A Digital Diabetes Storytelling Intervention for the Hmong Community: A Pilot Study.

Hmong-Americans experience higher rates of diabetes and poorer diabetes-related health outcomes than their White peers. Traditional methods of diabetes education do not reach Hmong patients effectively due to known socioeconomic and literacy barriers. The purpose of this study is to examine the acceptability of a culturally informed diabetes self-management education video tool, using digital storytelling that was created using a community-engaged approach, administered in a single academic clinic that sees a large percentage of Hmong patients. The video tool was successful in the areas of acceptability, story transformation, and story identification; 96% of participants stated that the video felt like something from their community, 88% stated that they could identify with the story, 79% stated that they wanted to know what happened next, and 70% of participants reported that they were motivated to do something different after watching. New methods to improve diabetes education and improve health outcomes in Hmong communities are needed. Culturally informed digital storytelling is one tool, which may be used to improve diabetes health outcomes in this population.

The role of physical examination in diagnosing common causes of vaginitis: a prospective study.

OBJECTIVE: We evaluated agreement in diagnoses for bacterial vaginosis (BV), Trichomonas vaginalis (TV) and vulvovaginal candidiasis (VVC) between clinicians examining the patient and performing diagnostic tests versus a clinician with access only to the patient's history and diagnostic findings from self-obtained vaginal swabs (SOVS). DESIGN: Women presenting with vaginal discharge to a sexually transmitted infections clinic provided SOVS for evaluation and completed the study and qualitative questionnaires. A clinician then obtained a history and performed speculum and bimanual examinations. Participants' history and diagnostic test results from SOVS were provided to a masked non-examining clinician who rendered independent diagnoses. Overall agreement in diagnoses and κ statistics was calculated. RESULTS: The prevalence of infections among the 197 participants was 63.4% (BV), 19% (TV) and 14% (VVC). The per cent agreement between the examining and non-examining clinician for the diagnoses of BV was 68.5%, 90.9% for TV and 91.9% for VVC. Of the 105 women diagnosed with BV by the examining clinician, 34 (32%) were missed by the non-examining clinician. The non-examining clinician missed 13 (48%) of 27 women and 12 (34%) of 35 women treated for VVC and TV, respectively. Four women who all presented with abdominal pain were diagnosed with pelvic inflammatory disease. CONCLUSIONS: Tests from SOVS and history alone cannot be used to adequately diagnose BV, TV and VVC in women presenting with symptomatic vaginal discharge. Cost benefits from eliminating the speculum examination and using only tests from SOVS may be negated by long-term costs of mistreatment.

Consideration of digitization precision when building local coordinate axes for a foot model.

This study investigated whether points digitized for the purpose of embedding coordinate systems into the foot accurately represented the orientation of the bone described. Eight complete data sets were collected from 9 adult cadaver specimens. Palpable landmarks defined 5 segments to include the calcaneus, navicular, medial cuneiform, first metatarsal, and hallux. With use of the Flock of Birds electromagnetic motion tracking device, a single examiner digitized a minimum of 3 points for each segment. Coordinate definitions followed the right-hand rule, with left-sided data converted to right-sided equivalency. Local axes were created where X projected approximately forward, Y upward, and Z laterally. Matrix transformation computations calculated the angular precision in degrees between coordinates built from points digitized pre- and post-dissection of surface tissues covering bone. The condition of post-dissection was considered the criterion standard for comparison. Change about the X-axis represented the angular precision of the coordinate in the frontal anatomical plane; Y-axis in the transverse plane; Z-axis in the sagittal plane. The calcaneus and navicular coordinate axes changed by an average of <3 degrees across conditions. Mean coordinate angulation of the cuneiform X, Y, Z axes changed by 6.0 degrees , 4.6 degrees , 11.9 degrees , respectively. Change in coordinate angulation was largest for the X-axis at the first metatarsal (48.6 degrees ) and hallux (36.5 degrees ). A two-way repeated measures ANOVA found a significant interaction between the axis and segment (F=8.87, P=0.00). Tukey post-hoc comparisons indicated the change in coordinate angulation at the X-axis for the cuneiform, metatarsal, and hallux to be significantly different (P <0.05) from the calcaneus and navicular. The X-axis of the first metatarsal and hallux was different from all other axis-segment combinations except for the Z-axis of the cuneiform. Differences in locating landmarks reduced angular precision of the coordinate axes most in the smallest foot segments where points digitized were located close together. We can recommend the proposed landmarks for the calcaneus and navicular segments, but kinematics determined about the coordinate axes for the small sized medial cuneiform, and the long (X) axis for the first metatarsal and hallux have excessive error.

Inactivation of CYP2A6 and CYP2A13 during nicotine metabolism.

