The art and science of patient storytelling-harnessing narrative communication for behavioral interventions: the ACCE project.

Narrative communication is an emerging form of persuasive communication used in health education to solicit actual patient stories. Eliciting a narrative is an open-ended process and may or may not map to desired intervention objectives or underlying behavioral constructs. In addition, incorporating actual, unscripted narratives into multimedia interventions is challenging. The authors evaluated a protocol of editing narratives for a multimedia intervention to promote smoking cessation in the African American community that maintains fidelity to the original message and was related to behavioral constructs from social cognitive theory. The authors used four steps: (a) narrative collection (videotaping), (b) narrative review (rating of content), (c) narrative editing (documentary style), and (d) pilot testing (usability and assessment of transportation). The authors videotaped 50 personal smoking cessation narratives. After coding for presence of theoretical constructs, perceived risks of smoking (present in 53% of narratives) was the most common related behavioral construct. Four narratives were chosen for inclusion in the DVD. Pilot testing showed viewers reported high level of transportation into the narrative. The authors found that some behavioral constructs were rare and difficult to solicit in this population but that the final product was engaging to the viewers. Lessons learned may be useful for other video-based behavioral interventions that incorporate personal narratives.

Subfertility in mice harboring a mutation in betaB2-crystallin.

PURPOSE: betaB2-crystallin is one of the most abundant proteins of the adult ocular lens of mammals although it is expressed at lower levels in several extralenticular locations. While mutations in betaB2-crystallin are known to result in lens opacities, alterations in tissues besides the lens have not been previously investigated in these mutants. Since we found mice harboring the Crybb2Phil mutation bred poorly, here we assess the contribution of betaB2-crystallin to mouse fertility and determine the expression pattern of betaB2-crystallin in the testis. METHODS: The expression pattern of betaB2-crystallin in the testis was analyzed by rt-PCR, western blotting, and immunohistochemistry. The fecundity of wildtype and Crybb2Phil mice was analyzed by quantitative fertility testing. The morphology of testes and ovaries was assessed by hematoxylin and eosin staining. RESULTS: In the mouse testis, betaB2-crystallin mRNA is found at low levels at birth, but its expression upregulates in this tissue as the testis is primed to initiate spermatogenesis. Western blotting detected betaB2-crystallin protein in sperm obtained from mice, cattle, and humans while immunolocalization detected this protein in developing sperm from the spermatocyte stage onward. Male and female mice homozygous for a 12 nucleotide inframe deletion mutation in betaB2-crystallin are subfertile when analyzed on a Swiss Webster derived background due to defects in egg and sperm production. However, mice harboring the same mutation on the C57Bl/6 genetic background did not exhibit any defects in reproductive function. CONCLUSIONS: betaB2-crystallin is expressed in developing and mature sperm and mice of both sexes harboring the Philly mutation in the betaB2-crystallin gene are subfertile when analyzed on a Swiss Webster genetic background. While these data are suggestive of a role for betaB2-crystallin in fertility, definitive determination of this will await the creation of a betaB2-crystallin null mouse.

The risk of diabetes during olanzapine use compared with risperidone use: a retrospective database analysis.

BACKGROUND: The relative risk of diabetes among patients undergoing risperidone treatment was compared with that of patients receiving olanzapine. METHOD: A cohort was formed of 33,946 patients with at least 1 prescription for either olanzapine (N = 19,153) or risperidone (N = 14,793) between January 1, 1997, and December 31, 1999, recorded in the Régie de l'Assurance Maladie du Québec database. Patients were excluded if clozapine was dispensed to them during the study period or if they were diagnosed with diabetes before beginning antipsychotic therapy. New diabetes diagnoses made after the first antipsychotic prescription during the period were tabulated until December 31, 1999; censoring occurred at this date or at the last service date, if there was no record of using services during the last 6 months of follow-up. Crude hazard ratio and proportional hazard analyses were carried out. RESULTS: 319 patients developed diabetes on olanzapine treatment, and 217 developed diabetes on risperidone treatment; a crude hazard ratio of 1.08 (95% CI = 0.89 to 1.31, p =.43) was determined. When age, gender, and haloperidol use were controlled for using proportional hazard analysis, there was a 20% increased risk of diabetes with olanzapine relative to risperidone (95% CI = 0% to 43%, p =.05). Proportional hazard analyses adjusted for duration of olanzapine exposure indicated that the first 3 months of olanzapine treatment was associated with an increased risk of diabetes of 90% (95% CI = 40% to 157%, p <.0001), after adjusting for age, gender, and haloperidol use. CONCLUSION: Compared with risperidone, olanzapine was associated with an increased risk of developing diabetes. More studies are required to further investigate this association.

Effects of Temperature on Albunex and FS069 Echocardiographic Contrast Agents: In Vitro Investigation Using Ultrasonic Irradiation.

