Acute Exposure to Stress Improves Performance in Trace Eyeblink Conditioning and Spatial Learning Tasks in Healthy Men

ERIC Educational Resources Information Center

Duncko, Roman; Cornwell, Brian; Cui, Lihong; Merikangas, Kathleen R.; Grillon, Christian

2007-01-01

The present study investigated the effects of acute stress exposure on learning performance in humans using analogs of two paradigms frequently used in animals. Healthy male participants were exposed to the cold pressor test (CPT) procedure, i.e., insertion of the dominant hand into ice water for 60 sec. Following the CPT or the control procedure,…

Nicotinic agonist-induced improvement of vigilance in mice in the 5-choice continuous performance test

PubMed Central

YOUNG, Jared W; MEVES, Jessica M; GEYER, Mark A

2012-01-01

Impaired attentional processing is prevalent in numerous neuropsychiatric disorders and may negatively impact other cognitive and functional domains. Nicotine – a nonspecific nicotinic acetylcholine receptor (nAChR) agonist – improves vigilance in healthy subjects and schizophrenia patients as measured by continuous performance tests (CPTs), but the nAChR mediating this effect remains unclear. Here we examine the effects of: a) nicotine; b) the selective α7 nAChR agonist PNU 282987; and c) the selective α4β2 nAChR agonist ABT-418 alone and in combination with scopolamine-induced disruption of mouse 5-choice (5C-)CPT performance. This task requires the inhibition of responses to non-target stimuli as well as active responses to target stimuli, consistent with human CPTs. C57BL/6N mice were trained to perform the 5C-CPT. Drug effects were examined in extended session and variable stimulus-duration challenges of performance. Acute drug effects on scopolamine-induced disruption in performance were also investigated. Nicotine and ABT-418 subtly but significantly improved performance of normal mice and attenuated scopolamine-induced disruptions in the 5C-CPT. PNU 282–987 had no effects on performance. The similarity of nicotine and ABT-418 effects provides support for an α4β2 nAChR mechanism of action for nicotine-induced improvement in attention/vigilance. Moreover, the data provide pharmacological predictive validation for the 5C-CPT because nicotine improved and scopolamine disrupted normal performance of the task, consistent with healthy humans in the CPT. Future studies using more selective agonists may result in more robust improvements in performance. PMID:23201359

Relations between Response Trajectories on the Continuous Performance Test and Teacher-Rated Problem Behaviors in Preschoolers

PubMed Central

Allan, Darcey M.; Lonigan, Christopher J.

2014-01-01

Although both the Continuous Performance Test (CPT) and behavior rating scales are used in both practice and research to assess inattentive and hyperactive/impulsive behaviors, the correlations between performance on the CPT and teachers' ratings are typically only small-to-moderate. This study examined trajectories of performance on a low target-frequency visual CPT in a sample of preschool children and how these trajectories were associated with teacher-ratings of problem behaviors (i.e., inattention, hyperactivity/impulsivity [H/I], and oppositional/defiant behavior). Participants included 399 preschool children (Mean age = 56 months; 49.4% female; 73.7% White/Caucasian). An ADHD-rating scale was completed by teachers, and the CPT was completed by the preschoolers. Results showed that children's performance across four temporal blocks on the CPT was not stable across the duration of the task, with error rates generally increasing from initial to later blocks. The predictive relations of teacher-rated problem behaviors to performance trajectories on the CPT were examined using growth curve models. Higher rates of teacher-reported inattention and H/I were uniquely associated with higher rates of initial omission errors and initial commission errors, respectively. Higher rates of teacher-reported overall problem behaviors were associated with increasing rates of omission but not commission errors during the CPT; however, the relation was not specific to one type of problem behavior. The results of this study indicate that the pattern of errors on the CPT in preschool samples is complex and may be determined by multiple behavioral factors. These findings have implications for the interpretation of CPT performance in young children. PMID:25419645

Relations between response trajectories on the continuous performance test and teacher-rated problem behaviors in preschoolers.

PubMed

Allan, Darcey M; Lonigan, Christopher J

2015-06-01

Although both the continuous performance test (CPT) and behavior rating scales are used in both practice and research to assess inattentive and hyperactive/impulsive behaviors, the correlations between performance on the CPT and teachers' ratings are typically only small-to-moderate. This study examined trajectories of performance on a low target-frequency visual CPT in a sample of preschool children and how these trajectories were associated with teacher-ratings of problem behaviors (i.e., inattention, hyperactivity/impulsivity [H/I], and oppositional/defiant behavior). Participants included 399 preschool children (mean age = 56 months; 49.4% female; 73.7% White/Caucasian). An attention deficit/hyperactivity disorder (ADHD) rating scale was completed by teachers, and the CPT was completed by the preschoolers. Results showed that children's performance across 4 temporal blocks on the CPT was not stable across the duration of the task, with error rates generally increasing from initial to later blocks. The predictive relations of teacher-rated problem behaviors to performance trajectories on the CPT were examined using growth curve models. Higher rates of teacher-reported inattention and H/I were uniquely associated with higher rates of initial omission errors and initial commission errors, respectively. Higher rates of teacher-reported overall problem behaviors were associated with increasing rates of omission but not commission errors during the CPT; however, the relation was not specific to 1 type of problem behavior. The results of this study indicate that the pattern of errors on the CPT in preschool samples is complex and may be determined by multiple behavioral factors. These findings have implications for the interpretation of CPT performance in young children. (c) 2015 APA, all rights reserved).

Impact of Threat Level, Task Instruction, and Individual Characteristics on Cold Pressor Pain and Fear among Children and Their Parents.

PubMed

Boerner, Katelynn E; Noel, Melanie; Birnie, Kathryn A; Caes, Line; Petter, Mark; Chambers, Christine T

2016-07-01

The cold pressor task (CPT) is increasingly used to induce experimental pain in children, but the specific methodology of the CPT is quite variable across pediatric studies. This study examined how subtle variations in CPT methodology (eg. provision of low- or high-threat information regarding the task; provision or omission of maximum immersion time) may influence children's and parents' perceptions of the pain experience. Forty-eight children (8 to 14 years) and their parents were randomly assigned to receive information about the CPT that varied on 2 dimensions, prior to completing the task: (i) threat level: high-threat (task described as very painful, high pain expressions depicted) or low-threat (standard CPT instructions provided, low pain expressions depicted); (ii) ceiling: informed (provided maximum immersion time) or uninformed (information about maximum immersion time omitted). Parents and children in the high-threat condition expected greater child pain, and these children reported higher perceived threat of pain and state pain catastrophizing. For children in the low-threat condition, an informed ceiling was associated with less state pain catastrophizing during the CPT. Pain intensity, tolerance, and fear during the CPT did not differ by experimental group, but were predicted by child characteristics. Findings suggest that provision of threatening information may impact anticipatory outcomes, but experienced pain was better explained by individual child variables. © 2015 World Institute of Pain.

Brain Activity Associated With Attention Deficits Following Chemotherapy for Childhood Acute Lymphoblastic Leukemia.

PubMed

Fellah, Slim; Cheung, Yin T; Scoggins, Matthew A; Zou, Ping; Sabin, Noah D; Pui, Ching-Hon; Robison, Leslie L; Hudson, Melissa M; Ogg, Robert J; Krull, Kevin R

2018-05-21

The impact of contemporary chemotherapy treatment for childhood acute lymphoblastic leukemia on central nervous system activity is not fully appreciated. Neurocognitive testing and functional magnetic resonance imaging (fMRI) were obtained in 165 survivors five or more years postdiagnosis (average age = 14.4 years, 7.7 years from diagnosis, 51.5% males). Chemotherapy exposure was measured as serum concentration of methotrexate following high-dose intravenous injection. Neurocognitive testing included measures of attention and executive function. fMRI was obtained during completion of two tasks, the continuous performance task (CPT) and the attention network task (ANT). Image analysis was performed using Statistical Parametric Mapping software, with contrasts targeting sustained attention, alerting, orienting, and conflict. All statistical tests were two-sided. Compared with population norms, survivors demonstrated impairment on number-letter switching (P < .001, a measure of cognitive flexibility), which was associated with treatment intensity (P = .048). Task performance during fMRI was associated with neurocognitive dysfunction across multiple tasks. Regional brain activation was lower in survivors diagnosed at younger ages for the CPT (bilateral parietal and temporal lobes) and the ANT (left parietal and right hippocampus). With higher serum methotrexate exposure, CPT activation decreased in the right temporal and bilateral frontal and parietal lobes, but ANT alerting activation increased in the ventral frontal, insula, caudate, and anterior cingulate. Brain activation during attention and executive function tasks was associated with serum methotrexate exposure and age at diagnosis. These findings provide evidence for compromised and compensatory changes in regional brain function that may help clarify the neural substrates of cognitive deficits in acute lymphoblastic leukemia survivors.

Response inhibition predicts painful task duration and performance in healthy individuals performing a cold pressor task in a motivational context.

PubMed

Karsdorp, P A; Geenen, R; Vlaeyen, J W S

2014-01-01

Long-term avoidance of painful activities has shown to be dysfunctional in chronic pain. Pain may elicit escape or avoidance responses automatically, particularly when pain-related fear is high. A conflict may arise between opposing short-term escape/avoidance goals to reduce pain and long-term approach goals to receive a reward. An inhibitory control system may resolve this conflict. It was hypothesized that reduced response inhibition would be associated with greater escape/avoidance during pain, particularly among subjects with higher pain-related fear. Response inhibition was measured with the stop-signal task, and pain-related fear with the Fear of Pain Questionnaire. Participants completed a tone-detection task (TDT) in which they could earn money while being exposed to cold pressor pain. Escape/avoidance was operationalized as the hand immersion time during a cold pressor task (CPT) and the performance on the TDT. Poorer response inhibition was associated with shorter CPT immersion duration and with worse TDT performance. Pain after the CPT was associated with pain-related fear, but not with response inhibition. No supportive evidence was found for the hypothesis that the relation between inhibition and escape/avoidance would be most pronounced for those with higher pain-related fear. In contrast, the relation between response inhibition and number of hits on the TDT was most pronounced for those with lower pain-related fear. The findings suggest that individuals with a stronger ability to inhibit responses in a stop-signal task are better able to inhibit escape/avoidance responses elicited by pain, in the service of a conflicting approach goal. © 2013 European Pain Federation - EFIC®

Null tDCS Effects in a Sustained Attention Task: The Modulating Role of Learning

PubMed Central

Jacoby, Noa; Lavidor, Michal

2018-01-01

The purpose of this study was to investigate sustained attention through modulation of the fronto-cerebral network with transcranial direct current stimulation (tDCS) in adults with attention-deficit/hyperactivity disorder (ADHD) and control participants. Thirty-seven participants (21 with ADHD) underwent three separate sessions (baseline, active tDCS, and sham) and performed the MOXO Continuous Performance Test (CPT). We applied double anodal stimulation of 1.8 mA tDCS for 20 min over the left and right dorsolateral prefrontal cortex (DLPFC), with the cathode over the cerebellum. Baseline session revealed significant differences between ADHD and control participants in the MOXO-CPT attention and hyperactivity scores, validating the MOXO as a diagnostic tool. However, there were no tDCS effects in most MOXO-CPT measures, except hyperactivity, due to a significant learning effect. We conclude that learning and repetition effects in cognitive tasks need to be considered when designing within-subjects tDCS experiments, as there are natural improvements between sessions that conceal potential stimulation effects. PMID:29681876

Null tDCS Effects in a Sustained Attention Task: The Modulating Role of Learning.

PubMed

Jacoby, Noa; Lavidor, Michal

2018-01-01

The purpose of this study was to investigate sustained attention through modulation of the fronto-cerebral network with transcranial direct current stimulation (tDCS) in adults with attention-deficit/hyperactivity disorder (ADHD) and control participants. Thirty-seven participants (21 with ADHD) underwent three separate sessions (baseline, active tDCS, and sham) and performed the MOXO Continuous Performance Test (CPT). We applied double anodal stimulation of 1.8 mA tDCS for 20 min over the left and right dorsolateral prefrontal cortex (DLPFC), with the cathode over the cerebellum. Baseline session revealed significant differences between ADHD and control participants in the MOXO-CPT attention and hyperactivity scores, validating the MOXO as a diagnostic tool. However, there were no tDCS effects in most MOXO-CPT measures, except hyperactivity, due to a significant learning effect. We conclude that learning and repetition effects in cognitive tasks need to be considered when designing within-subjects tDCS experiments, as there are natural improvements between sessions that conceal potential stimulation effects.

Desynchronization of Theta-Phase Gamma-Amplitude Coupling during a Mental Arithmetic Task in Children with Attention Deficit/Hyperactivity Disorder.

PubMed

Kim, Jun Won; Kim, Bung-Nyun; Lee, Jaewon; Na, Chul; Kee, Baik Seok; Min, Kyung Joon; Han, Doug Hyun; Kim, Johanna Inhyang; Lee, Young Sik

2016-01-01

Theta-phase gamma-amplitude coupling (TGC) measurement has recently received attention as a feasible method of assessing brain functions such as neuronal interactions. The purpose of this electroencephalographic (EEG) study is to understand the mechanisms underlying the deficits in attentional control in children with attention deficit/hyperactivity disorder (ADHD) by comparing the power spectra and TGC at rest and during a mental arithmetic task. Nineteen-channel EEGs were recorded from 97 volunteers (including 53 subjects with ADHD) from a camp for hyperactive children under two conditions (rest and task performance). The EEG power spectra and the TGC data were analyzed. Correlation analyses between the Intermediate Visual and Auditory (IVA) continuous performance test (CPT) scores and EEG parameters were performed. No significant difference in the power spectra was detected between the groups at rest and during task performance. However, TGC was reduced during the arithmetic task in the ADHD group compared with the normal group (F = 16.70, p < 0.001). The TGC values positively correlated with the IVA CPT scores but negatively correlated with theta power. Our findings suggest that desynchronization of TGC occurred during the arithmetic task in ADHD children. TGC in ADHD children is expected to serve as a promising neurophysiological marker of network deactivation during attention-demanding tasks.

Enhanced Cognitive Rehabilitation to Treat Comorbid TBI and PTSD

DTIC Science & Technology

2017-12-01

S) Amy Jak 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: ajak@ucsd.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES...symptoms resulting from mild to moderate TBI. These practice standards have been organized into a manualized treatment, Cognitive Symptom Management ...Processing Therapy; SMART-CPT=Cognitive Symptom Management and Rehabilitation Therapy combined with CPT; TBI=traumatic brain injury; PTSD=posttraumatic

Caffeine Does Not Modulate Inhibitory Control

ERIC Educational Resources Information Center

Tieges, Zoe; Snel, Jan; Kok, Albert; Ridderinkhof, K. Richard

2009-01-01

The effects of a 3 mg/kg body weight (BW) dose of caffeine were assessed on behavioral indices of response inhibition. To meet these aims, we selected a modified AX version of the Continuous Performance Test (CPT), the stop task, and the flanker task. In three double-blind, placebo-controlled, within-subjects experiments, these tasks were…

Attention.

PubMed

Callahan, Patrick M; Terry, Alvin V

2015-01-01

The ability to focus one's attention on important environmental stimuli while ignoring irrelevant stimuli is fundamental to human cognition and intellectual function. Attention is inextricably linked to perception, learning and memory, and executive function; however, it is often impaired in a variety of neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, depression, and attention deficit hyperactivity disorder (ADHD). Accordingly, attention is considered as an important therapeutic target in these disorders. The purpose of this chapter is to provide an overview of the most common behavioral paradigms of attention that have been used in animals (particularly rodents) and to review the literature where these tasks have been employed to elucidate neurobiological substrates of attention as well as to evaluate novel pharmacological agents for their potential as treatments for disorders of attention. These paradigms include two tasks of sustained attention that were developed as rodent analogues of the human Continuous Performance Task (CPT), the Five-Choice Serial Reaction Time Task (5-CSRTT) and the more recently introduced Five-Choice Continuous Performance Task (5C-CPT), and the Signal Detection Task (SDT) which was designed to emphasize temporal components of attention.

A laboratory study on attentional bias as an underlying mechanism affecting the link between cortisol and performance, leading to a discussion on the nature of the stressor (artificial vs. psychosocial).

PubMed

Lautenbach, Franziska

2017-06-01

Although cortisol is assumed to influence performance by affecting cognition during stressful and competitive situations, to date this assumption has not been tested empirically. Therefore, the aim of this study was to investigate whether the influence of cortisol on performance is mediated by attentional processing of emotional information. Forty-six male golfers were tested in a mixed design. The cold pressor task (CPT) was used to artificially increase cortisol levels in the experimental group relative to the control group, who had to put their forearm in warm water. Before and after water immersion the golfers performed one-armed 1.5-m puts and completed the Sport Emotional Stroop Task. Cortisol was significantly increased in the experimental group (CPT). Further, a significant decrease in attentional bias toward negative sport words was detected in the CPT group. However, no changes in putting performance due to an increase in cortisol were observed in the CPT group. Regarding the cortisol-performance relationship, the nature of the stressor (i.e., artificial vs. psychosocial) seems to play a role, as no connection was found in this study using an artificial stressor, whereas previous research using a psychosocial stressor (e.g., an actual competition) did find a connection. On the basis of these results I cautiously conclude that the subjective appraisal of a stressor, which is arguably higher for a psychosocial stressor, is more relevant for sport performance than just a change in cortisol level. However, as the stress response is psychophysiological in nature, future research should continue to investigate the role of cortisol. Copyright © 2017 Elsevier Inc. All rights reserved.

The effect of mental fatigue on sustained attention: an fNIRS study

NASA Astrophysics Data System (ADS)

Zhang, Zhen; Yang, Hanjun; Cao, Yong; Xu, Fenggang; Jiang, Jin; Jiao, Xuejun

2017-01-01

Sustained attention is the ability to keep focused and vigilance for long time in external stimulation, which was crucial in safe-critical human-machine system. While the ability of sustained attention will decline because of mental fatigue, even lead to serious accidents in fatigue state. Therefore, it is of great significance to explore the impact of fatigue on sustained attention. Functional Near-Infrared Spectroscopy (fNIRS) can measure cerebral hemoglobin in order to reflect cognitive function indirectly. In previous related fatigue studies, monotonous and long-time CPT (continuous performance test task) was often used to explore the performance change and brain activity, but the effect of time on task (TOT) was always involved. In this study, in order to avoid the TOT effect, the sustained attention task and fatigue task were separated. It was adopted in the study that the modified continuous performance test (CPT) was chosen as the sustained attention task and verbal 2-back task as the fatigue induced task. The fNIRS signals were extracted from 10 channels in the prefrontal cortex (PFC) from 20 healthy subjects. Studies found that cerebral lateralization increased significantly from alert to fatigue state in sustained attention task. Besides, Average oxyhemoglobin (HBO) of PFC increased significantly from alert to fatigue task, and the spatial pattern of activity of oxyhemoglobin also changed, which c be sensitive features to fatigue detection.

Developmental Differences in Cognitive Control: Goal Representation and Maintenance during a Continuous Performance Task

ERIC Educational Resources Information Center

Lorsbach, Thomas C.; Reimer, Jason F.

2010-01-01

The present study examined whether younger and older children differ in the use of the goal-related information in a continuous performance task (AX-CPT), and if so, whether those age differences are due to the ability to represent and/or maintain goal information. Experiment 1 compared third- and sixth-grade children in their ability to transform…

How can Continuous Performance Test help to assess inattention when mood and ADHD symptoms coexist?

PubMed

Mesquita, Cintia; Nazar, Bruno P; Pinna, Camilla M S; Rabelo, Beatriz; Serra-Pinheiro, Maria Antonia; Sergeant, Joseph; Mattos, Paulo

2016-09-30

Depression and attention-deficit/hyperactivity disorder (ADHD) are prevalent, and often comorbid, disorders, with varying severity levels among patients. Inattention is a symptom present in both disorders, which often makes their differential diagnosis difficult in clinical practice (depression only versus comorbidity). This study aimed to investigate the influence of depressive symptoms on attention performance using one of the most common tasks in clinical practice, the continuous performance test (CPT). Ninety-three college students (60 men, 33 women) with a mean age of 24 years old were investigated with self-reports and semi-structured interviews for ADHD; the Beck Depression Inventory (BDI) was used for depression ratings. Attention measures were derived from the CPT. There was no correlation between depression and ADHD symptoms; in addition, depression was not correlated with any of the CPT scores; ADHD symptomatology was the only predictor of changes in those CPT variables (commission and omission errors and d prime). ADHD-associated impairment on the CPT was not augmented by the presence of depressive symptoms, making neuropsychological results on this test helpful for the differential diagnosis. When attention deficits are observed in individuals with mild or moderate depression, they are most likely not attributed to depression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Initial Development of an E-cigarette Purchase Task: A Mixed Methods Study

PubMed Central

Cassidy, Rachel N.; Tidey, Jennifer W.; Colby, Suzanne M.; Long, Victoria; Higgins, Stephen T.

2017-01-01

Objectives Behavioral economic purchase tasks, which estimate demand for drugs, have been successfully developed for cigarettes and are widely used. However, a validated purchase task does not yet exist for e-cigarettes. The aim of this project was to identify the relevant units for an e-cigarette purchase task (E-CPT). Methods Focus groups (N=28 participants in 7 groups, 2-7 participants per group) consisting of current e-cigarette users were conducted. Participants discussed their daily use patterns, completed a preliminary E-CPT which asked how many puffs of their e-cigarette they would consume per day at escalating prices, and discussed the extent to which the task accurately reflected their real-world behavior. Groups were recorded and transcribed; analysis focused on statements related to daily consumption and the E-CPT. Results Participants were unlikely to quantify their daily use in terms of puffs, and perceptions about the appropriate unit for an E-CPT varied across device type. Users of first-generation devices (eg, cigalikes) reported that the relevant unit was the individual device/cartridge; however, participants who purchased nicotine liquid for their device emphasized that e-liquid volume in milliliters would better reflect their use. Conclusions Multiple versions of the E-CPT may be necessary to provide valid measures of e-cigarette demand. PMID:28824938

A meta-analysis of decision-making and attention in adults with ADHD.

PubMed

Mowinckel, Athanasia M; Pedersen, Mads Lund; Eilertsen, Espen; Biele, Guido

2015-05-01

Deficient reward processing has gained attention as an important aspect of ADHD, but little is known about reward-based decision-making (DM) in adults with ADHD. This article summarizes research on DM in adult ADHD and contextualizes DM deficits by comparing them to attention deficits. Meta-analytic methods were used to calculate average effect sizes for different DM domains and continuous performance task (CPT) measures. None of the 59 included studies (DM: 12 studies; CPT: 43; both: 4) had indications of publication bias. DM and CPT measures showed robust, small to medium effects. Large effect sizes were found for a drift diffusion model analysis of the CPT. The results support the existence of DM deficits in adults with ADHD, which are of similar magnitude as attention deficits. These findings warrant further examination of DM in adults with ADHD to improve the understanding of underlying neurocognitive mechanisms. © 2014 SAGE Publications.

Pay attention to impulsivity: modelling low attentive and high impulsive subtypes of adult ADHD in the 5-choice continuous performance task (5C-CPT) in female rats.

PubMed

Tomlinson, Anneka; Grayson, Ben; Marsh, Samuel; Harte, Michael K; Barnes, Samuel A; Marshall, Kay M; Neill, Joanna C

2014-08-01

Varying levels of attention and impulsivity deficits are core features of the three subtypes of adult attention deficit-hyperactivity disorder (ADHD). To date, little is known about the neurobiological correlates of these subtypes. Development of a translational animal model is essential to improve our understanding and improve therapeutic strategies. The 5-choice continuous performance task (5C-CPT) in rats can be used to examine different forms of attention and impulsivity. Adult rats were trained to pre-set 5C-CPT criterion and subsequently separated into subgroups according to baseline levels of sustained attention, vigilance, premature responding and response disinhibition in the 5C-CPT. The behavioural subgroups were selected to represent the different subtypes of adult ADHD. Consequently, effects of the clinically used pharmacotherapies (methylphenidate and atomoxetine) were assessed in the different subgroups. Four subgroups were identified: low-attentive (LA), high-attentive (HA), high-impulsive (HI) and low-impulsive (LI). Methylphenidate and atomoxetine produced differential effects in the subgroups. Methylphenidate increased sustained attention and vigilance in LA animals, and reduced premature responding in HI animals. Atomoxetine also improved sustained attention and vigilance in LA animals, and reduced response disinhibition and premature responding in HI animals. This is the first study using adult rats to demonstrate the translational value of the 5C-CPT to select subgroups of rats, which may be used to model the subtypes observed in adult ADHD. Our findings suggest that this as an important paradigm to increase our understanding of the neurobiological underpinnings of adult ADHD-subtypes and their response to pharmacotherapy. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Effects of nicotine on response inhibition and interference control.

PubMed

Ettinger, Ulrich; Faiola, Eliana; Kasparbauer, Anna-Maria; Petrovsky, Nadine; Chan, Raymond C K; Liepelt, Roman; Kumari, Veena

2017-04-01

Nicotine is a cholinergic agonist with known pro-cognitive effects in the domains of alerting and orienting attention. However, its effects on attentional top-down functions such as response inhibition and interference control are less well characterised. Here, we investigated the effects of 7 mg transdermal nicotine on performance on a battery of response inhibition and interference control tasks. A sample of N = 44 healthy adult non-smokers performed antisaccade, stop signal, Stroop, go/no-go, flanker, shape matching and Simon tasks, as well as the attentional network test (ANT) and a continuous performance task (CPT). Nicotine was administered in a within-subjects, double-blind, placebo-controlled design, with order of drug administration counterbalanced. Relative to placebo, nicotine led to significantly shorter reaction times on a prosaccade task and on CPT hits but did not significantly improve inhibitory or interference control performance on any task. Instead, nicotine had a negative influence in increasing the interference effect on the Simon task. Nicotine did not alter inter-individual associations between reaction times on congruent trials and error rates on incongruent trials on any task. Finally, there were effects involving order of drug administration, suggesting practice effects but also beneficial nicotine effects when the compound was administered first. Overall, our findings support previous studies showing positive effects of nicotine on basic attentional functions but do not provide direct evidence for an improvement of top-down cognitive control through acute administration of nicotine at this dose in healthy non-smokers.

The role of motivation in distracting attention away from pain: an experimental study.

PubMed

Verhoeven, Katrien; Crombez, Geert; Eccleston, Christopher; Van Ryckeghem, Dimitri M L; Morley, Stephen; Van Damme, Stefaan

2010-05-01

Research on the effectiveness of distraction as a method of pain control is inconclusive. One mechanism pertains to the motivational relevance of distraction tasks. In this study the motivation to engage in a distraction task during pain was experimentally manipulated. Undergraduate students (N=73) participated in a cold pressor test (CPT) and were randomly assigned to three groups: a distraction-only group performed a tone-detection task during the CPT, a motivated-distraction group performed the same task and received a monetary reward for good task performance, and a control group did not perform the tone-detection task. Results indicated that engagement in the distraction task was better in the motivated-distraction group in comparison with the distraction-only group. Participants in both distraction groups experienced less pain compared to the control group. There were no overall differences in pain intensity between the two distraction groups. The effect of distraction was influenced by the level of catastrophic thinking about pain. For low catastrophizers, both distraction groups reported less pain as compared to the non-distracted control group. This was not the case for high catastrophizers. For high catastrophizers it mattered whether the distraction task was motivationally relevant: high catastrophizers reported less intense pain in the motivated-distraction group, as compared to the non-distracted control group. We conclude that increasing the motivational relevance of the distraction task may increase the effects of distraction, especially for those who catastrophize about pain. Copyright 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Encoding vs. retention: differential effects of cue manipulation on working memory performance in schizophrenia.

PubMed

Javitt, Daniel C; Rabinowicz, Esther; Silipo, Gail; Dias, Elisa C

2007-03-01

Deficits in working memory performance are among the most widely replicated findings in schizophrenia. Roles of encoding vs. memory retention in working memory remain unresolved. The present study evaluated working memory performance in schizophrenia using an AX-type continuous performance test (AX-CPT) paradigm. Participants included 48 subjects with schizophrenia and 27 comparison subjects. Behavior was obtained in 3 versions of the task, which differed based upon ease of cue interoperability. In a simple cue version of the task, cue letters were replaced with red or green circles. In the complex cue version, letter/color conjunctions served as cues. In the base version of the task, patients showed increased rates of false alarms to invalidly cued targets, similar to prior reports. However, when the cue stimuli were replaced with green or red circles to ease interpretation, patients showed similar false alarm rates to controls. When feature conjunction cues were used, patients were also disproportionately affected relative to controls. No significant group by interstimulus interval interaction effects were observed in either the simple or complex cue conditions, suggesting normal retention of information even in the presence of overall performance decrements. These findings suggest first, that cue manipulation disproportionately affects AX-CPT performance in schizophrenia and, second, that substantial behavioral deficits may be observed on working memory tasks even in the absence of disturbances in mnemonic retention.

[Cognitive dysfunction in patients with subclinical hypothyroidism].

PubMed

Fernandes, Robertta Soares Miranda; Alvarenga, Nathália Bueno; Silva, Tamara Inácio da; Rocha, Felipe Filardi da

2011-04-01

Evaluate neuropsychological changes in patients with subclinical hypothyroidism (SH). Cross-sectional study comparing the results of the neuropsychological evaluation of 89 SH patients and 178 individuals without thyroid disease. The participants underwent the following neuropsychological assessment: Conner's Continuous Performance Test (CPT-II), Iowa Gambling Task, Stroop Test, Wisconsin Card Sorting Test (WCST), Verbal Fluency Test (semantic and phonologic categories) and Rey Auditory Verbal Learning Test. Among the neuropsychological tests, patients showed worse performance only in cognitive flexibility (WCST) and the ability to maintain sustained attention (omission errors on the CPT-II). These losses can cause detriments in the daily lives of patients, constituting potential treatment indications.

Temporal Dynamics of Motivation-Cognitive Control Interactions Revealed by High-Resolution Pupillometry

PubMed Central

Chiew, Kimberly S.; Braver, Todd S.

2013-01-01

Motivational manipulations, such as the presence of performance-contingent reward incentives, can have substantial influences on cognitive control. Previous evidence suggests that reward incentives may enhance cognitive performance specifically through increased preparatory, or proactive, control processes. The present study examined reward influences on cognitive control dynamics in the AX-Continuous Performance Task (AX-CPT), using high-resolution pupillometry. In the AX-CPT, contextual cues must be actively maintained over a delay in order to appropriately respond to ambiguous target probes. A key feature of the task is that it permits dissociable characterization of preparatory, proactive control processes (i.e., utilization of context) and reactive control processes (i.e., target-evoked interference resolution). Task performance profiles suggested that reward incentives enhanced proactive control (context utilization). Critically, pupil dilation was also increased on reward incentive trials during context maintenance periods, suggesting trial-specific shifts in proactive control, particularly when context cues indicated the need to overcome the dominant target response bias. Reward incentives had both transient (i.e., trial-by-trial) and sustained (i.e., block-based) effects on pupil dilation, which may reflect distinct underlying processes. The transient pupillary effects were present even when comparing against trials matched in task performance, suggesting a unique motivational influence of reward incentives. These results suggest that pupillometry may be a useful technique for investigating reward motivational signals and their dynamic influence on cognitive control. PMID:23372557

Laterality judgments are not impaired in patients with chronic whiplash associated disorders.

PubMed

Pedler, Ashley; Motlagh, Helena; Sterling, Michele

2013-02-01

Impaired integration of the body schema with motor processes may contribute to painful and/or restricted movement in chronic pain. Laterality judgment tasks assess this integration of the body schema with motor processes. The purpose of this study was to assess if patients with chronic whiplash associated disorders (WAD) are impaired on laterality judgment tasks. Accuracy (ACC) and reaction time (RT) for foot and neck laterality tasks were assessed in 64 (35 female) patients with chronic (>6 months) WAD and 24 (14 female) asymptomatic subjects. Pain characteristics, post-traumatic stress symptoms, cold pain thresholds (CPT) and pressure pain thresholds (PPT) were collected for patients with WAD. The effect of WAD and body part on laterality task performance was assessed. For patients with WAD, the correlations between neck task performance and pain characteristics, post-traumatic stress symptoms and pain thresholds were assessed. There was no effect of group on laterality performance. Subjects showed better RT (p < 0.001) and ACC (p = 0.001) on the neck task in comparison to the foot task. There was a significant correlation between CPT and ACC (r = 0.33) and RT (r = -0.33) on the neck laterality task in patients with WAD. Cervical spine PPT were significantly correlated with accuracy (r = 0.36) and RT (r = 0.29) in patients with WAD. These findings suggest that patients with chronic WAD are not impaired on neck or foot laterality judgment tasks. Laterality training is not indicated in the management of chronic WAD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Network-targeted cerebellar transcranial magnetic stimulation improves attentional control

PubMed Central

Esterman, Michael; Thai, Michelle; Okabe, Hidefusa; DeGutis, Joseph; Saad, Elyana; Laganiere, Simon E.; Halko, Mark A.

2018-01-01

Developing non-invasive brain stimulation interventions to improve attentional control is extremely relevant to a variety of neurologic and psychiatric populations, yet few studies have identified reliable biomarkers that can be readily modified to improve attentional control. One potential biomarker of attention is functional connectivity in the core cortical network supporting attention - the dorsal attention network (DAN). We used a network-targeted cerebellar transcranial magnetic stimulation (TMS) procedure, intended to enhance cortical functional connectivity in the DAN. Specifically, in healthy young adults we administered intermittent theta burst TMS (iTBS) to the midline cerebellar node of the DAN and, as a control, the right cerebellar node of the default mode network (DMN). These cerebellar targets were localized using individual resting-state fMRI scans. Participants completed assessments of both sustained (gradual onset continuous performance task, gradCPT) and transient attentional control (attentional blink) immediately before and after stimulation, in two sessions (cerebellar DAN and DMN). Following cerebellar DAN stimulation, participants had significantly fewer attentional lapses (lower commission error rates) on the gradCPT. In contrast, stimulation to the cerebellar DMN did not affect gradCPT performance. Further, in the DAN condition, individuals with worse baseline gradCPT performance showed the greatest enhancement in gradCPT performance. These results suggest that temporarily increasing functional connectivity in the DAN via network-targeted cerebellar stimulation can enhance sustained attention, particularly in those with poor baseline performance. With regard to transient attention, TMS stimulation improved attentional blink performance across both stimulation sites, suggesting increasing functional connectivity in both networks can enhance this aspect of attention. These findings have important implications for intervention applications of TMS and theoretical models of functional connectivity. PMID:28495634

Heritability of Pain Catastrophizing and Associations with Experimental Pain Outcomes: A Twin Study

PubMed Central

Trost, Zina; Strachan, Eric; Sullivan, Michael; Vervoort, Tine; Avery, Ally R.; Afari, Niloofar

2014-01-01

The current study employed a twin paradigm to examine the genetic and environmental contributions to pain catastrophizing as well as the observed association between pain catastrophizing and cold pressor task (CPT) outcomes. Male and female monozygotic (n=206) and dizygotic twins (n=194) from the University of Washington Twin Registry completed a measure of pain catastrophizing and performed a CPT challenge. As expected, pain catastrophizing emerged as a significant predictor of several CPT outcomes, including cold pressor immersion tolerance, pain tolerance, and delayed pain rating. The heritability estimate for pain catastrophizing was found to be 37% with the remaining 63% of variance attributable to unique environmental influence. Additionally, the observed associations between pain catastrophizing and CPT outcomes were not found attributable to shared genetics or environmental exposure, suggesting a direct relationship between catastrophizing and experimental pain outcomes. This study is the first to examine the heritability of pain catastrophizing and potential processes by which pain catastrophizing is related to experimental pain response. PMID:25599234

COGNITION-CHILDHOOD MALTREATMENT INTERACTIONS IN THE PREDICTION OF ANTIDEPRESSANT OUTCOMES IN MAJOR DEPRESSIVE DISORDER PATIENTS: RESULTS FROM THE iSPOT-D TRIAL.

PubMed

Miller, Shefali; McTeague, Lisa M; Gyurak, Anett; Patenaude, Brian; Williams, Leanne M; Grieve, Stuart M; Korgaonkar, Mayuresh S; Etkin, Amit

2015-08-01

Childhood maltreatment (CM) history has been associated with poor treatment response in major depressive disorder (MDD), but the mechanisms underlying this relationship remain opaque. Dysfunction in the neural circuits for executive cognition is a putative neurobiological consequence of CM that may contribute importantly to adverse clinical outcomes. We used behavioral and neuroimaging measures of executive functioning to assess their contribution to the relationship between CM and antidepressant response in MDD patients. Ninety eight medication-free MDD outpatients participating in the International Study to Predict Optimized Treatment in Depression were assessed at baseline on behavioral neurocognitive measures and functional magnetic resonance imaging during tasks probing working memory (continuous performance task, CPT) and inhibition (Go/No-go). Seventy seven patients completed 8 weeks of antidepressant treatment. Baseline behavioral and neuroimaging measures were assessed in relation to CM (history of childhood physical, sexual, and/or emotional abuse) and posttreatment depression outcomes. Patients with maltreatment exhibited decreased modulation of right dorsolateral prefrontal cortex (DLPFC) activity during working memory updating on the CPT, and a corresponding impairment in CPT behavioral performance outside the scanner. No between-group differences were found for imaging or behavior on the Go/No-go test of inhibition. Greater DLPFC activity during CPT significantly predicted posttreatment symptom improvement in patients without maltreatment, whereas the relationship between DLPFC activity and symptom change was nonsignificant, and in the opposite direction, in patients with maltreatment. The effect of CM on prefrontal circuitry involved in executive function is a potential predictor of antidepressant outcomes. © 2015 Wiley Periodicals, Inc.

Distractibility in Attention/Deficit/ Hyperactivity Disorder (ADHD): the virtual reality classroom.

PubMed

Adams, Rebecca; Finn, Paul; Moes, Elisabeth; Flannery, Kathleen; Rizzo, Albert Skip

2009-03-01

Nineteen boys aged 8 to 14 with a diagnosis of ADHD and 16 age-matched controls were compared in a virtual reality (VR) classroom version of a continuous performance task (CPT), with a second standard CPT presentation using the same projection display dome system. The Virtual Classroom included simulated "real-world" auditory and visual distracters. Parent ratings of attention, hyperactivity, internalizing problems, and adaptive skills on the Behavior Assessment System for Children (BASC) Monitor for ADHD confirmed that the ADHD children had more problems in these areas than controls. The difference between the ADHD group (who performed worse) and the control group approached significance (p = .05; adjusted p = .02) in the Virtual Classroom presentation, and the classification rate of the Virtual Classroom was better than when the standard CPT was used (87.5% versus 68.8%). Children with ADHD were more affected by distractions in the VR classroom than those without ADHD. Results are discussed in relation to distractibility in ADHD.

Event-related wave activity in the EEG provides new marker of ADHD.

PubMed

Alexander, David M; Hermens, Daniel F; Keage, Hannah A D; Clark, C Richard; Williams, Leanne M; Kohn, Michael R; Clarke, Simon D; Lamb, Chris; Gordon, Evian

2008-01-01

This study examines the utility of new measures of event-related spatio-temporal waves in the EEG as a marker of ADHD, previously shown to be closely related to the P3 ERP in an adult sample. Wave activity in the EEG was assessed during both an auditory Oddball and a visual continuous performance task (CPT) for an ADHD group ranging in age from 6 to 18 years and comprising mostly Combined and Inattentive subtypes, and for an age and gender matched control group. The ADHD subjects had less wave activity at low frequencies ( approximately 1 Hz) during both tasks. For auditory Oddball targets, this effect was shown to be related to smaller P3 ERP amplitudes. During CPT, the approximately 1 Hz wave activity in the ADHD subjects was inversely related to clinical and behavioral measures of hyperactivity and impulsivity. CPT wave activity at approximately 1 Hz was seen to "normalise" following treatment with stimulant medication. The results identify a deficit in low frequency wave activity as a new marker for ADHD associated with levels of hyperactivity and impulsivity. The marker is evident across a range of tasks and may be specific to ADHD. While lower approximately 1 Hz activity partly accounts for reduced P3 ERPs in ADHD, the effect also arises for tasks that do not elicit a P3. Deficits in behavioral inhibition are hypothesized to arise from underlying dysregulation of cortical inhibition.

Virtual-reality-based attention assessment of ADHD: ClinicaVR: Classroom-CPT versus a traditional continuous performance test.

PubMed

Neguț, Alexandra; Jurma, Anda Maria; David, Daniel

2017-08-01

Virtual-reality-based assessment may be a good alternative to classical or computerized neuropsychological assessment due to increased ecological validity. ClinicaVR: Classroom-CPT (VC) is a neuropsychological test embedded in virtual reality that is designed to assess attention deficits in children with attention deficit hyperactivity disorder (ADHD) or other conditions associated with impaired attention. The present study aimed to (1) investigate the diagnostic validity of VC in comparison to a traditional continuous performance test (CPT), (2) explore the task difficulty of VC, (3) address the effect of distractors on the performance of ADHD participants and typically-developing (TD) controls, and (4) compare the two measures on cognitive absorption. A total of 33 children diagnosed with ADHD and 42 TD children, aged between 7 and 13 years, participated in the study and were tested with a traditional CPT or with VC, along with several cognitive measures and an adapted version of the Cognitive Absorption Scale. A mixed multivariate analysis of covariance (MANCOVA) revealed that the children with ADHD performed worse on correct responses had more commissions and omissions errors than the TD children, as well as slower target reaction times . The results showed significant differences between performance in the virtual environment and the traditional computerized one, with longer reaction times in virtual reality. The data analysis highlighted the negative influence of auditory distractors on attention performance in the case of the children with ADHD, but not for the TD children. Finally, the two measures did not differ on the cognitive absorption perceived by the children.

Sustained attention in skilled and novice martial arts athletes: a study of event-related potentials and current sources.

PubMed

Sanchez-Lopez, Javier; Silva-Pereyra, Juan; Fernandez, Thalia

2016-01-01

Background. Research on sports has revealed that behavioral responses and event-related brain potentials (ERP) are better in expert than in novice athletes for sport-related tasks. Focused attention is essential for optimal athletic performance across different sports but mainly in combat disciplines. During combat, long periods of focused attention (i.e., sustained attention) are required for a good performance. Few investigations have reported effects of expertise on brain electrical activity and its neural generators during sport-unrelated attention tasks. The aim of the present study was to assess the effect of expertise (i.e., skilled and novice martial arts athletes) analyzing the ERP during a sustained attention task (Continuous Performance Task; CPT) and the cortical three-dimensional distribution of current density, using the sLORETA technique. Methods. CPT consisted in an oddball-type paradigm presentation of five stimuli (different pointing arrows) where only one of them (an arrow pointing up right) required a motor response (i.e., target). CPT was administered to skilled and novice martial arts athletes while EEG were recorded. Amplitude ERP data from target and non-target stimuli were compared between groups. Subsequently, current source analysis for each ERP component was performed on each subject. sLORETA images were compared by condition and group using Statistical Non-Parametric Mapping analysis. Results. Skilled athletes showed significant amplitude differences between target and non-target conditions in early ERP components (P100 and P200) as opposed to the novice group; however, skilled athletes showed no significant effect of condition in N200 but novices did show a significant effect. Current source analysis showed greater differences in activations in skilled compared with novice athletes between conditions in the frontal (mainly in the Superior Frontal Gyrus and Medial Frontal Gyrus) and limbic (mainly in the Anterior Cingulate Gyrus) lobes. Discussion. These results are supported by previous findings regarding activation of neural structures that underlie sustained attention. Our findings may indicate a better-controlled attention in skilled athletes, which suggests that expertise can improve effectiveness in allocation of attentional resources during the first stages of cognitive processing during combat.

Exercise Intensity-Dependent Effects on Cognitive Control Function during and after Acute Treadmill Running in Young Healthy Adults

PubMed Central

Wohlwend, Martin; Olsen, Alexander; Håberg, Asta K.; Palmer, Helen S.

2017-01-01

The idea that physical activity differentially impacts upon performance of various cognitive tasks has recently gained increased interest. However, our current knowledge about how cognition is altered by acute physical activity is incomplete. To measure how different intensity levels of physical activity affect cognition during and after 1 bout of physical activity, 30 healthy, young participants were randomized to perform a not-X continuous performance test (CPT) during low (LI)- and moderate intensity (MI) running. The same participants were subsequently randomized to perform the not-X CPT post LI, MI, and high intensity (HI) running. In addition, exercise related mood changes were assessed through a self-report measure pre and post running at LI, MI, and HI. Results showed worsening of performance accuracy on the not-X CPT during one bout of moderate compared to low intensity running. Post running, there was a linear decrease in reaction time with increasing running intensity and no change in accuracy or mood. The decreased reaction times post HI running recovered back to baseline within 20 min. We conclude that accuracy is acutely deteriorated during the most straining physical activity while a transient intensity-dependent enhancement of cognitive control function is present following physical activity. PMID:28377735

Acute Effects of Mecamylamine and Varenicline on Cognitive Performance in Non-smokers With and Without Schizophrenia

PubMed Central

Roh, Sungwon; Hoeppner, Susanne S.; Schoenfeld, David; Fullerton, Catherine A.; Stoeckel, Luke E.; Evins, A. Eden

2013-01-01

Rationale Nicotinic acetylcholine receptors (nAChRs) have been implicated in the pathophysiology of cognitive deficits in the domains of attention and memory in schizophrenia. While nicotinic agonists and antagonists have been proposed as smoking cessation aids, few comparisons have been made of these agents on cognitive performance in individuals with schizophrenia. Objectives This study investigated the acute effects of a nAChR antagonist, mecamylamine, and partial agonist, varenicline, on cognitive function in non-smokers with and without schizophrenia. Methods Single oral doses of mecamylamine, 10 mg, varenicline, 1 mg, and placebo were administered, one week apart, in random order to adults with schizophrenia (n=30) and to healthy volunteers (n=41) in a double-blind, crossover design. The primary outcome of interest was sustained attention as assessed with hit reaction time variability (HRT-SD) on the identical pairs continuous performance test (CPT-IP). Results Mecamylamine worsened performance on CPT-IP HRT-SD, a measure of attention, compared to varenicline in both groups. Performance on mecamylamine was worse than performance on both placebo and varenicline on several additional measures of attention, including CPT-IP hit reaction time (HRT) and random errors at various levels of task difficulty. There was a treatment by diagnosis interaction, such that mecamylamine worsened performance on CPT-IP 2-digit HRT, 3-digit random errors, and 4-digit hit rate compared to placebo and varenicline in participants with schizophrenia, effects not observed in controls. Conclusions These findings support a role for nAChR’s in attention and suggest that those with schizophrenia may be particularly sensitive to nAChR blockade. PMID:24114425

Impulsive behavior in adults with attention deficit/ hyperactivity disorder: characterization of attentional, motor and cognitive impulsiveness.

PubMed

Malloy-Diniz, L; Fuentes, D; Leite, W Borges; Correa, H; Bechara, A

2007-07-01

Attention-deficit/hyperactivity disorder (ADHD) is characterized by inattention and/or hyperactivity/impulsivity. Impulsivity persists in adults with ADHD and might be the basis of much of the impairment observed in the daily lives of such individuals. The objective of this study was to address the presence, and more importantly, the three dimensions of impulsivity: attentional, non-planning and motor, in how they may relate to neuropsychological mechanisms of impulse control. We studied a sample of 50 adults with ADHD and 51 healthy comparison controls using the Barratt Impulsivity Scale Version 11 (BIS), and neuropsychological tasks, namely the Continuous Performance Task (CPT-II) and the Iowa Gambling Task (IGT). The ADHD group showed more signs of impulsivity on the three dimensions of BIS, committed more errors of omission and commission on the CPT-II, and made more disadvantageous choices on the IGT. These results support the existence of deficits related to three components of impulsivity: motor, cognitive, and attentional among adults with ADHD. Most importantly, this study also highlights the complementary nature of self-report questionnaires and neuropsychological tasks in the assessment of impulsivity in ADHD adults.

Acute citalopram administration may disrupt contextual information processing in healthy males.

PubMed

Almeida, S; Glahn, D C; Argyropoulos, S V; Frangou, S

2010-03-01

Selective serotonin reuptake inhibitors (SSRI) are the most commonly prescribed antidepressants. It has been suggested however that SSRI administration may affect response inhibition and contextual processing but the available evidence is minimal. Therefore, the purpose of this study was to identify the effect size of acute (within 24 hours) and chronic (28 days) administration of the highly selective SSRI, Citalopram, compared to placebo on response inhibition (measured by the Degraded Symbol Continuous Performance Task [DS-CPT]) and contextual processing (assessed using a Delayed Non-Matching to Sample Task [DNMS]) in healthy males (n=20) using a randomised double-blind design. We found no effect of Citalopram on participants' performance on the DS-CPT which suggests either that SSRIs do not affect response inhibition or that this measure is insensitive to any potential disinhibition effects of SSRI. Acute, but not chronic, Citalopram administration was associated with a measurable decrement in the DNMS suggestive of a negative impact of SSRI administration on contextual processing at least during treatment initiation. These findings provide a useful guide for designing future studies in clinical populations. 2009. Published by Elsevier SAS.

Estradiol Therapy After Menopause Mitigates Effects of Stress on Cortisol and Working Memory.

PubMed

Herrera, Alexandra Ycaza; Hodis, Howard N; Mack, Wendy J; Mather, Mara

2017-12-01

Postmenopausal estradiol therapy (ET) can reduce the stress response. However, it remains unclear whether such reductions can mitigate effects of stress on cognition. Investigate effects of ET on cortisol response to a physical stressor, cold pressor test (CPT), and whether ET attenuates stress effects on working memory. Women completed the CPT or control condition across two sessions and subsequently completed a sentence span task. General community: Participants were recruited from the Early vs Late Intervention Trial with Estradiol (ELITE). ELITE participants (mean age = 66, standard deviation age = 6.8) in this study did not suffer from any major chronic illness or use medications known to affect the stress response or cognition. Participants had received a median of randomized 4.7 years of estradiol (n = 21) or placebo (n = 21) treatment at time of participation in this study. Salivary cortisol and sentence span task performance. Women assigned to estradiol exhibited blunted cortisol responses to CPT compared with placebo (P = 0.017) and lesser negative effects of stress on working memory (P = 0.048). We present evidence suggesting ET may protect certain types of cognition in the presence of stress. Such estrogenic protection against stress hormone exposure may prove beneficial to both cognition and the neural circuitry that maintains and propagates cognitive faculties. Copyright © 2017 Endocrine Society

Differences in behavioural phenotype between parental deletion and maternal uniparental disomy in Prader-Willi syndrome: an ERP study.

PubMed

Stauder, Johannes E A; Boer, Harm; Gerits, Rolf H A; Tummers, Anke; Whittington, Joyce; Curfs, Leopold M G

2005-06-01

Paternal deletion and maternal uniparental disomy are the principal genetic subtypes associated with Prader-Willi syndrome (PWS). Recent clinical findings suggest differences in phenotype between these subtypes. The present experimental study addresses this issue using a cognitive psycho-physiological setup. Behaviour and event-related brain activity (ERP) was recorded by a continuous performance response inhibition task (CPT-AX) in adults with paternal deletion PWS (n=11), maternal uniparental disomy PWS (n=11) and normal controls (n=11). The dependent behavioural variables of the CPT-AX task were reaction time and correct scores. For the ERPs the N200 and P300 components were included which are related to early modality-specific inhibition and late general inhibition, respectively. The disomy group had fewer correct scores and increased reaction times as compared to the CPT-AX task than the control and deletion group. Both PWS subgroups differed significantly from the control group for the N200 amplitude. Only the control group showed the typical task modulation for the N200 amplitude. The amplitude of the P300 component was considerably smaller in the uniparental disomy group than in the deletion and control groups. The ERP results suggest that early modality specific inhibition is impaired in both PWS genetic subtypes. Late general inhibition is impaired in the uniparental disomy group only. Thus, although the ERP data suggests a common impairment in early visual inhibition processing, uniparental disomy and parental deletion genetic PWS subtypes clearly differ in their behavioural and brain activation phenotypes. The present study is the first experimental demonstration which explains the two principal genetic mechanisms that hinder the expression of the genes at 15q11-q13g in PWS result in different behavioural phenotype.

Computerized assessment of sustained attention: interactive effects of task demand, noise, and anxiety.

PubMed

Ballard, J C

1996-12-01

In a sample of 163 college undergraduates, the effects of task demand, noise, and anxiety on Continuous Performance Test (CPT) errors were evaluated with multiple regression and multivariate analysis of variance. Results indicated significantly more omission errors on the difficult task. Complex interaction effects of noise and self-reported anxiety yielded more omissions in quiet intermittent white noise, particularly for high-anxious subjects performing the difficult task. Anxiety levels tended to increase from pretest to posttest, particularly for low-anxious subjects in the quiet, difficult-task condition, while a decrease was seen for high-anxious subjects in the loud, easy-task condition. Commission errors were unrelated to any predictor variables, suggesting that "attention" cannot be considered a unitary phenomenon. The variety of direct and interactive effects on vigilance performance underscore the need for clinicians to use a variety of measures to assess attentional skills, to avoid diagnosis of attention deficits on the basis of a single computerized task performance, and to rule out anxiety and other contributors to poor vigilance task performance.

A polarization converting device for an interfering enhanced CPT atomic clock.

PubMed

Wang, Kewei; Tian, Yuan; Yin, Yi; Wang, Yuanchao; Gu, Sihong

2017-11-01

With interfering enhanced coherent population trapping (CPT) signals, a CPT atomic clock with improved frequency stability performance can be realized. We explore an optical device that converts single-polarized bichromatic light to left and right circularly polarized superposed bichromatic light to generate interfering enhanced CPT resonance with atoms. We have experimentally studied a tabletop CPT atomic clock apparatus with a microfabricated 87 Rb atomic chip-scale cell, and the study results show that it is promising to realize a compact CPT atomic clock, even a chip-scale CPT atomic clock through microfabrication, with improved frequency stability performance.

A polarization converting device for an interfering enhanced CPT atomic clock

NASA Astrophysics Data System (ADS)

Wang, Kewei; Tian, Yuan; Yin, Yi; Wang, Yuanchao; Gu, Sihong

2017-11-01

With interfering enhanced coherent population trapping (CPT) signals, a CPT atomic clock with improved frequency stability performance can be realized. We explore an optical device that converts single-polarized bichromatic light to left and right circularly polarized superposed bichromatic light to generate interfering enhanced CPT resonance with atoms. We have experimentally studied a tabletop CPT atomic clock apparatus with a microfabricated 87Rb atomic chip-scale cell, and the study results show that it is promising to realize a compact CPT atomic clock, even a chip-scale CPT atomic clock through microfabrication, with improved frequency stability performance.

Physics-based approach to chemical source localization using mobile robotic swarms

NASA Astrophysics Data System (ADS)

Zarzhitsky, Dimitri

2008-07-01

Recently, distributed computation has assumed a dominant role in the fields of artificial intelligence and robotics. To improve system performance, engineers are combining multiple cooperating robots into cohesive collectives called swarms. This thesis illustrates the application of basic principles of physicomimetics, or physics-based design, to swarm robotic systems. Such principles include decentralized control, short-range sensing and low power consumption. We show how the application of these principles to robotic swarms results in highly scalable, robust, and adaptive multi-robot systems. The emergence of these valuable properties can be predicted with the help of well-developed theoretical methods. In this research effort, we have designed and constructed a distributed physicomimetics system for locating sources of airborne chemical plumes. This task, called chemical plume tracing (CPT), is receiving a great deal of attention due to persistent homeland security threats. For this thesis, we have created a novel CPT algorithm called fluxotaxis that is based on theoretical principles of fluid dynamics. Analytically, we show that fluxotaxis combines the essence, as well as the strengths, of the two most popular biologically-inspired CPT methods-- chemotaxis and anemotaxis. The chemotaxis strategy consists of navigating in the direction of the chemical density gradient within the plume, while the anemotaxis approach is based on an upwind traversal of the chemical cloud. Rigorous and extensive experimental evaluations have been performed in simulated chemical plume environments. Using a suite of performance metrics that capture the salient aspects of swarm-specific behavior, we have been able to evaluate and compare the three CPT algorithms. We demonstrate the improved performance of our fluxotaxis approach over both chemotaxis and anemotaxis in these realistic simulation environments, which include obstacles. To test our understanding of CPT on actual hardware, we have implemented chemotaxis on three laboratory-scale robots. Chemotaxis requires only chemical sensors; eventually, when small-scale anemometers capable of reliably detecting low air velocities become available, we plan to implement anemotaxis and fluxotaxis on the robots as well. Our chemotaxis robots use the physicomimetics control algorithm to arrange the team of vehicles into a triangular formation, which then traces an ethanol vapor plume to its source emitter. In agreement with our theoretical predictions, the swarm implementation shows a consistent gain in CPT performance as compared to a single-robot solution.

Spelling difficulties in school-aged girls with attention-deficit/hyperactivity disorder: behavioral, psycholinguistic, cognitive, and graphomotor correlates.

PubMed

Åsberg Johnels, Jakob; Kopp, Svenny; Gillberg, Christopher

2014-01-01

Writing difficulties are common among children with attention-deficit/hyperactivity disorder (ADHD), but the nature of these difficulties has not been well studied. Here we relate behavioral, psycholinguistic, cognitive (memory/executive), and graphomotor measures to spelling skills in school-age girls with ADHD (n = 30) and an age-matched group of typically developed spellers (TYPSP, n = 35). When subdividing the ADHD group into those with poor (ADHDPSP, n = 19) and typical spelling (ADHDTYPSP, n = 11), the two subgroups did not differ with regard to inattentive or hyperactive-impulsive symptom severity according to parent or teacher ratings. Both ADHD subgroups also had equally severe difficulties in graphomotor control-handwriting and (parent ratings of) written expression as compared to the TYPSP group. In contrast, ADHDPSP had problems relative to ADHDTYPSP and TYPSP on phonological and orthographic recoding (choice tasks) and verbal memory (digit span) and were more likely to make commissions on a continuous performance task (CPT). Further analyses using the collapsed ADHD group showed that both digit span and the presence of CPT commissions predicted spelling performance independently of each other. Finally, results showed that phonological recoding skills mediated the association between digit span and spelling performance in ADHD. Theoretical and educational implications are discussed. © Hammill Institute on Disabilities 2012.

The effects of experimental pain and induced optimism on working memory task performance.

PubMed

Boselie, Jantine J L M; Vancleef, Linda M G; Peters, Madelon L

2016-07-01

Pain can interrupt and deteriorate executive task performance. We have previously shown that experimentally induced optimism can diminish the deteriorating effect of cold pressor pain on a subsequent working memory task (i.e., operation span task). In two successive experiments we sought further evidence for the protective role of optimism on pain-induced working memory impairments. We used another working memory task (i.e., 2-back task) that was performed either after or during pain induction. Study 1 employed a 2 (optimism vs. no-optimism)×2 (pain vs. no-pain)×2 (pre-score vs. post-score) mixed factorial design. In half of the participants optimism was induced by the Best Possible Self (BPS) manipulation, which required them to write and visualize about a life in the future where everything turned out for the best. In the control condition, participants wrote and visualized a typical day in their life (TD). Next, participants completed either the cold pressor task (CPT) or a warm water control task (WWCT). Before (baseline) and after the CPT or WWCT participants working memory performance was measured with the 2-back task. The 2-back task measures the ability to monitor and update working memory representation by asking participants to indicate whether the current stimulus corresponds to the stimulus that was presented 2 stimuli ago. Study 2 had a 2 (optimism vs. no-optimism)×2 (pain vs. no-pain) mixed factorial design. After receiving the BPS or control manipulation, participants completed the 2-back task twice: once with painful heat stimulation, and once without any stimulation (counter-balanced order). Continuous heat stimulation was used with temperatures oscillating around 1°C above and 1°C below the individual pain threshold. In study 1, the results did not show an effect of cold pressor pain on subsequent 2-back task performance. Results of study 2 indicated that heat pain impaired concurrent 2-back task performance. However, no evidence was found that optimism protected against this pain-induced performance deterioration. Experimentally induced pain impairs concurrent but not subsequent working memory task performance. Manipulated optimism did not counteract pain-induced deterioration of 2-back performance. It is important to explore factors that may diminish the negative impact of pain on the ability to function in daily life, as pain itself often cannot be remediated. We are planning to conduct future studies that should shed further light on the conditions, contexts and executive operations for which optimism can act as a protective factor. Copyright © 2016 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Does the Component Processes Task Assess Text-Based Inferences Important for Reading Comprehension? A Path Analysis in Primary School Children

PubMed Central

Wassenburg, Stephanie I.; de Koning, Björn B.; de Vries, Meinou H.; van der Schoot, Menno

2016-01-01

Using a component processes task (CPT) that differentiates between higher-level cognitive processes of reading comprehension provides important advantages over commonly used general reading comprehension assessments. The present study contributes to further development of the CPT by evaluating the relative contributions of its components (text memory, text inferencing, and knowledge integration) and working memory to general reading comprehension within a single study using path analyses. Participants were 173 third- and fourth-grade children. As hypothesized, knowledge integration was the only component of the CPT that directly contributed to reading comprehension, indicating that the text-inferencing component did not assess inferential processes related to reading comprehension. Working memory was a significant predictor of reading comprehension over and above the component processes. Future research should focus on finding ways to ensure that the text-inferencing component taps into processes important for reading comprehension. PMID:27378989

Event Structure and Cognitive Control

PubMed Central

Reimer, Jason F.; Radvansky, Gabriel A.; Lorsbach, Thomas C.; Armendarez, Joseph J.

2017-01-01

Recently, a great deal of research has demonstrated that although everyday experience is continuous in nature, it is parsed into separate events. The aim of the present study was to examine whether event structure can influence the effectiveness of cognitive control. Across five experiments we varied the structure of events within the AX-CPT by shifting the spatial location of cues and probes on a computer screen. When location shifts were present, a pattern of AX-CPT performance consistent with enhanced cognitive control was found. To test whether the location shift effects were caused by the presence of event boundaries per se, other aspects of the AX-CPT were manipulated, such as the color of cues and probes and the inclusion of a distractor task during the cue-probe delay. Changes in cognitive control were not found under these conditions, suggesting that the location shift effects were specifically related to the formation of separate event models. Together, these results can be accounted for by the Event Horizon Model and a representation-based theory of cognitive control, and suggest that cognitive control can be influenced by the surrounding environmental structure. PMID:25603168

Communicative-Pragmatic Treatment in Schizophrenia: A Pilot Study

PubMed Central

Bosco, Francesca M.; Gabbatore, Ilaria; Gastaldo, Luigi; Sacco, Katiuscia

2016-01-01

This paper aims to verify the efficacy of Cognitive Pragmatic Treatment (CPT), a new remediation training for the improvement of the communicative-pragmatic abilities, in patients with schizophrenia. The CPT program is made up of 20 group sessions, focused on a number of communication modalities, i.e., linguistic, extralinguistic and paralinguistic, theory of mind (ToM) and other cognitive functions able to play a role on the communicative performance, such as awareness and planning. A group of 17 patients with schizophrenia took part in the training program. They were evaluated before and after training, through the equivalent forms of the Assessment Battery for Communication (ABaCo), a tool for testing, both in comprehension and in production, a wide range of pragmatic phenomena such as direct and indirect speech acts, irony and deceit, and a series of neuropsychological and ToM tests. The results showed a significant improvement in patients’ performance on both production and comprehension tasks following the program, and in all the communication modalities evaluated through the ABaCo, i.e., linguistic, extralinguistic, paralinguistic, and social appropriateness. This improvement persisted after 3 months from the end of the training program, as shown by the follow-up tests. These preliminary findings provide evidence of the efficacy of the CPT program in improving communicative-pragmatic abilities in schizophrenic individuals. PMID:26941667

Analysis of cigarette purchase task instrument data with a left-censored mixed effects model.

PubMed

Liao, Wenjie; Luo, Xianghua; Le, Chap T; Chu, Haitao; Epstein, Leonard H; Yu, Jihnhee; Ahluwalia, Jasjit S; Thomas, Janet L

2013-04-01

The drug purchase task is a frequently used instrument for measuring the relative reinforcing efficacy (RRE) of a substance, a central concept in psychopharmacological research. Although a purchase task instrument, such as the cigarette purchase task (CPT), provides a comprehensive and inexpensive way to assess various aspects of a drug's RRE, the application of conventional statistical methods to data generated from such an instrument may not be adequate by simply ignoring or replacing the extra zeros or missing values in the data with arbitrary small consumption values, for example, 0.001. We applied the left-censored mixed effects model to CPT data from a smoking cessation study of college students and demonstrated its superiority over the existing methods with simulation studies. Theoretical implications of the findings, limitations of the proposed method, and future directions of research are also discussed.

Analysis of Cigarette Purchase Task Instrument Data with a Left-Censored Mixed Effects Model

PubMed Central

Liao, Wenjie; Luo, Xianghua; Le, Chap; Chu, Haitao; Epstein, Leonard H.; Yu, Jihnhee; Ahluwalia, Jasjit S.; Thomas, Janet L.

2015-01-01

The drug purchase task is a frequently used instrument for measuring the relative reinforcing efficacy (RRE) of a substance, a central concept in psychopharmacological research. While a purchase task instrument, such as the cigarette purchase task (CPT), provides a comprehensive and inexpensive way to assess various aspects of a drug’s RRE, the application of conventional statistical methods to data generated from such an instrument may not be adequate by simply ignoring or replacing the extra zeros or missing values in the data with arbitrary small consumption values, e.g. 0.001. We applied the left-censored mixed effects model to CPT data from a smoking cessation study of college students and demonstrated its superiority over the existing methods with simulation studies. Theoretical implications of the findings, limitations of the proposed method and future directions of research are also discussed. PMID:23356731

The prevalence of visual hallucinations in non-affective psychosis, and the role of perception and attention.

PubMed

van Ommen, M M; van Beilen, M; Cornelissen, F W; Smid, H G O M; Knegtering, H; Aleman, A; van Laar, T

2016-06-01

Little is known about visual hallucinations (VH) in psychosis. We investigated the prevalence and the role of bottom-up and top-down processing in VH. The prevailing view is that VH are probably related to altered top-down processing, rather than to distorted bottom-up processing. Conversely, VH in Parkinson's disease are associated with impaired visual perception and attention, as proposed by the Perception and Attention Deficit (PAD) model. Auditory hallucinations (AH) in psychosis, however, are thought to be related to increased attention. Our retrospective database study included 1119 patients with non-affective psychosis and 586 controls. The Community Assessment of Psychic Experiences established the VH rate. Scores on visual perception tests [Degraded Facial Affect Recognition (DFAR), Benton Facial Recognition Task] and attention tests [Response Set-shifting Task, Continuous Performance Test-HQ (CPT-HQ)] were compared between 75 VH patients, 706 non-VH patients and 485 non-VH controls. The lifetime VH rate was 37%. The patient groups performed similarly on cognitive tasks; both groups showed worse perception (DFAR) than controls. Non-VH patients showed worse attention (CPT-HQ) than controls, whereas VH patients did not perform differently. We did not find significant VH-related impairments in bottom-up processing or direct top-down alterations. However, the results suggest a relatively spared attentional performance in VH patients, whereas face perception and processing speed were equally impaired in both patient groups relative to controls. This would match better with the increased attention hypothesis than with the PAD model. Our finding that VH frequently co-occur with AH may support an increased attention-induced 'hallucination proneness'.

Simulating demand for cigarettes among pregnant women: A Low-Risk method for studying vulnerable populations.

PubMed

Higgins, Stephen T; Reed, Derek D; Redner, Ryan; Skelly, Joan M; Zvorsky, Ivori A; Kurti, Allison N

2017-01-01

A substantive obstacle to experimentally studying cigarette smoking and use of other tobacco products in pregnant women is the risk of adverse effects on mother and fetus from experimenter administration of the product of interest. The purpose of this study is to investigate bypassing that obstacle by using behavioral economic simulation tasks. In the present study we used the Cigarette Purchase Task (CPT) to simulate changes in demand for hypothetical cigarettes as a function of varying cigarette prices. Participants were 95 pregnant women who completed the CPT prior to participation in a smoking-cessation trial. Aggregate and individual participant demand varied as an orderly function of price and those changes were well fitted by an exponential equation. Demand also varied in correspondence to two well-validated predictors of individual differences in smoking cessation among pregnant women (cigarettes smoked per day, pre-pregnancy quit attempts). Moreover, CPT indices were more effective than these two conventional variables in predicting individual differences in whether women made a quit attempt during the current pregnancy. Overall, these results represent a promising step in demonstrating the validity and utility of the CPT for experimentally examining demand for cigarettes, and potentially other tobacco and nicotine delivery products, among pregnant women. © 2016 Society for the Experimental Analysis of Behavior.

SIMULATING DEMAND FOR CIGARETTES AMONG PREGNANT WOMEN: A LOW-RISK METHOD FOR STUDYING VULNERABLE POPULATIONS

PubMed Central

Higgins, Stephen T.; Reed, Derek D.; Redner, Ryan; Skelly, Joan M.; Zvorsky, Ivori A.; Kurti, Allison N.

2016-01-01

A substantive obstacle to experimentally studying cigarette smoking and use of other tobacco products in pregnant women is the risk of adverse effects on mother and fetus from experimenter administration of the product of interest. The purpose of this study is to investigate bypassing that obstacle by using behavioral economic simulation tasks. In the present study we used the Cigarette Purchase Task (CPT) to simulate changes in demand for hypothetical cigarettes as a function of varying cigarette prices. Participants were 95 pregnant women who completed the CPT prior to participation in a smoking-cessation trial. Aggregate and individual participant demand varied as an orderly function of price and those changes were well fitted by an exponential equation. Demand also varied in correspondence to two well-validated predictors of individual differences in smoking cessation among pregnant women (cigarettes smoked per day, pre-pregnancy quit attempts). Moreover, CPT indices were more effective than these two conventional variables in predicting individual differences in whether women made a quit attempt during the current pregnancy. Overall, these results represent a promising step in demonstrating the validity and utility of the CPT for experimentally examining demand for cigarettes, and potentially other tobacco and nicotine delivery products, among pregnant women. PMID:28000917

The Role of Psychometrics in Individual Differences Research in Cognition: A Case Study of the AX-CPT

PubMed Central

Cooper, Shelly R.; Gonthier, Corentin; Barch, Deanna M.; Braver, Todd S.

2017-01-01

Investigating individual differences in cognition requires addressing questions not often thought about in standard experimental designs, especially regarding the psychometric properties of the task. Using the AX-CPT cognitive control task as a case study example, we address four concerns that one may encounter when researching the topic of individual differences in cognition. First, we demonstrate the importance of variability in task scores, which in turn directly impacts reliability, particularly when comparing correlations in different populations. Second, we demonstrate the importance of variability and reliability for evaluating potential failures to replicate predicted correlations, even within the same population. Third, we demonstrate how researchers can turn to evaluating psychometric properties as a way of evaluating the feasibility of utilizing the task in new settings (e.g., online administration). Lastly, we show how the examination of psychometric properties can help researchers make informed decisions when designing a study, such as determining the appropriate number of trials for a task. PMID:28928690

The Impact of Social Pressure and Monetary Incentive on Cognitive Control.

PubMed

Ličen, Mina; Hartmann, Frank; Repovš, Grega; Slapničar, Sergeja

2016-01-01

We compare the effects of two prominent organizational control mechanisms-social pressure and monetary incentive-on cognitive control. Cognitive control underlies the human ability to regulate thoughts and actions in the pursuit of behavioral goals. Previous studies show that monetary incentives can contribute to goal-oriented behavior by activating proactive control. There is, however, much less evidence of how social pressure affects cognitive control and task performance. In a within-subject experimental design, we tested 47 subjects performing the AX-CPT task to compare the activation of cognitive control modes under social pressure and monetary incentive beyond mere instructions to perform better. Our results indicate that instructing participants to improve their performance on its own leads to a significant shift from a reactive to a proactive control mode and that both social pressure and monetary incentive further enhance performance.

Comprehensive neurocognitive assessment of patients with anorexia nervosa.

PubMed

Phillipou, Andrea; Gurvich, Caroline; Castle, David Jonathan; Abel, Larry Allen; Rossell, Susan Lee

2015-12-22

To utilise a comprehensive cognitive battery to gain a better understanding of cognitive performance in anorexia nervosa (AN). Twenty-six individuals with AN and 27 healthy control participants matched for age, gender and premorbid intelligence, participated in the study. A standard cognitive battery, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery, was used to investigate performance on seven cognitive domains with the use of 10 different tasks: speed of processing [Brief Assessment Of Cognition In Schizophrenia: Symbol Coding, Category Fluency: Animal Naming (Fluency) and Trail Making Test: Part A], attention/vigilance [Continuous Performance Test - Identical Pairs (CPT-IP)], working memory [Wechsler Memory Scale (WMS(®)-III): Spatial Span, and Letter-Number Span (LNS)], verbal learning [Hopkins Verbal Learning Test - Revised], visual learning [Brief Visuospatial Memory Test - Revised], reasoning and problem solving [Neuropsychological Assessment Battery: Mazes], and social cognition [Mayer-Salovey-Caruso Emotional Intelligence Test: Managing Emotions]. Statistical analyses involved the use of multivariate and univariate analyses of variance. Analyses conducted on the cognitive domain scores revealed no overall significant difference between groups nor any interaction between group and domain score [F(1,45) = 0.73, P = 0.649]. Analyses conducted on each of the specific tasks within the cognitive domains revealed significantly slower reaction times for false alarm responses on the CPT-IP task in AN [F(1,51) = 12.80, P < 0.01, Cohen's d = 0.982] and a trend towards poorer performance in AN on the backward component of the WMS(®)-III Spatial Span task [F(1,51) = 5.88, P = 0.02, Cohen's d = -0.665]. The finding of slower reaction times of false alarm responses is, however, limited due to the small number of false alarm responses for either group. The findings are discussed in terms of poorer capacity to manipulate and process visuospatial material in AN.

