Primary Care Physicians’ Knowledge of and Experience with Pharmacogenetic Testing

It is anticipated that as the range of drugs for which pharmacogenetic testing becomes available expands, primary care physicians (PCPs) will become major users of these tests. To assess their training, familiarity, and attitudes toward pharmacogenetic testing in order to identify barriers to uptake that may be addressed at this early stage of test use, we conducted a national survey of a sample of PCPs. Respondents were mostly white (79%), based primarily in community-based primary care (81%) and almost evenly divided between family medicine and internal medicine. The majority of respondents had heard of PGx testing and anticipated that these tests are or would soon become a valuable tool to inform drug response. However, only a minority of respondents (13%) indicated they felt comfortable ordering PGx tests and almost a quarter reported not having any education about pharmacogenetics

Activation During Observed Parent–Child Interactions with Anxious Youths: A Pilot Study

Parent–child interaction paradigms are often used to observe dysfunctional family processes; however, the influence of such tasks on a participant’s level of activation remain unclear. The aim of this pilot project is to explore the stimulus value of interaction paradigms that have been commonly used in child anxiety research. Twenty-nine parent–child dyads with clinically anxious (n = 16) and non-anxious (n = 13) youths engaged in a series of tasks (threat and non-threat) used in previous studies of parenting and youth anxiety. Heart rate (HR) data, as an indicator of physiological activation, were collected across tasks, and participants rated the perceived representativeness of their interactions in the laboratory to their usual behavior at home. Significant HR changes were observed for both parent and child. Change in child HR from baseline to non-threat task was smaller than change in HR from baseline to threat tasks. Change in parent HR from baseline to ambiguous situations tasks was smaller than changes from baseline to other threat tasks. Differences in HR change between anxious and non-anxious children were explored. Participants rated laboratory interactions as similar to those experienced in the home. Results suggest that presumably emotionally-charged discussion tasks may produce increased activation compared to tasks that were designed to be more neutral. Implications for future research and limitations are discussed

A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.

There is great potential for host-based gene expression analysis to impact the early diagnosis of infectious diseases. In particular, the influenza pandemic of 2009 highlighted the challenges and limitations of traditional pathogen-based testing for suspected upper respiratory viral infection. We inoculated human volunteers with either influenza A (A/Brisbane/59/2007 (H1N1) or A/Wisconsin/67/2005 (H3N2)), and assayed the peripheral blood transcriptome every 8 hours for 7 days. Of 41 inoculated volunteers, 18 (44%) developed symptomatic infection. Using unbiased sparse latent factor regression analysis, we generated a gene signature (or factor) for symptomatic influenza capable of detecting 94% of infected cases. This gene signature is detectable as early as 29 hours post-exposure and achieves maximal accuracy on average 43 hours (p = 0.003, H1N1) and 38 hours (p-value = 0.005, H3N2) before peak clinical symptoms. In order to test the relevance of these findings in naturally acquired disease, a composite influenza A signature built from these challenge studies was applied to Emergency Department patients where it discriminates between swine-origin influenza A/H1N1 (2009) infected and non-infected individuals with 92% accuracy. The host genomic response to Influenza infection is robust and may provide the means for detection before typical clinical symptoms are apparent

Gene expression profiles link respiratory viral infection, platelet response to aspirin, and acute myocardial infarction

Background Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated blood gene expression signature of respiratory viral infection (viral GES) was associated with MI and 2) respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet GES) of platelet function in response to aspirin that is associated with MI. Methods A previously defined viral GES was projected into blood RNA data from 594 patients undergoing elective cardiac catheterization and used to classify patients as having evidence of viral infection or not and tested for association with acute MI using logistic regression. A previously defined platelet GES was projected into blood RNA data from 81 healthy subjects before and after exposure to four respiratory viruses: Respiratory Syncytial Virus (RSV) (n=20), Human Rhinovirus (HRV) (n=20), Influenza A virus subtype H1N1 (H1N1) (n=24), Influenza A Virus subtype H3N2 (H3N2) (n=17). We tested for the change in platelet GES with viral exposure using linear mixed-effects regression and by symptom status. Results In the catheterization cohort, 32 patients had evidence of viral infection based upon the viral GES, of which 25% (8/32) had MI versus 12.2%(69/567) among those without evidence of viral infection (OR 2.3; CI [1.03-5.5], p=0.04). In the infection cohorts, only H1N1 exposure increased platelet GES over time (time course p-value = 1e-04). Conclusions A viral GES of non-specific, respiratory viral infection was associated with acute MI; 18% of the top 49 genes in the viral GES are involved with hemostasis and/or platelet aggregation. Separately, H1N1 exposure, but not exposure to other respiratory viruses, increased a platelet GES previously shown to be associated with MI. Together, these results highlight specific genes and pathways that link viral infection, platelet activation, and MI especially in the case of H1N1 influenza infection

