Adjunctive screening devices for oral lesions: their use by Canadian Dental Hygienists and the need for knowledge translation.

Screening for oral cancer and other mucosal conditions is a knowledge-to-action objective that should be easy: there is supportive evidence, it is fast and non-invasive, and the oral cavity is easy to visualize. However, over 60% of oral cancers are diagnosed late, when treatment is complex and prognosis poor. Adjunctive screening devices (ASDs), e.g. toluidine blue (TB), fluorescence visualization (FV), chemiluminescence (CL) and brush biopsies, were designed to assess risk of oral lesions or aid in identification and localization of oral premalignant and malignant lesions. Little is known on how clinicians feel about using ASDs. OBJECTIVES: To evaluate use and level of comfort in using ASDs for oral cancer screening among dental hygienists. METHODS: Online email survey of a stratified random sample of nearly 3000 dental hygienists from four Canadian provinces. RESULTS: A total of 369 hygienists responded about ASDs. Ninety-three (25%) had used an ASD. Use was associated with six or more continuing education (CE) courses per year (P = 0.030), having a CE course in oral pathology within the last 3 years (P = 0.003) and having a screening protocol (P = 0.008). The most commonly used ASD is FV, which was the tool hygienists felt most comfortable using. Few used brush biopsies. Older graduates were more comfortable using TB (P = 0.014) and CL (0.033). CONCLUSION: Current evidence and education through CE appears to bolster knowledge translation efforts for hygienists to become more comfortable in the use of ASDs. ASDs with minimal supporting evidence and not specifically targeted to hygienists, such as the brush biopsies, are not well utilized.

The many faces of Ras: recognition of small GTP-binding proteins.

The structures of over 30 complexes of Ras superfamily small GTP-binding proteins bound to diverse protein partners have been reported. Comparison of these complexes using the sequences of the small GTP-binding proteins to align the contact sites shows that virtually all surface positions make contacts with at least one partner protein. Rather than highlighting a single consensus binding site, these comparisons illustrate the remarkable diversity of contacts of Ras superfamily members. Here, a new analysis technique, the interface array, is introduced to quantify patterns of surface contacts. The interface array shows that small GTP-binding proteins are recognized in at least nine distinct ways. Remarkably, binding partners with similar functions, including those with distinct folds, recognize small GTP-binding proteins in similar ways. These classes of shared surface contacts support the occurrence of both divergent and convergent evolutionary processes and suggest that specific effector functions require particular protein-protein contacts.

Evaluation of a vaccine passport to improve vaccine coverage in people living with HIV.

An increased risk of vaccine-preventable infections (VPIs) is seen in people living with HIV (PLWH), and current vaccine coverage and immunity is variable. Vaccine passports have the potential to improve vaccine coverage. The objective was to assess how successful a vaccine passport was in improving vaccine coverage in PLWH. Baseline immunity to VPIs was established in PLWH attending a single HIV clinic and vaccinations required were determined based on the BHIVA Vaccination Guidelines (2015). The passport was completed and the PLWH informed about additional vaccines they should obtain from primary care. After 6-9 months the passport was reviewed including confirmation if vaccines were given. PLWH satisfaction with the system was evaluated by a survey. Seventy-three PLWH provided sufficient data for analysis. At baseline significant proportions of PLWH were not immune/unvaccinated to the main VPIs, especially human papillomavirus, pneumococcus and measles. After the passport was applied immunity improved significantly (56% overall, p < 0.01) for most VPIs; however, full coverage was not achieved. The system was popular with PLWH. The passport was successful in increasing vaccination coverage although full or near-full coverage was not achieved. A more successful service would probably be achieved by commissioning English HIV clinics to provide all vaccines.

Ketoconazole inhibition of triazolam and alprazolam clearance: differential kinetic and dynamic consequences.