Reinforcement Enhances Vigilance Among Children With ADHD: Comparisons to Typically Developing Children and to the Effects of Methylphenidate

PubMed Central

Bubnik, Michelle G.; Hawk, Larry W.; Pelham, William E.; Waxmonsky, James G.; Rosch, Keri S.

2014-01-01

Sustained attention and reinforcement are posited as causal mechanisms in Attention-Deficit/Hyperactivity Disorder (ADHD), but their interaction has received little empirical study. In two studies, we examined the impact of performance-based reinforcement on sustained attention over time, or vigilance, among 9- to 12-year-old children. Study 1 demonstrated the expected vigilance deficit among children with ADHD (n=25; 12% female) compared to typically developing (TD) controls (n=33; 22% female) on a standard continuous performance task (CPT). During a subsequent visit, reinforcement improved attention more among children with ADHD than controls. Study 2 examined the separate and combined effects of reinforcement and acute methylphenidate (MPH) on CPT performance in children with ADHD (n=19; 21% female). Both reinforcement and MPH enhanced overall target detection and attenuated the vigilance decrement that occurred in no-reinforcement, placebo condition. Cross-study comparisons suggested that the combination of MPH and reinforcement eliminated the vigilance deficit in children with ADHD, normalizing sustained attention. This work highlights the clinically and theoretically interesting intersection of reinforcement and sustained attention. PMID:24931776

AKT1 Moderation of Cannabis-Induced Cognitive Alterations in Psychotic Disorder

PubMed Central

van Winkel, Ruud; van Beveren, Nico J M; Simons, Claudia; S Kahn, René S; Linszen, Don H; van Os, Jim; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; de Haan, Lieuwe; Krabbendam, Lydia; Myin-Germeys, Inez

2011-01-01

Genetic variation in AKT1 may be associated with sensitivity to the psychotomimetic effects of cannabis as well as with increased risk for psychotic disorder following cannabis use. Investigation of the effect of this interaction on relevant intermediate phenotypes for psychosis, such as cognition, may help to clarify the underlying mechanism. Thus, verbal memory (visually presented Word Learning Task), sustained attention (Continuous Performance Test, CPT), AKT1 rs2494732 genotype, and cannabis use were examined in a large cohort of patients with psychotic disorder. No evidence was found for AKT1 × cannabis interaction on verbal memory. Cannabis use preceding onset of psychotic disorder did interact significantly with AKT1 rs2494732 genotype to affect CPT reaction time (β=8.0, SE 3.9, p=0.037) and CPT accuracy (β=−1.2, SE 0.4, p=0.003). Cannabis-using patients with the a priori vulnerability C/C genotype were slower and less accurate on the CPT, whereas cannabis-using patients with the T/T genotype had similar or better performance than non-using patients with psychotic disorder. The interaction was also apparent in patients with psychotic disorder who had not used cannabis in the 12 months preceding assessment, but was absent in the unaffected siblings of these patients and in healthy controls. In conclusion, cannabis use before onset of psychosis may have long-lasting effects on measures of sustained attention, even in the absence of current use, contingent on AKT1 rs2494732 genotype. The results suggest that long-term changes in cognition may mediate the risk-increasing effect of the AKT1 × cannabis interaction on psychotic disorder. PMID:21775978

AKT1 moderation of cannabis-induced cognitive alterations in psychotic disorder.

PubMed

van Winkel, Ruud; van Beveren, Nico J M; Simons, Claudia

2011-11-01

Genetic variation in AKT1 may be associated with sensitivity to the psychotomimetic effects of cannabis as well as with increased risk for psychotic disorder following cannabis use. Investigation of the effect of this interaction on relevant intermediate phenotypes for psychosis, such as cognition, may help to clarify the underlying mechanism. Thus, verbal memory (visually presented Word Learning Task), sustained attention (Continuous Performance Test, CPT), AKT1 rs2494732 genotype, and cannabis use were examined in a large cohort of patients with psychotic disorder. No evidence was found for AKT1 × cannabis interaction on verbal memory. Cannabis use preceding onset of psychotic disorder did interact significantly with AKT1 rs2494732 genotype to affect CPT reaction time (β=8.0, SE 3.9, p=0.037) and CPT accuracy (β=-1.2, SE 0.4, p=0.003). Cannabis-using patients with the a priori vulnerability C/C genotype were slower and less accurate on the CPT, whereas cannabis-using patients with the T/T genotype had similar or better performance than non-using patients with psychotic disorder. The interaction was also apparent in patients with psychotic disorder who had not used cannabis in the 12 months preceding assessment, but was absent in the unaffected siblings of these patients and in healthy controls. In conclusion, cannabis use before onset of psychosis may have long-lasting effects on measures of sustained attention, even in the absence of current use, contingent on AKT1 rs2494732 genotype. The results suggest that long-term changes in cognition may mediate the risk-increasing effect of the AKT1 × cannabis interaction on psychotic disorder.

Event structure and cognitive control.

PubMed

Reimer, Jason F; Radvansky, Gabriel A; Lorsbach, Thomas C; Armendarez, Joseph J

2015-09-01

Recently, a great deal of research has demonstrated that although everyday experience is continuous in nature, it is parsed into separate events. The aim of the present study was to examine whether event structure can influence the effectiveness of cognitive control. Across 5 experiments we varied the structure of events within the AX-CPT by shifting the spatial location of cues and probes on a computer screen. When location shifts were present, a pattern of AX-CPT performance consistent with enhanced cognitive control was found. To test whether the location shift effects were caused by the presence of event boundaries per se, other aspects of the AX-CPT were manipulated, such as the color of cues and probes and the inclusion of a distractor task during the cue-probe delay. Changes in cognitive control were not found under these conditions, suggesting that the location shift effects were specifically related to the formation of separate event models. Together, these results can be accounted for by the Event Horizon Model and a representation-based theory of cognitive control, and suggest that cognitive control can be influenced by the surrounding environmental structure. (c) 2015 APA, all rights reserved).

Virtual Remediation Versus Methylphenidate to Improve Distractibility in Children With ADHD: A Controlled Randomized Clinical Trial Study.

PubMed

Bioulac, Stéphanie; Micoulaud-Franchi, Jean-Arthur; Maire, Jenna; Bouvard, Manuel P; Rizzo, Albert A; Sagaspe, Patricia; Philip, Pierre

2018-03-01

Virtual environments have been used to assess children with ADHD but have never been tested as therapeutic tools. We tested a new virtual classroom cognitive remediation program to improve symptoms in children with ADHD. In this randomized clinical trial, 51 children with ADHD (7-11 years) were assigned to a virtual cognitive remediation group, a methylphenidate group, or a psychotherapy group. All children were evaluated before and after therapy with an ADHD Rating Scale, a Continuous Performance Test (CPT), and a virtual classroom task. After therapy by virtual remediation, children exhibited significantly higher numbers of correct hits on the virtual classroom and CPT. These improvements were equivalent to those observed with methylphenidate treatment. Our study demonstrates for the first time that a cognitive remediation program delivered in a virtual classroom reduces distractibility in children with ADHD and could replace methylphenidate treatment in specific cases.

Cold-Blooded Attention: Finger Temperature Predicts Attentional Performance.

PubMed

Vergara, Rodrigo C; Moënne-Loccoz, Cristóbal; Maldonado, Pedro E

2017-01-01

Thermal stress has been shown to increase the chances of unsafe behavior during industrial and driving performances due to reductions in mental and attentional resources. Nonetheless, establishing appropriate safety standards regarding environmental temperature has been a major problem, as modulations are also be affected by the task type, complexity, workload, duration, and previous experience with the task. To bypass this attentional and thermoregulatory problem, we focused on the body rather than environmental temperature. Specifically, we measured tympanic, forehead, finger and environmental temperatures accompanied by a battery of attentional tasks. We considered a 10 min baseline period wherein subjects were instructed to sit and relax, followed by three attentional tasks: a continuous performance task (CPT), a flanker task (FT) and a counting task (CT). Using multiple linear regression models, we evaluated which variable(s) were the best predictors of performance. The results showed a decrement in finger temperature due to instruction and task engagement that was absent when the subject was instructed to relax. No changes were observed in tympanic or forehead temperatures, while the environmental temperature remained almost constant for each subject. Specifically, the magnitude of the change in finger temperature was the best predictor of performance in all three attentional tasks. The results presented here suggest that finger temperature can be used as a predictor of alertness, as it predicted performance in attentional tasks better than environmental temperature. These findings strongly support that peripheral temperature can be used as a tool to prevent unsafe behaviors and accidents.

Parent Cardiac Response in the Context of Their Child’s Completion of the Cold Pressor Task: A Pilot Study

PubMed Central

Constantin, Kaytlin; Moline, Rachel L.; Bailey, Heidi N.

2017-01-01

Parents’ ability to regulate their emotions is essential to providing supportive caregiving behaviours when their child is in pain. Extant research focuses on parent self-reported experience or observable behavioural responses. Physiological responding, such as heart rate (HR) and heart rate variability (HRV), is critical to the experience and regulation of emotions and provides a complementary perspective on parent experience; yet, it is scarcely assessed. This pilot study examined parent (n = 25) cardiac response (HR, HRV) at rest (neutral film clip), immediately before the cold pressor task (pre-CPT), and following the CPT (post-CPT). Further, variables that may influence changes in HR and HRV in the context of pediatric pain were investigated, including (1) initial HRV, and (2) parent perception of their child’s typical response to needle procedures. Time-domain (root mean square of successive differences; RMSSD) and frequency-domain (high-frequency heart rate variability; HF-HRV) parameters of HRV were computed. HR and HF-HRV varied as a function of time block. Typical negative responses to needle pain related to higher parental HR and lower HRV at rest. Parents with higher HRV at baseline experienced the greatest decreases in HRV after the CPT. Consequently, considering previous experience with pain and resting HRV levels are relevant to understanding parent physiological responses before and after child pain. PMID:29160828

The Impact of Social Pressure and Monetary Incentive on Cognitive Control

PubMed Central

Ličen, Mina; Hartmann, Frank; Repovš, Grega; Slapničar, Sergeja

2016-01-01

We compare the effects of two prominent organizational control mechanisms—social pressure and monetary incentive—on cognitive control. Cognitive control underlies the human ability to regulate thoughts and actions in the pursuit of behavioral goals. Previous studies show that monetary incentives can contribute to goal-oriented behavior by activating proactive control. There is, however, much less evidence of how social pressure affects cognitive control and task performance. In a within-subject experimental design, we tested 47 subjects performing the AX-CPT task to compare the activation of cognitive control modes under social pressure and monetary incentive beyond mere instructions to perform better. Our results indicate that instructing participants to improve their performance on its own leads to a significant shift from a reactive to a proactive control mode and that both social pressure and monetary incentive further enhance performance. PMID:26903901

Commonalities in EEG Spectral Power Abnormalities Between Women With ADHD and Women With Bipolar Disorder During Rest and Cognitive Performance.

PubMed

Rommel, Anna-Sophie; Kitsune, Glenn L; Michelini, Giorgia; Hosang, Georgina M; Asherson, Philip; McLoughlin, Gráinne; Brandeis, Daniel; Kuntsi, Jonna

2016-11-01

While attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) denote distinct psychiatric conditions, diagnostic delineation is impeded by considerable symptomatic overlap. Direct comparisons across ADHD and BD on neurophysiological measures are limited. They could inform us on impairments that are specific to or shared between the disorders and, therefore, potential biomarkers that may aid in the identification of the diagnostic boundaries. Our aim was to test whether quantitative EEG (QEEG) identifies differences or similarities between women with ADHD and women with BD during resting-state and task conditions. QEEG activity was directly compared between 20 ADHD, 20 BD and 20 control women during an eyes-open resting-state condition (EO) and a cued continuous performance task (CPT-OX). Both ADHD (t 38  = 2.50, p = 0.017) and BD (t 38  = 2.54, p = 0.018) participants showed higher absolute theta power during EO than controls. No significant differences emerged between the two clinical groups. While control participants showed a task-related increase in absolute theta power from EO to CPT-OX (t 19  = -3.77, p = 0.001), no such change in absolute theta power was observed in the ADHD (t 19  = -0.605, p = 0.553) or BD (t 19  = 1.82, p = 0.084) groups. Our results provide evidence for commonalities in brain dysfunction between ADHD and BD. Absolute theta power may play a role as a marker of neurobiological processes in both disorders.

Does the Effort of Processing Potential Incentives Influence the Adaption of Context Updating in Older Adults?

PubMed Central

Schmitt, Hannah; Kray, Jutta; Ferdinand, Nicola K.

2017-01-01

A number of aging studies suggest that older adults process positive and negative information differently. For instance, the socioemotional selectivity theory postulates that older adults preferably process positive information in service of emotional well-being (Reed and Carstensen, 2012). Moreover, recent research has started to investigate whether incentives like gains or losses can influence cognitive control in an ongoing task. In an earlier study (Schmitt et al., 2015), we examined whether incentive cues, indicating potential monetary gains, losses, or neutral outcomes for good performance in the following trial, would influence older adults’ ability to exert cognitive control. Cognitive control was measured in an AX-Continuous-Performance-Task (AX-CPT) in which participants had to select their responses to probe stimuli depending on a preceding context cue. In this study, we did not find support for a positivity effect in older adults, but both gains and losses led to enhanced context processing. As the trial-wise presentation mode may be too demanding on cognitive resources for such a bias to occur, the main goal of the present study was to examine whether motivational mindsets, induced by block-wise presentation of incentives, would result in a positivity effect. For this reason, we examined 17 older participants (65–76 years) in the AX-CPT using a block-wise presentation of incentive cues and compared them to 18 older adults (69–78 years) with the trial-wise presentation mode from our earlier study (Schmitt et al., 2015). Event-related potentials were recorded to the onset of the motivational cue and during the AX-CPT. Our results show that (a) older adults initially process cues signaling potential losses more strongly, but later during the AX-CPT invest more cognitive resources in preparatory processes like context updating in conditions with potential gains, and (b) block-wise and trial-wise presentation of incentive cues differentially influenced cognitive control. When incentives were presented block-wise, the above described valence effects were consistently found. In contrast, when incentives were presented trial-wise, the effects were mixed and salience as well as valence effects can be obtained. Hence, how positive and negative incentive cues influence cognitive control in older adults is dependent on demands of cue processing. PMID:29170649

Does the Effort of Processing Potential Incentives Influence the Adaption of Context Updating in Older Adults?

PubMed

Schmitt, Hannah; Kray, Jutta; Ferdinand, Nicola K

2017-01-01

A number of aging studies suggest that older adults process positive and negative information differently. For instance, the socioemotional selectivity theory postulates that older adults preferably process positive information in service of emotional well-being (Reed and Carstensen, 2012). Moreover, recent research has started to investigate whether incentives like gains or losses can influence cognitive control in an ongoing task. In an earlier study (Schmitt et al., 2015), we examined whether incentive cues, indicating potential monetary gains, losses, or neutral outcomes for good performance in the following trial, would influence older adults' ability to exert cognitive control. Cognitive control was measured in an AX-Continuous-Performance-Task (AX-CPT) in which participants had to select their responses to probe stimuli depending on a preceding context cue. In this study, we did not find support for a positivity effect in older adults, but both gains and losses led to enhanced context processing. As the trial-wise presentation mode may be too demanding on cognitive resources for such a bias to occur, the main goal of the present study was to examine whether motivational mindsets, induced by block-wise presentation of incentives, would result in a positivity effect. For this reason, we examined 17 older participants (65-76 years) in the AX-CPT using a block-wise presentation of incentive cues and compared them to 18 older adults (69-78 years) with the trial-wise presentation mode from our earlier study (Schmitt et al., 2015). Event-related potentials were recorded to the onset of the motivational cue and during the AX-CPT. Our results show that (a) older adults initially process cues signaling potential losses more strongly, but later during the AX-CPT invest more cognitive resources in preparatory processes like context updating in conditions with potential gains, and (b) block-wise and trial-wise presentation of incentive cues differentially influenced cognitive control. When incentives were presented block-wise, the above described valence effects were consistently found. In contrast, when incentives were presented trial-wise, the effects were mixed and salience as well as valence effects can be obtained. Hence, how positive and negative incentive cues influence cognitive control in older adults is dependent on demands of cue processing.

Comparison of visual and emotional continuous performance test related to sequence of presentation, gender and age.

PubMed

Markovska-Simoska, S; Pop-Jordanova, N

2009-07-01

(Full text is available at http://www.manu.edu.mk/prilozi). Continous Performance Tests (CPTs) form a group of paradigms for the evaluation of attention and, to a lesser degree, the response inhibition (or disinhibition) component of executive control. The object of this study was to compare performance on a CPT using both visual and emotional tasks in 46 normal adult subjects. In particular, it was to examine the effects of the type of task (VCPT or ECPT), sequence of presentation, and gender/age influence on performance as measured errors of omission, errors of commission, reaction time and variation of reaction time. From the results we can assume that there are significantly worse performance parameters for ECPT than VCPT tasks, with a probable explanation of the influence of emotional stimuli on attention and information-processing and no significant effect of order of presentation and gender on performance. Significant differences with more omission errors for older groups were obtained, showing better attention in younger subjects. Key words: VCPT, ECPT, omission errors, commission errors, reaction time, variation of reaction time, normal adults.

Amphetamine improves mouse and human attention in the 5-choice continuous performance test.

PubMed

MacQueen, David A; Minassian, Arpi; Kenton, Johnny A; Geyer, Mark A; Perry, William; Brigman, Jonathan L; Young, Jared W

2018-05-31

Non-medical use of prescription stimulants amongst college students is common, with claims of cognitive and academic benefits. The mechanism, magnitude, and pervasiveness of the cognitive enhancing effects of stimulants in healthy adults remain poorly understood however. The present study determined the effects of dextroamphetamine (D-amp) on the 5-choice continuous performance test (5C-CPT) of attention in healthy young adult humans and mice. A mixed gender sample received placebo (n = 29), 10 (n = 17) or 20 mg D-amp (n = 25) in a double-blind fashion before 5C-CPT testing. In addition, male C57BL/6J mice were trained on a touchscreen adaptation of the 5C-CPT and tested after receiving saline or D-amp (0.1, 0.3, 1.0 mg/kg; n = 8/dose). In humans, D-amp significantly improved 5C-CPT performance. Both doses improved signal detection driven by increased hit rate (reduced omissions). Both doses also improved response accuracy and reduced hit reaction time (HRT) variability. In mice, similar effects (improved signal detection, hit rate, and response accuracy) were observed at the moderate dose (0.3 mg/kg). In contrast to human participants however, no effect on HRT variability was detected in mice, with no effect on HRT in either species. Human 5C-CPT performance was consistent with prior studies and consistent with alternative CPT paradigms. The performance of C57BL/6J mice on the touchscreen 5C-CPT mirrored performance of this strain on 5-hole operant chambers. Importantly, comparable facilitation of attention with D-amp was observed in both species. The 5C-CPT provides a cross-species paradigm by which the cognitive enhancing properties of stimulants and the neural underpinnings of attention can be assessed. Copyright © 2018. Published by Elsevier Ltd.

Neurofeedback training with virtual reality for inattention and impulsiveness.

PubMed

Cho, Baek-Hwan; Kim, Saebyul; Shin, Dong Ik; Lee, Jang Han; Lee, Sang Min; Kim, In Young; Kim, Sun I

2004-10-01

In this research, the effectiveness of neurofeedback, along with virtual reality (VR), in reducing the level of inattention and impulsiveness was investigated. Twenty-eight male participants, aged 14-18, with social problems, took part in this study. They were separated into three groups: a control group, a VR group, and a non-VR group. The VR and non-VR groups underwent eight sessions of neurofeedback training over 2 weeks, while the control group just waited during the same period. The VR group used a head-mounted display (HMD) and a head tracker, which let them look around the virtual world. Conversely, the non-VR group used only a computer monitor with a fixed viewpoint. All participants performed a continuous performance task (CPT) before and after the complete training session. The results showed that both the VR and non-VR groups achieved better scores in the CPT after the training session, while the control group showed no significant difference. Compared with the other groups, the VR group presented a tendency to get better results, suggesting that immersive VR is applicable to neurofeedback for the rehabilitation of inattention and impulsiveness.

Usefulness and Validity of Continuous Performance Tests in the Diagnosis of Attention-Deficit Hyperactivity Disorder Children.

PubMed

Berger, Itai; Slobodin, Ortal; Cassuto, Hanoch

2017-02-01

Despite the popularity of continuous performance tests (CPT) in supporting the diagnostic procedure of attention-deficit hyperactivity disorder (ADHD), these measures are still controversial mainly due to limited sensitivity, specificity, and ecological validity. Thus, there continues to be a need for further validation of these objective attention measures. The purpose of this study was to evaluate the usefulness of a CPT that includes environmental distracting stimuli, in supporting the diagnosis of ADHD in children. Participants were 798 children aged 7-12 years (493 boys and 305 girls). The ADHD group included 339 children, whereas the control group included 459 children without ADHD. The study employed the MOXO-CPT, which incorporates visual and auditory stimuli serving as environmental distractors. Compared to their unaffected peers, children with ADHD received significantly lower scores in all 4 CPT indices: attention, timing, hyperactivity, and impulsivity. Specifically, ADHD children were less attended to the stimuli and performed fewer reactions on accurate timing. Furthermore, children with ADHD performed significantly more impulsive and hyperactive responses than controls. Receiver operating characteristic analysis revealed fair to excellent diagnostic ability of all CPT indices except impulsivity, which showed poor ability to distinguish ADHD children from controls. The test's total score yielded excellent diagnostic performance. MOXO-CPT consistently distinguished between children with ADHD and their unaffected peers, so that children with ADHD performed worse than controls in all study indices. Integration of CPT indices improves the diagnostic capacity of ADHD and may better reflect the complexity and heterogeneity of ADHD. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Preschool Neuropsychological Measures as Predictors of Later Attention Deficit Hyperactivity Disorder

PubMed Central

Breaux, Rosanna P.; Griffith, Shayl F.; Harvey, Elizabeth A.

2016-01-01

The present study examined preschool neuropsychological measures as predictors of school-age attention deficit hyperactivity disorder (ADHD). Participants included 168 children (91 males) who completed neuropsychological measures at ages 3 and 4, and who were evaluated for ADHD and oppositional defiant disorder at age 6. The Conners’ Kiddie Continuous Performance Test (K-CPT), NEPSY Statue subtest, and a delay aversion task significantly distinguished at-risk children who later did and did not meet criteria for ADHD, with poor to fair overall predictive power, specificity, and sensitivity. However, only the K-CPT ADHD Confidence Index and battery added incremental predictive validity beyond early ADHD symptoms. This battery approach, which required impairment on at least 2 of the 3 significant measures, yielded fair overall predictive power, specificity, and sensitivity, and correctly classified 67% of children. In addition, there was some support for the specificity hypothesis, with evidence that cool executive function measures (K-CPT and Statue subtest) tended to predict inattentive symptoms. These findings suggest that neuropsychological deficits are evident by preschool-age in children with ADHD, but neuropsychological tests may still misclassify approximately one-third of children if used alone. Thus, neuropsychological measures may be a useful component of early ADHD assessments, but should be used with caution and in combination with other assessment methods. PMID:26936037

Cardiovascular reactivity to stressors in Indian young adults with normotensive parents.

PubMed

Verma, Anjali; Kumar, Manoj; Saxena, Indu; Kumar, Jayballabh

2013-10-01

Stress-induced increase in heart-rate and blood pressure is termed cardiovascular reactivity (CVR). Various studies are designed to monitor the CVR and use different types of experimental stressors. We have compared the CVR to three different stressors used in CVR based studies (cold pressor task, hand grip test, and video game) to identify the best suited stressor for any study design. The study was conducted on 82 (38 female) young Indian adults with normal resting basal parameters and normotensive parents. Each volunteer was subjected to three stressors: cold pressor task (CPT), hand grip test (HGT), and video game (VG). The CVR to the three stressors was compared amongst female subjects and amongst male subjects by ANOVA, and between female and male subjects by unpaired Student's t-test. Maximum CVR was obtained to HGT, while maximum gender difference in CVR was obtained in case of CPT. Heart rate and blood pressure changes obtained on playing VG were not statistically significant. When the purpose of research is to generate maximum possible CVR, we suggest the use of HGT; while if the purpose of the research is to study gender related differences, the use of CPT would be more appropriate. Unlike young adults of Western countries, VG is not perceived as a challenging task or stressor by young Indian adults and produces little change in heart rate and blood pressure.

Return-to-Duty Toolkit: Assessments and Tasks for Determining Military Functional Performance Following Neurosensory Injury

DTIC Science & Technology

2017-09-29

the warfighter to engage in aerobic activity such as running in place or push-ups until 65–85% of the target heart rate is reached (the target heart...85% of the target heart rate is reached (the target heart rate is 220 minus age). Options for activity include but are not limited to running in...Time • Pursuit Tracking • Running Memory CPT • Simple Reaction Time • Sleep Scale • Spatial Processing – Sequential and Simultaneous • Manikin

Endoscopic and Histological Findings Are Predicted by Fecal Calprotectin in Acute Intestinal Graft-Versus-Host-Disease.

PubMed

Adam, Birgit; Koldehoff, Michael; Ditschkowski, Markus; Gromke, Tanja; Hlinka, Michal; Trenschel, Rudolf; Kordeals, Lambros; Steckel, Nina K; Beelen, Dietrich W; Liebregts, Tobias

2016-07-01

Gastrointestinal graft-versus-host-disease (GI-GVHD) is a major cause of nonrelapse mortality after hematopoietic stem cell transplantation (HSCT) necessitating endoscopic examinations and biopsies for diagnosis. Fecal calprotectin (CPT) has been widely used in gastrointestinal inflammation, but comprehensive data in GI-GVHD are lacking. We aimed to identify an association of CPT with endoscopic findings, mucosal damage and symptoms for diagnosing and monitoring acute GI-GVHD. Symptoms were prospectively evaluated in 110 consecutive HSCT recipients by standardized questionnaires and Bristol Stool Scale (BSS). CPT was assayed by ELISA. Symptom assessment and CPT were performed weekly and with onset of first symptoms. GVHD was diagnosed according to the Glucksberg criteria and by endoscopic biopsies. Patients with GI-GVHD received standard high-dose corticosteroid therapy and follow-up CPT, and symptom evaluation was performed after 28 days. Patients not responding to steroid treatment were re-evaluated by colonoscopy. GI-GVHD was diagnosed in 40 patients. Twelve patients with GI symptoms and CMV colitis and 24 patients with isolated skin GVHD were included as control subjects. CPT was significantly higher in GI-GVHD compared to skin GVHD and CMV colitis. Endoscopic findings, histological grading, abdominal cramps, diarrhea, urgency and BSS correlated with CPT. At follow-up, CPT correlated with abdominal cramps, diarrhea, urgency and BSS. In steroid refractory patients, CPT level was still significantly associated with severity of mucosal damage. CPT predicts endoscopic and histological findings in GI-GVHD and correlates with lower GI symptoms. It enables to discriminate GVHD from CMV colitis and to monitor therapeutic success.

Surgeon-Specific Reports in General Surgery: Establishing Benchmarks for Peer Comparison Within a Single Hospital.

PubMed

Hatfield, Mark D; Ashton, Carol M; Bass, Barbara L; Shirkey, Beverly A

2016-02-01

Methods to assess a surgeon's individual performance based on clinically meaningful outcomes have not been fully developed, due to small numbers of adverse outcomes and wide variation in case volumes. The Achievable Benchmark of Care (ABC) method addresses these issues by identifying benchmark-setting surgeons with high levels of performance and greater case volumes. This method was used to help surgeons compare their surgical practice to that of their peers by using merged National Surgical Quality Improvement Program (NSQIP) and Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) data to generate surgeon-specific reports. A retrospective cohort study at a single institution's department of surgery was conducted involving 107 surgeons (8,660 cases) over 5.5 years. Stratification of more than 32,000 CPT codes into 16 CPT clusters served as the risk adjustment. Thirty-day outcomes of interest included surgical site infection (SSI), acute kidney injury (AKI), and mortality. Performance characteristics of the ABC method were explored by examining how many surgeons were identified as benchmark-setters in view of volume and outcome rates within CPT clusters. For the data captured, most surgeons performed cases spanning a median of 5 CPT clusters (range 1 to 15 clusters), with a median of 26 cases (range 1 to 776 cases) and a median of 2.8 years (range 0 to 5.5 years). The highest volume surgeon for that CPT cluster set the benchmark for 6 of 16 CPT clusters for SSIs, 8 of 16 CPT clusters for AKIs, and 9 of 16 CPT clusters for mortality. The ABC method appears to be a sound and useful approach to identifying benchmark-setting surgeons within a single institution. Such surgeons may be able to help their peers improve their performance. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Differentiation of ileostomy from colostomy procedures: assessing the accuracy of current procedural terminology codes and the utility of natural language processing.

PubMed

Vo, Elaine; Davila, Jessica A; Hou, Jason; Hodge, Krystle; Li, Linda T; Suliburk, James W; Kao, Lillian S; Berger, David H; Liang, Mike K

2013-08-01

Large databases provide a wealth of information for researchers, but identifying patient cohorts often relies on the use of current procedural terminology (CPT) codes. In particular, studies of stoma surgery have been limited by the accuracy of CPT codes in identifying and differentiating ileostomy procedures from colostomy procedures. It is important to make this distinction because the prevalence of complications associated with stoma formation and reversal differ dramatically between types of stoma. Natural language processing (NLP) is a process that allows text-based searching. The Automated Retrieval Console is an NLP-based software that allows investigators to design and perform NLP-assisted document classification. In this study, we evaluated the role of CPT codes and NLP in differentiating ileostomy from colostomy procedures. Using CPT codes, we conducted a retrospective study that identified all patients undergoing a stoma-related procedure at a single institution between January 2005 and December 2011. All operative reports during this time were reviewed manually to abstract the following variables: formation or reversal and ileostomy or colostomy. Sensitivity and specificity for validation of the CPT codes against the mastery surgery schedule were calculated. Operative reports were evaluated by use of NLP to differentiate ileostomy- from colostomy-related procedures. Sensitivity and specificity for identifying patients with ileostomy or colostomy procedures were calculated for CPT codes and NLP for the entire cohort. CPT codes performed well in identifying stoma procedures (sensitivity 87.4%, specificity 97.5%). A total of 664 stoma procedures were identified by CPT codes between 2005 and 2011. The CPT codes were adequate in identifying stoma formation (sensitivity 97.7%, specificity 72.4%) and stoma reversal (sensitivity 74.1%, specificity 98.7%), but they were inadequate in identifying ileostomy (sensitivity 35.0%, specificity 88.1%) and colostomy (75.2% and 80.9%). NLP performed with greater sensitivity, specificity, and accuracy than CPT codes in identifying stoma procedures and stoma types. Major differences where NLP outperformed CPT included identifying ileostomy (specificity 95.8%, sensitivity 88.3%, and accuracy 91.5%) and colostomy (97.6%, 90.5%, and 92.8%, respectively). CPT codes can identify effectively patients who have had stoma procedures and are adequate in distinguishing between formation and reversal; however, CPT codes cannot differentiate ileostomy from colostomy. NLP can be used to differentiate between ileostomy- and colostomy-related procedures. The role of NLP in conjunction with electronic medical records in data retrieval warrants further investigation. Published by Mosby, Inc.

Exercise does not produce hypoalgesia when performed immediately after a painful stimulus.

PubMed

Gajsar, Hannah; Nahrwold, Katharina; Titze, Christina; Hasenbring, Monika I; Vaegter, Henrik B

2018-04-25

Exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM) are assumed to reflect descending pain inhibition. Potential interactions between EIH and CPM may be important in the therapy of chronic pain, as reduced CPM and increased pain after exercise are frequently observed. This study compared the EIH response after CPM was activated using a cold pressor task with the EIH response after a control condition. Thirty-one participants (age: 27.7±9.8; 15 female) completed two sessions: a cold pressor task (CPT) session, i.e. testing EIH with preceding CPM activation induced using a 2 min CPT at approximately 2°C, and a control session, i.e. testing EIH after a control condition (2 min of quiet rest). EIH was induced using a 15 min bicycling exercise at a target heart rate corresponding to 75% VO2 max. Repeated measures ANOVAs on pressure pain thresholds (PPTs) at the hand, back and leg were used to determine the effects of exercise after the cold pressor test and control condition. Furthermore, correlations between CPM and EIH, in the CPT session as well as control session, were calculated at each assessment site. A significant time x condition interaction (F(1, 30)=43.61, p<0.001, partial η2=0.59), with Bonferroni-corrected post-hoc t-tests showed that PPTs increased after exercise in the control session (p<0.001), but not in the CPT session (p=0.125). Furthermore, there was a small positive correlation of EIH in the control session and CPM at the hand (r=0.37, p=0.043). There was a moderate negative correlation of EIH in the CPT session and CPM at the hand (r=-0.50, p=0.004), and smaller negative correlations at the back (r=-0.37, p=0.036) and at the leg (r=-0.35, p=0.054). Attenuated EIH after the CPM activation in comparison to a control condition suggests that EIH and CPM may share underlying pain inhibitory mechanisms on a systemic level. This assumption is further supported by the finding of small to moderate significant correlations between EIH and CPM at the hand. The attenuated EIH response furthermore suggests that these mechanisms are exhaustible, i.e. that its effects decline after a certain amount of inhibition. In patients with chronic pain, assessing the current capacity of the descending pain inhibitory system - as indicated by the CPM response - may aid to make better predictions about how patients will respond to exercise with respect to acute pain reduction.

Assessing the temporal aspects of attention and its correlates in aging and chronic stroke patients.

PubMed

Shalev, Nir; Humphreys, Glyn; Demeyere, Nele

2016-11-01

Temporal dynamics of attention have been in the spotlight of research since the earliest days of cognitive psychology. Typically, researchers describe two different aspects of the temporal fluctuations of attention: one is in intervals of milliseconds (phasic alertness), and the other over minutes or even hours (tonic alertness or sustained attention). In order to evaluate individual capacities for sustained attention and phasic alertness, most studies rely on variations of the Continuous Performance Task (CPT). Indices of sustained attention and phasic alertness are typically based on reaction times to targets; phasic alertness is related to the change in reaction times following a cue, and sustained attention is related to variability of reaction times during the task. In the following study, we attempted to establish a new approach for studying sustained attention and phasic alertness, not reliant solely on reaction time measures. We developed a new variation of the CPT with conjunctive feature targets and forward and backward masking to induce a higher variability in accuracy. This allowed us to assess an individual's ability to maintain the same level of sensitivity to targets (d-prime) across a ten minute period on the task as an index for sustained attention. We also assessed reaction times as a function of previous trial type, and suggest previous trial RT benefit might be a marker for an individual's phasic alertness. We demonstrated the use of this task with healthy aging controls and stroke survivors. As a demonstration of external validity of the novel paradigm, we present a correlation between how individual performance drops over time and individual reports of distractibility in everyday life on the Cognitive Failures Questionnaire. In addition, we found significant differences between the patient and control groups in our proposed marker of phasic alertness. We discuss the implications of our study for current assessment tools, as well as general differences in phasic alertness between clinical and neurologically unimpaired groups. Copyright © 2016 Elsevier Ltd. All rights reserved.

Geotechnical parameter spatial distribution stochastic analysis based on multi-precision information assimilation

NASA Astrophysics Data System (ADS)

Wang, C.; Rubin, Y.

2014-12-01

Spatial distribution of important geotechnical parameter named compression modulus Es contributes considerably to the understanding of the underlying geological processes and the adequate assessment of the Es mechanics effects for differential settlement of large continuous structure foundation. These analyses should be derived using an assimilating approach that combines in-situ static cone penetration test (CPT) with borehole experiments. To achieve such a task, the Es distribution of stratum of silty clay in region A of China Expo Center (Shanghai) is studied using the Bayesian-maximum entropy method. This method integrates rigorously and efficiently multi-precision of different geotechnical investigations and sources of uncertainty. Single CPT samplings were modeled as a rational probability density curve by maximum entropy theory. Spatial prior multivariate probability density function (PDF) and likelihood PDF of the CPT positions were built by borehole experiments and the potential value of the prediction point, then, preceding numerical integration on the CPT probability density curves, the posterior probability density curve of the prediction point would be calculated by the Bayesian reverse interpolation framework. The results were compared between Gaussian Sequential Stochastic Simulation and Bayesian methods. The differences were also discussed between single CPT samplings of normal distribution and simulated probability density curve based on maximum entropy theory. It is shown that the study of Es spatial distributions can be improved by properly incorporating CPT sampling variation into interpolation process, whereas more informative estimations are generated by considering CPT Uncertainty for the estimation points. Calculation illustrates the significance of stochastic Es characterization in a stratum, and identifies limitations associated with inadequate geostatistical interpolation techniques. This characterization results will provide a multi-precision information assimilation method of other geotechnical parameters.

Madigan Army Medical Center Department of Clinical Investigation Annual Progress Report Fiscal Year 1999

DTIC Science & Technology

1999-09-30

Loaded Foot Marching vs Running on Injury , Fitness, and Performance In US Army Light Infantry Soldiers" presented by CPT Dan C. Norvell, SP Discovery...34Purple Toes" presented by CPT Brian P. Mulhall, MC Innovation - "Tracheal Mucosal Healing in Response to Moderate Mucosal Injury Induced by...Sports Medicine in U.S. Army Rangers: A Look at Injuries , Physical Training, and 08:20 Performance by CPT Daniel C. NorveU SP External Fixation of

ADHD Dimensions and Sluggish Cognitive Tempo Symptoms in Relation to Self-Report and Laboratory Measures of Neuropsychological Functioning in College Students.

PubMed

Jarrett, Matthew A; Rapport, Hannah F; Rondon, Ana T; Becker, Stephen P

2017-06-01

This study examined ADHD and sluggish cognitive tempo (SCT) symptoms in relation to self-report and laboratory measures of neuropsychological functioning in college students. College students ( N = 298, aged 17-25, 72% female) completed self-reports of ADHD, SCT, depression, sleep, functional impairment, and executive functioning (EF). Participants also completed a visual working memory task, a Stroop test, and the Conners' Continuous Performance Test-II (CPT-II). ADHD inattentive and SCT symptoms were strong predictors of self-reported EF, with inattention the strongest predictor of Time Management and Motivation and SCT the strongest predictor of Self-Organization/Problem Solving. SCT (but not inattention) was associated with Emotion Regulation. No relationships were found between self-reported symptoms and laboratory task performance. Between-group analyses were largely consistent with regression analyses. Self-reported ADHD and SCT symptoms are strongly associated with college students' self-reported EF, but relationships with laboratory task measures of neuropsychological functioning are limited.

Structural insight of DNA topoisomerases I from camptothecin-producing plants revealed by molecular dynamics simulations.

PubMed

Sirikantaramas, Supaart; Meeprasert, Arthitaya; Rungrotmongkol, Thanyada; Fuji, Hideyoshi; Hoshino, Tyuji; Sudo, Hiroshi; Yamazaki, Mami; Saito, Kazuki

2015-05-01

DNA topoisomerase I (Top1) catalyzes changes in DNA topology by cleaving and rejoining one strand of the double stranded (ds)DNA. Eukaryotic Top1s are the cellular target of the plant-derived anticancer indole alkaloid camptothecin (CPT), which reversibly stabilizes the Top1-dsDNA complex. However, CPT-producing plants, including Camptotheca acuminata, Ophiorrhiza pumila and Ophiorrhiza liukiuensis, are highly resistant to CPT because they possess point-mutated Top1. Here, the adaptive convergent evolution is reported between CPT production ability and mutations in their Top1, as a universal resistance mechanism found in all tested CPT-producing plants. This includes Nothapodytes nimmoniana, one of the major sources of CPT. To obtain a structural insight of the resistance mechanism, molecular dynamics simulations of CPT- resistant and -sensitive plant Top1s complexed with dsDNA and topotecan (a CPT derivative) were performed, these being compared to that for the CPT-sensitive human Top1. As a result, two mutations, Val617Gly and Asp710Gly, were identified in O. pumila Top1 and C. acuminata Top1, respectively. The substitutions at these two positions, surprisingly, are the same as those found in a CPT derivative-resistant human colon adenocarcinoma cell line. The results also demonstrated an increased linker flexibility of the CPT-resistant Top1, providing an additional explanation for the resistance mechanism found in CPT-producing plants. These mutations could reflect the long evolutionary adaptation of CPT-producing plant Top1s to confer a higher degree of resistance. Copyright © 2015 Elsevier Ltd. All rights reserved.

Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang, Zhong-Ze; Department of Toxicology, School of Public Health, Tianjin Medical University, Tianjin; Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian

Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showedmore » that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4{sup +} naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. - Highlights: • CPT-11 is an effective anticancer drug, but induced toxicity limits its application in the clinic. • CPT-11 decreased IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes. • CPT-11 altered the composition of bile acid metabolites, notably DCA and TDCA in liver, bile and intestine. • DCA and TDCA potentiated CPT-11-induced suppression of IL-10 secretion by active CD4{sup +} naive T cells.« less

Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism.

PubMed

Lee, Jieun; Wolfgang, Michael J

2012-10-25

Carnitine Palmitoyltransferase-1c (CPT1c) is a neuron specific homologue of the carnitine acyltransferase family of enzymes. CPT1 isoenzymes transfer long chain acyl groups to carnitine. This constitutes a rate setting step for mitochondrial fatty acid beta-oxidation by facilitating the initial step in acyl transfer to the mitochondrial matrix. In general, neurons do not heavily utilize fatty acids for bioenergetic needs and definitive enzymatic activity has been unable to be demonstrated for CPT1c. Although there are studies suggesting an enzymatic role of CPT1c, its role in neurochemistry remains elusive. In order to better understand how CPT1c functions in neural metabolism, we performed unbiased metabolomic profiling on wild-type (WT) and CPT1c knockout (KO) mouse brains. Consistent with the notion that CPT1c is not involved in fatty acid beta-oxidation, there were no changes in metabolites associated with fatty acid oxidation. Endocannabinoids were suppressed in the CPT1c KO, which may explain the suppression of food intake seen in CPT1c KO mice. Although products of beta-oxidation were unchanged, small changes in carnitine and carnitine metabolites were observed. Finally, we observed changes in redox homeostasis including a greater than 2-fold increase in oxidized glutathione. This indicates that CPT1c may play a role in neural oxidative metabolism. Steady-state metabolomic analysis of CPT1c WT and KO mouse brains identified a small number of metabolites that differed between CPT1c WT and KO mice. The subtle changes in a broad range of metabolites in vivo indicate that CPT1c does not play a significant or required role in fatty acid oxidation; however, it could play an alternative role in neuronal oxidative metabolism.

Sustained attention deficits among HIV-positive individuals with comorbid bipolar disorder.

PubMed

Posada, Carolina; Moore, David J; Deutsch, Reena; Rooney, Alexandra; Gouaux, Ben; Letendre, Scott; Grant, Igor; Atkinson, J Hampton

2012-01-01

Difficulties with sustained attention have been found among both persons with HIV infection (HIV+) and bipolar disorder (BD). The authors examined sustained attention among 39 HIV+ individuals with BD (HIV+/BD+) and 33 HIV-infected individuals without BD (HIV+/BD-), using the Conners' Continuous Performance Test-II (CPT-II). A Global Assessment of Functioning (GAF) score was also assigned to each participant as an overall indicator of daily functioning abilities. HIV+/BD+ participants had significantly worse performance on CPT-II omission errors, hit reaction time SE (Hit RT SE), variability of SE, and perseverations than HIV+/BD- participants. When examining CPT-II performance over the six study blocks, both HIV+/BD+ and HIV+/BD- participants evidenced worse performance on scores of commission errors and reaction times as the test progressed. The authors also examined the effect of current mood state (i.e., manic, depressive, euthymic) on CPT-II performance, but no significant differences were observed across the various mood states. HIV+/BD+ participants had significantly worse GAF scores than HIV+/BD- participants, which indicates poorer overall functioning in the dually-affected group; among HIV+/BD+ persons, significant negative correlations were found between GAF scores and CPT-II omission and commission errors, detectability, and perseverations, indicating a possible relationship between decrements in sustained attention and worse daily-functioning outcomes.

The utility of quantitative electroencephalography and Integrated Visual and Auditory Continuous Performance Test as auxiliary tools for the Attention Deficit Hyperactivity Disorder diagnosis.

PubMed

Kim, JunWon; Lee, YoungSik; Han, DougHyun; Min, KyungJoon; Kim, DoHyun; Lee, ChangWon

2015-03-01

This study investigated the clinical utility of quantitative electroencephalography (QEEG) and the Integrated Visual and Auditory Continuous Performance Test (IVA+CPT) as auxiliary tools for assessing Attention Deficit Hyperactivity Disorder (ADHD). All of 157 subjects were assessed using the Korean version of the Diagnostic Interview Schedule for Children Version IV (DISC-IV). We measured EGG absolute power in 21 channels and conducted IVA+CPT. We analyzed QEEG according to the Hz range: delta (1-4Hz), theta (4-8Hz), slow alpha (8-10Hz), fast alpha (10-13.5Hz), and beta (13.5-30Hz). To remove artifacts, independent component analysis was conducted (ICA), and the tester confirmed the results again. All of the IVA+CPT quotients showed significant differences between the ADHD and control groups. The ADHD group showed significantly increased delta and theta activity compared with the control group. The z-scores of theta were negatively correlated with the scores of IVA+CPT in ADHD combined type, and those of beta were positively correlated. IVA+CPT and QEEG significantly discriminated between ADHD and control groups. The commission error of IVA+CPT showed an accuracy of 82.1%, and the omission error of IVA+CPT showed an accuracy of 78.6%. The IVA+CPT and QEEG are expected to be valuable tools for aiding ADHD diagnosis accurately. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Constructive polarization modulation for coherent population trapping clock

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yun, Peter, E-mail: enxue.yun@obspm.fr; Danet, Jean-Marie; Holleville, David

2014-12-08

We propose a constructive polarization modulation scheme for atomic clocks based on coherent population trapping (CPT). In this scheme, the polarization of a bichromatic laser beam is modulated between two opposite circular polarizations to avoid trapping the atomic populations in the extreme Zeeman sublevels. We show that if an appropriate phase modulation between the two optical components of the bichromatic laser is applied synchronously, the two CPT dark states which are produced successively by the alternate polarizations add constructively. Measured CPT resonance contrasts up to 20% in one-pulse CPT and 12% in two-pulse Ramsey-CPT experiments are reported, demonstrating the potentialmore » of this scheme for applications to high performance atomic clocks.« less

[Comparison between the diagnosis of attention deficit hyperactivity disorder with the DSM-5 and neuropsychological evaluation of the executive functions].

PubMed

Abad-Mas, L; Caloca-Catala, O; Mulas, F; Ruiz-Andres, R

2017-02-24

The attention deficit-hyperactivity disorder (ADHD) has a prevalence among 3-7% in scholar population and it is associated with learning disabilities and executive dysfunctions. To study the relationship between the ADHD diagnostic through DSM-5 criteria and the neuropshychology evaluation of executive functions. The sample of this study consisted in 50 subjects, 12 females and 38 males, with an age between 8 and 10 years old. To evaluate the inhibitory control, we used the Stroop Test and the Continuous Performance Test (CPT), to evaluate intelligence and working memory we use the Wechsler Intelligence Scale WISC-IV, to evaluate attention we used the CPT and Selective Attention Test. There weren't significant differences between both subtypes of ADHD regarding working memory, on the other hand the female group had better abilities in cognitive flexibility task than males and subjects diagnosed with combined ADHD had more difficulties in inhibitory control. We can confirm that the definition of ADHD in DSM-5 isn't enough as them are imprecise. Therefore, the disease definition it's performed by a specific evaluation of attention and inhibitory control mechanisms and its necessary a neuropshychological evaluation of these brain functions.

Genetic and developmental factors in spontaneous selective attention: a study of normal twins.

PubMed

Myles-Worsley, M; Coon, H

1997-08-08

The Spontaneous Selective Attention Task (SSAT) is a visual word identification task designed to measure the type of selective attention that occurs spontaneously when there are multiple stimuli, all potentially relevant, and insufficient time to process each of them fully. These are conditions which are common in everyday life. SSAT performance is measured by word identification accuracy, first under a baseline divided attention condition with no predictability, then under a selective attention condition with partial predictability introduced via word repetition. Accuracy to identify novel words in the upper location which becomes partially predictable (P words) vs. the lower location which remains non-predictable (N words) can be used to calculate a baseline performance index and a P/N ratio measure of selective attention. The SSAT has been shown to identify an attentional abnormality that may be useful in the development of an attentional endophenotype for family-genetic studies of schizophrenia. This study examined age and genetic effects on SSAT performance in normal children in order to evaluate whether the SSAT has the potential to qualify as a candidate endophenotype for schizophrenia in studies of at-risk children. A total of 59 monozygotic twin pairs and 33 same-sex dizygotic twin pairs ranging from 10 to 18 years of age were tested on the SSAT, a Continuous Performance Test. (CPT), a Span of Apprehension Test (SPAN) and a full-scale IQ test. Baseline performance on the SSAT, which was correlated with verbal IQ and SPAN performance, improved with age but showed no significant heritability. The P/N selectivity ratio was stable over the 10-18-year age range, was not significantly correlated with IQ, CPT, or SPAN performance, and its heritability was estimated to be 0.41. These findings suggest that the P/N selectivity ratio measured by the SSAT may be useful as a vulnerability marker in studies of children born into families segregating schizophrenia.

Repeatability of cold pressor test-induced flow increase assessed with H(2)(15)O and PET.

PubMed

Siegrist, Patrick T; Gaemperli, Oliver; Koepfli, Pascal; Schepis, Tiziano; Namdar, Mehdi; Valenta, Ines; Aiello, Floreana; Fleischmann, Samuel; Alkadhi, Hatem; Kaufmann, Philipp A

2006-09-01

The aim of this study was to evaluate the repeatability of endothelium-related myocardial blood flow (MBF) responses to cold pressor testing (CPT) as assessed by PET. In 10 age-matched control subjects (26.6 +/- 3.4 y) and 10 tobacco smokers (24.9 +/- 3.3 y) MBF was assessed at rest and after repeated CPT (CPT1 and CPT2, 40 min apart) using PET with H(2)(15)O. CPT was performed by a 2-min immersion of the subject's foot in ice water. MBF values were corrected for cardiac workload (rate.pressure product), and the repeatability of CPT-related MBF values was assessed according to Bland and Altman. Corrected MBF at CPT1 and CPT2 were comparable in control subjects (1.79 +/- 0.37 vs. 1.70 +/- 0.35 mL/min/g; P = not significant [NS]) and in smokers (1.97 +/- 0.42 vs. 1.80 +/- 0.41 mL/min/g; P = NS). Repeatability coefficients in control subjects and smokers were 0.46 mL/min/g (27% of the mean MBF) and 0.51 mL/min/g (27%), respectively. MBF increased significantly after CPT in both groups but tended to be lower in smokers (P = 0.08). PET measured MBF combined with CPT is a feasible and repeatable method for the evaluation of endothelium-related changes of MBF.

Improving visual memory, attention, and school function with atomoxetine in boys with attention-deficit/hyperactivity disorder.

PubMed

Shang, Chi-Yung; Gau, Susan Shur-Fen

2012-10-01

Atomoxetine is efficacious in reducing symptoms of attention- deficit/hyperactivity disorder (ADHD), but its effect on visual memory and attention needs more investigation. This study aimed to assess the effect of atomoxetine on visual memory, attention, and school function in boys with ADHD in Taiwan. This was an open-label 12 week atomoxetine treatment trial among 30 drug-naíve boys with ADHD, aged 8-16 years. Before administration of atomoxetine, the participants were assessed using psychiatric interviews, the Wechsler Intelligence Scale for Children, 3rd edition (WISC-III), the school function of the Chinese version of the Social Adjustment Inventory for Children and Adolescents (SAICA), the Conners' Continuous Performance Test (CPT), and the tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB) involving visual memory and attention: Pattern Recognition Memory, Spatial Recognition Memory, and Reaction Time, which were reassessed at weeks 4 and 12. Our results showed there was significant improvement in pattern recognition memory and spatial recognition memory as measured by the CANTAB tasks, sustained attention and response inhibition as measured by the CPT, and reaction time as measured by the CANTAB after treatment with atomoxetine for 4 weeks or 12 weeks. In addition, atomoxetine significantly enhanced school functioning in children with ADHD. Our findings suggested that atomoxetine was associated with significant improvement in visual memory, attention, and school functioning in boys with ADHD.

Antifungal activity directed toward the Cell wall by 2-cyclohexylidenhydrazo-4-phenyl-thiazole against Candida albicans.

PubMed

de Sa, Nivea Pereira; Possa, Ana Paula; Perez, Pilar; Ferreira, Jaqueline Maria Siqueira; Fonseca, Nayara Cristina; Lino, Cleudiomar Inacio; Cruz, Lana Barreto; de Oliveira, Renata Barbosa; Rosa, Carlos Augusto; Borelli, Beatriz Martins; Mylonakis, Eleftherios; Fuchs, Beth Burgwyn; Johann, Susana

2018-05-30

Background The increasing incidence of invasive forms of candidiasis and resistance to antifungal therapy leads us to seek new and more effective antifungal compounds. Objectives Investigate the antifungal activity and toxicity as well as to evaluate the potential targets of 2-cyclohexylidenhydrazo-4-phenyl-thiazole (CPT) in Candida albicans. Methods The antifungal activity of CPT against the survival of C. albicans was investigated in Caenorhabditis elegans. Additionally, we determined the effect of CPT on the inhibition of C. albicans adhesion capacity to buccal epithelial cells (BECs), the toxicity of CPT in mammalian cells, and the potential targets of CPT in C. albicans. Results CPT exhibited a minimum inhibitory concentration (MIC) value of 0.4-1.9 µg/mL. Furthermore, CPT at high concentrations (>60 x MIC) showed no or low toxicity in HepG2 cells and <1% haemolysis in human erythrocytes. In addition, CPT decreased the adhesion capacity of yeasts to the BECs and prolonged the survival of C. elegans infected with C. albicans. Analysis of CPT-treated the cells showed that their cell wall was thinner than that of untreated cells, especially the glucan layer. We found that there was a significantly lower quantity of 1,3-β-D-glucan present in CPT-treated cells than that in untreated cells. Assays performed on several mutant strains showed that the MIC value of CPT was high for its antifungal activity on yeasts with defective 1,3-β-glucan synthase. Conclusions In conclusion, CPT appears to target the cell wall of C. albicans, exhibits low toxicity in mammalian cells, and prolongs the survival of C. elegans infected with C. albicans. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

High IQ May "Mask" the Diagnosis of ADHD by Compensating for Deficits in Executive Functions in Treatment-Naïve Adults With ADHD.

PubMed

Milioni, Ana Luiza Vidal; Chaim, Tiffany Moukbel; Cavallet, Mikael; de Oliveira, Nathalya Moleda; Annes, Marco; Dos Santos, Bernardo; Louzã, Mario; da Silva, Maria Aparecida; Miguel, Carmen Silvia; Serpa, Mauricio Henriques; Zanetti, Marcus V; Busatto, Geraldo; Cunha, Paulo Jannuzzi

2017-04-01

To evaluate and compare the performance of adults with ADHD with high and standard IQ in executive functions (EF) tasks. We investigated the neuropsychological performance of 51 adults with ADHD, compared with 33 healthy controls (HC) while performing a wide battery of neuropsychological tests that measure executive functioning. Adults with clinical diagnosis of ADHD were divided into two groups according to their IQ level (IQ ≥ 110-ADHD group with more elevated IQ, and IQ < 110-ADHD group with standard IQ). The ADHD group with standard IQ presented a worse executive functioning compared with the HC group in the following measures: Stroop 2 ( p = .000) and 3 ( p = .000), Trail Making Test (TMT) B ( p = .005), Wisconsin Card-Sorting Test (WCST)-perseverative errors ( p = .022) and failures to maintain set ( p = .020), Continuous Performance Test (CPT)-omission errors ( p = .005) and commission errors ( p = .000), and Frontal Assessment Battery (FAB)-conceptualization ( p = .016). The ADHD group with more elevated IQ presented only impairments in the CPT-commission errors ( p = .019) when compared with the control group. Adults with ADHD and more elevated IQ show less evidence of executive functioning deficits compared with those with ADHD and standard IQ, suggesting that a higher degree of intellectual efficiency may compensate deficits in executive functions, leading to problems in establishing a precise clinical diagnosis.

Cerebral glucose metabolic differences in patients with panic disorder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nordahl, T.E.; Semple, W.E.; Gross, M.

Regional glucose metabolic rates were measured in patients with panic disorder during the performance of auditory discrimination. Those regions examined by Reiman and colleagues in their blood flow study of panic disorder were examined with a higher resolution positron emission tomography (PET) scanner and with the tracer (F-18)-2-fluoro-2-deoxyglucose (FDG). In contrast to the blood flow findings of Reiman et al., we did not find global gray metabolic differences between patients with panic disorder and normal controls. Consistent with the findings of Reiman et al., we found hippocampal region asymmetry. We also found metabolic decreases in the left inferior parietal lobulemore » and in the anterior cingulate (trend), as well as an increase in the metabolic rate of the medial orbital frontal cortex (trend) of panic disorder patients. It is unclear whether the continuous performance task (CPT) enhanced or diminished findings that would have been noted in a study performed without task.« less

Experimental Psychological Stress on Quantitative Sensory Testing Response in Patients with Temporomandibular Disorders.

PubMed

Araújo Oliveira Ferreira, Dyna Mara; Costa, Yuri Martins; de Quevedo, Henrique Müller; Bonjardim, Leonardo Rigoldi; Rodrigues Conti, Paulo César

2018-05-15

To assess the modulatory effects of experimental psychological stress on the somatosensory evaluation of myofascial temporomandibular disorder (TMD) patients. A total of 20 women with myofascial TMD and 20 age-matched healthy women were assessed by means of a standardized battery of quantitative sensory testing. Cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), heat pain threshold (HPT), mechanical pain threshold (MPT), wind-up ratio (WUR), and pressure pain threshold (PPT) were performed on the facial skin overlying the masseter muscle. The variables were measured in three sessions: before (baseline) and immediately after the Paced Auditory Serial Addition Task (PASAT) (stress) and then after a washout period of 20 to 30 minutes (poststress). Mixed analysis of variance (ANOVA) was applied to the data, and the significance level was set at P = .050. A significant main effect of the experimental session on all thermal tests was found (ANOVA: F > 4.10, P < .017), where detection tests presented an increase in thresholds in the poststress session compared to baseline (CDT, P = .012; WDT, P = .040) and pain thresholds were reduced in the stress (CPT, P < .001; HPT, P = .001) and poststress sessions (CPT, P = .005; HPT, P = .006) compared to baseline. In addition, a significant main effect of the study group on all mechanical tests (MPT, WUR, and PPT) was found (ANOVA: F > 4.65, P < .037), where TMD patients were more sensitive than healthy volunteers. Acute mental stress conditioning can modulate thermal sensitivity of the skin overlying the masseter in myofascial TMD patients and healthy volunteers. Therefore, psychological stress should be considered in order to perform an unbiased somatosensory assessment of TMD patients.

Altered cortical thickness and attentional deficits in adolescent girls and women with bulimia nervosa

PubMed Central

Stefan, Mihaela; Lee, Seonjoo; Wang, Zhishun; Terranova, Kate; Attia, Evelyn; Marsh, Rachel

2018-01-01

Background Frontostriatal and frontoparietal abnormalities likely contribute to deficits in control and attentional processes in individuals with bulimia nervosa and to the persistence of dysregulated eating across development. This study assessed these processes and cortical thickness in a large sample of adolescent girls and women with bulimia nervosa compared with healthy controls. Methods We collected anatomical MRI data from adolescent girls and women (ages 12–38 yr) with full or subthreshold bulimia nervosa and age-matched healthy controls who also completed the Conners Continuous Performance Test-II (CPT-II). Groups were compared on task performance and cortical thickness. Mediation analyses explored associations among cortical thickness, CPT-II variables, bulimia nervosa symptoms and age. Results We included 60 girls and women with bulimia nervosa and 54 controls in the analyses. Compared with healthy participants, those with bulimia nervosa showed increased impulsivity and inattention on the CPT-II, along with reduced thickness of the right pars triangularis, right superior parietal and left dorsal posterior cingulate cortices. In the bulimia nervosa group, exploratory analyses revealed that binge eating frequency correlated inversely with cortical thickness of frontoparietal and insular regions and that reduced frontoparietal thickness mediated the association between age and increased symptom severity and inattention. Binge eating frequency also mediated the association between age and lower prefrontal cortical thickness. Limitations These findings are applicable to only girls and women with bulimia nervosa, and our cross-sectional design precludes understanding of whether cortical thickness alterations precede or result from bulimia nervosa symptoms. Conclusion Structural abnormalities in the frontoparietal and posterior cingulate regions comprising circuits that support control and attentional processes should be investigated as potential contributors to the maintenance of bulimia nervosa and useful targets for novel interventions. PMID:29688871

Altered cortical thickness and attentional deficits in adolescent girls and women with bulimia nervosa.

PubMed

Berner, Laura A; Stefan, Mihaela; Lee, Seonjoo; Wang, Zhishun; Terranova, Kate; Attia, Evelyn; Marsh, Rachel

2018-05-01

Frontostriatal and frontoparietal abnormalities likely contribute to deficits in control and attentional processes in individuals with bulimia nervosa and to the persistence of dysregulated eating across development. This study assessed these processes and cortical thickness in a large sample of adolescent girls and women with bulimia nervosa compared with healthy controls. We collected anatomical MRI data from adolescent girls and women (ages 12-38 yr) with full or subthreshold bulimia nervosa and age-matched healthy controls who also completed the Conners Continuous Performance Test-II (CPT-II). Groups were compared on task performance and cortical thickness. Mediation analyses explored associations among cortical thickness, CPT-II variables, bulimia nervosa symptoms and age. We included 60 girls and women with bulimia nervosa and 54 controls in the analyses. Compared with healthy participants, those with bulimia nervosa showed increased impulsivity and inattention on the CPT-II, along with reduced thickness of the right pars triangularis, right superior parietal and left dorsal posterior cingulate cortices. In the bulimia nervosa group, exploratory analyses revealed that binge eating frequency correlated inversely with cortical thickness of frontoparietal and insular regions and that reduced frontoparietal thickness mediated the association between age and increased symptom severity and inattention. Binge eating frequency also mediated the association between age and lower prefrontal cortical thickness. These findings are applicable to only girls and women with bulimia nervosa, and our cross-sectional design precludes understanding of whether cortical thickness alterations precede or result from bulimia nervosa symptoms. Structural abnormalities in the frontoparietal and posterior cingulate regions comprising circuits that support control and attentional processes should be investigated as potential contributors to the maintenance of bulimia nervosa and useful targets for novel interventions.

Altered cortical thickness and attentional deficits in adolescent girls and women with bulimia nervosa.

PubMed

Berner, Laura A; Stefan, Mihaela; Lee, Seonjoo; Wang, Zhishun; Terranova, Kate; Attia, Evelyn; Marsh, Rachel

2018-01-12

Frontostriatal and frontoparietal abnormalities likely contribute to deficits in control and attentional processes in individuals with bulimia nervosa and to the persistence of dysregulated eating across development. This study assessed these processes and cortical thickness in a large sample of adolescent girls and women with bulimia nervosa compared with healthy controls. We collected anatomical MRI data from adolescent girls and women (ages 12-38 yr) with full or subthreshold bulimia nervosa and age-matched healthy controls who also completed the Conners Continuous Performance Test-II (CPT-II). Groups were compared on task performance and cortical thickness. Mediation analyses explored associations among cortical thickness, CPT-II variables, bulimia nervosa symptoms and age. We included 60 girls and women with bulimia nervosa and 54 controls in the analyses. Compared with healthy participants, those with bulimia nervosa showed increased impulsivity and inattention on the CPT-II, along with reduced thickness of the right pars triangularis, right superior parietal and left dorsal posterior cingulate cortices. In the bulimia nervosa group, exploratory analyses revealed that binge eating frequency correlated inversely with cortical thickness of frontoparietal and insular regions and that reduced frontoparietal thickness mediated the association between age and increased symptom severity and inattention. Binge eating frequency also mediated the association between age and lower prefrontal cortical thickness. These findings are applicable to only girls and women with bulimia nervosa, and our cross-sectional design precludes understanding of whether cortical thickness alterations precede or result from bulimia nervosa symptoms. Structural abnormalities in the frontoparietal and posterior cingulate regions comprising circuits that support control and attentional processes should be investigated as potential contributors to the maintenance of bulimia nervosa and useful targets for novel interventions.

Anticipation of Monetary Reward Can Attenuate the Vigilance Decrement

PubMed Central

Grosso, Mallory; Liu, Guanyu; Mitko, Alex; Morris, Rachael; DeGutis, Joseph

2016-01-01

Motivation and reward can have differential effects on separate aspects of sustained attention. We previously demonstrated that continuous reward/punishment throughout a sustained attention task improves overall performance, but not vigilance decrements. One interpretation of these findings is that vigilance decrements are due to resource depletion, which is not overcome by increasing overall motivation. However, an alternative explanation is that as one performs a continuously rewarded task there are less potential gains/losses as the task progresses, which could decrease motivation over time, producing a vigilance decrement. This would predict that keeping future gains/losses consistent throughout the task would reduce the vigilance decrement. In the current study, we examined this possibility by comparing two versions (continuous-small loss vs. anticipate-large loss) of a 10-minute gradual onset continuous performance task (gradCPT), a challenging go/no-go sustained attention task. Participants began each task with the potential to keep $18. In the continuous-small-loss version, small monetary losses were accrued continuously throughout the task for each error. However, in the anticipate-large-loss version, participants lost all $18 if they erroneously responded to one target that always appeared toward the end of the vigil. Typical vigilance decrements were observed in the continuous-small-loss condition. In the anticipate-large-loss condition, vigilance decrements were reduced, particularly when the anticipate-large loss condition was completed second. This suggests that the looming possibility of a large loss can attenuate the vigilance decrement and that this attenuation may occur most consistently after sufficient task experience. We discuss these results in the context of current theories of sustained attention. PMID:27472785

Effects of high-intensity intermittent training on carnitine palmitoyl transferase activity in the gastrocnemius muscle of rats

PubMed Central

Carnevali, L.C.; Eder, R.; Lira, F.S.; Lima, W.P.; Gonçalves, D.C.; Zanchi, N.E.; Nicastro, H.; Lavoie, J.M.; Seelaender, M.C.L.

2012-01-01

We examined the capacity of high-intensity intermittent training (HI-IT) to facilitate the delivery of lipids to enzymes responsible for oxidation, a task performed by the carnitine palmitoyl transferase (CPT) system in the rat gastrocnemius muscle. Male adult Wistar rats (160-250 g) were randomly distributed into 3 groups: sedentary (Sed, N = 5), HI-IT (N = 10), and moderate-intensity continuous training (MI-CT, N = 10). The trained groups were exercised for 8 weeks with a 10% (HI-IT) and a 5% (MI-CT) overload. The HI-IT group presented 11.8% decreased weight gain compared to the Sed group. The maximal activities of CPT-I, CPT-II, and citrate synthase were all increased in the HI-IT group compared to the Sed group (P < 0.01), as also was gene expression, measured by RT-PCR, of fatty acid binding protein (FABP; P < 0.01) and lipoprotein lipase (LPL; P < 0.05). Lactate dehydrogenase also presented a higher maximal activity (nmol·min−1·mg protein−1) in HI-IT (around 83%). We suggest that 8 weeks of HI-IT enhance mitochondrial lipid transport capacity thus facilitating the oxidation process in the gastrocnemius muscle. This adaptation may also be associated with the decrease in weight gain observed in the animals and was concomitant to a higher gene expression of both FABP and LPL in HI-IT, suggesting that intermittent exercise is a “time-efficient” strategy inducing metabolic adaptation. PMID:22735180

Is There a Conjunction Fallacy in Legal Probabilistic Decision Making?

PubMed

Wojciechowski, Bartosz W; Pothos, Emmanuel M

2018-01-01

Classical probability theory (CPT) has represented the rational standard for decision making in human cognition. Even though CPT has provided many descriptively excellent decision models, there have also been some empirical results persistently problematic for CPT accounts. The tension between the normative prescription of CPT and human behavior is particularly acute in cases where we have higher expectations for rational decisions. One such case concerns legal decision making from legal experts, such as attorneys and prosecutors and, more so, judges. In the present research we explore one of the most influential CPT decision fallacies, the conjunction fallacy (CF), in a legal decision making task, involving assessing evidence that the same suspect had committed two separate crimes. The information for the two crimes was presented consecutively. Each participant was asked to provide individual ratings for the two crimes in some cases and conjunctive probability rating for both crimes in other cases, after all information had been presented. Overall, 360 probability ratings for guilt were collected from 120 participants, comprised of 40 judges, 40 attorneys and prosecutors, and 40 individuals without legal education. Our results provide evidence for a double conjunction fallacy (in this case, a higher probability of committing both crimes than the probability of committing either crime individually), in the group of individuals without legal education. These results are discussed in terms of their applied implications and in relation to a recent framework for understanding such results, quantum probability theory (QPT).

Is There a Conjunction Fallacy in Legal Probabilistic Decision Making?

PubMed Central

Wojciechowski, Bartosz W.; Pothos, Emmanuel M.

2018-01-01

Classical probability theory (CPT) has represented the rational standard for decision making in human cognition. Even though CPT has provided many descriptively excellent decision models, there have also been some empirical results persistently problematic for CPT accounts. The tension between the normative prescription of CPT and human behavior is particularly acute in cases where we have higher expectations for rational decisions. One such case concerns legal decision making from legal experts, such as attorneys and prosecutors and, more so, judges. In the present research we explore one of the most influential CPT decision fallacies, the conjunction fallacy (CF), in a legal decision making task, involving assessing evidence that the same suspect had committed two separate crimes. The information for the two crimes was presented consecutively. Each participant was asked to provide individual ratings for the two crimes in some cases and conjunctive probability rating for both crimes in other cases, after all information had been presented. Overall, 360 probability ratings for guilt were collected from 120 participants, comprised of 40 judges, 40 attorneys and prosecutors, and 40 individuals without legal education. Our results provide evidence for a double conjunction fallacy (in this case, a higher probability of committing both crimes than the probability of committing either crime individually), in the group of individuals without legal education. These results are discussed in terms of their applied implications and in relation to a recent framework for understanding such results, quantum probability theory (QPT). PMID:29674983

Relating children's attentional capabilities to intelligence, memory, and academic achievement: a test of construct specificity in children with asthma.

PubMed

Annett, Robert D; Bender, Bruce G; Gordon, Michael

2007-01-01

The relationship between attention, intelligence, memory, achievement, and behavior in a large population (N = 939) of children without neuropsychologic problems was investigated in children with mild and moderate asthma. It was hypothesized that different levels of children's attentional capabilities would be associated with different levels of intellectual, memory, and academic abilities. Children ages 6-12 at the eight clinical centers of the Childhood Asthma Management Program (CAMP) were enrolled in this study. Standardized measures of child neuropsychological and behavioral performance were administered to all participants, with analyses examining both the developmental trajectory of child attentional capabilities and the associations between Continuous Performance Test (CPT) scores and intellectual functioning, and measures of memory, academic achievement, and behavioral functioning. Findings demonstrated that correct responses on the CPT increase significantly with age, while commission errors decrease significantly with age. Performance levels on the CPT were associated with differences in child intellectual function, memory, and academic achievement. Overall these findings reveal how impairments in child attention skills were associated with normal levels of performance on measures of children's intelligence, memory, academic achievement, and behavioral functioning, suggesting that CPT performance is a salient marker of brain function.

Coherent Population Trapping and Optical Ramsey Interference for Compact Rubidium Clock Development

NASA Astrophysics Data System (ADS)

Warren, Zachary Aron

Coherent population trapping (CPT) and optical Ramsey interference provide new avenues for developing compact, high-performance atomic clocks. In this work, I have studied the fundamental aspects of CPT and optical Ramsey interference for Raman clock development. This thesis research is composed of two parts: theoretical and experimental studies. The theoretical component of the research was initially based on pre-existing atomic models of a three-level ?-type system in which the phenomena of CPT and Ramsey interference are formed. This model served as a starting point for studying basic characteristics of CPT and Ramsey interference such as power dependence of CPT, effects of average detuning, and ground-state decoherence on linewidth, which directly impact the performance of the Raman clock. The basic three-level model was also used to model pulsed CPT excitation and measure light shift in Ramsey interference which imposes a fundamental limit on the long-term frequency stability of the Raman clock. The theoretical calculations illustrate reduction (or suppression) of light shift in Ramsey interference as an important advantage over CPT for Raman clock development. To make the model more accurate than an ideal three-level system, I developed a comprehensive atomic model using density-matrix equations including all sixteen Zeeman sublevels in the D1 manifold of 87Rb atoms in a vapor medium. The multi-level atomic model has been used for investigating characteristics of CPT and Ramsey interference under different optical excitation schemes pertaining to the polarization states of the frequency-modulated CPT beam in a Raman clock. It is also used to study the effects of axial and traverse magnetic fields on the contrast of CPT and Ramsey interference. More importantly, the multi-level atomic model is also used to accurately calculate light shift in Ramsey interference in the D1 manifold of 87Rb atoms by taking into account all possible off-resonant excitations and the ground-state decoherence among the Zeeman sublevels. Light shift suppression in Ramsey interference with pulse saturation is also found to be evident in this comprehensive model. In the experimental component of the research, I designed a prototype of the Raman clock using a small (2 cm in length), buffer-gas filled, and isotopically pure 87Rb cell. A fiber-coupled waveguide electro-optic modulator was used to generate the frequency-modulated CPT beam for the experiments. The experimental setup was operated either by continuous excitation or pulsed excitation for experimentally characterizing CPT and Ramsey interference under different experimental conditions and for testing different optical excitation schemes which were investigated theoretically. Several iterations of the clock physics package were developed in order to attain better frequency stability performance in the Raman clock. The experimental work also provided a basis to develop a new repeated-query technique for producing an ultra-narrow linewidth central fringe with a high S/N ratio, and suppressing the side fringes in Ramsey interference. The above described research was carried out keeping in mind compact, high-performance clock development, which relies on technologies that can be miniaturized. Vapor cell based atomic clocks are ideal candidates for compact clock technology. The CPT phenomenon, observed by Raman excitation in a vapor medium, is a promising candidate for compact, high-performance Raman clock development. However, atom-field interaction involved in a vapor medium is often more complex than other media such as cold atom or atomic beam. It is difficult to model this interaction in order to predict its influence on CPT characteristics and, hence, the performance of the Raman clock. This dissertation addresses one such problem by developing a comprehensive atomic model to investigate light shift and modification of light shift in the Raman clock, particularly with pulsed excitation. It demonstrates a clear possibility of reducing (or suppressing) the light shift associated with Ramsey interference in a vapor medium for achieving higher frequency stability in the Raman clock. Additionally, theoretical comparisons of various optical excitation techniques have been calculated to demonstrate the relative strengths and weaknesses of different schemes for Raman clock development. (Abstract shortened by ProQuest.).

