Hydrodynamics of the VanA-type VanS histidine kinase: an extended solution conformation and first evidence for interactions with vancomycin

VanA-type resistance to glycopeptide antibiotics in clinical enterococci is regulated by the VanSARA two-component signal transduction system. The nature of the molecular ligand that is recognised by the VanSA sensory component has not hitherto been identified. Here we employ purified, intact and active VanSA membrane protein (henceforth referred to as VanS) in analytical ultracentrifugation experiments to study VanS oligomeric state and conformation in the absence and presence of vancomycin. A combination of sedimentation velocity and sedimentation equilibrium in the analytical ultracentrifuge (SEDFIT, SEDFIT-MSTAR and MULTISIG analysis) showed that VanS in the absence of the ligand is almost entirely monomeric (molar mass M = 45.7 kDa) in dilute aqueous solution with a trace amount of high molar mass material (M ~ 200 kDa). The sedimentation coefficient s suggests the monomer adopts an extended conformation in aqueous solution with an equivalent aspect ratio of ~ (12+2). In the presence of vancomycin over a 33% increase in the sedimentation coefficient is observed with the appearance of additional higher s components, demonstrating an interaction, an observation consistent with our circular dichroism measurements. The two possible causes of this increase in s – either a ligand induced dimerization and/or compaction of the monomer are considered

Early physical health consequences of disaster exposure and acute disaster-related PTSD

A sample of adults (N=666) was interviewed 6 months after the devastating 1999 floods and mudslides in Mexico. Comparisons between sample data and population norms pointed to significant postdisaster elevations in physical health symptoms across a variety of domains. With age, gender, and predisaster mental health and living conditions controlled, severity of exposure was related to higher physical symptoms. The effects of severity of exposure dropped out of the equations when postdisaster posttraumatic stress disorder (PTSD) symptoms were taken into account. The effects of acute PTSD on health symptoms were largely, but not completely, accounted for by concurrent depressed affect, with criterion symptoms reflecting intrusion and arousal most likely to show a specific effect. Although previous research examined stressors from the distant past, here the role of PTSD as a mediator of the trauma-health relation was demonstrated with recent disaster exposure and acute PTSD, in a very different population

The ATXN1 and TRIM31 genes are related to intelligence in an ADHD background: Evidence from a large collaborative study totaling 4,963 Subjects.

Intelligence is a highly heritable trait for which it has proven difficult to identify the actual genes. In the past decade, five whole-genome linkage scans have suggested genomic regions important to human intelligence; however, so far none of the responsible genes or variants in those regions have been identified. Apart from these regions, a handful of candidate genes have been identified, although most of these are in need of replication. The recent growth in publicly available data sets that contain both whole genome association data and a wealth of phenotypic data, serves as an excellent resource for fine mapping and candidate gene replication. We used the publicly available data of 947 families participating in the International Multi-Centre ADHD Genetics (IMAGE) study to conduct an in silico fine mapping study of previously associated genomic locations, and to attempt replication of previously reported candidate genes for intelligence. Although this sample was ascertained for attention deficit/hyperactivity disorder (ADHD), intelligence quotient (IQ) scores were distributed normally. We tested 667 single nucleotide polymorphisms (SNPs) within 15 previously reported candidate genes for intelligence and 29451 SNPs in five genomic loci previously identified through whole genome linkage and association analyses. Significant SNPs were tested in four independent samples (4,357 subjects), one ascertained for ADHD, and three population-based samples. Associations between intelligence and SNPs in the ATXN1 and TRIM31 genes and in three genomic locations showed replicated association, but only in the samples ascertained for ADHD, suggesting that these genetic variants become particularly relevant to IQ on the background of a psychiatric disorder

The WISC-III Freedom From Distractibility factor: It’s utility in identifying children with Attention Deficit Hyperactivity Disorder.

Factor analytic studies of the Wechsler Intelligence Scale for Children—Revised (WISC–R; Wechsler, 1974) have consistently identified what is commonly known as the Freedom From Distractibility (FFD) factor, consisting of the Arithmetic, Digit Span, and Coding subtests (Kaufman, 1979). Support for the validity of this factor stems in part from studies that found significant correlations between the WISC–R FFD subtests and other established measures of attention, such as Continuous Performance Tests (Klee & Garfinkel, 1983) and teacher ratings (Reschly & Reschly, 1979). Additional support comes from investigations that detected significantly lower FFD scores among groups of children with attention deficit hyperactivity disorder (ADHD; American Psychiatric Association, 1987) in comparison with control children (Lufi, Cohen, & Parish-Plass, 1990)

An attribution training study with learning disabled children.