The effects of temperature on the stability of two contrast agents, Albunex and perfluoropropane filled albumin microspheres (FS069), were investigated by studying the variations in their reflective properties, induced by high dose ultrasound irradiation at different temperatures. Diluted contrast agents were introduced into a 3.5-mL latex balloon, placed in a plastic water tank, and continuously irradiated over a period of 6 minutes using different power levels: 0, 20, 25, and 30 dB. The irradiation was interrupted for imaging every 30 seconds for 2 seconds. The protocol was carried out at three different temperatures: 8 degrees C, 22 degrees C, and 37 degrees C. For each temperature, the concentration of contrast solution was matched to produce approximately the same initial video intensity. Time variations in mean video intensity in the balloon cross section were studied. Contrast enhancement was found to be directly related to temperature. Under continuous ultrasonic irradiation, video intensity gradually decreased over time. This decrease was dependent on both transmitted power and temperature, and was more pronounced with Albunex when compared to FS069 (P < 0.05). Abruptly dropping temperature consistently resulted in rapid, irreversible disappearance of contrast induced by Albunex. Temperature affects the reflectivity and stability of diluted Albunex and FS069. To enhance the reproducibility of contrast enhancement achieved by these agents, their temperature should be carefully controlled.

The phospholipase D1 pathway modulates macroautophagy.

Although macroautophagy is known to be an essential degradative process whereby autophagosomes mediate the engulfment and delivery of cytoplasmic components into lysosomes, the lipid changes underlying autophagosomal membrane dynamics are undetermined. Here, we show that phospholipase D1 (PLD1), which is primarily associated with the endosomal system, partially relocalizes to the outer membrane of autophagosome-like structures upon nutrient starvation. The localization of PLD1, as well as the starvation-induced increase in PLD activity, are altered by wortmannin, a phosphatidylinositol 3-kinase inhibitor, suggesting PLD1 may act downstream of Vps34. Pharmacological inhibition of PLD and genetic ablation of PLD1 in mouse cells decreased the starvation-induced expansion of LC3-positive compartments, consistent with a role of PLD1 in the regulation of autophagy. Furthermore, inhibition of PLD results in higher levels of Tau and p62 aggregates in organotypic brain slices. Our in vitro and in vivo findings establish a role for PLD1 in autophagy.

Loop 2 of limulus myosin III is phosphorylated by protein kinase A and autophosphorylation.

Little is known about the functions of class III unconventional myosins although, with an N-terminal kinase domain, they are potentially both signaling and motor proteins. Limulus myosin III is particularly interesting because it is a phosphoprotein abundant in photoreceptors that becomes more heavily phosphorylated at night by protein kinase A. This enhanced nighttime phosphorylation occurs in response to signals from an endogenous circadian clock and correlates with dramatic changes in photoreceptor structure and function. We seek to understand the role of Limulus myosin III and its phosphorylation in photoreceptors. Here we determined the sites that become phosphorylated in Limulus myosin III and investigated its kinase, actin binding, and myosin ATPase activities. We show that Limulus myosin III exhibits kinase activity and that a major site for both protein kinase A and autophosphorylation is located within loop 2 of the myosin domain, an important actin binding region. We also identify the phosphorylation of an additional protein kinase A and autophosphorylation site near loop 2, and a predicted phosphorylation site within loop 2. We show that the kinase domain of Limulus myosin III shares some pharmacological properties with protein kinase A, and that it is a potential opsin kinase. Finally, we demonstrate that Limulus myosin III binds actin but lacks ATPase activity. We conclude that Limulus myosin III is an actin-binding and signaling protein and speculate that interactions between actin and Limulus myosin III are regulated by both second messenger mediated phosphorylation and autophosphorylation of its myosin domain within and near loop 2.

Risk of weight gain associated with antipsychotic treatment: results from the Canadian National Outcomes Measurement Study in Schizophrenia.

BACKGROUND: Antipsychotic-induced weight gain occurs in a substantial percentage of treated persons. There remains a paucity of naturalistic data that describe relative weight-gain liability with the available novel atypical antipsychotics (NAPs). This investigation describes comparative NAP-induced weight gain in a prospective naturalistic cohort of persons with schizophrenia and related psychotic disorders. METHODS: The Canadian National Outcomes Measurement Study in Schizophrenia (CNOMSS) is an ongoing prospective, longitudinal, naturalistic study involving 32 academic and community sites across Canada. Persons with DSM-IV-defined schizophrenia, schizophreniform or schizoaffective disorder, and psychosis not otherwise specified were consecutively enrolled. The overarching objectives of this initiative were to collect and compare global effectiveness, tolerability, safety, and humanistic outcomes in persons receiving commercially available NAPs in Canada. This analysis reports only weight change with the respective NAPs. Other outcomes were reported in separate companion papers. RESULTS: A spectrum of weight-gain liability was noted with quetiapine (QUE) (mean 7.55 kg, SD 9.20; P = 0.28), olanzapine (OLZ) (mean 3.72 kg, SD 0.56; P = 0.15), and risperidone (RIS) (mean 1.62 kg, SD 7.72; P = 0.43). Categorically defined weight gain (that is, over 7% of baseline weight) was observed in 55.6% of QUE patients, 24.1% of OLZ patients, and 23.7% of RIS patients. Adjusting for demographic and disease-specific confounding factors, QUE patients had greater odds of gaining over 7% of their baseline weight compared with RIS patients (odds ratio [OR] 3.62; 95% CI, 1.02 to 12.83; P = 0.05). No statistical difference was detected between OLZ patients and RIS patients for over 7% of baseline weight (OR 1.54; 95% CI, 0.63 to 3.75; P = 0.12) or over 10% weight gain (OR 1.44; 95% CI, 0.50 to 4.13; P = 0.58). CONCLUSION: Clinicians are reminded to monitor anthropometric and metabolic parameters in all NAP-treated persons. Clinically significant differences in weight gain liability exist among the available NAPs.