Stress and selective attention: Immediate and delayed stress effects on inhibition of return.

PubMed

Larra, Mauro F; Pramme, Lisa; Schächinger, Hartmut; Frings, Christian

2016-10-01

The relationship between attention and stress is far from understood. In fact, some studies reported better attentional selection during and after stress, some studies reported worse attentional selection, and some studies reported no effects of stress on attentional selection at all. We argue that given the complexity of both concepts more data are needed as to ultimately understand this relationship. Here we use an established attentional task that yields the inhibition of return (IOR) effect which is assumed to tap attentional control of oculomotor behavior. Participants were stressed with a Cold Pressor Test (CPT) and immediate and delayed effects of stress on hypothalamus-pituitary-adrenal (HPA) axis activation and IOR were analyzed. IOR was neither by immediate nor by delayed after-effects of the CPT stress procedure modulated, instead, we observed reliable and significant IOR in all experimental conditions. Attentional control of oculomotor behavior is therefore not altered after CPT stress, nor related to the post-stress activity of the HPA axis. Copyright © 2016 Elsevier Inc. All rights reserved.

Objectively-measured impulsivity and attention-deficit/hyperactivity disorder (ADHD): testing competing predictions from the working memory and behavioral inhibition models of ADHD.

PubMed

Raiker, Joseph S; Rapport, Mark D; Kofler, Michael J; Sarver, Dustin E

2012-07-01

Impulsivity is a hallmark of two of the three DSM-IV ADHD subtypes and is associated with myriad adverse outcomes. Limited research, however, is available concerning the mechanisms and processes that contribute to impulsive responding by children with ADHD. The current study tested predictions from two competing models of ADHD-working memory (WM) and behavioral inhibition (BI)-to examine the extent to which ADHD-related impulsive responding was attributable to model-specific mechanisms and processes. Children with ADHD (n = 21) and typically developing children (n = 20) completed laboratory tasks that provided WM (domain-general central executive [CE], phonological/visuospatial storage/rehearsal) and BI indices (stop-signal reaction time [SSRT], stop-signal delay, mean reaction time). These indices were examined as potential mediators of ADHD-related impulsive responding on two objective and diverse laboratory tasks used commonly to assess impulsive responding (CPT: continuous performance test; VMTS: visual match-to-sample). Bias-corrected, bootstrapped mediation analyses revealed that CE processes significantly attenuated between-group impulsivity differences, such that the initial large-magnitude impulsivity differences were no longer significant on either task after accounting for ADHD-related CE deficits. In contrast, SSRT partially mediated ADHD-related impulsive responding on the CPT but not VMTS. This partial attenuation was no longer significant after accounting for shared variance between CE and SSRT; CE continued to attenuate the ADHD-impulsivity relationship after accounting for SSRT. These findings add to the growing literature implicating CE deficits in core ADHD behavioral and functional impairments, and suggest that cognitive interventions targeting CE rather than storage/rehearsal or BI processes may hold greater promise for alleviating ADHD-related impairments.

Effects of tiapride on electroencephalograms and cognitive functions in the elderly.

PubMed

Patat, A; Alberini, H; Bonhomme, D; Soubrane, C; Allain, H; Gandon, J M

1999-07-01

Tiapride is a substituted benzamide with selective dopamine D2 and D3-antagonist properties which appears to have preferential affinity for extra-striatal dopamine receptors. Tiapride is used in the treatment of agitation, aggressiveness and anxiety in the elderly. To define the effects of a single dose of tiapride 100 mg on psychomotor performance and cognitive functions and electroencephalogram (EEG), a randomized, double-blind, three-way crossover, placebo-controlled study using lorazepam 1 mg as a positive control was carried out in 12 elderly individuals (six women and six men, mean age +/- SD: 69 +/- 3 years). A 1-week wash-out interval was allowed between each administration. Psychomotor and cognitive functions were assessed using both objective [EEG, critical flicker fusion, simple reaction time, tapping, body sway, continuous performance task (CPT), digit symbol substitution test, Sternberg memory scanning and a learning memory test using word lists] and subjective (visual analogue scales) measures before and up to 6 h after dosing. Tiapride was devoid of any detrimental or sedative effects on EEG and all of the performance tasks used and did not impair memory compared with-placebo. In contrast, a single dose of lorazepam produced significant deleterious effects on psychomotor performance (decrease in tapping and in sustained attention (CPT) and an increase in reaction time and body sway), and sedative effects on EEG (significant increase in delta and decrease in alpha waves) as well as significant impairment in working memory (Sternberg) and anterograde amnesia (decrease in immediate and delayed free recall) up to 6 h after dosing compared with placebo and tiapride. In conclusion, the present study showed that in contrast to lorazepam 1 mg there is no evidence to suggest that a single dose of tiapride 100 mg has any sedative and amnestic effects in the elderly which may interfere with everyday life activities.

Paired Comparison Survey Analyses Utilizing Rasch Methodology of the Relative Difficulty and Estimated Work Relative Value Units of CPT® Code 27279.

PubMed

Lorio, Morgan; Martinson, Melissa; Ferrara, Lisa

2016-01-01

Minimally invasive sacroiliac joint arthrodesis ("MI SIJ fusion") received a Category I CPT ® code (27279) effective January 1, 2015 and was assigned a work relative value unit ("RVU") of 9.03. The International Society for the Advancement of Spine Surgery ("ISASS") conducted a study consisting of a Rasch analysis of two separate surveys of surgeons to assess the accuracy of the assigned work RVU. A survey was developed and sent to ninety-three ISASS surgeon committee members. Respondents were asked to compare CPT ® 27279 to ten other comparator CPT ® codes reflective of common spine surgeries. The survey presented each comparator CPT ® code with its code descriptor as well as the description of CPT ® 27279 and asked respondents to indicate whether CPT ® 27279 was greater, equal, or less in terms of work effort than the comparator code. A second survey was sent to 557 U.S.-based spine surgeon members of ISASS and 241 spine surgeon members of the Society for Minimally Invasive Spine Surgery ("SMISS"). The design of the second survey mirrored that of the first survey except for the use of a broader set of comparator CPT ® codes (27 vs. 10). Using the work RVUs of the comparator codes, a Rasch analysis was performed to estimate the relative difficulty of CPT ® 27279, after which the work RVU of CPT ® 27279 was estimated by regression analysis. Twenty surgeons responded to the first survey and thirty-four surgeons responded to the second survey. The results of the regression analysis of the first survey indicate a work RVU for CPT ® 27279 of 14.36 and the results of the regression analysis of the second survey indicate a work RVU for CPT ® 27279 of 14.1. The Rasch analysis indicates that the current work RVU assigned to CPT ® 27279 is undervalued at 9.03. Averaging the results of the regression analyses of the two surveys indicates a work RVU for CPT ® 27279 of 14.23.

Integrated Advanced Microwave Sounding Unit-A (AMSU-A). Performance Verification Report: Final Comprehensive Performance Test Report, P/N 1331720-2TST, S/N 105/A1

NASA Technical Reports Server (NTRS)

Platt, R.

1999-01-01

This is the Performance Verification Report, Final Comprehensive Performance Test (CPT) Report, for the Integrated Advanced Microwave Sounding Unit-A (AMSU-A). This specification establishes the requirements for the CPT and Limited Performance Test (LPT) of the AMSU-1A, referred to here in as the unit. The sequence in which the several phases of this test procedure shall take place is shown.

A Multi-Informant Multi-Method Investigation of Family Functioning and Parent–Child Coping During Children’s Acute Pain

PubMed Central

Birnie, Kathryn A.; Chambers, Christine T.; Chorney, Jill; Fernandez, Conrad V.; McGrath, Patrick J.

2017-01-01

Objective To explore relations between family functioning and child acute pain, including pain ratings, coping, and parent–child behaviors. Methods Community sample of 171 dyads including one child aged 8–12 years (52% girls) and one parent (79% mothers). Family functioning was assessed via child and parent self-report, and observation during a conflict discussion task. Children and parents rated pain catastrophizing at baseline, and child pain and distress following a cold pressor task (CPT). Parent–child interactions during the CPT were coded for observed behaviors during child pain. Results Self-report of poorer family functioning predicted greater child and parent pain catastrophizing, and parent distress. Less observed family negativity/conflict and cohesiveness, and greater family focus of problems and parent emotional support predicted more child symptom complaints. Family functioning was not associated with child pain or distress. Conclusions Family functioning influenced parent and child coping and child behavioral responses, but not the experience, of acute pain. PMID:28165527

Chemoproteomics reveals baicalin activates hepatic CPT1 to ameliorate diet-induced obesity and hepatic steatosis.

PubMed

Dai, Jianye; Liang, Kai; Zhao, Shan; Jia, Wentong; Liu, Yuan; Wu, Hongkun; Lv, Jia; Cao, Chen; Chen, Tao; Zhuang, Shentian; Hou, Xiaomeng; Zhou, Shijie; Zhang, Xiannian; Chen, Xiao-Wei; Huang, Yanyi; Xiao, Rui-Ping; Wang, Yan-Ling; Luo, Tuoping; Xiao, Junyu; Wang, Chu

2018-06-11

Obesity and related metabolic diseases are becoming worldwide epidemics that lead to increased death rates and heavy health care costs. Effective treatment options have not been found yet. Here, based on the observation that baicalin, a flavonoid from the herbal medicine Scutellaria baicalensis , has unique antisteatosis activity, we performed quantitative chemoproteomic profiling and identified carnitine palmitoyltransferase 1 (CPT1), the controlling enzyme for fatty acid oxidation, as the key target of baicalin. The flavonoid directly activated hepatic CPT1 with isoform selectivity to accelerate the lipid influx into mitochondria for oxidation. Chronic treatment of baicalin ameliorated diet-induced obesity (DIO) and hepatic steatosis and led to systemic improvement of other metabolic disorders. Disruption of the predicted binding site of baicalin on CPT1 completely abolished the beneficial effect of the flavonoid. Our discovery of baicalin as an allosteric CPT1 activator opens new opportunities for pharmacological treatment of DIO and associated sequelae.

Simultaneous measurement of time-domain fNIRS and physiological signals during a cognitive task

NASA Astrophysics Data System (ADS)

Jelzow, A.; Tachtsidis, I.; Kirilina, E.; Niessing, M.; Brühl, R.; Wabnitz, H.; Heine, A.; Ittermann, B.; Macdonald, R.

2011-07-01

Functional near-infrared spectroscopy (fNIRS) is a commonly used technique to measure the cerebral vascular response related to brain activation. It is known that systemic physiological processes, either independent or correlated with the stimulation task, can influence the optical signal making its interpretation challenging. The aim of the present work is to investigate the impact of task-evoked changes in the systemic physiology on fNIRS measurements for a cognitive paradigm. For this purpose we carried out simultaneous measurements of time-domain fNIRS on the forehead and systemic physiological signals, i.e. mean blood pressure, heart rate, respiration, galvanic skin response, scalp blood flow (flux) and red blood cell (RBC) concentration changes. We performed measurements on 15 healthy volunteers during a semantic continuous performance task (CPT). The optical data was analyzed in terms of depth-selective moments of distributions of times of flight of photons through the tissue. In addition, cerebral activation was localized by a subsequent fMRI experiment on the same subject population using the same task. We observed strong non-cerebral task-evoked changes in concentration changes of oxygenated hemoglobin in the forehead. We investigated the temporal behavior and mutual correlations between hemoglobin changes and the systemic processes. Mean blood pressure (BP), galvanic skin response (GSR) and heart rate exhibited significant changes during the activation period, whereby BP and GSR showed the highest correlation with optical measurements.

The impact of adult vitamin D deficiency on behaviour and brain function in male Sprague-Dawley rats.

PubMed

Byrne, Jacqueline H; Voogt, Meggie; Turner, Karly M; Eyles, Darryl W; McGrath, John J; Burne, Thomas H J

2013-01-01

Vitamin D deficiency is common in the adult population, and this has been linked to depression and cognitive outcomes in clinical populations. The aim of this study was to investigate the effects of adult vitamin D (AVD) deficiency on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague-Dawley rats. Ten-week old male Sprague-Dawley rats were fed a control or vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We first examined a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception. We then assessed locomotor response to the psychomimetic drugs, amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice serial reaction time task (5C-SRT) and the 5 choice continuous performance task (5C-CPT) and, in a separate cohort, working memory was assessed using the delay match to sample (DMTS) task. We also examined excitatory and inhibitory neurotransmitters in prefrontal cortex and striatum. AVD-deficient rats were deficient in vitamin D3 (<10 nM) and had normal calcium and phosphate levels after 8-10 weeks on the diet. Overall, AVD deficiency was not associated with an altered phenotype across the range of behavioural domains tested. On the 5C-SRT AVD-deficient rats made more premature responses and more head entries during longer inter-trial intervals (ITI) than control rats. On the 5C-CPT AVD-deficient rats took longer to make false alarm (FA) responses than control rats. AVD-deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA within the striatum. AVD-deficient rats exhibited no major impairments in any of the behavioural domains tested. Impairments in premature responses in AVD-deficient rats may indicate that these animals have specific alterations in striatal systems governing compulsive or reward-seeking behaviour.

Patterns of change in withdrawal symptoms, desire to smoke, reward motivation and response inhibition across 3 months of smoking abstinence.

PubMed

Dawkins, Lynne; Powell, Jane H; Pickering, Alan; Powell, John; West, Robert

2009-05-01

We have demonstrated previously that acute smoking abstinence is associated with lowered reward motivation and impaired response inhibition. This prospective study explores whether these impairments, along with withdrawal-related symptoms, recover over 3 months of sustained abstinence. Participants completed a 12-hour abstinent baseline assessment and were then allocated randomly to quit unaided or continue smoking. All were re-tested after 7 days, 1 month and 3 months. Successful quitters' scores were compared with those of continuing smokers, who were tested after ad libitum smoking. Goldsmiths, University of London. A total of 33 smokers who maintained abstinence to 3 months, and 31 continuing smokers. Indices demonstrated previously in this cohort of smokers to be sensitive to the effect of nicotine versus acute abstinence: reward motivation [Snaith-Hamilton pleasure scale (SHAPS), Card Arranging Reward Responsivity Objective Test (CARROT), Stroop], tasks of response inhibition [anti-saccade task; Continuous Performance Task (CPT)], clinical indices of mood [Hospital Anxiety and Depression Scale (HADS)], withdrawal symptoms [Mood and Physical Symptoms Scale (MPSS)] and desire to smoke. SHAPS anhedonia and reward responsivity (CARROT) showed significant improvement and plateaued after a month of abstinence, not differing from the scores of continuing smokers tested in a satiated state. Mood, other withdrawal symptoms and desire to smoke all declined from acute abstinence to 1 month of cessation and were equivalent to, or lower than, the levels reported by continuing, satiated smokers. Neither group showed a change in CPT errors over time while continuing smokers, but not abstainers, showed improved accuracy on the anti-saccade task at 3 months. Appetitive processes and related affective states appear to improve in smokers who remain nicotine-free for 3 months, whereas response inhibition does not. Although in need of replication, the results suggest tentatively that poor inhibitory control may constitute a long-term risk factor for relapse and could be a target for intervention.

Genome-Wide Linkage and Regional Association Study of Blood Pressure Response to the Cold Pressor Test in Han Chinese: The GenSalt Study

PubMed Central

Yang, Xueli; Gu, Dongfeng; He, Jiang; Hixson, James E.; Rao, Dabeeru C.; Lu, Fanghong; Mu, Jianjun; Jaquish, Cashell E.; Chen, Jing; Huang, Jianfeng; Shimmin, Lawrence C.; Rice, Treva K.; Chen, Jichun; Wu, Xigui; Liu, Depei; Kelly, Tanika N.

2014-01-01

Background Blood pressure (BP) response to cold pressor test (CPT) is associated with increased risk of cardiovascular disease. We performed a genome-wide linkage scan and regional association analysis to identify genetic determinants of BP response to CPT. Methods and Results A total of 1,961 Chinese participants completed the CPT. Multipoint quantitative trait linkage analysis was performed, followed by single-marker and gene-based analyses of variants in promising linkage regions (logarithm of odds, LOD ≥ 2). A suggestive linkage signal was identified for systolic BP (SBP) response to CPT at 20p13-20p12.3, with a maximum multipoint LOD score of 2.37. Based on regional association analysis with 1,351 SNPs in the linkage region, we found that marker rs2326373 at 20p13 was significantly associated with mean arterial pressure (MAP) responses to CPT (P = 8.8×10−6) after FDR adjustment for multiple comparisons. A similar trend was also observed for SBP response (P = 0.03) and DBP response (P = 4.6×10−5). Results of gene-based analyses showed that variants in genes MCM8 and SLC23A2 were associated with SBP response to CPT (P = 4.0×10−5 and 2.7×10−4, respectively), and variants in genes MCM8 and STK35 were associated with MAP response to CPT (P = 1.5×10−5 and 5.0×10−5, respectively). Conclusions Within a suggestive linkage region on chromosome 20, we identified a novel variant associated with BP responses to CPT. We also found gene-based associations of MCM8, SLC23A2 and STK35 in this region. Further work is warranted to confirm these findings. Clinical Trial Registration URL: http://www.clinicaltrials.gov; Unique identifier: NCT00721721. PMID:25028485

Effective conversion of irinotecan to SN-38 after intratumoral drug delivery to an intracranial murine glioma model in vivo. Laboratory investigation.

PubMed

Wang, Weijun; Ghandi, Alex; Liebes, Leonard; Louie, Stan G; Hofman, Florence M; Schönthal, Axel H; Chen, Thomas C

2011-03-01

Irinotecan (CPT-11), a topoisomerase I inhibitor, is a cytotoxic agent with activity against malignant gliomas and other tumors. After systemic delivery, CPT-11 is converted to its active metabolite, SN-38, which displays significantly higher cytotoxic potency. However, the achievement of therapeutically effective plasma levels of CPT-11 and SN-38 is seriously complicated by variables that affect drug metabolism in the liver. Thus the capacity of CPT-11 to be converted to the active SN38 intratumorally in gliomas was addressed. For in vitro studies, 2 glioma cell lines, U87 and U251, were tested to determine the cytotoxic effects of CPT-11 and SN-38 in a dose-dependent manner. In vivo studies were performed by implanting U87 intracranially into athymic/nude mice. For a period of 2 weeks, SN-38, CPT-11, or vehicle was administered intratumorally by means of an osmotic minipump. One series of experiments measured the presence of SN-38 or CPT-11 in the tumor and surrounding brain tissues after 2 weeks' exposure to the drug. In a second series of experiments, after 2 weeks' exposure to the drug, the animals were maintained, in the absence of drug, until death. The survival curves were then calculated. The results show that the animals that had CPT-11 delivered intratumorally by the minipump expressed SN-38 in vivo. Furthermore, both CPT-11 and SN-38 accumulated at higher levels in tumor tissues compared with uninvolved brain. Intratumoral delivery of CPT-11 or SN-38 extended the average survival time of tumor-bearing animals from 22 days to 46 and 65 days, respectively. These results demonstrate that intratumorally administered CPT-11 can be effectively converted to SN-38 and this method of drug delivery is effective in extending the survival time of animals bearing malignant gliomas.

Further examination of embedded performance validity indicators for the Conners' Continuous Performance Test and Brief Test of Attention in a large outpatient clinical sample.

PubMed

Sharland, Michael J; Waring, Stephen C; Johnson, Brian P; Taran, Allise M; Rusin, Travis A; Pattock, Andrew M; Palcher, Jeanette A

2018-01-01

Assessing test performance validity is a standard clinical practice and although studies have examined the utility of cognitive/memory measures, few have examined attention measures as indicators of performance validity beyond the Reliable Digit Span. The current study further investigates the classification probability of embedded Performance Validity Tests (PVTs) within the Brief Test of Attention (BTA) and the Conners' Continuous Performance Test (CPT-II), in a large clinical sample. This was a retrospective study of 615 patients consecutively referred for comprehensive outpatient neuropsychological evaluation. Non-credible performance was defined two ways: failure on one or more PVTs and failure on two or more PVTs. Classification probability of the BTA and CPT-II into non-credible groups was assessed. Sensitivity, specificity, positive predictive value, and negative predictive value were derived to identify clinically relevant cut-off scores. When using failure on two or more PVTs as the indicator for non-credible responding compared to failure on one or more PVTs, highest classification probability, or area under the curve (AUC), was achieved by the BTA (AUC = .87 vs. .79). CPT-II Omission, Commission, and Total Errors exhibited higher classification probability as well. Overall, these findings corroborate previous findings, extending them to a large clinical sample. BTA and CPT-II are useful embedded performance validity indicators within a clinical battery but should not be used in isolation without other performance validity indicators.

Controlling the light shift of the CPT resonance by modulation technique

NASA Astrophysics Data System (ADS)

Tsygankov, E. A.; Petropavlovsky, S. V.; Vaskovskaya, M. I.; Zibrov, S. A.; Velichansky, V. L.; Yakovlev, V. P.

2017-12-01

Motivated by recent developments in atomic frequency standards employing the effect of coherent population trapping (CPT), we propose a theoretical framework for the frequency modulation spectroscopy of the CPT resonances. Under realistic assumptions we provide simple yet non-trivial analytical formulae for the major spectroscopic signals such as the CPT resonance line and the in-phase/quadrature responses. We discuss the influence of the light shift and, in particular, derive a simple expression for the displacement of the resonance as a function of modulation index. The performance of the model is checked against numerical simulations, the agreement is good to perfect. The obtained results can be used in more general models accounting for light absorption in the thick optical medium.

In-treatment cigarette demand among treatment-seeking smokers with depressive symptoms.

PubMed

Weidberg, S; Vallejo-Seco, G; González-Roz, A; García-Pérez, Á; Secades-Villa, R

2018-07-01

Despite previous evidence supporting the use of the Cigarette Purchase Task (CPT) as a valid tool for assessing smoking reinforcement, research assessing how environmental changes affect CPT performance is scarce. This study addressed for the first time the differential effect of treatment condition [Cognitive Behavioral Treatment (CBT) + Behavioral Activation (BA) versus CBT + BA + Contingency Management (CM)] on cigarette demand among treatment seeking smokers with depressive symptoms. It also sought to assess whether reductions in smoking consumption arranged over the course of an intervention for smoking cessation impact on in-treatment cigarette demand. Participants were 92 smokers with depressive symptoms from a randomized clinical trial that received eight weeks of either CBT + BA or CBT + BA + CM. Individuals completed the CPT 8 times; the first during the intake visit and the remaining 7 scheduled once a week in midweek sessions. Cotinine samples were collected in each session. Participants receiving CBT + BA + CM showed higher reduction in cigarette demand across sessions than participants receiving CBT + BA, although this comparison was only significant for the intensity index (p = .004). Cotinine was positively related to cigarette demand (all p values < .001), although this association became less prominent across sessions. In-treatment cotinine decreases were associated with demand reductions (all p values < .001), but this association was not significant for elasticity. Reductions in nicotine intake arranged over the course of an intervention for smoking cessation impact in-treatment cigarette demand. Copyright © 2018 Elsevier Ltd. All rights reserved.

Metabolic Pathway Signatures Associated with Urinary Metabolite Biomarkers Differentiate Bladder Cancer Patients from Healthy Controls.

PubMed

Kim, Won Tae; Yun, Seok Joong; Yan, Chunri; Jeong, Pildu; Kim, Ye Hwan; Lee, Il Seok; Kang, Ho Won; Park, Sunghyouk; Moon, Sung Kwon; Choi, Yung Hyun; Choi, Young Deuk; Kim, Isaac Yi; Kim, Jayoung; Kim, Wun Jae

2016-07-01

Our previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome. A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed. The association between specific urinary metabolites and their related encoding genes was analyzed. Significant alterations in the carnitine-acylcarnitine and tryptophan metabolic pathways were detected in urine specimens from BCA patients compared to those of healthy controls. The expression of eight genes involved in the carnitine-acylcarnitine metabolic pathway (CPT1A, CPT1B, CPT1C, CPT2, SLC25A20, and CRAT) or tryptophan metabolism (TPH1 and IDO1) was assessed by RT-PCR in our BCA cohort (n=135). CPT1B, CPT1C, SLC25A20, CRAT, TPH1, and IOD1 were significantly downregulated in tumor tissues compared to normal bladder tissues (p<0.05 all) of patients with non-muscle invasive BCA, whereas CPT1B, CPT1C, CRAT, and TPH1 were downregulated in those with muscle invasive BCA (p<0.05), with no changes in IDO1 expression. Alterations in the expression of genes associated with the carnitine-acylcarnitine and tryptophan metabolic pathways, which were the most perturbed pathways in BCA, were determined.

Community-based advocacy training: applying asset-based community development in resident education.

PubMed

Hufford, Laura; West, Daniel C; Paterniti, Debora A; Pan, Richard J

2009-06-01

Communities and Physicians Together (CPT) at University of California, Davis Health System provides a novel approach to teaching residents to be effective community advocates. Founded in 1999, CPT is a partnership between a pediatric residency program, five community collaboratives located in diverse neighborhoods, and a grassroots child advocacy organization. Using the principles of Asset-Based Community Development, the program emphasizes establishing partnerships with community members and organizations to improve child health and identifies community assets and building capacity. Community members function as the primary faculty for CPT.The authors describe the CPT curriculum, which teaches residents to build partnerships with their assigned community. Residents have three, two-week blocks each year for CPT activities and maintain a longitudinal relationship with their community. In the first year, collaborative coordinators from each community orient residents to their community. Residents identify community assets and perform activities designed to provide them with a community member's perspective. In the second and third years, residents partner with community members and organizations to implement a project to improve the health of children in that community. CPT also provides faculty development to community partners including a workshop on medical culture and resident life. A qualitative evaluation demonstrated residents' attitudes of their role as pediatricians in the community changed with CPT.CPT is unique because it provides a model of service learning that emphasizes identifying and utilizing strengths and building capacity. This approach differs from the traditional medical model, which emphasizes deficits and needs.

Evidence of a malonyl-CoA-insensitive carnitine palmitoyltransferase I activity in red skeletal muscle.

PubMed

Kim, Jong-Yeon; Koves, Timothy R; Yu, Geng-Sheng; Gulick, Tod; Cortright, Ronald N; Dohm, G Lynis; Muoio, Deborah M

2002-05-01

Carnitine palmitoyltransferase I (CPT I), which is expressed as two distinct isoforms in liver (alpha) and muscle (beta), catalyzes the rate-limiting step in the transport of fatty acid into the mitochondria. Malonyl-CoA, a potent inhibitor of CPT I, is considered a key regulator of fatty acid oxidation in both tissues. Still unanswered is how muscle beta-oxidation proceeds despite malonyl-CoA concentrations that exceed the IC(50) for CPT Ibeta. We evaluated malonyl-CoA-suppressible [(14)C]palmitate oxidation and CPT I activity in homogenates of red (RG) and white (WG) gastrocnemius, soleus (SOL), and extensor digitorum longus (EDL) muscles. Adding 10 microM malonyl-CoA inhibited palmitate oxidation by 29, 39, 60, and 89% in RG, SOL, EDL, and WG, respectively. Thus malonyl-CoA resistance, which correlated strongly (0.678) with absolute oxidation rates (RG > SOL > EDL > WG), was greater in red than in white muscles. Similarly, malonyl-CoA-resistant palmitate oxidation and CPT I activity were greater in mitochondria from RG compared with WG. Ribonuclease protection assays were performed to evaluate whether our data might be explained by differential expression of CPT I splice variants. We detected the presence of two CPT Ibeta splice variants that were more abundant in red compared with white muscle, but the relative expression of the two mRNA species was unrelated to malonyl-CoA resistance. These results provide evidence of a malonyl-CoA-insensitive CPT I activity in red muscle, suggesting fiber type-specific expression of distinct CPT I isoforms and/or posttranslational modulations that have yet to be elucidated.

A Quantitative Analysis of the Relationship between Medicare Payment and Service Volume for Glaucoma Procedures from 2005 through 2009.

PubMed

Gong, Dan; Jun, Lin; Tsai, James C

2015-05-01

To calculate the association between Medicare payment and service volume for 6 commonly performed glaucoma procedures. Retrospective, longitudinal database study. A 100% dataset of all glaucoma procedures performed on Medicare Part B beneficiaries within the United States from 2005 to 2009. Fixed-effects regression model using Medicare Part B carrier data for all 50 states and the District of Columbia, controlling for time-invariant carrier-specific characteristics, national trends in glaucoma service volume, Medicare beneficiary population, number of ophthalmologists, and income per capita. Payment-volume elasticities, defined as the percent change in service volume per 1% change in Medicare payment, for laser trabeculoplasty (Current Procedural Terminology [CPT] code 65855), trabeculectomy without previous surgery (CPT code 66170), trabeculectomy with previous surgery (CPT code 66172), aqueous shunt to reservoir (CPT code 66180), laser iridotomy (CPT code 66761), and scleral reinforcement with graft (CPT code 67255). The payment-volume elasticity was nonsignificant for 4 of 6 procedures studied: laser trabeculoplasty (elasticity, -0.27; 95% confidence interval [CI], -1.31 to 0.77; P = 0.61), trabeculectomy without previous surgery (elasticity, -0.42; 95% CI, -0.85 to 0.01; P = 0.053), trabeculectomy with previous surgery (elasticity, -0.28; 95% CI, -0.83 to 0.28; P = 0.32), and aqueous shunt to reservoir (elasticity, -0.47; 95% CI, -3.32 to 2.37; P = 0.74). Two procedures yielded significant associations between Medicare payment and service volume. For laser iridotomy, the payment-volume elasticity was -1.06 (95% CI, -1.39 to -0.72; P < 0.001): for every 1% decrease in CPT code 66761 payment, laser iridotomy service volume increased by 1.06%. For scleral reinforcement with graft, the payment-volume elasticity was -2.92 (95% CI, -5.72 to -0.12; P = 0.041): for every 1% decrease in CPT code 67255 payment, scleral reinforcement with graft service volume increased by 2.92%. This study calculated the association between Medicare payment and service volume for 6 commonly performed glaucoma procedures and found varying magnitudes of payment-volume elasticities, suggesting that the volume response to changes in Medicare payments, if present, is not uniform across all Medicare procedures. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Possible effect of norepinephrine transporter polymorphisms on methylphenidate-induced changes in neuropsychological function in attention-deficit hyperactivity disorder.

PubMed

Park, Subin; Kim, Jae-Won; Yang, Young-Hui; Hong, Soon-Beom; Park, Min-Hyeon; Kim, Boong-Nyun; Shin, Min-Sup; Yoo, Hee-Jeong; Cho, Soo-Churl

2012-05-16

Dysregulation of noradrenergic system may play important roles in pathophysiology of attention-deficit/hyperactivity disorder (ADHD). We examined the relationship between polymorphisms in the norepinephrine transporter SLC6A2 gene and attentional performance before and after medication in children with ADHD. Fifty-three medication-naïve children with ADHD were genotyped and evaluated using the continuous performance test (CPT). After 8-weeks of methylphenidate treatment, these children were evaluated by CPT again. We compared the baseline CPT measures and the post-treatment changes in the CPT measures based on the G1287A and the A-3081T polymorphisms of SLC6A2. There was no significant difference in the baseline CPT measures associated with the G1287A or A-3081T polymorphisms. After medication, however, ADHD subjects with the G/G genotype at the G1287A polymorphism showed a greater decrease in the mean omission error scores (p = 0.006) than subjects with the G/A or A/A genotypes, and subjects with the T allele at the A-3081T polymorphism (T/T or A/T) showed a greater decrease in the mean commission error scores (p = 0.003) than those with the A/A genotypes. Our results provide evidence for the possible role of the G1287A and A-3081T genotypes of SLC6A2 in methylphenidate-induced improvement in attentional performance and support the noradrenergic hypothesis for the pathophysiology of ADHD.

Heidelberg Neuro-Music Therapy Restores Attention-Related Activity in the Angular Gyrus in Chronic Tinnitus Patients

PubMed Central

Krick, Christoph M.; Argstatter, Heike; Grapp, Miriam; Plinkert, Peter K.; Reith, Wolfgang

2017-01-01

Background: Tinnitus is the perception of a phantom sound without external acoustic stimulation. Recent tinnitus research suggests a relationship between attention processes and tinnitus-related distress. It has been found that too much focus on tinnitus comes at the expense of the visual domain. The angular gyrus (AG) seems to play a crucial role in switching attention to the most salient stimulus. This study aims to evaluate the involvement of the AG during visual attention tasks in tinnitus sufferers treated with Heidelberg Neuro-Music Therapy (HNMT), an intervention that has been shown to reduce tinnitus-related distress. Methods: Thirty-three patients with chronic tinnitus, 45 patients with recent-onset tinnitus, and 35 healthy controls were tested. A fraction of these (21/21/22) were treated with the “compact” version of the HNMT lasting 1 week with intense treatments, while non-treated participants were included as passive controls. Visual attention was evaluated during functional Magnet-Resonance Imaging (fMRI) by a visual Continous Performance Task (CPT) using letter-based alarm cues (“O” and “X”) appearing in a sequence of neutral letters, “A” through “H.” Participants were instructed to respond via button press only if the letter “O” was followed by the letter “X” (GO condition), but not to respond if a neutral letter appeared instead (NOGO condition). All participants underwent two fMRI sessions, before and after a 1-week study period. Results: The CPT results revealed a relationship between error rates and tinnitus duration at baseline whereby the occurrence of erroneous “GO omissions” and the reaction time increased with tinnitus duration. Patients with chronic tinnitus who were treated with HNMT had decreasing error rates (fewer GO omissions) compared to treated recent-onset patients. fMRI analyses confirmed greater activation of the AG during CPT in chronic patients after HNMT treatment compared to treated recent-onset patients. Conclusions: Our findings suggest that HNMT treatment helps shift the attention from the auditory phantom percept toward visual cues in chronic tinnitus patients and that this shift in attention may involve the AG. PMID:28775679

Shengjiang Xiexin Decoction Alters Pharmacokinetics of Irinotecan by Regulating Metabolic Enzymes and Transporters: A Multi-Target Therapy for Alleviating the Gastrointestinal Toxicity.

PubMed

Guan, Huan-Yu; Li, Peng-Fei; Wang, Xiao-Ming; Yue, Jia-Jing; He, Yang; Luo, Xiao-Mei; Su, Mei-Feng; Liao, Shang-Gao; Shi, Yue

2017-01-01

Shengjiang Xiexin decoction (SXD), a classic traditional Chinese medical formula chronicled in Shang Han Lun , is used in modern clinical practice to decrease gastrointestinal toxicity induced by the chemotherapeutic drug irinotecan (CPT-11). In this study, the effect of SXD on the pharmacokinetics of CPT-11 and its active metabolites (SN-38 and SN-38G), and the underlying mechanisms were further examined. An ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the simultaneous quantification of CPT-11, SN-38, and SN-38G in the plasma, bile, liver, intestine, and intestinal contents of control and SXD-pre-treated rats after intravenous administration of CPT-11. SXD pretreatment increased the area under the curve (AUC) and the initial plasma concentration (C 0 ) of CPT-11 but decreased the plasma clearance (CL). The AUC and the maximum plasma concentration (C max ) of SN-38 decreased, whereas the C max of SN-38G increased. Compared with that of the control group, the biliary excretion of CPT-11, SN-38, and SN-38G was inhibited. The CPT-11, SN-38, and SN-38G concentrations in the liver, intestine, and intestinal contents were different between the two groups. Furthermore, the hepatic expression of multidrug resistance-associated protein-2 (Mrp-2), P-glycoprotein (P-gp), and carboxylesterase 2 (CES2) was significantly down-regulated by SXD, while the hepatic and jejunal uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) expression was elevated. The hydrolysis of CPT-11 to SN-38 by CES and the glucuronidation of SN-38 to SN-38G by UGT were affected by liver and jejunum S9 fractions from rats pre-treated with SXD. Therefore, this study demonstrated for the first time that SXD could alter the pharmacokinetics of CPT-11 and its metabolites to alleviate CPT-11-induced diarrhea. And the underlying mechanism of drug interaction between CPT-11 and SXD involves decreasing hepatic Mrp-2 and P-gp expression and altering the activities of CES and UGT.

Putative therapeutic targets for symptom subtypes of adult ADHD: D4 receptor agonism and COMT inhibition improve attention and response inhibition in a novel translational animal model.

PubMed

Tomlinson, Anneka; Grayson, Ben; Marsh, Samuel; Hayward, Andrew; Marshall, Kay M; Neill, Joanna C

2015-04-01

Prefrontal cortical dopamine plays an important role in cognitive control, specifically in attention and response inhibition; the core deficits in ADHD. We have previously shown that methylphenidate and atomoxetine differentially improve these deficits dependent on baseline performance. The present study extends this work to investigate the effects of putative therapeutic targets in our model. A selective dopamine D4 receptor agonist (A-412997) and the catechol-O-methyl-transferase (COMT) inhibitor; tolcapone, were investigated in the combined subtype of adult ADHD (ADHD-C). Adult female rats were trained to criterion in the 5C-CPT (5-Choice Continuous Performance Task) and then separated into subgroups according to baseline levels of sustained attention, vigilance, and response disinhibition. The subgroups included: high-attentive (HA) and low-attentive with high response disinhibition (ADHD-C). The ADHD-C subgroup was selected to represent the combined subtype of adult ADHD. Effects of tolcapone (3.0, 10.0, 15.0mg/kg) and A-412997 (0.1, 0.3, 1.0µmol/kg) were tested by increasing the variable inter-trial-interval (ITI) duration in the 5C-CPT. Tolcapone (15mg/kg) significantly increased sustained attention, vigilance and response inhibition in ADHD-C animals, and impaired attention in HA animals. A-412997 (1.0µmol/kg) significantly increased vigilance and response inhibition in ADHD-C animals only, with no effect in HA animals. This is the first study to use the translational 5C-CPT to model the adult ADHD-C subtype in rats and to study new targets in this model. Both tolcapone and A-412997 increased vigilance and response inhibition in the ADHD-C subgroup. D4 and COMT are emerging as important potential therapeutic targets in adult ADHD that warrant further investigation. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

A fluid response: Alpha-amylase reactions to acute laboratory stress are related to sample timing and saliva flow rate.

PubMed

Nagy, Tamás; van Lien, René; Willemsen, Gonneke; Proctor, Gordon; Efting, Marieke; Fülöp, Márta; Bárdos, György; Veerman, Enno C I; Bosch, Jos A

2015-07-01

Salivary alpha-amylase (sAA) is used as a sympathetic (SNS) stress marker, though its release is likely co-determined by SNS and parasympathetic (PNS) activation. The SNS and PNS show asynchronous changes during acute stressors, and sAA responses may thus vary with sample timing. Thirty-four participants underwent an eight-minute memory task (MT) and cold pressor task (CPT). Cardiovascular SNS (pre-ejection period, blood pressure) and PNS (heart rate variability) activity were monitored continuously. Unstimulated saliva was collected repeatedly during and after each laboratory stressor, and sAA concentration (U/ml) and secretion (U/minute) determined. Both stressors increased anxiety. The MT caused an immediate and continued cardiac SNS activation, but sAA concentration increased at task cessation only (+54%); i.e., when there was SNS-PNS co-activation. During the MT sAA secretion even decreased (-35%) in conjunction with flow rate and vagal tone. The CPT robustly increased blood pressure but not sAA. In summary, sAA fluctuations did not parallel changes in cardiac SNS activity or anxiety. sAA responses seem contingent on sample timing and flow rate, likely involving both SNS and PNS influences. Verification using other stressors and contexts seems warranted. Copyright © 2015 Elsevier B.V. All rights reserved.

Reverse translation of the rodent 5C-CPT reveals that the impaired attention of people with schizophrenia is similar to scopolamine-induced deficits in mice

PubMed Central

Young, J W; Geyer, M A; Rissling, A J; Sharp, R F; Eyler, L T; Asgaard, G L; Light, G A

2013-01-01

Attentional dysfunction in schizophrenia (SZ) is a core deficit that contributes to multiple cognitive deficits and the resulting functional disability. However, developing procognitive therapeutics for neuropsychiatric disorders have been limited by a ‘translational gap'—a lack of cognitive paradigms having cross-species translational validity and relevance. The present study was designed to perform an initial validation of the cross-species homology of the 5-choice Continuous Performance Test (5C-CPT) in healthy nonpsychiatric comparison subjects (NCS), SZ patients and mice under pharmacologic challenge. The 5C-CPT performance in SZ patients (n=20) was compared with age-matched NCS (n=23). The effects of the general muscarinic receptor antagonist scopolamine on mice (n=21) performing the 5C-CPT were also assessed. SZ subjects exhibited significantly impaired attention in the 5C-CPT, driven by reduced target detection over time and nonsignificantly increased impulsive responding. Similarly, scopolamine significantly impaired attention in mice, driven by reduced target detection and nonsignificantly increased impulsive responding. Scopolamine also negatively affected accuracy and speed of responding in mice, although these measures failed to differentiate SZ vs NCS. Thus, mice treated with scopolamine exhibited similar impairments in vigilance as seen in SZ, although the differences between the behavioral profiles warrant further study. The availability of rodent and human versions of this paradigm provides an opportunity to: (1) investigate the neuroanatomic, neurochemical and genomic architecture of abnormalities in attention observed in clinical populations such as SZ; (2) develop and refine animal models of cognitive impairments; and (3) improve cross-species translational testing for the development of treatments for these impairments. PMID:24217494

Preventing Health Damaging Behaviors in Male and Female Army Recruits

DTIC Science & Technology

2013-08-01

completed in 2004: 1. Fort Bragg, NC: MAJ Lolita Burrell (then CPT (P), Richard Carr, and Crystal Ross were briefed. MAJ Burrell was tasked with...BCT, Fort Jackson, SC (July 2006). As a result of several conference calls with LTC Corum, Drs. Boyer and Shafer and MAJ Lolita Burrell, WAMC-Ft

Effects of smoking abstinence on reaction time variability in smokers with and without ADHD: an ex-Gaussian analysis.

PubMed

Kollins, Scott H; McClernon, F Joseph; Epstein, Jeff N

2009-02-01

Smoking abstinence differentially affects cognitive functioning in smokers with ADHD, compared to non-ADHD smokers. Alternative approaches for analyzing reaction time data from these tasks may further elucidate important group differences. Adults smoking > or = 15 cigarettes with (n=12) or without (n=14) a diagnosis of ADHD completed a continuous performance task (CPT) during two sessions under two separate laboratory conditions--a 'Satiated' condition wherein participants smoked up to and during the session; and an 'Abstinent' condition, in which participants were abstinent overnight and during the session. Reaction time (RT) distributions from the CPT were modeled to fit an ex-Gaussian distribution. The indicator of central tendency for RT from the normal component of the RT distribution (mu) showed a main effect of Group (ADHD < Control) and a Group x Session interaction (ADHD group RTs decreased when abstinent). RT standard deviation for the normal component of the distribution (sigma) showed no effects. The ex-Gaussian parameter tau, which describes the mean and standard deviation of the non-normal component of the distribution, showed significant effects of session (Abstinent > Satiated), Group x Session interaction (ADHD increased significantly under Abstinent condition compared to Control), and a trend toward a main effect of Group (ADHD > Control). Alternative approaches to analyzing RT data provide a more detailed description of the effects of smoking abstinence in ADHD and non-ADHD smokers and results differ from analyses using more traditional approaches. These findings have implications for understanding the neuropsychopharmacology of nicotine and nicotine withdrawal.

Effects of smoking abstinence on reaction time variability in smokers with and without ADHD: An ex-Gaussian analysis

PubMed Central

Kollins, Scott H.; McClernon, F. Joseph; Epstein, Jeff N.

2009-01-01

Smoking abstinence differentially affects cognitive functioning in smokers with ADHD, compared to non-ADHD smokers. Alternative approaches for analyzing reaction time data from these tasks may further elucidate important group differences. Adults smoking ≥15 cigarettes with (n = 12) or without (n = 14) a diagnosis of ADHD completed a continuous performance task (CPT) during two sessions under two separate laboratory conditions—a ‘Satiated’ condition wherein participants smoked up to and during the session; and an ‘Abstinent’ condition, in which participants were abstinent overnight and during the session. Reaction time (RT) distributions from the CPT were modeled to fit an ex-Gaussian distribution. The indicator of central tendency for RT from the normal component of the RT distribution (mu) showed a main effect of Group (ADHD Satiated), Group × Session interaction (ADHD increased significantly under Abstinent condition compared to Control), and a trend toward a main effect of Group (ADHD > Control). Alternative approaches to analyzing RT data provide a more detailed description of the effects of smoking abstinence in ADHD and non-ADHD smokers and results differ from analyses using more traditional approaches. These findings have implications for understanding the neuropsychopharmacology of nicotine and nicotine withdrawal. PMID:19041198

Does Comorbid Disruptive Behavior Modify the Effects of Atomoxetine on ADHD Symptoms as Measured by a Continuous Performance Test and a Motion Tracking Device?

PubMed

Wehmeier, Peter M; Kipp, Laura; Banaschewski, Tobias; Dittmann, Ralf W; Schacht, Alexander

2015-07-01

To compare the reduction of ADHD symptoms under atomoxetine in patients with and without comorbid oppositional defiant disorder (ODD) or conduct disorder (CD) using a computer-based continuous performance test (cb-CPT) combined with an infrared motion tracking (MT) device. Secondary analysis of a placebo-controlled study in ADHD patients (6-12 years old) treated with atomoxetine (target dose: 1.2 mg/kg per day). Cb-CPT/MT scores were analyzed using ANCOVA (last observation carried forward [LOCF]). The data (N = 125) suggested a more pronounced atomoxetine effect in the group with comorbid ODD/CD as measured by all cb-CPT/MT parameters except for "normalized variation of reaction time" (nVRT). The results showed that atomoxetine reduced ADHD severity as measured by cb-CPT and MT parameters regardless of whether comorbid ODD/CD was present. The treatment effect of atomoxetine on hyperactivity appears to be more pronounced in the subgroup of patients with comorbid ODD/CD than in the subgroup without this comorbidity. © 2012 SAGE Publications.

Correspondence of Parent Report and Laboratory Measures of Inattention and Hyperactivity in Children with Heavy Prenatal Alcohol Exposure

PubMed Central

Glass, Leila; Graham, Diana M.; Deweese, Benjamin N.; Jones, Kenneth Lyons; Riley, Edward P.; Mattson, Sarah N.

2014-01-01

Clinical research and practice support a multi-method approach to validating behavioral problems in children. We examined whether parent-reported symptoms of hyperactivity and inattention (using the Disruptive Behavior Disorder Rating Scale) were substantiated by objective laboratory measures [hyperactivity measured by wrist-worn actigraphy (ACT) and inattention assessed using a 20-minute continuous performance task (CPT)] in three age- and demographically-matched groups of school-age children: children with prenatal alcohol exposure (AE), non-exposed children with idiopathic ADHD (ADHD), and controls (CON). Results indicated that the clinical groups (AE, ADHD) had significantly higher parent-reported levels for both domains compared to the CON group, and did not differ from each other. On the laboratory measures, the clinical groups were more inattentive than controls on the CPT, but did not differ from each other. In contrast, the ADHD group had higher objective activity on the ACT than AE and CON, which did not differ from each other. Thus, laboratory measures differentially validated parent reports in a group-dependent manner. Actigraphy substantiated parent-reported hyperactivity for children in the ADHD group but not for children in the AE group, while the CPT validated parent-reported inattention for both clinical groups. Although the majority of children in the AE group met criteria for ADHD, objective activity levels were not different from controls, indicating that hyperactivity may be a less prominent feature in the AE group. Thus, while there is considerable overlap between the effects of prenatal alcohol exposure and ADHD, differences in behavioral profiles may be clinically useful in differential diagnosis. Further, these data indicate that objective measures should be used to validate parent reports. PMID:24512965

Reduced Electromyographic Fatigue Threshold after Performing a Cognitive Fatiguing Task.

PubMed

Ferris, Justine R; Tomlinson, Mary A; Ward, Tayler N; Pepin, Marie E; Malek, Moh H

2018-02-22

Cognitive fatigue tasks performed prior to exercise may reduce exercise capacity. The electromyographic fatigue threshold (EMGFT) is the highest exercise intensity that can be maintained without significant increase in the EMG amplitude versus time relationship. To date, no studies have examined the effect of cognitive fatigue on the estimation of the EMGFT. The purpose of this study, therefore, was to determine whether or not cognitive fatigue prior to performing exercise reduces the estimated EMGFT. Eight healthy college-aged men were recruited from a university student population and visited the laboratory on multiple occasions. In a randomized order, subjects performed either the cognitive fatigue task (AX Continuous Performance Test; AX-CPT) for 60 min on one visit (experimental condition) or watched a video on trains for 60 min on the other visit (control condition). After each condition, subjects performed the incremental single-leg knee-extensor ergometry test while the EMG amplitude was recorded from the rectus femoris muscle and heart rate was monitored throughout. Thereafter, the EMGFT was calculated for each participant for each visit and compared using paired samples t-test. For exercise outcomes, there were no significant mean differences for maximal power output between the two conditions (control: 51 ± 5 vs. fatigue: 50 ± 3 W), but a significant decrease in EMGFT between the two conditions (control: 31 ± 3 vs. fatigue: 24 ± 2 W; p = 0.013). Moreover, maximal heart rate was significantly different between the two conditions (control: 151 ± 5 vs. fatigue: 132 ± 6; p = 0.027). These results suggest that performing the cognitive fatiguing task reduces the EMGFT with a corresponding reduction in maximal heart rate response.

A Preliminary Design of a Calibration Chamber for Evaluating the Stability of Unsaturated Soil Slope

NASA Astrophysics Data System (ADS)

Hsu, H.-H.

2012-04-01

The unsaturated soil slopes, which have ground water tables and are easily failure caused by heavy rainfalls, are widely distributed in the arid and semi-arid areas. For analyzing the stability of slope, in situ tests are the direct methods to obtain the test site characteristics. The cone penetration test (CPT) is a popular in situ test method. Some of the CPT empirical equations established from calibration chamber tests. The CPT performed in calibration chamber was commonly used clean quartz sand as testing material in the past. The silty sand is observed in many actual slopes. Because silty sand is relatively compressible than quartz sand, it is not suitable to apply the correlations between soil properties and CPT results built from quartz sand to silty sand. The experience on CPT calibration in silty sand has been limited. CPT calibration tests were mostly performed in dry or saturated soils. The condition around cone tip during penetration is assumed to be fully drained or fully undrained, yet it was observed to be partially drained for unsaturated soils. Because of the suction matrix has a great effect on the characteristics of unsaturated soils, they are much sensitive to the water content than saturated soils. The design of an unsaturated calibration chamber is in progress. The air pressure is supplied from the top plate and the pore water pressure is provided through the high air entry value ceramic disks located at the bottom plate of chamber cell. To boost and uniform distribute the unsaturated effect, four perforated burettes are installed onto the ceramic disks and stretch upwards to the midheight of specimen. This paper describes design concepts, illustrates this unsaturated calibration chamber, and presents the preliminary test results.

Correlation between plasma concentration ratios of SN-38 glucuronide and SN-38 and neutropenia induction in patients with colorectal cancer and wild-type UGT1A1 gene

PubMed Central

HIROSE, KOICHI; KOZU, CHIHIRO; YAMASHITA, KOSHIRO; MARUO, EIJI; KITAMURA, MIZUHO; HASEGAWA, JUNICHI; OMODA, KEI; MURAKAMI, TERUO; MAEDA, YORINOBU

2011-01-01

In irinotecan (CPT-11)-based chemotherapy, neutropenia and diarrhea are often induced. In the present study, the clinical significance of the concentration ratios of 7-ethyl-10-hydroxycamptothecin (SN-38) glucuronide (SN-38G) and SN-38 in the plasma in predicting CPT-11-induced neutropenia was examined. A total of 17 patients with colorectal cancer and wild-type UDP-glucuronosyltransferase (UGT)1A1 gene were enrolled and treated with CPT-11 as part of the FOLFIRI regimen [CPT-11 and fluorouracil (5-FU)]. Blood was taken exactly 15 min following a 2-h continuous infusion of CPT-11. Plasma concentrations of SN-38, SN-38G and CPT-11 were determined by a modified high-performance liquid chromatography (HPLC) method. The median, maximum and minimum values of plasma SN-38G/SN-38 ratios were 4.25, 7.09 and 1.03, respectively, indicating that UGT activities are variable among patients with the wild-type UGT1A1 gene. The plasma SN-38G/SN-38 ratios decreased with an increase in the trial numbers of chemotherapy (r=0.741, p=0.000669), suggesting that CPT-11 treatment suppresses UGT activity, and the low plasma SN-38G/SN-38 ratios resulted in the induction of greater neutropenia. However, in this analysis, 2 clearly separated regression lines were observed between plasma SN-38G/SN-38 ratios and neutropenia induction. In conclusion, UGT activity involved in SN-38 metabolism is variable among patients with the wild-type UGT1A1 gene, and each CPT-11 treatment suppresses UGT activity. One-point determination of the plasma SN-38G/SN-38 ratio may provide indications for the prediction of CPT-11-induced neutropenia and adjustment of the optimal dose, although further studies are required. PMID:22740978

Prehospital Interventions Performed in a Combat Zone: A Prospective Multicenter Study of 1,003 Combat Wounded

DTIC Science & Technology

2012-01-01

Howell, Maj Dean Hudson, LTC Marjorie Johnson, MAJ Colin Meghoo, MAJ Kyle Remick, MAJ Felecia Rivers, LTC James Sebesta, MAJ Leilani Siaki, Maj Adrian K... Stull , CPT Martha Swift, Capt Travis Taylor, Maj Ryan P. Tyner, Maj Gregory Watson, CPT Jennifer G. Ysmael. DISCLOSURE The views expressed in this

Targeting CPT1A-mediated fatty acid oxidation sensitizes nasopharyngeal carcinoma to radiation therapy

PubMed Central

Tan, Zheqiong; Xiao, Lanbo; Tang, Min; Bai, Fang; Li, Jiangjiang; Li, Liling; Shi, Feng; Li, Namei; Li, Yueshuo; Du, Qianqian; Lu, Jingchen; Weng, Xinxian; Yi, Wei; Zhang, Hanwen; Fan, Jia; Zhou, Jian; Gao, Qiang; Onuchic, José N.; Bode, Ann M.; Luo, Xiangjian; Cao, Ya

2018-01-01

Nasopharyngeal carcinoma (NPC) has a particularly high prevalence in southern China, southeastern Asia and northern Africa. Radiation resistance remains a serious obstacle to successful treatment in NPC. This study aimed to explore the metabolic feature of radiation-resistant NPC cells and identify new molecular-targeted agents to improve the therapeutic effects of radiotherapy in NPC. Methods: Radiation-responsive and radiation-resistant NPC cells were used as the model system in vitro and in vivo. Metabolomics approach was used to illustrate the global metabolic changes. 13C isotopomer tracing experiment and Seahorse XF analysis were undertaken to determine the activity of fatty acid oxidation (FAO). qRT-PCR was performed to evaluate the expression of essential FAO genes including CPT1A. NPC tumor tissue microarray was used to investigate the prognostic role of CPT1A. Either RNA interference or pharmacological blockade by Etomoxir were used to inhibit CPT1A. Radiation resistance was evaluated by colony formation assay. Mitochondrial membrane potential, apoptosis and neutral lipid content were measured by flow cytometry analysis using JC-1, Annexin V and LipidTOX Red probe respectively. Molecular markers of mitochondrial apoptosis were detected by western blot. Xenografts were treated with Etomoxir, radiation, or a combination of Etomoxir and radiation. Mitochondrial apoptosis and lipid droplets content of tumor tissues were detected by cleaved caspase 9 and Oil Red O staining respectively. Liquid chromatography coupled with tandem mass spectrometry approach was used to identify CPT1A-binding proteins. The interaction of CPT1A and Rab14 were detected by immunoprecipitation, immunofluorescence and in situ proximity ligation analysis. Fragment docking and direct coupling combined computational protein-protein interaction prediction method were used to predict the binding interface. Fatty acid trafficking was measured by pulse-chase assay using BODIPY C16 and MitoTracker Red probe. Results: FAO was active in radiation-resistant NPC cells, and the rate-limiting enzyme of FAO, carnitine palmitoyl transferase 1 A (CPT1A), was consistently up-regulated in these cells. The protein level of CPT1A was significantly associated with poor overall survival of NPC patients following radiotherapy. Inhibition of CPT1A re-sensitized NPC cells to radiation therapy by activating mitochondrial apoptosis both in vitro and in vivo. In addition, we identified Rab14 as a novel CPT1A binding protein. The CPT1A-Rab14 interaction facilitated fatty acid trafficking from lipid droplets to mitochondria, which decreased radiation-induced lipid accumulation and maximized ATP production. Knockdown of Rab14 attenuated CPT1A-mediated fatty acid trafficking and radiation resistance. Conclusion: An active FAO is a vital signature of NPC radiation resistance. Targeting CPT1A could be a beneficial regimen to improve the therapeutic effects of radiotherapy in NPC patients. Importantly, the CPT1A-Rab14 interaction plays roles in CPT1A-mediated radiation resistance by facilitating fatty acid trafficking. This interaction could be an attractive interface for the discovery of novel CPT1A inhibitors. PMID:29721083

Distinct Neural Activity Associated with Focused-Attention Meditation and Loving-Kindness Meditation

PubMed Central

Lee, Tatia M. C.; Leung, Mei-Kei; Hou, Wai-Kai; Tang, Joey C. Y.; Yin, Jing; So, Kwok-Fai; Lee, Chack-Fan; Chan, Chetwyn C. H.

2012-01-01

This study examined the dissociable neural effects of ānāpānasati (focused-attention meditation, FAM) and mettā (loving-kindness meditation, LKM) on BOLD signals during cognitive (continuous performance test, CPT) and affective (emotion-processing task, EPT, in which participants viewed affective pictures) processing. Twenty-two male Chinese expert meditators (11 FAM experts, 11 LKM experts) and 22 male Chinese novice meditators (11 FAM novices, 11 LKM novices) had their brain activity monitored by a 3T MRI scanner while performing the cognitive and affective tasks in both meditation and baseline states. We examined the interaction between state (meditation vs. baseline) and expertise (expert vs. novice) separately during LKM and FAM, using a conjunction approach to reveal common regions sensitive to the expert meditative state. Additionally, exclusive masking techniques revealed distinct interactions between state and group during LKM and FAM. Specifically, we demonstrated that the practice of FAM was associated with expertise-related behavioral improvements and neural activation differences in attention task performance. However, the effect of state LKM meditation did not carry over to attention task performance. On the other hand, both FAM and LKM practice appeared to affect the neural responses to affective pictures. For viewing sad faces, the regions activated for FAM practitioners were consistent with attention-related processing; whereas responses of LKM experts to sad pictures were more in line with differentiating emotional contagion from compassion/emotional regulation processes. Our findings provide the first report of distinct neural activity associated with forms of meditation during sustained attention and emotion processing. PMID:22905090

Preliminary findings of the effects of rivastigmine, an acetylcholinesterase inhibitor, on working memory in cocaine-dependent volunteers

PubMed Central

Mahoney, James J.; Kalechstein, Ari D.; Verrico, Christopher D.; Arnoudse, Nicholas M.; Shapiro, Benjamin A.; De La Garza, Richard

2015-01-01

Long-term cocaine use is a risk factor for the onset of neurocognitive impairment. This study sought to determine whether the cholinesterase inhibitor rivastigmine could improve neurocognitive performance in cocaine-dependent individuals. Cocaine-dependent individuals who were not seeking treatment at the time of enrollment in the study were randomly assigned to receive placebo (n = 16), rivastigmine 3 mg (n = 13), or rivastigmine 6 mg (n = 12). The baseline neurocognitive assessment, which included measures of attention/information processing (as measured by the Continuous Performance Task-II (CPT-II)), verbal learning/episodic memory (as measured by the Hopkins Verbal Learning Test-Revised (HVLT-R)), and working memory (as measured by the Dual N-Back Task), was conducted prior to the administration of study medication (Day 0). The follow-up assessment was conducted on Day 8 after the participants had received rivastigmine or placebo for 7 days (Day 2–8). Rivastigmine administration significantly improved performance on one measure of working memory span (mean n-back span). This study provides additional data showing that cocaine-associated neurocognitive impairment, specifically working memory deficits, can be remediated, at least to some degree. PMID:24239594

Preliminary findings of the effects of rivastigmine, an acetylcholinesterase inhibitor, on working memory in cocaine-dependent volunteers.

PubMed

Mahoney, James J; Kalechstein, Ari D; Verrico, Christopher D; Arnoudse, Nicholas M; Shapiro, Benjamin A; De La Garza, Richard

2014-04-03

Long-term cocaine use is a risk factor for the onset of neurocognitive impairment. This study sought to determine whether the cholinesterase inhibitor rivastigmine could improve neurocognitive performance in cocaine-dependent individuals. Cocaine-dependent individuals who were not seeking treatment at the time of enrollment in the study were randomly assigned to receive placebo (n=16), rivastigmine 3mg (n=13), or rivastigmine 6mg (n=12). The baseline neurocognitive assessment, which included measures of attention/information processing (as measured by the Continuous Performance Task-II (CPT-II)), verbal learning/episodic memory (as measured by the Hopkins Verbal Learning Test-Revised (HVLT-R)), and working memory (as measured by the Dual N-Back Task), was conducted prior to the administration of study medication (Day 0). The follow-up assessment was conducted on Day 8 after the participants had received rivastigmine or placebo for 7days (Day 2-8). Rivastigmine administration significantly improved performance on one measure of working memory span (mean n-back span). This study provides additional data showing that cocaine-associated neurocognitive impairment, specifically working memory deficits, can be remediated, at least to some degree. Copyright © 2013. Published by Elsevier Inc.

Predictive Validity of a Cigarette Purchase Task in a Randomized Controlled Trial of Contingent Vouchers for Smoking in Individuals With Substance Use Disorders

PubMed Central

Mackillop, James; Murphy, Cara M.; Martin, Rosemarie A.; Stojek, Monika; Tidey, Jennifer W.; Colby, Suzanne M.

2016-01-01

Abstract Introduction: A cigarette purchase task (CPT) is a behavioral economic measure of the reinforcing value of smoking in monetary terms (ie, cigarette demand). This study investigated whether cigarette demand predicted response to contingent monetary rewards for abstinence among individuals with substance use disorders. It also sought to replicate evidence for greater price sensitivity at whole-dollar pack price transitions (ie, left-digit effects). Methods: Participants ( N = 338) were individuals in residential substance use disorder treatment who participated in a randomized controlled trial that compared contingent vouchers to noncontingent vouchers for smoking abstinence. Baseline demand indices were used to predict number of abstinent days during the 14-day voucher period (after the reduction lead-in) and at 1 and 3 months afterward. Results: Demand indices correlated with measures of smoking and nicotine dependence. As measured by elasticity, intensity and Omax , higher demand significantly predicted fewer abstinent exhaled carbon monoxide readings during voucher period for individuals in the noncontingent vouchers condition. Breakpoint exhibited a trend-level association with abstinent exhaled carbon monoxide readings. Demand indices did not predict abstinence in the contingent vouchers group, and did not predict abstinence at 1- and 3-month follow-ups. Left-digit price transitions were associated with significantly greater reductions in consumption. Conclusions: The association of cigarette demand with smoking behavior only in the group for whom abstinence was not incentivized indicates that CPT assesses the value of smoking more than the value of money per se and that vouchers counteract the effects of the intrinsic reinforcing value of cigarettes. Results provide initial short-term evidence of predictive validity for the CPT indices. Implications: This study provides the first evidence of the validity of the CPT for predicting early response to brief advice for smoking cessation plus nicotine replacement in smokers with substance dependence. However, demand for cigarettes did not predict voucher-based treatment response, indicating that incentives serve as a powerful motivator not to smoke that acts in opposition to the intrinsic reinforcing value of cigarettes and that the indices reflect the value of smoking more than the value of money per se. PMID:26498173

The effect of prenatal drug exposure and caregiving context on children's performance on a task of sustained visual attention.

PubMed

Ackerman, John P; Llorente, Antolin M; Black, Maureen M; Ackerman, Claire S; Mayes, Lacy A; Nair, Prasanna

2008-12-01

Three groups of children from low-income, urban environments were examined to determine the effects of prenatal drug exposure (PDE) and caregiving environment on sustained visual attention (SVA) at 7 years of age. Drug-exposed children remaining in maternal care (n = 43), drug-exposed children placed in nonmaternal care (n = 45), and community comparison (CC) children (n = 56) were administered a battery of neurocognitive tests, including the Conners' Continuous Performance Test (CPT). PDE children remaining in maternal care displayed more omission errors than CC children. PDE children in nonmaternal care had intermediate scores that did not differ significantly from PDE children in maternal care or CC children. There were no group differences with respect to commission errors or reaction time. CPT errors of omission and commission were significantly correlated with parent-reported attention problems and academic achievement scores. PDE in the context of care provided by a maternal caregiver with persistent drug use patterns may contribute to problems in children's SVA at school-age. As parental drug abuse can interfere with the provision of early care, children raised in a drug-using context may be highly vulnerable to problems with self-regulation, including sustained attention. SVA problems may contribute to subsequent academic and behavioral problems as demands for concentration and sustained effort increase throughout childhood. Children who have been prenatally exposed to drugs or raised in a drug-using household may benefit from early intervention services to avoid problems in SVA that may interfere with subsequent neurocognitive functioning and academic performance.

The Influence of Methylphenidate on Hyperactivity and Attention Deficits in Children With ADHD: A Virtual Classroom Test.

PubMed

Mühlberger, A; Jekel, K; Probst, T; Schecklmann, M; Conzelmann, A; Andreatta, M; Rizzo, A A; Pauli, P; Romanos, M

2016-05-13

This study compares the performance in a continuous performance test within a virtual reality classroom (CPT-VRC) between medicated children with ADHD, unmedicated children with ADHD, and healthy children. N = 94 children with ADHD (n = 26 of them received methylphenidate and n = 68 were unmedicated) and n = 34 healthy children performed the CPT-VRC. Omission errors, reaction time/variability, commission errors, and body movements were assessed. Furthermore, ADHD questionnaires were administered and compared with the CPT-VRC measures. The unmedicated ADHD group exhibited more omission errors and showed slower reaction times than the healthy group. Reaction time variability was higher in the unmedicated ADHD group compared with both the healthy and the medicated ADHD group. Omission errors and reaction time variability were associated with inattentiveness ratings of experimenters. Head movements were correlated with hyperactivity ratings of parents and experimenters. Virtual reality is a promising technology to assess ADHD symptoms in an ecologically valid environment. © The Author(s) 2016.

Neural circuitry of emotional and cognitive conflict revealed through facial expressions.

PubMed

Chiew, Kimberly S; Braver, Todd S

2011-03-09

Neural systems underlying conflict processing have been well studied in the cognitive realm, but the extent to which these overlap with those underlying emotional conflict processing remains unclear. A novel adaptation of the AX Continuous Performance Task (AX-CPT), a stimulus-response incompatibility paradigm, was examined that permits close comparison of emotional and cognitive conflict conditions, through the use of affectively-valenced facial expressions as the response modality. Brain activity was monitored with functional magnetic resonance imaging (fMRI) during performance of the emotional AX-CPT. Emotional conflict was manipulated on a trial-by-trial basis, by requiring contextually pre-cued facial expressions to emotional probe stimuli (IAPS images) that were either affectively compatible (low-conflict) or incompatible (high-conflict). The emotion condition was contrasted against a matched cognitive condition that was identical in all respects, except that probe stimuli were emotionally neutral. Components of the brain cognitive control network, including dorsal anterior cingulate cortex (ACC) and lateral prefrontal cortex (PFC), showed conflict-related activation increases in both conditions, but with higher activity during emotion conditions. In contrast, emotion conflict effects were not found in regions associated with affective processing, such as rostral ACC. These activation patterns provide evidence for a domain-general neural system that is active for both emotional and cognitive conflict processing. In line with previous behavioural evidence, greatest activity in these brain regions occurred when both emotional and cognitive influences additively combined to produce increased interference.

Neural Circuitry of Emotional and Cognitive Conflict Revealed through Facial Expressions

PubMed Central

Chiew, Kimberly S.; Braver, Todd S.

2011-01-01

Background Neural systems underlying conflict processing have been well studied in the cognitive realm, but the extent to which these overlap with those underlying emotional conflict processing remains unclear. A novel adaptation of the AX Continuous Performance Task (AX-CPT), a stimulus-response incompatibility paradigm, was examined that permits close comparison of emotional and cognitive conflict conditions, through the use of affectively-valenced facial expressions as the response modality. Methodology/Principal Findings Brain activity was monitored with functional magnetic resonance imaging (fMRI) during performance of the emotional AX-CPT. Emotional conflict was manipulated on a trial-by-trial basis, by requiring contextually pre-cued facial expressions to emotional probe stimuli (IAPS images) that were either affectively compatible (low-conflict) or incompatible (high-conflict). The emotion condition was contrasted against a matched cognitive condition that was identical in all respects, except that probe stimuli were emotionally neutral. Components of the brain cognitive control network, including dorsal anterior cingulate cortex (ACC) and lateral prefrontal cortex (PFC), showed conflict-related activation increases in both conditions, but with higher activity during emotion conditions. In contrast, emotion conflict effects were not found in regions associated with affective processing, such as rostral ACC. Conclusions/Significance These activation patterns provide evidence for a domain-general neural system that is active for both emotional and cognitive conflict processing. In line with previous behavioural evidence, greatest activity in these brain regions occurred when both emotional and cognitive influences additively combined to produce increased interference. PMID:21408006

Effects of caffeine ingestion on endurance performance in mentally fatigued individuals.

PubMed

Azevedo, Rafael; Silva-Cavalcante, Marcos David; Gualano, Bruno; Lima-Silva, Adriano E; Bertuzzi, Romulo

2016-12-01

To examine the effects of caffeine ingestion on physiological and perceptual responses in mentally fatigued individuals. Eight male physically active subjects completed four cycling constant-workload tests in four experimental conditions at 80 % of maximal power output: control (C), mental fatigue (MF), mental fatigue plus caffeine ingestion (5 mg/kg) (MF-CAF), and mental fatigue plus placebo (MF-PLA). The mental fatigue was induced by a continuous performance task A-X version (AX-CPT). Before and after the AX-CPT, the profile of mood state (POMS) and blood samples for lactate measurement were collected. Oxygen consumption ([Formula: see text]), rating of perceived exertion (RPE), and electromyography (EMG) activity were measured during the cycling test. The time to exhaustion in C, MF, MF-PLA, and MF-CAF were 251 ± 30, 222 ± 23, 248 ± 28, and 285 ± 42 s, respectively. Delta values (corrected by C condition) were higher in MF-CAF than MF (P = 0.031). MF-CAF reported higher Vigor scores when compared with C (P = 0.046) and MF (P = 0.020). RPE at the first minute was significantly higher in MF-PLA than in C (P = 0.050); at the second minute, RPE was higher in MF-PLA than in C (P = 0.049) and MF-CAF (P = 0.048). EMG activity was not different between the conditions. Caffeine ingestion increased approximately 14 % endurance performance after the induction of mental fatigue. This effect was accompanied by a tendency to improvement in mood state (i.e., vigor). Therefore, caffeine ingestion can promote a beneficial effect on endurance performance in mentally fatigued individuals.

Partial agonism at the α7 nicotinic acetylcholine receptor improves attention, impulsive action and vigilance in low attentive rats.

PubMed

Hayward, Andrew; Adamson, Lisa; Neill, Joanna C

2017-04-01

Inattention is a disabling symptom in conditions such as schizophrenia and attention deficit/hyperactivity disorder. Nicotine can improve attention and vigilance, but is unsuitable for clinical use due to abuse liability. Genetic knockout of the α7 nicotinic acetylcholine receptor (nAChR) induces attention deficits therefore selective agonism may improve attention, without the abuse liability associated with nicotine. The α7 nAChR partial agonist encenicline (formerly EVP-6124) enhances memory in rodents and humans. Here we investigate, for the first time, efficacy of encenicline to improve attention and vigilance in animals behaviourally grouped for low attentive traits in the 5 choice-continuous performance task (5C-CPT). Female Lister Hooded rats were trained to perform the 5C-CPT with a variable stimulus duration (SD). Animals were then grouped based on performance into upper and lower quartiles of d' (vigilance) and accuracy (selective attention), producing high-attentive (HA) and low-attentive (LA) groups. LA animals showed an increase in selective attention and vigilance at 0.3mg/kg encenicline, a reduction in impulsive action (probability of false alarms) and increase in vigilance following 1mg/kg at 0.75sSD. At 1mg/kg, HA animals had reduced selective attention at 0.75sSD and reduced vigilance at 0.75 and 1.25sSD. Improvement of attention, vigilance and impulsive action in LA animals demonstrates that encenicline has pro-attentive properties dependent on baseline levels of performance. Our work suggests that α7 nAChR partial agonism may improve attention particularly in conditions with low attention. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Adapting an Ant Colony Metaphor for Multi-Robot Chemical Plume Tracing

PubMed Central

Meng, Qing-Hao; Yang, Wei-Xing; Wang, Yang; Li, Fei; Zeng, Ming

2012-01-01

We consider chemical plume tracing (CPT) in time-varying airflow environments using multiple mobile robots. The purpose of CPT is to approach a gas source with a previously unknown location in a given area. Therefore, the CPT could be considered as a dynamic optimization problem in continuous domains. The traditional ant colony optimization (ACO) algorithm has been successfully used for combinatorial optimization problems in discrete domains. To adapt the ant colony metaphor to the multi-robot CPT problem, the two-dimension continuous search area is discretized into grids and the virtual pheromone is updated according to both the gas concentration and wind information. To prevent the adapted ACO algorithm from being prematurely trapped in a local optimum, the upwind surge behavior is adopted by the robots with relatively higher gas concentration in order to explore more areas. The spiral surge (SS) algorithm is also examined for comparison. Experimental results using multiple real robots in two indoor natural ventilated airflow environments show that the proposed CPT method performs better than the SS algorithm. The simulation results for large-scale advection-diffusion plume environments show that the proposed method could also work in outdoor meandering plume environments. PMID:22666056

Adapting an ant colony metaphor for multi-robot chemical plume tracing.