Based on the success of attribution training programs in alleviating learned helplessness and upon current research suggesting that some learning disabled children may be experiencing learned helplessness, it was the purpose of the present investigation to determine whether altering causal attributions for failure would enable helpless learning disabled children to deal more effectively with failure in an experimental reading situation. Sixteen "helpless" learning disabled students were assigned to an attribution training group or to an assessment control group. The results revealed that following training, the subjects in the attribution training group demonstrated greater reading persistence, showed significant increases in effort attributions for failure as well as more internal attributions for achievement situations when compared to subjects in the control group. Treatment gains for effort attributions and for reading persistence were maintained at follow—up. Implications for remedial programs are discussed

Adapting an Emerging Empirically Supported Cognitive Behavioral Therapy for Adults With ADHD and Comorbid Complications an example of two case studies

Attention-deficit/hyperactivity disorder (ADHD) is commonly considered a disorder thataffects children and adolescents; however, follow-up studies of those diagnosed with ADHDindicate significant continuation and impairment into adulthood. For these adults, pharmacotherapy is effective in some cases, but residual symptoms and secondary problematic behaviors resulting from ADHD symptoms (e.g., depressed mood) are typical. Several researchers have identified cognitive-behavioral approaches as a promising adjunct to pharmacotherapy. In particular, a recently manualized cognitive-behavioral therapy has demonstrated significant reductions in ADHD symptoms in a controlled study. The primary purpose of this article is to demonstrate the potential of this approach. To do so, we review two case studies of adults diagnosed with ADHD to illustrate (a) the heterogeneity associated with ADHD cases and the unique challenges they present, (b) issues related to comorbid disorders and symptoms with ADHD, and (c) how to adapt this emerging empirically supported treatment

Multi-method assessment of Attention Deficit Hyperactivity Disorder: The diagnostic utility of clinic-based tests.

Investigated the utility of two clinic-based tests, the Matching Familiar Figures Test (MFFT; Kagan, 1966) and a version of the Continuous Performance Test (CPT; Gordon, 1983), in the assessment of children with attention-deficit hyperactivity disorder (ADHD). At a group level of analysis, scores on the CPT and MFFT were found to share little variance with parent and teacher report on several behavior rating scales used to evaluate ADHD. Further, clinic test scores, either alone or in combination, resulted in classification decisions that frequently disagreed with a diagnosis of ADHD based on parent interview and behavior-rating-scale data. The limited utility of currently available tests in the evaluation of ADHD suggests the need to develop clinic-based measures of sufficient ecological validity, which can be used in conjunction with parent and teacher report

Parenting stress among families of children with Attention Deficit Hyperactivity Disorder

Prior research has shown that parenting stress levels can be quite high among families of children with attention deficit hyperactivity disorder (ADHD). This study investigated the degree to which such stress was related not only to the child's ADHD, but also to various other child, parent, and family—environment circumstances. Multimethod assessments were conducted on 104 clinic-referred children with ADHD. Data collected from these subjects were entered into hierarchical multiple-regression analyses, utilizing the Parenting Stress Index as the criterion. The results showed that child and parent characteristics accounted for a substantial portion of the variance in overall parenting stress. The child's oppositional—defiant behavior and maternal psychopathology were especially potent predictors. The severity of the child's ADHD, the child's health status, and maternal health status also emerged as significant predictors. These findings are discussed in terms of their impact upon the clinical management of children with ADHD

Biological factors in Attention Deficit Hyperactivity Disorder.

For a number of years, clinicians and researchers have recognized the existence of a subgrouping of children who exhibit chronic and pervasive signs of inattention, impulsivity, and physical restlessness, as well as deficiencies in rule-governed behavior, which deviate significantly from age and gender expectations (Barkley; 1981; Ross & Ross, 1982; Wender, 1971). Since first being identified by Still (1902), this particular pattern of behavioral difficulties has undergone numerous changes in the diagnostic terminology used to describe it. Attention Deficit Disorder (with or without Hyperactivity), Hyperkinesis, Hyperkinetic Reaction of Childhood, Hyperactive Child Syndrome, Minimal Brain Damage, and Minimal Brain Dysfunction are some of the many labels that have been applied to this disorder in the past. With the arrival of the recently revised third edition of the Diagnostic and Statistical Manual (DSM III-R, American Psychiatric Association, 1987), this same behavioral constellation is now known as Attention Deficit- Hyperactivity Disorder (ADHD)