Dual neurocircuitry dysfunctions in disruptive behavior disorders: emotional responding and response inhibition.

BACKGROUND: To determine the functional integrity of the neural systems involved in emotional responding/regulation and response control/inhibition in youth (age 10-18 years) with disruptive behavioral disorders (DBDs: conduct disorder and/or oppositional defiant disorder) as a function of callous-unemotional (CU) traits. METHOD: Twenty-eight healthy youths and 35 youths with DBD [high CU (HCU), n = 18; low CU (LCU), n = 17] performed the fMRI Affective Stroop task. Participants viewed positive, neutral, and negative images under varying levels of cognitive load. A 3-way ANOVA (group×emotion by task) was conducted on the BOLD response data. RESULTS: Youth with DBD-HCU showed significantly less activation of ventromedial prefrontal cortex (vmPFC) and amygdala in response to negative stimuli, compared to healthy youth and youth with DBD-LCU. vmPFC responsiveness was inversely related to CU symptoms in DBD. Youth with DBD-LCU showed decreased functional connectivity between amygdala and regions including inferior frontal gyrus in response to emotional stimuli. Youth with DBD (LCU and HCU) additionally showed decreased insula responsiveness to high load (incongruent trials) compared to healthy youth. Insula responsiveness was inversely related to ADHD symptoms in DBD. CONCLUSIONS: These data reveal two forms of pathophysiology in DBD. One associated with reduced amygdala and vmPFC responses to negative stimuli and related to increased CU traits. Another associated with reduced insula responses during high load task trials and related to ADHD symptoms. Appropriate treatment will need to be individualized according to the patient's specific pathophysiology.

Survey of pharmacists' subtherapeutic INR management and anticoagulation bridging practices.

WHAT IS KNOWN AND OBJECTIVE: Despite extensive warfarin use, optimal management of subtherapeutic international normalized ratios (INRs) remains unclear. This study assessed the differences in bridging practices among pharmacists with varying levels of experience, residency training and prescribing privileges. METHODS: An electronic survey was distributed to two ambulatory care pharmacist e-mail lists. Respondents indicated if they would utilize parenteral anticoagulation bridging in 16 clinical scenarios at three therapeutic time points. The scenarios included patients with atrial fibrillation (AFib) (CHADS2 score of 3-4), AFib (CHADS2 score of 5-6) and venous thromboembolism (VTE). The AFib time points were as follows: anticoagulation initiation, early phase (<1 month) and maintenance phase (>1 month). VTE time points included early phase (<1 month), months 2-3 and maintenance phase (>3 months). RESULTS AND DISCUSSION: The survey was completed by 143 respondents. In only three of the scenarios did >50% of respondents indicate they would utilize parenteral anticoagulation bridging. No statistically significant differences in bridging practices were identified between pharmacists providing anticoagulation services in different clinic settings. However, there were significant differences in bridging practices between pharmacists with varying levels of experience, residency training and prescribing privileges in some, but not all of the scenarios. WHAT IS NEW AND CONCLUSION: The standards of care for subtherapeutic INRs warrant further definition.

Development of a disposable pyruvate biosensor to determine pungency in onions (Allium cepa L.).

A disposable prototype pyruvate biosensor was constructed using pyruvate oxidase immobilised on mediated meldolas blue electrodes to determine pungency in onions (Allium cepa L.). The optimum operating potential was +150 mV (versus Ag/AgCl). A strong correlation between the biosensor response and untreated onion juice of known pyruvate concentration 2-12 micromol/g fresh weight (FW) was demonstrated. The biosensor was able to differentiate between low and high pungency onions. The detection limit using 1 unit of pyruvate oxidase was 1-2 micromol/g FW. Optimum concentrations of co-factors TPP, FAD and MgSO4 comprising the enzyme cocktail were determined as being 0.04, 0.1 and 30 mM, respectively.

Development of a common biosensor format for an enzyme based biosensor array to monitor fruit quality.

