Signaling cascades triggered by bacterial metabolic end products during reactivation of Kaposi's sarcoma-associated herpesvirus.

The present studies explore the role of polymicrobial infection in the reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) and analyze signaling pathways activated upon this induction. We hypothesized that activation of the cellular stress-activated mitogen-activated protein kinase (MAPK) p38 pathway would play a key role in the bacterium-mediated disruption of viral latency similar to that of previously reported results obtained with other inducers of gammaherpesvirus lytic replication. KSHV within infected BCBL-1 cells was induced to replicate following exposure to metabolic end products from gram-negative or -positive bacteria that were then simultaneously exposed to specific inhibitors of signal transduction pathways. We have determined that bacterium-mediated induction of lytic KSHV infection is significantly reduced by the inhibition of the p38 MAPK pathway. In contrast, inhibition of the phosphatidylinositol 3-kinase pathway did not impair induction of lytic replication or p38 phosphorylation. Protein kinase C, though activated, was not the major pathway used for bacterium-induced viral reactivation. Furthermore, hyperacetylation of histones 3 and 4 was detected. Collectively, our results show that metabolic end products from these pathogens induce lytic replication of KSHV in BCBL-1 cells primarily via the activation of a stress-activated MAPK pathway. Importantly, we demonstrate for the first time a mechanism by which polymicrobial bacterial infections result in KSHV reactivation and pathogenesis.

Estimating bulk density in vertically exposed stoney alluvium using a modified excavation method.

Despite many decades of education and refining land-use practices, accelerated stream bank erosion is still prevalent in the United States. Eroding stream banks produce a sediment load to the riverine system and can cause reduced water quality as a result of increased suspended sediment. As total maximum daily loads (TMDLs) for water bodies impaired by turbidity or suspended sediments become more numerous, a simple, in situ field technique will be needed to estimate the bulk density of readily erodible stream bank material so that reasonably accurate sediment loading rates can be estimated. In this study, the excavation/polyurethane-foam technique for estimating total bulk density was applied to vertically exposed alluvium with high coarse-fragment content. Though not previously attempted in vertically exposed alluvium with high coarse-fragment content, the excavation/polyurethane-foam technique appears to provide a reasonably accurate estimate of the total and soil (<2-mm size fraction) bulk density from vertically exposed, alluvial deposits with high coarse-fragment content (i.e., >70%) along eroding stream banks. Obtaining bulk density estimates using this method would facilitate calculation of sediment loading rates to riverine systems with actual field data.

Distribution of Lewis (FUT3)genotype and allele: frequencies in a biethnic United States population.

The objective of the study was to examine the prevalence and distribution of four major single nucleotide polymorphisms (SNPs) (T59G, T1067G, T202C, and C314T) of the Lewis ( FUT3)gene in a biethnic United States population. This population-based cross-sectional study was based on data from the Atherosclerosis Risk in Communities (ARIC) Study, which included 761 males and females aged 45-64 years, who had no known/detected clinical atherosclerotic disease (577 Caucasians, 184 African Americans). The main outcome measures were prevalence of the Lewis genotype and allele frequencies for four SNPs of the FUT3gene. The most common genotype was the "wild type" at all four nucleotide positions ( WWWW), which was found to be present in 46.9% of ARIC participants. At least one mutant allele was detected in 51.7% of Caucasians, and 56.7% of African Americans ( P=0.59). The frequencies of mutant alleles ranged from 6.3% to 18.4% at the four FUT3gene sites examined. The distribution of the Lewis genotype and allele frequencies differed significantly by ethnicity at sites 59, 202, and 314. The prevalence of the Lewis genotype suggesting a lack of alpha(1,3/1,4) fucosyltransferase activity was 11.6% in Caucasians and 9.9% in African Americans ( P=0.67). Four specific SNPs of the Lewis genotype are common in the population at large. However, these four SNPs seem to fail to explain the majority of Lewis-negative phenotype in African Americans, given that Lewis-negative genotype prevalence was about one-third of what was expected. Use of rapid DNA sequencing and simultaneous Lewis phenotype determination could avoid the problems associated with haplotype determination and Lewis genotype grouping. Further studies testing SNPs of the Lewisgene are warranted, in particular among African Americans.

Childhood anxiety disorders: etiology, assessment, and treatment in the new millennium.

