Search

Background: Study participation bias can affect inferences regarding outcomes., Objective: The objective is to compare characteristics of participants and non-participants of two literacy studies., Methods: Two studies of literacy and health-related quality of life were conducted in English- and Spanish-speaking cancer patients. Patients had a range of literacy skills, and each enrolled patient received $20., Results: Nine hundred and twenty-two English-speaking patients were approached. Among the 651 who met eligibility criteria, 420 were enrolled (64.5 per cent). Four hundred and eighty-seven Spanish-speaking patients were approached. Among the 455 who met eligibility criteria, 414 were enrolled (91.0 per cent) (p<0.001). Multiple imputations were performed to impute missing data. Multivariable logistic regression revealed that recruiting site was the only factor predictive of enrollment in Spanish-speaking patients. Age, education, and recruiting site were important predictors in English-speaking patients. Sensitivity analysis using patients with complete data generated similar results., Conclusions: Spanish-speaking patients enrolled at a much higher rate than English-speaking patients, which is encouraging for future research in this underserved population. One important literacy-related factor (education) did not affect enrollment in Spanish-speaking patients, suggesting that there was no selection bias in this study. Recruiting sites with more indigent patients and long clinic waiting times had higher enrollment, suggesting that monetary compensation and time availability may be important considerations in study participation.

Cigarette consumption and smoking cessation are influenced in part by genes. Personality traits have also been implicated in the aetiology of smoking. Neuroticism, a personality trait with a heritable component, correlates well with anxiety and depression, increasing the risk of being a smoker and decreasing the chance of smoking cessation. Several prior studies in non-British populations have given conflicting results as to whether some genetic polymorphisms affect the relationship between smoking and neuroticism. This study investigated the influence of serotonin transporter (5HTTLPR) genotypes on a composite measure of neuroticism and cigarette consumption/smoking cessation in a British population. Although neuroticism was significantly associated with cigarette consumption and smoking cessation, genotype did not affect this relationship. Our results do not support initial interest in utilising 5HTTLPR genotypes in combination with neuroticism ratings for predicting outcome in smoking cessation clinical settings.

Background: An explanation of the etiology of atopic conditions based on the hygiene hypothesis remains controversial., Objective: To analyze exposure variables in childhood to assess their impact on hay fever, asthma, and sensitization., Methods: Data were collected on 1,232 young Chilean adults born between 1974 and 1978. Information was available on consultations for infections early in life, number of siblings, sharing a bedroom, nursery school attendance, and contact with animals in the first 5 years of life. Information on asthma symptoms and rhinitis were obtained from a standardized questionnaire. Sensitization to eight allergens and bronchial hyper responsiveness (BHR) to methacholine were assessed. The study design was non-concurrent longitudinal for infectious episodes and nutritional status in the first year and cross-sectional for the other outcomes., Results: Number of siblings was associated with sensitization only (p = 0.0048). Nursery school attendance was negatively associated with positive BHR (odds ratio (OR) 0.54, 95% CI 0.30-0.95). A severe respiratory infection early in life was protective of sensitization and wheeze combined (OR 0.29, 95%CI 0.12-0.74). Contact with dogs in the first year was a protective factor of rhinitis (OR 0.47, 95%CI 0.28-0.80), but contact with poultry and cats early in life increased the risk of rhinitis (OR 1.42, 95%CI 1.06-1.88; 1.82, 95%CI 1.06-3.14)., Conclusion: The pattern of associations between environmental exposure in early life and atopic conditions was inconsistent. The significant associations were evenly distributed as protective and risk factors of atopic conditions.

Unlabelled: Coronal fractures of the anterior teeth are a common form of dental trauma that mainly affects children and adolescents. One of the options for managing coronal tooth fractures when the tooth fragment is available and there is no or minimal violation of the biological width is the reattachment of the dental fragment. Reattachment of fractured tooth fragments can provide good and long-lasting esthetics (because the tooth's original anatomic form, color, and surface texture are maintained). It also restores function, provides a positive psychological response, and is a relatively simple procedure. Patient cooperation and understanding of the limitations of the treatment is of utmost importance for good prognosis. This article reports on two coronal tooth fracture cases that were successfully treated using tooth fragment reattachment., Clinical Significance: Reattachment of fractured tooth fragments offers a viable restorative option for the clinician because ot restores tooth function and esthetics with the use of a very conservative and cost-effective approach.