BACKGROUND: Kinetic and dynamic consequences of metabolic inhibition were evaluated in a study of the interaction of ketoconazole, a P4503A inhibitor, with alprazolam and triazolam, two 3A substrate drugs with different kinetic profiles. METHODS: In a double-blind, 5-way crossover study, healthy volunteers received (A) ketoconazole placebo plus 1.0 mg alprazolam orally, (B) 200 mg ketoconazole twice a day plus 1.0 mg alprazolam, (C) ketoconazole placebo plus 0.25 mg triazolam orally, (D) 200 mg ketoconazole twice a day plus 0.25 mg triazolam, and (E) 200 mg ketoconazole twice a day plus benzodiazepine placebo. Plasma concentrations and pharmacodynamic parameters were measured after each dose. RESULTS: For trial B versus trial A, alprazolam clearance was reduced (27 versus 86 mL/min; P < .002) and apparent elimination half-life (t1/2) prolonged (59 versus 15 hours; P < .03), whereas peak plasma concentration (Cmax) was only slightly increased (16.1 versus 14.7 ng/mL). The 8-hour pharmacodynamic effect areas for electroencephalographic (EEG) beta activity were increased by a factor of 1.35, and those for digit-symbol substitution test (DSST) decrement were increased by 2.29 for trial B versus trial A. For trial D versus trial C, triazolam clearance was reduced (40 versus 444 mL/min; P < .002), t1/2 was prolonged (18.3 versus 3.0 hours; P < .01), and Cmax was increased (2.6 versus 5.4 ng/mL; P < .001). The 8-hour effect area for EEG was increased by a factor of 2.51, and that for DSST decrement was increased by 4.33. Observed in vivo clearance decrements due to ketoconazole were consistent with those anticipated on the basis of an in vitro model, together with in vivo plasma concentrations of ketoconazole. CONCLUSION: For triazolam, an intermediate-extraction compound, impaired clearance by ketoconazole has more profound clinical consequences than those for alprazolam, a low extraction compound.

Comparative kinetics and dynamics of zaleplon, zolpidem, and placebo.

PURPOSE: This study evaluated the relationship of dose, plasma concentration, and time to the pharmacodynamics of zaleplon and zolpidem, 2 structurally distinct benzodiazepine receptor agonists. METHOD: Ten healthy male volunteers received single oral doses of placebo, 10 mg zaleplon, 20 mg zaleplon, 10 mg zolpidem, and 20 mg zolpidem in a double-blind, 5-condition crossover study, with 48 hours elapsing between trials. Plasma drug concentrations and pharmacodynamic effects were measured during the 8 to 24 hours after administration. RESULTS: Kinetics of zaleplon and zolpidem were not significantly related to dose. However, zaleplon had more rapid elimination (apparent elimination half-life [t1/2] of 1 hour) and higher apparent oral clearance (approximately 4300 mL/min) than zolpidem (t1/2, 2.0 to 2.2 hours; apparent oral clearance, 340 to 380 mL/min). Active treatments produced pharmacodynamic effects consistent with benzodiazepine agonist activity: self- and observer-rated sedation, impairment of digit symbol substitution test (DSST) performance, impaired memory, and increased electroencephalographic activity in the beta frequency range. The overall order of agonist potency was as follows: placebo < 10 mg zaleplon < 20 mg zaleplon < 10 mg zolpidem < 20 mg zolpidem; on a number of measures, 20 mg zaleplon was comparable to 10 mg zolpidem. Quantitative effects of zolpidem 20 mg far exceeded those of other treatments. Dynamic effects of both drugs were significantly related to plasma concentration. CONCLUSIONS: Benzodiazepine agonist effects of zaleplon and zolpidem were dose and concentration dependent. At the usual clinically effective hypnotic dose (10 mg of either drug), agonist effects of zolpidem exceeded those of zaleplon.

Tailoring the substrate specificity of the beta-glycosidase from the thermophilic archaeon Sulfolobus solfataricus.