The following article reviews the literature on childhood anxiety disorders published during the past year. Publication trajectories suggest ever increasing empirical focus on the nature, developmental influences, assessment, and treatment of anxiety in children. The past year witnessed significant events on a national level with respect to public policy development. Despite such forward progress, research on childhood anxiety remains disproportionally behind that of the disruptive behavior disorders. With respect to treatment, cognitive-behavioral approaches have demonstrated strong empirical support. Although there is limited data yet available, selective serotonin reuptake inhibitors appear to be efficacious in treating anxiety in children.

Treating childhood shyness and related behavior: empirically evaluated approaches to promote positive social interactions.

Behavioral and cognitive-behavioral strategies, including exposure, social skills training, and peer-mediated approaches, used to treat childhood shyness and related impairments are described. In addition, relevant outcome studies published within the past 20 years are evaluated, and limitations regarding the generalization, maintenance, and social validity of the reported treatment gains are addressed. Although the interventions reviewed have demonstrated short-term merit in ameliorating social and emotional impairments, such as problematic peer relations and internalizing difficulties, there currently is a lack of evidence to support the social validity and long-term generalization and maintenance of such behavioral gains. Thus, recommendations for future research are made, including the need to (a) assess the social validity of treatment outcomes, (b) utilize important socialization agents (e.g., parents, teachers, peers), and (c) conduct prevention research and longitudinal outcome studies.

Genetic background of Lewis negative blood group phenotype and its association with atherosclerotic disease in the NHLBI family heart study.

OBJECTIVES: To examine the prevalence of four mutations, T59G, T1067A, T202C and C314T, of the human alpha(1,3/1,4) fucosyltransferase 3 (FUT 3) gene amongst persons with Lewis negative and those with Lewis positive blood group phenotype. An additional objective was to explore the hypothesis that these mutations are associated with coronary heart disease and inflammatory reaction. DESIGN: A population-based cross-sectional study. SETTING: Analysis of samples and data from the National Heart Lung and Blood Institute Family Heart Study. SUBJECTS: All Lewis (a-b-) participants (n = 136) and a sample of Lewis positive participants (n = 136) of the Family Heart Study; all were of Caucasian ethnicity. MAIN OUTCOME MEASURES: The prevalence of examined mutations by Lewis phenotype. RESULTS: The examined mutations were common and strongly associated with the Lewis (a-b-) phenotype. Accordingly, 90-95% of Lewis (a-b-) individuals amongst Caucasians can be identified by screening for these four mutations. Exploratory analyses suggested that with the exception of T59G, all examined mutations were positively associated with prevalent coronary heart disease, although not statistically significantly, perhaps due to the small number of prevalent coronary heart disease cases. C-reactive protein tended to be higher amongst persons with a TC or CC genotype at position 202 (3.07 +/- 0.41 vs. 2.08 +/- 0.32 mg L-1, P = 0.06). CONCLUSIONS: Four specific mutations of fucosyltransferase 3 gene are responsible for the vast majority of Lewis (a-b-) phenotypes in Caucasians. These mutations are common in the population at large and may be associated with increased risk of coronary heart disease. Further studies using larger samples are warranted.

Behavioral treatment of childhood social phobia.

Sixty-seven children (ages 8 and 12) with social phobia were randomized to either a behavioral treatment program designed to enhance social skills and decrease social anxiety (Social Effectiveness Therapy for Children, SET-C) or an active, but nonspecific intervention (Testbusters). Children treated with SET-C were significantly more improved across multiple dimensions, including enhanced social skill, reduced social fear and anxiety, decreased associated psychopathology, and increased social interaction. Furthermore, 67% of the SET-C group participants did not meet diagnostic criteria for social phobia at posttreatment compared with 5% of those in the Testbusters group. Treatment gains were maintained at 6-month follow-up. The results are discussed in terms of treatment of preadolescent children with social phobia and the durability of treatment effects.

Investigative interviewing with children: evaluation of the effectiveness of a training program for child protective service workers.

OBJECTIVE: Previous research suggests that training workshops on investigative interviewing conducted with front-line workers, such as police officers or child protective service (CPS) workers, may result in improved knowledge about appropriate strategies to use. Limited research has addressed whether such training programs result in improvements in actual interviewing skills. The present investigation assessed the impact of a training workshop on CPS workers' knowledge about conducting and behavior during investigative interviews. METHOD: Twelve CPS workers participated. To evaluate the impact of the training, a quasi-experimental design was used. Participants completed outcome measures prior to, immediately following, and 3 months following the training. Outcome measures included (a) a questionnaire to assess knowledge about interviewing practices, (b) simulated interviews with a confederate to assess participant behavior during an investigative interview, and (c) questionnaires to gather information related to the simulated interviews (e.g., materials requested for use during interview, abuse status of confederate). All participants completed 6 hours of training during 3 weekly 2-hour sessions. RESULTS: Participants' knowledge on the topic, as well as several interviewing skills during simulated interviews, improved following the training. However, the training failed to impact several key interviewing skills such as the types of questions asked or the length of the interview. CONCLUSIONS: Knowledge-based workshop training programs may not adequately prepare CPS workers to conduct appropriate investigative interviews with children who were allegedly abused. Further, knowledge about how to conduct such interviews may not be the best indicator of whether someone is prepared for this aspect of the job.