Nicotine is the major addictive agent in tobacco. The primary catalyst of nicotine metabolism in humans is CYP2A6. However, the closely related enzyme CYP2A13 is a somewhat better catalyst. CYP2A13 is an extrahepatic enzyme that is an excellent catalyst of the metabolic activation of the tobacco-specific carcinogen 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK). Here we report that both CYP2A6 and CYP2A13 were inactivated during nicotine metabolism. Inactivation of both enzymes was dependent on NADPH and increased with time and concentration. Alternate substrates for CYP2A6 and CYP2A13 protected these enzymes from inactivation. Inactivation of CYP2A13 was irreversible upon extensive dialysis and seems to be mechanism-based. The K(I) of CYP2A13 inactivation by nicotine was 17 microM, the rate of inactivation, k(inact), was 0.1 min(-1), and the t(1/2) was 7 min. However, the loss in enzyme activity occurred after nicotine metabolism was complete, suggesting that a secondary or possible tertiary metabolite of nicotine may be responsible. [5-(3)H]Nicotine metabolism by CYP2A13 was monitored by radioflow high-pressure liquid chromatography during the course of enzyme inactivation; the major product was the Delta(1'(5'))iminium ion. However, cotinine was a significant metabolite even at short reaction times. The metabolism of the nicotine Delta(1'(5'))iminium ion to cotinine did not require the addition of aldehyde oxidase. CYP2A13 catalyzed this reaction as well as further metabolism of cotinine to 5'-hydroxycotinine, trans-3'-hydroxycotinine, and N-(hydroxymethyl)-norcotinine as enzyme inactivation occurred. Studies are on-going to identify the metabolite responsible for nicotine-mediated inactivation of CYP2A13.

Identification of N-(hydroxymethyl) norcotinine as a major product of cytochrome P450 2A6, but not cytochrome P450 2A13-catalyzed cotinine metabolism.

Cotinine formation is the major pathway of nicotine metabolism in smokers, and the primary pathway of cotinine metabolism is trans-3'-hydroxylation. trans-3'-Hydroxycotinine and its glucuronide conjugate account for up to 50% of the nicotine metabolites excreted by smokers. Minor metabolites of cotinine excreted by smokers include norcotinine and cotinine N-oxide, each of which account for <5% of the nicotine dose. It has been reported that P450 2A6 is the catalyst of cotinine metabolism. However, we report here that the major product of P450 2A6-catalyzed cotinine metabolism is N-(hydroxymethyl)norcotinine, a previously unknown human metabolite of cotinine. N-(Hydroxymethyl)norcotinine was chemically synthesized, and its stability under the conditions of the enzyme reactions was confirmed. The products of P450 2A6-catalyzed [5-3H]cotinine metabolism were quantified by radioflow HPLC. The identification of N-(hydroxymethyl)norcotinine as the major metabolite was based on HPLC analysis on three unique systems and coelution with N-(hydroxymethyl)norcotinine standard. 5'-Hydroxycotinine and trans-3'-hydroxycotinine were minor products of P450 2A6-catalyzed cotinine metabolism, accounting for 14 and 8% of the total cotinine metabolites, respectively. N-(Hydroxymethyl)norcotinine was a product of cotinine metabolism by the extrahepatic P450, 2A13, but it was a minor one. The major product of P450 2A13-catalyzed cotinine metabolism was 5'-hydroxycotinine, which was formed at twice the rate of trans-3'-hydroxycotinine. The identification of all cotinine metabolites formed by both enzymes was confirmed by LC/MS/MS analysis. Kinetic parameters for cotinine metabolism were determined for P450 2A6 and P450 2A13. This work has confirmed that the major metabolite of cotinine in smokers, trans-3'-hydroxycotinine, is only a minor metabolite of P450 2A6-catalyzed cotinine metabolism.

Nicotine 5'-oxidation and methyl oxidation by P450 2A enzymes.

In smokers, the primary pathway of nicotine metabolism is P450 2A6-catalyzed 5'-oxidation. The nicotine Delta(5'(1'))-iminium ion product of this reaction is further metabolized to cotinine by aldehyde oxidase. Previous investigators have reported kinetic parameters for cotinine formation using human liver cytosol as a source of aldehyde oxidase. Using [5-(3)H]nicotine and radioflow high-performance liquid chromatography analysis, we determined kinetic parameters for nicotine 5'-oxidation by P450 2A6 and the closely related human extrahepatic P450 2A13 as well as the rodent P450s 2A3, 2A4, and 2A5. The formation of both cotinine and nicotine Delta(5'(1'))-iminium ion was monitored. The K(m) and V(max) values for P450 2A6 were 144 +/- 15 muM and 1.30 +/- 0.05 pmol/min/pmol, respectively. Previously reported K(m) values for cotinine formation by P450 2A6 in the presence of cytosol were much lower, ranging from 11 to 45 muM. P450 2A13 was a somewhat better catalyst of nicotine Delta(5'(1'))-iminium formation, with 2-fold lower K(m) and 2-fold higher V(max) values than P450 2A6. The rat P450 2A3 and the mouse P450 2A5, which are 85 and 84% identical to P450 2A6, were much more efficient catalysts of nicotine 5'-oxidation. P450 2A4 was not an efficient catalyst of nicotine metabolism. Whereas 5'-oxidation was the major pathway of nicotine metabolism for all five P450 2A enzymes, these enzymes also catalyzed methyl oxidation. Nornicotine, the product of this reaction was detected as 5 to 15% of the total nicotine metabolites. Nornicotine is the amine precursor to the esophageal carcinogen N'-nitrosonornicotine. Therefore, methyl oxidation of nicotine by P450 2A6 or P450 2A13 followed by nitrosation of nornicotine are possible endogenous pathways of N'-nitrosonornicotine formation.