The substrate specificity of the thermophilic beta-glycosidase (lacS) from the archaeon Sulfolobus solfataricus (SSbetaG), a member of the glycohydrolase family 1, has been analysed at a molecular level using predictions from known protein sequences and structures and through site-directed mutagenesis. Three critical residues were identified and mutated to create catalysts with altered and broadened specificities for use in glycoside synthesis. The wild-type (WT) and mutated sequences were expressed as recombinant fusion proteins in Escherichia coli, with an added His(6)-tag to allow one-step chromatographic purification. Consistent with side-chain orientation towards OH-6, the single Met439-->Cys mutation enhances D-xylosidase specificity 4.7-fold and decreases D-fucosidase activity 2-fold without greatly altering its activity towards other D-glycoside substrates. Glu432-->Cys and Trp433-->Cys mutations directed towards OH-4 and -3, respectively, more dramatically impair glucose (Glc), galactose (Gal), fucose specificity than for other glycosides, resulting in two glycosidases with greatly broadened substrate specificities. These include the first examples of stereospecificity tailoring in glycosidases (e.g. WT-->W433C, k(cat)/K(M) (Gal):k(cat)/K(M) (mannose (Man))=29.4:1-->1.2:1). The robustness and high utility of these broad specificity SSbetaG mutants in parallel synthesis were demonstrated by the formation of libraries of beta-glycosides of Glc, Gal, xylose, Man in one-pot preparations at 50 degrees C in the presence of organic solvents, that could not be performed by SSbetaG-WT.

Comparison of the effects of pravastatin and lovastatin on sleep disturbance in hypercholesterolemic subjects.

We have studied the effects of two cholesterol-lowering medications, lovastatin and pravastatin, on different sleep parameters in hypercholesterolemic subjects. These medications are 3-hydroxy-methylglutaryl coenzyme A inhibitors. Only subjects who had complained of sleep disturbance while on previous treatment with lovastatin were enrolled. Sixteen subjects (11 men and 5 women) underwent a randomized, double-blind, three-way crossover treatment with lovastatin, pravastatin, and placebo. Each phase of the study lasted 4 weeks. A placebo wash-out period of 4 weeks separated each treatment phase. At the end of each treatment phase, subjects were admitted to the sleep laboratory for 2 consecutive nights. No statistical differences were detected during treatment with lovastatin, pravastatin, and placebo for sleep parameters such as total sleep time, total awake time, wake time after sleep onset, efficiency of sleep, and percent of different phases of sleep. Our study suggests that lovastatin and pravastatin do not have a significant effect on sleep parameters in hypercholesterolemic subjects that could explain their complaints of insomnia. Nevertheless, the subjects did have moderate sleep disturbances that could account for insomnia and most likely predate the use of HMG-CoA reductase inhibitors.

Relative contribution of CYP3A to amitriptyline clearance in humans: in vitro and in vivo studies.

The relative contribution of cytochrome P450 3A (CYP3A) to the oral clearance of amitriptyline in humans has been assessed using a combination of in vitro approaches together with a clinical pharmacokinetic interaction study using the CYP3A-selective inhibitor ketoconazole. Lymphoblast-expressed CYPs were used to study amitriptyline N-demethylation and E-10 hydroxylation in vitro. The relative activity factor (RAF) approach was used to predict the relative contribution of each CYP isoform to the net hepatic intrinsic clearance (sum of N-demethylation and E-10 hydroxylation). Assuming no extrahepatic metabolism, the model-predicted contribution of CYP3A to net intrinsic clearance should equal the fractional decrement in apparent oral clearance of amitriptyline upon complete inhibition of the enzyme. This hypothesis was tested in a clinical study of amitriptyline (50 mg, p.o.) with ketoconazole (three 200 mg doses spaced 12 hours apart) in 8 healthy volunteers. The RAF approach predicted CYP2C19 to be the dominant contributor (34%), with a mean 21% contribution of CYP3A (range: 8%-42% in a panel of 12 human livers). The mean apparent oral clearance of amitriptyline in 8 human volunteers was decreased from 2791 ml/min in the control condition to 2069 ml/min with ketoconazole. The average 21% decrement (range: 2%-40%) was identical to the mean value predicted in vitro using the RAF approach. The central nervous system (CNS) sedative effects of amitriptyline were slightly greater when ketoconazole was coadministered, but the differences were not statistically significant. In conclusion, CYP3A plays a relatively minor role in amitriptyline clearance in vivo, which is consistent with in vitro predictions using the RAF approach.