Discriminant validity of self-reported anxiety and depression in children: generalizability to clinic-referred and ethnically diverse populations.

In the present study, we investigated the relation of childhood anxiety and depression with 240 children (56% clinical referrals, 44% nonclinical referrals) ages 8 to 14 years. Participants were administered the State-Trait Anxiety Inventory for Children (STAIC) and the Children s Depression Inventory (CDI), two commonly used self-report measures of childhood anxiety and depression. The principal focus of this study was to examine the discriminant validity of these measures at the level of individual items through factor analysis. Although high correlations were found between overall scores on the CDI and STAIC, factor analysis yielded distinct factors of anxiety and depression. Thus, with the inclusion of clinic-referred and ethnically diverse groups, the present study provided support for the generalizability of findings of similar research with non-clinic-referred, primarily-Caucasian samples.

Using item analysis to facilitate interpretation of empirical findings.

Researchers often present and interpret empirical findings with reference to hypothetical constructs and diagnostic labels. Such interpretations commonly are based upon "summary" scores obtained through interview, self-report, or rating-scale assessment instruments. Although there are advantages associated with communicating empirical findings through analysis with summary scores, there also are weaknesses that may limit the interpretability of empirical findings and impede theory development. We discuss the importance of item analysis as a tool that may guide presentation of empirical findings, and we describe how it may be used to minimize these limitations of assessment, facilitate data interpretation, and increase the opportunity for theoretical advances.

Psychopathology of childhood social phobia.

OBJECTIVE: To describe the clinical syndrome of social phobia in preadolescent children. METHOD: Fifty children with DSM-IV social phobia were assessed with semistructured diagnostic interviews, self-report instruments, parental and teacher ratings, a behavioral assessment, and daily diary recordings. In addition, the behaviors of these children were compared with those of a sample of normal peers. RESULTS: Children with social phobia had a high level of general emotional over-responsiveness, social fear and inhibition, dysphoria, loneliness, and general fearfulness. Sixty percent suffered from a second, concurrent disorder. Socially distressing events occurred quite frequently and were accompanied by maladaptive coping behaviors. In addition, children with social phobia had significantly poorer social skills. There were few differences based on gender or race. CONCLUSIONS: Children with social phobia suffer pervasive and serious functional impairment. In addition, the clinical presentation suggests specific avenues for psychosocial interventions.

Psychometric evaluation of the social phobia and anxiety inventory for children: concurrent validity and normative data.

Examined the relation of the Social Phobia and Anxiety Inventory for Children (SPAI-C) to the Social Anxiety Scale for Children-Revised (SASC-R). The association between the SPAI-C and the SASC-R was moderate, suggesting that the measures assess overlapping, although not identical, constructs. Initial normative data are reported on the SPAI-C for a community sample of 277 4th-through 6th-grade children. Girls reported higher social anxiety on both measures than did boys. Notably, a substantial proportion of children were found to exceed suggested cut-off scores on both measures for identifying children with high levels of social anxiety, which suggests the importance of screening elementary-age children for social fears.

Developmental and adjustment issues of gay, lesbian, and bisexual adolescents: a review of the empirical literature.

Various studies have reported adjustment problems experienced by gay, lesbian, and bisexual (GLB) adolescents. A primary purpose of this paper is to critically review this literature. Difficulties that have been studied include past suicide attempts, substance use and abuse, conduct problems, and academic concerns. For example, a considerable number of GLB youth report a history of suicide attempts, with prevalence rates ranging from 11 to 42%. However, among other methodological concerns, studies in this area have not used a comparison sample of heterosexual youths. Characteristics of development particular to GLB adolescents are described, the empirical research on adjustment issues is reviewed, and potential risk and protective factors for GLB youths are discussed.

DSM-IV and disorders of childhood and adolescence: can structural criteria be functional?