PubMed

Meng, Qing-Hao; Yang, Wei-Xing; Wang, Yang; Li, Fei; Zeng, Ming

2012-01-01

We consider chemical plume tracing (CPT) in time-varying airflow environments using multiple mobile robots. The purpose of CPT is to approach a gas source with a previously unknown location in a given area. Therefore, the CPT could be considered as a dynamic optimization problem in continuous domains. The traditional ant colony optimization (ACO) algorithm has been successfully used for combinatorial optimization problems in discrete domains. To adapt the ant colony metaphor to the multi-robot CPT problem, the two-dimension continuous search area is discretized into grids and the virtual pheromone is updated according to both the gas concentration and wind information. To prevent the adapted ACO algorithm from being prematurely trapped in a local optimum, the upwind surge behavior is adopted by the robots with relatively higher gas concentration in order to explore more areas. The spiral surge (SS) algorithm is also examined for comparison. Experimental results using multiple real robots in two indoor natural ventilated airflow environments show that the proposed CPT method performs better than the SS algorithm. The simulation results for large-scale advection-diffusion plume environments show that the proposed method could also work in outdoor meandering plume environments.

Charged Particle Radiation Therapy for Uveal Melanoma: A Systematic Review and Meta-Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Zhen, E-mail: Wang.Zhen@mayo.edu; Nabhan, Mohammed; Schild, Steven E.

2013-05-01

Charged particle therapy (CPT) delivered with either protons, helium ions, or carbon ions, has been used to treat uveal melanoma. The present analysis was performed to systematically evaluate the efficacy and adverse effects of CPT for uveal melanoma. We searched EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and SciVerse Scopus and cross-referenced recent systematic reviews through January 2012. Two independent reviewers identified clinical trials and observational studies of CPT (protons, helium ions, and carbon ions). These reviewers extracted data and assessed study quality. Twenty-seven studies enrolling 8809 uveal melanoma patients met inclusion criteria. Themore » rate of local recurrence was significantly less with CPT than with brachytherapy (odds ratio [OR] = 0.22, 95% confidence interval [CI], 0.21-0.23). There were no significant differences in mortality or enucleation rates. Results were robust in multiple sensitivity analyses. CPT was also associated with lower retinopathy and cataract formation rates. Data suggest better outcomes may be possible with charged particle therapy with respect to local recurrence, retinopathy, and cataract formation rates. The overall quality of the evidence is low, and higher quality comparative effectiveness studies are needed to provide better evidence.« less

Camptothecin-producing endophytic fungus Trichoderma atroviride LY357: isolation, identification, and fermentation conditions optimization for camptothecin production.

PubMed

Pu, Xiang; Qu, Xixing; Chen, Fei; Bao, Jinku; Zhang, Guolin; Luo, Yinggang

2013-11-01

Camptothecin (CPT), the third largest anticancer drug, is produced mainly by Camptotheca acuminata and Nothapodytes foetida. CPT itself is the starting material for clinical CPT-type drugs, but the plant-derived CPT cannot support the heavy demand from the global market. Research efforts have been made to identify novel sources for CPT. In this study, three CPT-producing endophytic fungi, Aspergillus sp. LY341, Aspergillus sp. LY355, and Trichoderma atroviride LY357, were isolated and identified from C. acuminata. Most CPT produced by these fungi was found in the fermentation broth, and their corresponding CPT yields were 7.93, 42.92, and 197.82 μg l(-1), respectively. The CPT-producing capability of LY341 and LY355 was completely lost after repeat subculturing. A substantial decrease of CPT production was also observed in the second generation of LY357. However, a stable and sustainable production of CPT was found from the second generation through the eighth generation of LY357. The fermentation medium, time, pH, temperature, and agitation rate were optimized for CPT production. Methyl jasmonate and XAD16 were proven to be an optimum elicitor and adsorbent resin, respectively, in view of that CPT yield was increased 3.4- and 11-fold through their use. A 50- to 75-fold increase of CPT yield was obtained when the optimized fermentation conditions, elicitor, and adsorbent resin were combined and applied to the culture of the seventh and eighth generations of LY357, and the highest CPT yield was 142.15 μg l(-1). The CPT-producing T. atroviride LY357 paves a potential to uncover the mysteries of CPT biosynthesis.

Individual and combined effects of cannabis and tobacco on drug reward processing in non-dependent users.

PubMed

Hindocha, Chandni; Lawn, Will; Freeman, Tom P; Curran, H Valerie

2017-11-01

Cannabis and tobacco are often smoked simultaneously in joints, and this practice may increase the risks of developing tobacco and/or cannabis use disorders. Currently, there is no human experimental research on how these drugs interact on addiction-related measures. This study aimed to investigate how cannabis and tobacco, each alone and combined together in joints, affected individuals' demand for cannabis puffs and cigarettes, explicit liking of drug and non-drug-related stimuli and craving. A double-blind, 2 (active cannabis, placebo cannabis) × 2 (active tobacco, placebo tobacco) crossover design was used with 24 non-dependent cannabis and tobacco smokers. They completed a pleasantness rating task (PRT), a marijuana purchase task (MPT) and a cigarette purchase task (CPT) alongside measures of craving pre- and post-drug administration. Relative to placebo cannabis, active cannabis reduced liking of cannabis-associated stimuli and increased response time to all stimuli except cigarette-related stimuli. Relative to placebo cannabis, active cannabis decreased demand for cannabis puffs (trends for breakpoint and elasticity) and cigarettes (breakpoint, P max , O max ) on several characteristics of the purchase tasks. We found no evidence that active tobacco, both alone or combined with cannabis, had an effect on liking, demand or craving. Acutely, cannabis reduced liking of cannabis-related stimuli and demand for cannabis itself. Acute cannabis also reduced demand for cigarettes on the CPT. Acute tobacco administration did not affect demand or pleasantness ratings for cigarettes themselves or cannabis. In non-dependent cannabis and tobacco co-users, tobacco did not influence the rewarding effects of cannabis.

A dyadic analysis of siblings' relationship quality, behavioural responses, and pain experiences during experimental pain.

PubMed

Schinkel, Meghan G; Chambers, Christine T; Corkum, Penny; Jacques, Sophie

2018-04-16

Research on family factors in paediatric pain has primarily focused on parents; the role of siblings has been largely ignored. This study examined whether sibling relationship quality was related to siblings' behaviours during experimental pain, and whether the behaviours of an observing sibling were related to children's pain outcomes. Ninety-two sibling dyads between 8-12 years old completed both observational and questionnaire measures of sibling relationship quality. Children took turns completing the cold pressor task (CPT) in a counterbalanced order with their sibling present. Pain outcomes (intensity, fear, tolerance) were recorded for each sibling, and the behaviour of the observing and participating siblings during the CPT were coded as attending, non-attending, and coping/encouragement. Structural equation modelling, using the actor-partner interdependence model, was conducted to analyse the dyadic data. While participating in the CPT with their sibling present, greater levels of warmth and positivity in the sibling relationship were related to children engaging in more non-attending behaviours and less attending behaviours. Greater levels of attending behaviours by the observing child was related to the sibling having a lower pain tolerance, and greater levels of coping/encouragement behaviours by the observing child was related to the sibling reporting greater pain intensity and fear during the CPT. Children with warmer/positive sibling relationships were more likely to respond to acute pain by shifting the focus away from their pain experience (e.g., through distraction) when a sibling was present. Pain-focused behaviours by an observing sibling are related to greater child pain and fear during experimental pain.

Pain catastrophizing mediates the relationship between self-reported strenuous exercise involvement and pain ratings: moderating role of anxiety sensitivity.

PubMed

Goodin, Burel R; McGuire, Lynanne M; Stapleton, Laura M; Quinn, Noel B; Fabian, Lacy A; Haythornthwaite, Jennifer A; Edwards, Robert R

2009-11-01

To investigate the cross-sectional associations among self-reported weekly strenuous exercise bouts, anxiety sensitivity, and their interaction with pain catastrophizing and pain responses to the cold pressor task (CPT) in healthy, ethnically diverse young adults (n = 79). Exercise involvement has been shown to have hypoalgesic effects and cognitive factors may partially explain this effect. Particularly, alterations in pain catastrophizing have been found to mediate the positive pain outcomes of multidisciplinary treatments incorporating exercise. Further, recent evidence suggests that exercise involvement and anxiety sensitivity may act together, as interacting factors, to exert an effect on catastrophizing and pain outcomes; however, further research is needed to clarify the nature of this interaction. Before the CPT, participants were asked to complete the Godin Leisure-Time Exercise Questionnaire, the Beck Depression Inventory, and the Anxiety Sensitivity Index. After the CPT, participants completed a modified version of the Pain Catastrophizing Scale and the Short Form-McGill Pain Questionnaire. At a high level of anxiety sensitivity, controlling for depressive symptoms, CPT immersion time, and sex differences, a bias-corrected (BC), bootstrapped confidence interval revealed that pain catastrophizing significantly mediated the relationship between self-reported weekly strenuous exercise bouts and pain response (95% BC Confidence Interval = -9.558, -0.800 with 1000 resamples). At intermediate and low levels of anxiety sensitivity, no significant mediation effects were found. These findings support that, for pain catastrophizing to mediate the strenuous exercise-pain response relation, individuals must possess a high level of anxiety sensitivity.

An experimental investigation of the effect of a justice violation on pain experience and expression among individuals with high and low just world beliefs.

PubMed

Trost, Z; Scott, W; Lange, J M; Manganelli, L; Bernier, E; Sullivan, M J

2014-03-01

Perceptions of injustice are linked with poorer physical and psychological outcomes in the context of pain and injury. Violations of injustice can arise out of violations of just world belief (JWB). However, no study has yet examined whether JWB moderates the effect of justice violation on pain experience. The current study examined the effect of an experimental justice violation on acute pain outcomes and whether JWB moderated this effect. Participants completed the JWB scale and then engaged in two cold pressor tasks (CPT). Half the participants were told that the second CPT immersion was part of standard protocol; the other half were told that the painful procedure had to be repeated due to experimenter negligence. Participants provided report of pain intensity following each CPT immersion. Video records of participants undergoing the CPT were coded for presence and duration of pain behaviour. Exposure to the justice violation resulted in elevated pain intensity from the first to the second immersion only among participants with high JWB. For participants with low JWB and participants in the control condition, there was no significant difference in pain intensity across immersions. Control participants showed a decrease in pain behaviour from the first to the second immersion. In the negligence/ justice violation condition, reductions in pain behaviour were observed only among participants with low JWB. Our results indicate that individuals with high JWB may show particularly adverse reactions in response to justice violations in the context of acute pain experience. © 2013 European Pain Federation - EFIC®

The Plant Alkaloid Camptothecin as a Novel Antifouling Compound for Marine Paints: Laboratory Bioassays and Field Trials.

PubMed

Feng, Dan Qing; He, Jian; Chen, Si Yu; Su, Pei; Ke, Cai Huan; Wang, Wei

2018-06-02

The extensive use of copper and booster biocides in antifouling (AF) paints has raised environmental concerns and the need to develop new AF agents. In the present study, 18 alkaloids derived from terrestrial plants were initially evaluated for AF activity using laboratory bioassays with the bryozoan Bugula neritina and the barnacle Balanus albicostatus. The results showed that 4 of the 18 alkaloids were effective in inhibiting larval settlement of B. neritina, with an EC 50 range of 6.18 to 43.11 μM, and 15 of the 18 alkaloids inhibited larval settlement of B. albicostatus, with EC 50 values ranging from 1.18 to 67.58 μM. Field trials that incorporated five alkaloids respectively into paints with 20% w/w indicated an in situ AF efficiency of evodiamine, strychnine, camptothecin (CPT), and cepharanthine, with the most potent compound being CPT, which also exhibited stronger AF efficiency than the commercial antifoulants cuprous oxide and zinc pyrithione in the field over a period of 12 months. Further field trials with different CPT concentrations (0.1 to 20% w/w) in the paints suggested a concentration-dependent AF performance in the natural environment, and the effective concentrations to significantly inhibit settlement of biofoulers in the field were ≥ 0.5% w/w (the efficiency of 0.5% w/w lasted for 2 months). Moreover, CPT toxicity against the crustacean Artemia salina, the planktonic microalgae Phaeodactylum tricornutum and Isochrysis galbana, was examined. The results showed that 24 h LC 50 of CPT against A. salina was 20.75 μM, and 96 h EC 50 (growth inhibition) values of CPT to P. tricornutum and I. galbana were 55.81 and 6.29 μM, respectively, indicating that CPT was comparatively less toxic than several commercial antifoulants previously reported. Our results suggest the novel potential application of CPT as an antifoulant.

Gene-carried hepatoma targeting complex induced high gene transfection efficiency with low toxicity and significant antitumor activity.

PubMed

Zhao, Qing-Qing; Hu, Yu-Lan; Zhou, Yang; Li, Ni; Han, Min; Tang, Gu-Ping; Qiu, Feng; Tabata, Yasuhiko; Gao, Jian-Qing

2012-01-01

The success of gene transfection is largely dependent on the development of a vehicle or vector that can efficiently deliver a gene to cells with minimal toxicity. A liver cancer-targeted specific peptide (FQHPSF sequence) was successfully synthesized and linked with chitosan-linked polyethylenimine (CP) to form a new targeted gene delivery vector called CPT (CP/peptide). The structure of CPT was confirmed by (1)H nuclear magnetic resonance spectroscopy and ultraviolet spectrophotometry. The particle size of CPT/ DNA complexes was measured using laser diffraction spectrometry and the cytotoxicity of the copolymer was evaluated by methylthiazol tetrazolium method. The transfection efficiency evaluation of the CP copolymer was performed using luciferase activity assay. Cellular internalization of the CP/DNA complex was observed under confocal laser scanning microscopy. The targeting specificity of the polymer coupled to peptide was measured by competitive inhibition transfection study. The liver targeting specificity of the CPT copolymer in vivo was demonstrated by combining the copolymer with a therapeutic gene, interleukin-12, and assessed by its abilities in suppressing the growth of ascites tumor in mouse model. The results showed that the liver cancer-targeted specific peptide was successfully synthesized and linked with CP to form a new targeted gene delivery vector called CPT. The composition of CPT was confirmed and the vector showed low cytotoxicity and strong targeting specificity to liver tumors in vitro. The in vivo study results showed that interleukin-12 delivered by the new gene vector CPT/DNA significantly enhanced the antitumor effect on ascites tumor-bearing imprinting control region mice as compared with polyethylenimine (25 kDa), CP, and other controls, which further demonstrate the targeting specificity of the new synthesized polymer. The synthesized CPT copolymer was proven to be an effective liver cancer-targeted vector for therapeutic gene delivery, which could be a potential candidate for targeted cancer gene therapy.

The Effect of Citicoline Supplementation on Motor Speed and Attention in Adolescent Males.

PubMed

McGlade, Erin; Agoston, Anna Monica; DiMuzio, Jennifer; Kizaki, Miho; Nakazaki, Eri; Kamiya, Toshikazu; Yurgelun-Todd, Deborah

2015-07-15

This study assessed the effects of citicoline, a nutraceutical, on attention, psychomotor function, and impulsivity in healthy adolescent males. Seventy-five healthy adolescent males were randomly assigned to either the citicoline group (n = 51 with 250 or 500 mg citicoline) or placebo (n = 24). Participants completed the Ruff 2&7 Selective Attention Test, Finger Tap Test, and the Computerized Performance Test, Second Edition (CPT-II) at baseline and after 28 days of supplementation. Individuals receiving citicoline exhibited improved attention (p = 0.02) and increased psychomotor speed (p = 0.03) compared with those receiving placebo. Higher weight-adjusted dose significantly predicted increased accuracy on an attention task (p = 0.01), improved signal detectability on a computerized attention task (p = 0.03), and decreased impulsivity (p = 0.01). Adolescent males receiving 28 days of Cognizin® citicoline showed improved attention and psychomotor speed and reduced impulsivity compared to adolescent males who received placebo. © 2015 SAGE Publications.

Individual and group cognitive processing therapy: Effectiveness across two veterans affairs posttraumatic stress disorder treatment clinics.

PubMed

Lamp, Kristen E; Avallone, Kimberly M; Maieritsch, Kelly P; Buchholz, Katherine R; Rauch, Sheila A M

2018-05-14

In accordance with Veterans Affairs (VA) policy, VA posttraumatic stress disorder (PTSD) clinics offer evidence-based treatments including cognitive processing therapy (CPT). To facilitate access to care, CPT is offered in both group and individual formats in many VA PTSD clinics. Group and individual delivery of CPT have been directly compared in active duty samples, but these findings have not been extended to VA populations. The present article directly compares the effectiveness of group and individual CPT with a written trauma account (CPT+A) across two VA PTSD clinics. Veterans (N = 465) completed initial evaluations and enrolled in either group CPT+A (N = 146) or individual CPT+A (N = 319). Self-report measures of PTSD and depression symptoms were collected at pre-, mid-, and posttreatment; combined across treatment sites; and analyzed using hierarchical linear modeling. PTSD and depression symptoms reduced significantly over the course of group and individual CPT+A. Medium treatment effects were found for group CPT+A (d = .66 for PTSD, d = .68 for depression), and large treatment effects were found for individual CPT+A (d = .96 for PTSD, d = .79 for depression). Individual CPT+A led to significantly greater PTSD and depression symptom reduction than group CPT+A, indicating that in VA outpatient PTSD clinic settings, individual CPT+A may be a more effective approach than group CPT-A. In addition, PTSD symptoms reduced significantly more for Caucasian veterans than for African American veterans during CPT+A, indicating the importance of providing culturally competent trauma-focused care. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Multi-Method Assessment of ADHD Characteristics in Preschool Children: Relations between Measures

PubMed Central

Sims, Darcey M.; Lonigan, Christopher J.

2011-01-01

Several forms of assessment tools, including behavioral rating scales and objective tests such as the Continuous Performance Test (CPT), can be used to measure inattentive and hyperactive/impulsive behaviors associated with Attention-Deficit/Hyperactivity Disorder (ADHD). However, research with school-age children has shown that the correlations between parent ratings, teacher ratings, and scores on objective measures of ADHD-characteristic behaviors are modest at best. In this study, we examined the relations between parent and teacher ratings of ADHD and CPT scores in a sample of 65 preschoolers ranging from 50 to 72 months of age. No significant associations between teacher and parent ratings of ADHD were found. Parent-ratings of both inattention and hyperactivity/impulsivity accounted for variance in CPT omission errors but not CPT commission errors. Teacher ratings showed evidence of convergent and discriminant validity when entered simultaneously in a hierarchical regression. These tools may be measuring different aspects of inattention and hyperactivity/impulsivity. PMID:22518069

High-precision comparison of the antiproton-to-proton charge-to-mass ratio.

PubMed

Ulmer, S; Smorra, C; Mooser, A; Franke, K; Nagahama, H; Schneider, G; Higuchi, T; Van Gorp, S; Blaum, K; Matsuda, Y; Quint, W; Walz, J; Yamazaki, Y

2015-08-13

Invariance under the charge, parity, time-reversal (CPT) transformation is one of the fundamental symmetries of the standard model of particle physics. This CPT invariance implies that the fundamental properties of antiparticles and their matter-conjugates are identical, apart from signs. There is a deep link between CPT invariance and Lorentz symmetry--that is, the laws of nature seem to be invariant under the symmetry transformation of spacetime--although it is model dependent. A number of high-precision CPT and Lorentz invariance tests--using a co-magnetometer, a torsion pendulum and a maser, among others--have been performed, but only a few direct high-precision CPT tests that compare the fundamental properties of matter and antimatter are available. Here we report high-precision cyclotron frequency comparisons of a single antiproton and a negatively charged hydrogen ion (H(-)) carried out in a Penning trap system. From 13,000 frequency measurements we compare the charge-to-mass ratio for the antiproton (q/m)p- to that for the proton (q/m)p and obtain (q/m)p-/(q/m)p − 1 =1(69) × 10(-12). The measurements were performed at cyclotron frequencies of 29.6 megahertz, so our result shows that the CPT theorem holds at the atto-electronvolt scale. Our precision of 69 parts per trillion exceeds the energy resolution of previous antiproton-to-proton mass comparisons as well as the respective figure of merit of the standard model extension by a factor of four. In addition, we give a limit on sidereal variations in the measured ratio of <720 parts per trillion. By following the arguments of ref. 11, our result can be interpreted as a stringent test of the weak equivalence principle of general relativity using baryonic antimatter, and it sets a new limit on the gravitational anomaly parameter of |α − 1| < 8.7 × 10(-7).

Hospital-based child protection teams that care for parents who abuse or neglect their children recognize the need for multidisciplinary collaborative practice involving perinatal care and mental health professionals: a questionnaire survey conducted in Japan.

PubMed

Okato, Ayumi; Hashimoto, Tasuku; Tanaka, Mami; Tachibana, Masumi; Machizawa, Akira; Okayama, Jun; Endo, Mamiko; Senda, Masayoshi; Saito, Naoki; Iyo, Masaomi

2018-01-01

Child abuse and/or neglect is a serious issue, and in many cases, parents are the perpetrators. Hospital-based child protection teams (CPTs) play pivotal roles in the management of not only abused and/or neglected children but also of their parents; this is generally conducted through multidisciplinary practice. The aim of this study is to survey hospital-based CPT members to determine the professions they perceive to be most applicable to participation in CPTs. The participants were members of CPTs affiliated with hospitals that had pediatric emergency departments and which were located in Chiba Prefecture; specifically, 114 CPT members from 23 hospitals responded to this survey. The two main questionnaire items concerned are as follows: 1) each respondent's evaluation of conducting assessments, providing support, and implementing multidisciplinary collaborative practice in the treatment of abusive and negligent parents, and 2) each CPT member's opinion on the professions that are most important for CPT activities. An exploratory factor analysis (EFA) was performed to explore the factor structure of the data, and a correlation analysis was performed using the result obtained. The EFA returned two factors: multidisciplinary collaborative practice (α = 0.84) and assessment and support (α = 0.89). A correlational analysis showed that multidisciplinary collaborative practice had a positive correlation for obstetricians ( r = 0.315, p = 0.001), neonatologists ( r = 0.261, p = 0.007), midwives ( r = 0.248, p = 0.011), and psychiatrists ( r = 0.194, p = 0.048); however, assessment and support was only significantly correlated with midwives ( r = 0.208, p = 0.039). This study showed that hospital-based CPT members highly evaluate multidisciplinary collaborative practice for the management of abusive and/or negligent parents, and they believe that, in addition to pediatric physicians and nurses, perinatal care and mental health professionals are the most important participants in advanced CPT activities.

Camptothecin (CPT) and its derivatives are known to target topoisomerase I (Top1) as their mechanism of action: did we miss something in CPT analogue molecular targets for treating human disease such as cancer?

PubMed Central

Li, Fengzhi; Jiang, Tao; Li, Qingyong; Ling, Xiang

2017-01-01

Camptothecin (CPT) was discovered from plant extracts more than 60 years ago. Since then, only two CPT analogues (irinotecan and topotecan) have been approved for cancer treatment, although several thousand CPT derivatives have been synthesized and many of them were actively studied in our research community over the past 6+ decades. In this review article, we briefly summarize: (1) the discovery and early development of CPTs, (2) the recognized CPT mechanism of action (MOA), (3) the synthesis of CPT and CPT analogues, and (4) the structure-activity relationship (SAR) of CPT and its analogues. Next, we provide evidence that certain CPT analogues can exert improved efficacy with low toxicity independently of topoisomerase I (Top1) inhibition; instead, these CPT analogues use novel MOAs by targeting important cancer survival-associated oncogenic proteins and/or by bypassing various treatment-resistant mechanisms. We then present a comprehensive review of the most advanced CPT analogues in clinical development, with the goal of resolving why no new CPTs have been FDA approved for cancer treatment, beyond irinotecan and topotecan. We argue that new CPT Top1 inhibitor drugs are unlikely being found to be significantly better than irinotecan and/or topotecan in terms of the overall antitumor activity and toxicity. The significance of CPT analogues that possess novel MOAs has not been sufficiently recognized so far. In our opinion, this is a research area with great potential to make a breakthrough for development of the next generation of CPT analogues that possess high efficacy (due to novel targets) and low toxicity (due to low inhibition of Top1 activity/function) for effective treatment of human disease, including cancer. PMID:29312794

Social and leadership abilities in attention deficit/hyperactivity disorder: relation with cognitive-attentional capacities.

PubMed

Fernández-Jaén, Alberto; Martín Fernández-Mayoralas, Daniel; López-Arribas, Sonia; Pardos-Véglia, Alexandra; Muñiz-Borrega, Blanca; García-Savaté, Carolina; Prados-Parra, Baldomero; Calleja-Pérez, Beatriz; Muñoz-Jareño, Nuria; Fernández-Perrone, Ana L

2012-01-01

We have analyzed social and leadership abilities in children with ADHD and their relationship with execution of tasks involving sustained attention and inhibitory control. A retrospective analysis of 170 patients with ADHD was performed. We evaluated leadership and social abilities, measured through the Behavior Assessment System for Children (BASC) and their relations with the results of different neuropsychological tests, including Wechsler scale for children (WISC-IV) and Conners' continuous performance (CPT II). In the differential analysis between the IQ, results of the tests and their relation to BASC scores, a statistically significant relation was observed between attentional capacity expected according to the patient's intelligence and social skills scores (according to BASC filled out by mothers and teachers) and leadership (according to all informants) sections. Attentional difficulties are closely related to social competence in patients with ADHD, either by a direct cause-effect relationship or a shared dysexecutive substrate of this disorder.

Inducing Proactive Control Shifts in the AX-CPT

PubMed Central

Gonthier, Corentin; Macnamara, Brooke N.; Chow, Michael; Conway, Andrew R. A.; Braver, Todd S.

2016-01-01

The Dual Mechanisms of Control (DMC) account (Braver, 2012) proposes two distinct mechanisms of cognitive control, proactive and reactive. This account has been supported by a large number of studies using the AX-CPT paradigm that have demonstrated not only between-group differences, but also within-subjects variability in the use of the two control mechanisms. Yet there has been little investigation of task manipulations that can experimentally modulate the use of proactive control in healthy young adults; such manipulations could be useful to better understand the workings of cognitive control mechanisms. In the current study, a series of three experiments demonstrate how individuals can be systematically biased toward and away from the utilization of proactive control, via strategy training and no-go manipulations, respectively. These results provide increased support for the DMC framework, and provide a new basis from which to examine group-based differences and neural mechanisms underlying the two control modes. PMID:27920741

Homozygous carnitine palmitoyltransferase 1a (liver isoform) deficiency is lethal in the mouse.

PubMed

Nyman, Lara R; Cox, Keith B; Hoppel, Charles L; Kerner, Janos; Barnoski, Barry L; Hamm, Doug A; Tian, Liqun; Schoeb, Trenton R; Wood, Philip A

2005-01-01

To better understand carnitine palmitoyltransferase 1a (liver isoform, gene=Cpt-1a, protein=CPT-1a) deficiency in human disease, we developed a gene knockout mouse model. We used a replacement gene targeting strategy in ES cells that resulted in the deletion of exons 11-18, thus producing a null allele. Homozygous deficient mice (CPT-1a -/-) were not viable. There were no CPT-1a -/- pups, embryos or fetuses detected from day 10 of gestation to term. FISH analysis demonstrated targeting vector recombination at the expected single locus on chromosome 19. The inheritance pattern from heterozygous matings was skewed in both C57BL/6NTac, 129S6/SvEvTac (B6;129 mixed) and 129S6/SvEvTac (129 coisogenic) genetic backgrounds biased toward CPT-1a +/- mice (>80%). There was no sex preference with regard to germ-line transmission of the mutant allele. CPT-1a +/- mice had decreased Cpt-1a mRNA expression in liver, heart, brain, testis, kidney, and white fat. This resulted in 54.7% CPT-1 activity in liver from CPT-1a +/- males but no significant difference in females as compared to CPT-1a +/+ controls. CPT-1a +/- mice showed no fatty change in liver and were cold tolerant. Fasting free fatty acid concentrations were significantly elevated, while blood glucose concentrations were significantly lower in 6-week-old CPT-1a +/- mice compared to controls. Although the homozygous mutants were not viable, we did find some aspects of haploinsufficiency in the CPT-1a +/- mutants, which will make them an important mouse model for studying the role of CPT-1a in human disease.

Liquefaction assessment based on combined use of CPT and shear wave velocity measurements

NASA Astrophysics Data System (ADS)

Bán, Zoltán; Mahler, András; Győri, Erzsébet

2017-04-01

Soil liquefaction is one of the most devastating secondary effects of earthquakes and can cause significant damage in built infrastructure. For this reason liquefaction hazard shall be considered in all regions where moderate-to-high seismic activity encounters with saturated, loose, granular soil deposits. Several approaches exist to take into account this hazard, from which the in-situ test based empirical methods are the most commonly used in practice. These methods are generally based on the results of CPT, SPT or shear wave velocity measurements. In more complex or high risk projects CPT and VS measurement are often performed at the same location commonly in the form of seismic CPT. Furthermore, VS profile determined by surface wave methods can also supplement the standard CPT measurement. However, combined use of both in-situ indices in one single empirical method is limited. For this reason, the goal of this research was to develop such an empirical method within the framework of simplified empirical procedures where the results of CPT and VS measurements are used in parallel and can supplement each other. The combination of two in-situ indices, a small strain property measurement with a large strain measurement, can reduce uncertainty of empirical methods. In the first step by careful reviewing of the already existing liquefaction case history databases, sites were selected where the records of both CPT and VS measurement are available. After implementing the necessary corrections on the gathered 98 case histories with respect to fines content, overburden pressure and magnitude, a logistic regression was performed to obtain the probability contours of liquefaction occurrence. Logistic regression is often used to explore the relationship between a binary response and a set of explanatory variables. The occurrence or absence of liquefaction can be considered as binary outcome and the equivalent clean sand value of normalized overburden corrected cone tip resistance (qc1Ncs), the overburden corrected shear wave velocity (V S1), and the magnitude and effective stress corrected cyclic stress ratio (CSRM=7.5,σv'=1atm) were considered as input variables. In this case the graphical representation of the cyclic resistance ratio curve for a given probability has been replaced by a surface that separates the liquefaction and non-liquefaction cases.

Old and in pain: Enduring and situational effects of cultural aging stereotypes on older people's pain experiences.

PubMed

Bernardes, S F; Marques, S; Matos, M

2015-08-01

This study aimed to investigate the interplay between enduring and situational aging stereotype (AS) effects in older adults' self-reports of clinical and experimentally induced pain. We expected that, as compared with the situational activation of positive AS or a neutral condition, the activation of negative AS would lead to more severe self-reports of clinical pain (H1, hypothesis 1), higher cold pressor task (CPT) pain threshold (H2) and lower CPT pain tolerance (H3), especially among older adults who more strongly endorsed AS. This was a prospective study across two moments in time. At time 1 (T1), 52 older adults (Mage  = 74.7; 51.9% women) filled out measures of cultural AS endorsement, clinical pain severity and interference. Three months afterwards (T2), some of these participants collaborated in an experimental study on the effects of AS activation on reported clinical pain (n = 40) and experimentally induced (using CPT) pain threshold and tolerance (n = 35). Our results supported H2, i.e., as compared with the activation of positive AS or a neutral condition, when negative AS were activated older adults showed higher CPT pain thresholds, but this effect was more salient among those who more strongly endorsed AS at T1. This study stresses the influence of cultural AS in older adults' pain experiences showing that the situational activation of negative AS greatly increases experimentally induced pain thresholds of elders who more strongly endorse those stereotypes. It also highlights the relevance of interventions at the level of the physical and/or social environments surrounding elders in pain. © 2014 European Pain Federation - EFIC®

The Effect of Parental Modeling on Child Pain Responses: The Role of Parent and Child Sex.

PubMed

Boerner, Katelynn E; Chambers, Christine T; McGrath, Patrick J; LoLordo, Vincent; Uher, Rudolf

2017-06-01

Social modeling is a process by which pain behaviors are learned, and research has found parents act as models for their children's behavior. Despite social learning theory predicting that same-sex models have greater effect, no experimental investigation to date has examined the role of sex of the model or observer in social learning of pediatric pain. The present study recruited 168 parent-child dyads (equal father-son, father-daughter, mother-son, and mother-daughter dyads) in which children were generally healthy and 6 to 8 years old. Unbeknownst to their child, parents were randomly assigned to exaggerate their expression of pain, minimize their expression of pain, or act naturally during the cold pressor task (CPT). Parents completed the CPT while their child observed, then children completed the CPT themselves. Children whose parents were in the exaggerate condition reported higher anxiety than children of parents in the minimize condition. Additionally, girls in the exaggerate condition rated their overall pain intensity during the CPT significantly higher than boys in the same condition. No child sex differences were observed in pain intensity for the control or minimize conditions. Parent expressions of pain affects children's anxiety, and sex-specific effects of parental exaggerated pain expression on children's own subsequent pain experience are present. This article describes how parental expressions of pain influence children's pain and anxiety, specifically examining the relevance of parent and child sex in this process. These findings have implications for children of parents with chronic pain, or situations in which parents experience pain in the presence of their child (eg, vaccinations). Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

Toward a High-Stability Coherent Population Trapping Cs Vapor-Cell Atomic Clock Using Autobalanced Ramsey Spectroscopy

NASA Astrophysics Data System (ADS)

Abdel Hafiz, Moustafa; Coget, Grégoire; Petersen, Michael; Rocher, Cyrus; Guérandel, Stéphane; Zanon-Willette, Thomas; de Clercq, Emeric; Boudot, Rodolphe

2018-06-01

Vapor-cell atomic clocks are widely appreciated for their excellent short-term fractional frequency stability and their compactness. However, they are known to suffer on medium and long time scales from significant frequency instabilities, generally attributed to light-induced frequency-shift effects. In order to tackle this limitation, we investigate the application of the recently proposed autobalanced Ramsey (ABR) interrogation protocol onto a pulsed hot-vapor Cs vapor-cell clock based on coherent population trapping (CPT). We demonstrate that the ABR protocol, developed initially to probe the one-photon resonance of quantum optical clocks, can be successfully applied to a two-photon CPT resonance. The applied method, based on the alternation of two successive Ramsey-CPT sequences with unequal free-evolution times and the subsequent management of two interconnected phase and frequency servo loops, is found to allow a relevant reduction of the clock-frequency sensitivity to laser-power variations. This original ABR-CPT approach, combined with the implementation of advanced electronics laser-power stabilization systems, yields the demonstration of a CPT-based Cs vapor-cell clock with a short-term fractional frequency stability at the level of 3.1×10 -13τ-1 /2 , averaging down to the level of 6 ×10-15 at 2000-s integration time. These encouraging performances demonstrate that the use of the ABR interrogation protocol is a promising option towards the development of high-stability CPT-based frequency standards. Such clocks could be attractive candidates in numerous applications including next-generation satellite-based navigation systems, secure communications, instrumentation, or defense systems.

Assessing the Temporal Stability of a Cigarette Purchase Task After an Excise Tax Increase for Factory-Made and Roll-Your-Own Smokers.

PubMed

Grace, Randolph C; Kivell, Bronwyn M; Laugesen, Murray

2015-11-01

Cigarette purchase tasks (CPTs) are used increasingly to measure simulated demand curves for tobacco. However, there is currently limited information about the temporal stability of demand curves obtained from these tasks. We interviewed a sample (N = 210) of smokers in New Zealand both before and after a 10% increase in the tobacco excise tax that took effect on January 1, 2013. Participants were interviewed in November-December 2012 (wave 1) and February-March 2013 (wave 2). At each interview, participants completed a high-resolution CPT with 64 prices ranging from NZ $0.00 to NZ $5.00/cigarette, and questionnaires regarding their smoking habit. Roll-your-own smokers had higher levels of nicotine dependence and tobacco demand based on CPT responses than factory-made smokers. Although demand curves for waves 1 and 2 were similar, intentions to purchase cigarettes were significantly less at wave 2 for three prices (NZ $0.85, NZ $0.90, and NZ $0.95) that were just higher than the actual price after the tax increase, for both roll-your-own and factory-made smokers. Measures of elasticity (α) derived from Hursh and Silberberg's model were significantly greater at wave 2 than wave 1, and there was a significant reduction in smoking habit as measured by cigarettes/day and the Fagerström Test for Nicotine Dependence at wave 2. Purchase tasks can discriminate between smokers based on their tobacco preference, and although results are relatively stable over time, they depend on contextual factors such as the current real price for tobacco. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Hydrophobically modified glycol chitosan nanoparticles-encapsulated camptothecin enhance the drug stability and tumor targeting in cancer therapy.

PubMed

Min, Kyung Hyun; Park, Kyeongsoon; Kim, Yoo-Shin; Bae, Sang Mun; Lee, Seulki; Jo, Hyung Gon; Park, Rang-Woon; Kim, In-San; Jeong, Seo Young; Kim, Kwangmeyung; Kwon, Ick Chan

2008-05-08

To prepare a water-insoluble camptothecin (CPT) delivery carrier, hydrophobically modified glycol chitosan (HGC) nanoparticles were constructed by chemical conjugation of hydrophobic 5beta-cholanic acid moieties to the hydrophilic glycol chitosan backbone. Insoluble anticancer drug, CPT, was easily encapsulated into HGC nanoparticles by a dialysis method and the drug loading efficiency was above 80%. CPT-encapsulated HGC (CPT-HGC) nanoparticles formed nano-sized self-aggregates in aqueous media (280-330 nm in diameter) and showed sustained release of CPT for 1 week. Also, HGC nanoparticles effectively protected the active lactone ring of CPT from the hydrolysis under physiological condition, due to the encapsulation of CPT into the hydrophobic cores in the HGC nanoparticles. The CPT-HGC nanoparticles exhibited significant antitumor effects and high tumor targeting ability towards MDA-MB231 human breast cancer xenografts subcutaneously implanted in nude mice. Tumor growth was significantly inhibited after i.v. injection of CPT-HGC nanoparticles at doses of 10 mg/kg and 30 mg/kg, compared to free CPT at dose of 30 mg/kg. The significant antitumor efficacy of CPT-HGC nanoparticles was attributed to the ability of the nanoparticles to show both prolonged blood circulation and high accumulation in tumors, as confirmed by near infrared (NIR) fluorescence imaging systems. Thus, the delivery of CPT to tumor tissues at a high concentration, with the assistance of HGC nanoparticles, exerted a potent therapeutic effect. These results reveal the promising potential of HGC nanoparticles-encapsulated CPT as a stable and effective drug delivery system in cancer therapy.

Pupillometric and behavioral markers of a developmental shift in the temporal dynamics of cognitive control

PubMed Central

Chatham, Christopher H.; Frank, Michael J.; Munakata, Yuko

2009-01-01

The capacity to anticipate and prepare for future events is thought to be critical for cognitive control. Dominant accounts of cognitive control treat the developing system as merely a weaker version of the adult system, progressively strengthening over time. Using the AX Continuous Performance Task (AX-CPT) in combination with high-resolution pupillometry, we find that whereas 8-year-old children resemble adults in their proactive use of cognitive control, 3.5-year-old children exhibit a qualitatively different, reactive form of cognitive control, responding to events only as they unfold and retrieving information from memory as needed in the moment. These results demonstrate the need to reconsider the origins of cognitive control and the basis for children's behaviors across domains. PMID:19321427

Supporting cognitive control through competition and cooperation in childhood.

PubMed

Fischer, Paula; Camba, Letizia; Ooi, Seok Hui; Chevalier, Nicolas

2018-04-12

Cognitive control is often engaged in social contexts where actions are socially relevant. Yet, little is known about the immediate influence of the social context on childhood cognitive control. To examine whether competition or cooperation can enhance cognitive control, preschool and school-age children completed the AX Continuous Performance Task (AX-CPT) in competitive, cooperative, and neutral contexts. Children made fewer errors, responded faster, and engaged more cognitive effort, as shown by greater pupil dilation, in the competitive and cooperative social contexts relative to the neutral context. Competition and cooperation yielded greater cognitive control engagement but did not change how control was engaged (reactively or proactively). Manipulating the social context can be a powerful tool to support cognitive control in childhood. Copyright © 2018 Elsevier Inc. All rights reserved.

Attachment and attention: protection in relation to gender and cumulative social-contextual adversity.

PubMed

Fearon, R M Pasco; Belsky, Jay

2004-01-01

Data from 918 children from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care were examined to test the interrelation of attachment and attentional performance and 2 known risks for poor attentional performance: male gender and social-contextual adversity. Attachment was measured using the Strange Situation at 15 months, attentional performance by a Continuous Performance Test (CPT) and maternal questionnaires at 54 months, and social-contextual adversity by a variety of measures from birth to 54 months. Findings indicated (a) that children with secure attachment were less susceptible to the effects of cumulative risk and gender on CPT attentional performance than their insecure counterparts and that (b) no such differential risk susceptibility was evident for maternal reports of attention-related behavior problems.

The Rice COLEOPTILE PHOTOTROPISM1 Gene Encoding an Ortholog of Arabidopsis NPH3 Is Required for Phototropism of Coleoptiles and Lateral Translocation of AuxinW⃞

PubMed Central

Haga, Ken; Takano, Makoto; Neumann, Ralf; Iino, Moritoshi

2005-01-01

We isolated a mutant, named coleoptile phototropism1 (cpt1), from γ-ray–mutagenized japonica-type rice (Oryza sativa). This mutant showed no coleoptile phototropism and severely reduced root phototropism after continuous stimulation. A map-based cloning strategy and transgenic complementation test were applied to demonstrate that a NPH3-like gene deleted in the mutant corresponds to CPT1. Phylogenetic analysis of putative CPT1 homologs of rice and related proteins indicated that CPT1 has an orthologous relationship with Arabidopsis thaliana NPH3. These results, along with those for Arabidopsis, demonstrate that NPH3/CPT1 is a key signal transduction component of higher plant phototropism. In an extended study with the cpt1 mutant, it was found that phototropic differential growth is accompanied by a CPT1-independent inhibition of net growth. Kinetic investigation further indicated that a small phototropism occurs in cpt1 coleoptiles. This response, induced only transiently, was thought to be caused by the CPT1-independent growth inhibition. The 3H-indole-3-acetic acid applied to the coleoptile tip was asymmetrically distributed between the two sides of phototropically responding coleoptiles. However, no asymmetry was induced in cpt1 coleoptiles, indicating that lateral translocation of auxin occurs downstream of CPT1. It is concluded that the CPT1-dependent major phototropism of coleoptiles is achieved by lateral auxin translocation and subsequent growth redistribution. PMID:15598797

The Rice COLEOPTILE PHOTOTROPISM1 gene encoding an ortholog of Arabidopsis NPH3 is required for phototropism of coleoptiles and lateral translocation of auxin.

PubMed

Haga, Ken; Takano, Makoto; Neumann, Ralf; Iino, Moritoshi

2005-01-01

We isolated a mutant, named coleoptile phototropism1 (cpt1), from gamma-ray-mutagenized japonica-type rice (Oryza sativa). This mutant showed no coleoptile phototropism and severely reduced root phototropism after continuous stimulation. A map-based cloning strategy and transgenic complementation test were applied to demonstrate that a NPH3-like gene deleted in the mutant corresponds to CPT1. Phylogenetic analysis of putative CPT1 homologs of rice and related proteins indicated that CPT1 has an orthologous relationship with Arabidopsis thaliana NPH3. These results, along with those for Arabidopsis, demonstrate that NPH3/CPT1 is a key signal transduction component of higher plant phototropism. In an extended study with the cpt1 mutant, it was found that phototropic differential growth is accompanied by a CPT1-independent inhibition of net growth. Kinetic investigation further indicated that a small phototropism occurs in cpt1 coleoptiles. This response, induced only transiently, was thought to be caused by the CPT1-independent growth inhibition. The 3H-indole-3-acetic acid applied to the coleoptile tip was asymmetrically distributed between the two sides of phototropically responding coleoptiles. However, no asymmetry was induced in cpt1 coleoptiles, indicating that lateral translocation of auxin occurs downstream of CPT1. It is concluded that the CPT1-dependent major phototropism of coleoptiles is achieved by lateral auxin translocation and subsequent growth redistribution.

Support vector machines-based modelling of seismic liquefaction potential

NASA Astrophysics Data System (ADS)

Pal, Mahesh

2006-08-01

This paper investigates the potential of support vector machines (SVM)-based classification approach to assess the liquefaction potential from actual standard penetration test (SPT) and cone penetration test (CPT) field data. SVMs are based on statistical learning theory and found to work well in comparison to neural networks in several other applications. Both CPT and SPT field data sets is used with SVMs for predicting the occurrence and non-occurrence of liquefaction based on different input parameter combination. With SPT and CPT test data sets, highest accuracy of 96 and 97%, respectively, was achieved with SVMs. This suggests that SVMs can effectively be used to model the complex relationship between different soil parameter and the liquefaction potential. Several other combinations of input variable were used to assess the influence of different input parameters on liquefaction potential. Proposed approach suggest that neither normalized cone resistance value with CPT data nor the calculation of standardized SPT value is required with SPT data. Further, SVMs required few user-defined parameters and provide better performance in comparison to neural network approach.

Coherent population trapping resonances at lower atomic levels of Doppler broadened optical lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Şahin, E; Hamid, R; Çelik, M

2014-11-30

We have detected and analysed narrow high-contrast coherent population trapping (CPT) resonances, which are induced in absorption of a weak monochromatic probe light beam by counterpropagating two-frequency pump radiation in a cell with rarefied caesium vapour. The experimental investigations have been performed by the example of nonclosed three level Λ-systems formed by spectral components of the D{sub 2} line of caesium atoms. The applied method allows one to analyse features of the CPT phenomenon directly at a given low long-lived level of the selected Λ-system even in sufficiently complicated spectra of atomic gases with large Doppler broadening. We have establishedmore » that CPT resonances in transmission of the probe beam exhibit not only a higher contrast but also a much lesser width in comparison with well- known CPT resonances in transmission of the corresponding two-frequency pump radiation. The results obtained can be used in selective photophysics, photochemistry and ultra-high resolution atomic (molecular) spectroscopy. (laser applications and other topics in quantum electronics)« less

Cannabis use and cognitive function in first episode psychosis: differential effect of heavy use.

PubMed

Núñez, Christian; Ochoa, Susana; Huerta-Ramos, Elena; Baños, Iris; Barajas, Ana; Dolz, Montserrat; Sánchez, Bernardo; Del Cacho, Núria; Usall, Judith

2016-03-01

First episode patients and patients with schizophrenia exhibit increased rates of cannabis use compared to the general population. Contrary to what has been reported in studies with healthy people, most of the published studies so far have reported no impairments or even beneficial effects on neurocognition associated with cannabis consumption in psychotic patients. However, these studies did not address the effects of very high cannabis consumption. Our aim in this study was to assess the effects on neurocognition of medium and heavy cannabis consumption in first psychotic episode patients. A total of 74 patients were included in the study and assigned to three different groups according to their mean cannabis consumption during the last year (non-users, medium users, and heavy users). Participants were administered verbal memory and other neurocognitive tasks. Heavy cannabis users were significantly impaired in all the verbal memory measures with respect to non-users, including immediate (p = .026), short-term (p = .005), and long-term (p = .002) memory. There were no significant differences between medium and non-users. Moreover, non-users performed better than all cannabis users in the arithmetic task (p = .020). Heavy cannabis consumption was associated with more commission errors in the continuous performance task (CPT) (p = .008) and more time to complete trail making test A (TMT-A) (p = .008), compared to the group of medium users. Heavy cannabis consumption seems to impair verbal memory in first psychotic episode patients. Heavy users also perform worse than medium users in other neurocognitive tasks. Based on the results and the available evidence, a dose-related effect of cannabis consumption is suggested.

Cognitive Improvement of Attention and Inhibition in the Late Afternoon in Children With Attention-Deficit Hyperactivity Disorder (ADHD) Treated With Osmotic-Release Oral System Methylphenidate.

PubMed

Slama, Hichem; Fery, Patrick; Verheulpen, Denis; Vanzeveren, Nathalie; Van Bogaert, Patrick

2015-07-01

Long-acting medications have been developed and approved for use in the treatment of attention-deficit hyperactivity disorder (ADHD). These compounds are intended to optimize and maintain symptoms control throughout the day. We tested prolonged effects of osmotic-release oral system methylphenidate on both attention and inhibition, in the late afternoon. A double-blind, randomized, placebo-controlled study was conducted in 36 boys (7-12 years) with ADHD and 40 typically developing children. The ADHD children received an individualized dose of placebo or osmotic-release oral system methylphenidate. They were tested about 8 hours after taking with 2 continuous performance tests (continuous performance test-X [CPT-X] and continuous performance test-AX [CPT-AX]) and a counting Stroop. A positive effect of osmotic-release oral system methylphenidate was present in CPT-AX with faster and less variable reaction times under osmotic-release oral system methylphenidate than under placebo, and no difference with typically developing children. In the counting Stroop, we found a decreased interference with osmotic-release oral system methylphenidate but no difference between children with ADHD under placebo and typically developing children. © The Author(s) 2014.

Kampo medicine "Dai-kenchu-to" prevents CPT-11-induced small-intestinal injury in rats.

PubMed

Chikakiyo, Motoya; Shimada, Mitsuo; Nakao, Toshihiro; Higashijima, Jun; Yoshikawa, Kozo; Nishioka, Masanori; Iwata, Takashi; Kurita, Nobuhiro

2012-01-01

The key anticancer agent, CPT-11 (irinotecan hydrochloride), induces severe diarrhea clinically. We investigated the effect of a Kampo medicine, Dai-kenchu-to (DKT), on CPT-11-induced intestinal injuries in rats. Twenty-four male Wistar rats were divided into three groups: a control group; a CPT-11 group, given CPT-11 150 mg/kg intraperitoneally for 2 days; and a DKT group, given DKT 300 mg/kg orally for 5 days with CPT-11 150 mg/kg intraperitoneally on days 4 and 5. The rats were killed on day 6. Interleukin (IL)-1β, IL-12, interferon (IFN)-γ, and tumor necrosis factor-α expression in the small intestine of the CPT-11 group was significantly higher than that of the control group. Interleukin-1β and IFN-γ expression was improved significantly by DKT (P < 0.05). The number and height of jejuna villi, injury score, and apoptosis index in the CPT-11 group were improved significantly by DKT (P < 0.05). DKT suppressed CPT-11 induced inflammatory cytokines and apoptosis in the intestinal mucosa and maintained the mucosal integrity.

Risperidone Added to Psychostimulant in Children with Severe Aggression and Attention-Deficit/Hyperactivity Disorder: Lack of Effect on Attention and Short-Term Memory.

PubMed

Farmer, Cristan A; Epstein, Jeffery N; Findling, Robert L; Gadow, Kenneth D; Arnold, L Eugene; Kipp, Heidi; Kolko, David J; Butter, Eric; Schneider, Jayne; Bukstein, Oscar G; McNamara, Nora K; Molina, Brooke S G; Aman, Michael G

2017-03-01

Professionals have periodically expressed concern that atypical antipsychotics may cause cognitive blunting in treated patients. In this study, we report data from a double-blind, randomized, controlled study of stimulant plus placebo versus combined stimulant and risperidone to evaluate the effects of the atypical antipsychotic on attention and short-term memory. A total of 165 (n = 83 combined treatment; n = 82 stimulant plus placebo) children with attention-deficit/hyperactivity disorder and severe physical aggression, aged 6-12 years, were evaluated with Conners' Continuous Performance Test (CPT-II) and the Wechsler Intelligence Scale for Children-III (WISC) Digit Span subscale at baseline, after 3 weeks of stimulant-only treatment, and after six additional weeks of randomized treatment (stimulant+placebo vs. stimulant+risperidone). At 3 weeks, improvement on CPT-II performance (Commissions and Reaction Time Standard Error; p < 0.001) and on Digit Span memory performance (p < 0.006) was noted for the full sample. At study week 9, no difference in CPT-II or Digit Span performance was observed between the randomized groups (ps = 0.41 to 0.83). Similar to other studies, we found no deleterious effects on attention and short-term memory associated with short-term use of risperidone. NCT00796302.

Interactions of task and subject variables among continuous performance tests.

PubMed

Denney, Colin B; Rapport, Mark D; Chung, Kyong-Mee

2005-04-01

Contemporary models of working memory suggest that target paradigm (TP) and target density (TD) should interact as influences on error rates derived from continuous performance tests (CPTs). The present study evaluated this hypothesis empirically in a typically developing, ethnically diverse sample of children. The extent to which scores based on different combinations of these task parameters showed different patterns of relationship to age, intelligence, and gender was also assessed. Four continuous performance tests were derived by combining two target paradigms (AX and repeated letter target stimuli) with two levels of target density (8.3% and 33%). Variations in mean omission (OE) and commission (CE) error rates were examined within and across combinations of TP and TD. In addition, a nested series of structural equation models was utilized to examine patterns of relationship among error rates, age, intelligence, and gender. Target paradigm and target density interacted as influences on error rates. Increasing density resulted in higher OE and CE rates for the AX paradigm. In contrast, the high density condition yielded a decline in OE rates accompanied by a small increase in CEs using the repeated letter CPT. Target paradigms were also distinguishable on the basis of age when using OEs as the performance measure, whereas combinations of age and intelligence distinguished between density levels but not target paradigms using CEs as the dependent measure. Different combinations of target paradigm and target density appear to yield scores that are conceptually and psychometrically distinguishable. Consequently, developmentally appropriate interpretation of error rates across tasks may require (a) careful analysis of working memory and attentional resources required for successful performance, and (b) normative data bases that are differently stratified with respect to combinations of age and intelligence.

Controlled drug delivery from composites of nanostructured porous silicon and poly(L-lactide).

PubMed

McInnes, Steven J P; Irani, Yazad; Williams, Keryn A; Voelcker, Nicolas H

2012-07-01

Porous silicon (pSi) and poly(L-lactide) (PLLA) both display good biocompatibility and tunable degradation behavior, suggesting that composites of both materials are suitable candidates as biomaterials for localized drug delivery into the human body. The combination of a pliable and soft polymeric material with a hard inorganic porous material of high drug loading capacity may engender improved control over degradation and drug release profiles and be beneficial for the preparation of advanced drug delivery devices and biodegradable implants or scaffolds. In this work, three different pSi and PLLA composite formats were prepared. The first format involved grafting PLLA from pSi films via surface-initiated ring-opening polymerization (pSi-PLLA [grafted]). The second format involved spin coating a PLLA solution onto oxidized pSi films (pSi-PLLA [spin-coated]) and the third format consisted of a melt-cast PLLA monolith containing dispersed pSi microparticles (pSi-PLLA [monoliths]). The surface characterization of these composites was performed via infrared spectroscopy, scanning electron microscopy, atomic force microscopy and water contact angle measurements. The composite materials were loaded with a model cytotoxic drug, camptothecin (CPT). Drug release from the composites was monitored via fluorimetry and the release profiles of CPT showed distinct characteristics for each of the composites studied. In some cases, controlled CPT release was observed for more than 5 days. The PLLA spin coat on pSi and the PLLA monolith containing pSi microparticles both released a CPT payload in accordance with the Higuchi and Ritger-Peppas release models. Composite materials were also brought into contact with human lens epithelial cells to determine the extent of cytotoxicity. We observed that all the CPT containing materials were highly efficient at releasing bioactive CPT, based on the cytotoxicity data.

RELIABILITY CONCERNS IN THE REPEATED COMPUTERIZED ASSESSMENT OF ATTENTION IN CHILDREN

PubMed Central

Zabel, T. Andrew; von Thomsen, Christian; Cole, Carolyn; Martin, Rebecca; Mahone, E. Mark

2010-01-01

Assessment of attentional processes via computerized assessment is frequently used to quantify intra-individual cognitive improvement or decline in response to treatment. However, assessment of intra-individual change is highly dependent on sufficient test reliability. We examined the test–retest reliability of selected variables from one popular computerized continuous performance test (CPT)—i.e., the Conners’ CPT – Second Edition (CPT-II). Participants were 39 healthy children (20 girls) ages 6–18 without intellectual impairment (mean PPVT-III SS = 102.6), LD, or psychiatric disorders (DICA-IV). Test–retest reliability over the 3–8 month interval (mean = 6 months) was acceptable (Intraclass Correlations [ICC] = .82 to .92) on comparison measures (Beery Test of Visual Perception, WISC-IV Block Design, PPVT-III). In contrast, test–retest reliability was only modest for CPT-II raw scores (ICCs ranging from .62 to .82) and T-scores (ICCs ranging from .33 to .65) for variables of interest (Omissions, Commissions, Variability, Hit Reaction Time, and Attentiveness). Using test–retest reliability information published in the CPT-II manual, 90% confidence intervals based on reliable change index (RCI) methodology were constructed to examine the significance of test–retest difference/change scores. Of the participants in this sample of typically developing youth, 30% generated intra-individual changes in T-scores on the Omissions and Attentiveness variables that exceeded the 90% confidence intervals and qualified as “statistically rare” changes in score. These results suggest a considerable degree of normal variability in CPT-II test scores over extended test–retest intervals, and suggest a need for caution when interpreting test score changes in neurologically unstable clinical populations. PMID:19452302

Reproducibility of current perception threshold with the Neurometer(®) vs the Stimpod NMS450 peripheral nerve stimulator in healthy volunteers: an observational study.

PubMed

Tsui, Ban C H; Shakespeare, Timothy J; Leung, Danika H; Tsui, Jeremy H; Corry, Gareth N

2013-08-01

Current methods of assessing nerve blocks, such as loss of perception to cold sensation, are subjective at best. Transcutaneous nerve stimulation is an alternative method that has previously been used to measure the current perception threshold (CPT) in individuals with neuropathic conditions, and various devices to measure CPT are commercially available. Nevertheless, the device must provide reproducible results to be used as an objective tool for assessing nerve blocks. We recruited ten healthy volunteers to examine CPT reproducibility using the Neurometer(®) and the Stimpod NMS450 peripheral nerve stimulator. Each subject's CPT was determined for the median (second digit) and ulnar (fifth digit) nerve sensory distributions on both hands - with the Neurometer at 5 Hz, 250 Hz, and 2000 Hz and with the Stimpod at pulse widths of 0.1 msec, 0.3 msec, 0.5 msec, and 1.0 msec, both at 5 Hz and 2 Hz. Intraclass correlation coefficients (ICC) were also calculated to assess reproducibility; acceptable ICCs were defined as ≥ 0.4. The ICC values for the Stimpod ranged from 0.425-0.79, depending on pulse width, digit, and stimulation; ICCs for the Neurometer were 0.615 and 0.735 at 250 and 2,000 Hz, respectively. These values were considered acceptable; however, the Neurometer performed less efficiently at 5 Hz (ICCs for the second and fifth digits were 0.292 and 0.318, respectively). Overall, the Stimpod device displayed good to excellent reproducibility in measuring CPT in healthy volunteers. The Neurometer displayed poor reproducibility at low frequency (5 Hz). These results suggest that peripheral nerve stimulators may be potential devices for measuring CPT to assess nerve blocks.

Tempering Proactive Cognitive Control by Transcranial Direct Current Stimulation of the Right (but Not the Left) Lateral Prefrontal Cortex

PubMed Central

Gómez-Ariza, Carlos J.; Martín, María C.; Morales, Julia

2017-01-01

Behavioral and neuroimaging data support the distinction of two different modes of cognitive control: proactive, which involves the active and sustained maintenance of task-relevant information to bias behavior in accordance with internal goals; and reactive, which entails the detection and resolution of interference at the time it occurs. Both control modes may be flexibly deployed depending on a variety of conditions (i.e., age, brain alterations, motivational factors, prior experience). Critically, and in line with specific predictions derived from the dual mechanisms of control account (Braver, 2012), findings from neuroimaging studies indicate that the same lateral prefrontal regions (i.e., left dorsolateral cortex and right inferior frontal junction) may implement different control modes on the basis of temporal dynamics of activity, which would be modulated in response to external or internal conditions. In the present study, we aimed to explore whether transcraneal direct current stimulation over either the left dorsolateral prefrontal cortex or the right inferior frontal junction would differentially modulate performance on the AX-CPT, a well-validated task that provides sensitive and reliable behavioral indices of proactive/reactive control. The study comprised six conditions of real stimulation [3 (site: left dorsolateral, right dorsolateral and right inferior frontal junction) × 2 (polarity: anodal and cathodal)], and one sham condition. The reference electrode was always placed extracephalically. Performance on the AX-CPT was assessed through two blocks of trials. The first block took place while stimulation was being delivered, whereas the second block was administered after stimulation completion. The results indicate that both offline cathodal stimulation of the right dorsolateral prefrontal cortex and online anodal stimulation of the right inferior frontal junction led participants to be much less proactive, with such a dissociation suggesting that both prefrontal regions differentially contribute to the adjustment of cognitive control modes. tDCS of the left-DLPFC failed to modulate cognitive control. These results partially support the predictions derived from the dual mechanisms of control account. PMID:28588441

Effects of Sex, Gender Role Identification, and Gender Relevance of Two Types of Stressors on Cardiovascular and Subjective Responses: Sex and Gender Match and Mismatch Effects

ERIC Educational Resources Information Center

van Well, Sonja; Kolk, Annemarie M.; Klugkist, Irene G.

2008-01-01

The authors tested the hypothesis that a match between the gender relevance of a stressor and one's sex or gender role identification would elicit higher cardiovascular responses. Healthy female and male undergraduates (n = 108) were exposed to two stressors: the Cold Pressor Test (CPT) and the n-back task. Stressor relevance was manipulated to be…

Antitumor effects with apoptotic death in human promyelocytic leukemia HL-60 cells and suppression of leukemia xenograft tumor growth by irinotecan HCl.

PubMed

Chen, Yung-Liang; Chueh, Fu-Shin; Yang, Jai-Sing; Hsueh, Shu-Ching; Lu, Chi-Cheng; Chiang, Jo-Hua; Lee, Ching-Sung; Lu, Hsu-Feng; Chung, Jing-Gung

2015-07-01

Irinotecan HCl (CPT-11) is an anticancer prodrug, but there is no available information addressing CPT-11-inhibited leukemia cells in in vitro and in vivo studies. Therefore, we investigated the cytotoxic effects of CPT-11 in promyelocytic leukemia HL-60 cells and in vivo and tumor growth in a leukemia xenograft model. Effects of CPT-11 on HL-60 cells were determined using flow cytometry, immunofluorescence staining, comet assay, real-time PCR, and Western blotting. CPT-11 demonstrated a dose- and time-dependent inhibition of cell growth, induction of apoptosis, and cell-cycle arrest at G0/G1 phase in HL-60 cells. CPT-11 promoted the release of AIF from mitochondria and its translocation to the nucleus. Bid, Bax, Apaf-1, caspase-9, AIF, Endo G, caspase-12, ATF-6b, Grp78, CDK2, Chk2, and cyclin D were all significantly upregulated and Bcl-2 was down-regulated by CPT-11 in HL-60 cells. Induction of cell-cycle arrest by CPT-11 was associated with changes in expression of key cell-cycle regulators such as CDK2, Chk2, and cyclin D in HL-60 cells. To test whether CPT-11 could augment antitumor activity in vivo, athymic BALB/c(nu/nu) nude mice were inoculated with HL-60 cells, followed by treatment with either CPT-11. The treatments significantly inhibited tumor growth and reduced tumor weight and volume in the HL-60 xenograft mice. The present study demonstrates the schedule-dependent antileukemia effect of CPT-11 using both in vitro and in vivo models. CPT-11 could potentially be a promising agent for the treatment of promyelocytic leukemia and requires further investigation. © 2014 Wiley Periodicals, Inc.

CPT-11 activates NLRP3 inflammasome through JNK and NF-κB signalings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Qian; Zhang, Xiong; Wang, Weicheng

CPT-11 is widely used for cancer therapy as a chemotherapeutic agent. Despite its good efficacy, a large number of side effects appeared during decades of clinical application. Delayed diarrhea, at dose limiting toxicity, happens after 24 h of treatment and the rate of occurrence is up to 90%. Although many investments have been made on this negative impact, the real molecular mechanism of delayed diarrhea is poorly understood. In this study, we have discovered that CPT-11 promotes macrophage infiltration into intestinal tissues and activates the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, resulting in a robust IL-1β responsemore » and colonic inflammation similar to DSS (dextran sodium sulfate) induced experimental colitis. CPT-11 plus LPS primed mouse bone marrow-derived macrophages (BMDMs) and human acute monocytic leukemia cells (THP-1 cells) staying in a highly activated status, showing increased caspase-1 activity and releasing great amounts of IL-1β and IL-18 as detected by ELISA and western blot. A further mechanism showed that JNK and NF-κB signaling pathways participated in inflammatory responses activated by CPT-11. These results prompted us to suggest that the NLRP3-IL-1β signaling pathway might play an important role in CPT11-induced colitis. Our findings provide a basis for developing novel strategies that improve clinical implications of CPT-11. - Highlights: • CPT-11 induced experimental colitis in vivo. • CPT-11 induced intestine injury and macrophage infiltration. • CPT-11 significantly elevated levels of macrophage derived inflammatory cytokines in mice intestines. • CPT-11 activated NLRP3 inflammasome in vitro and in vivo. • CPT-11 activated JNK and NF-κB signalings in THP-1 and BMDMs.« less

A numerical similarity approach for using retired Current Procedural Terminology (CPT) codes for electronic phenotyping in the Scalable Collaborative Infrastructure for a Learning Health System (SCILHS).

PubMed

Klann, Jeffrey G; Phillips, Lori C; Turchin, Alexander; Weiler, Sarah; Mandl, Kenneth D; Murphy, Shawn N

2015-12-11

Interoperable phenotyping algorithms, needed to identify patient cohorts meeting eligibility criteria for observational studies or clinical trials, require medical data in a consistent structured, coded format. Data heterogeneity limits such algorithms' applicability. Existing approaches are often: not widely interoperable; or, have low sensitivity due to reliance on the lowest common denominator (ICD-9 diagnoses). In the Scalable Collaborative Infrastructure for a Learning Healthcare System (SCILHS) we endeavor to use the widely-available Current Procedural Terminology (CPT) procedure codes with ICD-9. Unfortunately, CPT changes drastically year-to-year - codes are retired/replaced. Longitudinal analysis requires grouping retired and current codes. BioPortal provides a navigable CPT hierarchy, which we imported into the Informatics for Integrating Biology and the Bedside (i2b2) data warehouse and analytics platform. However, this hierarchy does not include retired codes. We compared BioPortal's 2014AA CPT hierarchy with Partners Healthcare's SCILHS datamart, comprising three-million patients' data over 15 years. 573 CPT codes were not present in 2014AA (6.5 million occurrences). No existing terminology provided hierarchical linkages for these missing codes, so we developed a method that automatically places missing codes in the most specific "grouper" category, using the numerical similarity of CPT codes. Two informaticians reviewed the results. We incorporated the final table into our i2b2 SCILHS/PCORnet ontology, deployed it at seven sites, and performed a gap analysis and an evaluation against several phenotyping algorithms. The reviewers found the method placed the code correctly with 97 % precision when considering only miscategorizations ("correctness precision") and 52 % precision using a gold-standard of optimal placement ("optimality precision"). High correctness precision meant that codes were placed in a reasonable hierarchal position that a reviewer can quickly validate. Lower optimality precision meant that codes were not often placed in the optimal hierarchical subfolder. The seven sites encountered few occurrences of codes outside our ontology, 93 % of which comprised just four codes. Our hierarchical approach correctly grouped retired and non-retired codes in most cases and extended the temporal reach of several important phenotyping algorithms. We developed a simple, easily-validated, automated method to place retired CPT codes into the BioPortal CPT hierarchy. This complements existing hierarchical terminologies, which do not include retired codes. The approach's utility is confirmed by the high correctness precision and successful grouping of retired with non-retired codes.

Improved selectivity and cytotoxic effects of irinotecan via liposomal delivery: A comparative study on Hs68 and HeLa cells.

PubMed

Casadó, Ana; Mora, Margarita; Sagristá, Maria Lluïsa; Rello-Varona, Santi; Acedo, Pilar; Stockert, Juan Carlos; Cañete, Magdalena; Villanueva, Angeles

2017-11-15

Irinotecan (CPT-11) is an effective chemotherapeutic agent widely used to treat different cancers. Otherwise, the liposomal delivery of anti-tumor agents has been shown to be a promising strategy. The aim of this study has been to analyze the effect of liposomal CPT-11 (CPT-11lip) on two human cell lines (Hs68 and HeLa) to establish the suitability of this CPT-11 nanocarrier. We have demonstrated the highest uptake of CPT-11lip in comparison with that of CPT-11sol, in lactate buffer, and that CPT-11lip was internalized in the cells through an endocytic process whereas CPT-11sol does so by passive diffusion. CPT-11lip was not cytotoxic to normal fibroblast Hs68 cells, but induced a massive apoptosis accompanied by cell senescence in HeLa cells. CPT-11lip treatment modified the morphology of HeLa cells, induced different cell cycle alterations and accumulated into lysosomes in both cell lines. In particular, CPT-11lip treatment showed that surviving HeLa cells remained in a state of senescence whereas only a temporal growth arrest was induced in Hs68 cells. Results of RT-PCR indicated that the different responses in Hs68 (survival) and HeLa cells (apoptotic death), seemed to be induced by a p53- and p53- independent mechanism, respectively. An analysis of DNA damage also determined that released CPT-11 from liposomes was able to reach the nucleus and exert a genotoxic effect in both cell lines, which was repaired in Hs68 but not in HeLa cells. All results indicate that phospholipid-cholesterol liposomes possess optimum properties for CPT-11 delivery, being biocompatible and selectively cytotoxic against HeLa tumorigenic cells. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Risk Factors for Revision Surgery After Superior Labral Anterior-Posterior Repair: A National Perspective.

PubMed

Taylor, Samuel A; Degen, Ryan M; White, Alexander E; McCarthy, Moira M; Gulotta, Lawrence V; O'Brien, Stephen J; Werner, Brian C

2017-06-01

Data regarding risk factors for revision surgery after superior labral anterior-posterior (SLAP) repair are limited to institutional series. To define risk factors for revision surgery after SLAP repair among patients in a large national database. Case-control study; Level of evidence, 3. A national insurance database was queried for patients undergoing arthroscopic SLAP repair (Current Procedural Terminology [CPT] code 29807) for the diagnosis of a SLAP tear. Patients without a CPT modifier for laterality were excluded. Revision surgery was defined as (1) subsequent ipsilateral SLAP repair (CPT 29807), (2) ipsilateral arthroscopic debridement for the diagnosis of a SLAP tear (CPT 29822 or 29823, with diagnosis code 840.7), (3) subsequent ipsilateral arthroscopic biceps tenodesis (CPT 29828), (4) subsequent ipsilateral open biceps tenodesis (CPT 23430), and (5) subsequent biceps tenotomy (CPT 23405). Multivariable binomial logistic regression analysis was performed to identify risk factors for revision surgery after SLAP repair, including patient demographics/comorbidities, concomitant diagnoses, and concomitant procedures performed. Odds ratios (ORs), 95% CIs, and P values were calculated. The estimated financial impact of revision surgery was also calculated. There were 4751 patients who met inclusion and exclusion criteria. Overall, 121 patients (2.5%) required revision surgery after SLAP repair. Regression analysis identified numerous risk factors for revision surgery, including age >40 years (OR, 1.5; 95% CI, 1.2-1.8; P = .045), female sex (OR, 1.5; 95% CI, 1.3-1.8; P = .010), obesity (OR, 1.8; 95% CI, 1.5-2.2; P = .001), smoking (OR, 2.0; 95% CI, 1.6-2.4; P < .0001), and diagnosis of biceps tendinitis (OR, 3.5; 95% CI, 3.0-4.2; P < .0001) or long head of the biceps tearing (OR, 5.1; 95% CI, 4.1-6.3; P < .0001) at or before the time of surgery. Concomitant rotator cuff repair and distal clavicle excision were not significant risk factors for revision surgery. The cost of revision surgery averaged almost $9000. Risk factors for revision surgery after SLAP repair include age >40 years, female sex, obesity, smoking, and diagnosis of biceps tendinitis or long head of the biceps tearing. The diagnosis of biceps tendinitis (OR, 3.5) or long head of the biceps tearing (OR, 5.1) at or before the time of surgery was an especially significant risk factor for revision surgery. The high cost of revision surgery highlights the importance of appropriate indications to avoid the need for subsequent procedures.

Evaluation of the onset and duration of effect of azelastine eye drops (0.05%) versus placebo in patients with allergic conjunctivitis using an allergen challenge model.

