glucose repression of dagA in glkA-ORF3 mutants and led to loss of glucose repression of dagA in a glkA ⁺ strain. These results suggest that glucose phosphorylation itself is not sufficient for glucose repression and that glkA-ORF3 plays a specific regulatory role in triggering glucose repression in S. coelicolor A3(2).