Women gain weight 1 year after smoking cessation while dietary intake temporarily increases.

OBJECTIVE: To examine the relationship of dietary change to weight change in women who quit smoking and remained abstinent for 1 year. METHODS: For 1 year, 582 women participating in smoking cessation classes were studied. Weight, diet, and physical activity were measured at baseline and at 1, 6, and 12 months after smoking cessation. Multivariate regression models were used to predict 1-year weight change for the 139 women who remained abstinent. RESULTS: Women gained, on average, 9.9 lb over a 1-year period while increasing their intake of energy for 1 and 6 months but returning to baseline levels by 1 year. Sucrose, total carbohydrate, and fat intake increased significantly for the first month; fat and total carbohydrate intake remained at an increased level for 6 months. In unadjusted analyses, older women and those who smoked more cigarettes gained more weight than younger women and lighter smokers; lighter and heavier women gained more weight than women of intermediate weight. In adjusted analyses, age remained a significant factor and number of cigarettes remained of borderline significance. Change in energy intake was predictive of weight change only in women with the highest energy intake at baseline. APPLICATIONS: Dietitians should acknowledge that most women who quit smoking gain weight in the short term. Although many women increase their energy intake, change in energy level is only one factor in weight change. Over the long term, women with high baseline intakes appear to be able to affect their weight change by reducing their energy intake.

Gender, social pressure, and smoking cessations: the Community Intervention Trial for Smoking Cessation (COMMIT) at baseline.

This study was undertaken to examine gender differences in the perception of social constraints against smoking and to explore the role of other sociodemographic and smoking factors that influence the perception of social pressure. Baseline data from the 20 U.S. sites in the National Cancer Institute's Community Intervention Trial for Smoking Cessation (COMMIT) were analyzed. We found that women were less likely than men to be heavy smokers and to report that smoking had affected their health, but more likely to report behavior indicating physiological addiction (timing of first cigarette). At all smoking levels, women were about twice as likely as men to report feeling pressure to quit, after adjusting for education, income, ethnic group, age, and other factors. The source of pressure, however, was different: more women report pressure from their children, whereas more men report pressure from friends and coworkers. Women were equally likely as men to make quit attempts, after adjusting for other factors, but were less likely to remain abstinent for at least 10 days. Women, regardless of education, ethnicity, and age, reported a greater tendency to ask permission before smoking in non-restricted public places. College-educated men were less likely than men without college education to smoke without asking in non-restricted places, but education did not influence whether women asked permission. For both sexes, smoking level and nicotine dependence were significant predictors of lighting up without asking in public places, after adjustment for other variables. We discuss these findings and their implications for the gender gap in smoking cessation and women's conflicting pressures to stop/continue smoking. Tobacco control efforts are discussed within the context of gender differences in social norms, roles, socialization, and communication cultures.

In their own words: a model of healthy aging.

Many previous studies have assessed the aging process by measuring clinical and functional variables. To supplement that quantitative understanding, we asked older people what constitutes their health and contributes to it. Using grounded theory-type methods, we analyzed semi-structured interviews with 22 study subjects, who were randomly selected from among those whose reported perceived health differed from that predicted by a regression model constructed from data from a randomized trial of a primary care intervention. We focused on disparate cases to identify factors that best discriminate between more and less healthy aging. Interview questions targeted perceptions of health; well-being; valued abilities, activities, and relationships; social support; control; sense of coherence; and personal outlook. A model of healthy aging emerged. To these older people health meant going and doing something meaningful, which required four components: something worthwhile to do, balance between abilities and challenges, appropriate external resources, and personal attitudinal characteristics (e.g., positive attitude vs. "poor me"). By reframing healthy aging in older people's own terms, this model encourages interdisciplinary support of their desired goals and outcomes rather than only medical approaches to deficits and challenges.

Information needs in terminal illness.