PubMed

Friedlaender, M H; Harris, J; LaVallee, N; Russell, H; Shilstone, J

2000-12-01

The trial evaluated the effectiveness of the investigational antihistaminic and antiallergic compound Azelastine Eye Drops (AZE) in the treatment of allergic conjunctivitis using an allergen challenge model. Randomized, double-blind, placebo-controlled, paired-eye study. Adults with a history of allergic conjunctivitis (>/=2 years) who were asymptomatic throughout the trial, had a positive skin test (cat dander, grass, or ragweed pollen within the last year), and had a positive conjunctival reaction (score 2+ or more for itching and redness in both eyes on a 0-4 scale) during two separate conjunctival provocation tests (CPT) before randomization. Eighty patients underwent a 2-week screening period (visits 1 and 2) that included a CPT during visit 1 to establish the allergen threshold dose and a second confirmatory CPT performed at visit 2. Eye symptom assessments for itching (evaluated by patient) and conjunctival redness (evaluated by physician) were performed 5 and 10 minutes after CPT using a 5-point scale (from 0 = none to 4+ = severe). Qualified patients were randomized to receive one drop of AZE (0.015 mg of azelastine hydrochloride) in one eye and one drop of placebo in the other eye 20 minutes before CPT at visit 3 (onset) and 8 or 10 hours before CPT at visit 4 (duration). Individual severity scores for itching (evaluated by patient) and conjunctival redness (evaluated by physician) for each eye at 3, 5, and 10 minutes after CPT at visits 3 and 4 using a 5-point scale (0 = none to 4+ = very severe). Each of the 80 randomized patients completed the trial. Mean itching and conjunctival redness scores at visit 3 (onset) were significantly lower (P: < 0.001) in the AZE-treated eyes than in the placebo-treated eyes. At visit 4 (duration), mean itching and conjunctival redness scores (P:

CPT-11-Induced Delayed Diarrhea Develops via Reduced Aquaporin-3 Expression in the Colon

PubMed Central

Kon, Risako; Tsubota, Yuika; Minami, Moe; Kato, Saki; Matsunaga, Yukari; Kimura, Hiroshi; Murakami, Yuta; Fujikawa, Tetsuya; Sakurai, Ryoya; Tomimoto, Rei; Machida, Yoshiaki; Ikarashi, Nobutomo; Sugiyama, Kiyoshi

2018-01-01

While irinotecan (CPT-11) has a potent anti-cancer effect, it also causes serious diarrhea as an adverse reaction. In this study, we analyzed the pathogenic mechanism of CPT-11-induced delayed diarrhea by focusing on water channel aquaporin-3 (AQP3) in the colon. When rats received CPT-11, the expression level of AQP3 was reduced during severe diarrhea. It was found that the expression levels of inflammatory cytokines and the loss of crypt cells were increased in the colon when CPT-11 was administered. When celecoxib, an anti-inflammatory drug, was concomitantly administered, both the diarrhea and the reduced expression of AQP3 induced by CPT-11 were suppressed. The inflammation in the rat colon during diarrhea was caused via activated macrophage by CPT-11. These results showed that when CPT-11 is administered, the expression level of AQP3 in the colon is reduced, resulting in delayed diarrhea by preventing water transport from the intestinal tract. It was also suggested that the reduced expression of AQP3 might be due to the inflammation that occurs following the loss of colonic crypt cells and to the damage caused by the direct activation of macrophages by CPT-11. Therefore, it was considered that anti-inflammatory drugs that suppress the reduction of AQP3 expression could prevent CPT-11-induced delayed diarrhea. PMID:29316651

CPT-11-Induced Delayed Diarrhea Develops via Reduced Aquaporin-3 Expression in the Colon.

PubMed

Kon, Risako; Tsubota, Yuika; Minami, Moe; Kato, Saki; Matsunaga, Yukari; Kimura, Hiroshi; Murakami, Yuta; Fujikawa, Tetsuya; Sakurai, Ryoya; Tomimoto, Rei; Machida, Yoshiaki; Ikarashi, Nobutomo; Sugiyama, Kiyoshi

2018-01-06

While irinotecan (CPT-11) has a potent anti-cancer effect, it also causes serious diarrhea as an adverse reaction. In this study, we analyzed the pathogenic mechanism of CPT-11-induced delayed diarrhea by focusing on water channel aquaporin-3 (AQP3) in the colon. When rats received CPT-11, the expression level of AQP3 was reduced during severe diarrhea. It was found that the expression levels of inflammatory cytokines and the loss of crypt cells were increased in the colon when CPT-11 was administered. When celecoxib, an anti-inflammatory drug, was concomitantly administered, both the diarrhea and the reduced expression of AQP3 induced by CPT-11 were suppressed. The inflammation in the rat colon during diarrhea was caused via activated macrophage by CPT-11. These results showed that when CPT-11 is administered, the expression level of AQP3 in the colon is reduced, resulting in delayed diarrhea by preventing water transport from the intestinal tract. It was also suggested that the reduced expression of AQP3 might be due to the inflammation that occurs following the loss of colonic crypt cells and to the damage caused by the direct activation of macrophages by CPT-11. Therefore, it was considered that anti-inflammatory drugs that suppress the reduction of AQP3 expression could prevent CPT-11-induced delayed diarrhea.

The effect of cotrimoxazole prophylactic treatment on malaria, birth outcomes, and postpartum CD4 count in HIV-infected women.

PubMed

Dow, Anna; Kayira, Dumbani; Hudgens, Michael G; Van Rie, Annelies; King, Caroline C; Ellington, Sascha; Chome, Nelecy; Kourtis, Athena; Turner, Abigail Norris; Kacheche, Zebrone; Jamieson, Denise J; Chasela, Charles; van der Horst, Charles

2013-01-01

Limited data exist on cotrimoxazole prophylactic treatment (CPT) in pregnant women, including protection against malaria versus standard intermittent preventive therapy with sulfadoxine-pyrimethamine (IPTp). Using observational data we examined the effect of CPT in HIV-infected pregnant women on malaria during pregnancy, low birth weight and preterm birth using proportional hazards, logistic, and log binomial regression, respectively. We used linear regression to assess effect of CPT on CD4 count. Data from 468 CPT-exposed and 768 CPT-unexposed women were analyzed. CPT was associated with protection against malaria versus IPTp (hazard ratio: 0.35, 95% Confidence Interval (CI): 0.20, 0.60). After adjustment for time period this effect was not statistically significant (adjusted hazard ratio: 0.66, 95% CI: 0.28, 1.52). Among women receiving and not receiving CPT, rates of low birth weight (7.1% versus 7.6%) and preterm birth (23.5% versus 23.6%) were similar. CPT was associated with lower CD4 counts 24 weeks postpartum in women receiving (-77.6 cells/ μ L, 95% CI: -125.2, -30.1) and not receiving antiretrovirals (-33.7 cells/ μ L, 95% CI: -58.6, -8.8). Compared to IPTp, CPT provided comparable protection against malaria in HIV-infected pregnant women and against preterm birth or low birth weight. Possible implications of CPT-associated lower CD4 postpartum warrant further examination.

Hyaluronic acid-functionalized polymeric nanoparticles for colon cancer-targeted combination chemotherapy

NASA Astrophysics Data System (ADS)

Xiao, Bo; Han, Moon Kwon; Viennois, Emilie; Wang, Lixin; Zhang, Mingzhen; Si, Xiaoying; Merlin, Didier

2015-10-01

Nanoparticle (NP)-based combination chemotherapy has been proposed as an effective strategy for achieving synergistic effects and targeted drug delivery for colon cancer therapy. Here, we fabricated a series of hyaluronic acid (HA)-functionalized camptothecin (CPT)/curcumin (CUR)-loaded polymeric NPs (HA-CPT/CUR-NPs) with various weight ratios of CPT to CUR (1 : 1, 2 : 1 and 4 : 1). The resultant spherical HA-CPT/CUR-NPs had a desirable particle size (around 289 nm), relative narrow size distribution, and slightly negative zeta potential. These NPs exhibited a simultaneous sustained release profile for both drugs throughout the time frame examined. Subsequent cellular uptake experiments demonstrated that the introduction of HA to the NP surface endowed NPs with colon cancer-targeting capability and markedly increased cellular uptake efficiency compared with chitosan-coated NPs. Importantly, the combined delivery of CPT and CUR in one HA-functionalized NP exerted strong synergistic effects. HA-CPT/CUR-NP (1 : 1) showed the highest antitumor activity among the three HA-CPT/CUR-NPs, resulting in an extremely low combination index. Collectively, our findings indicate that this HA-CPT/CUR-NP can be exploited as an efficient formulation for colon cancer-targeted combination chemotherapy.Nanoparticle (NP)-based combination chemotherapy has been proposed as an effective strategy for achieving synergistic effects and targeted drug delivery for colon cancer therapy. Here, we fabricated a series of hyaluronic acid (HA)-functionalized camptothecin (CPT)/curcumin (CUR)-loaded polymeric NPs (HA-CPT/CUR-NPs) with various weight ratios of CPT to CUR (1 : 1, 2 : 1 and 4 : 1). The resultant spherical HA-CPT/CUR-NPs had a desirable particle size (around 289 nm), relative narrow size distribution, and slightly negative zeta potential. These NPs exhibited a simultaneous sustained release profile for both drugs throughout the time frame examined. Subsequent cellular uptake experiments demonstrated that the introduction of HA to the NP surface endowed NPs with colon cancer-targeting capability and markedly increased cellular uptake efficiency compared with chitosan-coated NPs. Importantly, the combined delivery of CPT and CUR in one HA-functionalized NP exerted strong synergistic effects. HA-CPT/CUR-NP (1 : 1) showed the highest antitumor activity among the three HA-CPT/CUR-NPs, resulting in an extremely low combination index. Collectively, our findings indicate that this HA-CPT/CUR-NP can be exploited as an efficient formulation for colon cancer-targeted combination chemotherapy. Electronic supplementary information (ESI) available: Representative flow cytometry plots of cells incubated with or without cationic CPT/CUR-NPs (1 : 1) for 3 h; Cytotoxicity of blank chitosan-coated NPs and blank HA-functionalized NPs at different concentrations against Colon-26 cells after 48 h of co-incubation. See DOI: 10.1039/c5nr04831a

Treatment initiation and dropout from prolonged exposure and cognitive processing therapy in a VA outpatient clinic.

PubMed

Kehle-Forbes, Shannon M; Meis, Laura A; Spoont, Michele R; Polusny, Melissa A

2016-01-01

Emerging data suggest that few veterans are initiating prolonged exposure (PE) and cognitive processing therapy (CPT) and dropout levels are high among those who do start the therapies. The goal of this study was to use a large sample of veterans seen in routine clinical care to 1) report the percent of eligible and referred veterans who (a) initiated PE/CPT, (b) dropped out of PE/CPT, (c) were early PE/CPT dropouts, 2) examine predictors of PE/CPT initiation, and 3) examine predictors of early and late PE/CPT dropout. We extracted data from the medical records of 427 veterans who were offered PE/CPT following an intake at a Veterans Health Administration (VHA) PTSD Clinical Team. Eighty-two percent (n = 351) of veterans initiated treatment by attending Session 1 of PE/CPT; among those veterans, 38.5% (n = 135) dropped out of treatment. About one quarter of veterans who dropped out were categorized as early dropouts (dropout before Session 3). No significant predictors of initiation were identified. Age was a significant predictor of treatment dropout; younger veterans were more likely to drop out of treatment than older veterans. Therapy type was also a significant predictor of dropout; veterans receiving PE were more likely to drop out late than veterans receiving CPT. Findings demonstrate that dropout from PE/CPT is a serious problem and highlight the need for additional research that can guide the development of interventions to improve PE/CPT engagement and adherence. (c) 2016 APA, all rights reserved).

The Effects of Cotrimoxazole Prophylactic Treatment on Adverse Health Outcomes among Human Immunodeficiency Virus-Exposed, Uninfected Infants

PubMed Central

Dow, Anna; Kayira, Dumbani; Hudgens, Michael; Van Rie, Annelies; King, Caroline C.; Ellington, Sascha; Kourtis, Athena; Turner, Abigail Norris; Meshnick, Steven; Kacheche, Zebrone; Jamieson, Denise J.; Chasela, Charles; van der Horst, Charles

2012-01-01

Background The World Health Organization guidelines recommend cotrimoxazole prophylactic treatment (CPT) for all HIV-exposed infants from age 6 weeks to the cessation of breastfeeding and the exclusion of HIV infection. There are limited data about the effects of CPT among this population of infants. We examined the effects of CPT on adverse health outcomes among HIV-exposed infants during the first 36 weeks of life by using data from the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study, a large clinical trial of antiretroviral drugs given to the mother or infant for prevention of HIV transmission during breastfeeding. Methods For the analysis, we assigned a status of CPT-exposed to infants who were participating in the study after the CPT program started. We estimated unadjusted and adjusted hazard ratios (HRs) for the effect of CPT status on time to incident malaria, severe illness or death, anemia, and weight-for-age Z score < −2.0. Participation in the study was limited to focus exclusively on HIV-exposed, uninfected infants. Results The HR for the effect of CPT on incident malaria was 0.35 (95% confidence interval [CI]: 0.21, 0.57) during the first 10 weeks of CPT exposure, and 0.93 (95% CI: 0.67, 1.29) for the remaining 20 weeks. CPT was not associated with the other outcomes examined. Conclusions CPT offered temporary protection against malaria among HIV-exposed, uninfected infants. However, CPT offered no protection against anemia, low weight for age, or the collapsed outcome of severe illness or death. PMID:22801093

Technology consumption and cognitive control: Contrasting action video game experience with media multitasking

PubMed Central

Cardoso-Leite, Pedro; Kludt, Rachel; Vignola, Gianluca; Ma, Wei Ji; Green, C. Shawn; Bavelier, Daphne

2015-01-01

Technology has the potential to impact cognition in many ways. Here we contrast two forms of technology usage: 1) media multitasking (i.e., the simultaneous consumption of multiple streams of media, such a texting while watching TV) and 2) playing action video games (a particular sub-type of video game). Previous work has outlined an association between high levels of media multitasking and specific deficits in handling distracting information, while playing action video games has been associated with enhanced attentional control. As these two factors are linked with reasonably opposing effects, failing to take them jointly into account may result in inappropriate conclusions as to the impact of technology use on attention. Across four experiments (AX-CPT, N-back, Task-switching and Filter task), testing different aspects of attention and cognition, we show that heavy media multitaskers perform worse than light media multitaskers. Contrary to previous reports though, the performance deficit was not specifically tied to distractors, but was instead more global in nature. Interestingly, participants with intermediate levels of media multitasking occasionally performed better than both light and heavy media multitaskers suggesting that the effects of increasing media multitasking are not monotonic. Action video game players, as expected, outperformed non-video game players on all tasks. However, surprisingly this was true only for participants with intermediate levels of media multitasking, suggesting that playing action video games does not protect against the deleterious effect of heavy media multitasking. Taken together this study shows that media consumption can have complex and counter-intuitive effects on attentional control. PMID:26474982

THERMODYNAMICS OF ION-EXCHANGED NATURAL CLINOPTILOLITE

EPA Science Inventory

Natural clinoptilolite from Castle Creek, Idaho, and its cation-exchanged variants (Na-Cpt, NaK-Cpt, K-Cpt, and Ca-Cpt) were studied by high-temperature calorimetry. The hydration enthalpy for all clinoptilolites is about -30 kJ/mol H2O (liquid water reference state) at 25 C. T...

Certification Examination Cases of Candidates for Certification by the American Board of Plastic Surgery: Trends in Practice Profiles Spanning a Decade (2000–2009)

PubMed Central

Chung, Kevin C.; Song, Jae W.; Shauver, Melissa J.; Cullison, Terry M.; Noone, R. Barrett

2011-01-01

Background To evaluate the case mix of plastic surgeons in their early years of practice by examining candidate case-logs submitted for the Oral Examination. Methods De-identified data from 2000–2009 consisting of case-logs submitted by young plastic surgery candidates for the Oral Examination were analyzed. Data consisted of exam year, CPT (Current Procedural Terminology) Codes and the designation of each CPT code as cosmetic or reconstructive by the candidate, and patient age and gender. Subgroup analyses for comprehensive, cosmetic, craniomaxillofacial, and hand surgery modules were performed by using the CPT code list designated by the American Board of Plastic Surgery Maintenance of Certification in Plastic Surgery ( ) module framework. Results We examined case-logs from a yearly average of 261 candidates over 10 years. Wider variations in yearly percent change in median cosmetic surgery case volumes (−62.5% to 30%) were observed when compared to the reconstructive surgery case volumes (−18.0% to 25.7%). Compared to cosmetic surgery cases per candidate, which varied significantly from year-to-year (p<0.0001), reconstructive surgery cases per candidate did not vary significantly (p=0.954). Subgroup analyses of proportions of types of surgical procedures based on CPT code categories, revealed hand surgery to be the least performed procedure relative to comprehensive, craniomaxillofacial, and cosmetic surgery procedures. Conclusions Graduates of plastic surgery training programs are committed to performing a broad spectrum of reconstructive and cosmetic surgical procedures in their first year of practice. However, hand surgery continues to have a small presence in the practice profiles of young plastic surgeons. PMID:21788850

The effect of methylphenidate on sustained attention among adolescents with attention-deficit hyperactivity disorder.

PubMed

Lufi, Dubi; Bassin-Savion, Shiry; Rubel, Lilach

2015-01-01

Twenty-seven adolescents diagnosed as having attention-deficit hyperactivity disorder (ADHD) were tested twice with a computerized MATH-CPT (mathematics continuous performance test). In one administration, the participants took medication (methylphenidate, MPH) 1.5 hr before being tested. In another administration, the MATH-CPT was administered without the medication. Treatment with MPH improved the "overall attention level" and in measures of "reaction time" and "impulsivity." MPH did not improve the performance in the four measures of sustained attention. Knowing that treatment with MPH does not improve sustained attention can be helpful in reaching a decision of whether or not a child should be treated with MPH.

Two- and four-dimensional representations of the PT - and CPT -symmetric fermionic algebras

NASA Astrophysics Data System (ADS)

Beygi, Alireza; Klevansky, S. P.; Bender, Carl M.

2018-03-01

Fermionic systems differ from their bosonic counterparts, the main difference with regard to symmetry considerations being that T2=-1 for fermionic systems. In PT -symmetric quantum mechanics an operator has both PT and CPT adjoints. Fermionic operators η , which are quadratically nilpotent (η2=0 ), and algebras with PT and CPT adjoints can be constructed. These algebras obey different anticommutation relations: η ηPT+ηPTη =-1 , where ηPT is the PT adjoint of η , and η ηCPT+ηCPTη =1 , where ηCPT is the CPT adjoint of η . This paper presents matrix representations for the operator η and its PT and CPT adjoints in two and four dimensions. A PT -symmetric second-quantized Hamiltonian modeled on quantum electrodynamics that describes a system of interacting fermions and bosons is constructed within this framework and is solved exactly.

The N+CPT resonance

NASA Astrophysics Data System (ADS)

Crescimanno, Michael; Hohensee, Michael; Hancox, Cindy; Phillips, David; Walsworth, Ron

2007-06-01

Of relevance to compact atomic frequency standards, we investigate a model of the N+CPT joint optical resonance. We compare analytical solutions of a 4-state theory, as well as numerical solutions of the optical Bloch equations, to experimental investigations of N+CPT resonances in 87Rb. Our results inform the optimization of N+CPT based frequency standards.

Induction of oncogene addiction shift to NF-{kappa}B by camptothecin in solid tumor cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Togano, Tomiteru; Sasaki, Masataka; Watanabe, Mariko

2009-12-04

The biological basis of the resistance of solid tumor cells to chemotherapy is not well understood. While addressing this problem, we found that gastric cancer cell line St-4/CPT, lung cancer cell line A549/CPT, and colon cancer cell line HT-29/CPT, all of which are resistant to camptothecin (CPT), showed strong and constitutive nuclear factor (NF)-{kappa}B activity driven by I{kappa}B kinase compared with their parental cell lines St-4, A549, and HT-29. A new NF-{kappa}B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), reduced viability and induced apoptosis in St-4/CPT, A549/CPT, and HT-29/CPT cell lines, while their parental cell lines were resistant to DHMEQ. The results in thismore » study present an example of the shift in signals that support the survival of solid tumor cells to NF-{kappa}B during the acquisition of resistance to CPT. The results also indicate that solid tumor cells that become resistant to chemotherapy may be more easily treated by NF-{kappa}B inhibitors.« less

An Ultra-Sensitive Electrometer based on the Cavity-Embedded Cooper-Pair Transistor

NASA Astrophysics Data System (ADS)

Li, Juliang; Miller, Marco; Rimberg, Alex

2015-03-01

We discuss use of a cavity-embedded Cooper-pair transistor (cCPT) as a potentially quantum-limited electrometer. The cCPT consists of a Cooper pair transistor placed at the voltage antinode of a 5.7 GHz shorted quarter-wave resonator so that the CPT provides a galvanic connection between the cavity's central conductor and ground plane. The quantum inductance of the CPT, which appears in parallel with the effective inductance of the cavity resonance, can be modulated by application of either a gate voltage to the CPT island or a flux bias to the CPT/cavity loop. Changes in the CPT inductance shift the cavity resonant frequency, and therefore the phase of a microwave signal reflected from the cavity. The reflected wave is amplified by both SLUG and HEMT amplifiers before its phase is measured. Results of recent measurements on the cCPT electrometer will be compared with theoretical predictions. This work was supported by the NSF under Grant No. DMR-1104821, by the ARO under Contract No, W911NF-13-1-0377 and by AFOSR/DARPA under Agreement No. FA8750-12-2-0339.

Ultrasensitive Electrometry with a Cavity-Embedded Cooper Pair Transistor

NASA Astrophysics Data System (ADS)

Rimberg, A. J.; Li, Juliang

In this experiment a cavity-embedded Cooper-pair transistor (cCPT) is used as a potentially quantum-limited electrometer. The cCPT consists of a Cooper pair transistor placed at the voltage antinode of a 5.7 GHz shorted quarter-wave resonator so that the CPT provides a galvanic connection between the cavity's central conductor and ground plane. The quantum inductance of the CPT, which appears in parallel with the effective inductance of the cavity resonance, can be modulated by application of either a gate voltage to the CPT island or a flux bias to the CPT/cavity loop. Changes in the CPT inductance shift the cavity resonant frequency, and therefore the phase of a microwave signal reflected from the cavity. The reflected wave is amplified by both SLUG and HEMT amplifiers before its phase is measured. The cCPT can also be operated as a Josephson parametric amplifier (JPA). A pump tone at 11.4 GHz sent into the flux bias line has been shown to provide about 10dB gain. The possibility of parametrically amplifying the side bands produced by a charge detection measurement, thereby increasing the overall sensitivity of the cCPT, will also be investigated. Supported by Grants ARO W911NF-13-10377 and NSF DMR 1507400.

Comparative evaluation of polymeric and amphiphilic cyclodextrin nanoparticles for effective camptothecin delivery.

PubMed

Cirpanli, Yasemin; Bilensoy, Erem; Lale Doğan, A; Caliş, Sema

2009-09-01

Camptothecin (CPT) is a potent anticancer agent. The clinical application of CPT is restricted by poor water solubility and instability under physiological conditions. Solubilization and stabilization of CPT were realized through nanoparticulate systems of amphiphilic cyclodextrins, poly(lactide-co-glycolide) (PLGA) or poly-epsilon-caprolactone (PCL). Nanoparticles were prepared with nanoprecipitation technique, whereas cyclodextrin nanoparticles were prepared from preformed inclusion complexes of CPT with amphiphilic cyclodextrins. Polymeric nanoparticles, on the other hand, were loaded with CPT:HP-beta-CD inclusion complex to solubilize and stabilize the drug. Mean particle sizes were under 275 nm, and polydispersity indices were lower than 0.2 for all formulations. Drug-loading values were significantly higher for amphiphilic cyclodextrin nanoparticles when compared with those for PLGA and PCL nanoparticles. Nanoparticle formulations showed a significant controlled release profile extended up to 12 days for amphiphilic cyclodextrin nanoparticles and 48h for polymeric nanoparticles. Anticancer efficacy of the nanoparticles was evaluated in comparison with CPT solution in dimethyl sulfoxide (DMSO) on MCF-7 breast adenocarcinoma cells. Amphiphilic cyclodextrin nanoparticles showed higher anticancer efficacy than PLGA or PCL nanoparticles loaded with CPT and the CPT solution in DMSO. These results indicated that CPT-loaded amphiphilic cyclodextrin nanoparticles might provide a promising carrier system for the effective delivery of this anticancer drug having bioavailability problems.

The Effect of Cotrimoxazole Prophylactic Treatment on Malaria, Birth Outcomes, and Postpartum CD4 Count in HIV-Infected Women

PubMed Central

Dow, Anna; Hudgens, Michael G.; Van Rie, Annelies; King, Caroline C.; Ellington, Sascha; Chome, Nelecy; Turner, Abigail Norris; Kacheche, Zebrone; Jamieson, Denise J.; Chasela, Charles; van der Horst, Charles

2013-01-01

Background. Limited data exist on cotrimoxazole prophylactic treatment (CPT) in pregnant women, including protection against malaria versus standard intermittent preventive therapy with sulfadoxine-pyrimethamine (IPTp). Methods. Using observational data we examined the effect of CPT in HIV-infected pregnant women on malaria during pregnancy, low birth weight and preterm birth using proportional hazards, logistic, and log binomial regression, respectively. We used linear regression to assess effect of CPT on CD4 count. Results. Data from 468 CPT-exposed and 768 CPT-unexposed women were analyzed. CPT was associated with protection against malaria versus IPTp (hazard ratio: 0.35, 95% Confidence Interval (CI): 0.20, 0.60). After adjustment for time period this effect was not statistically significant (adjusted hazard ratio: 0.66, 95% CI: 0.28, 1.52). Among women receiving and not receiving CPT, rates of low birth weight (7.1% versus 7.6%) and preterm birth (23.5% versus 23.6%) were similar. CPT was associated with lower CD4 counts 24 weeks postpartum in women receiving (−77.6 cells/μL, 95% CI: −125.2, −30.1) and not receiving antiretrovirals (−33.7 cells/μL, 95% CI: −58.6, −8.8). Conclusions. Compared to IPTp, CPT provided comparable protection against malaria in HIV-infected pregnant women and against preterm birth or low birth weight. Possible implications of CPT-associated lower CD4 postpartum warrant further examination. PMID:24363547

Increased Missense Mutation Burden of Fatty Acid Metabolism Related Genes in Nunavik Inuit Population

PubMed Central

Zhou, Sirui; Xiong, Lan; Xie, Pingxing; Ambalavanan, Amirthagowri; Bourassa, Cynthia V.; Dionne-Laporte, Alexandre; Spiegelman, Dan; Turcotte Gauthier, Maude; Henrion, Edouard; Diallo, Ousmane; Dion, Patrick A.; Rouleau, Guy A.

2015-01-01

Background Nunavik Inuit (northern Quebec, Canada) reside along the arctic coastline where for generations their daily energy intake has mainly been derived from animal fat. Given this particular diet it has been hypothesized that natural selection would lead to population specific allele frequency differences and unique variants in genes related to fatty acid metabolism. A group of genes, namely CPT1A, CPT1B, CPT1C, CPT2, CRAT and CROT, encode for three carnitine acyltransferases that are important for the oxidation of fatty acids, a critical step in their metabolism. Methods Exome sequencing and SNP array genotyping were used to examine the genetic variations in the six genes encoding for the carnitine acyltransferases in 113 Nunavik Inuit individuals. Results Altogether ten missense variants were found in genes CPT1A, CPT1B, CPT1C, CPT2 and CRAT, including three novel variants and one Inuit specific variant CPT1A p.P479L (rs80356779). The latter has the highest frequency (0.955) compared to other Inuit populations. We found that by comparison to Asians or Europeans, the Nunavik Inuit have an increased mutation burden in CPT1A, CPT2 and CRAT; there is also a high level of population differentiation based on carnitine acyltransferase gene variations between Nunavik Inuit and Asians. Conclusion The increased number and frequency of deleterious variants in these fatty acid metabolism genes in Nunavik Inuit may be the result of genetic adaptation to their diet and/or the extremely cold climate. In addition, the identification of these variants may help to understand some of the specific health risks of Nunavik Inuit. PMID:26010953

Increased missense mutation burden of Fatty Acid metabolism related genes in nunavik inuit population.

PubMed

Zhou, Sirui; Xiong, Lan; Xie, Pingxing; Ambalavanan, Amirthagowri; Bourassa, Cynthia V; Dionne-Laporte, Alexandre; Spiegelman, Dan; Turcotte Gauthier, Maude; Henrion, Edouard; Diallo, Ousmane; Dion, Patrick A; Rouleau, Guy A

2015-01-01

Nunavik Inuit (northern Quebec, Canada) reside along the arctic coastline where for generations their daily energy intake has mainly been derived from animal fat. Given this particular diet it has been hypothesized that natural selection would lead to population specific allele frequency differences and unique variants in genes related to fatty acid metabolism. A group of genes, namely CPT1A, CPT1B, CPT1C, CPT2, CRAT and CROT, encode for three carnitine acyltransferases that are important for the oxidation of fatty acids, a critical step in their metabolism. Exome sequencing and SNP array genotyping were used to examine the genetic variations in the six genes encoding for the carnitine acyltransferases in 113 Nunavik Inuit individuals. Altogether ten missense variants were found in genes CPT1A, CPT1B, CPT1C, CPT2 and CRAT, including three novel variants and one Inuit specific variant CPT1A p.P479L (rs80356779). The latter has the highest frequency (0.955) compared to other Inuit populations. We found that by comparison to Asians or Europeans, the Nunavik Inuit have an increased mutation burden in CPT1A, CPT2 and CRAT; there is also a high level of population differentiation based on carnitine acyltransferase gene variations between Nunavik Inuit and Asians. The increased number and frequency of deleterious variants in these fatty acid metabolism genes in Nunavik Inuit may be the result of genetic adaptation to their diet and/or the extremely cold climate. In addition, the identification of these variants may help to understand some of the specific health risks of Nunavik Inuit.

How Can Paresthesia After Zygomaticomaxillary Complex Fracture Be Determined After Long-Term Follow-Up? A New and Quantitative Evaluation Method Using Current Perception Threshold Testing.

PubMed

Okochi, Masayuki; Ueda, Kazuki; Mochizuki, Yasushi; Okochi, Hiromi

2015-08-01

The aims of the present study were to analyze the effectiveness of current perception threshold (CPT) testing to determine patients' minor paresthesia of the infraorbital region after open reduction and internal fixation (ORIF) for unilateral zygomaticomaxillary bone fracture (UZF) and to clarify which nerve fiber was related to the paresthesia. We conducted a retrospective cohort study of patients who had undergone ORIF after UZF. We also performed neurosensory testing for healthy volunteers who served as the control group. The predictor variables were the period of measurement of Semmes-Weinstein monofilament (S-W) testing and CPT testing (preoperatively and 1 and 5 years postoperatively), measurement side, and disease status (UZF or control). The outcome variables were paresthesia status of the infraorbital nerve region and the results of S-W and CPT testing in both UZF and control groups. The differences in the S-W and CPT values between the affected and unaffected sides in the UZF group and between the UZF and control groups were analyzed by t test (P < .05 was considered significant). The present study included 10 patients (6 males and 4 females), with an average age of 25.0 ± 12.7 years, and 21 controls (10 males and 11 females), with an average age of 24.3 ± 1.7 years. In the control group, the CPT and S-W test results did not show any significant differences between the left and right sides. All 10 patients had paresthesia at 1 and 5 years postoperatively. At 5 years postoperatively, the S-W values in all patients showed normalization. From the results of CPT testing, only the A-β fiber function showed significant improvement at 5 years postoperatively. The CPT test was an effective sensory test for determining minor paresthesia that could not be detected using S-W testing. Paresthesia of the infraorbital nerve region was caused by the damaged A-δ and C fibers. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Cerebrovascular response to the cold pressor test - the critical role of carbon dioxide.

PubMed

Tymko, Michael M; Kerstens, Thijs P; Wildfong, Kevin W; Ainslie, Philip N

2017-12-01

What is the central question of this study? What is the role of carbon dioxide in the cerebral blood flow (CBF) response to the cold pressor test (CPT)? What is the main finding and its importance? The CBF response was elevated during the isocapnic (controlled CO 2 ) CPT in the middle cerebral artery and the internal carotid artery compared with the poikilocapnic (uncontrolled CO 2 ) CPT, owing to ventilation-associated reductions in end-tidal CO 2 . Furthermore, the common carotid artery vasodilated to a greater extent during the isocapnic compared with the poikilocapnic CPT, whereas the internal carotid artery vasoconstricted during both CPTs. Our data highlight the importance of CO 2 control when investigating the CBF response to the CPT. In addition to increasing sympathetic nervous activity, blood pressure and cerebral blood flow (CBF), the cold pressor test (CPT) stimulates pain receptors, which may increase ventilation above metabolic demand; this response is likely to reduce the partial pressure of end-tidal carbon dioxide (P ET ,CO2) and will attenuate elevations in CBF. Our hypotheses were as follows: (i) the CPT will elicit hyperventilation, effectively lowering P ET ,CO2; (ii) the CBF response will be elevated during an isocapnic (controlled P ET ,CO2) compared with a poikilocapnic CPT (uncontrolled P ET ,CO2); and (iii) in response to the CPT, the common carotid artery (CCA) will vasodilate, while the internal carotid artery (ICA) will remain unchanged to help regulate CBF. Using a new, randomized experimental design, we measured the cerebrovascular response in the middle cerebral artery (MCA), CCA and internal carotid artery (ICA), during an isocapnic and poikilocapnic CPT in 15 participants. Blood pressure and cardiac output (finger photoplethysmography), heart rate (ECG), MCA mean velocity (transcranial Doppler ultrasound) and CCA and ICA CBF (Duplex ultrasound) were recorded during both CPT trials. Our findings were as follows: (i) ventilation increased, which reduced P ET ,CO2 (-5.3 ± 6.4 mmHg) during the poikilocapnic compared with the isocapnic CPT; (ii) the CBF response was elevated during the isocapnic compared with the poikilocapnic CPT in the MCA and ICA, but not in the CCA; and (iii) the CCA dilated to a greater extent during the isocapnic compared with the poikilocapnic CPT, and the ICA vasoconstricted during both trials. Our data emphasize the importance of P ET ,CO2 control in the CBF response to the CPT and in the differential vasomotor regulation between the CCA and ICA. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Risperidone Added to Psychostimulant in Children with Severe Aggression and Attention-Deficit/Hyperactivity Disorder: Lack of Effect on Attention and Short-Term Memory

PubMed Central

Epstein, Jeffery N.; Findling, Robert L.; Gadow, Kenneth D.; Arnold, L. Eugene; Kipp, Heidi; Kolko, David J.; Butter, Eric; Schneider, Jayne; Bukstein, Oscar G.; McNamara, Nora K.; Molina, Brooke S.G.; Aman, Michael G.

2017-01-01

Abstract Objective: Professionals have periodically expressed concern that atypical antipsychotics may cause cognitive blunting in treated patients. In this study, we report data from a double-blind, randomized, controlled study of stimulant plus placebo versus combined stimulant and risperidone to evaluate the effects of the atypical antipsychotic on attention and short-term memory. Methods: A total of 165 (n = 83 combined treatment; n = 82 stimulant plus placebo) children with attention-deficit/hyperactivity disorder and severe physical aggression, aged 6–12 years, were evaluated with Conners' Continuous Performance Test (CPT-II) and the Wechsler Intelligence Scale for Children-III (WISC) Digit Span subscale at baseline, after 3 weeks of stimulant-only treatment, and after six additional weeks of randomized treatment (stimulant+placebo vs. stimulant+risperidone). Results: At 3 weeks, improvement on CPT-II performance (Commissions and Reaction Time Standard Error; p < 0.001) and on Digit Span memory performance (p < 0.006) was noted for the full sample. At study week 9, no difference in CPT-II or Digit Span performance was observed between the randomized groups (ps = 0.41 to 0.83). Conclusions: Similar to other studies, we found no deleterious effects on attention and short-term memory associated with short-term use of risperidone. NCT00796302. PMID:27348211

Art Therapy and Cognitive Processing Therapy for Combat-Related PTSD: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Campbell, Melissa; Decker, Kathleen P.; Kruk, Kerry; Deaver, Sarah P.

2016-01-01

This randomized controlled trial was designed to determine if art therapy in conjunction with Cognitive Processing Therapy (CPT) was more effective for reducing symptoms of combat posttraumatic stress disorder (PTSD) than CPT alone. Veterans (N = 11) were randomized to receive either individual CPT, or individual CPT in conjunction with individual…

Potential of poly(amidoamine) dendrimers as drug carriers of camptothecin based on encapsulation studies.

PubMed

Cheng, Yiyun; Li, Mingzhong; Xu, Tongwen

2008-08-01

Camptothecin (CPT), a plant alkaloid isolated from Camptotheca acuminata, has an extremely low solubility in aqueous medium, which presents a major challenge during drug formulation in clinical trails. In the present study we investigated the potential of poly(amidoamine) (PAMAM) dendrimers as drug carriers of CPT through aqueous solubility studies. Results showed that the aqueous solubility of CPT was significantly increased by PAMAM dendrimers. The effect of PAMAM generation on CPT solubility was also evaluated. These studies indicated that PAMAM dendrimers might be considered as biocompatible carriers of CPT.

Occupational factors and reproductive outcomes among a cohort of female veterinarians.

PubMed

Wilkins, J R; Steele, L L

1998-07-01

To estimate absolute and relative risks of preterm delivery (PTD) and small-for-gestational-age (SGA) births among a cohort of female veterinarians in relation to selected occupational factors, including clinical practice type (CPT). Retrospective cohort survey. 2,997 female graduates from US veterinary colleges between 1970 and 1980. Relevant health and occupational data were collected through a self-administered mail questionnaire with telephone follow-up of nonrespondents. Absolute and relative risks of PTD and SGA births were estimated in relation to maternal CPT at the time of conception and exposure to 13 occupational factors. Attempts were made to control confounding by use of multiple logistic regression analyses. Absolute and relative risks of PTD were highest for veterinarians employed in exclusively equine clinical practice. Although several increased, none of the CPT-specific relative risk estimates were significantly different from the null value of 1. Exposure-specific analyses indicated that occupational involvement with solvents among exclusively small animal practitioners was associated with the highest relative risk of PTD. A small number of SGA births limited information that could be obtained from these analyses. Overall absolute risks of PTD and SGA births among cohort members were much lower in comparison with the general female population. Given the large number of women currently practicing and entering the profession of veterinary medicine, clinical tasks associated with potential reproductive hazards should be approached with heightened awareness and increased caution, especially activities that may involve exposure to solvents.

Noxa/Mcl-1 Balance Regulates Susceptibility of Cells to Camptothecin-Induced Apoptosis1

PubMed Central

Mei, Yide; Xie, Chongwei; Xie, Wei; Tian, Xu; Li, Mei; Wu, Mian

2007-01-01

Although camptothecin (CPT) has been reported to induce apoptosis in various cancer cells, the molecular details of this regulation remain largely unknown. In this study, we demonstrate that BH3-only protein Noxa is upregulated during CPT-induced apoptosis, which is independent of p53. In addition, we show that phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is responsible for Noxa's induction. Luciferase assay and cAMP response element binding protein (CREB) knockdown experiments further demonstrate that CREB is involved in the transcriptional upregulation of Noxa. Moreover, blocking Noxa expression using specific small interfering ribonucleic acid (siRNA) significantly reduces the apoptosis in response to CPT, indicating that Noxa is an essential mediator for CPT-induced apoptosis. Interestingly, antiapoptotic Mcl-1 was also upregulated through PI3K/Akt signaling pathway upon CPT treatment. Using immunoprecipitation assay, Noxa was found to interact with Mcl-1 in the presence or absence of CPT. Knockdown of Mcl-1 expression by short hairpin ribonucleic acid (shRNA) was shown to potentiate CPT-induced apoptosis. Consistently, ectopic overexpression of Mcl-1 rescued cells from apoptosis induced by CPT. Cells coexpressing Noxa and Mcl-1 at different ratio correlates well with the extent of apoptosis, suggesting that the balance between Noxa and Mcl-1 may determine the susceptibility of HeLa cells to CPT-induced apoptosis. PMID:17971907

Ghrelin Causes a Decline in GABA Release by Reducing Fatty Acid Oxidation in Cortex.

PubMed

Mir, Joan Francesc; Zagmutt, Sebastián; Lichtenstein, Mathieu P; García-Villoria, Judit; Weber, Minéia; Gracia, Ana; Fabriàs, Gemma; Casas, Josefina; López, Miguel; Casals, Núria; Ribes, Antònia; Suñol, Cristina; Herrero, Laura; Serra, Dolors

2018-02-02

Lipid metabolism, specifically fatty acid oxidation (FAO) mediated by carnitine palmitoyltransferase (CPT) 1A, has been described to be an important actor of ghrelin action in hypothalamus. However, it is not known whether CPT1A and FAO mediate the effect of ghrelin on the cortex. Here, we show that ghrelin produces a differential effect on CPT1 activity and γ-aminobutyric acid (GABA) metabolism in the hypothalamus and cortex of mice. In the hypothalamus, ghrelin enhances CPT1A activity while GABA transaminase (GABAT) activity, a key enzyme in GABA shunt metabolism, is unaltered. However, in cortex CPT1A activity and GABAT activity are reduced after ghrelin treatment. Furthermore, in primary cortical neurons, ghrelin reduces GABA release through a CPT1A reduction. By using CPT1A floxed mice, we have observed that genetic ablation of CPT1A recapitulates the effect of ghrelin on GABA release in cortical neurons, inducing reductions in mitochondrial oxygen consumption, cell content of citrate and α-ketoglutarate, and GABA shunt enzyme activity. Taken together, these observations indicate that ghrelin-induced changes in CPT1A activity modulate mitochondrial function, yielding changes in GABA metabolism. This evidence suggests that the action of ghrelin on GABA release is region specific within the brain, providing a basis for differential effects of ghrelin in the central nervous system.

Cognitive models of risky choice: parameter stability and predictive accuracy of prospect theory.

PubMed

Glöckner, Andreas; Pachur, Thorsten

2012-04-01

In the behavioral sciences, a popular approach to describe and predict behavior is cognitive modeling with adjustable parameters (i.e., which can be fitted to data). Modeling with adjustable parameters allows, among other things, measuring differences between people. At the same time, parameter estimation also bears the risk of overfitting. Are individual differences as measured by model parameters stable enough to improve the ability to predict behavior as compared to modeling without adjustable parameters? We examined this issue in cumulative prospect theory (CPT), arguably the most widely used framework to model decisions under risk. Specifically, we examined (a) the temporal stability of CPT's parameters; and (b) how well different implementations of CPT, varying in the number of adjustable parameters, predict individual choice relative to models with no adjustable parameters (such as CPT with fixed parameters, expected value theory, and various heuristics). We presented participants with risky choice problems and fitted CPT to each individual's choices in two separate sessions (which were 1 week apart). All parameters were correlated across time, in particular when using a simple implementation of CPT. CPT allowing for individual variability in parameter values predicted individual choice better than CPT with fixed parameters, expected value theory, and the heuristics. CPT's parameters thus seem to pick up stable individual differences that need to be considered when predicting risky choice. Copyright © 2011 Elsevier B.V. All rights reserved.

CPT1{alpha} over-expression increases long-chain fatty acid oxidation and reduces cell viability with incremental palmitic acid concentration in 293T cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jambor de Sousa, Ulrike L.; Koss, Michael D.; Fillies, Marion

2005-12-16

To test the cellular response to an increased fatty acid oxidation, we generated a vector for an inducible expression of the rate-limiting enzyme carnitine palmitoyl-transferase 1{alpha} (CPT1{alpha}). Human embryonic 293T kidney cells were transiently transfected and expression of the CPT1{alpha} transgene in the tet-on vector was activated with doxycycline. Fatty acid oxidation was measured by determining the conversion of supplemented, synthetic cis-10-heptadecenoic acid (C17:1n-7) to C15:ln-7. CPT1{alpha} over-expression increased mitochondrial long-chain fatty acid oxidation about 6-fold. Addition of palmitic acid (PA) decreased viability of CPT1{alpha} over-expressing cells in a concentration-dependent manner. Both, PA and CPT1{alpha} over-expression increased cell death. Interestingly,more » PA reduced total cell number only in cells over-expressing CPT1{alpha}, suggesting an effect on cell proliferation that requires PA translocation across the mitochondrial inner membrane. This inducible expression system should be well suited to study the roles of CPT1 and fatty acid oxidation in lipotoxicity and metabolism in vivo.« less

Mitochondrial Carnitine Palmitoyltransferase 1a (CPT1a) Is Part of an Outer Membrane Fatty Acid Transfer Complex*

PubMed Central

Lee, Kwangwon; Kerner, Janos; Hoppel, Charles L.

2011-01-01

CPT1a (carnitine palmitoyltransferase 1a) in the liver mitochondrial outer membrane (MOM) catalyzes the primary regulated step in overall mitochondrial fatty acid oxidation. It has been suggested that the fundamental unit of CPT1a exists as a trimer, which, under native conditions, could form a dimer of the trimers, creating a hexamer channel for acylcarnitine translocation. To examine the state of CPT1a in the MOM, we employed a combined approach of sizing by mass and isolation using an immunological method. Blue native electrophoresis followed by detection with immunoblotting and mass spectrometry identified large molecular mass complexes that contained not only CPT1a but also long chain acyl-CoA synthetase (ACSL) and the voltage-dependent anion channel (VDAC). Immunoprecipitation with antisera against the proteins revealed a strong interaction between the three proteins. Immobilized CPT1a-specific antibodies immunocaptured not only CPT1a but also ACSL and VDAC, further strengthening findings with blue native electrophoresis and immunoprecipitation. This study shows strong protein-protein interaction between CPT1a, ACSL, and VDAC. We propose that this complex transfers activated fatty acids through the MOM. PMID:21622568

Mental Health Providers' Decision-Making Around the Implementation of Evidence-Based Treatment for PTSD.

PubMed

Osei-Bonsu, Princess E; Bolton, Rendelle E; Wiltsey Stirman, Shannon; Eisen, Susan V; Herz, Lawrence; Pellowe, Maura E

2017-04-01

It is estimated that <15% of veterans with posttraumatic stress disorder (PTSD) have engaged in two evidence-based psychotherapies highly recommended by VA-cognitive processing therapy (CPT) and prolonged exposure (PE). CPT and PE guidelines specify which patients are appropriate, but research suggests that providers may be more selective than the guidelines. In addition, PTSD clinical guidelines encourage "shared decision-making," but there is little research on what processes providers use to make decisions about CPT/PE. Sixteen licensed psychologists and social workers from two VA medical centers working with ≥1 patient with PTSD were interviewed about patient factors considered and decision-making processes for CPT/PE use. Qualitative analyses revealed that patient readiness and comorbid conditions influenced decisions to use or refer patients with PTSD for CPT/PE. Providers reported mentally derived and instances of patient-involved decision-making around CPT/PE use. Continued efforts to assist providers in making informed and collaborative decisions about CPT/PE use are discussed.

Impact of Sleep Restriction on Neurobehavioral Functioning of Children with Attention Deficit Hyperactivity Disorder

PubMed Central

Gruber, Reut; Wiebe, Sabrina; Montecalvo, Lisa; Brunetti, Bianca; Amsel, Rhonda; Carrier, Julie

2011-01-01

Study Objectives: The objective of this study was to assess the cumulative impact of 1 hour of nightly sleep restriction over the course of 6 nights on the neurobehavioral functioning (NBF) of children with attention deficit hyperactivity disorder (ADHD) and healthy controls. Design: Following 6 nights of actigraphic monitoring of sleep to determine baseline sleep duration, children were asked to restrict sleep duration by 1 hour for 6 consecutive nights. NBF was assessed at baseline (Day 6) and following sleep manipulation (Day 12). Setting: A quiet location within their home environments. Participants: Forty-three children (11 ADHD, 32 Controls, mean age = 8.7 years, SD = 1.3) between the ages of 7 and 11 years. Interventions: NA Measurements: Sleep was monitored using actigraphy. In addition, parents were asked to complete nightly sleep logs. Sleepiness was evaluated using a questionnaire. The Conners' Continuous Performance Test (CPT) was used to assess NBF. Results: Restricted sleep led to poorer CPT scores on two-thirds of CPT outcome measures in both healthy controls and children with ADHD. The performance of children with ADHD following sleep restriction deteriorated from subclinical levels to the clinical range of inattention on two-thirds of CPT outcome measures. Conclusions: Moderate sleep restriction leads to a detectable negative impact on the NBF of children with ADHD and healthy controls, leading to a clinical level of impairment in children with ADHD. Citation: Gruber R; Wiebe S; Montecalvo L; Brunetti B; Amsel R; Carrier J. Impact of sleep restriction on neurobehavioral functioning of children with attention deficit hyperactivity disorder. SLEEP 2011;34(3):315-323. PMID:21358848

Traditional games resulted in post-exercise hypotension and a lower cardiovascular response to the cold pressor test in healthy children

PubMed Central

Rauber, Suliane B.; Boullosa, Daniel A.; Carvalho, Ferdinando O.; de Moraes, José F. V. N.; de Sousa, Ioranny R. C.; Simões, Herbert G.; Campbell, Carmen S. G.

2014-01-01

The present study aimed to verify if blood pressure (BP) reactivity could be reduced through a previous single session of active playing when compared to sedentary leisure. Sixteen pre-pubertal healthy children participated in this study. After familiarization with procedures and anthropometric evaluation, participants performed three sessions in randomized order: (1) 30 min of traditional Brazilian games (PLAY); (2) 30 min of video game playing (DDR); and (3) 30 min of watching TV (TV). Each session lasted 80 min, being 10 min of rest; 30 min of intervention activity; and 40 min of recovery. After recovery, the Cold Pressor Test (CPT) was used for the assessment of acute cardiovascular reactivity. BP was recorded at 30 s and 1 min during the CPT. Analysis of variance showed post-exercise hypotension (PEH) only after PLAY, and that systolic and diastolic BP were significantly increased in all conditions during CPT. However, the magnitude of the CPT-induced BP response was significantly less in PLAY compared to DDR and TV. The PEH observed during recovery and the reduced BP response to CPT following playing traditional games may be due its higher cardiovascular and metabolic demand as was indicated by the increased heart rate, oxygen consumption, and BP. It was concluded that BP reactivity to stress may be reduced through a previous single session of traditional games and that PEH was recorded only after this exercise form. This benefit indicates a potential role of playing strategies for cardiovascular health in childhood. PMID:25009506

Traditional games resulted in post-exercise hypotension and a lower cardiovascular response to the cold pressor test in healthy children.

PubMed

Rauber, Suliane B; Boullosa, Daniel A; Carvalho, Ferdinando O; de Moraes, José F V N; de Sousa, Ioranny R C; Simões, Herbert G; Campbell, Carmen S G

2014-01-01

The present study aimed to verify if blood pressure (BP) reactivity could be reduced through a previous single session of active playing when compared to sedentary leisure. Sixteen pre-pubertal healthy children participated in this study. After familiarization with procedures and anthropometric evaluation, participants performed three sessions in randomized order: (1) 30 min of traditional Brazilian games (PLAY); (2) 30 min of video game playing (DDR); and (3) 30 min of watching TV (TV). Each session lasted 80 min, being 10 min of rest; 30 min of intervention activity; and 40 min of recovery. After recovery, the Cold Pressor Test (CPT) was used for the assessment of acute cardiovascular reactivity. BP was recorded at 30 s and 1 min during the CPT. Analysis of variance showed post-exercise hypotension (PEH) only after PLAY, and that systolic and diastolic BP were significantly increased in all conditions during CPT. However, the magnitude of the CPT-induced BP response was significantly less in PLAY compared to DDR and TV. The PEH observed during recovery and the reduced BP response to CPT following playing traditional games may be due its higher cardiovascular and metabolic demand as was indicated by the increased heart rate, oxygen consumption, and BP. It was concluded that BP reactivity to stress may be reduced through a previous single session of traditional games and that PEH was recorded only after this exercise form. This benefit indicates a potential role of playing strategies for cardiovascular health in childhood.

Enhanced Cognitive Rehabilitation to Treat Comorbid TBI and PTSD

DTIC Science & Technology

2017-12-01

13. SUPPLEMENTARY NOTES 14. ABSTRACT This was a randomized controlled treatment study to test a modification of Cognitive Processing Therapy (CPT) for...combination of conditions which often complicates recovery from either condition. Emotional symptoms are likely a main cause of the persistence of post ... tested a modification of CPT in which CPT was enhanced with compensatory cognitive rehabilitation principles detailed in CogSMART. The enhanced CPT

Alkaline phosphatase: the next independent predictor of the poor 90-day outcome in alcoholic hepatitis.

PubMed

Kasztelan-Szczerbinska, Beata; Slomka, Maria; Celinski, Krzysztof; Szczerbinski, Mariusz

2013-01-01

Determination of risk factors relevant to 90-day prognosis in AH. Comparison of the conventional prognostic models such as Maddrey's modified discriminant function (mDF) and Child-Pugh-Turcotte (CPT) score with newer ones: the Glasgow Alcoholic Hepatitis Score (GAHS); Age, Bilirubin, INR, Creatinine (ABIC) score, Model for End-Stage Liver Disease (MELD), and MELD-Na in the death prediction. The clinical and laboratory variables obtained at admission were assessed. The mDF, CPT, GAHS, ABIC, MELD, and MELD-Na scores' different areas under the curve (AUCs) and the best threshold values were compared. Logistic regression was used to assess predictors of the 90-day outcome. One hundred sixteen pts fulfilled the inclusion criteria. Twenty (17.4%) pts died and one underwent orthotopic liver transplantation (OLT) within 90 days of follow-up. No statistically significant differences in the models' performances were found. Multivariate logistic regression identified CPT score, alkaline phosphatase (AP) level higher than 1.5 times the upper limit of normal (ULN), and corticosteroids (CS) nonresponse as independent predictors of mortality. The CPT score, AP > 1.5 ULN, and the CS nonresponse had an independent impact on the 90-day survival in AH. Accuracy of all studied scoring systems was comparable.

Association between urine phthalate levels and poor attentional performance in children with attention-deficit hyperactivity disorder with evidence of dopamine gene-phthalate interaction.

PubMed

Park, Subin; Kim, Bung-Nyun; Cho, Soo-Churl; Kim, Yeni; Kim, Jae-Won; Lee, Ju-Young; Hong, Soon-Beom; Shin, Min-Sup; Yoo, Hee Jeong; Im, Hosub; Cheong, Jae Hoon; Han, Doug Hyun

2014-06-27

Although there is some evidence supporting the existence of an association between prenatal maternal or postnatal child's urine phthalate metabolite concentrations and poor attentional performances, the interaction between urine phthalate metabolite levels and genetic variation for neuropsychological deficit of attention-deficit hyperactivity disorder (ADHD) has not been examined. The aim of this study was to determine whether phthalate metabolites in urine are associated with poor neuropsychological performance in children with ADHD, and whether such association is affected by genotype-phthalate interaction. A cross-sectional examination of urine phthalate metabolite concentrations and the continuous performance test (CPT) were performed in 179 Korean children with ADHD recruited from department of psychiatry of university hospital. Correlations between urine phthalate metabolite concentrations and the CPT scores were investigated, and the interaction of phthalate metabolite levels with the selected polymorphisms at major candidate genes for ADHD, namely dopamine receptor D4 (DRD4), dopamine transporter, α-2A-adrenergic receptor, and norepinephrine transporter genes. For the subjects with the DRD4 4/4 genotype, there were significant associations of the urine phthalate metabolite concentrations with the number of omission errors, the number of commission errors, and the response time variability scores on the CPT. However, for the subjects without the DRD4 4/4 genotype, no significant associations were found. The results of this study suggest a possible association between phthalate metabolite concentrations and poor attentional performances of ADHD as well as a genetic influence on this association. Further prospective and epigenetic studies are needed to investigate causality and pathophysiological mechanisms.

Teaching of clinical pharmacology and therapeutics in UK medical schools: current status in 2009.

PubMed

O'Shaughnessy, Lelia; Haq, Inam; Maxwell, Simon; Llewelyn, Martin

2010-07-01

Junior doctors feel poorly prepared by their training in Clinical Pharmacology and Therapeutics and commonly make prescribing errors. Since 1993 the General Medical Council's guidance on undergraduate medical education 'Tomorrow's Doctors' has emphasized the integration of Clinical Pharmacology and Therapeutics teaching within the medical curriculum. With the publication of a new version of Tomorrow's Doctors in 2009, medical schools will be further revising their Clinical Pharmacology and Therapeutics teaching. Although we know what the recommendations for undergraduate teaching of Clinical Pharmacology and Therapeutics teaching are, there are no published data describing what is currently happening in UK medical schools. This paper describes the course structures, volume and range of teaching and assessment of Clinical Pharmacology and Therapeutics in the UK in 2009. Our data provide a foundation for schools looking to revise the Clinical Pharmacology and Therapeutics Teaching in the light of Tomorrow's Doctors 2009. To describe the current structure, delivery and assessment of Clinical Pharmacology and Therapeutics (CPT) teaching in UK medical schools. An online questionnaire was distributed to the person with overall responsibility for CPT teaching at all UK medical schools in June 2009. Thirty of the 32 UK medical schools responded. 60% of schools have a CPT course although in 72% this was an integrated vertical theme. At 70% of schools pharmacologists have overall responsibility for CPT teaching (clinical 67%, non-clinical 33%); at 20% teaching is run by a non-specialist clinician and at 7% by a pharmacist. Teaching is commonly delivered by NHS clinicians (87%) and clinical pharmacists (80%) using lectures (90%) but additionally 50% of schools use e-Learning and 63% have a student formulary. CPT is assessed throughout the curriculum at many schools through written, practical examinations and course work. 90% of schools have specific CPT content in their written examinations. 90% of respondents believed that their students were 'fairly' to 'well' prepared for the foundation year but only 37% of schools gather data on the competence of their graduates. CPT teaching in UK medical schools is very diverse. Most schools do not assess the performance of their graduates as prescribers and there is a lack of evidence that many of the teaching approaches employed are suitable for the development of prescribing skills. It is vital that developments in CPT teaching are driven by validated, real-world assessments of the prescribing skills of medical students and newly qualified doctors.

Long-term neurocognitive outcome and auditory event-related potentials after complex febrile seizures in children.

PubMed

Tsai, Min-Lan; Hung, Kun-Long; Tsan, Ying-Ying; Tung, William Tao-Hsin

2015-06-01

Whether prolonged or complex febrile seizures (FS) produce long-term injury to the hippocampus is a critical question concerning the neurocognitive outcome of these seizures. Long-term event-related evoked potential (ERP) recording from the scalp is a noninvasive technique reflecting the sensory and cognitive processes associated with attention tasks. This study aimed to investigate the long-term outcome of neurocognitive and attention functions and evaluated auditory event-related potentials in children who have experienced complex FS in comparison with other types of FS. One hundred and forty-seven children aged more than 6 years who had experienced complex FS, simple single FS, simple recurrent FS, or afebrile seizures (AFS) after FS and age-matched healthy controls were enrolled. Patients were evaluated with Wechsler Intelligence Scale for Children (WISC; Chinese WISC-IV) scores, behavior test scores (Chinese version of Conners' continuous performance test, CPT II V.5), and behavior rating scales. Auditory ERPs were recorded in each patient. Patients who had experienced complex FS exhibited significantly lower full-scale intelligence quotient (FSIQ), perceptual reasoning index, and working memory index scores than did the control group but did not show significant differences in CPT scores, behavior rating scales, or ERP latencies and amplitude compared with the other groups with FS. We found a significant decrease in the FSIQ and four indices of the WISC-IV, higher behavior rating scales, a trend of increased CPT II scores, and significantly delayed P300 latency and reduced P300 amplitude in the patients with AFS after FS. We conclude that there is an effect on cognitive function in children who have experienced complex FS and patients who developed AFS after FS. The results indicated that the WISC-IV is more sensitive in detecting cognitive abnormality than ERP. Cognition impairment, including perceptual reasoning and working memory defects, was identified in patients with prolonged, multiple, or focal FS. These results may have implications for the pathogenesis of complex FS. Further comprehensive psychological evaluation and educational programs are suggested. Copyright © 2015 Elsevier Inc. All rights reserved.

Neutrinos, DUNE and the world best bound on CPT invariance

NASA Astrophysics Data System (ADS)

Barenboim, G.; Ternes, C. A.; Tórtola, M.

2018-05-01

CPT symmetry, the combination of Charge Conjugation, Parity and Time reversal, is a cornerstone of our model building strategy and therefore the repercussions of its potential violation will severely threaten the most extended tool we currently use to describe physics, i.e. local relativistic quantum fields. However, limits on its conservation from the Kaon system look indeed imposing. In this work we will show that neutrino oscillation experiments can improve this limit by several orders of magnitude and therefore are an ideal tool to explore the foundations of our approach to Nature. Strictly speaking testing CPT violation would require an explicit model for how CPT is broken and its effects on physics. Instead, what is presented in this paper is a test of one of the predictions of CPT conservation, i.e., the same mass and mixing parameters in neutrinos and antineutrinos. In order to do that we calculate the current CPT bound on all the neutrino mixing parameters and study the sensitivity of the DUNE experiment to such an observable. After deriving the most updated bound on CPT from neutrino oscillation data, we show that, if the recent T2K results turn out to be the true values of neutrino and antineutrino oscillations, DUNE would measure the fallout of CPT conservation at more than 3σ. Then, we study the sensitivity of the experiment to measure CPT invariance in general, finding that DUNE will be able to improve the current bounds on Δ (Δ m312) by at least one order of magnitude. We also study the sensitivity to the other oscillation parameters. Finally we show that, if CPT is violated in nature, combining neutrino with antineutrino data in oscillation analysis will produce imposter solutions.

Multiple shoot cultures of Ophiorrhiza rugosa var. decumbens Deb and Mondal--a viable renewable source for the continuous production of bioactive Camptotheca alkaloids apart from stems of the parent plant of Nothapodytes foetida (Wight) Sleumer.

PubMed

Gopalakrishnan, Roja; Shankar, Bhavani

2014-02-15

Camptotheca alkaloids were isolated from multiple shoot cultures of O. decumbens (0.056% dry weight) and stems of N. foetida. The cytotoxicity of the extracts and products were tested in a panel of five cell lines. Crude extract from O. decumbens (Cr-Od) and N. foetida (Cr-Nf) showed more potent cytotoxic activity as compared to the isolated camptothecin from O. decumbens (CPT-Od) and N. foetida (CPT-Nf). CPT isolated from shoot cultures contained biological activity suggesting the possibility of using this system of O. decumbens as a renewable source for the production of camptotheca alkaloids. 9-Methoxy camptothecin (9-mCPT), isolated from N. foetida, was a very effective cytotoxic agent as compared to Cr-Nf or CPT-Nf. The IC50 of 9-mCPT was 0.84, 0.32, and 0.35 μg/ml for A549, MCF7 and Jurkat cell lines and >3 μg/ml for U937. Viability assays using MTT dye were further confirmed by assessing extent of apoptosis in these cells. These findings suggest that shoot cultures of O. decumbens offer a rich alternative plant source for the anticancer compound, CPT and 9-mCPT is a more potent compound in N. foetida as compared to CPT. Copyright © 2013 Elsevier GmbH. All rights reserved.

Cryptotanshinone suppresses the proliferation and induces the apoptosis of pancreatic cancer cells via the STAT3 signaling pathway.

PubMed

Ge, Yuqing; Yang, Bo; Chen, Zhe; Cheng, Rubin

2015-11-01

Pancreatic cancer remains a challenging disease worldwide. Cryptotanshinone (CPT) is one of the active constituents of Salvia miltiorrhiza Bunge and exhibits significant antitumor activities in several human cancer cells. However, the efficacy and molecular mechanism of CPT in pancreatic cancer remains to be elucidated. In the present study, the effect of CPT on the proliferation, apoptosis and cell cycle of human pancreatic cancer cell BxPC‑3 cells was evaluated. The results demonstrated that CPT inhibited proliferation of the BxPC‑3 cells in a concentration‑dependent manner, and significantly induced cell apoptosis and cell cycle arrest. The protein levels of cleaved caspase‑3, caspase‑9 and poly ADP ribose polymerase were upregulated, while the levels of c‑myc, survivin and cyclin D1 were downregulated following treatment with CPT. In addition, CPT decreased the activities of signal transducer and activator of transcription 3 (STAT3) and several upstream regulatory signaling pathways after 24 h. However, CPT only inhibited the phosphorylation of STAT3 Tyr705 within 30 min, without marked effects on the phosphorylation of the other proteins. These results suggested that the inhibition of STAT3 activity by CPT was directly and independent of the upstream regulators in human pancreatic cancer. The present study demonstrated that CPT exerts anticancer effects by inducing apoptosis and cell cycle arrest via inhibition of the STAT3 signaling pathway in human BxPC-3 cells.

Joint CPT and N resonance in compact atomic time standards

NASA Astrophysics Data System (ADS)

Crescimanno, Michael; Hohensee, Michael; Xiao, Yanhong; Phillips, David; Walsworth, Ron

2008-05-01

Currently development efforts towards small, low power atomic time standards use current-modulated VCSELs to generate phase-coherent optical sidebands that interrogate the hyperfine structure of alkali atoms such as rubidium. We describe and use a modified four-level quantum optics model to study the optimal operating regime of the joint CPT- and N-resonance clock. Resonant and non-resonant light shifts as well as modulation comb detuning effects play a key role in determining the optimal operating point of such clocks. We further show that our model is in good agreement with experimental tests performed using Rb-87 vapor cells.

Nationwide lithological interpretation of cone penetration tests using neural networks

NASA Astrophysics Data System (ADS)

van Maanen, Peter-Paul; Schokker, Jeroen; Harting, Ronald; de Bruijn, Renée

2017-04-01

The Geological Survey of the Netherlands (GSN) systematically produces 3D stochastic geological models of the Dutch subsurface. These voxel models are regarded essential in answering subsurface-related questions on, for example, aggregate resource potential, groundwater flow, land subsidence hazard and the planning and realization of large-scale infrastructural works. GeoTOP is the most recent and detailed generation of 3D voxel models. This model describes 3D stratigraphical and lithological variability up to a depth of 50 m using voxels of 100 × 100 × 0.5 m. Currently, visually described borehole samples are the primary input of these large-scale 3D geological models, both when modeling architecture and composition. Although tens of thousands of cone penetration tests (CPTs) are performed each year, mainly in the reconnaissance phase of construction activities, these data are hardly used as geological model input. There are many reasons why it is of interest to utilize CPT data for geological and lithological modeling of the Dutch subsurface, such as: 1) CPTs are more abundant than borehole descriptions, 2) CPTs are cheaper and easier to gather, and 3) CPT data are more quantitative and uniform than visual sample descriptions. This study uses CPTs and the lithological descriptions of associated nearby undisturbed drilling cores collected by the GSN to establish a nationwide reference dataset for physical and chemical properties of the shallow subsurface. The 167 CPT-core pairs were collected at 160 locations situated in the North, West and South of the Netherlands. These locations were chosen to cover the full extent of geological units and lithological composition in the upper 30 to 40 m of the subsurface in these areas. The distance between the CPT location and associated borehole is small, varying between 0 and 30 m, with an average of 6 m. For each 2 cm CPT interval the data was automatically annotated with the lithoclass from the associated core using a lithological classification script that is also used in GeoTOP to classify the visual sample descriptions. Based on this data a three-layer feedforward neural network was trained containing 5 different inputs: cone resistance, friction ratio, coordinates x and y, and interval depth z. Previous training attempts showed an increased performance when using additional inputs such as pore water pressure, but since these variables are not measured in the majority of CPTs, these were left out in the training procedure. The Newton conjugate-gradient algorithm was applied to train the network. 20-Fold cross-validation yielded 20 different trained nets and independent performance outcomes. Significant performance increase was found as compared to performances of conventional lithological classification charts. A similar neural network was then applied to new CPT data from a pilot area in the city of Rotterdam. This area has a limited number of visual sample descriptions and therefore, additional lithological information of the subsurface is desirable. The results of an evaluation of the neural network's outcomes in this area by geological experts are positive, which paves the way for future nationwide application of this method.

Evaluation of Mycology Laboratory Proficiency Testing

PubMed Central

Reilly, Andrew A.; Salkin, Ira F.; McGinnis, Michael R.; Gromadzki, Sally; Pasarell, Lester; Kemna, Maggi; Higgins, Nancy; Salfinger, Max

1999-01-01

Changes over the last decade in overt proficiency testing (OPT) regulations have been ostensibly directed at improving laboratory performance on patient samples. However, the overt (unblinded) format of the tests and regulatory penalties associated with incorrect values allow and encourage laboratorians to take extra precautions with OPT analytes. As a result OPT may measure optimal laboratory performance instead of the intended target of typical performance attained during routine patient testing. This study addresses this issue by evaluating medical mycology OPT and comparing its fungal specimen identification error rates to those obtained in a covert (blinded) proficiency testing (CPT) program. Identifications from 188 laboratories participating in the New York State mycology OPT from 1982 to 1994 were compared with the identifications of the same fungi recovered from patient specimens in 1989 and 1994 as part of the routine procedures of 88 of these laboratories. The consistency in the identification of OPT specimens was sufficient to make accurate predictions of OPT error rates. However, while the error rates in OPT and CPT were similar for Candida albicans, significantly higher error rates were found in CPT for Candida tropicalis, Candida glabrata, and other common pathogenic fungi. These differences may, in part, be due to OPT’s use of ideal organism representatives cultured under optimum growth conditions. This difference, as well as the organism-dependent error rate differences, reflects the limitations of OPT as a means of assessing the quality of routine laboratory performance in medical mycology. PMID:10364601

Threat affects risk preferences in movement decision making

PubMed Central

O'Brien, Megan K.; Ahmed, Alaa A.

2015-01-01

Emotional states such as sadness, anger, and threat have been shown to play a critical role in decision-making processes. Here we addressed the question of whether risk preferences are influenced by postural threat and whether this influence generalizes across motor tasks. We examined risk attitudes in the context of arm-reaching (ARM) and whole-body (WB) leaning movements, expecting that increased postural threat would lead to proportionally similar changes in risk-sensitivity for each motor task. Healthy young adults were shown a series of two-alternative forced-choice lotteries, where they were asked to choose between a riskier lottery and a safer lottery on each trial. Our lotteries consisted of different monetary rewards and target sizes. Subjects performed each choice task at ground level and atop an elevated platform. In the presence of this postural threat, increased physiological arousal was correlated with decreased movement variability. To determine risk-sensitivity, we quantified the frequency with which a subject chose the riskier lottery and fit lottery responses to a choice model based on cumulative prospect theory (CPT). Subjects exhibited idiosyncratic changes in risk-sensitivity between motor tasks and between elevations. However, we found that overweighting of small probabilities increased with postural threat in the WB task, indicating a more cautious, risk-averse strategy is ascribed to the possibility of a fall. Subjects were also more risk-seeking in the WB movements than in ARM at low elevation; this behavior does not seem to derive from consistent distortions in utility or probability representations but may be explained by subjects' inaccurate estimation of their own motor variability. Overall, our findings suggest that implicit threat can modify risk attitudes in the motor domain, and the threat may induce risk-aversion in salient movement tasks. PMID:26106311

Threat affects risk preferences in movement decision making.

PubMed

O'Brien, Megan K; Ahmed, Alaa A

2015-01-01

Emotional states such as sadness, anger, and threat have been shown to play a critical role in decision-making processes. Here we addressed the question of whether risk preferences are influenced by postural threat and whether this influence generalizes across motor tasks. We examined risk attitudes in the context of arm-reaching (ARM) and whole-body (WB) leaning movements, expecting that increased postural threat would lead to proportionally similar changes in risk-sensitivity for each motor task. Healthy young adults were shown a series of two-alternative forced-choice lotteries, where they were asked to choose between a riskier lottery and a safer lottery on each trial. Our lotteries consisted of different monetary rewards and target sizes. Subjects performed each choice task at ground level and atop an elevated platform. In the presence of this postural threat, increased physiological arousal was correlated with decreased movement variability. To determine risk-sensitivity, we quantified the frequency with which a subject chose the riskier lottery and fit lottery responses to a choice model based on cumulative prospect theory (CPT). Subjects exhibited idiosyncratic changes in risk-sensitivity between motor tasks and between elevations. However, we found that overweighting of small probabilities increased with postural threat in the WB task, indicating a more cautious, risk-averse strategy is ascribed to the possibility of a fall. Subjects were also more risk-seeking in the WB movements than in ARM at low elevation; this behavior does not seem to derive from consistent distortions in utility or probability representations but may be explained by subjects' inaccurate estimation of their own motor variability. Overall, our findings suggest that implicit threat can modify risk attitudes in the motor domain, and the threat may induce risk-aversion in salient movement tasks.

Evaluation of Alternatives for an Army Precision Landing System.

DTIC Science & Technology

1985-09-01

U FL - ! - Vv3- LN1.N V"VVu 𔄀V- - - UW Vr - V V 416 -60 ,.1 :0 4 - L DG6 -46. 0𔃺- Iii V34 0 c 0.- to C aIa a id4 C13 a ’hO. i 410 Id...USAAVNC CPT E. Veiga . Concepts and Studies Division CPT R. Wilson. Concepts Branch CPT R. Roberts. USAATCA Liaison CPT Flynn, Force Structures

Coenzyme Q10 plus Multivitamin Treatment Prevents Cisplatin Ototoxicity in Rats

PubMed Central

Astolfi, Laura; Simoni, Edi; Valente, Filippo; Ghiselli, Sara; Hatzopoulos, Stavros; Chicca, Milvia; Martini, Alessandro

2016-01-01

Cisplatin (Cpt) is known to induce a high level of oxidative stress, resulting in an increase of reactive oxygen species damaging the inner ear and causing hearing loss at high frequencies. Studies on animal models show that antioxidants may lower Cpt-induced ototoxicity. The aim of this study is to evaluate the ototoxic effects of two different protocols of Cpt administration in a Sprague-Dawley rat model, and to test in the same model the synergic protective effects of a solution of coenzyme Q10 terclatrate and Acuval 400®, a multivitamin supplement containing antioxidant agents and minerals (Acu-Qter). The Cpt was administered intraperitoneally in a single dose (14 mg/kg) or in three daily doses (4.6 mg/kg/day) to rats orally treated or untreated with Acu-Qter for 5 days. The auditory function was assessed by measuring auditory brainstem responses from 2 to 32 kHz at day 0 and 5 days after treatment. Similar hearing threshold and body weight alterations were observed in both Cpt administration protocols, but mortality reduced to zero when Cpt was administered in three daily doses. The Acu-Qter treatment was able to prevent and completely neutralize ototoxicity in rats treated with three daily Cpt doses, supporting the synergic protective effects of coenzyme Q terclatrate and Acuval 400® against Cpt-induced oxidative stress. The administration protocol involving three Cpt doses is more similar to common human chemotherapy protocols, therefore it appears more useful for long-term preclinical studies on ototoxicity prevention. PMID:27632426

Evaluation of the validity of the Psychology Experiment Building Language tests of vigilance, auditory memory, and decision making.

