Psychometrics of a new questionnaire to assess glaucoma adherence: the Glaucoma Treatment Compliance Assessment Tool (an American Ophthalmological Society thesis).

PURPOSE: To report the psychometrics of the Glaucoma Treatment Compliance Assessment Tool (GTCAT), a new questionnaire designed to assess adherence with glaucoma therapy. METHODS: We developed the questionnaire according to the constructs of the Health Belief Model. We evaluated the questionnaire using data from a cross-sectional study with focus groups (n = 20) and a prospective observational case series (n=58). Principal components analysis provided assessment of construct validity. We repeated the questionnaire after 3 months for test-retest reliability. We evaluated predictive validity using an electronic dosing monitor as an objective measure of adherence. RESULTS: Focus group participants provided 931 statements related to adherence, of which 88.7% (826/931) could be categorized into the constructs of the Health Belief Model. Perceived barriers accounted for 31% (288/931) of statements, cues-to-action 14% (131/931), susceptibility 12% (116/931), benefits 12% (115/931), severity 10% (91/931), and self-efficacy 9% (85/931). The principal components analysis explained 77% of the variance with five components representing Health Belief Model constructs. Reliability analyses showed acceptable Cronbach's alphas (>.70) for four of the seven components (severity, susceptibility, barriers [eye drop administration], and barriers [discomfort]). Predictive validity was high, with several Health Belief Model questions significantly associated (P <.05) with adherence and a correlation coefficient (R (2)) of .40. Test-retest reliability was 90%. CONCLUSION: The GTCAT shows excellent repeatability, content, construct, and predictive validity for glaucoma adherence. A multisite trial is needed to determine whether the results can be generalized and whether the questionnaire accurately measures the effect of interventions to increase adherence.

Protein complexing in a methanogen suggests electron bifurcation and electron delivery from formate to heterodisulfide reductase.

In methanogenic Archaea, the final step of methanogenesis generates methane and a heterodisulfide of coenzyme M and coenzyme B (CoM-S-S-CoB). Reduction of this heterodisulfide by heterodisulfide reductase to regenerate HS-CoM and HS-CoB is an exergonic process. Thauer et al. [Thauer, et al. 2008 Nat Rev Microbiol 6:579-591] recently suggested that in hydrogenotrophic methanogens the energy of heterodisulfide reduction powers the most endergonic reaction in the pathway, catalyzed by the formylmethanofuran dehydrogenase, via flavin-based electron bifurcation. Here we present evidence that these two steps in methanogenesis are physically linked. We identify a protein complex from the hydrogenotrophic methanogen, Methanococcus maripaludis, that contains heterodisulfide reductase, formylmethanofuran dehydrogenase, F(420)-nonreducing hydrogenase, and formate dehydrogenase. In addition to establishing a physical basis for the electron-bifurcation model of energy conservation, the composition of the complex also suggests that either H(2) or formate (two alternative electron donors for methanogenesis) can donate electrons to the heterodisulfide-H(2) via F(420)-nonreducing hydrogenase or formate via formate dehydrogenase. Electron flow from formate to the heterodisulfide rather than the use of H(2) as an intermediate represents a previously unknown path of electron flow in methanogenesis. We further tested whether this path occurs by constructing a mutant lacking F(420)-nonreducing hydrogenase. The mutant displayed growth equal to wild-type with formate but markedly slower growth with hydrogen. The results support the model of electron bifurcation and suggest that formate, like H(2), is closely integrated into the methanogenic pathway.

Sequences within the gag gene of mouse mammary tumor virus needed for mammary gland cell transformation.

Previously, we identified a group of replication-competent exogenous mouse mammary tumor viruses that failed to induce mammary tumors in susceptible mice. Sequence comparison of tumorigenic and tumor-attenuated virus variants has linked the ability of virus to cause high-frequency mammary tumors to the gag gene. To determine the specific sequences within the gag gene that contribute to tumor induction, we constructed five distinct chimeric viruses that have various amino acid coding sequences of gag derived from a tumor-attenuated virus replaced by those of highly tumorigenic virus and tested these viruses for tumorigenic capacities in virus-susceptible C3H/HeN mice. Comparing the tumorigenic potentials of these viruses has allowed us to map the region responsible for tumorigenesis to a 253-amino-acid region within the CA and NC regions of the Gag protein. Unlike C3H/HeN mice, BALB/cJ mice develop tumors when infected with all viral variants, irrespective of the gag gene sequences. Using genetic crosses between BALB/cJ and C3H/HeN mice, we were able to determine that the mechanism that confers susceptibility to Gag-independent mammary tumors in BALB/cJ mice is inherited as a dominant trait and is controlled by a single gene, called mammary tumor susceptibility (mts), that maps to chromosome 14.