Despite evidence that doctor-patient communication affects important patient outcomes, patient expectations are often not met. Communication is especially important in terminal illness, when the appropriate course of action may depend more on patient values than on medical dogma. We sought to describe the issues important to terminally ill patients receiving palliative care and to determine whether patient characteristics influence the needs of these patients. We utilized a multimethod approach, first conducting interviews with 22 terminally ill individuals, then using these data to develop a more structured instrument which was administered to a second population of 56 terminally ill patients. Patient needs and concerns were described and associations between patient characteristics and issues of importance were evaluated. Seven key issues were identified in the initial interviews: change in functional status or activity level; role change; symptoms, especially pain; stress of the illness on family members; loss of control; financial burden and conflict between wanting to know what is going on and fearing bad news. Overall, respondent needs were both disease- and illness-oriented. Few easily identifiable patient characteristics were associated with expressed concerns or needs, suggesting that physicians need to individually assess patient needs. Terminally ill patients receiving palliative care had needs that were broad in scope. Given that few patient characteristics predicted responses, and that the majority opinion may not accurately reflect that of an individual patient, health care providers must be aware of the diverse concerns among this population and individualize assessment of each patient's needs and expectations.

Quantitative estimate of bilaterally projecting medial olivocochlear neurones in the guinea pig brainstem.

Bilateral intracochlear injections of the fluorescent retrograde neuronal tracers fast blue and diamidino yellow were used to identify efferent neurones in the guinea pig brainstem which project to the inner ear on both sides. Bilaterally projecting neurones, detected by their double-labelled appearance in fluorescence microscopy, were found in all the nuclei of origin of the large neurone extra-LSO system of olivocochlear neurones. No double-labelled neurones were found in the small neurone LSO system. When precautions were taken to maximize their capture, these bilaterally projecting neurones comprised 5.4% of the total extra-LSO system neurones projecting to any one cochlea. On the basis of these quantitative data, it was suggested that the bilaterally projecting neurones may correspond to the small group of binaurally activated cochlear efferents identified in physiological studies.

Worksite characteristics and changes in worksite tobacco-control initiatives. Results from the COMMIT study.

Few studies have prospectively examined the characteristics associated with worksite adoption of tobacco-control initiatives. Data were collected as part of the Community Intervention Trial (COMMIT) for Smoking Cessation, which conducted interventions in 11 communities. This smoking cessation intervention was based on community organization principles and delivered through multiple community channels, including worksites, health care providers, the media, and cessation resources. This article reports results from telephone interviews of intervention community worksites having 50 or more employees, conducted at baseline and the end of the intervention period. Among worksites that responded to both baseline and final surveys, 83% had not adopted a smoke-free policy at baseline, and 61% did not offer any cessation aid or quitting resources at baseline. By the final survey, 34% of those with no smoking ban at baseline had become smoke-free, and 36% of those offering no cessation assistance at baseline were offering cessation resources at the follow-up. The prevalence of policy adoption was higher among worksites employing more female employees and offering other health-promotion activities; manufacturing businesses were significantly less likely than businesses other than service and wholesale/retail businesses to adopt policies. Adoption of cessation programs was significantly more likely among worksites employing 100 to 249 workers, compared with those employing 50 to 99 workers; those predominantly employing men; those offering other types of health-promotion activities; and those with a higher rate of turnover. These results provide important information about the characteristics of worksites likely to engage in tobacco-control efforts. Health educators and others may choose to target those worksites most ready for adoption of tobacco control policies and programs, as indicated by these findings.

Compliance with worksite nonsmoking policies: baseline results from the COMMIT study of worksites.

PURPOSE: Little is known about compliance with worksite nonsmoking policies. This study provides an examination of the relationship of policy compliance to characteristics of the organization and the manner in which the policy was implemented. DESIGN: Data came from two separate surveys of 1) representatives of worksites that reported having a nonsmoking policy and 2) employed residents from the same communities whose worksites had nonsmoking policies. SETTING: This study was conducted as part of the Community Intervention Trial for Smoking Cessation (COMMIT), being conducted in 11 diverse intervention communities. SUBJECTS: Data are presented from surveys of 710 worksites (response rate = 90%) and 3,143 employed residents (response rate = 80%) of the same communities. MEASURES: Compliance with nonsmoking policies was measured by self-report in both surveys and is compared with worksite and respondent characteristics, type of policy, and methods of policy implementation. RESULTS: Compliance with nonsmoking policies was high; 55% of worksites with a policy restricting smoking reported that employees always adhered to the policy. Compliance was highest in worksites with more restrictive policies and where labor-management relations were reported to be good. Compliance also was high where the policy was effectively communicated to workers, as through worksite distribution channels, the absence of cigarette vending machines, and the availability of cessation assistance. CONCLUSIONS: These findings indicate that compliance with worksite nonsmoking policies is generally high, especially in the presence of more stringent policies.