PubMed

Piper, Brian; Mueller, Shane T; Talebzadeh, Sara; Ki, Min Jung

2016-01-01

Background. The Psychology Experimental Building Language (PEBL) test battery (http://pebl.sourceforge.net/) is a popular application for neurobehavioral investigations. This study evaluated the correspondence between the PEBL and the non-PEBL versions of four executive function tests. Methods. In one cohort, young-adults (N = 44) completed both the Conner's Continuous Performance Test (CCPT) and the PEBL CPT (PCPT) with the order counter-balanced. In a second cohort, participants (N = 47) completed a non-computerized (Wechsler) and a computerized (PEBL) Digit Span (WDS or PDS) both Forward and Backward. Participants also completed the Psychological Assessment Resources or the PEBL versions of the Iowa Gambling Task (PARIGT or PEBLIGT). Results. The between-test correlations were moderately high (reaction time r = 0.78, omission errors r = 0.65, commission errors r = 0.66) on the CPT. DS Forward was significantly greater than DS Backward on the WDS (p < .0005) and the PDS (p < .0005). The total WDS score was moderately correlated with the PDS (r = 0.56). The PARIGT and the PEBLIGTs showed a very similar pattern for response times across blocks, development of preference for Advantageous over Disadvantageous Decks, and Deck selections. However, the amount of money earned (score-loan) was significantly higher in the PEBLIGT during the last Block. Conclusions. These findings are broadly supportive of the criterion validity of the PEBL measures of sustained attention, short-term memory, and decision making. Select differences between workalike versions of the same test highlight how detailed aspects of implementation may have more important consequences for computerized testing than has been previously acknowledged.

A 12-week DBPC dose-finding study with sublingual monomeric allergoid tablets in house dust mite-allergic patients.

PubMed

Hüser, C; Dieterich, P; Singh, J; Shah-Hosseini, K; Allekotte, S; Lehmacher, W; Compalati, E; Mösges, R

2017-01-01

In sublingual immunotherapy, optimal doses are a key factor for therapeutic outcomes. The aim of this study with tablets containing carbamylated monomeric house dust mite allergoids was to determine the most effective and safe dose. In this double-blind, placebo-controlled dose-finding study, 131 patients with house dust mite-induced allergic rhinoconjunctivitis were randomized to 12-week treatments with 300 UA/day, 1000 UA/day, 2000 UA/day, 3000 UA/day or placebo. Conjunctival provocation tests (CPT) were performed before, during and after treatment. The change in mean allergic severity (primary endpoint), calculated from the severity of the CPT reaction, and the proportion of patients with an improved CPT threshold (secondary endpoint) determined the treatment effect. The mean allergic severity decreased in all groups, including the placebo group. It was lower in all active treatment groups (300 UA/day: 0.14, 1000 UA/day: 0.15, 2000 UA/day: 0.10, 3000 UA/day: 0.15) than in the placebo group (0.30). However, this difference was not statistically significant (P < 0.1). The percentage of patients with an improved CPT threshold was higher in the active treatment groups (300 UA/day: 73.9%; 1000 UA/day: 76.0%; 2000 UA/day: 88.5%; 3000 UA/day: 76.0%) than in the placebo group (64.3%). The difference between placebo and 2000 UA/day was statistically significant (P = 0.04). In 13 (10%) exposed patients, a total of 20 treatment-related adverse events of mild severity were observed. The 12-week daily treatment using 2000 UA/day monomeric allergoid sublingual tablets is well tolerated and reduces the CPT reaction in house dust mite-allergic patients. © 2016 The Authors. Allergy Published by John Wiley & Sons Ltd.

Proteomic and Metabolic Analyses of S49 Lymphoma Cells Reveal Novel Regulation of Mitochondria by cAMP and Protein Kinase A*

PubMed Central

Wilderman, Andrea; Guo, Yurong; Divakaruni, Ajit S.; Perkins, Guy; Zhang, Lingzhi; Murphy, Anne N.; Taylor, Susan S.; Insel, Paul A.

2015-01-01

Cyclic AMP (cAMP), acting via protein kinase A (PKA), regulates many cellular responses, but the role of mitochondria in such responses is poorly understood. To define such roles, we used quantitative proteomic analysis of mitochondria-enriched fractions and performed functional and morphologic studies of wild-type (WT) and kin− (PKA-null) murine S49 lymphoma cells. Basally, 75 proteins significantly differed in abundance between WT and kin− S49 cells. WT, but not kin−, S49 cells incubated with the cAMP analog 8-(4-chlorophenylthio)adenosine cAMP (CPT-cAMP) for 16 h have (a) increased expression of mitochondria-related genes and proteins, including ones in pathways of branched-chain amino acid and fatty acid metabolism and (b) increased maximal capacity of respiration on branched-chain keto acids and fatty acids. CPT-cAMP also regulates the cellular rate of ATP-utilization, as the rates of both ATP-linked respiration and proton efflux are decreased in WT but not kin− cells. CPT-cAMP protected WT S49 cells from glucose or glutamine deprivation, In contrast, CPT-cAMP did not protect kin− cells or WT cells treated with the PKA inhibitor H89 from glutamine deprivation. Under basal conditions, the mitochondrial structure of WT and kin− S49 cells is similar. Treatment with CPT-cAMP produced apoptotic changes (i.e. decreased mitochondrial density and size and loss of cristae) in WT, but not kin− cells. Together, these findings show that cAMP acts via PKA to regulate multiple aspects of mitochondrial function and structure. Mitochondrial perturbation thus likely contributes to cAMP/PKA-mediated cellular responses. PMID:26203188

Prognostic scores in cirrhotic patients admitted to a gastroenterology intensive care unit.

PubMed

Freire, Paulo; Romãozinho, José M; Amaro, Pedro; Ferreira, Manuela; Sofia, Carlos

2011-04-01

prognostic scores have been validated in cirrhotic patients admitted to general Intensive Care Units. No assessment of these scores was performed in cirrhotics admitted to specialized Gastroenterology Intensive Care Units (GICUs). to assess the prognostic accuracy of Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA), Model for End-stage Liver Disease (MELD) and Child-Pugh-Turcotte (CPT) in predicting GICU mortality in cirrhotic patients. the study involved 124 consecutive cirrhotic admissions to a GICU. Clinical data, prognostic scores and mortality were recorded. Discrimination was evaluated with area under receiver operating characteristic curves (AUC). Calibration was assessed with Hosmer-Lemeshow goodness-of-fit test. GICU mortality was 9.7%. Mean APACHE II, SAPS II, SOFA, MELD and CPT scores for survivors (13.6, 25.4, 3.5,18.0 and 8.6, respectively) were found to be significantly lower than those of non-survivors (22.0, 47.5, 10.1, 30.7 and 12.5,respectively) (p < 0.001). All the prognostic systems showed good discrimination, with AUC = 0.860, 0.911, 0.868, 0.897 and 0.914 for APACHE II, SAPS II, SOFA, MELD and CPT, respectively. Similarly, APACHE II, SAPS II, SOFA, MELD and CPT scores achieved good calibration, with p = 0.146, 0.120, 0.686,0.267 and 0.120, respectively. The overall correctness of prediction was 81.9%, 86.1%, 93.3%, 90.7% and 87.7% for the APA-CHE II, SAPS II, SOFA, MELD and CPT scores, respectively. in cirrhotics admitted to a GICU, all the tested scores have good prognostic accuracy, with SOFA and MELD showing the greatest overall correctness of prediction.

Recent Results on T and CP Violation at BABAR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perez Perez, Alejandro

2015-02-06

CP-violation (CPV) and Time-reversal violation (TRV) are intimately related through the CPT theorem: if one of these discrete symmetries is violated the other one has to be violated in such a way to conserve CPT. Although CPV in the B 0B 0-bar system has been established by the B-factories, implying indirectly TRV, there is still no direct evidence of TRV. We report on the observation of TRV in the B-meson system performed with a dataset of 468 × 10 6 BB-bar pairs produced in Υ(4S) decays collected by the BABAR detector at the PEP-II asymmetric-energy e +e - collider atmore » the SLAC National Accelerator Laboratory. We also report on other CPV measurements recently performed on the B-meson system« less

Tipin functions in the protection against topoisomerase I inhibitor.

PubMed

Hosono, Yoshifumi; Abe, Takuya; Higuchi, Masato; Kajii, Kosa; Sakuraba, Shuichi; Tada, Shusuke; Enomoto, Takemi; Seki, Masayuki

2014-04-18

The replication fork temporarily stalls when encountering an obstacle on the DNA, and replication resumes after the barrier is removed. Simultaneously, activation of the replication checkpoint delays the progression of S phase and inhibits late origin firing. Camptothecin (CPT), a topoisomerase I (Top1) inhibitor, acts as a DNA replication barrier by inducing the covalent retention of Top1 on DNA. The Timeless-Tipin complex, a component of the replication fork machinery, plays a role in replication checkpoint activation and stabilization of the replication fork. However, the role of the Timeless-Tipin complex in overcoming the CPT-induced replication block remains elusive. Here, we generated viable TIPIN gene knock-out (KO) DT40 cells showing delayed S phase progression and increased cell death. TIPIN KO cells were hypersensitive to CPT. However, homologous recombination and replication checkpoint were activated normally, whereas DNA synthesis activity was markedly decreased in CPT-treated TIPIN KO cells. Proteasome-dependent degradation of chromatin-bound Top1 was induced in TIPIN KO cells upon CPT treatment, and pretreatment with aphidicolin, a DNA polymerase inhibitor, suppressed both CPT sensitivity and Top1 degradation. Taken together, our data indicate that replication forks formed without Tipin may collide at a high rate with Top1 retained on DNA by CPT treatment, leading to CPT hypersensitivity and Top1 degradation in TIPIN KO cells.

Co-overexpression of geraniol-10-hydroxylase and strictosidine synthase improves anti-cancer drug camptothecin accumulation in Ophiorrhiza pumila

PubMed Central

Cui, Lijie; Ni, Xiaoling; Ji, Qian; Teng, Xiaojuan; Yang, Yanru; Wu, Chao; Zekria, David; Zhang, Dasheng; Kai, Guoyin

2015-01-01

Camptothecin (CPT) belongs to a group of monoterpenoidindole alkaloids (TIAs) and its derivatives such as irinothecan and topothecan have been widely used worldwide for the treatment of cancer, giving rise to rapidly increasing market demands. Genes from Catharanthus roseus encoding strictosidine synthase (STR) and geraniol 10-hydroxylase (G10H), were separately and simultaneously introduced into Ophiorrhiza pumila hairy roots. Overexpression of individual G10H (G lines) significantly improved CPT production with respect to non-transgenic hairy root cultures (NC line) and single STR overexpressing lines (S lines), indicating that G10H plays a more important role in stimulating CPT accumulation than STR in O. pumila. Furthermore, co-overexpression of G10H and STR genes (SG Lines) caused a 56% increase on the yields of CPT compared to NC line and single gene transgenic lines, showed that simultaneous introduction of G10H and STR can produce a synergistic effect on CPT biosynthesis in O. pumila. The MTT assay results indicated that CPT extracted from different lines showed similar anti-tumor activity, suggesting that transgenic O. pumila hairy root lines could be an alternative approach to obtain CPT. To our knowledge, this is the first report on the enhancement of CPT production in O. pumila employing a metabolic engineering strategy. PMID:25648209

Attention-based classification pattern, a research domain criteria framework, in youths with bipolar disorder and attention-deficit/hyperactivity disorder.

PubMed

Kleinman, Ana; Caetano, Sheila Cavalcante; Brentani, Helena; Rocca, Cristiana Castanho de Almeida; dos Santos, Bernardo; Andrade, Enio Roberto; Zeni, Cristian Patrick; Tramontina, Silzá; Rohde, Luis Augusto Paim; Lafer, Beny

2015-03-01

The National Institute of Mental Health has initiated the Research Domain Criteria (RDoC) project. Instead of using disorder categories as the basis for grouping individuals, the RDoC suggests finding relevant dimensions that can cut across traditional disorders. Our aim was to use the RDoC's framework to study patterns of attention deficit based on results of Conners' Continuous Performance Test (CPT II) in youths diagnosed with bipolar disorder (BD), attention-deficit/hyperactivity disorder (ADHD), BD+ADHD and controls. Eighteen healthy controls, 23 patients with ADHD, 10 with BD and 33 BD+ADHD aged 12-17 years old were assessed. Pattern recognition was used to partition subjects into clusters based simultaneously on their performance in all CPT II variables. A Fisher's linear discriminant analysis was used to build a classifier. Using cluster analysis, the entire sample set was best clustered into two new groups, A and B, independently of the original diagnoses. ADHD and BD+ADHD were divided almost 50% in each subgroup, and there was an agglomeration of controls and BD in group B. Group A presented a greater impairment with higher means in all CPT II variables and lower Children's Global Assessment Scale. We found a high cross-validated classification accuracy for groups A and B: 95.2%. Variability of response time was the strongest CPT II measure in the discriminative pattern between groups A and B. Our classificatory exercise supports the concept behind new approaches, such as the RDoC framework, for child and adolescent psychiatry. Our approach was able to define clinical subgroups that could be used in future pathophysiological and treatment studies. © The Royal Australian and New Zealand College of Psychiatrists 2014.

Evaluation of cone penetration testing (CPT) for use with transportation projects.

DOT National Transportation Integrated Search

2011-04-01

Cone Penetration Testing (CPT) has many advantages as a means for subsurface investigation. CPT consists of pushing a steel : cone into the ground and recording the penetration resistance using sensors. Pore pressure, shear wave velocity and other : ...

Physicochemical characterization of camptothecin membrane binding properties and polymeric microsphere formulations

NASA Astrophysics Data System (ADS)

Selvi, Bilge

In an effort to design novel formulation strategies to optimize the antitumor activity of camptothecin (CPT), the physicochemical and membrane binding properties of the drug, were investigated by various techniques in acidic and physiological pH. The intrinsic solubility of the CPT-lactone free base was determined to be 3.44 muM and 5.11 muM at 22°C and 37°C, respectively. The equilibrium solubility of the drug was found to increase with increasing temperature and decreasing pH. The enhanced solubility of the drug at very low pH is attributed to the protonation of the nitrogen atom in the ring B and the increased solvency of the highly acidic media. The logarithmic value of the intrinsic partition coefficient P of the free base CPT-lactone form was estimated to be 1.65, characteristic of a molecule suitable for oral absorption. The association constants Kf of the drug for bilayers composed of the zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and the negatively-charged 1,2-dioleoyl-sn-glycero-3-phospho- rac-(1-glycerol) (DOPG) were studied at acidic pH by fluorescence anisotropy and determined to be 35.4 +/- 4.5 M-1 and 93.1 +/- 11.0 M-1 for DOPC and DOPG, respectively, indicating a tendency of CPT to preferentially bind to negatively charged membranes. The energy of activation for the hydrolysis of CPT at physiological pH was found to be 114.3 +/- 33.4 kj/mole. The calculated t½ of the reaction at pH 7.2 at temperatures 25°C and 10°C was found to be 0.07 days and 5.12 days, respectively, whereas the time required for 1% of CPT-lactone to hydrolyze to CPT-carboxylate (t99%) was determined to be 1.8 hours, thus offering enough time to safely handle CPT-lactone at low temperatures. The preformulation results indicated that at highly acidic media CPT is positively charged and exists at its stable lactone form of increased solubility and has a capacity to bind to negatively charged membranes. Taking advantage of the increased stability of CPT in acidic media CPT-loaded microspheres were prepared in a 10 N HCl-methylene chloride mixture using the H-series of poly(D,L-lactide-co-glycolide) (H-PLGA). The system was then compared with a standard microsphere formation method and the results were evaluated with respect to particle morphology and drug release profile. Rough surface of the particles were obtained from the preparation method where a 10 N HCl solution was used. The release pattern of CPT was biphasic comprising a first burst effect followed by zero order release for all the formulations. However, the release of the drug was slightly faster from the microspheres formed with the modified method compared to the standard. Until now clinical application of CPT has been highly restricted by the insolubility and instability of the drug in its active lactone form, resulting in less antitumor potency and poor bioavailability. The pH-dependent release of the CPT-loaded microspheres was also compared and faster initial release (burst phase) was found at neutral pH, whereas at low pH the release was zero order for all the formulations. The results indicate that the stabilization and sustained release of CPT from H-PLGA microspheres might reduce local toxicity while simultaneously prolonging efficiency, suggesting new perspectives in CPT chemotherapy.

Reduction of brain mitochondrial β-oxidation impairs complex I and V in chronic alcohol intake: the underlying mechanism for neurodegeneration.

PubMed

Haorah, James; Rump, Travis J; Xiong, Huangui

2013-01-01

Neuropathy and neurocognitive deficits are common among chronic alcohol users, which are believed to be associated with mitochondrial dysfunction in the brain. The specific type of brain mitochondrial respiratory chain complexes (mRCC) that are adversely affected by alcohol abuse has not been studied. Thus, we examined the alterations of mRCC in freshly isolated mitochondria from mice brain that were pair-fed the ethanol (4% v/v) and control liquid diets for 7-8 weeks. We observed that alcohol intake severely reduced the levels of complex I and V. A reduction in complex I was associated with a decrease in carnitine palmitoyltransferase 1 (cPT1) and cPT2 levels. The mitochondrial outer (cPT1) and inner (cPT2) membrane transporter enzymes are specialized in acylation of fatty acid from outer to inner membrane of mitochondria for ATP production. Thus, our results showed that alterations of cPT1 and cPT2 paralleled a decrease β-oxidation of palmitate and ATP production, suggesting that impairment of substrate entry step (complex I function) can cause a negative impact on ATP production (complex V function). Disruption of cPT1/cPT2 was accompanied by an increase in cytochrome C leakage, while reduction of complex I and V paralleled a decrease in depolarization of mitochondrial membrane potential (ΔΨ, monitored by JC-1 fluorescence) and ATP production in alcohol intake. We noted that acetyl-L-carnitine (ALC, a cofactor of cPT1 and cPT2) prevented the adverse effects of alcohol while coenzyme Q10 (CoQ10) was not very effective against alcohol insults. These results suggest that understanding the molecular, biochemical, and signaling mechanisms of the CNS mitochondrial β-oxidation such as ALC can mitigate alcohol related neurological disorders.

'I've got to get something out of it. And so do they': experiences of people with aphasia and university students participating in a communication partner training programme for healthcare professionals.

PubMed

Cameron, Ashley; Hudson, Kyla; Finch, Emma; Fleming, Jennifer; Lethlean, Jennifer; McPhail, Steven

2018-06-05

Communication partner training (CPT) has been used to support communication partners to interact successfully with people with aphasia (PWA). Through successful CPT interaction PWA's accessibility to healthcare is notably improved. The present study sought to build on prior studies by investigating the experiences of individuals with aphasia and healthcare providers to ascertain what they deemed to be beneficial from CPT and what could be refined or improved, dependent on the setting and skill set of those participating. To gain an understanding of the experiences of PWA involved in the provision of CPT to health professional (HP) students. Also to investigate the experiences of HP students who participated in the CPT programme. Eight PWA and 77 HP students who had completed a CPT programme participated in a focus group/semi-structured interview (PWA) and feedback session (HP students) moderated by two speech-language pathologists (SLPs). These sessions were recorded (audio and video), transcribed verbatim, including non-verbal communication, and analyzed using qualitative content analysis. Overall, the study sought to understand experiences of the training. Both the PWA and HP students reported positive experiences of CPT. PWA discussed their perception that CPT improved HPs and HP students' understanding and interactions conversing with them and emphasized the need for training and education for all health related professions. HP students enjoyed the opportunity to experience interacting with PWA, without being 'assessed' and felt it consolidated their learning based on lecture content. Inclusive and accessible healthcare is paramount to ensure the engagement of patients and providers. Based on the experiences and feedback of the participants in this current study, CPT offers a salient and practical training method with potential to improve practice. Participants perceived CPT to be beneficial and validated the need for the training to support PWA accessing healthcare. © 2018 Royal College of Speech and Language Therapists.

Cell-specific expression of tryptophan decarboxylase and 10-hydroxygeraniol oxidoreductase, key genes involved in camptothecin biosynthesis in Camptotheca acuminata Decne (Nyssaceae)

PubMed Central

2010-01-01

Background Camptotheca acuminata is a major natural source of the terpenoid indole alkaloid camptothecin (CPT). At present, little is known about the cellular distribution of the biosynthesis of CPT, which would be useful knowledge for developing new strategies and technologies for improving alkaloid production. Results The pattern of CPT accumulation was compared with the expression pattern of some genes involved in CPT biosynthesis in C. acuminata [i.e., Ca-TDC1 and Ca-TDC2 (encoding for tryptophan decarboxylase) and Ca-HGO (encoding for 10-hydroxygeraniol oxidoreductase)]. Both CPT accumulation and gene expression were investigated in plants at different degrees of development and in plantlets subjected to drought-stress. In all organs, CPT accumulation was detected in epidermal idioblasts, in some glandular trichomes, and in groups of idioblast cells localized in parenchyma tissues. Drought-stress caused an increase in CPT accumulation and in the number of glandular trichomes containing CPT, whereas no increase in epidermal or parenchymatous idioblasts was observed. In the leaf, Ca-TDC1 expression was detected in some epidermal cells and in groups of mesophyll cells but not in glandular trichomes; in the stem, it was observed in parenchyma cells of the vascular tissue; in the root, no expression was detected. Ca-TDC2 expression was observed exclusively in leaves of plantlets subjected to drought-stress, in the same sites described for Ca-TDC1. In the leaf, Ca-HGO was detected in all chlorenchyma cells; in the stem, it was observed in the same sites described for Ca-TDC1; in the root, no expression was detected. Conclusions The finding that the sites of CPT accumulation are not consistently the same as those in which the studied genes are expressed demonstrates an organ-to-organ and cell-to-cell translocation of CPT or its precursors. PMID:20403175

Cell-specific expression of tryptophan decarboxylase and 10-hydroxygeraniol oxidoreductase, key genes involved in camptothecin biosynthesis in Camptotheca acuminata Decne (Nyssaceae).

PubMed

Valletta, Alessio; Trainotti, Livio; Santamaria, Anna Rita; Pasqua, Gabriella

2010-04-19

Camptotheca acuminata is a major natural source of the terpenoid indole alkaloid camptothecin (CPT). At present, little is known about the cellular distribution of the biosynthesis of CPT, which would be useful knowledge for developing new strategies and technologies for improving alkaloid production. The pattern of CPT accumulation was compared with the expression pattern of some genes involved in CPT biosynthesis in C. acuminata [i.e., Ca-TDC1 and Ca-TDC2 (encoding for tryptophan decarboxylase) and Ca-HGO (encoding for 10-hydroxygeraniol oxidoreductase)]. Both CPT accumulation and gene expression were investigated in plants at different degrees of development and in plantlets subjected to drought-stress. In all organs, CPT accumulation was detected in epidermal idioblasts, in some glandular trichomes, and in groups of idioblast cells localized in parenchyma tissues. Drought-stress caused an increase in CPT accumulation and in the number of glandular trichomes containing CPT, whereas no increase in epidermal or parenchymatous idioblasts was observed. In the leaf, Ca-TDC1 expression was detected in some epidermal cells and in groups of mesophyll cells but not in glandular trichomes; in the stem, it was observed in parenchyma cells of the vascular tissue; in the root, no expression was detected. Ca-TDC2 expression was observed exclusively in leaves of plantlets subjected to drought-stress, in the same sites described for Ca-TDC1. In the leaf, Ca-HGO was detected in all chlorenchyma cells; in the stem, it was observed in the same sites described for Ca-TDC1; in the root, no expression was detected. The finding that the sites of CPT accumulation are not consistently the same as those in which the studied genes are expressed demonstrates an organ-to-organ and cell-to-cell translocation of CPT or its precursors.

Triterpenic acids-enriched fraction from Cyclocarya paliurus attenuates non-alcoholic fatty liver disease via improving oxidative stress and mitochondrial dysfunction.

PubMed

Zhao, Meng-Ge; Sheng, Xue-Ping; Huang, Ya-Ping; Wang, Yi-Ting; Jiang, Cui-Hua; Zhang, Jian; Yin, Zhi-Qi

2018-08-01

The effects of triterpenic acids-enriched fraction from Cyclocarya paliurus (CPT) on nonalcoholic fatty liver disease (NAFLD) were investigated using in vivo and in vitro models. In high fat diet-induced Wister rats, CPT significantly increased superoxide dismutase (SOD) activity and glutathione/oxidized glutathione (GSH/GSSG) ratio, reduced malondialdehyde (MDA) and protein carbonyl (PCO) levels. Moreover, CPT restored mitochondrial membrane potential dysfunction, decreased cytochrome P450 enzyme 2E1 (CYP2E1) activity, improved nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-mediated antioxidant enzyme heme oxygenase1 (HO-1) expression. In free fatty acids-induced HepG2 cells, CPT dramatically decreased ROS content, increased mitochondrial NADH dehydrogenase (Complex I) and mitochondrial cytochrome C oxidase (Complex IV) levels. Furthermore, CPT could upregulate HO-1, quinine oxidoreductase 1 (NQO1) expression, and increase Nrf2 translocation from cytoplasm-to-nucleus. The results indicated CPT could protect mitochondria function and improve oxidative stress by activating Nrf2. Therefore, it can be inferred that CPT may be a potential agent against NAFLD. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Persistence and amplitude of cigarette demand in relation to quit intentions and attempts

PubMed Central

O’Connor, Richard J.; Heckman, Bryan W.; Adkison, Sarah E.; Rees, Vaughan W.; Hatsukami, Dorothy K.; Bickel, Warren K.; Cummings, K. Michael

2016-01-01

INTRODUCTION The cigarette purchase task (CPT) is a method that can be used to assess relative value of cigarettes. Based on cigarettes purchased across a price range, five derived metrics (Omax, Pmax, breakpoint, intensity, elasticity) can assess cigarette demand. A study with adolescent smokers found that these could be reduced to two latent factors: Persistence (price insensitivity) and Amplitude (volumetric consumption). We sought to replicate this structure with adult smokers, and examine how these variables relate to cessation efforts. METHOD Web-based survey conducted in 2014 among adult (18+) current daily cigarette smokers (N=1194). Participants completed the CPT, Fagerstrom Test for Nicotine Dependence (FTND), reported past-year quit attempts, and future quit intentions. We included published scales assessing perceived prevalence of smoking, social reactivity, smoker identity, and risk perception. RESULTS Our analysis supported two latent variables, Persistence and Amplitude, which correlated positively with FTND. Persistence correlated with several psychosocial factors, and was higher among those intending to quit very soon, but did not vary by number of past-year quit attempts. Amplitude differed across quit attempts and intention (p’s <.001), and in multivariable models was significantly associated with lower 30-day quit intention [OR=0.76, p=.001]. CONCLUSIONS Persistence and Amplitude factors characterized CPT data in adults, discriminated known groups (e.g., smokers by intentions to quit), and were positively associated with nicotine dependence. Factor scores also appear to relate to certain psychosocial factors, such as smoker identity and perceptions of risk. Future research should examine the predictive validity of these constructs. PMID:27048156

Persistence and amplitude of cigarette demand in relation to quit intentions and attempts.

PubMed

O'Connor, Richard J; Heckman, Bryan W; Adkison, Sarah E; Rees, Vaughan W; Hatsukami, Dorothy K; Bickel, Warren K; Cummings, K Michael

2016-06-01

The cigarette purchase task (CPT) is a method that can be used to assess the relative value of cigarettes. Based on cigarettes purchased across a price range, five derived metrics (Omax, Pmax, breakpoint, intensity, and elasticity) can assess cigarette demand. A study with adolescent smokers found that these could be reduced to two latent factors: persistence (price insensitivity) and amplitude (volumetric consumption). We sought to replicate this structure with adult smokers and examine how these variables relate to cessation efforts. Web-based survey conducted in 2014 among adult (18 years and above) current daily cigarette smokers (N = 1194). Participants completed the CPT, Fagerstrom Test for Nicotine Dependence (FTND), reported past-year quit attempts, and future quit intentions. We included published scales assessing perceived prevalence of smoking, social reactivity, smoker identity, and risk perception. Our analysis supported two latent variables, persistence and amplitude, which correlated positively with FTND. Persistence was correlated with several psychosocial factors and was higher among those intending to quit very soon, but did not vary by number of past-year quit attempts. Amplitude differed across quit attempts and intention (p < 0.001) and, in multivariable models, was significantly associated with lower 30-day quit intention (OR = 0.76, p = 0.001). Persistence and amplitude factors characterized CPT data in adults, discriminated known groups (e.g., smokers by intentions to quit), and were positively associated with nicotine dependence. Factor scores also appear to relate to certain psychosocial factors, such as smoker identity and perceptions of risk. Future research should examine the predictive validity of these constructs.

Association between Urine Phthalate Levels and Poor Attentional Performance in Children with Attention-Deficit Hyperactivity Disorder with Evidence of Dopamine Gene-Phthalate Interaction

PubMed Central

Park, Subin; Kim, Bung-Nyun; Cho, Soo-Churl; Kim, Yeni; Kim, Jae-Won; Lee, Ju-Young; Hong, Soon-Beom; Shin, Min-Sup; Yoo, Hee Jeong; Im, Hosub; Cheong, Jae Hoon; Han, Doug Hyun

2014-01-01

Although there is some evidence supporting the existence of an association between prenatal maternal or postnatal child’s urine phthalate metabolite concentrations and poor attentional performances, the interaction between urine phthalate metabolite levels and genetic variation for neuropsychological deficit of attention-deficit hyperactivity disorder (ADHD) has not been examined. The aim of this study was to determine whether phthalate metabolites in urine are associated with poor neuropsychological performance in children with ADHD, and whether such association is affected by genotype-phthalate interaction. A cross-sectional examination of urine phthalate metabolite concentrations and the continuous performance test (CPT) were performed in 179 Korean children with ADHD recruited from department of psychiatry of university hospital. Correlations between urine phthalate metabolite concentrations and the CPT scores were investigated, and the interaction of phthalate metabolite levels with the selected polymorphisms at major candidate genes for ADHD, namely dopamine receptor D4 (DRD4), dopamine transporter, α-2A-adrenergic receptor, and norepinephrine transporter genes. For the subjects with the DRD4 4/4 genotype, there were significant associations of the urine phthalate metabolite concentrations with the number of omission errors, the number of commission errors, and the response time variability scores on the CPT. However, for the subjects without the DRD4 4/4 genotype, no significant associations were found. The results of this study suggest a possible association between phthalate metabolite concentrations and poor attentional performances of ADHD as well as a genetic influence on this association. Further prospective and epigenetic studies are needed to investigate causality and pathophysiological mechanisms. PMID:24978879

Channeled polarimetric technique for the measurement of spectral dependence of linearly Stokes parameters

NASA Astrophysics Data System (ADS)

Quan, Naicheng; Zhang, Chunmin; Mu, Tingkui; Li, Qiwei

2018-05-01

The principle and experimental demonstration of a method based on channeled polarimetric technique (CPT) to measure spectrally resolved linearly Stokes parameters (SRLS) is presented. By replacing front retarder with an achromatic quarter wave-plate of CPT, the linearly SRLS can be measured simultaneously. It also retains the advantages of static and compact of CPT. Besides, comparing with CPT, it can reduce the RMS error by nearly a factor of 2-5 for the individual linear Stokes parameters.

Characteristics of multiple tropopauses in the tropics

NASA Astrophysics Data System (ADS)

Mehta, Sanjay Kumar; Ratnam Madineni, Venkat; Krishna Murthy, B. V.

The characteristics of multiple tropopauses (MTs) in the tropics are studied using radiosonde data from 5 stations (Truk,Rochambeau, Singapore, Seychelles and Darwin) in the tropical belt during 1999 to 2008 and COSMIC GPS RO data during 2006-2008. In this study we emphasized the limitations of the WMO criteria for identifying the MTs and evolved an alternative criterion to effectively delineate MTs over tropical region. The current method is based on cold point tropopause (CPT) and points of inflections in the temperature profile rather than lapse rate as in WMO criteria. The points of inflection can occur both below and above the CPT. The one which occurs below the CPT is designated as the lower tropopause (LT) and those occurring above the CPT as second tropopause (ST) and third tropopause (TT) according to their heights of occurrence with CPT as the first tropopause. The percentage occurrences (25-50) of MTs are observed to be higher using the current method than by the WMO criteria (10-30). There is significant seasonal variation in the LT, CPT and ST temperatures (heights) with lower (higher) values occurring in the Northern Hemisphere winter. While the CPT temperatures are lowest at the equator the CPT heights are not highest at the equator. The occurrences of MTs are higher over equator and decrease away towards higher latitudes in the tropics. Longitudinal variation of the MTs is observed with relatively high occurrences during NH summer season over placeIndian Ocean. The equatorial minimum in the CPT temperature is broader and colder in the eastern hemisphere than the western hemisphere It is found that MTs can either occur on consecutive days in groups or on isolated days. The plausible causative mechanisms will be presented in the conference.

Activation of a camptothecin prodrug by specific carboxylesterases as predicted by quantitative structure-activity relationship and molecular docking studies.

PubMed

Yoon, Kyoung Jin P; Krull, Erik J; Morton, Christopher L; Bornmann, William G; Lee, Richard E; Potter, Philip M; Danks, Mary K

2003-11-01

7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (irinotecan, CPT-11) is a camptothecin prodrug that is metabolized by carboxylesterases (CE) to the active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38), a topoisomerase I inhibitor. CPT-11 has shown encouraging antitumor activity against a broad spectrum of tumor types in early clinical trials, but hematopoietic and gastrointestinal toxicity limit its administration. To increase the therapeutic index of CPT-11 and to develop other prodrug analogues for enzyme/prodrug gene therapy applications, our laboratories propose to develop camptothecin prodrugs that will be activated by specific CEs. Specific analogues might then be predicted to be activated, for example, predominantly by human liver CE(hCE1), by human intestinal CE (hiCE), or in gene therapy approaches using a rabbit liver CE (rCE). This study describes a molecular modeling approach to relate the structure of rCE-activated camptothecin prodrugs with their biological activation. Comparative molecular field analysis, comparative molecular similarity index analysis, and docking studies were used to predict the biological activity of a 4-benzylpiperazine derivative of CPT-11 [7-ethyl-10-[4-(1-benzyl)-1-piperazino]carbonyloxycamptothecin (BP-CPT)] in U373MG glioma cell lines transfected with plasmids encoding rCE or hiCE. BP-CPT has been reported to be activated more efficiently than CPT-11 by a rat serum esterase activity; however, three-dimensional quantitative structure-activity relationship studies predicted that rCE would activate BP-CPT less efficiently than CPT-11. This was confirmed by both growth inhibition experiments and kinetic studies. The method is being used to design camptothecin prodrugs predicted to be activated by specific CEs.

Nutritional modulation of antitumor efficacy and diarrhea toxicity related to irinotecan chemotherapy in rats bearing the ward colon tumor.

PubMed

Xue, Hongyu; Sawyer, Michael B; Field, Catherine J; Dieleman, Levinus A; Baracos, Vickie E

2007-12-01

To evaluate and compare the influence of dietary elements on cancer progression, chemotherapy efficacy, and toxicity, particularly severe, late-onset diarrhea related to irinotecan (CPT-11) treatment. We used laboratory rats fed a standardized basal diet, Ward colon tumor, and CPT-11 therapy for the study of CPT-11-induced diarrhea. Dietary interventions were selected from nutrients already established to modify other forms of colitis and which have been hypothesized to mitigate chemotherapy-induced gastrointestinal injury (glutamine, n-3 fatty acids, prebiotic oligosaccharides). Animals adapted to test diets were treated with CPT-11 at the maximum tolerated dose (125 mg/kg x 3 days) and diarrhea was followed continuously for 1 week. The inclusion of n-3 fatty acids in the diet (5%, w/w of total fat) suppressed tumor growth and enhanced CPT-11's efficacy; this treatment did not affect the incidence or severity of diarrhea. By contrast, oral glutamine bolus (0.75 g/kg) administered prior to each CPT-11 treatment reduced the incidence of severe diarrhea (34.1 +/- 4.7% versus 53.8 +/- 4.2%, P < 0.005) and decreased the area under the curve of diarrhea score (16.5 +/- 1.0 versus 18.8 +/- 0.5, P < 0.05). Identical results were obtained with i.v. bolus glutamine administration. Glutamine treatment did not alter CPT-11's antitumor efficacy. The addition of prebiotic oligosaccharides to the diet (8%, w/w of diet) did not mitigate the severity of diarrhea, and it raised the activity of beta-glucuronidase in cecal contents, a key bacterial enzyme mediating CPT-11-related intestinal toxicity. Our experiments suggest that glutamine and n-3 fatty acids might be potentially useful adjuncts to CPT-11 treatment.

Differential epigenetic and transcriptional response of the skeletal muscle carnitine palmitoyltransferase 1B (CPT1B) gene to lipid exposure with obesity

PubMed Central

Maples, Jill M.; Brault, Jeffrey J.; Witczak, Carol A.; Park, Sanghee; Hubal, Monica J.; Weber, Todd M.; Houmard, Joseph A.

2015-01-01

The ability to increase fatty acid oxidation (FAO) in response to dietary lipid is impaired in the skeletal muscle of obese individuals, which is associated with a failure to coordinately upregulate genes involved with FAO. While the molecular mechanisms contributing to this metabolic inflexibility are not evident, a possible candidate is carnitine palmitoyltransferase-1B (CPT1B), which is a rate-limiting step in FAO. The present study was undertaken to determine if the differential response of skeletal muscle CPT1B gene transcription to lipid between lean and severely obese subjects is linked to epigenetic modifications (DNA methylation and histone acetylation) that impact transcriptional activation. In primary human skeletal muscle cultures the expression of CPT1B was blunted in severely obese women compared with their lean counterparts in response to lipid, which was accompanied by changes in CpG methylation, H3/H4 histone acetylation, and peroxisome proliferator-activated receptor-δ and hepatocyte nuclear factor 4α transcription factor occupancy at the CPT1B promoter. Methylation of specific CpG sites in the CPT1B promoter that correlated with CPT1B transcript level blocked the binding of the transcription factor upstream stimulatory factor, suggesting a potential causal mechanism. These findings indicate that epigenetic modifications may play important roles in the regulation of CPT1B in response to a physiologically relevant lipid mixture in human skeletal muscle, a major site of fatty acid catabolism, and that differential DNA methylation may underlie the depressed expression of CPT1B in response to lipid, contributing to the metabolic inflexibility associated with severe obesity. PMID:26058865

The anterior component of occlusal force revisited: direct measurement and theoretical considerations.

PubMed

Al Qassar, Sarmad S Salih; Mavragani, Maria; Psarras, Vasilis; Halazonetis, Demetrios J

2016-04-01

The anterior component of occlusal force (ACF), considered to result from the mesial inclination of teeth relative to the occlusal plane, has been estimated by indirectly measuring contact point tightness (CPT) through interproximal insertion of metal strips. ACF has been observed concurrently with a posterior component, whose theoretical origin is difficult to explain. Evaluate ACF by measuring CPT directly, and integrate current data to propose a theoretical basis for ACF. The sample comprised 14 females (age: 22.3±2.8) and 16 males (age: 20.8±2.5). Our device consisted of two force sensors: one for measuring maximum bite force (MBF) (overall thickness: 4mm), and one for measuring CPT directly (0.2mm thick), inserted between the lower first molar and second premolar. ACF was computed as the difference in CPT between the biting (at 75 per cent of MBF) and non-biting conditions. Averages of MBF, CPT, and ACF were 666.67 [standard deviation (SD): 36.06], 6.74 (SD: 1.17), and 20.59 (SD: 4.60) N, respectively. ACF, CPT, and MBF were higher in males by approximately 28, 18 and 7 per cent, respectively. A positive correlation was observed between ACF and MBF (R (2): 0.64). CPT was also significantly correlated to MBF (R (2): 0.40). Biomechanical analysis indicates that previously offered explanations do not unriddle the concurrent increase of CPT at anterior and posterior contact points. ACF was related to bite force by a logarithmic model. We speculate that CPT increases during biting through a combination of mesial tipping of teeth and mandibular bending. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Root coverage using acellular dermal matrix and comparing a coronally positioned tunnel with and without platelet-rich plasma: a pilot study in humans.

PubMed

Shepherd, Neal; Greenwell, Henry; Hill, Margaret; Vidal, Ricardo; Scheetz, James P

2009-03-01

The primary aim of this randomized, controlled, blinded clinical pilot study was to compare the percentage of recession defect coverage obtained with a coronally positioned tunnel (CPT) plus an acellular dermal matrix allograft (ADM) to that of a CPT plus ADM and platelet-rich plasma (CPT/PRP) 4 months post-surgically. Eighteen patients with Miller Class I or II recession >or=3 mm at one site were treated and followed for 4 months. Nine patients received a CPT plus ADM and were considered the positive control group. The test group consisted of nine patients treated with a CPT plus ADM and PRP. Patients were randomly selected by a coin toss to receive the test or positive control treatment. The mean recession at the initial examination for the CPT group was 3.6 +/- 1.0 mm, which was reduced to 1.0 +/- 1.0 mm at the 4-month examination for a gain of 2.6 +/- 1.5 mm or 70% defect coverage (P <0.05). The mean recession at the initial examination for the CPT/PRP group was 3.3 +/- 0.7 mm, which was reduced to 0.4 +/- 0.7 mm at the 4-month examination for a gain of 2.9 +/- 0.5 mm or 90% defect coverage (P <0.05). There were no statistically significant differences between the groups (P >0.05). The CPT plus ADM and PRP produced defect coverage of 90%, whereas the CPT with ADM produced only 70% defect coverage. This difference was not statistically significant, but it may be clinically significant.

Distinct CPT-induced deaths in lung cancer cells caused by clathrin-mediated internalization of CP micelles

NASA Astrophysics Data System (ADS)

Liu, Yu-Sheng; Cheng, Ru-You; Lo, Yu-Lun; Hsu, Chin; Chen, Su-Hwei; Chiu, Chien-Chih; Wang, Li-Fang

2016-02-01

We previously synthesized a chondroitin sulfate-graft-poly(ε-caprolactone) copolymer (H-CP) with a high content of poly(ε-caprolactone) (18.7 mol%), which self-assembled in water into a rod-like micelle to encapsulate hydrophobic camptothecin (CPT) in the core (micelle/CPT) for tumor-targeted drug delivery. As a result of the recognition of the micelle by CD44, the micelle/CPT entered CRL-5802 cells efficiently and released CPT efficaciously, resulting in higher tumor suppression than commercial CPT-11. In this study, H1299 cells were found to have a higher CD44 expression than CRL-5802 cells. However, the lower CD44-expressing CRL-5802 cells had a higher percentage of cell death and higher cellular uptake of the micelle/CPT than the higher CD44-expressing H1299 cells. Examination of the internalization pathway of the micelle/CPT in the presence of different endocytic chemical inhibitors showed that the CRL-5802 cells involved clathrin-mediated endocytosis, which was not found in the H1299 cells. Analysis of the cell cycle of the two cell lines exposed to the micelle/CPT revealed that the CRL-5802 cells arrested mainly in the S phase and the H1299 cells arrested mainly in the G2-M phase. A consistent result was also found in the evaluation of γ-H2AX expression, which was about three-fold higher in the CRL-5802 cells than in the H1299 cells. A near-infrared dye, IR780, was encapsulated into the micelle to observe the in vivo biodistribution of the micelle/IR780 in tumor-bearing mice. The CRL-5802 tumor showed a higher fluorescence intensity than the H1299 tumor at any tracing time after 1 h. Thus we tentatively concluded that CRL-5802 cells utilized the clathrin-mediated internalization pathway and arrested in the S phase on exposure to the micelle/CPT; all are possible reasons for the better therapeutic outcome in CRL-5802 cells than in H1299 cells.We previously synthesized a chondroitin sulfate-graft-poly(ε-caprolactone) copolymer (H-CP) with a high content of poly(ε-caprolactone) (18.7 mol%), which self-assembled in water into a rod-like micelle to encapsulate hydrophobic camptothecin (CPT) in the core (micelle/CPT) for tumor-targeted drug delivery. As a result of the recognition of the micelle by CD44, the micelle/CPT entered CRL-5802 cells efficiently and released CPT efficaciously, resulting in higher tumor suppression than commercial CPT-11. In this study, H1299 cells were found to have a higher CD44 expression than CRL-5802 cells. However, the lower CD44-expressing CRL-5802 cells had a higher percentage of cell death and higher cellular uptake of the micelle/CPT than the higher CD44-expressing H1299 cells. Examination of the internalization pathway of the micelle/CPT in the presence of different endocytic chemical inhibitors showed that the CRL-5802 cells involved clathrin-mediated endocytosis, which was not found in the H1299 cells. Analysis of the cell cycle of the two cell lines exposed to the micelle/CPT revealed that the CRL-5802 cells arrested mainly in the S phase and the H1299 cells arrested mainly in the G2-M phase. A consistent result was also found in the evaluation of γ-H2AX expression, which was about three-fold higher in the CRL-5802 cells than in the H1299 cells. A near-infrared dye, IR780, was encapsulated into the micelle to observe the in vivo biodistribution of the micelle/IR780 in tumor-bearing mice. The CRL-5802 tumor showed a higher fluorescence intensity than the H1299 tumor at any tracing time after 1 h. Thus we tentatively concluded that CRL-5802 cells utilized the clathrin-mediated internalization pathway and arrested in the S phase on exposure to the micelle/CPT; all are possible reasons for the better therapeutic outcome in CRL-5802 cells than in H1299 cells. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08345a

Art Therapy and Cognitive Processing Therapy for Combat-Related PTSD: A Randomized Controlled Trial

PubMed Central

Campbell, Melissa; Decker, Kathleen P.; Kruk, Kerry; Deaver, Sarah P.

2018-01-01

This randomized controlled trial was designed to determine if art therapy in conjunction with Cognitive Processing Therapy (CPT) was more effective for reducing symptoms of combat posttraumatic stress disorder (PTSD) than CPT alone. Veterans (N = 11) were randomized to receive either individual CPT, or individual CPT in conjunction with individual art therapy. PTSD Checklist–Military Version and Beck Depression Inventory–II scores improved with treatment in both groups with no significant difference in improvement between the experimental and control groups. Art therapy in conjunction with CPT was found to improve trauma processing and veterans considered it to be an important part of their treatment as it provided healthy distancing, enhanced trauma recall, and increased access to emotions. PMID:29332989

Exploring Ramsey-coherent population trapping atomic clock realized with pulsed microwave modulated laser

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Jing; Yun, Peter; Tian, Yuan

2014-03-07

A scheme for a Ramsey-coherent population trapping (CPT) atomic clock that eliminates the acousto-optic modulator (AOM) is proposed and experimentally studied. Driven by a periodically microwave modulated current, the vertical-cavity surface-emitting laser emits a continuous beam that switches between monochromatic and multichromatic modes. Ramsey-CPT interference has been studied with this mode-switching beam. In eliminating the AOM, which is used to generate pulsed laser in conventional Ramsey-CPT atomic clock, the physics package of the proposed scheme is virtually the same as that of a conventional compact CPT atomic clock, although the resource budget for the electronics will slightly increase as amore » microwave switch should be added. By evaluating and comparing experimentally recorded signals from the two Ramsey-CPT schemes, the short-term frequency stability of the proposed scheme was found to be 46% better than the scheme with AOM. The experimental results suggest that the implementation of a compact Ramsey-CPT atomic clock promises better frequency stability.« less

Study and Optimization of CPT Resonance Parameters in 87 Rb/Ar/Ne Microcells Aimed for Application in Metrology

NASA Astrophysics Data System (ADS)

Masian, Y.; Sivak, A.; Sevostianov, D.; Vassiliev, V.; Velichansky, V.

The paper shows the presents results of studies of small-size rubidium cells with argon and neon buffer gases, produced by a patent pended technique of laser welding [Fishman et al. (2014)]. Cells were designed for miniature frequency standard. Temperature dependence of the frequency of the coherent population trapping (CPT) resonance was measured and used to optimize the ratio of partial pressures of buffer gases. The influence of duration and regime of annealing on the CPT-resonance frequency drift was investigated. The parameters of the FM modulation of laser current for two cases which correspond to the highest amplitude of CPT resonance and to the smallest light shifts of the resonance frequency were determined. The temperature dependences of the CPT resonance frequency were found to be surprisingly different in the two cases. A non-linear dependence of CPT resonance frequency on the temperature of the cell with the two extremes was revealed for one of these cases.

Pharmacology and Therapeutics Education in the European Union Needs Harmonization and Modernization: A Cross‐sectional Survey Among 185 Medical Schools in 27 Countries

PubMed Central

Tichelaar, J; Okorie, M; Bissell, L; Christiaens, T; Likic, R; Mačìulaitis, R; Costa, J; Sanz, EJ; Tamba, BI; Maxwell, SR; Richir, MC; van Agtmael, MA

2017-01-01

Effective teaching in pharmacology and clinical pharmacology and therapeutics (CPT) is necessary to make medical students competent prescribers. However, the current structure, delivery, and assessment of CPT education in the European Union (EU) is unknown. We sent an online questionnaire to teachers with overall responsibility for CPT education in EU medical schools. Questions focused on undergraduate teaching and assessment of CPT, and students' preparedness for prescribing. In all, 185 medical schools (64%) from 27 EU countries responded. Traditional learning methods were mainly used. The majority of respondents did not provide students with the opportunity to practice real‐life prescribing and believed that their students were not well prepared for prescribing. There is a marked difference in the quality and quantity of CPT education within and between EU countries, suggesting that there is considerable scope for improvement. A collaborative approach should be adopted to harmonize and modernize the undergraduate CPT education across the EU. PMID:28295236

Plasma cortisol levels in response to a cold pressor test did not predict appetite or ad libitum test meal intake in obese women.

PubMed

Geliebter, Allan; Gibson, Charlisa D; Hernandez, Dominica B; Atalayer, Deniz; Kwon, Anne; Lee, Michelle I; Mehta, Nandini; Phair, Donna; Gluck, Marci E

2012-12-01

Heightened cortisol response to stress due to hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis may stimulate appetite and food intake. In this study, we assessed cortisol responsivity to a cold pressor test (CPT) as well as appetite ratings and subsequent test meal intake (TMI) in obese women. Following an overnight fast on two counterbalanced days, 20 obese women immersed their non-dominant hand for 2min in ice water (CPT) or warm water (WW) as a control. Plasma cortisol (ng/ml), heart rate, and blood pressure, as well as ratings of stress, pain, and appetite, were serially acquired. An ad libitum liquid meal was offered at 45min and intake measured covertly. Fasting cortisol was higher at 15min (mean peak cortisol) following the CPT compared to WW. Higher stress was reported at 2 and 15min for the CPT compared to WW. Pain, an indirect marker of the acute stress, systolic and diastolic blood pressure increased following the CPT at 2min compared to WW. Hunger decreased after the CPT at 2 and 15min, and desire to eat ratings were lower following CPT compared to WW. Subjects did not have greater test meal intake (TMI) following CPT compared to WW. There was also no significant relationship between cortisol levels following stress and TMI, indicating that cortisol did not predict subsequent intake in obese women. Copyright © 2012 Elsevier Ltd. All rights reserved.

Plasma Cortisol Levels in Response to a Cold Pressor Test Did Not Predict Appetite or Ad Libitum Test Meal Intake in Obese Women

PubMed Central

Geliebter, Allan; Gibson, Charlisa D.; Hernandez, Dominica B.; Atalayer, Deniz; Kwon, Anne; Lee, Michelle I; Mehta, Nandini; Phair, Donna; Gluck, Marci E.

2012-01-01

Heightened cortisol response to stress due to hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis may stimulate appetite and food intake. In this study, we assessed cortisol responsivity to a cold pressor test (CPT) as well as appetite ratings and subsequent test meal intake (TMI) in obese women. Following an overnight fast on two counterbalanced days, 20 obese women immersed their non-dominant hand for 2 min in ice water (CPT) or warm water (WW) as a control. Plasma cortisol (ng/ml), heart rate, and blood pressure, as well as ratings of stress, pain, and appetite, were serially acquired. An ad libitum liquid meal was offered at 45 min and intake measured covertly. Fasting cortisol was higher at 15 min (mean peak cortisol) following the CPT compared to WW. Higher stress was reported at 2 and 15 min for the CPT compared to WW. Pain, an indirect marker of the acute stress, systolic and diastolic blood pressure increased following the CPT at 2 min compared to WW Hunger decreased after the CPT at 2 and 15 min, and desire to eat ratings were lower following CPT compared to WW . Subjects did not have greater test meal intake (TMI) following CPT compared to WW. There was also no significant relationship between cortisol levels following stress and TMI, indicating that cortisol did not predict subsequent intake in obese women. PMID:22983369

Dextran vesicular carriers for dual encapsulation of hydrophilic and hydrophobic molecules and delivery into cells.

PubMed

Pramod, P S; Takamura, Kathryn; Chaphekar, Sonali; Balasubramanian, Nagaraj; Jayakannan, M

2012-11-12

Dextran vesicular nanoscaffolds were developed based on polysaccharide and renewable resource alkyl tail for dual encapsulation of hydrophilic and hydrophobic molecules (or drugs) and delivery into cells. The roles of the hydrophobic segments on the molecular self-organization of dextran backbone into vesicles or nanoparticles were investigated in detail. Dextran vesicles were found to be a unique dual carrier in which water-soluble molecules (like Rhodamine-B, Rh-B) and polyaromatic anticancer drug (camptothecin, CPT) were selectively encapsulated in the hydrophilic core and hydrophobic layer, respectively. The dextran vesicles were capable of protecting the plasma-sensitive CPT lactone pharmacophore against the hydrolysis by 10× better than the CPT alone in PBS. The aliphatic ester linkage connecting the hydrophobic tail with dextran was found to be cleaved by esterase under physiological conditions for fast releasing of CPT or Rh-B. Cytotoxicity of the dextran vesicle and its drug conjugate were tested on mouse embryonic fibroblast cells (MEFs) using MTT assay. The dextran vesicular scaffold was found to be nontoxic to living cells. CPT loaded vesicles were found to be 2.5-fold more effective in killing fibroblasts compared to that of CPT alone in PBS. Confocal microscopic images confirmed that both Rh-B and CPT loaded vesicles to be taken up by fibroblasts compared to CPT alone, showing a distinctly perinuclear localization in cells. The custom designed dextran vesicular provides new research opportunities for dual loading and delivering of hydrophilic and hydrophobic drug molecules.

Cold pressor test in spinal cord injury-revisited.

PubMed

Hubli, Michèle; Bolt, Doris; Krassioukov, Andrei V

2018-06-01

Systematic review. A spinal cord injury (SCI) commonly results in alterations of cardiovascular physiology. In order to investigate such alterations, the cold pressor test (CPT) has been used as an established challenge test. This review summarizes the basic physiology underlying a CPT, discusses potential mechanisms responsible for abnormal pressor responses following SCI, and highlights the utility of CPT in the SCI population. Canada and Switzerland. We have completed a comprehensive review of studies that have investigated the effect of foot or hand CPT on hemodynamic indices in individuals with SCI. Depending on the level of spinal cord lesion and the location of cold application, i.e., above or below the lesion, mean arterial pressure typically increases (ranging between 4 and 23 mmHg), while heart rate responses demonstrated either a decrease or an increase (ranging between -4 and 24 bpm) during CPT. The increase in blood pressure during foot CPT in high-level lesions might not necessarily be attributed to a physiological CPT response as seen in able-bodied individuals, but rather due to a reflexic sympathetic discharge below the level of lesion, known as autonomic dysreflexia. Further investigations in a wider range of individuals with SCI including incomplete injuries might be helpful to examine the ability of CPT assessing the integrity of the autonomic nervous system following SCI. Furthermore, additional autonomic tests are needed to emphasize the integrity of autonomic pathways and to account for the complexity of the autonomic nervous system.

The use of experimental design in the development of an HPLC-ECD method for the analysis of captopril.

PubMed

Khamanga, Sandile M; Walker, Roderick B

2011-01-15

An accurate, sensitive and specific high performance liquid chromatography-electrochemical detection (HPLC-ECD) method that was developed and validated for captopril (CPT) is presented. Separation was achieved using a Phenomenex(®) Luna 5 μm (C(18)) column and a mobile phase comprised of phosphate buffer (adjusted to pH 3.0): acetonitrile in a ratio of 70:30 (v/v). Detection was accomplished using a full scan multi channel ESA Coulometric detector in the "oxidative-screen" mode with the upstream electrode (E(1)) set at +600 mV and the downstream (analytical) electrode (E(2)) set at +950 mV, while the potential of the guard cell was maintained at +1050 mV. The detector gain was set at 300. Experimental design using central composite design (CCD) was used to facilitate method development. Mobile phase pH, molarity and concentration of acetonitrile (ACN) were considered the critical factors to be studied to establish the retention time of CPT and cyclizine (CYC) that was used as the internal standard. Twenty experiments including centre points were undertaken and a quadratic model was derived for the retention time for CPT using the experimental data. The method was validated for linearity, accuracy, precision, limits of quantitation and detection, as per the ICH guidelines. The system was found to produce sharp and well-resolved peaks for CPT and CYC with retention times of 3.08 and 7.56 min, respectively. Linear regression analysis for the calibration curve showed a good linear relationship with a regression coefficient of 0.978 in the concentration range of 2-70 μg/mL. The linear regression equation was y=0.0131x+0.0275. The limits of detection (LOQ) and quantitation (LOD) were found to be 2.27 and 0.6 μg/mL, respectively. The method was used to analyze CPT in tablets. The wide range for linearity, accuracy, sensitivity, short retention time and composition of the mobile phase indicated that this method is better for the quantification of CPT than the pharmacopoeial methods. Copyright © 2010 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bonnefont, J.P.; Cepanec, C.; Leroux, J.P.

Carnitine palmitoyltransferase (CPT) II deficiency, an inherited disorder of mitochondrial long-chain fatty-acid (LCFA) oxidation, results in two distinct clinical act phenotypes, namely, an adult (muscular) form and an infantile (hepatocardiomuscular) form. The rationale of this phenotypic heterogeneity is poorly understood. The adult form of the disease is commonly ascribed to the Ser-113-Leu substitution in CPT II. Only few data are available regarding the molecular basis of the infantile form of the disease. We report herein a homozygous A-2399-C transversion predicting a Tyr-628-Ser substitution in a CPT II-deficient infant. In vitro expression of mutant cDNA in COS-1 cells demonstrated the responsibilitymore » of this mutation for the disease. Metabolic consequences of the Ser-113-Leu and Tyr-628-Ser substitutions were studied in fibroblasts. The Tyr-628-Ser substitution (infantile form) resulted in a 10% CPT II residual activity, markedly impairing LCFA oxidation, whereas the Ser-113-Leu substitution (adult form) resulted in a 20% CPT II residual activity, without consequence on LCFA oxidation. These data show that CPT II activity has to be reduced below a critical threshold in order for LCFA oxidation in fibroblasts to be impaired. The hypothesis that this critical threshold differs among tissues could provide a basis to explain phenotypic heterogeneity of CPT II deficiency. 32 refs., 5 figs.« less

Optimal antidiarrhea treatment for antitumor agent irinotecan hydrochloride (CPT-11)-induced delayed diarrhea.

PubMed

Takasuna, K; Hagiwara, T; Watanabe, K; Onose, S; Yoshida, S; Kumazawa, E; Nagai, E; Kamataki, T

2006-10-01

An antitumor camptothecin derivative CPT-11 has proven a broad spectrum of solid tumor malignancy, but its severe diarrhea has often limited its more widespread use. We have demonstrated from a rat model that intestinal beta-glucuronidase may play a key role in the development of CPT-11-induced delayed diarrhea by the deconjugation of the luminal SN-38 glucuronide, and the elimination of the intestinal microflora by antibiotics or dosing of TJ-14, a Kampo medicine that contains beta-glucuronidase inhibitor baicalin, exerted a protective effect. In the present study, we assessed the efficacy of several potential treatments in our rat model to clarify which is the most promising treatment for CPT-11-induced delayed diarrhea. Oral dosing (twice daily from days -1 to 4) of streptomycin 20 mg/kg and penicillin 10 mg/kg (Str/Pen), neomycin 20 mg/kg and bacitracin 10 mg/kg (Neo/Bac), both of which inhibited almost completely the fecal beta-glucuronidase activity, or TJ-14 1,000 mg/kg improved the decrease in body weight and the delayed diarrhea symptoms induced by CPT-11 (60 mg/kg i.v. from days 1 to 4) to a similar extent. The efficacy was less but significant in activated charcoal (1,000 mg/kg p.o. twice daily from days -1 to 4). In a separate experiment using rats bearing breast cancer (Walker 256-TC), TJ-14, Neo/Bac, and charcoal at the same dose regimen improved CPT-11-induced intestinal toxicity without reducing CPT-11's antitumor activity. In contrast, oral dosing (twice a day) of cyclosporin A (50 mg/kg), a P-glycoprotein and cMOAT/MRP2 inhibitor or valproic acid (200 mg/kg), a UDP-glucuronosyltranferase inhibitor, exacerbated the intestinal toxicity without modifying CPT-11's antitumor activity. The result clearly demonstrated the ability of Neo/Bac, Str/Pen, and TJ-14, less but significant ability of activated charcoal, to ameliorate CPT-11-induced delayed-onset diarrhea, suggesting the treatments decreasing the exposure of the intestines to the luminal SN-38 are valuable for improvement of CPT-11-induced intestinal toxicity. In contrast, the treatments affecting the biliary excretion of CPT-11 and its metabolites might have undesirable results.

Developing a Performance Brain Training™ approach for baseball: a process analysis with descriptive data.

PubMed

Sherlin, Leslie H; Larson, Noel C; Sherlin, Rebecca M

2013-03-01

Neurofeedback may be useful for improving sports performance but few studies have examined this potential. Here we present data of five development players from a major league baseball team. The aims were to evaluate the feasibility of conducting sessions within a professional organization, assess changes in quantitative electroencephalograph (QEEG), NeuroPerformance Profile™, and report qualitative self-report data before and after brain training. The EEG was recorded with 19 electrodes for 20 min of baseline conditions and approximately 21 min of a continuous performance test. The fast Fourier transform analysis provided average cross-spectral matrices for bands delta (1-3.5 Hz), theta (4-7.5 Hz), alpha (8-12 Hz), low beta (13-16 Hz), beta 1 (13-21 Hz), beta 2 (22-32 Hz), and gamma (32-45 Hz) from the pre and post intervention evaluations in the baseline condition of eyes open. The continuous performance test metrics included the errors of omission, errors of commission, response time and response time variability. The 9 scales of the NeuroPerformance Profile™ were examined. The QEEG data, CPT data and NeuroPerformance Profile™ data were all compared between the pre and post 15 sessions of brain training using a within subject paired t test design corrected for multiple comparisons using false discovery rate method. Following brain training, comparative QEEG, CPT and NeuroPerformance Profile™ analyses illustrated significant differences. The QEEG findings of all participants illustrated significant changes within the training parameters but also across other frequency bands and electrode sites. Overall, the positive findings in both objective and subjective measures suggest further inquiry into the utility of brain training for performance enhancement with the specific application of sport is warranted. Particularly QEEG and CPT gains were noted in the areas that correspond to client self-report data demonstrating improvement in attention, decreased intrusive thought patterns and improvements in sleep patterns.

How the twain can meet: Prospect theory and models of heuristics in risky choice.

PubMed

Pachur, Thorsten; Suter, Renata S; Hertwig, Ralph

2017-03-01

Two influential approaches to modeling choice between risky options are algebraic models (which focus on predicting the overt decisions) and models of heuristics (which are also concerned with capturing the underlying cognitive process). Because they rest on fundamentally different assumptions and algorithms, the two approaches are usually treated as antithetical, or even incommensurable. Drawing on cumulative prospect theory (CPT; Tversky & Kahneman, 1992) as the currently most influential instance of a descriptive algebraic model, we demonstrate how the two modeling traditions can be linked. CPT's algebraic functions characterize choices in terms of psychophysical (diminishing sensitivity to probabilities and outcomes) as well as psychological (risk aversion and loss aversion) constructs. Models of heuristics characterize choices as rooted in simple information-processing principles such as lexicographic and limited search. In computer simulations, we estimated CPT's parameters for choices produced by various heuristics. The resulting CPT parameter profiles portray each of the choice-generating heuristics in psychologically meaningful ways-capturing, for instance, differences in how the heuristics process probability information. Furthermore, CPT parameters can reflect a key property of many heuristics, lexicographic search, and track the environment-dependent behavior of heuristics. Finally, we show, both in an empirical and a model recovery study, how CPT parameter profiles can be used to detect the operation of heuristics. We also address the limits of CPT's ability to capture choices produced by heuristics. Our results highlight an untapped potential of CPT as a measurement tool to characterize the information processing underlying risky choice. Copyright © 2017 Elsevier Inc. All rights reserved.

Prospect theory reflects selective allocation of attention.

PubMed

Pachur, Thorsten; Schulte-Mecklenbeck, Michael; Murphy, Ryan O; Hertwig, Ralph

2018-02-01

There is a disconnect in the literature between analyses of risky choice based on cumulative prospect theory (CPT) and work on predecisional information processing. One likely reason is that for expectation models (e.g., CPT), it is often assumed that people behaved only as if they conducted the computations leading to the predicted choice and that the models are thus mute regarding information processing. We suggest that key psychological constructs in CPT, such as loss aversion and outcome and probability sensitivity, can be interpreted in terms of attention allocation. In two experiments, we tested hypotheses about specific links between CPT parameters and attentional regularities. Experiment 1 used process tracing to monitor participants' predecisional attention allocation to outcome and probability information. As hypothesized, individual differences in CPT's loss-aversion, outcome-sensitivity, and probability-sensitivity parameters (estimated from participants' choices) were systematically associated with individual differences in attention allocation to outcome and probability information. For instance, loss aversion was associated with the relative attention allocated to loss and gain outcomes, and a more strongly curved weighting function was associated with less attention allocated to probabilities. Experiment 2 manipulated participants' attention to losses or gains, causing systematic differences in CPT's loss-aversion parameter. This result indicates that attention allocation can to some extent cause choice regularities that are captured by CPT. Our findings demonstrate an as-if model's capacity to reflect characteristics of information processing. We suggest that the observed CPT-attention links can be harnessed to inform the development of process models of risky choice. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Cryptotanshinone inhibits oxidized LDL-induced adhesion molecule expression via ROS dependent NF-κB pathways

PubMed Central

Zhao, Wenwen; Wu, Chuanhong; Chen, Xiuping

2016-01-01

ABSTRACT Adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, play important roles in the initial stage of atherosclerosis. Cryptotanshinone (CPT), a natural compound isolated from Salvia miltiorrhiza Bunge, exhibits anti-atherosclerotic activity although the underlying mechanisms remain elusive. In this study, the protective effect of CPT against oxidized low-density lipoprotein (ox-LDL)-induced adhesion molecule expression was investigated in human umbilical vein endothelial cells. Ox-LDL significantly induced ICAM-1, VCAM-1, and E-selectin expression at the mRNA and protein levels but reduced eNOS phosphorylation and NO generation, which were reversed by CPT pretreatment. Sodium nitroprusside, a NO donor, N-acetyl-L-cysteine (NAC), a reactive oxygen species (ROS) scavenger, and BAY117082, a NF-κB inhibitor, inhibited ox-LDL-induced ICAM-1, VCAM-1, and E-selectin expression. Ox-LDL-induced ROS production was significantly inhibited by CPT and NAC. Furthermore, ox-LDL activated the NF-κB signaling pathway by inducing phosphorylation of IKKβ and IκBα, promoting the interaction of IKKβ and IκBα, and increasing p65 nuclear translocation, which were significantly inhibited by CPT. In addition, CPT, NAC, and BAY117082 inhibited ox-LDL-induced membrane expression of ICAM-1, VCAM-1, E-selectin, and endothelial–monocyte adhesion and restored eNOS phosphorylation and NO generation. Results suggested that CPT inhibited ox-LDL-induced adhesion molecule expression by decreasing ROS and inhibiting the NF-κB pathways, which provides new insight into the anti-atherosclerotic mechanism of CPT. PMID:26647279

Antimatter Past, Present and Future

NASA Astrophysics Data System (ADS)

Zichichi, Antonino

2001-11-01

In order to have matter we need fundamental fermions (quarks and leptons), particles (mesons and baryons) and nuclei. For antimatter to exist, the antifundamental fermions, as well as the antiparticles and the antinuclei, are needed. The masses associated with these components of matter are the "intrinsic" (quarks and leptons), the "confinement" (mesons and baryons) and the "binding" [either nuclear (nuclei), or electromagnetic (atoms)]. The first two are positive, the two "binding" ones are negative. These masses have different origins. No one has been able to establish the origin of the "intrinsic" masses (it could be the Higgs mechanism, but this lacks experimental confirmation so far). The "confinement" masses are QCD non-perturbative effects. The nuclear "binding" masses are QCD-induced colour neutral effects; the electromagnetic "binding" is due to QED and, since QED is the best experimentally checked RQFT, its validity in terms of the CPT symmetry cannot easily be questioned and this is why the electromagnetic "binding" is not included in this review. If CPT were theoretically well established as it was when discovered, all mass differences, between any matter and its antimatter partner, should be zero. The best limits for the validity of CPT invariance in the field of masses are two: i) the determination of a very small upper limit on Δ {m}{{Kbar K}} (the mass difference between a meson and an antimeson) derived from the mass difference between the long- and the short-lived K-mesons, ΔmKLKS ii) the measurements of the charge over mass ratio ({{Q} / {M}}) for protons and antiprotons. These experimental results are discussed in terms of their relevance to check CPT invariance for the "intrinsic" and for the "confinement" masses. It is pointed out that the value of Δ {m}{{Kbar K}} could be totally insensitive to a large CPT breaking in the intrinsic quark masses. Furthermore, the physics of "intrinsic" and "confinement" masses has nothing to do with the nuclear "binding" masses, where the limits are very poor. A deuteron-antideuteron mass difference Δ {m}{{Dbar D}} , many orders of magnitude larger than the present limits in the "confinement" and in the "intrinsic" masses, could exist and have no effects on the CPT limits known so far, including the very high precision measurements on Δ {m}{{Kbar K}} and on ({{Q} / {M}}). New experiments need to be performed in nuclear matter-antimatter in order to establish the validity of CPT invariance in non-perturbative - colour neutral - QCD effects, such as the nuclear binding forces which no one is able to describe in terms of a fundamental RQFT.

The CPT Reading Comprehension Test: A Validity Study.

ERIC Educational Resources Information Center

Napoli, Anthony R.; Raymond, Lanette A.; Coffey, Cheryl A.; Bosco, Diane M.

1998-01-01

Describes a study done at Suffolk County Community College (New York) that assessed the validity of the College Board's Computerized Placement Test in Reading Comprehension (CPT-R) by comparing test results of 1,154 freshmen with the results of the Degree of Power Reading Test. Results confirmed the CPT-R's reliability in identifying basic…

The invariance of classical electromagnetism under Charge-conjugation, Parity and Time-reversal (CPT) transformations

NASA Technical Reports Server (NTRS)

Norbury, John W.

1989-01-01

The invariance of classical electromagnetism under charge-conjugation, parity, and time-reversal (CPT) is studied by considering the motion of a charged particle in electric and magnetic fields. Upon applying CPT transformations to various physical quantities and noting that the motion still behaves physically demonstrates invariance.

78 FR 72576 - Criteria for a Catastrophically Disabled Determination for Purposes of Enrollment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-03

... Procedural Terminology (CPT[supreg]) codes. The revisions ensure that the regulation is not out of date when... trademark of the American Medical Association. CPT codes and descriptions are copyrighted by the American Medical Association. All rights reserved.) This approach will soon be outdated; the ICD-9-CM and CPT...

Micropropagation and hairy root culture of Ophiorrhiza alata Craib for camptothecin production.

PubMed

Ya-ut, Pornwilai; Chareonsap, Piyarat; Sukrong, Suchada

2011-12-01

An efficient system was developed for the in vitro micropropagation and hairy root culture of Ophiorrhiza alata Craib for camptothecin (CPT) production. Shoot multiplication on leaf and node explants from germinated seeds of O. alata was successful on half-strength Murashige and Skoog medium supplemented with varying amounts of kinetin and α-naphthaleneacetic acid. Node explants grown in vitro were successfully infected by Agrobacterium rhizogenes TISTR 1450 for the establishment of hairy root culture. The amount of CPT in various parts of O. alata was analyzed by HPLC. The accumulation of CPT in transformed hairy roots was twice that in soil-grown plants (785 ± 52 and 388 ± 32 μg/g dry wt, respectively). In the presence of a polystyrene resin (Diaion HP-20) that absorbed CPT, the CPT content in the culture media increased sevenfold compared with controls (1,036 and 151 μg per 250 ml medium, respectively). These results enable the feasible production of CPT of O. alata by means of a cell culture strategy. These measures can help safeguard the plant from extinction. © Springer Science+Business Media B.V. 2011

CPT-based probabilistic and deterministic assessment of in situ seismic soil liquefaction potential

USGS Publications Warehouse

Moss, R.E.S.; Seed, R.B.; Kayen, R.E.; Stewart, J.P.; Der Kiureghian, A.; Cetin, K.O.

