Development of Health Equity Indicators in Primary Health Care Organizations Using a Modified Delphi

Objective

The purpose of this study was to develop a core set of indicators that could be used for measuring and monitoring the performance of primary health care organizations'' capacity and strategies for enhancing equity-oriented care.

Methods

Indicators were constructed based on a review of the literature and a thematic analysis of interview data with patients and staff (n = 114) using procedures for qualitatively derived data. We used a modified Delphi process where the indicators were circulated to staff at the Health Centers who served as participants (n = 63) over two rounds. Indicators were considered part of a priority set of health equity indicators if they received an overall importance rating of>8.0, on a scale of 1–9, where a higher score meant more importance.

Results

Seventeen indicators make up the priority set. Items were eliminated because they were rated as low importance (<8.0) in both rounds and were either redundant or more than one participant commented that taking action on the indicator was highly unlikely. In order to achieve health care equity, performance at the organizational level is as important as assessing the performance of staff. Two of the highest rated “treatment” or processes of care indicators reflects the need for culturally safe and trauma and violence-informed care. There are four indicators that can be used to measure outcomes which can be directly attributable to equity responsive primary health care.

Discussion

These indicators and subsequent development of items can be used to measure equity in the domains of treatment and outcomes. These areas represent targets for higher performance in relation to equity for organizations (e.g., funding allocations to ongoing training in equity-oriented care provision) and providers (e.g., reflexive practice, skill in working with the health effects of trauma).     

Host immunity increases Mycobacterium tuberculosis reliance on cytochrome bd oxidase

In order to sustain a persistent infection, Mycobacterium tuberculosis (Mtb) must adapt to a changing environment that is shaped by the developing immune response. This necessity to adapt is evident in the flexibility of many aspects of Mtb metabolism, including a respiratory chain that consists of two distinct terminal cytochrome oxidase complexes. Under the conditions tested thus far, the bc₁/aa₃ complex appears to play a dominant role, while the alternative bd oxidase is largely redundant. However, the presence of two terminal oxidases in this obligate pathogen implies that respiratory requirements might change during infection. We report that the cytochrome bd oxidase is specifically required for resisting the adaptive immune response. While the bd oxidase was dispensable for growth in resting macrophages and the establishment of infection in mice, this complex was necessary for optimal fitness after the initiation of adaptive immunity. This requirement was dependent on lymphocyte-derived interferon gamma (IFNγ), but did not involve nitrogen and oxygen radicals that are known to inhibit respiration in other contexts. Instead, we found that ΔcydA mutants were hypersusceptible to the low pH encountered in IFNγ-activated macrophages. Unlike wild type Mtb, cytochrome bd-deficient bacteria were unable to sustain a maximal oxygen consumption rate (OCR) at low pH, indicating that the remaining cytochrome bc₁/aa₃ complex is preferentially inhibited under acidic conditions. Consistent with this model, the potency of the cytochrome bc₁/aa₃ inhibitor, Q203, is dramatically enhanced at low pH. This work identifies a critical interaction between host immunity and pathogen respiration that influences both the progression of the infection and the efficacy of potential new TB drugs.     

β-Galactosidase activity assay using far-red-shifted fluorescent substrate DDAOG

β-Galactosidase (β-gal) is commonly used as a reporter gene in biological research, and a wide variety of substrates have been developed to assay its activity. One substrate, 9H-(1,3-dichloro-9,9-dimethylacridin-2-one-7-yl) β-d-galactopyranoside (DDAOG), can be cleaved by β-gal to produce 7-hydroxy-9H(I,3-dichloro-9,9-dimethylacridin-2-one) (DDAO). On excitation, DDAO generates a far-red-shifted fluorescent signal. Using this substrate, we developed a β-gal activity assay method. The DDAO signal was stable for at least 18 h. The signal intensity was linearly related to both the enzyme amount and substrate concentration. An optimized buffer for the β-gal/DDAOG assay was also formulated. When compared with the colorimetric substrate o-nitrophenyl-β-d-galactopyranoside (ONPG), the signal-to-background ratio of the DDAOG method was approximately 12-fold higher. The β-gal/DDAOG assay method was also tested in transiently transfected cells employing both pharmacologically and genetically inducible gene expression systems. The ability to detect signal induction is comparable to a similar assay using luciferase as the signal generating moiety. The β-gal/DDAOG assay method should provide a fluorescent reporter assay system for the wide variety of β-gal systems currently in use.     