The structural, descriptive basis of the diagnostic categories outlined in the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) is contrasted to a system of functional analysis, with regard to (a) clinical diagnosis, (b) target behavior identification, (c) treatment design, (d) treatment evaluation, and (e) clinical research. It is noted that structural classification is a useful starting point for these activities but that functional analysis has greater utility for target behavior identification and treatment design by giving consideration to antecedent and consequent events, skills repertoires, response interrelations, and support systems. Examples of melding structural classification and functional analytic systems are provided with reference to certain childhood disorders: mental retardation, disruptive behavior disorders, and anxiety disorders. Recommendations are made for an elaboration of the DSM axes to include (a) psychosocial and environmental resources and deficits, and (b) idiographic case analysis. It is suggested that these axes will assist in systematizing functional analysis and making it more accessible to all clinicians and researchers.

Electrooculographic and performance indices of fatigue during simulated flight.

The investigation evaluated specific components of eye and eyelid movement as predictors of performance decrements resulting from pilot fatigue. Ten partially sleep deprived pilots flew a GAT-1 moving-base flight simulator on a 4.5-h sortie. The scored flight portion consisted of eight legs, each leg made up of two segments, a flight maneuvers task (FMT) and a straight and level flying task (SLT). Error scores were calculated across altitude, airspeed, heading, and vertical velocity. An electrooculogram provided measures of blink rate (BR), blink duration, long closure rate (LCR), blink amplitude (BA), saccade velocity, saccade rate, and peak saccade velocity. Subjective fatigue, workload and sleepiness were estimated using the USAFSAM seven-point forced-choice scales, the Stanford Sleepiness Scale, and the USAFSAM Sleep Survey Form. Error scores increased significantly during the first seven legs of the sortie and decreased slightly for the last leg. Subjective reports of fatigue increased significantly over time and were positively correlated with increased error. For the combined data set and for FMTs alone, BA was the best predictor of changes in error with decreased amplitude corresponding to increased error. BR and LCR were the second and third best predictors, respectively. For SLTs alone, LCR and BA were the first and second best predictors of increased error, respectively. The investigation demonstrated that measurable flying performance decrements do occur due to changes in fatigue and that one can measure physiological correlates of those performance decrements.

Solubilized HLA class I antigen enzyme-linked immunoassay to identify HLA-typing reagents.

The objective of this study was to evaluate the use of sHLA in a solid-phase EIA as a rapid and sensitive way to identify potential IgG HLA class-I-typing reagents. To evaluate the efficacy of the sHLA EIA, we used the assay to screen 259 HLA-A, -B, and -C antisera that our laboratory had procured using the standard NIH LCA. A positive result obtained by the sHLA EIA, which was defined as an EIA ratio of 3 SD above the mean of 91 anti-HLA-negative sera, revealed that 91% (79 of 87) of the A-locus-typing reagents were positive, 96% (150 of 156) of the B-locus antisera were positive, and only 75% (12 of 16) of the C-locus reagents were positive. The typing reagents that were negative by EIA (n = 18) fell into two categories. First, 38% (7 of 18) were negative by sHLA EIA, as they were IgM-typing reagents (NIH LCA reactivity ameliorated by DTT). The second group of the 11 remaining typing reagents had a mean EIA ratio of 1.0 +/- 0.246 (mean +/- 1 SD), which was significantly (P < 0.001) higher than the mean of the 91 negative controls that were used to establish the negative cutoff. The overall sensitivity of the sHLA EIA to detect HLA class-I-directed IgG was 97.2%.

Use of antimicrobial drugs in adults before and after removal of a restriction policy.

The effects on the quantity and quality of antimicrobial drug use of removing an antimicrobial restriction policy are reported. Monthly totals for the number of courses of antimicrobial therapy and expenditures based on grams used were obtained from pharmacy records on adult inpatients for a portion (July-December 1987) of the restriction policy term and for the six months (July-December 1988) immediately after the policy ended. Data were obtained for nine restricted drugs and for three that were never restricted. Retrospective drug-use reviews were conducted for ceftazidime and imipenem-cilastatin. For the restricted agents, the total number of courses of therapy increased by 158% after the restriction policy was removed, and total expenditures increased by 103%. There were no significant changes in the number of courses of therapy or cost for the unrestricted antimicrobials. In the postrestriction period, ceftazidime and imipenem-cilastatin were used more often in patients who were less critically ill. Inappropriate use of imipenem-cilastatin occurred significantly more often after the restrictions were removed. Other factors potentially affecting the use of antimicrobials, such as patient age and the incidence of nosocomial infections, did not differ substantially between the two periods. The removal of an antimicrobial restriction policy resulted in increased use of and higher expenditures for previously restricted agents, as well as an increase in the inappropriate use of at least one agent.