2006-01-01

This paper presents a complete methodology for both probabilistic and deterministic assessment of seismic soil liquefaction triggering potential based on the cone penetration test (CPT). A comprehensive worldwide set of CPT-based liquefaction field case histories were compiled and back analyzed, and the data then used to develop probabilistic triggering correlations. Issues investigated in this study include improved normalization of CPT resistance measurements for the influence of effective overburden stress, and adjustment to CPT tip resistance for the potential influence of "thin" liquefiable layers. The effects of soil type and soil character (i.e., "fines" adjustment) for the new correlations are based on a combination of CPT tip and sleeve resistance. To quantify probability for performancebased engineering applications, Bayesian "regression" methods were used, and the uncertainties of all variables comprising both the seismic demand and the liquefaction resistance were estimated and included in the analysis. The resulting correlations were developed using a Bayesian framework and are presented in both probabilistic and deterministic formats. The results are compared to previous probabilistic and deterministic correlations. ?? 2006 ASCE.

Pharmacology and Therapeutics Education in the European Union Needs Harmonization and Modernization: A Cross-sectional Survey Among 185 Medical Schools in 27 Countries.

PubMed

Brinkman, D J; Tichelaar, J; Okorie, M; Bissell, L; Christiaens, T; Likic, R; Mačìulaitis, R; Costa, J; Sanz, E J; Tamba, B I; Maxwell, S R; Richir, M C; van Agtmael, M A

2017-11-01

Effective teaching in pharmacology and clinical pharmacology and therapeutics (CPT) is necessary to make medical students competent prescribers. However, the current structure, delivery, and assessment of CPT education in the European Union (EU) is unknown. We sent an online questionnaire to teachers with overall responsibility for CPT education in EU medical schools. Questions focused on undergraduate teaching and assessment of CPT, and students' preparedness for prescribing. In all, 185 medical schools (64%) from 27 EU countries responded. Traditional learning methods were mainly used. The majority of respondents did not provide students with the opportunity to practice real-life prescribing and believed that their students were not well prepared for prescribing. There is a marked difference in the quality and quantity of CPT education within and between EU countries, suggesting that there is considerable scope for improvement. A collaborative approach should be adopted to harmonize and modernize the undergraduate CPT education across the EU. © 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Oxidation of Hepatic Carnitine Palmitoyl Transferase-I (CPT-I) Impairs Fatty Acid Beta-Oxidation in Rats Fed a Methionine-Choline Deficient Diet

PubMed Central

Bellanti, Francesco; Priore, Paola; Rollo, Tiziana; Tamborra, Rosanna; Siculella, Luisa; Vendemiale, Gianluigi; Altomare, Emanuele; Gnoni, Gabriele V.

2011-01-01

There is growing evidence that mitochondrial dysfunction, and more specifically fatty acid β-oxidation impairment, is involved in the pathophysiology of non-alcoholic steatohepatitis (NASH). The goal of the present study was to achieve more understanding on the modification/s of carnitinepalmitoyltransferase-I (CPT-I), the rate-limiting enzyme of the mitochondrial fatty acid β-oxidation, during steatohepatitis. A high fat/methionine-choline deficient (MCD) diet, administered for 4 weeks, was used to induce NASH in rats. We demonstrated that CPT-Iactivity decreased, to the same extent, both in isolated liver mitochondria and in digitonin-permeabilized hepatocytes from MCD-diet fed rats. At the same time, the rate of total fatty acid oxidation to CO2 and ketone bodies, measured in isolated hepatocytes, was significantly lowered in treated animals when compared to controls. Finally, an increase in CPT-I mRNA abundance and protein content, together with a high level of CPT-I protein oxidation was observed in treated rats. A posttranslational modification of rat CPT-I during steatohepatitis has been here discussed. PMID:21909411

Differential impact of the first and second wave of a stress response on subsequent fear conditioning in healthy men.

PubMed

Antov, Martin I; Wölk, Christoph; Stockhorst, Ursula

2013-10-01

Stress is a process of multiple neuroendocrine changes over time. We examined effects of the first-wave and second-wave stress response on acquisition and immediate extinction of differential fear conditioning, assessed by skin conductance responses. In Experiment 1, we placed acquisition either close to the (second-wave) salivary cortisol peak, induced by a psychosocial stressor (experimental group, EG), or after non-stressful pretreatment (control group, CG). Contrary to predictions, groups did not differ in differential responding. In the EG only, mean differential responding was negatively correlated with cortisol increases. In Experiment 2, we placed conditioning near the first-wave stress response, induced by a cold pressor test (CPT), or after a warm-water condition (CG). CPT-stress increased extinction resistance. Moreover, acquisition performance after CPT was positively correlated with first-wave blood pressure increases. Data suggest that mediators of the first-wave stress response enhance fear maintenance whereas second-wave cortisol responsivity to stress might attenuate fear learning. Copyright © 2013 Elsevier B.V. All rights reserved.

Preparation of a mesoporous silica-based nano-vehicle for dual DOX/CPT pH-triggered delivery.

PubMed

Llinàs, Maria C; Martínez-Edo, Gabriel; Cascante, Anna; Porcar, Irene; Borrós, Salvador; Sánchez-García, David

2018-11-01

A dual doxorubicin/camptothecin (DOX/CPT) pH-triggered drug delivery mesoporous silica nanoparticle (MSN)-based nano-vehicle has been prepared. In this drug-delivery system (DDS), CPT is loaded inside the pores of the MSNs, while DOX is covalently attached to the surface of an aldehyde-functionalized MSN through a dihydrazide-polyethylene glycol chain. Thus, DOX and the linker act as pH-sensitive gatekeeper. The system is versatile and easy to assemble, not requiring the chemical modification of the drugs. While at physiological conditions the release of the drugs is negligible, at acidic pH a burst release of DOX and a gradual release of CPT take place. In vitro cytotoxicity tests have demonstrated that this DDS can deliver efficiently DOX and CPT for combination therapy.

Role of cytokines (TNF-alpha, IL-1beta and KC) in the pathogenesis of CPT-11-induced intestinal mucositis in mice: effect of pentoxifylline and thalidomide.

PubMed

Melo, Maria Luisa P; Brito, Gerly A C; Soares, Rudy C; Carvalho, Sarah B L M; Silva, Johan V; Soares, Pedro M G; Vale, Mariana L; Souza, Marcellus H L P; Cunha, Fernando Q; Ribeiro, Ronaldo A

2008-04-01

Irinotecan (CPT-11) is an inhibitor of DNA topoisomerase I and is clinically effective against several cancers. A major toxic effect of CPT-11 is delayed diarrhea; however, the exact mechanism by which the drug induces diarrhea has not been established. Elucidate the mechanisms of induction of delayed diarrhea and determine the effects of the cytokine production inhibitor pentoxifylline (PTX) and thalidomide (TLD) in the experimental model of intestinal mucositis, induced by CPT-11. Intestinal mucositis was induced in male Swiss mice by intraperitoneal administration of CPT-11 (75 mg/kg) daily for 4 days. Animals received subcutaneous PTX (1.7, 5 and 15 mg/kg) or TLD (15, 30, 60 mg/kg) or 0.5 ml of saline daily for 5 and 7 days, starting 1 day before the first CPT-11 injection. The incidence of delayed diarrhea was monitored by scores and the animals were sacrificed on the 5th and 7th experimental day for histological analysis, immunohistochemistry for TNF-alpha and assay of myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and KC ELISA. CPT-11 caused significant diarrhea, histopathological alterations (inflammatory cell infiltration, loss of crypt architecture and villus shortening) and increased intestinal tissue MPO activity, TNF-alpha, IL-1beta and KC level and TNF-alpha immuno-staining. PTX inhibited delayed diarrhea of mice submitted to intestinal mucositis and reduced histopathological damage, intestinal MPO activity, tissue level of TNF-alpha, IL-1beta and KC and TNF-alpha immuno-staining. TLD significantly reduced the lesions induced by CPT-11 in intestinal mucosa, decreased MPO activity, TNF-alpha tissue level and TNF-alpha immuno-staining, but did not reduce the severity of diarrhea. These results suggest an important role of TNF-alpha, IL-1beta and KC in the pathogenesis of intestinal mucositis induced by CPT-11.

Inhibition of intestinal microflora beta-glucuronidase modifies the distribution of the active metabolite of the antitumor agent, irinotecan hydrochloride (CPT-11) in rats.

PubMed

Takasuna, K; Hagiwara, T; Hirohashi, M; Kato, M; Nomura, M; Nagai, E; Yokoi, T; Kamataki, T

1998-01-01

SN-38, a metabolite of irinotecan hydrochloride (CPT-11), is considered to play a key role in the development of diarrhea as well as in the antitumor activity of CPT-11. We have previously found that the inhibition of beta-glucuronidase, which hydrolyzes detoxified SN-38 (SN-38 glucuronide) to reform SN-38, in the lumen by eliminating the intestinal microflora with antibiotics, markedly ameliorates the intestinal toxicity of CPT-11 in rats. In this study we compared the disposition of CPT-11 and its metabolites in rats treated with and without antibiotics. Rats were given drinking water containing 1 mg/ml penicillin and 2 mg/ml streptomycin from 5 days before the administration of CPT-11 (60 mg/kg i.v.) and throughout the experiment. CPT-11, SN-38 glucuronide and SN-38 concentrations in the blood, intestinal tissues and intestinal luminal contents were determined by HPLC. Antibiotics had little or no effect on the pharmacokinetics of CPT-11, SN-38 glucuronide or SN-38 in the blood, or in the tissues or contents of the small intestine, which has less beta-glucuronidase activity in its luminal contents. In contrast, antibiotics markedly reduced the AUC1-24 h of SN-38 (by about 85%) in the large intestine tissue without changing that of CPT-11, and this was accompanied by a complete inhibition of the deconjugation of SN-38 glucuronide in the luminal contents. These results suggest that SN-38, which results from the hydrolysis of SN-38 glucuronide by beta-glucuronidase in the intestinal microflora, contributes considerably to the distribution of SN-38 in the large intestine tissue, and that inhibition of the beta-glucuronidase activity by antibiotics results in decreased accumulation of SN-38 in the large intestine.

Repetitive TMS to augment cognitive processing therapy in combat veterans of recent conflicts with PTSD: A randomized clinical trial.

PubMed

Kozel, F Andrew; Motes, Michael A; Didehbani, Nyaz; DeLaRosa, Bambi; Bass, Christina; Schraufnagel, Caitlin D; Jones, Penelope; Morgan, Cassie Rae; Spence, Jeffrey S; Kraut, Michael A; Hart, John

2018-03-15

The objective was to test whether repetitive Transcranial Magnetic Stimulation (rTMS) just prior to Cognitive Processing Therapy (CPT) would significantly improve the clinical outcome compared to sham rTMS prior to CPT in veterans with PTSD. Veterans 18-60 years of age with current combat-related PTSD symptoms were randomized, using a 1:1 ratio in a parallel design, to active (rTMS+CPT) versus sham (sham+CPT) rTMS just prior to weekly CPT for 12-15 sessions. Blinded raters evaluated veterans at baseline, after the 5th and 9th treatments, and at 1, 3, and 6 months post-treatment. Clinician Administered PTSD Scale (CAPS) was the primary outcome measure with the PTSD Checklist (PCL) as a secondary outcome measure. The TMS coil (active or sham) was positioned over the right dorsolateral prefrontal cortex (110% MT, 1Hz continuously for 30min, 1800 pulses/treatment). Of the 515 individuals screened for the study, 103 participants were randomized to either active (n = 54) or sham rTMS (n = 49). Sixty-two participants (60%) completed treatment and 59 (57%) completed the 6-month assessment. The rTMS+CPT group showed greater symptom reductions from baseline on both CAPS and PCL across CPT sessions and follow-up assessments, t(df ≥ 325) ≤ -2.01, p ≤ 0.023, one-tailed and t(df ≥ 303) ≤ -2.14, p ≤ 0.017, one-tailed, respectively. Participants were predominantly male and limited to one era of conflicts as well as those who could safely undergo rTMS. The addition of rTMS to CPT compared to sham with CPT produced significantly greater PTSD symptom reduction early in treatment and was sustained up to six months post-treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

In vitro effects of citrus oils against Mycobacterium tuberculosis and non-tuberculous Mycobacteria of clinical importance.

PubMed

Crandall, Philip G; Ricke, Steven C; O'Bryan, Corliss A; Parrish, Nicole M

2012-01-01

We evaluated the in vitro activity of citrus oils against Mycobacterium tuberculosis and other non-tuberculous Mycobacterium species. Citrus essential oils were tested against a variety of Mycobacterium species and strains using the BACTEC radiometric growth system. Cold pressed terpeneless Valencia oil (CPT) was further tested using the Wayne model of in vitro latency. Exposure of M. tuberculosis and M. bovis BCG to 0.025 % cold pressed terpeneless Valencia orange oil (CPT) resulted in a 3-log decrease in viable counts versus corresponding controls. Inhibition of various clinical isolates of the M. avium complex and M. abscessus ranged from 2.5 to 5.2-logs. Some species/strains were completely inhibited in the presence of CPT including one isolate each of the following: the M. avium complex, M. chelonae and M. avium subsp. paratuberculosis. CPT also inhibited the growth of BCG more than 99 % in an in vitro model of latency which mimics anaerobic dormancy thought to occur in vivo. The activity of CPT against drug-resistant strains of the M. avium complex and M. abscessus suggest that the mechanism of action for CPT is different than that of currently available drugs. Inhibition of latently adapted bacilli offers promise for treatment of latent infections of MTB. These results suggest that the antimycobacterial properties of CPT warrant further study to elucidate the specific mechanism of action and clarify the spectrum of activity.

Cystic pancreatic tumors (CPT): predictors of malignant behavior.

PubMed

Javle, Milind; Shah, Pankaj; Yu, Jihnhee; Bhagat, Vishal; Litwin, Alan; Iyer, Renuka; Gibbs, John

2007-03-01

Due to widespread use of imaging studies, increasing cystic pancreatic tumor (CPT) cases are being detected. The diagnosis of malignancy in CPT cases requires pancreatectomy. Clinical and laboratory characteristics of CPT may predict underlying malignancy. CPT cases treated between 1994 and 2004 at our institution were included. Pseudocysts were excluded. Serous cystadenoma (SCA), mucinous cystadenoma (MCA), intrapapillary mucinous tumor, cystic endocrine tumor, and lymphoepithelial cysts were classified as benign or pre-malignant. Serous cystadenocarcinoma (SCACA), mucinous cystadenocarcinoma (MCACA), and adenocarcinoma (ACA) were classified as malignant. Thirty-five patients had histological confirmation. Median age was 65 years. Male/female ratio was higher in malignant group (P = 0.0284). Weight loss and abdominal mass were more prevalent in malignant group (P = 0.042 and 0.028, respectively). Malignant lesions were larger, associated with local invasion (superior mesenteric artery (SMA), superior mesenteric vein (SMV), portal vein (PV) complex or celiac encasement) and CA 19-9 elevation. On univariate analyses, local invasion (P = 0.0029), negative surgical intervention (P = 0.0010), presence of ACA (P = 0.0044), or malignant CPT (P = 0.0018) were associated with shorter survival. On a multivariate analysis, local invasion was associated with shorter survival [Hazard ratio (HR) = 4.322, P = 0.0218], while surgical intervention was associated with improved survival (HR = 0.179, P = 0.0124). Male sex, abdominal mass, weight loss, larger tumor size, local invasion, and elevated CA 19-9 were associated with malignant CPT.

Neutrinos as the messengers of CPT violation

NASA Astrophysics Data System (ADS)

Borissov, Liubomir Anguelov

CPT violation has the potential to explain all three existing neutrino oscillation signals without enlarging the neutrino sector. CPT violation in the Dirac mass terms of the three neutrino flavors preserves Lorentz invariance, but generates in dependent masses for neutrinos and antineutrinos. This specific signature can be motivated by braneworld scenarios with extra dimensions, where neutrinos are the natural messengers for Standard Model physics of CPT violation in the bulk. A simple model of maximal CPT violation is sufficient to explain the exisiting neutrino data, while accommodating the recent results from the KamLAND experiment and making dramatic predictions for the ongoing MiniBooNE experiment. In addition, the model fits the existing SuperKamiokande data, at least as well as the standard atmospheric neutrino oscillation models. Another attractive feature of the presented model is that it provides a new promising mechanism for baryogenesis, which obviates two of the three Sakharov conditions necessary to generate the baryon asymmetry of the universe. CPT-violating scenarios can give new insights about the possible nature of neutrinos. Majorana neutrino masses are still allowed, but in general, there are no longer Majorana neutrinos in the conventional sense. However, CPT-violating models still have interesting consequences for neutrinoless double beta decay. Compared to the usual case, while the larger mass scale (from LSND) may appear, a greater degree of suppression can also occur.

Anthocyanin-rich blackberry extract suppresses the DNA-damaging properties of topoisomerase I and II poisons in colon carcinoma cells.

PubMed

Esselen, Melanie; Boettler, Ute; Teller, Nicole; Bachler, Simone; Hutter, Melanie; Rufer, Corinna E; Skrbek, Susanne; Marko, Doris

2011-07-13

In the present study, we addressed the question whether cyanidin-3-glucoside (C3G) or complex C3G-rich blackberry extracts affect human topoisomerases with special emphasis on the contribution of the potential degradation products phloroglucinol aldehyde (PGA) and protocatechuic acid (PCA). In HT29 colon carcinoma cells a C3G-rich blackberry extract suppressed camptothecin- (CPT-) or doxorubicin- (DOX-) induced stabilization of the covalent DNA-topoisomerase intermediate, thus antagonizing the effects of these classical topoisomerase poisons on DNA integrity. As a single compound, C3G (100 μM) decreased the DNA-damaging effects of CPT as well, but did not significantly affect those induced by DOX. At the highest applied concentration (100 μM), cyanidin protected DNA from CPT- and DOX-induced damage. Earlier reports on DNA-damaging properties of cyanidin were found to result most likely from the formation of hydrogen peroxide as an artifact in the cell culture medium when the incubation was performed in the absence of catalase. The suppression of hydrogen peroxide accumulation, achieved by the addition of catalase, demonstrated that cyanidin does not exhibit DNA-damaging properties in HT29 cells (up to 100 μM). The observed effects on topoisomerase interference and DNA protection against CPT or DOX were clearly limited to the parent compound and were not observed for the potential cyanidin degradation products PGA and PCA.

Integrated Advanced Microwave Sounding Unit-A (AMSU-A). Performance Verification Reports: Final Comprehensive Performance Test Report, P/N: 1356006-1, S.N: 202/A2

NASA Technical Reports Server (NTRS)

Platt, R.

1998-01-01

This is the Performance Verification Report. the process specification establishes the requirements for the comprehensive performance test (CPT) and limited performance test (LPT) of the earth observing system advanced microwave sounding unit-A2 (EOS/AMSU-A2), referred to as the unit. The unit is defined on drawing 1356006.

[A case of neuroendocrine cell carcinoma of the esophagus with lung metastases successfully treated with CPT-11/CDDP].

PubMed

Takeoka, Tomohira; Hirao, Motohiro; Fujitani, Kazumasa; Yamamoto, Kazuyoshi; Asaoka, Tadafumi; Ikenaga, Masakazu; Miyamoto, Atsushi; Ikeda, Masataka; Nakamori, Shoji; Sekimoto, Mitsugu

2013-11-01

A 70-year-old man presented with dysphagia to another institution and was referred to our hospital. We diagnosed the patient with primary neuroendocrine cell carcinoma and squamous cell carcinoma of the esophagus. Following 2 courses of CDDP+5-FU+ADM combination neoadjuvant chemotherapy, the primary tumor had reduced in size. Thereafter, we performed subtotal esophagectomy by right thoracotomy, retrosternal gastric tube reconstruction, and 2-field lymph node dissection. Computed tomography scan 3 months after the surgery revealed lung metastasis. He received CPT-11+CDDP chemotherapy, and the disease was diagnosed as cCR. At present, he is alive without any evidence of recurrence 12 months after the surgery.

Effects of varenicline versus transdermal nicotine replacement therapy on cigarette demand on quit day in individuals with substance use disorders.

PubMed

Murphy, Cara M; MacKillop, James; Martin, Rosemarie A; Tidey, Jennifer W; Colby, Suzanne M; Rohsenow, Damaris J

2017-08-01

Cigarette demand is a behavioral economic measure of the relative value of cigarettes. Decreasing the value of cigarette reinforcement may help with quitting smoking. This study aimed to evaluate the effects of initial use of varenicline (VAR) versus nicotine replacement therapy (NRT) on demand for cigarettes on quit day among smokers with substance use disorders (SUD) and to determine whether reduced demand was associated with subsequent abstinence from smoking at 1 and 3 months. Participants (N = 110) were randomized to double-blind, double-placebo conditions: VAR with placebo NRT or NRT with placebo capsules. The cigarette purchase task (CPT) was used to assess demand for cigarettes at baseline and on quit day, following a 1-week medication dose run-up/placebo capsule lead-in and first day use of the patch. Demand for cigarettes decreased from baseline to quit day without significant differences between medications. Reductions in CPT intensity (number of cigarettes that would be smoked if they were free) and CPT breakpoint (lowest price at which no cigarettes would be purchased) predicted greater likelihood of abstaining on quit day. Reduced intensity predicted length of abstinence at 1 and 3 months while reduced breakpoint predicted only 1 month length of abstinence. Initial therapeutic doses of VAR and NRT resulted in similar reductions in cigarette reinforcement. Larger initial reductions in demand on quit day were associated with early success with abstaining from cigarettes. Behavioral economic approaches may be useful for identifying individuals who benefit less from pharmacotherapy and may need additional treatment resources. https://clinicaltrials.gov/ct2/show/NCT00756275.

Out-of-Hospital Combat Casualty Care in the Current War in Iraq

DTIC Science & Technology

2009-02-01

could not be cleared with available suction equipment (3). There were 10 instances of chitosan hemostatic dressing use (3% of wounded in action). A...Eagle: MAJ David Mathias, MD, CPT Tommy Laird, MPAS, EMPA-C, CPT Scott G. Sullivan, MPAS, PA-C, and CPT Anthony Freiler, PA-C. We also express our

Music-evoked incidental happiness modulates probability weighting during risky lottery choices

PubMed Central

Schulreich, Stefan; Heussen, Yana G.; Gerhardt, Holger; Mohr, Peter N. C.; Binkofski, Ferdinand C.; Koelsch, Stefan; Heekeren, Hauke R.

2014-01-01

We often make decisions with uncertain consequences. The outcomes of the choices we make are usually not perfectly predictable but probabilistic, and the probabilities can be known or unknown. Probability judgments, i.e., the assessment of unknown probabilities, can be influenced by evoked emotional states. This suggests that also the weighting of known probabilities in decision making under risk might be influenced by incidental emotions, i.e., emotions unrelated to the judgments and decisions at issue. Probability weighting describes the transformation of probabilities into subjective decision weights for outcomes and is one of the central components of cumulative prospect theory (CPT) that determine risk attitudes. We hypothesized that music-evoked emotions would modulate risk attitudes in the gain domain and in particular probability weighting. Our experiment featured a within-subject design consisting of four conditions in separate sessions. In each condition, the 41 participants listened to a different kind of music—happy, sad, or no music, or sequences of random tones—and performed a repeated pairwise lottery choice task. We found that participants chose the riskier lotteries significantly more often in the “happy” than in the “sad” and “random tones” conditions. Via structural regressions based on CPT, we found that the observed changes in participants' choices can be attributed to changes in the elevation parameter of the probability weighting function: in the “happy” condition, participants showed significantly higher decision weights associated with the larger payoffs than in the “sad” and “random tones” conditions. Moreover, elevation correlated positively with self-reported music-evoked happiness. Thus, our experimental results provide evidence in favor of a causal effect of incidental happiness on risk attitudes that can be explained by changes in probability weighting. PMID:24432007

Hyperactivity persists in male and female adults with ADHD and remains a highly discriminative feature of the disorder: a case-control study

PubMed Central

2012-01-01

Background Symptoms of hyperactivity are believed to fade with age leaving ADHD adults mostly inattentive and impulsive. Our aim was to test this assertion using objective measures of hyperactivity, impulsivity and inattention. Method Participants were 40 subjects with ADHD (23M/17F; 35±10 yrs) and 60 healthy adults (28M/32F; 29±9 yrs) blindly assessed using Wender-Reimherr interview ratings, Structured Clinical Interview for DSM-IV Disorders and DSM-IV criteria. Infrared motion capture systems tracked head and leg movements during performance of a No-4’s cognitive control task. Subjects also completed the Conners’ CPT-II. Results ADHD and controls differed significantly in activity and attention. Effect sizes for activity measures (d’ = 0.7–1.6) were, on average, two-fold larger than differences in attention or impulsivity, correlated more strongly with executive function ratings and were more discriminatory (ROC area = 0.83 for activity composite, 0.65 for No-4’s distraction composite, 0.63 for Conners’ CPT-II confidence index, 0.96 for the combined activity and attention diagnostic index). This finding was true for subjects with the predominantly inattentive subtype as well as subjects with combined or predominantly hyperactive/impulsive subtype. Males and females with ADHD were equally active. The superior accuracy of activity measures was confirmed using Random Forest and predictive modeling techniques. Conclusions Objectively measured hyperactivity persists in adults with ADHD and is a more discriminative feature of the disorder than computerized measures of inattention or impulsivity. This finding supports the hypothesis that a deficient ability to sit still remains a defining feature of the disorder in adults when it is measured objectively. PMID:23134619

Evaluation of the validity of the Psychology Experiment Building Language tests of vigilance, auditory memory, and decision making

PubMed Central

Mueller, Shane T.; Talebzadeh, Sara; Ki, Min Jung

2016-01-01

Background. The Psychology Experimental Building Language (PEBL) test battery (http://pebl.sourceforge.net/) is a popular application for neurobehavioral investigations. This study evaluated the correspondence between the PEBL and the non-PEBL versions of four executive function tests. Methods. In one cohort, young-adults (N = 44) completed both the Conner’s Continuous Performance Test (CCPT) and the PEBL CPT (PCPT) with the order counter-balanced. In a second cohort, participants (N = 47) completed a non-computerized (Wechsler) and a computerized (PEBL) Digit Span (WDS or PDS) both Forward and Backward. Participants also completed the Psychological Assessment Resources or the PEBL versions of the Iowa Gambling Task (PARIGT or PEBLIGT). Results. The between-test correlations were moderately high (reaction time r = 0.78, omission errors r = 0.65, commission errors r = 0.66) on the CPT. DS Forward was significantly greater than DS Backward on the WDS (p < .0005) and the PDS (p < .0005). The total WDS score was moderately correlated with the PDS (r = 0.56). The PARIGT and the PEBLIGTs showed a very similar pattern for response times across blocks, development of preference for Advantageous over Disadvantageous Decks, and Deck selections. However, the amount of money earned (score–loan) was significantly higher in the PEBLIGT during the last Block. Conclusions. These findings are broadly supportive of the criterion validity of the PEBL measures of sustained attention, short-term memory, and decision making. Select differences between workalike versions of the same test highlight how detailed aspects of implementation may have more important consequences for computerized testing than has been previously acknowledged. PMID:27014512

Music-evoked incidental happiness modulates probability weighting during risky lottery choices.

PubMed

Schulreich, Stefan; Heussen, Yana G; Gerhardt, Holger; Mohr, Peter N C; Binkofski, Ferdinand C; Koelsch, Stefan; Heekeren, Hauke R

2014-01-07

We often make decisions with uncertain consequences. The outcomes of the choices we make are usually not perfectly predictable but probabilistic, and the probabilities can be known or unknown. Probability judgments, i.e., the assessment of unknown probabilities, can be influenced by evoked emotional states. This suggests that also the weighting of known probabilities in decision making under risk might be influenced by incidental emotions, i.e., emotions unrelated to the judgments and decisions at issue. Probability weighting describes the transformation of probabilities into subjective decision weights for outcomes and is one of the central components of cumulative prospect theory (CPT) that determine risk attitudes. We hypothesized that music-evoked emotions would modulate risk attitudes in the gain domain and in particular probability weighting. Our experiment featured a within-subject design consisting of four conditions in separate sessions. In each condition, the 41 participants listened to a different kind of music-happy, sad, or no music, or sequences of random tones-and performed a repeated pairwise lottery choice task. We found that participants chose the riskier lotteries significantly more often in the "happy" than in the "sad" and "random tones" conditions. Via structural regressions based on CPT, we found that the observed changes in participants' choices can be attributed to changes in the elevation parameter of the probability weighting function: in the "happy" condition, participants showed significantly higher decision weights associated with the larger payoffs than in the "sad" and "random tones" conditions. Moreover, elevation correlated positively with self-reported music-evoked happiness. Thus, our experimental results provide evidence in favor of a causal effect of incidental happiness on risk attitudes that can be explained by changes in probability weighting.

Patterns of change in withdrawal symptoms, desire to smoke, reward motivation, and response inhibition across three months of smoking abstinence

PubMed Central

Dawkins, Lynne; Powell, Jane H.; Pickering, Alan; Powell, John; West, Robert

2009-01-01

Aims We have previously demonstrated that acute smoking abstinence is associated with lowered reward motivation and impaired response inhibition. This prospective study explores whether these impairments, along with withdrawal-related symptoms, recover over three months of sustained abstinence. Design Participants completed a 12-hour abstinent baseline assessment and were then randomly allocated to quit unaided or continue smoking. All were re-tested after 7 days, 1 month and 3 months. Successful quitters’ scores were compared with those of continuing smokers, who were tested after ad libitum smoking. Setting Goldsmiths, University of London. Participants 33 smokers who maintained abstinence to 3 months, and 31 continuing smokers. Measurements Indices previously demonstrated in this cohort of smokers to be sensitive to the effect of nicotine vs. acute abstinence: reward motivation (SHAPS, CARROT, Stroop); tasks of response inhibition (antisaccade task; CPT) and clinical indices of mood (HADS), withdrawal symptoms (MPSS) and desire to smoke. Findings SHAPS anhedonia and reward responsivity (CARROT) showed significant improvement and plateaued after a month of abstinence, not differing from the scores of continuing smokers tested in a satiated state. Mood, other withdrawal symptoms and desire to smoke all declined from acute abstinence to 1 month of cessation and were equivalent, or lower than, the levels reported by continuing, satiated smokers. Neither group showed a change in CPT errors over time whilst continuing smokers, but not abstainers, showed improved accuracy on the antisaccade task at 3 months. Conclusion Appetitive processes and related affective states appear to improve in smokers who remain nicotine-free for 3 months whereas response inhibition does not. Although in need of replication, the results tentatively suggest that poor inhibitory control may constitute a long-term risk factor for relapse and could be a target for intervention. PMID:19344444

A critique of a UK standardized test of finger rewarming after cold provocation in the diagnosis and staging of hand-arm vibration syndrome.

PubMed

Mason, H J; Poole, K; Saxton, J

2003-08-01

Accurate diagnosis and staging of hand-arm vibration syndrome (HAVS) is important in health surveillance of vibration-exposed workers and the substantial number of related medico-legal cases. The measurement of the rewarming rate of fingers after cold provocation to the hands (CPT) has been suggested as a useful test in diagnosing HAVS. To investigate the diagnostic value of a standardized version of the CPT test using a 15 degrees C cold challenge for 5 min applied in the recent compensation assessment of UK miners. Analysis of a subset of UK miners assessed at our unit, together with data from a small repeatability study of the standardized CPT in normal subjects. Rewarming time in the CPT was significantly lower in those subjects classified as vascular Stockholm stage 0 compared with Stockholm stages 1-3 combined, but did not discriminate between the stages of abnormality. Using the suggested cut-off in the CPT test, the sensitivity and specificity were calculated as 43 and 78%, respectively. Receiver operator characteristic analysis suggested that the rewarming time of highest accuracy gave a sensitivity of 66% and specificity of 59%. In 10 miners who reported unilateral hand blanching, there was no significant difference in CPT measurements between blanching and non-blanching hands. Repeat CPT measurements in normal subjects suggested mean differences of 52 and 107 s for each hand, and the Bland-Altman coefficient of repeatability was approximately 600 s for all fingers. Single application of this standardized CPT test may have limited value in diagnosing the vascular component of HAVS in an individual.

[Evaluation of a child protecting team by an independent cooperation partner - suggestions for an optimized procedure].

PubMed

Verocai, E; Kitzelmann, I; Juen, F; Simma, B

2013-07-01

Cooperation between different institutions in cases of child abuse is essential for the children and their families. The aim of this study is to evaluate the cooperation between the Child Protection Team (CPT) and the Youth Welfare Agency (YWF) in an academic teaching hospital. Is the child or the family already be known to the YWF? Was the suspicion of child abuse confirmed by the CPT? What impact did the CPT's report to the YWF have on the situation of the children, their families, and the members of the YWF?Between 1999 and 2009 196 cases were investigated by the CPT; 80 of them had been reported to the YWF. In 45 of the 80 cases, structured interviews were completed by the YWF social workers. In the remaining 35, the questionnaires were not fully completed (n=15), the responsible social workers not present (n=6), or data were not available due to change of -residence (n=14).Maltreatment was suspected in 21/45 (47%), child abuse in 7 (16%), child neglect in 12 (26%), and a combination of the above in 5 (11%) children. Of the children, 26/45 (58%) were already known to the YWF before being contacted by the CPT, and in 34/45 (75%) children either institutions reported the case to the criminal prosecution authorities. Positive changes were seen in 35/45 (78%) children and in 19/45 (42%) families and the CPT's report was considered helpful for the social workers in 41/45 (91%) children.A CPT is able to correctly identify new cases of child abuse. The activity of the CPT has a positive influence on the situation of affected children, their families, and the respective staff members of the YWF. © Georg Thieme Verlag KG Stuttgart · New York.

SYMPATHETIC NEURAL AND HEMODYNAMIC RESPONSES DURING COLD PRESSOR TEST IN ELDERLY BLACKS AND WHITES

PubMed Central

Okada, Yoshiyuki; Jarvis, Sara S.; Best, Stuart A.; Edwards, Jeffrey G.; Hendrix, Joseph M.; Adams-Huet, Beverley; Vongpatanasin, Wanpen; Levine, Benjamin D.; Fu, Qi

2016-01-01

The sympathetic response during the cold pressor test (CPT) has been reported to be greater in young blacks than whites, especially in those with a family history of hypertension. Since blood pressure (BP) increases with age, we evaluated whether elderly blacks have greater sympathetic activation during CPT than age-matched whites. BP, heart rate (HR), cardiac output (Qc), and muscle sympathetic nerve activity (MSNA) were measured during supine baseline, 2-min CPT, and 3-min recovery in 47 elderly [68±7 (SD) yrs] volunteers (12 blacks, 35 whites). Baseline BP, HR, Qc, or MSNA did not differ between races. Systolic and diastolic BP (DBP) and HR increased during CPT (all P<0.001) with no racial differences (all P>0.05). Qc increased during CPT and up to 30 sec of recovery in both groups, but was lower in blacks than whites. MSNA increased during CPT in both groups (both P<0.001); the increase in burst frequency was similar between groups, while the increase in total activity was smaller in blacks (P=0.030 for interaction). Peak change (Δ) in DBP was correlated with Δ total activity at 1 min into CPT in both blacks (r=0.78, P=0.003) and whites (r=0.43, P=0.009), while the slope was significantly greater in blacks (P=0.007). Thus, elderly blacks have smaller sympathetic and central hemodynamic (e.g., Qc) responses, but a greater pressor response for a given sympathetic activation during CPT than elderly whites. This response may stem from augmented sympathetic vascular transduction, greater sympathetic activation to other vascular bed(s), and/or enhanced non-adrenergically mediated vasoconstriction in elderly blacks. PMID:27021009

Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics.

PubMed

Innocenti, Federico; Kroetz, Deanna L; Schuetz, Erin; Dolan, M Eileen; Ramírez, Jacqueline; Relling, Mary; Chen, Peixian; Das, Soma; Rosner, Gary L; Ratain, Mark J

2009-06-01

We aim to identify genetic variation, in addition to the UGT1A1*28 polymorphism, that can explain the variability in irinotecan (CPT-11) pharmacokinetics and neutropenia in cancer patients. Pharmacokinetic, genetic, and clinical data were obtained from 85 advanced cancer patients treated with single-agent CPT-11 every 3 weeks at doses of 300 mg/m(2) (n = 20) and 350 mg/m(2) (n = 65). Forty-two common variants were genotyped in 12 candidate genes of the CPT-11 pathway using several methodologies. Univariate and multivariate models of absolute neutrophil count (ANC) nadir and pharmacokinetic parameters were evaluated. Almost 50% of the variation in ANC nadir is explained by UGT1A1*93, ABCC1 IVS11 -48C>T, SLCO1B1*1b, ANC baseline levels, sex, and race (P < .0001). More than 40% of the variation in CPT-11 area under the curve (AUC) is explained by ABCC2 -24C>T, SLCO1B1*5, HNF1A 79A>C, age, and CPT-11 dose (P < .0001). Almost 30% of the variability in SN-38 (the active metabolite of CPT-11) AUC is explained by ABCC1 1684T>C, ABCB1 IVS9 -44A>G, and UGT1A1*93 (P = .004). Other models explained 17%, 23%, and 27% of the variation in APC (a metabolite of CPT-11), SN-38 glucuronide (SN-38G), and SN-38G/SN-38 AUCs, respectively. When tested in univariate models, pretreatment total bilirubin was able to modify the existing associations between genotypes and phenotypes. On the basis of this exploratory analysis, common polymorphisms in genes encoding for ABC and SLC transporters may have a significant impact on the pharmacokinetics and pharmacodynamics of CPT-11. Confirmatory studies are required.

Camptothecin-loaded fusogenic nanodroplets as ultrasound theranostic agent in stem cell-mediated drug-delivery system.

PubMed

Ho, Yi-Ju; Chiang, Yu-Jung; Kang, Shih-Tsung; Fan, Ching-Hsiang; Yeh, Chih-Kuang

2018-05-28

Adipose-derived stem cells (ADSCs) have been utilized in cellular delivery systems to carry therapeutic agents into tumors by migration. Drug-loaded nanodroplets release drugs and form bubbles after acoustic droplet vaporization (ADV) triggered by ultrasound stimulation, providing a system for ultrasound-induced cellular delivery of theranostic agents. In order to improve the efficiency of drug release, fusogenic nanodroplets were designed to go from nano to micron size upon uptake by ADSCs for reducing ADV threshold. The purpose of our study was to demonstrate the utility of camptothecin-loaded fusogenic nanodroplets (CPT-FNDs) as ultrasound theranostic agents in an ADSCs delivery system. CPT-FNDs showed an increase in size from 81.6 ± 3.5 to 1043.5 ± 28.3 nm and improved CPT release from 22.0 ± 1.8% to 37.6 ± 2.1%, demonstrating the fusion ability of CPT-FNDs. CPT-FNDs-loaded ADSCs demonstrated a cell viability of 77 ± 4%, and the in vitro migration ability was 3.2 ± 1.2-fold for the tumor condition compared to the cell growth condition. Ultrasound enhancement imaging showed intratumoral ADV-generated bubble formation (increasing 3.24 ± 0.47 dB) triggered by ultrasound after CPT-FNDs-loaded ADSCs migration into B16F0 tumors. Histological images revealed intratumoral distribution of CPT-FNDs-loaded ADSCs and tissue damage due to the ADV. The CPT-FNDs can be used as theranostic agents in an ADSCs delivery system to provide the ultrasound contrast imaging and deliver combination therapy of drug release and physical damage after ADV. Copyright © 2018 Elsevier B.V. All rights reserved.

Cotrimoxazole prophylactic treatment prevents malaria in children in sub-Saharan Africa: systematic review and meta-analysis.

PubMed

Mbeye, Nyanyiwe M; ter Kuile, Feiko O; Davies, Mary-Ann; Phiri, Kamija S; Egger, Matthias; Wandeler, Gilles

2014-09-01

Cotrimoxazole prophylactic treatment (CPT) prevents opportunistic infections in HIV-infected or HIV-exposed children, but estimates of the effectiveness in preventing malaria vary. We reviewed studies that examined the effect of CPT on incidence of malaria in children in sub-Saharan Africa. We searched PubMed and EMBASE for randomised controlled trials (RCTs) and cohort studies on the effect of CPT on incidence of malaria and mortality in children and extracted data on the prevalence of sulphadoxine-pyrimethamine resistance-conferring point mutations. Incidence rate ratios (IRR) from individual studies were combined using random effects meta-analysis; confounder-adjusted estimates were used for cohort studies. The importance of resistance was examined in meta-regression analyses. Three RCTs and four cohort studies with 5039 children (1692 HIV-exposed; 2800 HIV-uninfected; 1486 HIV-infected) were included. Children on CPT were less likely to develop clinical malaria episodes than those without prophylaxis (combined IRR 0.37, 95% confidence interval: 0.21-0.66), but there was substantial between-study heterogeneity (I-squared = 94%, P < 0.001). The protective efficacy of CPT was highest in an RCT from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta-regression analyses, there was some evidence that the efficacy of CPT declined with increasing levels of resistance. Mortality was reduced with CPT in an RCT from Zambia, but not in a cohort study from Côte d'Ivoire. Cotrimoxazole prophylactic treatment reduces incidence of malaria and mortality in children in sub-Saharan Africa, but study designs, settings and results were heterogeneous. CPT appears to be beneficial for HIV-infected and HIV-exposed as well as HIV-uninfected children. © 2014 John Wiley & Sons Ltd.

Flux control exerted by overt carnitine palmitoyltransferase over palmitoyl-CoA oxidation and ketogenesis is lower in suckling than in adult rats.

PubMed Central

Krauss, S; Lascelles, C V; Zammit, V A; Quant, P A

1996-01-01

We examined the potential of overt carnitine palmitoyltransferase (CPT I) to control the hepatic catabolism of palmitoyl-CoA in suckling and adult rats, using a conceptually simplified model of fatty acid oxidation and ketogenesis. By applying top-down control analysis, we quantified the control exerted by CPT I over total carbon flux from palmitoyl-CoA to ketone bodies and carbon dioxide. Our results show that in both suckling and adult rat, CPT I exerts very significant control over the pathways under investigation. However, under the sets of conditions we studied, less control is exerted by CPT I over total carbon flux in mitochondria isolated from suckling rats than in those isolated from adult rats. Furthermore the flux control coefficient of CPT I changes with malonyl-CoA concentration and ATP turnover rate. PMID:8912677

Estimating the costs of VA ambulatory care.

PubMed

Phibbs, Ciaran S; Bhandari, Aman; Yu, Wei; Barnett, Paul G

2003-09-01

This article reports how we matched Common Procedure Terminology (CPT) codes with Medicare payment rates and aggregate Veterans Affairs (VA) budget data to estimate the costs of every VA ambulatory encounter. Converting CPT codes to encounter-level costs was more complex than a simple match of Medicare reimbursements to CPT codes. About 40 percent of the CPT codes used in VA, representing about 20 percent of procedures, did not have a Medicare payment rate and required other cost estimates. Reconciling aggregated estimated costs to the VA budget allocations for outpatient care produced final VA cost estimates that were lower than projected Medicare reimbursements. The methods used to estimate costs for encounters could be replicated for other settings. They are potentially useful for any system that does not generate billing data, when CPT codes are simpler to collect than billing data, or when there is a need to standardize cost estimates across data sources.

Teaching clinical pharmacology and therapeutics with an emphasis on the therapeutic reasoning of undergraduate medical students

PubMed Central

Richir, Milan C.; Tichelaar, Jelle; Geijteman, Eric C. T.

2008-01-01

Background The rational prescribing of drugs is an essential skill of medical doctors. Clinical pharmacologists play an important role in the development of these skills by teaching clinical pharmacology and therapeutics (CP&T) to undergraduate medical students. Although the approaches to teaching CP&T have undergone many changes over the last decennia, it is essential that the actual teaching of CP&T continues to be a major part of the undergraduate medical curriculum. Objectives The learning objectives of CP&T teaching in terms of developing the therapeutic competencies of undergraduate medical students are described, with an emphasis on therapeutic decision-making. On the basis of current theories of cognitive psychology and medical education, context-learning is presented as an effective approach by which to achieve therapeutic competencies. An example of a CP&T curriculum is presented. PMID:18228012

Medical decision making: guide to improved CPT coding.

PubMed

Holt, Jim; Warsy, Ambreen; Wright, Paula

2010-04-01

The Current Procedural Terminology (CPT) coding system for office visits, which has been in use since 1995, has not been well studied, but it is generally agreed that the system contains much room for error. In fact, the available literature suggests that only slightly more than half of physicians will agree on the same CPT code for a given visit, and only 60% of professional coders will agree on the same code for a particular visit. In addition, the criteria used to assign a code are often related to the amount of written documentation. The goal of this study was to evaluate two novel methods to assess if the most appropriate CPT code is used: the level of medical decision making, or the sum of all problems mentioned by the patient during the visit. The authors-a professional coder, a residency faculty member, and a PGY-3 family medicine resident-reviewed 351 randomly selected visit notes from two residency programs in the Northeast Tennessee region for the level of documentation, the level of medical decision making, and the total number of problems addressed. The authors assigned appropriate CPT codes at each of those three levels. Substantial undercoding occurred at each of the three levels. Approximately 33% of visits were undercoded based on the written documentation. Approximately 50% of the visits were undercoded based on the level of documented medical decision making. Approximately 80% of the visits were undercoded based on the total number of problems which the patient presented during the visit. Interrater agreement was fair, and similar to that noted in other coding studies. Undercoding is not only common in a family medicine residency program but it also occurs at levels that would not be evident from a simple audit of the documentation on the visit note. Undercoding also occurs from not exploring problems mentioned by the patient and not documenting additional work that was performed. Family physicians may benefit from minor alterations in their documentation of office visit notes.

Quantitative sensory test for primary restless legs syndrome/Willis-Ekbom disease using the current perception threshold test.

PubMed

Cho, Yong Won; Kang, Min-Sung; Kim, Keun Tae; Do, So Young; Lim, Jung-Geun; Lee, So Young; Motamedi, Gholam K

2017-02-01

Restless legs syndrome/Willis-Ekbom disease (RLS/WED) is a sensorimotor neurological disorder, and it is especially aggravated at night. The purpose of this study was to investigate the diurnal sensory dysfunction in primary RLS/WED using the current perception threshold (CPT) test, compared to healthy controls. Thirty primary RLS/WED subjects and 30 healthy controls were enrolled. The severity of RLS/WED and sleep problems were evaluated in all subjects. Peripheral polyneuropathy was excluded through neurological examination and nerve conduction study. We used the Neurometer ® system for the CPT test and applied three different parameters (2000 Hz, 250 Hz, and 5 Hz), to stimulate both big toes. The CPT test was performed twice, once during the asymptomatic daytime period and again in the evening, when the patients were symptomatic. The mean ages of the RLS/WED group and controls were 50.5 ± 11.7 (22; 73.3% female), and 46.3 ± 11.4 (24; 80.0% female), respectively. The mean international RLS/WED study group severity scale score was 28.6 ± 4.25. There was no significant difference in the current perception thresholds between the RLS/WED patients and controls in daytime. However, the RLS/WED patients had lower mean CPT measurements for all three stimulation protocols in the evening (2000 Hz: 393.2 ± 93.7 vs 430.8 ± 79.6, 250 Hz: 172.0 ± 48.4 vs 198.5 ± 38.2, and 5 Hz: 98.0 ± 34.1 vs 124.6 ± 31.3), while the healthy controls showed no difference. RLS patients showed a lower CPT in the evening. The diurnal variation of hyperalgesia in RLS/WED patients indicates a central (circadian) sensory processing disturbance rather than a peripheral disturbance. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical utility of the Conners' Continuous Performance Test-II to detect poor effort in U.S. military personnel following traumatic brain injury.

PubMed

Lange, Rael T; Iverson, Grant L; Brickell, Tracey A; Staver, Tara; Pancholi, Sonal; Bhagwat, Aditya; French, Louis M

2013-06-01

The purpose of this study is to examine the clinical utility of the Conners' Continuous Performance Test (CPT-II) as an embedded marker of poor effort in military personnel undergoing neuropsychological evaluations following traumatic brain injury. Participants were 158 U.S. military service members divided into 3 groups on the basis of brain injury severity and performance (pass/fail) on 2 symptom validity tests: Mild Traumatic Brain Injury (MTBI)-Pass (n = 87), MTBI-Fail (n = 42), and severe traumatic brain injury (STBI)-Pass (n = 29). The MTBI-Fail group performed worse on the majority of CPT-II measures compared with both the MTBI-Pass and STBI-Pass groups. When comparing the MTBI-Fail group and MTBI-Pass groups, the most accurate measure for identifying poor effort was the Commission T score. When selected measures were combined (i.e., Omissions, Commissions, and Perseverations), there was a very small increase in sensitivity (from .26 to .29). When comparing the MTBI-Fail group and STBI-Pass groups, the most accurate measure for identifying poor effort was the Omission and Commissions T score. When selected measures were combined, sensitivity again increased (from .24 to .45). Overall, these results suggest that individual CPT-II measures can be useful for identifying people who are suspected of providing poor effort from those who have provided adequate effort. However, due to low sensitivity and modest negative predictive power values, this measure cannot be used in isolation to detect poor effort, and is largely useful as a test to "rule in," not "rule out" poor effort. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Differentiating Motivational from Affective Influence of Performance-contingent Reward on Cognitive Control: The Wanting Component Enhances Both Proactive and Reactive Control.

PubMed

Chaillou, Anne-Clémence; Giersch, Anne; Hoonakker, Marc; Capa, Rémi L; Bonnefond, Anne

2017-04-01

Positive affect strongly modulates goal-directed behaviors and cognitive control mechanisms. It often results from the presence of a pleasant stimulus in the environment, whether that stimulus appears unpredictably or as a consequence of a particular behavior. The influence of positive affect linked to a random pleasant stimulus differs from the influence of positive affect resulting from performance-contingent pleasant stimuli. However, the mechanisms by which the performance contingency of pleasant stimuli modulates the influence of positive affect on cognitive control mechanisms have not been elucidated. Here, we tested the hypothesis that these differentiated effects are the consequence of the activation of the motivational "wanting" component specifically under performance contingency conditions. To that end, we directly compared the effects on cognitive control of pleasant stimuli (a monetary reward) attributed in a performance contingent manner, and of random pleasant stimuli (positive picture) not related to performance, during an AX-CPT task. Both proactive and reactive modes of control were increased specifically by performance contingency, as reflected by faster reaction times and larger amplitude of the CNV and P3a components. Our findings advance our understanding of the respective effects of affect and motivation, which is of special interest regarding alterations of emotion-motivation interaction found in several psychopathological disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Sonic CPT Probing in Support of DNAPL Characterization

DTIC Science & Technology

2000-11-21

directed at developing advanced sensors for delivery by the cone penetrometer. To accommodate these new sensors , probe sizes have increased (from 1.44-in...capability of the CPT, a sonic vibratory system was integrated with conventional CPT to advance cone penetrometer sensor packages past currently attainable...Sonic, Cone Penetrometer, Site Characterization, Fluorescense, Sensor , Shock Hardened Sensors , Geoprobe• 17. SECURITY CLASSIFICATION OF REPORT

Josephson Parametric Amplifer Based on a Cavity-Embedded Cooper Pair Transistor

NASA Astrophysics Data System (ADS)

Li, Juliang; Rimberg, A. J.

In this experiment a cavity-embedded Cooper-pair transistor (cCPT) is used as a Josephson parametric amplifier. The cCPT consists of a Cooper pair transistor placed at the voltage antinode of a 5.7 GHz shorted quarter-wave resonator so that the CPT provides a galvanic connection between the cavity's central conductor and ground plane, which forms a SQUID loop. Both the flux threading the loop as well as the gate charge can be modulated, and each can provide the parametric pumping. The reflected signal from the cCPT is further amplified by both SLUG and HEMT amplifiers for characterizing the parametric amplification. A first application of the parametric amplification is to improve the charge sensitivity of a single electron charge detector. This can be done either by pumping on a side band or by shifting the charge state of the cCPT near a bifurcation point. Stimulated emission has been also observed when the cCPT is pumped at twice the resonant frequency in the absence of an input signal. This could allow investigation of the dynamic Casimir effect as well as generation of non-classical photon states. Supported by Grants ARO W911NF-13-10377 and NSF DMR 1507400.

New cancer-treatment model of photodynamic therapy combined with a type I topoisomerase inhibitor, CPT-11, against HeLa cell tumors in nude mice used by OPO parametric tunable laser

NASA Astrophysics Data System (ADS)

Yoshida, Takato O.; Matsuzawa, Eiji; Matsuo, Tetsumichi; Koide, Yukio; Terakawa, Susumu; Yokokura, Teruo; Hirano, Toru

1995-03-01

A new cancer-treatment model, photodynamic therapy (PDT) combined with a type I topoisomerase inhibitor, camptothecin derivative (CPT-11), against HeLa cell tumors in BALB/c nude mice has been developed using a wide-band tunable coherent light source operated on optical parametric oscillation (OPO parametric tunable laser). The Photosan-3 PDT and CPT-11 combined therapy was remarkably effective, that is the inhibition rate (I.R.) 40 - 80%, as compared to PDT only in vivo. The analysis of HpD (Photosan-3) and CPT-11 effects on cultured HeLa cells in vitro has been studied by a video-enhanced contrast differential interference contrast microscope (VEC-DIC). Photosan-3 with 600 nm light killed cells by mitochondrial damage within 50 min, but not with 700 nm light. CPT-11 with 700 - 400 nm light killed cells within 50 min after nucleolus damage appeared after around 30 min. The localization of CPT-11 in cells was observed as fluorescence images in the nucleus, particularly the nucleoral area produced clear images using an Argus 100.

Multidisciplinary Child Protection Decision Making About Physical Abuse: Determining Substantiation Thresholds and Biases

PubMed Central

Jent, Jason F.; Eaton, Cyd K.; Knickerbocker, Lauren; Lambert, Walter F.; Merrick, Melissa T.; Dandes, Susan K.

2011-01-01

The current study examined the threshold at which multidisciplinary child protection team (CPT) professionals substantiate physical abuse allegations and the extent that they utilize potentially biased constructs in their decision making when presented with the same case evidence. State legal definitions of child maltreatment are broad. Therefore, the burden of interpretation is largely on CPT professionals who must determine at what threshold physical acts by parents surpass corporal discipline and constitute child physical abuse. Biased or subjective decisions may be made if certain case-specific characteristics or CPT professionals’ personal characteristics are used in making physical abuse determinations. Case vignettes with visual depictions of inflicted injuries were sent to CPT professionals in Florida and their substantiation decisions, personal beliefs about corporal discipline, and coercive discipline were collected. Results of the study demonstrated relatively high agreement among professionals across vignettes about what constitutes physical abuse. Further, CPT professionals strongly considered their perceptions of the severity of inflicted injuries in substantiation decisions. Although case specific characteristics did not bias decisions in a systematic way, some CPT professional characteristics influenced the substantiation of physical abuse. Practice implications and future directions of research are discussed. PMID:21804681

A Comparative Study of Performance in the Conners' Continuous Performance Test between Brazilian and North American Children

ERIC Educational Resources Information Center

Miranda, Monica Carolina; Sinnes, Elaine Girao; Pompeia, Sabine; Bueno, Orlando Francisco Amodeo

2008-01-01

Objective: The present study investigated the performance of Brazilian children in the Continuous Performance Test, CPT-II, and compared results to those of the norms obtained in the United States. Method: The U.S. norms were compared to those of a Brazilian sample composed of 6- to 11-year-olds separated into 4 age-groups (half boys) that…

Validity of the Factor Structure of Conners' CPT

ERIC Educational Resources Information Center

Egeland, Jens; Kovalik-Gran, Iwona

2010-01-01

Objective: A previous factor analysis of the Conners' Continuous Performance Test (CCPT) indicates that the test measures 5 sub-functions of attention, namely "focused attention," "hyperactivity/impulsivity," "sustained attention," "vigilance," and "change in control." The present study further…

Psychotherapy for Military-Related PTSD: A Review of Randomized Clinical Trials.

PubMed

Steenkamp, Maria M; Litz, Brett T; Hoge, Charles W; Marmar, Charles R

2015-08-04

Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder common among military personnel and veterans. First-line psychotherapies most often recommended for PTSD consist mainly of "trauma-focused" psychotherapies that involve focusing on details of the trauma or associated cognitive and emotional effects. To examine the effectiveness of psychotherapies for PTSD in military and veteran populations. PubMed, PsycINFO, and PILOTS were searched for randomized clinical trials (RCTs) of individual and group psychotherapies for PTSD in military personnel and veterans, published from January 1980 to March 1, 2015. We also searched reference lists of articles, selected reviews, and meta-analyses. Of 891 publications initially identified, 36 were included. Two trauma-focused therapies, cognitive processing therapy (CPT) and prolonged exposure, have been the most frequently studied psychotherapies for military-related PTSD. Five RCTs of CPT (that included 481 patients) and 4 RCTs of prolonged exposure (that included 402 patients) met inclusion criteria. Focusing on intent-to-treat outcomes, within-group posttreatment effect sizes for CPT and prolonged exposure were large (Cohen d range, 0.78-1.10). CPT and prolonged exposure also outperformed waitlist and treatment-as-usual control conditions. Forty-nine percent to 70% of participants receiving CPT and prolonged exposure attained clinically meaningful symptom improvement (defined as a 10- to 12-point decrease in interviewer-assessed or self-reported symptoms). However, mean posttreatment scores for CPT and prolonged exposure remained at or above clinical criteria for PTSD, and approximately two-thirds of patients receiving CPT or prolonged exposure retained their PTSD diagnosis after treatment (range, 60%-72%). CPT and prolonged exposure were marginally superior compared with non-trauma-focused psychotherapy comparison conditions. In military and veteran populations, trials of the first-line trauma-focused interventions CPT and prolonged exposure have shown clinically meaningful improvements for many patients with PTSD. However, nonresponse rates have been high, many patients continue to have symptoms, and trauma-focused interventions show marginally superior results compared with active control conditions. There is a need for improvement in existing PTSD treatments and for development and testing of novel evidence-based treatments, both trauma-focused and non-trauma-focused.

[A Case of Advanced Gastric Cancer with Long-Term Survival after Chemotherapy with Combined S-1 and CPT-11].

PubMed

Hiratsuka, Miyuki; Ishibashi, Yuji; Suematsu, Yuki; Suda, Hiroshi; Takahashi, Miyuki; Saito, Hiroyuki; Omori, Keita; Morita, Akihiko; Wakabayashi, Kazuhiko; Ito, Yutaka

2015-11-01

Here, we report a 54-year-old man diagnosed with type 3 advanced gastric cancer who underwent a total gastrectomy and splenectomy plus D2 lymphadenectomy. The pathologic diagnosis was Stage Ⅳ (T3N0H0P0CY1M1). Sixteen courses of combined S-1/CPT-11 chemotherapy were completed, at which time the CPT-11 was discontinued because of malaise, and S-1 alone was continued for a year. The patient is well and has been recurrence-free for 7 years. Thus, he is considered a long- term survivor who was treated with combination S-1/CPT-11 chemotherapy.

Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia

PubMed Central

Rinaldi, Carlo; Schmidt, Thomas; Situ, Alan J.; Johnson, Janel O.; Lee, Philip R.; Chen, Ke-lian; Bott, Laura C.; Fadó, Rut; Harmison, George H.; Parodi, Sara; Grunseich, Christopher; Renvoisé, Benoît; Biesecker, Leslie G.; De Michele, Giuseppe; Santorelli, Filippo M.; Filla, Alessandro; Stevanin, Giovanni; Dürr, Alexandra; Brice, Alexis; Casals, Núria; Traynor, Bryan J.; Blackstone, Craig; Ulmer, Tobias S.; Fischbeck, Kenneth H.

2017-01-01

IMPORTANCE The family of genes implicated in hereditary spastic paraplegias (HSPs) is quickly expanding, mostly owing to the widespread availability of next-generation DNA sequencing methods. Nevertheless, a genetic diagnosis remains unavailable for many patients. OBJECTIVE To identify the genetic cause for a novel form of pure autosomal dominant HSP. DESIGN, SETTING, AND PARTICIPANTS We examined and followed up with a family presenting to a tertiary referral center for evaluation of HSP for a decade until August 2014. Whole-exome sequencing was performed in 4 patients from the same family and was integrated with linkage analysis. Sanger sequencing was used to confirm the presence of the candidate variant in the remaining affected and unaffected members of the family and screen the additional patients with HSP. Five affected and 6 unaffected participants from a 3-generation family with pure adult-onset autosomal dominant HSP of unknown genetic origin were included. Additionally, 163 unrelated participants with pure HSP of unknown genetic cause were screened. MAIN OUTCOME AND MEASURE Mutation in the neuronal isoform of carnitine palmitoyl-transferase (CPT1C) gene. RESULTS We identified the nucleotide substitution c.109C>T in exon 3 of CPT1C, which determined the base substitution of an evolutionarily conserved Cys residue for an Arg in the gene product. This variant strictly cosegregated with the disease phenotype and was absent in online single-nucleotide polymorphism databases and in 712 additional exomes of control participants. We showed that CPT1C, which localizes to the endoplasmic reticulum, is expressed in motor neurons and interacts with atlastin-1, an endoplasmic reticulum protein encoded by the ATL1 gene known to be mutated in pure HSPs. The mutation, as indicated by nuclear magnetic resonance spectroscopy studies, alters the protein conformation and reduces the mean (SD) number (213.0 [46.99] vs 81.9 [14.2]; P < .01) and size (0.29 [0.01] vs 0.26 [0.01]; P < .05) of lipid droplets on overexpression in cells. We also observed a reduction of mean (SD) lipid droplets in primary cortical neurons isolated from Cpt1c−/− mice as compared with wild-type mice (1.0 [0.12] vs 0.44 [0.05]; P < .001), suggesting a dominant negative mechanism for the mutation. CONCLUSIONS AND RELEVANCE This study expands the genetics of autosomal dominant HSP and is the first, to our knowledge, to link mutation in CPT1C with a human disease. The association of the CPT1C mutation with changes in lipid droplet biogenesis supports a role for altered lipid-mediated signal transduction in HSP pathogenesis. PMID:25751282

Corporal artistic training influences attention: a pilot study.

PubMed

Ribeiro, Mônica Medeiros; Lima, Isabela; Malloy-Diniz, Leandro; Lage, Guilherme; Pimentel, Lucia Gouvêa; Teixeira, Antônio Lúcio

2014-06-01

This study assessed the effect of the Body Rhythmics (BRIM) on actors' attentional processes. BRIM is a combination of exercises using numbers and rules that enact musical parameters in the moving body through displacements. Male actors (N = 22) participated in the study: 7 in the BRIM (Study) group and 15 in the Control group (groups were equivalent on mean Raven's IQ). The Continuous Performance Test (CPT-II) was administered before and after an intensive period of BRIM training. There was no significant difference on the CPT-II before training. Group results for before vs after training showed a significant difference for reaction time for the Study group. There was also a trend to increased errors of commission in the Study group after BRIM training.

The effects of exposure to traumatic stressors on inhibitory control in police officers: a dense electrode array study using a Go/NoGo continuous performance task.

PubMed

Covey, Thomas J; Shucard, Janet L; Violanti, John M; Lee, Jeff; Shucard, David W

2013-03-01

Exposure to psychologically stressful and traumatic experiences and the requirement of heightened attention to environmental stimuli are common in police work. Police officers are at increased risk for stress-related disorders such as Post-Traumatic Stress Disorder (PTSD). Traumatic experiences can result in changes to brain structure and function associated with attention and cognitive control processes (such as response inhibition). Despite the significance that these cognitive functions may have on job performance in police officers, few studies have examined the effects of exposure to traumatic events on top-down cognitive control functions in police. In the present study, a dense electrode array system was used to examined the N2 and P3 components of the event-related potential (ERP) during a Go/NoGo continuous performance task (Go/NoGo CPT) in trauma-exposed police officers who did not meet criteria for a current diagnosis of PTSD and in non-trauma exposed civilian controls. Amplitude and latency were obtained to Go, NoGo, and non-target trials. The major between-group findings were for P3 amplitude. There were no group effects for N2. Both groups had an enhanced fronto-central P3 amplitude to NoGo compared to Go trials. However, police had greater P3 amplitude compared to controls for all trial types (Go, NoGo, non-target). PTSD symptom scores in police officers were positively correlated with fronto-central NoGo P3 amplitude, but not with posterior NoGo amplitude. This study provides evidence of heightened attention and/or arousal in police officers as indicated by the generally greater P3 amplitude in police compared to controls during a task requiring sustained attention and inhibitory control. Greater PTSD symptom severity in trauma-exposed individuals may affect frontal cognitive control systems related to response inhibition. Copyright © 2013 Elsevier B.V. All rights reserved.

Compound Specific Extraction of Camptothecin from Nothapodytes nimmoniana and Piperine from Piper nigrum Using Accelerated Solvent Extractor

PubMed Central

Upadhya, Vinayak; Pai, Sandeep R.; Sharma, Ajay K.; Hegde, Harsha V.; Kholkute, Sanjiva D.; Joshi, Rajesh K.

2014-01-01

Effects of varying temperatures with constant pressure of solvent on extraction efficiency of two chemically different alkaloids were studied. Camptothecin (CPT) from stem of Nothapodytes nimmoniana (Grah.) Mabb. and piperine from the fruits of Piper nigrum L. were extracted using Accelerated Solvent Extractor (ASE). Three cycles of extraction for a particular sample cell at a given temperature assured complete extraction. CPT and piperine were determined and quantified by using a simple and efficient UFLC-PDA (245 and 343 nm) method. Temperature increased efficiency of extraction to yield higher amount of CPT, whereas temperature had diminutive effect on yield of piperine. Maximum yield for CPT was achieved at 80°C and for piperine at 40°C. Thus, the study determines compound specific extraction of CPT from N. nimmoniana and piperine from P. nigrum using ASE method. The present study indicates the use of this method for simple, fast, and accurate extraction of the compound of interest. PMID:24527258

Conventional physical therapy and physical therapy based on reflex stimulation showed similar results in children with myelomeningocele.

PubMed

Aizawa, Carolina Y P; Morales, Mariana P; Lundberg, Carolina; Moura, Maria Clara D Soares de; Pinto, Fernando C G; Voos, Mariana C; Hasue, Renata H

2017-03-01

We aimed to investigate whether infants with myelomeningocele would improve their motor ability and functional independence after ten sessions of physical therapy and compare the outcomes of conventional physical therapy (CPT) to a physical therapy program based on reflex stimulation (RPT). Twelve children were allocated to CPT (n = 6, age 18.3 months) or RPT (n = 6, age 18.2 months). The RPT involved proprioceptive neuromuscular facilitation. Children were assessed with the Gross Motor Function Measure and the Pediatric Evaluation of Disability Inventory before and after treatment. Mann-Whitney tests compared the improvement on the two scales of CPT versus RPT and the Wilcoxon test compared CPT to RPT (before vs. after treatment). Possible correlations between the two scales were tested with Spearman correlation coefficients. Both groups showed improvement on self-care and mobility domains of both scales. There were no differences between the groups, before, or after intervention. The CPT and RPT showed similar results after ten weeks of treatment.

Evaluation of an implementation model: a national investigation of VA residential programs.

PubMed

Cook, Joan M; Dinnen, Stephanie; Coyne, James C; Thompson, Richard; Simiola, Vanessa; Ruzek, Josef; Schnurr, Paula P

2015-03-01

This national investigation utilizes qualitative data to evaluate an implementation model regarding factors influencing provider use of two evidence-based treatments for posttraumatic stress disorder (PTSD). Semi-structured qualitative interviews with 198 mental health providers from 38 Department of Veterans Affairs' (VA) residential treatment programs were used to explore these issues regarding prolonged exposure (PE) and cognitive processing therapy (CPT) in VA residential PTSD programs. Several unique and some overlapping predictors emerged. Leadership was viewed as an influence on implementation for both CPT and PE, while a lack of dedicated time and resources was viewed as a deterrent for both. Compatibility of CPT with providers' existing practices and beliefs, the ability to observe noticeable patient improvement, a perceived relative advantage of CPT over alternative treatments, and the presence of a supportive peer network emerged as influential on CPT implementation. Leadership was associated with PE implementation. Implications for the design and improvement of training and implementation efforts are discussed.

Microstructural Evolution of Inconel 625 and Inconel 686CPT Weld Metal for Clad Carbon Steel Linepipe Joints: A Comparator Study

NASA Astrophysics Data System (ADS)

Maltin, Charles A.; Galloway, Alexander M.; Mweemba, Martin

2014-07-01

Microstructural evolution of Inconel 625 and Inconel 686CPT filler metals, used for the fusion welding of clad carbon steel linepipe, has been investigated and compared. The effects of iron dilution from the linepipe parent material on the elemental segregation potential of the filler metal chemistry have been considered. The results obtained provide significant evidence to support the view that, in Inconel 686CPT weld metal, the segregation of tungsten is a function of the level of iron dilution from the parent material. The data presented indicate that the incoherent phase precipitated in the Inconel 686CPT weld metal has a morphology that is dependent on tungsten enrichment and, therefore, iron dilution. Furthermore, in the same weld metal, a continuous network of finer precipitates was observed. The Charpy impact toughness of each filler metal was evaluated, and the results highlighted the superior impact toughness of the Inconel 625 weld metal over that of Inconel 686CPT.

A Comparative Evaluation of Hydroxycamptothecin Drug Nanorods With and Without Methotrexate Prodrug Functionalization for Drug Delivery

NASA Astrophysics Data System (ADS)

Guo, Fuqiang; Fan, Zhongxiong; Yang, Jinbin; Li, Yang; Wang, Yange; Zhao, Hai; Xie, Liya; Hou, Zhenqing

2016-08-01

We developed a novel self-targeted multi-drug co-delivery system based on rod-shaped 10-hydroxycamptothecin (CPT) nanoanticancer drug (CPT NRs) followed by a surface functionalization with self-targeting PEGylated lipid-conjugated methotrexate (MTX) pro-anticancer drug. The self-targeting effect and in vitro cell viability of the MTX-PEG-CPT NRs on HeLa cells were demonstrated by comparative cellular uptake and MTT assay of the PEG-CPT NRs. In vitro studies showed the feasibility of using this high drug-loading MTX-PEG-CPT NRs in self-targeted drug delivery, controlled-/sustained-release, and synergistic cancer therapy. More importantly, this work would stimulate interest in the use of PEGylated lipid-conjugated MTX by introducing an early-phase tumor-targeting role and then driving a late-phase anticancer role for the highly convergent design of nanomulti-drug, which may advantageously offer a new and simple strategy for simultaneously targeting and treating FA receptor-overexpressing cancer cells.

Evaluation of Cone Penetrometer Testing (CPT) for Use with Transportation Projects Phase 1

DOT National Transportation Integrated Search

2008-07-01

The ODOT Office of Geotechnical Engineering (OGE) currently uses conventional drilling methods (e.g., hollow stem auger, solid stem auger) to perform subsurface investigations in unconsolidated materials. These techniques have been used for decades a...

Evaluation of cone penetration testing (CPT) for use with transportation projects : executive summary report.

DOT National Transportation Integrated Search

2011-04-01

The ODOT Office of Geotechnical : Engineering (OGE) currently uses : conventional drilling methods (e.g., hollow : stem auger, solid stem auger) to perform : subsurface investigations in soil. These : techniques have been used for decades and : have ...

Test of CPT and Lorentz symmetry in entangled neutral kaons with the KLOE experiment

NASA Astrophysics Data System (ADS)

Babusci, D.; Balwierz-Pytko, I.; Bencivenni, G.; Bloise, C.; Bossi, F.; Branchini, P.; Budano, A.; Caldeira Balkeståhl, L.; Capon, G.; Ceradini, F.; Ciambrone, P.; Curciarello, F.; Czerwiński, E.; Danè, E.; De Leo, V.; De Lucia, E.; De Robertis, G.; De Santis, A.; De Simone, P.; Di Cicco, A.; Di Domenico, A.; Di Donato, C.; Di Salvo, R.; Domenici, D.; Erriquez, O.; Fanizzi, G.; Fantini, A.; Felici, G.; Fiore, S.; Franzini, P.; Gajos, A.; Gauzzi, P.; Giardina, G.; Giovannella, S.; Graziani, E.; Happacher, F.; Heijkenskjöld, L.; Höistad, B.; Jacewicz, M.; Johansson, T.; Kacprzak, K.; Kamińska, D.; Kupsc, A.; Lee-Franzini, J.; Loddo, F.; Loffredo, S.; Mandaglio, G.; Martemianov, M.; Martini, M.; Mascolo, M.; Messi, R.; Miscetti, S.; Morello, G.; Moricciani, D.; Moskal, P.; Nguyen, F.; Palladino, A.; Passeri, A.; Patera, V.; Prado Longhi, I.; Ranieri, A.; Santangelo, P.; Sarra, I.; Schioppa, M.; Sciascia, B.; Silarski, M.; Taccini, C.; Tortora, L.; Venanzoni, G.; Wiślicki, W.; Wolke, M.; Zdebik, J.

2014-03-01

Neutral kaon pairs produced in ϕ decays in anti-symmetric entangled state can be exploited to search for violation of CPT symmetry and Lorentz invariance. We present an analysis of the CP-violating process ϕ→KSKL→π+π-π+π- based on 1.7 fb of data collected by the KLOE experiment at the Frascati ϕ-factory DAΦNE. The data are used to perform a measurement of the CPT-violating parameters Δaμ for neutral kaons in the context of the Standard Model Extension framework. The parameters measured in the reference frame of the fixed stars are: Δa0=(-6.0±7.7stat±3.1syst)×10-18 GeV, ΔaX=(0.9±1.5stat±0.6syst)×10-18 GeV, ΔaY=(-2.0±1.5stat±0.5syst)×10-18 GeV, ΔaZ=(3.1±1.7stat±0.5syst)×10-18 GeV. These are presently the most precise measurements in the quark sector of the Standard Model Extension.

Communication partner training for health care professionals in an inpatient rehabilitation setting: A parallel randomised trial.