Lymphocyte coreceptors

The activation of the immune system is tightly regulated by positive and negative receptors that allow the fine tuning of the immune cells. This regulation relies on receptors that were initially described in T lymphocytes, but have now been identified on cells from both innate and acquired immunity. The co-stimulatory receptors can allow cell activation or amplify it, regulate cell suvival and determine their effector functions. The co-inhibitory receptors can either prevent, decrease of inhibit the activation and differentiation process. The co-stimulatory and co-inhibitory molecules belong mainly to the so-called Ig superfamily and historically were called < CD28 and B7 family >. The members of the tumor necrosis factor receptor (TNFR) family devoid of intra-cytoplasmic death domain but binding TNF receptor associated factors (TRAF) are also important but are up to now mainly co-stimulatory. The prototypical co-stimulatory molecules belonging to CD28 family are CD28 and ICOS, whereas the co-inhibitory molecules identified so far are CTLA-4, PD-1 and BTLA. Their receptors belong in most instances to the B7 family. For instance, B7.1/CD80 and B7.2/CD86 interact both with CD28 and CTLA-4 ; PDL1 and PDL2 bind to PD-1. The exception being so far BTLA which interacts with the TNFR family member HVEM (Herpes virus entry mediator). Three other B7 family members B7-H3, B7-H4 and BT3.1 are orphan receptors until now. The basis of co-inhibition rely on distinct mechanisms, one that has been postulated being the ability of the intracytoplasmic domain of PD-1 and BTLA to bind to the protein tyrosine phosphatases SHP-1 and SHP-2. The pathways used by the co-stimulatory receptors are also not completely understood and rely for CD28 both on signal similar to the one elicited by TcR and consequently increasing the overall signal and other more specific, elicited by the activation of PI3-OH kinase, vav1 and rearrangement of cytoskeleton. Recently, reverse signaling has been described for B7 family members which further increases the spectrum of functions elicited by these families. Co-stimulation and co-inhibition are among the most promising molecules and pathways to be targeted by mAbs, recombinant proteins and drugs in auto-immune diseases, transplantation and cancer.     

Cloning and characterization of two genes encoding sulfate transporters from rice (Oryza sativa L.)*

Two genes were isolated from a rice genomic library and the coding region of their corresponding cDNAs generated by RT-PCR. These single copy genes, designated ORYsa;Sultr1;1 and ORYsa;Sultr4;1, encode putative sulfate transporters. Both genes encode proteins with predicted topologies and signature sequences of the H⁺/SO₄^2- symporter family of transporters and exhibit a high degree of homology to other plant sulfate transporters. ORYsa;Sultr1;1 is expressed in roots with levels of expression being strongly enhanced by sulfate starvation. In situ hybridization experiments revealed that ORYsa;Sultr1;1 expression is localized to the main absorptive region of roots. This gene probably encodes a transporter that is responsible for uptake of sulfate from the soil solution. In contrast, ORYsa;Sultr4;1 was expressed in both roots and shoots and was unresponsive to the sulfur status of the plant. The sequence of ORYsa;Sultr4;1 contains a possible plastid-targeting transit peptide which may indicate a role in transport of sulfate to sites of sulfate reduction in plastids. The role of the transporter encoded by ORYsa;Sultr4;1 is likely to be significantly different fromORYsa;Sultr1;1. These are the first reports of isolation of genes encoding sulfate transporters from rice and provide a basis for further studies involving sulfate transport.     

GENETICS OF SORDARIA FIMICOLA. IV. LINKAGE GROUP I

El -Ani , Arif S., L. S. Olive , and Y. Kitani . (Columbia U., New York City.) Genetics of Sordaria fimicola. IV. Linkage group I. Amer. Jour. Bot. 48(8): 716–723. Illus. 1961.—A general technique for isolating and testing various morphological mutants induced by X ray is described. Eleven mutants differing in ascospore color, fertility, and rate and type of growth were studied in different crosses. This has led to the construction of the first linkage group in S. fimicola. The chromosome on which the 11 mutant loci occur is marked by a single locus on one arm and 10 on the opposite arm. The ascospore color mutant gray is autonomous, maintaining the mutant spore color in both homozygous and heterozygous asci, whereas milky, the other color mutant studied. expresses its mutant effect only in asci homozygous for the factor. Certain crosses involving 2 sterility mutants controlled by 2 non-allelic loci are fertile, and the progeny give rise to parentals as well as double-mutant and fertile recombinants.     

GENETICS OF SORDARIA FIMICOLA. III. CROSS-COMPATIBILITY AMONG SELF-FERTILE AND SELF-STERILE CULTURES

Carr , A. J. H. (Univ. Coll. Wales, Aberystwyth), and Lindsay S. Olive . Genetics of Sordaria fimicola. III. Cross compatibility among self-fertile and self-sterile cultures. Amer. Jour. Bot. 46(2) : 81-91. Illis. 1959.—Cross-compatibility in Sordaria fimicola is shown to be dependent upon a number of factors controlling the sexual process, from hyphal anastomosis and nuclear migration on through to perithecial formation and nuclear compatibility. Fertile cultures which were incompatible through inability to anastomose were induced to cross by the use of a third culture which would anastomose with both. Certain spontaneous or irradiation-produced sterility mutants were found to be compatible if the sterility genes were at different loci, through complementation by the wild-type alleles. In some pairings, cross-karyogamy was preferential, and in one case, only hybrid perithecia were produced. Fully fertile recombinants segregated from these crosses in frequencies which indicated that the sterility loci were unlinked. Certain sterility genes were found to influence hyphal anastomosis, nuclear migration, and the development of fertile sector heterokaryons from the zone of anastomosis. Mutant factors at two loci in a U.V. mutant causing self-sterility were found also to be responsible for lethality in ascospore germination. Factors in one sterility mutant controlled the production of a sterility-inducing substance which diffused into the medium. In some crosses, complementation of two sterile cultures towards fertility is shown to require a balanced nuclear ratio. Factors are described which increase the inhibitory effect of one sterility gene, while another factor was found to suppress its effect and thereby make the culture self-fertile. It is concluded that, since there is recombination between the sterility loci, these results do not represent the derivation of balanced heterothallism from a normally homothallic system, although it may lead by evolutionary progression to such a life cycle. The possible physiologic action of the sterility genes is discussed.