Drinking patterns and drinking-related problems of Mexican-American husbands and wives.

The present research builds on previous studies' findings of alcohol-related gender differences between Mexican-American men and women, through examination of drinking levels, norms and related problems within the context of marriage and family. A survey of husbands and wives in 206 married couples randomly selected from eligible households in East San Jose, California, was carried out. Highlights in our findings include significant gender differences in reports of drinking patterns, frequency of heavier drinking, tangible consequences of drinking and expectancies regarding alcohol. Most notably, correlations were found between husbands' and wives' quantity-frequency drinking measures, the frequency of heavier drinking, tangible consequences of drinking and expectancies regarding alcohol. Although men have higher levels of drinking and greater drinking-related problems, husbands' and wives' patterns are correlated with one another. These links between spouses' drinking-related variables have important implications for family prevention and education about alcohol use.

Professional nursing issues in the administration of investigational antiarrhythmic medications.

This article examined the trepidation that is often present with the use of investigational antiarrhythmic medications. It specifically addressed the professional and legal responsibilities to which coinvestigator nurses are accountable in the administration of these drugs. In addition, recommendations were given on how the coinvestigator nurse can assess the special needs, particularly the socioeconomic needs, of the patient who receives investigational antiarrhythmic medication so that appropriate interventions may be provided.

Skeletal muscle metabolism in the offspring of trained rats.

To determine the effects of maternal exercise training during pregnancy on skeletal muscle metabolism of the progeny, eleven female Sprague-Dawley rats were divided into an exercise and a control group. The maternal training group (6) ran on a rodent treadmill for 4 weeks prior to pregnancy and daily throughout gestation (21 days) at 26.8 m/min, 1 hour/day, 5 days per week. The measurements were taken 28 days postpartum. No differences were noted between the sedentary and trained maternal animals for succinic dehydrogenase (SDH), phosphofructokinase (PFK), and myosin ATPase activities of the soleus, plantaris and gastrocnemius muscles. Maternal gastrocnemius SDH and soleus PFK levels were significantly (p less than 0.05) lower than levels found in the offspring. The liver glycogen of trained maternal animals was significantly higher than that found in all other groups. As well it was shown that maternal exercise had no effect on any of the aforementioned physiological parameters measured in the pups. The results indicate that exercise training during pregnancy does not modify the skeletal muscle metabolism of the offspring as observed 28 days after birth.

Cross-gendered identifications and homosexual boyhood: toward a more complex theory of gender.

This paper focuses on a subset of homosexual boys whose mixed gender experience moves beyond the conventional categories of masculinity and femininity, and who are often labeled as pathological due to a reluctance to recognize the reality of gender variance and cross-gendered identifications within the domain of mental health. Clinical examples are offered to highlight the need for a theory of gender that accounts for the interweaving of gender and psychic structure as they co-evolve and reflect the chaos inherent in human subjectivity.

Infant feeding styles of West Indian women.

An ethnographic field study design was used to explore infant feeding among 20 West Indian women on the island of St. Croix, United States Virgin Islands. Two styles of infant feeding emerged from the data, "older style" and "contemporary style." Three patterns of combined breast and bottle feeding were identified: day/night, supplemental, and random. Older style mothers followed a day/night pattern, whereas contemporary style mothers used a supplemental pattern. A folk explanatory model of infant feeding was constructed and included why infants were fed in certain ways, as well as the meaning of feeding practices. The health care system had an impact on both styles of infant feeding through hospital practices and provision of formula through the Women, Infants, and Children (WIC) program.