Gene expression is regulated by a complex series of events that take place both at the transcriptional and post-transcriptional levels. The mechanisms and factors involved in transcriptional regulation are relatively well understood, whereas post-transcriptional regulation, in comparison, is still a poorly appreciated process. RNA binding proteins (RBPs) are the key regulators of all post-transcriptional events (RNA splicing, stability, transport and translation). Essentially, in order to improve our knowledge in post-transcriptional regulation, we need to elucidate the mechanisms employed by RBPs to control gene expression. The combination of genomic tools with traditional biochemical approaches generated novel technologies, like ribonomics. The application of these novel technologies not only had a profound impact in the study of RBPs but also created the ground work necessary for the identification of post-transcriptional gene networks; a selected group of mRNAs associated with a particular function or biological pathway/ process that is regulated by the same RBP. In this review article, we explore the latest achievements and discuss future challenges that lie ahead in the RBP world.

Streptococci are the primary component of the multispecies oral biofilm known as supragingival dental plaque; they grow by fermentation of sugars to organic acids, e.g., lactic acid. Veillonellae, a ubiquitous component of early plaque, are unable to use sugars; they ferment organic acids, such as lactate, to a mixture of shorter-chain-length acids, CO(2), and hydrogen. Certain veillonellae bind to (coaggregate with) streptococci in vitro. We show that, between 4 and 8 hours into plaque development, the dominant strains of Veillonella change in their phenotypic characteristics (coaggregation and antibody reactivity) as well as in their genotypic characteristics (16S RNA gene sequences as well as strain level fingerprint patterns). This succession is coordinated with the development of mixed-species bacterial colonies. Changes in community structure can occur very rapidly in natural biofilm development, and we suggest that this process may influence evolution within this ecosystem.

The initial microbial colonization of tooth surfaces is a repeatable and selective process, with certain bacterial species predominating in the nascent biofilm. Characterization of the initial microflora is the first step in understanding interactions among community members that shape ensuing biofilm development. Using molecular methods and a retrievable enamel chip model, we characterized the microbial diversity of early dental biofilms in three subjects. A total of 531 16S rRNA gene sequences were analyzed, and 97 distinct phylotypes were identified. Microbial community composition was shown to be statistically different among subjects. In all subjects, however, 4-h and 8-h communities were dominated by Streptococcus spp. belonging to the Streptococcus oralis/Streptococcus mitis group. Other frequently observed genera (comprising at least 5% of clone sequences in at least one of the six clone libraries) were Actinomyces, Gemella, Granulicatella, Neisseria, Prevotella, Rothia, and Veillonella. Fluorescence in situ hybridization (FISH) confirmed that the proportion of Streptococcus sp. sequences in the clone libraries coincided with the proportion of streptococcus probe-positive organisms on the chip. FISH also revealed that, in the undisturbed plaque, not only Streptococcus spp. but also the rarer Prevotella spp. were usually seen in small multigeneric clusters of cells. This study shows that the initial dental plaque community of each subject is unique in terms of diversity and composition. Repetitive and distinctive community composition within subjects suggests that the spatiotemporal interactions and ecological shifts that accompany biofilm maturation also occur in a subject-dependent manner.

Porphyromonas gingivalis is an anaerobic microorganism that inhabits the oral cavity, where oxidative stress represents a constant challenge. A putative transcriptional regulator associated with oxidative stress, an oxyR homologue, is known from the P. gingivalis W83 genome sequence. We used microarrays to characterize the response of P. gingivalis to H2O2 and examine the role of oxyR in the regulation of this response. Most organisms in which oxyR has been investigated are facultative anaerobes or aerobes. In contrast to the OxyR-regulated response of these microorganisms to H2O2, the main feature of the response in P. gingivalis was a concerted up-regulation of insertion sequence elements related to IS1 transposases. Common OxyR-regulated genes such as dps and ahpFC were not positively regulated in P. gingivalis in response to H2O2. However, their expression was dependent on the presence of a functional OxyR, as revealed by microarray comparison of an oxyR mutant to the wild type. Phenotypic characterization of the oxyR mutant showed that OxyR plays a role in both the resistance to H2O2 and the aerotolerance of P. gingivalis. Escherichia coli and other bacteria with more complex respiratory requirements use OxyR for regulating resistance to H2O2 and use a separate regulator for aerotolerance. In P. gingivalis, the presence of a single protein combining the two functions might be related to the comparatively smaller genome size of this anaerobic microorganism. In conclusion, these results suggest that OxyR does not act as a sensor of H2O2 in P. gingivalis but constitutively activates transcription of oxidative-stress-related genes under anaerobic growth.