Effect of maternal panic disorder on mother-child interaction and relation to child anxiety and child self-efficacy

To determine whether mothers with panic disorder with or without agoraphobia interacted differently with their children than normal control mothers, 86 mothers and their adolescents (aged between 13 and 23 years) were observed during a structured play situation. Maternal as well as adolescent anxiety status was assessed according to a structured diagnostic interview. Results showed that mothers with panic disorder/agoraphobia showed more verbal control, were more criticizing and less sensitive during mother-child interaction than mothers without current mental disorders. Moreover, more conflicts were observed between mother and child dyadic interactions when the mother suffered from panic disorder. The comparison of parenting behaviors among anxious and non-anxious children did not reveal any significant differences. These findings support an association between parental over-control and rejection and maternal but not child anxiety and suggest that particularly mother anxiety status is an important determinant of parenting behavior. Finally, an association was found between children’s perceived self-efficacy, parental control and child anxiety symptoms

Paediatric obsessive-compulsive disorder and depressive symptoms: clinical correlates and CBT treatment outcomes.

Depression frequently co-occurs with paediatric obsessive-compulsive disorder (OCD), yet the clinical correlates and impact of depression on CBT outcomes remain unclear. The prevalence and clinical correlates of depression were examined in a paediatric specialist OCD-clinic sample (N = 295; Mean = 15 [7 - 18] years, 42 % female), using both dimensional (Beck Depression Inventory-youth; n = 261) and diagnostic (Development and Wellbeing Assessment; n = 127) measures of depression. The impact of depressive symptoms and suspected disorders on post-treatment OCD severity was examined in a sub-sample who received CBT, with or without SSRI medication (N = 100). Fifty-one per-cent of patients reported moderately or extremely elevated depressive symptoms and 26 % (95 % CI: 18 - 34) met criteria for a suspected depressive disorder. Depressive symptoms and depressive disorders were associated with worse OCD symptom severity and global functioning prior to CBT. Individuals with depression were more likely to be female, have had a psychiatric inpatient admission and less likely to be attending school (ps < 0.01). OCD and depressive symptom severity significantly decreased after CBT. Depressive symptoms and depressive disorders predicted worse post-treatment OCD severity (βs = 0.19 and 0.26, ps < 0.05) but became non-significant when controlling for pre-treatment OCD severity (βs = 0.05 and 0.13, ns). Depression is common in paediatric OCD and is associated with more severe OCD and poorer functioning. However, depression severity decreases over the course of CBT for OCD and is not independently associated with worse outcomes, supporting the recommendation for treatment as usual in the presence of depressive symptoms

Facing the Beast Apart Together: Fear in Boys and Girls after Processing Information about Novel Animals Individually or in a Duo

In this experimental study, we made an attempt to examine gender-related peer influences on childhood fear. Nine- to 12-year-old boys and girls were provided with ambiguous and positive information about novel animals and then asked to provide a subjective fear rating of the animals under two conditions: fear of one animal was assessed individually by the child on its own, whereas fear of the other animal was measured after a brief discussion on fear-related issues with a same-gender peer. Results indicated that children who completed the FBQ after a discussion with a same-gender peer displayed lower fear beliefs scores than children who completed the questionnaire fully on their own. This fear-suppression effect was mainly evident in boys after hearing ambiguous information about the novel animals. The implications of these findings are briefly discussed

Superparamagnetic properties of hemozoin

We report that hemozoin nanocrystals demonstrate superparamagnetic properties, with direct measurements of the synthetic hemozoin magnetization. The results show that the magnetic permeability constant varies from mu = 4585 (at -20 degrees C) to 3843 (+20 degrees C), with the values corresponding to a superparamagnetic system. Similar results were obtained from the analysis of the diffusion separation of natural hemozoin nanocrystals in the magnetic field gradient, with mu = 6783 exceeding the value obtained in direct measurements by the factor of 1.8. This difference is interpreted in terms of structural differences between the synthetic and natural hemozoin. The ab initio analysis of the hemozoin elementary cell showed that the Fe3+ ion is in the high-spin state (S = 5/2), while the exchange interaction between Fe3+ electron-spin states was much stronger than k(B)T at room temperature. Thus, the spin dynamics of the neighboring Fe3+ ions are strongly correlated, lending support to the superparamagnetism