Individual enzyme-based biosensors involving three-electrode systems were developed for the detection of analytes comprising markers of the stage of maturity and quality in selected fruits of economic importance to tropical countries. Importantly, a common fabrication format has been developed to simplify manufacture and allow future integration of the individual sensors into a single multi-sensor array. Specifically, sensors for beta-D-glucose, total D-glucose, sucrose and ascorbic acid have been developed. Pectin, a natural polysaccharide present in plant cells, was used as a novel matrix to enhance enzyme entrapment and stabilisation in the sensors. Except for ascorbic acid, all the sensors function via the detection of enzymatically generated H2O2 at rhodinised carbon electrodes. Since ascorbic acid is electrochemically active at the working potential chosen (+350 mV vs. Ag/AgCl), it was measured directly. Enzyme sensors demonstrated expected response with respect to their substrates, typically 0-0.8 microA/20 mm2 electrode area response over analyte ranges of 0-7 mM. Interferences related to electrochemically active compounds present in fruits under study were significantly reduced by inclusion of a suitable cellulose acetate (CA) membrane or by enzymatic inactivation with ascorbate oxidase. Initial development was carried out into production of biosensor arrays. CA membranes were used to improve the linear range of the sensors, producing up to a fivefold improvement in the detection range compared to sensors without an additional diffusion barrier.

Patients' perceptions of overall function, pain, and appearance after primary posterior instrumentation and fusion for idiopathic scoliosis.

STUDY DESIGN: This outcome study used patients' responses to the Scoliosis Research Society Outcomes Instrument to discriminate among patients who had undergone surgery for correction of juvenile or adolescent idiopathic scoliosis. OBJECTIVES: To evaluate a surgically treated population by using the SRS Outcomes Instrument. SUMMARY OF BACKGROUND DATA: The Scoliosis Research Society outcomes instrument was developed to help evaluate patient-perceived outcomes after treatment for idiopathic scoliosis. It includes 24 questions designed to investigate seven domains. METHODS: Eligible patients underwent posterior surgery for the first time before their 21st birthdays. One surgeon performed the surgery at one medical center. Of 168 eligible patients, 121 (72%) completed the Scoliosis Research Society outcomes questionnaire. RESULTS: Females reported better outcomes in the function after surgery (P = 0.005) and self-image after surgery (P = 0.01) domains. Preoperative curve pattern comparison demonstrated a significant difference in self-image after surgery among four groups classified according to curve pattern. The thoracolumbar and lumbar group recorded image scores of 5, the highest possible score, 85% of the time. The King-Moe (KM) V group scored 5, 75% of the time; the KM I and II group 48%; and the KM III and IV group 46% (P = 0.0015). After eliminating confounding variables, it was found that white patients reported experiencing less pain in follow-up than did black patients (P = 0.0098). Results were also suggestive that less pain was associated with increased number of fused vertebrae (P = 0.027). CONCLUSIONS: The strongest predictors of self-perceived favorable outcome among patients were female sex and white race. It is also suggested that longer fusions to L1 through L3 lead to less perceived pain than with shorter fusions.

On-line monitoring of glucose, glutamate and glutamine during mammalian cell cultivations.

Amperometric biosensors (based on rhodinised carbon electrodes) for glucose, glutamine and glutamate were constructed. The sensors were incorporated into a three cell parallel FIA system and used to monitor the three analytes on-line during two mammalian cell perfusion cultures. All measurements were made simultaneously from undiluted media sample. Use of the FIA system enabled easy and rapid exchange of the sensors, during cultivation. The inclusion of a calibration step, regularly for all sensors, helped to maintain the accuracy of all measurements. Comparison with off-line measurements indicated that all three biosensors operated successfully, providing accurate information.

The effect of pitressin on esophageal blood flow of the dog.

In a previous study on canine esophagus, we reported that intravenous infusion of isoproterenol caused mucosal (i.e., mucosal + submucosal) vasodilation only in the lower esophageal sphincter (but not in the body) and muscularis vasodilation only in the body (not in the lower esophageal sphincter). In the present study, we have investigated in dogs whether these esophageal tissues also exhibit a similar difference in their vasoconstrictory response to intravenous infusion of pitressin. All measurements were made before (basal) and after infusion of 0.02 U pitressin.min-1.kg-1 for 15 min. Pitressin significantly decreased portal venous pressure and blood flow, and increased vascular resistance of all tissues of the esophagus. This vasoconstriction of the tissues, however, was higher in the squamous mucosa of the body than in the columnar mucosa of the lower esophageal sphincter. In contrast, it was higher in the smooth muscle of the lower esophageal sphincter than in the striated muscle of the body. These data together with those of our previous report on isoproterenol demonstrate that pitressin causes a pronounced vasoconstriction in those esophageal tissues where isoproterenol had no effect. Conversely, pitressin causes least vasoconstriction in those tissues where isoproterenol produced a significant vasodilation. These differences could be the result of partial agonist actions or differences in receptor density or in receptor-effector coupling mechanism.