Asthma epidemiology relies heavily on standardized questionnaires, but little is known about the understanding of asthma symptoms among adults in the community. In 2004, the authors assessed the level of agreement between responses to a standardized questionnaire and responses to a questionnaire completed by participants after viewing a demonstration of asthma symptoms. The study involved 601 young adults from Chile. The field-workers were trained to explain and demonstrate the asthma symptoms to the participants. The symptoms were wheeze, waking at night with breathlessness, breathlessness following exercise, and waking with cough. The kappa statistic did not exceed 0.4, and the recorded prevalence of asthma symptoms following the demonstration was 30-60% lower than that for the standardized questionnaire. Using bronchial responsiveness as the proxy gold standard, the positive likelihood ratios for wheeze and waking short of breath were higher following symptom demonstration. The low agreement between the standardized questionnaire and the postdemonstration questionnaire and the likelihood ratios' closeness to 1 for the standardized questionnaire decreases the authors' confidence in the appropriateness of this tool for estimating the prevalence of asthma in the community. For etiologic studies of asthma, it may contribute to the lack of consistency between different studies analyzing the same etiologic exposures.

Background: Budesonide is the only inhaled corticosteroid to be given a category B pregnancy rating by the US Food and Drug Administration, based on observational data from the Swedish Medical Birth Registry. However, data from large randomized controlled trials are lacking., Objective: To compare pregnancy outcomes among patients with recent-onset mild-to-moderate persistent asthma receiving low-dose budesonide vs placebo., Methods: In a randomized, double-blind, placebo-controlled trial, 7241 patients aged 5 to 66 years with mild-to-moderate persistent asthma for less than 2 years and no previous regular corticosteroid therapy received once-daily budesonide or placebo via dry powder inhaler in addition to their usual asthma medication for 3 years. This trial was followed by a 2-year open-label treatment period. The daily dose of budesonide was 400 microg for adults. The study included 2473 females aged 15 to 50 years at randomization. Pregnancy was not an exclusion criterion (except for U.S. patients)., Results: Of 319 pregnancies reported, 313 were analyzed. Healthy children were delivered in 81% and 77% of all pregnancies in the budesonide and placebo groups, respectively. Of the 196 pregnancies reported by participants taking budesonide, 38 (19%) had adverse outcomes: 23 (12%) had miscarriages, 3 (2%) had congenital malformations, and 12 (6%) had other outcomes. Of the 117 pregnancies reported in the placebo group, 27 (23%) had adverse outcomes: 11 (9%) had miscarriages, 4 (3%) had congenital malformations, and 12 (10%) had other outcomes., Conclusions: Treatment with low-dose inhaled budesonide in females with mild-to-moderate persistent asthma does not seem to affect the outcome of pregnancy.

There is considerable evidence that genetic factors play a major role in the etiology of unipolar depression. Investigations into vulnerability genes for unipolar depression are underway and for more broadly defined depression-related traits, such as anxiety, neuroticism, and harm avoidance. This review discusses some of the core issues related to study design and molecular genetic methodology, followed by an overview of recent molecular genetic findings for unipolar depression. The research to date has identified regions within certain chromosomes that may contain risk genes. Improved study design and the use of new molecular techniques hold promise for the identification of more specific vulnerability genes for unipolar depression.

The usual context for genome-genome interactions is DNA-DNA interactions, but the manifestation of the genome is the cell. Here we focus on cell-cell interactions and relate them to the process of building multi-species biofilm communities. We propose that dental plaque communities originate as a result of intimate interactions between cells (genomes) of different species and not through clonal growth of genetically identical cells. Although DNA exchange might occur between cells within these communities, we limit our opinions to discussions of the spatiotemporal and metabolic relationships that exist here. We believe the multi-species interactions occurring during the early stages of biofilm formation determine the species composition and nature of the mature biofilm. The human oral cavity provides easy access to natural biofilms on a retrievable enamel chip, which is an excellent model for the study of genome-genome interactions.

Objective: The aim of this study was to determine characteristics of drug allergy alert overrides, assess how often they lead to preventable adverse drug events (ADEs), and suggest methods for improving the allergy-alerting system., Design: Chart review was performed on a stratified random subset of all allergy alerts occurring during a 3-month period (August through October 2002) at a large academic hospital., Measurements: Factors that were measured were drug/allergy combinations that triggered alerts, frequency of specific override reasons, characteristics of ADEs, and completeness of allergy documentation., Results: A total of 6,182 (80%) of 7,761 alerts were overridden in 1,150 patients. In this sample, only 10% of alerts were triggered by an exact match between the drug ordered and allergy listed. Physicians' most common reasons for overriding alerts were "Aware/Will monitor" (55%), "Patient does not have this allergy/tolerates" (33%), and "Patient taking already" (10%). In a stratified random subset of 320 patients (28% of 1,150) on chart review, 19 (6%) experienced ADEs attributed to the overridden drug; of these, 9 (47%) were serious. None of the ADEs was considered preventable, because the overrides were deemed clinically justifiable. The degree of completeness of patients' allergy lists was highly variable and generally low in both paper charts and the CPOE system., Conclusion: Overrides of drug-allergy alerts were common and about 1 in 20 resulted in ADEs, but all of the overrides resulting in ADEs appeared clinically justifiable. The high rate of alert overrides was attributable to frequent nonexact match alerts and infrequent updating of allergy lists. Based on these findings, we have made specific recommendations for increasing the specificity of alerting and thereby improving the clinical utility of the drug allergy alerting system.

There is considerable evidence to suggest that the genetic vulnerabilities to depression and anxiety substantially overlap and quantitatively act to alter risk to both disorders. Continuous scales can be used to index this shared liability and are a complementary approach to the use of clinical phenotypes in the genetic analysis of depression and anxiety. The aim of this study (Genetic and Environmental Nature of Emotional States in Siblings) was to identify genetic variants for the liability to depression and anxiety after the application of quantitative genetic methodology to a large community-based sample (n = 34,371), using four well-validated questionnaires of depression and anxiety. Genetic model fitting was performed on 2658 unselected sibships, which provided evidence for a single common familial factor that accounted for a substantial proportion of the genetic variances and covariances of the four scales. Using the parameter estimates from this model, a composite index of liability (G) was constructed. This index was then used to select a smaller--but statistically powerful--sample for DNA collection (757 individuals, 297 sibships). These individuals were genotyped with more than 400 microsatellite markers. After the data were checked and cleaned, linkage analysis was performed on G and the personality scale of neuroticism using the regression-based linkage program MERLIN-REGRESS. The results indicated two potential quantitative trait loci (QTL): one on chromosome 1p (LOD 2.2) around 64 cM (43-70 cM) near marker D1S2892 and another on chromosome 6p (LOD 2.7) around 47 cM (34-63 cM) near marker D6S1610. Further exploratory sex-specific analyses suggested that these QTLs might have sex-limited effects.

Cancer patients who have limited literacy skills or English language proficiency are particularly vulnerable to receiving sub-optimal care. Outcome measurement in these patients may provide new insight into previously undetected problems. This report describes the development and testing of a Spanish language, multimedia program for quality of life (QOL) assessment. Pilot testing was conducted with 30 Latino cancer patients with a range of education levels and computer experience. Patients found the program easy to use and understand. The "Talking Touchscreen" is a practical, user-friendly method that provides greater opportunities to assess QOL in Spanish-speaking patients with a range of literacy skills.

Clozapine is a potent antagonist of 5-HT3 receptors, which are ligand-gated ion channels that mediate rapid excitatory responses in the central nervous system. Two different isoforms of 5-HT3 receptor subunit genes (HTR3A and HTR3B) have been identified. They have been assigned to chromosome 11q23.1-q23.2, a region which in the past has been linked to schizophrenia and bipolar disorder. In this study, we performed a systematic mutation screening of the 5-HT3A and 5-HT3B receptor genes and tested the variants for association with clozapine response in a sample of 266 clozapine-treated patients. Two polymorphisms at the 5-HT3A gene and five new variants in the 5-HT3B gene were finally detected. Of these, only the more frequent mutations (178-C/T and 1596-A/G in 5-HT3A and a CA-repeat in 5-HT3B) were genotyped in our clozapine sample. Association analysis showed similar allele and genotype distributions among clozapine responders and nonresponders. These results make unlikely the possibility that 5-HT3A and 5-HT3B receptor genes underlie variation in clinical response to clozapine. However, the promoter regions of both genes have yet to be investigated., (Copyright 2002 Elsevier Science B.V.)

The relationship of leptin gene expression to adipocyte volume was investigated in lean 10-wk-old male C57BL/6J mice. mRNA levels for leptin, insulin receptor, glucocorticoid receptor, and tumor necrosis factor (TNF)-alpha in inguinal, epididymal, and retroperitoneal adipose tissues were quantified and related to adipocyte volume. Leptin mRNA levels were highly correlated with adipocyte volume within each fat depot. Multiple regression analysis of pooled data from the three depots showed that leptin mRNA levels were strongly correlated with adipocyte volumes (beta = 0.84, P < 0.001) and, to a smaller degree, with glucocorticoid receptor mRNA levels (beta = 0.36, P < 0.001). Depot of origin had no effect (P > 0.9). Rates of leptin secretion in vitro were strongly correlated with leptin mRNA levels (r = 0.89, P < 0.001). mRNA levels for TNF-alpha, insulin receptor, and glucocorticoid receptor showed no significant correlation with adipocyte volume. These results demonstrate that depot-specific differences in leptin gene expression are mainly related to the volumes of the constituent adipocytes. The strong correlation between leptin gene expression and adipocyte volume supports leptin's physiological role as a humoral signal of fat mass.