PubMed

Heard, Renee; O'Halloran, Robyn; McKinley, Kathryn

2017-06-01

The purpose of this study is to determine if the E-Learning Plus communication partner training (CPT) programme is as effective as the Supported Conversation for Adults with Aphasia (SCA TM ) CPT programme in improving healthcare professionals' confidence and knowledge communicating with patients with aphasia. Forty-eight healthcare professionals working in inpatient rehabilitation participated. Participants were randomised to one of the CPT programmes. The three outcome measures were self-rating of confidence, self-rating of knowledge and a test of knowledge of aphasia. Measures were taken pre-, immediately post- and 3-4 months post-training. Data were analysed using mixed between within ANOVAs. Homogeneity of variance was adequate for self-rating of confidence and test of knowledge of aphasia data to continue analysis. There was a statistically significant difference in self-rating of confidence and knowledge of aphasia for both interventions across time. No statistically significant difference was found between the two interventions. Both CPT interventions were associated with an increase in health care professionals' confidence and knowledge of aphasia, but neither programme was superior. As the E-Learning Plus CPT programme is more accessible and sustainable in the Australian healthcare context, further work will continue on this CPT programme.

Brain Oscillations Elicited by the Cold Pressor Test: A Putative Index of Untreated Essential Hypertension.

PubMed

Papageorgiou, Christos; Manios, Efstathios; Tsaltas, Eleftheria; Koroboki, Eleni; Alevizaki, Maria; Angelopoulos, Elias; Dimopoulos, Meletios-Athanasios; Papageorgiou, Charalabos; Zakopoulos, Nikolaos

2017-01-01

Essential hypertension is associated with reduced pain sensitivity of unclear aetiology. This study explores this issue using the Cold Pressor Test (CPT), a reliable pain/stress model, comparing CPT-related EEG activity in first episode hypertensives and controls. 22 untreated hypertensives and 18 matched normotensives underwent 24-hour ambulatory blood pressure monitoring (ABPM). EEG recordings were taken before, during, and after CPT exposure. Significant group differences in CPT-induced EEG oscillations were covaried with the most robust cardiovascular differentiators by means of a Canonical Analysis. Positive correlations were noted between ABPM variables and Delta (1-4 Hz) oscillations during the tolerance phase; in high-alpha (10-12 Hz) oscillations during the stress unit and posttest phase; and in low-alpha (8-10 Hz) oscillations during CPT phases overall. Negative correlations were found between ABPM variables and Beta2 oscillations (16.5-20 Hz) during the posttest phase and Gamma (28.5-45 Hz) oscillations during the CPT phases overall. These relationships were localised at several sites across the cerebral hemispheres with predominance in the right hemisphere and left frontal lobe. These findings provide a starting point for increasing our understanding of the complex relationships between cerebral activation and cardiovascular functioning involved in regulating blood pressure changes.

Role of Borderline Personality Disorder in the Treatment of Military Sexual Trauma-related Posttraumatic Stress Disorder with Cognitive Processing Therapy.

PubMed

Holder, Nicholas; Holliday, Ryan; Pai, Anushka; Surís, Alina

2017-01-01

Cognitive Processing Therapy (CPT) is an effective evidence-based treatment for many, but not all, veterans with posttraumatic stress disorder (PTSD). Understanding the factors that contribute to poorer response to CPT is important for providing the best care to veterans diagnosed with PTSD. Researchers investigating the effectiveness of CPT for individuals with comorbid personality symptoms have found that borderline personality disorder (BPD) characteristics do not negatively affect treatment outcome; however, participants in those studies were not diagnosed with BPD. The current pilot study investigated the effect of a BPD diagnosis on CPT dropout and outcomes. Data were compiled from a larger randomized clinical trial. Twenty-seven female veterans with military sexual trauma-related PTSD received CPT. Dropout was evaluated by treatment completion and number of sessions attended. Treatment outcome was assessed by the Clinician Administered PTSD Scale (CAPS) and the PTSD Checklist (PCL). No significant differences were observed between veterans with and without BPD comorbidity for number of treatment sessions attended, and there was not a significant relationship between comorbidity status and treatment completion. A hierarchical linear modeling approach was used with BPD entered as a level 2 predictor of outcome. In our sample, veterans with BPD had higher PTSD symptom severity on the CAPS at baseline compared to veterans without BPD comorbidity. CPT was effective in reducing PTSD symptoms; however, BPD diagnosis did not influence treatment response over time on the CAPS or PCL. Our results provide initial support for the use of CPT in female veterans with MST-related PTSD and comorbid BPD.

Off-target effect of the Epac agonist 8-pCPT-2'-O-Me-cAMP on P2Y12 receptors in blood platelets.

PubMed

Herfindal, Lars; Nygaard, Gyrid; Kopperud, Reidun; Krakstad, Camilla; Døskeland, Stein Ove; Selheim, Frode

2013-08-09

The primary target of the cAMP analogue 8-pCPT-2'-O-Me-cAMP is exchange protein directly activated by cAMP (Epac). Here we tested potential off-target effects of the Epac activator on blood platelet activation signalling. We found that the Epac analogue 8-pCPT-2'-O-Me-cAMP inhibits agonist-induced-GPCR-stimulated, but not collagen-stimulated, P-selectin surface expression on Epac1 deficient platelets. In human platelets, 8-pCPT-2'-O-Me-cAMP inhibited P-selectin expression elicited by the PKC activator PMA. This effect was abolished in the presence of the extracellular ADP scavenger system CP/CPK. In silico modelling of 8-pCPT-2'O-Me-cAMP binding into the purinergic platelet receptor P2Y12 revealed that the analogue docks similar to the P2Y12 antagonist 2MeSAMP. The 8-pCPT-2'-O-Me-cAMP analogue per se, did not provoke Rap 1 (Rap 1-GTP) activation or phosphorylation on the vasodilator-stimulated phosphoprotein (VASP) at Ser-157. In addition, the protein kinase A (PKA) antagonists Rp-cAMPS and Rp-8-Br-cAMPS failed to block the inhibitory effect of 8-pCPT-2'-O-Me-cAMP on thrombin- and TRAP-induced Rap 1 activation, thus suggesting that PKA is not involved. We conclude that the 8-pCPT-2'-O-Me-cAMP analogue is able to inhibit agonist-induced-GPCR-stimulated P-selectin independent from Epac1; the off-target effect of the analogue appears to be mediated by antagonistic P2Y12 receptor binding. This has implications when using cAMP analogues on specialised system involving such receptors. We found, however that the Epac agonist 8-Br-2'-O-Me-cAMP did not affect platelet activation at similar concentrations. Copyright © 2013 Elsevier Inc. All rights reserved.

Bolus oral glutamine protects rats against CPT-11-induced diarrhea and differentially activates cytoprotective mechanisms in host intestine but not tumor.

PubMed

Xue, Hongyu; Sawyer, Michael B; Field, Catherine J; Dieleman, Levinus A; Murray, David; Baracos, Vickie E

2008-04-01

Dietary glutamine has been suggested to preserve structural and functional integrity of the gut and high dose bolus glutamine has been hypothesized to protect against potentially fatal endotoxic shock, hyperthermic stress, and side effects of chemotherapy. In this study, we aimed to relate the ability of high dose oral bolus glutamine to mitigate the severe diarrhea induced by 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11) chemotherapy to specific cytoprotective mechanisms [heat shock response, glutathione (GSH)] in gut and tumor tissues. Female rats bearing Ward colon tumor received CPT-11 (125 mg x kg(-1) x d(-1)x 3 d) with or without an oral glutamine bolus (0.75 g/kg) administered 30 min prior to each CPT-11 dose. Glutamine reduced incidence and severity of late-onset diarrhea following CPT-11 treatment (P < 0.05) and was associated with potentially beneficial and protective responses in the colon: 1) a 3.1- to 7.2-fold increase of heat shock protein (Hsp)25,-70, and -90alpha (P < 0.05); 2) increased reduced GSH (rGSH):oxidized GSH ratio (P < 0.05); 3) prevention of upregulated activity of a key bacterial enzyme (beta-glucuronidase) in the cecal content that mediates CPT-11 intestinal toxicity (P < 0.05); and 4) increased proportions of CD3+CD8+ lymphocytes and memory CD8+ subset in mesenteric lymph nodes following CPT-11 therapy. By contrast, glutamine treatment did not alter CPT-11's antitumor activity, the amino acid concentrations, Hsp expression, or the ratio of rGSH:oxidized GSH in the tumor. Our data demonstrate a striking dichotomy in the response of tumor and host to oral glutamine administration, concurring with the concept that this nutrient may favorably alter the balance between the host and tumor.

The Role of Intestinal Microbiota in Development of Irinotecan Toxicity and in Toxicity Reduction through Dietary Fibres in Rats

PubMed Central

Lin, Xiaoxi B.; Farhangfar, Arazm; Valcheva, Rosica; Sawyer, Michael B.; Dieleman, Levinus; Schieber, Andreas; Gänzle, Michael G.; Baracos, Vickie

2014-01-01

CPT-11 is a drug used as chemotherapy for colorectal cancer. CPT-11 causes toxic side-effects in patients. CPT-11 toxicity has been attributed to the activity of intestinal microbiota, however, intestinal microbiota may also have protective effects in CP!-11 chemotherapy. This study aimed to elucidate mechanisms through which microbiota and dietary fibres could modify host health. Rats bearing a Ward colon carcinoma were treated with a two-cycle CPT-11/5-fluorouracil therapy recapitulating clinical therapy of colorectal cancer. Animals were fed with a semi-purified diet or a semi-purified diet was supplemented with non-digestible carbohydrates (isomalto-oligosaccharides, resistant starch, fructo-oligosaccharides, or inulin) in 3 independent experiments. Changes in intestinal microbiota, bacteria translocating to mesenteric lymphnodes, cecal GUD activity, and cecal SCFA production, and the intestinal concentration of CPT-11 and its metabolites were analysed. Non-digestible carbohydrates significantly influenced feed intake, body weight and other indicators of animal health. The identification of translocating bacteria and their quantification in cecal microbiota indicated that overgrowth of the intestine by opportunistic pathogens was not a major contributor to CPT-11 toxicity. Remarkably, fecal GUD activity positively correlated to body weight and feed intake but negatively correlated to cecal SN-38 concentrations and IL1-β. The reduction in CPT-11 toxicity by non-digestible carbohydrates did not correlate to stimulation of specific bacterial taxa. However, cecal butyrate concentrations and feed intake were highly correlated. The protective role of intestinal butyrate production was substantiated by a positive correlation of the host expression of MCT1 (monocarboxylate transporter 1) with body weight as well as a positive correlation of the abundance of bacterial butyryl-CoA gene with cecal butyrate concentrations. These correlations support the interpretation that the influence of dietary fibre on CPT-11 toxicity is partially mediated by an increased cecal production of butyrate. PMID:24454707

Polysaccharopeptides derived from Coriolus versicolor potentiate the S-phase specific cytotoxicity of Camptothecin (CPT) on human leukemia HL-60 cells

PubMed Central

2010-01-01

Background Polysaccharopeptide (PSP) from Coriolus versicolor (Yunzhi) is used as a supplementary cancer treatment in Asia. The present study aims to investigate whether PSP pre-treatment can increase the response of the human leukemia HL-60 cells to apoptosis induction by Camptothecin (CPT). Methods We used bivariate bromodeoxyuridine/propidium iodide (BrdUrd/PI) flow cytometry analysis to measure the relative movement (RM) of the BrdUrd positively labeled cells and DNA synthesis time (Ts) on the HL-60 cell line. We used annexin V/PI flow cytometry analysis to quantify the viable, necrotic and apoptotic cells. The expression of cyclin E and cyclin B1 was determined with annexin V/PI flow cytometry and western blotting. Human peripheral blood mononuclear cells were used to test the cytotoxicity of PSP and CPT. Results PSP reduced cellular proliferation; inhibited cells progression through both S and G2 phase, reduced 3H-thymidine uptake and prolonged DNA synthesis time (Ts) in HL-60 cells. PSP-pretreated cells enhanced the cytotoxicity of CPT. The sensitivity of cells to the cytotoxic effects of CPT was seen to be the highest in the S-phase and to a small extent of the G2 phase of the cell cycle. On the other hand, no cell death (measured by annexin V/PI) was evident with the normal human peripheral blood mononuclear cells with treatment of either PSP or CPT. Conclusion The present study shows that PSP increases the sensitization of the HL-60 cells to undergo effective apoptotic cell death induced by CPT. The pattern of sensitivity of cancer cells is similar to that of HL-60 cells. PSP rapidly arrests and/or kills cells in S-phase and did not interfere with the anticancer action of CPT. PSP is a potential adjuvant to treat human leukemia as rapidly proliferating tumors is characterized by a high proportion of S-phase cells. PMID:20423495

Polysaccharopeptides derived from Coriolus versicolor potentiate the S-phase specific cytotoxicity of Camptothecin (CPT) on human leukemia HL-60 cells.

PubMed

Wan, Jennifer Man-Fan; Sit, Wai-Hung; Yang, Xiaotong; Jiang, Pingping; Wong, Leo Lap-Yan

2010-04-27

Polysaccharopeptide (PSP) from Coriolus versicolor (Yunzhi) is used as a supplementary cancer treatment in Asia. The present study aims to investigate whether PSP pre-treatment can increase the response of the human leukemia HL-60 cells to apoptosis induction by Camptothecin (CPT). We used bivariate bromodeoxyuridine/propidium iodide (BrdUrd/PI) flow cytometry analysis to measure the relative movement (RM) of the BrdUrd positively labeled cells and DNA synthesis time (Ts) on the HL-60 cell line. We used annexin V/PI flow cytometry analysis to quantify the viable, necrotic and apoptotic cells. The expression of cyclin E and cyclin B1 was determined with annexin V/PI flow cytometry and western blotting. Human peripheral blood mononuclear cells were used to test the cytotoxicity of PSP and CPT. PSP reduced cellular proliferation; inhibited cells progression through both S and G2 phase, reduced 3H-thymidine uptake and prolonged DNA synthesis time (Ts) in HL-60 cells. PSP-pretreated cells enhanced the cytotoxicity of CPT. The sensitivity of cells to the cytotoxic effects of CPT was seen to be the highest in the S-phase and to a small extent of the G2 phase of the cell cycle. On the other hand, no cell death (measured by annexin V/PI) was evident with the normal human peripheral blood mononuclear cells with treatment of either PSP or CPT. The present study shows that PSP increases the sensitization of the HL-60 cells to undergo effective apoptotic cell death induced by CPT. The pattern of sensitivity of cancer cells is similar to that of HL-60 cells. PSP rapidly arrests and/or kills cells in S-phase and did not interfere with the anticancer action of CPT. PSP is a potential adjuvant to treat human leukemia as rapidly proliferating tumors is characterized by a high proportion of S-phase cells.

Transportan 10 improves the anticancer activity of cisplatin.

PubMed

Izabela, Rusiecka; Jarosław, Ruczyński; Magdalena, Alenowicz; Piotr, Rekowski; Ivan, Kocić

2016-05-01

The aim of this paper was to examine whether cell-penetrating peptides (CPPs) such as transportan 10 (TP10) or protein transduction domain (PTD4) may improve the anticancer activity of cisplatin (cPt). The complexes of TP10 or PTD4 with cPt were used in the experiments. They were carried out on two non-cancer (HEK293 (human embryonic kidney) and HEL299 (human embryo lung)) and two cancer (HeLa (human cervical cancer) and OS143B (human osteosarcoma 143B)) cell lines. Both complexes were tested (MTT assay) with respect to their anticancer or cytotoxic actions. TAMRA (fluorescent dye)-stained preparations were visualized in a fluorescence microscope. The long-term effect of TP10 + cPt and its components on non-cancer and cancer cell lines was observed in inverted phase contrast microscopy. In the MTT test (cell viability assay), the complex of TP10 + cPt produced a more potent effect on the cancer cell lines (HeLa, OS143B) in comparison to that observed after separate treatment with TP10 or cPt. At the same time, the action of the complex and its components was rather small on non-cancer cell lines. On the other hand, a complex of another CPP with cPt, i.e., PTD4 + cPt, was without a significant effect on the cancer cell line (OS143B). The images of the fluorescent microscopy showed TAMRA-TP10 or TAMRA-TP10 + cPt in the interior of the HeLa cells. In the case of TAMRA-PTD4 or TAMRA-PTD4 + cPt, only the first compound was found inside the cancer cell line. In contrast, none of the tested compounds gained access to the interior of the non-cancer cells (HEK293, HEL299). Long-term incubation with the TP10 + cPt (estimated by inverted phase contrast microscopy) lead to an enhanced action of the complex on cell viability (decrease in the number of cells and change in their morphology) as compared with that produced by each single agent. With regard to the tested CPPs, only TP10 improved the anticancer activity of cisplatin if both compounds were used in the form of a complex. Additionally, the complex was relatively safe for non-cancer cells. What is more, TP10 also produced an anticancer effect on HeLa and OS143B cell lines.

Evaluation of bearing capacity of piles from cone penetration test data.

DOT National Transportation Integrated Search

1999-11-01

This study presents an evaluation of the performance of eight cone penetration test (CPT) methods in predicting the ultimate load carrying capacity of square precast prestressed concrete (PPC) piles driven into Louisiana soils. A search in the DOTD f...

Target-D: a stratified individually randomized controlled trial of the diamond clinical prediction tool to triage and target treatment for depressive symptoms in general practice: study protocol for a randomized controlled trial.

PubMed

Gunn, Jane; Wachtler, Caroline; Fletcher, Susan; Davidson, Sandra; Mihalopoulos, Cathrine; Palmer, Victoria; Hegarty, Kelsey; Coe, Amy; Murray, Elizabeth; Dowrick, Christopher; Andrews, Gavin; Chondros, Patty

2017-07-20

Depression is a highly prevalent and costly disorder. Effective treatments are available but are not always delivered to the right person at the right time, with both under- and over-treatment a problem. Up to half the patients presenting to general practice report symptoms of depression, but general practitioners have no systematic way of efficiently identifying level of need and allocating treatment accordingly. Therefore, our team developed a new clinical prediction tool (CPT) to assist with this task. The CPT predicts depressive symptom severity in three months' time and based on these scores classifies individuals into three groups (minimal/mild, moderate, severe), then provides a matched treatment recommendation. This study aims to test whether using the CPT reduces depressive symptoms at three months compared with usual care. The Target-D study is an individually randomized controlled trial. Participants will be 1320 general practice patients with depressive symptoms who will be approached in the practice waiting room by a research assistant and invited to complete eligibility screening on an iPad. Eligible patients will provide informed consent and complete the CPT on a purpose-built website. A computer-generated allocation sequence stratified by practice and depressive symptom severity group, will randomly assign participants to intervention (treatment recommendation matched to predicted depressive symptom severity group) or comparison (usual care plus Target-D attention control) arms. Follow-up assessments will be completed online at three and 12 months. The primary outcome is depressive symptom severity at three months. Secondary outcomes include anxiety, mental health self-efficacy, quality of life, and cost-effectiveness. Intention-to-treat analyses will test for differences in outcome means between study arms overall and by depressive symptom severity group. To our knowledge, this is the first depressive symptom stratification tool designed for primary care which takes a prognosis-based approach to provide a tailored treatment recommendation. If shown to be effective, this tool could be used to assist general practitioners to implement stepped mental-healthcare models and contribute to a more efficient and effective mental health system. Australian New Zealand Clinical Trials Registry (ANZCTR 12616000537459 ). Retrospectively registered on 27 April 2016. See Additional file 1 for trial registration data.

Continuous performance test in pediatric obsessive-compulsive disorder and tic disorders: the role of sustained attention.

PubMed

Lucke, Ilse M; Lin, Charlotte; Conteh, Fatmata; Federline, Amanda; Sung, Huyngmo; Specht, Matthew; Grados, Marco A

2015-10-01

Pediatric obsessive-compulsive disorder (OCD) and tic disorders (TD) are often associated with attention-deficit hyperactivity disorder (ADHD). In order to clarify the role of attention and inhibitory control in pediatric OCD and TD, a continuous performance test (CPT) was administered to a cohort of children and adolescents with OCD alone, TD alone, and OCD+TD. A clinical cohort of 48 children and adolescents with OCD alone (n=20), TD alone (n=15), or OCD+TD (n=13) was interviewed clinically and administered the Conners Continuous Performance Test II (CPT-II). The Conners CPT-II is a 14-minute normed computerized test consisting of 6 blocks. It taps into attention, inhibitory control, and sustained attention cognitive domains. Key parameters include errors of omission (distractability), commission (inhibitory control), and variable responding over time (sustained attention). Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria were applied in a best-estimate process to diagnose OCD, TD, ADHD, and anxiety disorders. Children with OCD+TD had more errors of omission (p=0.03), and more hit RT block change (p=0.003) and hit SE block change (p=0.02) than subjects with OCD alone and TD alone. These deficits in sustained attention were associated with younger age and hoarding tendencies. A clinical diagnosis of ADHD in the OCD+TD group also determined worse sustained attention. A deficit in sustained attention, a core marker of ADHD, is also a marker of OCD+TD, compared to OCD alone and TD alone. Biological correlates of sustained attention may serve to uncover the pathophysiology of OCD and TD through genetic and imaging studies.

What's Gender Got to Do With It: Difference in the Proportion of Traditionally Female Cases Performed by General Urologists of Each Gender.

PubMed

Rotker, Katherine; Iosifescu, Sarah; Baird, Grayson; Thavaseelan, Simone; Hwang, Kathleen

2018-06-01

To examine surgical case volume characteristics in certifying urologists to evaluate practice patterns, given the long-standing understanding but unproven hypothesis that non-fellowship trained female general urologists perform more urogynecologic procedures compared with their equally trained male counterparts. Case log data from certifying and recertifying urologists from 2000 to 2015 were obtained from the American Board of Urology. Thirty-seven Current Procedural Terminology (CPT) codes were chosen to represent traditionally urogynecologic cases. Logistic regression analysis models were used to determine the percentage of total CPT codes logged during the certification period made up by traditionally urogynecologic cases. Male and female non-fellowship trained, self-described general urologists were compared. The case logs of 4032 non-fellowship trained general urologists were reviewed from 2000 to 2015, 297 of whom were female and 3735 of whom were male. Urogynecologic cases made up 1.27% of the total CPT codes logged by the women and 0.59% of those codes logged by the men (P <.001), an increase of 2.2 times (P <.001). This statistically significant difference persisted regardless of certification period, geographic location, population density, or full-time vs part-time employment. Traditional urogynecologic cases represented a significantly greater percentage of the total cases logged by non-fellowship trained female general urologists compared with their non-fellowship trained, generalist male colleagues. The percentage of total cases performed by both is very small. However, it supports a belief that patient populations differ for male and female general urologists, which may impact training or career choices. Copyright © 2018 Elsevier Inc. All rights reserved.

Models and (some) Searches for CPT Violation: From Early Universe to the Present Era

NASA Astrophysics Data System (ADS)

Mavromatos, Nick E.

2017-07-01

In the talk, I review theoretical models, inspired by quantum gravity, that may violate CPT symmetry. The amount of violation today (which is constrained severely by a plethora of experiments that I will not describe due to lack of space) need not be the same with the one that occurred in the Early Universe,. In certain models, one can obtain a precise temperature dependence of CPT violating effects, which is such that these effects are significant during the radiation era of the Universe, but are damped quickly so that they do not to affect nucleosynthesis and are negligible in the present epoch (that is, beyond experimental detection with the current experimental sensitivity). The CPT Violation (CPTV) in these models may arise from special properties of the background over which the fields of the model are propagating upon and be responsible for the generation of a matter-antimatter asymmetry, where any CP violation effects could only assist in the creation of the asymmetry, the dominant effect being CPTV. However, there are cases, where the CPTV arises as a consequence of an ill-defined CPT operator due to decoherence as a result of quantum gravity environmental degrees of freedom, inaccessible to a low-energy observer. I also discuss briefly the current-era phenomenology of some of the above models; in particular, for the ones involving decoherence-induced CPT violation, I argue that entangled states of neutral mesons (Kaons or B-systems) can provide smoking-gun sensitive tests or even falsify some of these models. If CPT is ill-defined one may also encounter violations of the spin-statistics theorem, with possible consequences for the Pauli Exclusion Principle.

Fatty acid oxidation is required for active and quiescent brown adipose tissue maintenance and thermogenic programing.

PubMed

Gonzalez-Hurtado, Elsie; Lee, Jieun; Choi, Joseph; Wolfgang, Michael J

2018-01-01

To determine the role of fatty acid oxidation on the cellular, molecular, and physiologic response of brown adipose tissue to disparate paradigms of chronic thermogenic stimulation. Mice with an adipose-specific loss of Carnitine Palmitoyltransferase 2 (Cpt2 A-/- ), that lack mitochondrial long chain fatty acid β-oxidation, were subjected to environmental and pharmacologic interventions known to promote thermogenic programming in adipose tissue. Chronic administration of β3-adrenergic (CL-316243) or thyroid hormone (GC-1) agonists induced a loss of BAT morphology and UCP1 expression in Cpt2 A-/- mice. Fatty acid oxidation was also required for the browning of white adipose tissue (WAT) and the induction of UCP1 in WAT. In contrast, chronic cold (15 °C) stimulation induced UCP1 and thermogenic programming in both control and Cpt2 A-/- adipose tissue albeit to a lesser extent in Cpt2 A-/- mice. However, thermoneutral housing also induced the loss of UCP1 and BAT morphology in Cpt2 A-/- mice. Therefore, adipose fatty acid oxidation is required for both the acute agonist-induced activation of BAT and the maintenance of quiescent BAT. Consistent with this data, Cpt2 A-/- BAT exhibited increased macrophage infiltration, inflammation and fibrosis irrespective of BAT activation. Finally, obese Cpt2 A-/- mice housed at thermoneutrality exhibited a loss of interscapular BAT and were refractory to β3-adrenergic-induced energy expenditure and weight loss. Mitochondrial long chain fatty acid β-oxidation is critical for the maintenance of the brown adipocyte phenotype both during times of activation and quiescence. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Side-Effects of Irinotecan (CPT-11), the Clinically Used Drug for Colon Cancer Therapy, Are Eliminated in Experimental Animals Treated with Latex Proteins from Calotropis procera (Apocynaceae).

PubMed

de Alencar, Nylane Maria Nunes; da Silveira Bitencourt, Flávio; de Figueiredo, Ingrid Samantha Tavares; Luz, Patrícia Bastos; Lima-Júnior, Roberto César P; Aragão, Karoline Sabóia; Magalhães, Pedro Jorge Caldas; de Castro Brito, Gerly Anne; Ribeiro, Ronaldo Albuquerque; de Freitas, Ana Paula Fragoso; Ramos, Marcio Viana

2017-02-01

Intestinal mucositis (IM) is the critical side effect of irinotecan (CPT-11), which is the front-line drug used for the treatment of colorectal cancer. This study aimed to evaluate the effectiveness of latex proteins (LP) from Calotropis procera to prevent IM and diarrhea in animals. Swiss mice were treated daily with saline or LP (1, 5, or 50 mg/kg, i.v.) 24 h prior to CTP-11 (75 mg/kg/4 days, i.p) and for additional 6 days. Animal survival, body weight variation, and diarrhea were registered. After animal sacrifice (day 7 post first injection of CPT-11), intestinal samples were collected to study morphology and inflammatory parameters. Animals given LP exhibited improved parameters (survival, body weight, and absence of diarrhea) as compared with the CPT-11 control. The severity of IM observed in animals given CPT-11 was reduced in animals treated with LP. Treatment with LP also prevented the reduction in the villus/crypt ratio promoted by CPT-11. The rise in MPO activity and pro-inflammatory cytokines, over-contractility of the smooth muscle, and diarrhea were all abrogated in LP-treated mice. Markedly reduced immunostaining intensity for COX-2, TNF-α, IL-1β, iNOS, and NF-κB was observed in the intestinal tissue of animals treated with LP. The side-effects of CPT-11 were eliminated by LP treatment in experimental animals and improved clinical parameters characteristic of IM All known biochemical pathogenesis. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Distinguishing neglect from abuse and accident: analysis of the case files of a hospital child protection team in Israel.

PubMed

Davidson-Arad, Bilha; Benbenishty, Rami; Chen, Wendy; Glasser, Saralee; Zur, Shmuel; Lerner-Geva, Liat

2010-11-01

The study compares the characteristics of children assessed as neglected, physically abused, or accident victims by a hospital child protection team (CPT) and identifies the information on which the CPT based its assessments. The comparison is based on content analysis of records of 414 children examined by the CPT in a major hospital in Israel between 1991 and 2006, of whom 130 (31.4%) were neglected, 54 (13.0%) were physically abused, and 230 (55.6%) were accident victims. Findings of three hierarchical logistic regressions show that the children classified as neglected had the most early development problems, but were the least likely to have received psychological treatment, and that that their families were the most likely to be receiving state financial support and to have had prior contact with the social services. They also show that the CPT had received the least information indicative of maltreatment about these children from the community and that their medical and physical examinations aroused the least suspicion. Finally, they show that the impressions the hospital staff and CPT had of the parents during the hospital visit had greater power to distinguish between the groups than the children's characteristics or the parents' socio-demographic background. The findings attest to the ability of the CPT to differentiate between neglect victims and physical abuse or accident victims. With this, they also point to ambiguities in the classification process that should be addressed by further research and training and to the need for detailed and thorough documentation of the information and observations on which the CPT's assessments are based. © 2010 Blackwell Publishing Ltd.

Organ-specific carboxylesterase profiling identifies the small intestine and kidney as major contributors of activation of the anticancer prodrug CPT-11

PubMed Central

Hatfield, M. Jason; Tsurkan, Lyudmila; Garrett, Michael; Shaver, Timothy M.; Hyatt, Janice L.; Edwards, Carol C.; Hicks, Latorya D.; Potter, Philip M.

2010-01-01

The activation of the anticancer prodrug CPT-11, to its active metabolite SN-38, is primarily mediated by carboxylesterases (CE). In humans, three CEs have been identified, of which human liver CE (hCE1; CES1) and human intestinal CE (hiCE; CES2) demonstrate significant ability to hydrolyze the drug. However, while the kinetic parameters of CPT-11 hydrolysis have been measured, the actual contribution of each enzyme to activate the drug in biological samples has not been addressed. Hence, we have used a combination of specific CE inhibition and conventional chromatographic techniques to determine the amounts, and hydrolytic activity, of CEs present within human liver, kidney, intestinal and lung specimens. These studies confirm that hiCE demonstrates the most efficient kinetic parameters for CPT-11 activation, however, due to the high levels of hCE1 that are expressed in liver, the latter enzyme can contribute up to 50% of the total of drug hydrolysis in this tissue. Conversely, in human duodenum, jejunum, ileum and kidney, where hCE1 expression is very low, greater than 99% of the conversion of CPT-11 to SN-38 was mediated by hiCE. Furthermore, analysis of lung microsomal extracts indicated that CPT-11 activation was more proficient in samples obtained from smokers. Overall, our studies demonstrate that hCE1 plays a significant role in CPT-11 hydrolysis even though it is up to 100-fold less efficient at drug activation than hiCE, and that drug activation in the intestine and kidney are likely major contributors to SN-38 production in vivo. PMID:20833148

Efficacy of combination chemotherapy using irinotecan and nedaplatin for patients with recurrent and refractory endometrial carcinomas: preliminary analysis and literature review.

PubMed

Miyamoto, Morikazu; Takano, Masashi; Kuwahara, Mika; Soyama, Hiroaki; Kato, Kento; Matuura, Hiroko; Sakamoto, Takahiro; Takasaki, Kazuki; Aoyama, Tadashi; Yoshikawa, Tomoyuki; Furuya, Kenichi

2018-01-01

We aimed to retrospectively evaluate the efficacy and toxicity of an irinotecan hydrochloride (CPT) and nedaplatin (N) combination therapy for recurrent and refractory endometrial carcinoma, administered based on UGT1A1 genotype. Between 2009 and 2017, 21 patients who received CPT-N therapy for recurrent endometrial carcinoma as second- or third-line chemotherapy at our hospital were identified. The CPT-N regimen included 40-70 mg/m 2 of CPT-11 on days 1, 8, and 15, and 50 mg/m 2 of nedaplatin on day 1, q4 weeks. The median patient age was 63 years. The number of prior chemotherapeutic regimens ranged from 1 to 2. Two patients had prior pelvic irradiation. The response rate [ratio of complete remission (CR) to partial remission (PR)] of CPT-N therapy was 3 of 21 (14.3%), and clinical benefit rate (CBR) [the combined percentages of CR, PR, and stable disease (SD)] was 9 of 21 (42.8%). Toxicities included grade 3 neutropenia [4 (19.0%) cases], grade 3 febrile neutropenia [2 (9.5%) cases], and grade 3 diarrhea [3 (14.3%) cases]; all resolved with conservative treatment. Patients with a wild-type UGT1A1 status received higher doses of CPT-11 (p = 0.048) and had similar RR and CBR compared to those with a UGT1A1*6 and *28 status. There were no significant differences in frequencies of hematological or non-hematological toxicities, regardless of UGT1A1 status. The CPT-N regimen for recurrent and refractory endometrial carcinoma had tolerable side effects and significant efficacy. This regimen is a viable treatment option for endometrial carcinoma.

Chest physiotherapy on the respiratory mechanics and elimination of sputum in paralyzed and mechanically ventilated patients with acute lung injury: a pilot study.

PubMed

Suh, Minhee; Heitkemper, Margaret; Smi, Choi-Kwon

2011-03-01

Chest physiotherapy (CPT) is commonly used for mechanically ventilated patients, but little is known about its physiological effects, particularly in patients with acute lung injury (ALI). The aim of the study was to determine the benefits and risks of delivering multimodal respiratory physiotherapy to mechanically ventilated patients with ALI receiving paralytic agents. A repeated measure-experimental design using a counterbalancing method was employed. Fifteen patients received CPT (vibration, percussion, or palm-cup percussion) in addition to the routine CPT in a randomized order. Another 15 patients, contraindicated for the percussion technique, received routine CPT including manual hyperinflation and position change, and were observed as a comparative group. The effects of CPT were evaluated by measuring the volume of aspirated secretions and the dynamic lung compliance (Cd) over time. For the adverse effects, peripheral oxygen saturation (SpO2) was recorded. Cd and SpO2 were recorded at the baseline period, immediately after the physiotherapy treatment, and at 10, 20, 30 and 60 minutes posttreatment. The volume of collected secretions did not differ significantly when compared between the groups (p = .838). Cd increased significantly over time in the manual percussion (p = .042) and palm-cup percussion (p = .046) group, where Cd in the latter remained elevated twice longer than in the former. None of the CPT techniques exerted major detrimental effects on SpO2. We found that the palm-cup percussion technique was the most effective in increasing Cd without any accompanying detrimental effects on SpO2. However, additional CPT did not affect the volume of aspirated secretions. Copyright © 2011 Korean Society of Nursing Science. Published by Elsevier B.V. All rights reserved.

A Lettuce (Lactuca sativa) Homolog of Human Nogo-B Receptor Interacts with cis-Prenyltransferase and Is Necessary for Natural Rubber Biosynthesis*

PubMed Central

Qu, Yang; Chakrabarty, Romit; Tran, Hue T.; Kwon, Eun-Joo G.; Kwon, Moonhyuk; Nguyen, Trinh-Don; Ro, Dae-Kyun

2015-01-01

Natural rubber (cis-1,4-polyisoprene) is an indispensable biopolymer used to manufacture diverse consumer products. Although a major source of natural rubber is the rubber tree (Hevea brasiliensis), lettuce (Lactuca sativa) is also known to synthesize natural rubber. Here, we report that an unusual cis-prenyltransferase-like 2 (CPTL2) that lacks the conserved motifs of conventional cis-prenyltransferase is required for natural rubber biosynthesis in lettuce. CPTL2, identified from the lettuce rubber particle proteome, displays homology to a human NogoB receptor and is predominantly expressed in latex. Multiple transgenic lettuces expressing CPTL2-RNAi constructs showed that a decrease of CPTL2 transcripts (3–15% CPTL2 expression relative to controls) coincided with the reduction of natural rubber as low as 5%. We also identified a conventional cis-prenyltransferase 3 (CPT3), exclusively expressed in latex. In subcellular localization studies using fluorescent proteins, cytosolic CPT3 was relocalized to endoplasmic reticulum by co-occurrence of CPTL2 in tobacco and yeast at the log phase. Furthermore, yeast two-hybrid data showed that CPTL2 and CPT3 interact. Yeast microsomes containing CPTL2/CPT3 showed enhanced synthesis of short cis-polyisoprenes, but natural rubber could not be synthesized in vitro. Intriguingly, a homologous pair CPTL1/CPT1, which displays ubiquitous expressions in lettuce, showed a potent dolichol biosynthetic activity in vitro. Taken together, our data suggest that CPTL2 is a scaffolding protein that tethers CPT3 on endoplasmic reticulum and is necessary for natural rubber biosynthesis in planta, but yeast-expressed CPTL2 and CPT3 alone could not synthesize high molecular weight natural rubber in vitro. PMID:25477521

A lettuce (Lactuca sativa) homolog of human Nogo-B receptor interacts with cis-prenyltransferase and is necessary for natural rubber biosynthesis.

PubMed

Qu, Yang; Chakrabarty, Romit; Tran, Hue T; Kwon, Eun-Joo G; Kwon, Moonhyuk; Nguyen, Trinh-Don; Ro, Dae-Kyun

2015-01-23

Natural rubber (cis-1,4-polyisoprene) is an indispensable biopolymer used to manufacture diverse consumer products. Although a major source of natural rubber is the rubber tree (Hevea brasiliensis), lettuce (Lactuca sativa) is also known to synthesize natural rubber. Here, we report that an unusual cis-prenyltransferase-like 2 (CPTL2) that lacks the conserved motifs of conventional cis-prenyltransferase is required for natural rubber biosynthesis in lettuce. CPTL2, identified from the lettuce rubber particle proteome, displays homology to a human NogoB receptor and is predominantly expressed in latex. Multiple transgenic lettuces expressing CPTL2-RNAi constructs showed that a decrease of CPTL2 transcripts (3-15% CPTL2 expression relative to controls) coincided with the reduction of natural rubber as low as 5%. We also identified a conventional cis-prenyltransferase 3 (CPT3), exclusively expressed in latex. In subcellular localization studies using fluorescent proteins, cytosolic CPT3 was relocalized to endoplasmic reticulum by co-occurrence of CPTL2 in tobacco and yeast at the log phase. Furthermore, yeast two-hybrid data showed that CPTL2 and CPT3 interact. Yeast microsomes containing CPTL2/CPT3 showed enhanced synthesis of short cis-polyisoprenes, but natural rubber could not be synthesized in vitro. Intriguingly, a homologous pair CPTL1/CPT1, which displays ubiquitous expressions in lettuce, showed a potent dolichol biosynthetic activity in vitro. Taken together, our data suggest that CPTL2 is a scaffolding protein that tethers CPT3 on endoplasmic reticulum and is necessary for natural rubber biosynthesis in planta, but yeast-expressed CPTL2 and CPT3 alone could not synthesize high molecular weight natural rubber in vitro. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The effect of anxiety sensitivity on psychological and biological variables during the cold pressor test.

PubMed

Dodo, Naomi; Hashimoto, Ryusaku

2017-07-01

We examined the relationship between anxiety sensitivity (AS) and autonomic nervous system responses (ANS) during the cold pressor test (CPT). Seventy-four university students participated and were divided into low-AS (M=9.06, SD=3.97) and high-AS groups (M=28.68, SD=6.63) based on AS Index scores (n's=36 and 38, respectively). The study included three phases: Rest, CPT, and Recovery. We measured the psychological variables (fear of pain and subjective pain) at pre- and post-CPT. ANS response data were collected during each phase. Fear of pain was experienced more strongly in the high-AS group (M=4.74, SD=3.25) relative to the low-AS group (M=2.72, SD=2.31), and subjective pain was also stronger in the high-AS group (M=3.08, SD=1.91) relative to the low-AS group (M=2.47, SD=1.00) in post-CPT. While parasympathetic nervous system (PNS) responses did not differ between the two groups during the CPT, the high AS-group demonstrated lower PNS activity during the Recovery phase. The high-AS group reported significantly more anticipatory fear and pain prior to the CPT, which appeared to aggravate subjective pain experiences. Furthermore, for individuals with anxiety sensitivity, ANS reactivity may be the mechanism underlying the relationship between negative affect and subjective pain. Copyright © 2017. Published by Elsevier B.V.

Genetic polymorphisms in carnitine palmitoyltransferase 1A gene are associated with variation in body composition and fasting lipid traits in Yup'ik Eskimos[S

PubMed Central

Lemas, Dominick J.; Wiener, Howard W.; O'Brien, Diane M.; Hopkins, Scarlett; Stanhope, Kimber L.; Havel, Peter J.; Allison, David B.; Fernandez, Jose R.; Tiwari, Hemant K.; Boyer, Bert B.

2012-01-01

Variants of carnitine palmitoyltransferase 1A (CPT1A), a key hepatic lipid oxidation enzyme, may influence how fatty acid oxidation contributes to obesity and metabolic outcomes. CPT1A is regulated by diet, suggesting interactions between gene variants and diet may influence outcomes. The objective of this study was to test the association of CPT1A variants with body composition and lipids, mediated by consumption of polyunsaturated fatty acids (PUFA). Obesity phenotypes and fasting lipids were measured in a cross-sectional sample of Yup'ik Eskimo individuals (n = 1141) from the Center of Alaska Native Health Research (CANHR) study. Twenty-eight tagging CPT1A SNPs were evaluated with outcomes of interest in regression models accounting for family structure. Several CPT1A polymorphisms were associated with HDL-cholesterol and obesity phenotypes. The P479L (rs80356779) variant was associated with all obesity-related traits and fasting HDL-cholesterol. Interestingly, the association of P479L with HDL-cholesterol was still significant after correcting for body mass index (BMI), percentage body fat (PBF), or waist circumference (WC). Our findings are consistent with the hypothesis that the L479 allele of the CPT1A P479L variant confers a selective advantage that is both cardioprotective (through increased HDL-cholesterol) and associated with reduced adiposity. PMID:22045927

Effect of dietary copper addition on lipid metabolism in rabbits

PubMed Central

Lei, Liu; Xiaoyi, Sui; Fuchang, Li

2017-01-01

ABSTRACT The present study was conducted to investigate the effect of copper supplementation on lipid metabolism in rabbits. Our study showed dietary copper addition (5-45 mg/kg) increased body mass gain, but decreased fat and liver weights compared with those in the control group (P < 0.05). Copper (45 mg/kg) addition significantly increased the skeletal muscle weight, but inhibited cytoplasmic lipid accumulation in liver, skeletal muscle and adipose tissue (P < 0.05). Compared with the control group, dietary copper addition (45 mg/kg) significantly increased plasma triglyceride levels but decreased very low density lipoprotein levels (P < 0.05). Copper treatment significantly increased gene expression of carnitine palmitoyltransferase (CPT) 1, CPT2 and peroxisome proliferator-activated receptor (PPAR) a in liver (P < 0.05). In skeletal muscle, CPT1, CPT2, fatty acid transport protein, fatty acid-binding protein, and PPARa mRNA as well as phosphorylated AMP-activated protein kinase (AMPK) levels were significantly up-regulated by copper treatment (P < 0.05). Rabbits receiving copper supplementation had higher CPT1, CPT2, PPARa and hormone-sensitive lipase mRNA levels in adipose tissue (P < 0.05). In conclusion, copper promoted skeletal muscle growth and reduced fat accretion. PPARa signaling in liver, skeletal muscle and adipose tissues and AMPK signaling in skeletal muscle tissue were involved in the regulation of lipid metabolism by copper. PMID:28747869

The use of experimental design for the development of a capillary zone electrophoresis method for the quantitation of captopril.

PubMed

Mukozhiwa, S Y; Khamanga, S M M; Walker, R B

2017-09-01

A capillary zone electrophoresis (CZE) method for the quantitation of captopril (CPT) using UV detection was developed. Influence of electrolyte concentration and system variables on electrophoretic separation was evaluated and a central composite design (CCD) was used to optimize the method. Variables investigated were pH, molarity, applied voltage and capillary length. The influence of sodium metabisulphite on the stability of test solutions was also investigated. The use of sodium metabisulphite prevented degradation of CPT over 24 hours. A fused uncoated silica capillary of 67.5cm total and 57.5 cm effective length was used for analysis. The applied voltage and capillary length affected the migration time of CPT significantly. A 20 mM phosphate buffer adjusted to pH 7.0 was used as running buffer and an applied voltage of 23.90 kV was suitable to effect a separation. The optimized electrophoretic conditions produced sharp, well-resolved peaks for CPT and sodium metabisulphite. Linear regression analysis of the response for CPT standards revealed the method was linear (R2 = 0.9995) over the range 5-70 μg/mL. The limits of quantitation and detection were 5 and 1.5 μg/mL. A simple, rapid and reliable CZE method has been developed and successfully applied to the analysis of commercially available CPT products.

Proteomic approaches in understanding a detected relationship between chemotherapy-induced nephrotoxicity and cell respiration in HK-2 cells.

PubMed

Perez, Juliana Dinéia; Colucci, Juliana Almada; Sakata, Maísa Mayumi; Cunha, Tatiana Sousa; Arita, Danielle Yuri; Casarini, Dulce Elena

2011-01-01

Nephrotoxicity is a prominent component of the profile of chemotherapeutic agents and to date proteomics has represented the main technique to identify protein profiles in response to xenobiotic exposure. We made use of two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight analysis to evaluate chemotoxicity effects of cisplatin (CPT) and carboplatin (CB) on proteins from human renal proximal tubule epithelial cells (HK-2). Tandem mass spectrometry analysis showed that ATP synthase subunit α and serine hydroxymethyltransferase were only expressed in HK-2 cells exposed to CPT. Since CPT causes damage in cellular respiration, we suggest that this might be a protective adaptation to CPT-induced nephrotoxicity. Thioredoxin-dependent peroxide reductase disappeared in the CPT group and was upregulated in the CB group, suggesting that CB exposure stimulates preventive apoptotic mechanisms. We suggest a relationship between chemotherapeutic agent-induced nephrotoxicity and cell respiration. The identification of proteins differentially expressed in HK-2 cells, when exposed to CPT and CB, not only supplies important information to understand the molecular action mechanisms, which are triggered by metal-based drugs in cell nephrotoxicity, but also can lead to the design of more effective anticancer drugs. These results provide important insights into the investigation of possible biomarker(s) of toxicity that could eventually reduce the side effects of chemotherapeutic agents. Copyright © 2011 S. Karger AG, Basel.

Cone-penetrometer exploration of sinkholes: Stratigraphy and soil properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bloomberg, D.; Upchurch, S.B.; Hayden, M.L.

1988-10-01

Four sinkholes with varying surficial expressions were subjected to detailed stratigraphic and soil analysis by means of Standard Penetration Tests (SPT) and Electric Friction Cone Penetration Tests (CPT) in order to evaluate applications of CPT to sinkhole investigations. Although widely used, SPT data are of limited value and difficult to apply to sinkhole mapping. CPT is sensitive to minor lithologic variability and is superior to SPT as a cost-effective technique for determining geotechnical properties of sinkholes. The effectiveness of CPT data results from the force measurements made along the sleeve of the cone. The friction ratio (ratio of sleeve tomore » tip resistance) is a good indicator of soil stratigraphy and properties. By smoothing the friction-ratio data, general stratigraphy and changes in soil properties are easily identified. Stratigraphy of the sinks has been complicated by intense weathering, karstification and marine transgressions. The resulting deposits include five stratigraphic units. 1 and 2 represent Plio-Pleistocene marine sediments with Unit 2 being the zone of soil clay accumulation. 3 and 4 are horizons residual from Miocene strata and indicate an episode of karstification prior to deposition of Units 1 and 2. CPT provides sufficient information for recognition of sinkhole stratigraphy and geotechnical properties. When coupled with laboratory soil analysis, CPT provides unique information about sinkhole geometry and dynamics. In contrast, SPT indicates general, inconclusive trends.« less

Brain Oscillations Elicited by the Cold Pressor Test: A Putative Index of Untreated Essential Hypertension

PubMed Central

Tsaltas, Eleftheria; Koroboki, Eleni; Alevizaki, Maria; Angelopoulos, Elias; Dimopoulos, Meletios-Athanasios; Papageorgiou, Charalabos; Zakopoulos, Nikolaos

2017-01-01

Objective Essential hypertension is associated with reduced pain sensitivity of unclear aetiology. This study explores this issue using the Cold Pressor Test (CPT), a reliable pain/stress model, comparing CPT-related EEG activity in first episode hypertensives and controls. Method 22 untreated hypertensives and 18 matched normotensives underwent 24-hour ambulatory blood pressure monitoring (ABPM). EEG recordings were taken before, during, and after CPT exposure. Results Significant group differences in CPT-induced EEG oscillations were covaried with the most robust cardiovascular differentiators by means of a Canonical Analysis. Positive correlations were noted between ABPM variables and Delta (1–4 Hz) oscillations during the tolerance phase; in high-alpha (10–12 Hz) oscillations during the stress unit and posttest phase; and in low-alpha (8–10 Hz) oscillations during CPT phases overall. Negative correlations were found between ABPM variables and Beta2 oscillations (16.5–20 Hz) during the posttest phase and Gamma (28.5–45 Hz) oscillations during the CPT phases overall. These relationships were localised at several sites across the cerebral hemispheres with predominance in the right hemisphere and left frontal lobe. Conclusions These findings provide a starting point for increasing our understanding of the complex relationships between cerebral activation and cardiovascular functioning involved in regulating blood pressure changes. PMID:28573048

The Nature and Consequences of Cognitive Deficits among Tobacco Smokers with HIV: A Comparison to Tobacco Smokers without HIV

PubMed Central

Harrison, Joseph D.; Dochney, Jessica A.; Blazekovic, Sonja; Leone, Frank; Metzger, David; Frank, Ian; Gross, Robert; Hole, Anita; Mounzer, Karam; Siegel, Steven; Schnoll, Robert A.; Ashare, Rebecca L.

2017-01-01

HIV-infected smokers lose more years of life to tobacco-related disease than HIV. Since neurocognitive deficits are common among those with HIV and are associated with smoking persistence, these deficits may be a unique barrier to smoking cessation among HIV-infected smokers. Documenting unique differences in and correlates of cognition among HIV-infected smokers is a critical step towards developing a population-specific tobacco cessation treatment. We compared neurocognitive function between HIV-infected (n=103) and HIV-uninfected smokers (n=70), accounting for demographic and smoking-related variables. We also evaluated whether HIV-related health outcomes (e.g., CD4 count, viral load, depression ratings, quality of life [QoL]) and HAART adherence were associated with cognition. Participants completed neurocognitive tasks (N-back and Continuous Performance Task [CPT]) measuring working memory, attention, and processing speed, and intra-individual variability. Stepwise regression models were conducted and validated with resampling techniques. HIV-infected smokers performed worse than HIV-uninfected smokers on working memory, processing speed, and intra-individual variability (all p<0.01). ROC analysis for the model including cognitive measures demonstrated 85% area under the curve, which indicates “good prediction” for distinguishing between HIV-infected and HIV-uninfected smokers. This was a significant improvement over the model including demographic and smoking-related variables only (p=0.0003). Among HIV-infected smokers, neurocognitive performance was negatively associated with QoL and depression ratings. Smoking cessation interventions for HIV-infected smokers should consider cognitive neurorehabilitation as a potential strategy to decrease the likelihood of nicotine relapse and decrease tobacco-related morbidity in this population. PMID:28429289

EEG indices correlate with sustained attention performance in patients affected by diffuse axonal injury.

PubMed

Coelli, Stefania; Barbieri, Riccardo; Reni, Gianluigi; Zucca, Claudio; Bianchi, Anna Maria

2018-06-01

The aim of this study is to assess the ability of EEG-based indices in providing relevant information about cognitive engagement level during the execution of a clinical sustained attention (SA) test in healthy volunteers and DAI (diffused axonal injury)-affected patients. We computed three continuous power-based engagement indices (P β /P α , 1/P α , and P β / (P α + P θ )) from EEG recordings in a control group (n = 7) and seven DAI-affected patients executing a 10-min Conners' "not-X" continuous performance test (CPT). A correlation analysis was performed in order to investigate the existence of relations between the EEG metrics and behavioral parameters in both the populations. P β /P α and 1/P α indices were found to be correlated with reaction times in both groups while P β / (P α + P θ ) and P β /P α also correlated with the errors rate for DAI patients. In line with previous studies, time course fluctuations revealed a first strong decrease of attention after 2 min from the beginning of the test and a final fading at the end. Our results provide evidence that EEG-derived indices extraction and evaluation during SA tasks are helpful in the assessment of attention level in healthy subjects and DAI patients, offering motivations for including EEG monitoring in cognitive rehabilitation practice. Graphical abstract Three EEG-derived indices were computed from four electrodes montages in a population of seven healthy volunteers and a group of seven DAI-affected patients. Results show a significant correlation between the time course of the indices and behavioral parameters, thus demonstrating their usefulness in monitoring mental engagement level during a sustained attention task.

Analysis of UGT1A1*28 genotype and SN-38 pharmacokinetics for irinotecan-based chemotherapy in patients with advanced colorectal cancer: results from a multicenter, retrospective study in Shanghai.

PubMed

Cai, Xun; Cao, Weiguo; Ding, Honghua; Liu, Tianshu; Zhou, Xinli; Wang, Mei; Zhong, Ming; Zhao, Ziyi; Xu, Qing; Wang, Liwei

2013-09-01

The UGT1A1*28 polymorphism, although closely linked with CPT-11-related adverse effects, cannot be used alone to guide individualized treatment decisions. However, CPT-11 dosage can be adjusted according to measured SN-38 pharmacokinetics. Our study is designed to investigate whether there is a relationship between SN-38 peak or valley concentrations and efficacy or adverse effects of CPT-11-based chemotherapy. We retrospectively studied 98 patients treated with advanced colorectal cancer in various UGT1A1*28 genotype groups (mainly (TA)6/(TA)6 and (TA)6/(TA)7 genotypes) treated with CPT-11 as first-line chemotherapy in Shanghai. One hundred and sixty-four advanced colorectal cancer patients were enrolled. To understand differences in genotype expression, the frequency of UGT1A1*28 thymine-adenine (TA) repeats in TATA box arrangement was assessed by PCR with genomic DNA extracted from peripheral blood. For ninety-eight cases with the (TA)6/(TA)6 and (TA)6/(TA)7 genotypes treated with CPT-11 as first-line chemotherapy, the plasma concentration of SN-38 was detected by HPLC 1.5 and 49 h after CPT-11 infusion. Efficacy and adverse effects were observed subsequently, and the relationship between SN-38 plasma concentration and efficacy or adverse effects within genotype groups, as well as differences in efficacy and adverse effects between (TA)6/(TA)6 and (TA)6/(TA)7 genotypes were analyzed statistically. One hundred and fourteen patients (69.51 %) were identified with the (TA)6/(TA)6 genotype, forty-eight patients (29.27 %) with the (TA)6/(TA)7 genotype, and two patients (1.22 %) with the (TA)7/(TA)7 genotype. The average peak and valley concentrations of SN-38 after CPT-11 infusion and plasma bilirubin average levels before and after CPT-11 treatment in the (TA)6/(TA)7 genotype group were all higher than those in (TA)6/(TA)6 group, and the difference was statistically significant (p = 0.00). Stepwise regression analysis showed that SN-38 peak and valley concentration was correlated with PFS in the (TA)6/(TA)6 genotype. In the (TA)6/(TA)7 group, SN-38 peak concentration was correlated with CPT-11 starting dose and OS, valley concentration correlated with plasma bilirubin levels before CPT-11 treatment, delayed diarrhea, and OS. For the (TA)6/(TA)6 genotype, mPFS of the SN-38 peak concentration >43.2 ng/ml subgroup was significantly longer than that of ≤43.2 ng/ml subgroup (8.0 ± 0.35 vs. 6.5 ± 0.79 months, χ (2) = 17.18, p = 0.00) with a relatively high incidence of Grade I/II° myelosuppression; for the (TA)6/(TA)7 genotype, there was no significant difference in mOS between the SN-38 valley concentration >16.83 ng/ml and ≤16.83 subgroups (17.3 ± 0.45 vs. 18.8 ± 0.50 months, χ (2) = 1.38, p = 0.24), but the former had a higher incidence of Grade III/IV° mucositis and delayed diarrhea. For 2 (TA)7/(TA)7 cases, although 25 % dose reduction of CPT-11, which is calculated according to body surface area, Grade IV° bone marrow suppression and Grade III° delayed diarrhea still occurred after CPT-11 treatment, though both adverse effects resolved and did not recur again after a 50 % dose reduction. The (TA)6/(TA)6 genotype and (TA)6/(TA)7 genotype accounted for the most, and (TA)7/(TA)7 genotype only account for a very small portion of advanced colorectal cancer patients in Shanghai. For the (TA)6/(TA)6 genotype, CPT-11 dosage can be increased gradually to improve efficacy for patients with SN-38 peak concentration ≤43.2 ng/ml after CPT-11 infusion; and for (TA)6/(TA)7 genotype patients, CPT-11 dosage may be lowered appropriately to reduce serious adverse effects such as bone marrow suppression and delayed diarrhea without affecting the efficacy for those with SN-38 valley concentration >16.83 ng/ml. For (TA)7/(TA)7 genotype patients, adverse effects should be closely observed after treatment even if CPT-11 dosage has been reduced.

External validation of scoring instruments for evaluating pediatric resuscitation.

PubMed

Levy, Arielle; Donoghue, Aaron; Bailey, Benoit; Thompson, Nathan; Jamoulle, Olivier; Gagnon, Robert; Gravel, Jocelyn

2014-12-01

Although many methods have been proposed to assess clinical performance during resuscitation, robust and generalizable metrics are still lacking. Further research is necessary to develop validated clinical performance assessment tools and show an improvement in outcomes after training. We aimed to establish evidence for validity of a previously published scoring instrument--the Clinical Performance Tool (CPT)--designed to evaluate clinical performance during simulated pediatric resuscitations. This was a prospective experimental trial performed in the simulation laboratory of a pediatric tertiary care facility, with a pretest/posttest design that assessed residents before and after pediatric advanced life support (PALS) certification. Thirteen postgraduate year 1 (PGY1) and 11 PGY3 pediatric residents completed 5 simulated pediatric resuscitation scenarios each during 2 consecutive sessions; between the 2 sessions, they completed a full PALS certification course. All sessions were video recorded. Sessions were scored by raters using the CPT; total scores were expressed as a percentage of maximum points possible for each scenario. Validity evidence was established and interpreted according to Messick's framework. Evidence regarding relations to other variables was assessed by calculating differences in scores between pre-PALS and post-PALS certification and PGY1 and PGY3 using a repeated-measures analysis of variance test. Internal structure evidence was established by assessing interrater reliability using intraclass correlation coefficients (ICCs) for each scenario, a G-study, and a variance component analysis of individual measurement facets (scenarios, raters, and occasions) and associated interactions. Overall scores for the entire study cohort improved by 10% after PALS training. Scores improved by 9.9% (95% confidence interval [CI], 4.5-15.4) for the pulseless nonshockable arrest (ICC, 0.85; 95% CI, 0.74-0.92), 14.6% (95% CI, 6.7-22.4) for the pulseless shockable arrest (ICC, 0.98; 95% CI, 0.96-0.99), 4.1% (95% CI, -4.5 to 12.8) for the dysrhythmias (ICC, 0.92; 95% CI, 0.87-0.96), 18.4% (95% CI, 9.7-27.1) for the respiratory scenario (ICC, 0.97; 95% CI, 0.95-0.98), and 5.3% (95% CI, -1.4 to 2.0) for the shock scenarios (ICC, 0.94; 95% CI, 0.90-0.97). There were no differences between PGY1 and PGY3 scores before or after the PALS course. Reliability of the instrument was acceptable as demonstrated by a mean ICC of 0.95 (95% CI, 0.94-0.96). The G-study coefficient was 0.94. Most variance could be attributed to the subject (57%). Interactions between subject and scenario and subject and occasion were 9.9% and 1.4%, respectively, and variance attributable to rater was minimal (0%). Pediatric residents improved scores on CPT after completion of a PALS course. Clinical Performance Tool scores are sensitive to the increase in skills and knowledge resulting from such a course but not to learners' levels. Validity evidence from scores for the CPT confirms implementation in new contexts and partially supports internal structure. More evidence is required to further support internal structure and especially to support relations with other variables and consequence evidence. Additional modifications should be made to the CPT before considering its use for high-stakes certification such as PALS.

hMSH5 Facilitates the Repair of Camptothecin-induced Double-strand Breaks through an Interaction with FANCJ*

PubMed Central

Xu, Yang; Wu, Xiling; Her, Chengtao

2015-01-01

Replication stress from stalled or collapsed replication forks is a major challenge to genomic integrity. The anticancer agent camptothecin (CPT) is a DNA topoisomerase I inhibitor that causes fork collapse and double-strand breaks amid DNA replication. Here we report that hMSH5 promotes cell survival in response to CPT-induced DNA damage. Cells deficient in hMSH5 show elevated CPT-induced γ-H2AX and RPA2 foci with concomitant reduction of Rad51 foci, indicative of impaired homologous recombination. In addition, CPT-treated hMSH5-deficient cells exhibit aberrant activation of Chk1 and Chk2 kinases and therefore abnormal cell cycle progression. Furthermore, the hMSH5-FANCJ chromatin recruitment underlies the effects of hMSH5 on homologous recombination and Chk1 activation. Intriguingly, FANCJ depletion desensitizes hMSH5-deficient cells to CPT-elicited cell killing. Collectively, our data point to the existence of a functional interplay between hMSH5 and FANCJ in double-strand break repair induced by replication stress. PMID:26055704

Evaluation of an integrated treatment for active duty service members with comorbid posttraumatic stress disorder and major depressive disorder: Study protocol for a randomized controlled trial.

PubMed

Walter, Kristen H; Glassman, Lisa H; Michael Hunt, W; Otis, Nicholas P; Thomsen, Cynthia J

2018-01-01

Posttraumatic stress disorder (PTSD) commonly co-occurs with major depressive disorder (MDD) in both civilian and military/veteran populations. Existing, evidence-based PTSD treatments, such as cognitive processing therapy (CPT), often reduce symptoms of both PTSD and depression; however, findings related to the influence of comorbid MDD on PTSD treatment outcomes are mixed, and few studies use samples of individuals with both conditions. Behavioral activation (BA), an approach that relies on behavioral principles, is an effective treatment for depression. We have integrated BA into CPT (BA+CPT), a more cognitive approach, to address depressive symptoms among active duty service members with both PTSD and comorbid MDD. We describe an ongoing randomized controlled trial investigating the efficacy of our innovative, integrated BA+CPT intervention, compared with standard CPT, for active duty service members with PTSD and comorbid MDD. We detail the development of this integrated treatment, as well as the design and implementation of the randomized controlled trial, to evaluate its effect on symptoms. Copyright © 2017 Elsevier Inc. All rights reserved.

Hepatic beta-oxidation and carnitine palmitoyltransferase I in neonatal pigs after dietary treatments of clofibric acid, isoproterenol, and medium-chain triglycerides.

PubMed

Peffer, Pasha Lyvers; Lin, Xi; Odle, Jack

2005-06-01

A suckling piglet model was used to study nutritional and pharmacologic means of stimulating hepatic fatty acid beta-oxidation. Newborn pigs were fed milk diets containing either long- or medium-chain triglycerides (LCT or MCT). The long-chain control diet was supplemented further with clofibric acid (0.5%) or isoproterenol (40 ppm), and growth was monitored for 10-12 days. Clofibrate increased rates of hepatic peroxisomal and mitochondrial beta-oxidation of [1-(14)C]-palmitate by 60 and 186%, respectively. Furthermore, malonyl-CoA sensitive carnitine palmitoyltransferase (CPT I) activity increased 64% (P < 0.05) in pigs receiving clofibrate. Increased CPT I activity was not congruent with changes in message, as elevated abundance of CPT I mRNA was not detected (P = 0.16) when assessed by qRT-PCR. Neither rates of beta-oxidation nor CPT activities were affected by dietary MCT or by isoproterenol treatment (P > 0.1). Collectively, these findings indicate that clofibrate effectively induced hepatic CPT activity concomitant with increased fatty acid beta-oxidation.

Cognitive Processing Therapy for Spanish-speaking Latinos: A Formative Study of a Model-Driven Cultural Adaptation of the Manual to Enhance Implementation in a Usual Care Setting.

PubMed

Valentine, Sarah E; Borba, Christina P C; Dixon, Louise; Vaewsorn, Adin S; Guajardo, Julia Gallegos; Resick, Patricia A; Wiltsey Stirman, Shannon; Marques, Luana

2017-03-01

As part of a larger implementation trial for cognitive processing therapy (CPT) for posttraumatic stress disorder (PTSD) in a community health center, we used formative evaluation to assess relations between iterative cultural adaption (for Spanish-speaking clients) and implementation outcomes (appropriateness and acceptability) for CPT. Qualitative data for the current study were gathered through multiple sources (providers: N = 6; clients: N = 22), including CPT therapy sessions, provider fieldnotes, weekly consultation team meetings, and researcher fieldnotes. Findings from conventional and directed content analysis of the data informed refinements to the CPT manual. Data-driven refinements included adaptations related to cultural context (i.e., language, regional variation in wording), urban context (e.g., crime/violence), and literacy level. Qualitative findings suggest improved appropriateness and acceptability of CPT for Spanish-speaking clients. Our study reinforces the need for dual application of cultural adaptation and implementation science to address the PTSD treatment needs of Spanish-speaking clients. © 2016 Wiley Periodicals, Inc.

Enhanced pain perception prior to smoking cessation is associated with early relapse.

PubMed

Nakajima, Motohiro; al'Absi, Mustafa

2011-09-01

Accumulated evidence suggests that nicotine induces analgesia, and endogenous pain regulatory mechanisms may be altered by chronic smoking. The extent to which individual differences in pain perception are related to smokers' ability to abstain from smoking has not been directly examined. Seventy-one smokers who were interested in quitting completed a pre-cessation laboratory session which included the cold pressor test (CPT). Pain ratings were collected during and after CPT. Also, mood changes, cardiovascular measures, and salivary cortisol samples were evaluated prior to, during, and after CPT. Participants attended 4 weekly follow-up assessment sessions after their quit day. Cox regression analysis revealed that higher pain ratings during and after CPT predicted greater risk for smoking relapse. These results remained significant after affective and physiological responses to CPT were controlled, suggesting that pain ratings prior to smoking cessation are potentially useful in identifying smokers who are at greater risk of early smoking relapse and may reflect underlying putative risk for nicotine dependence and relapse. Copyright © 2011 Elsevier B.V. All rights reserved.

The Effect of Cognitive Therapy on Structural Social Capital: Results From a Randomized Controlled Trial Among Sexual Violence Survivors in the Democratic Republic of the Congo

PubMed Central

Bolton, Paul A.; Annan, Jeannie; Kaysen, Debra; Robinette, Katie; Cetinoglu, Talita; Wachter, Karin; Bass, Judith K.

2014-01-01

Objectives. We evaluated changes in social capital following group-based cognitive processing therapy (CPT) for female survivors of sexual violence. Methods. We compared CPT with individual support in a cluster-randomized trial in villages in South Kivu province, Democratic Republic of the Congo. Local psychosocial assistants delivered the interventions from April through July 2011. We evaluated differences between CPT and individual support conditions for structural social capital (i.e., time spent with nonkin social network, group membership and participation, and the size of financial and instrumental support networks) and emotional support seeking. We analyzed intervention effects with longitudinal random effects models. Results. We obtained small to medium effect size differences for 2 study outcomes. Women in the CPT villages increased group membership and participation at 6-month follow-up and emotional support seeking after the intervention compared with women in the individual support villages. Conclusions. Results support the efficacy of group CPT to increase dimensions of social capital among survivors of sexual violence in a low-income conflict-affected context. PMID:25033113

Cognitive Processing Therapy for Spanish-speaking Latinos: A formative study of a model-driven cultural adaptation of the manual to enhance implementation in a usual care setting

PubMed Central

Valentine, Sarah E.; Borba, Christina P. C.; Dixon, Louise; Vaewsorn, Adin S.; Guajardo, Julia Gallegos; Resick, Patricia A.; Wiltsey-Stirman, Shannon; Marques, Luana

2016-01-01

Objective As part of a larger implementation trial for Cognitive Processing Therapy (CPT) for posttraumatic stress disorder (PTSD) in a community health center, we used formative evaluation to assess relations between iterative cultural adaption (for Spanish-speaking clients) and implementation outcomes (appropriateness & acceptability) for CPT. Method Qualitative data for the current study were gathered through multiple sources (providers: N=6; clients: N=22), including CPT therapy sessions, provider field notes, weekly consultation team meetings, and researcher field notes. Findings from conventional and directed content analysis of the data informed refinements to the CPT manual. Results Data-driven refinements included adaptations related to cultural context (i.e., language, regional variation in wording), urban context (e.g., crime/violence), and literacy level. Qualitative findings suggest improved appropriateness and acceptability of CPT for Spanish-speaking clients. Conclusion Our study reinforces the need for dual application of cultural adaptation and implementation science to address the PTSD treatment needs of Spanish-speaking clients. PMID:27378013

Investigating the Role of Hypothalamic Tumor Involvement in Sleep and Cognitive Outcomes Among Children Treated for Craniopharyngioma

PubMed Central

Conklin, Heather M.; Scoggins, Matthew A.; Ashford, Jason M.; Merchant, Thomas E.; Mandrell, Belinda N.; Ogg, Robert J.; Curtis, Elizabeth; Wise, Merrill S.; Indelicato, Daniel J.; Crabtree, Valerie M.

2016-01-01

Objective: Despite excellent survival prognosis, children treated for craniopharyngioma experience significant morbidity. We examined the role of hypothalamic involvement (HI) in excessive daytime sleepiness (EDS) and attention regulation in children enrolled on a Phase II trial of limited surgery and proton therapy. Methods: Participants completed a sleep evaluation (N = 62) and a continuous performance test (CPT) during functional magnetic resonance imaging (fMRI; n = 29) prior to proton therapy. Results: EDS was identified in 76% of the patients and was significantly related to increased HI extent (p = .04). There was no relationship between CPT performance during fMRI and HI or EDS. Visual examination of group composite fMRI images revealed greater spatial extent of activation in frontal cortical regions in patients with EDS, consistent with a compensatory activation hypothesis. Conclusion: Routine screening for sleep problems during therapy is indicated for children with craniopharyngioma, to optimize the timing of interventions and reduce long-term morbidity. PMID:27189690

Mindfulness Meditation Improves Mood, Quality of Life, and Attention in Adults with Attention Deficit Hyperactivity Disorder

PubMed Central

2015-01-01

Objective. Adults with attention deficit hyperactivity disorder (ADHD) display affective problems and impaired attention. Mood in ADHD can be improved by mindful awareness practices (MAP), but results are mixed regarding the enhancement of attentional performance. Here we evaluated MAP-induced changes in quality of life (QoL), mood, and attention in adult ADHD patients and controls using more measures of attention than prior studies. Methods. Twenty-one ADHD patients and 8 healthy controls underwent 8 weekly MAP sessions; 22 similar patients and 9 controls did not undergo the intervention. Mood and QoL were assessed using validated questionnaires, and attention was evaluated using the Attentional Network Test (ANT) and the Conners Continuous Performance Test (CPT II), before and after intervention. Results. MAP enhanced sustained attention (ANT) and detectability (CPT II) and improved mood and QoL of patients and controls. Conclusion. MAP is a complementary intervention that improves affect and attention of adults with ADHD and controls. PMID:26137496

Mindfulness Meditation Improves Mood, Quality of Life, and Attention in Adults with Attention Deficit Hyperactivity Disorder.

PubMed

Bueno, Viviane Freire; Kozasa, Elisa H; da Silva, Maria Aparecida; Alves, Tânia Maria; Louzã, Mario Rodrigues; Pompéia, Sabine

2015-01-01

Adults with attention deficit hyperactivity disorder (ADHD) display affective problems and impaired attention. Mood in ADHD can be improved by mindful awareness practices (MAP), but results are mixed regarding the enhancement of attentional performance. Here we evaluated MAP-induced changes in quality of life (QoL), mood, and attention in adult ADHD patients and controls using more measures of attention than prior studies. Twenty-one ADHD patients and 8 healthy controls underwent 8 weekly MAP sessions; 22 similar patients and 9 controls did not undergo the intervention. Mood and QoL were assessed using validated questionnaires, and attention was evaluated using the Attentional Network Test (ANT) and the Conners Continuous Performance Test (CPT II), before and after intervention. MAP enhanced sustained attention (ANT) and detectability (CPT II) and improved mood and QoL of patients and controls. MAP is a complementary intervention that improves affect and attention of adults with ADHD and controls.

Information Processing Differences and Similarities in Adults with Dyslexia and Adults with Attention Deficit Hyperactivity Disorder during a Continuous Performance Test: A Study of Cortical Potentials

ERIC Educational Resources Information Center

Dhar, Monica; Been, Pieter H.; Minderaa, Ruud B.; Althaus, Monika

2010-01-01

Twenty male adults with ADHD, 16 dyslexic adults, 15 comorbid adults, and 16 normal controls were compared on performance and underlying brain responses, during a cued Continuous Performance Test (O-X CPT), with the aim of discovering features of information processing differentiating between the groups. The study evaluated both cue- and…

The Neuroeconomics of Tobacco Demand: An Initial Investigation of the Neural Correlates of Cigarette Cost-Benefit Decision Making in Male Smokers

PubMed Central

Gray, Joshua C.; Amlung, Michael T.; Owens, Max; Acker, John; Brown, Courtney L.; Brody, Gene H.; Sweet, Lawrence H.; MacKillop, James

2017-01-01

How the brain processes cigarette cost-benefit decision making remains largely unknown. Using functional magnetic resonance imaging (fMRI), this study investigated the neural correlates of decisions for cigarettes (0–10 cigarettes) at varying levels of price during a Cigarette Purchase Task (CPT) in male regular smokers (N = 35). Differential neural activity was examined between choices classified as inelastic, elastic, and suppressed demand, operationalized as consumption unaffected by cost, partially suppressed by cost, and entirely suppressed by cost, respectively. Decisions reflecting elastic demand, putatively the most effortful decisions, elicited greater activation in regions associated with inhibition and planning (e.g., middle frontal gyrus and inferior frontal gyrus), craving and interoceptive processing (anterior insula), and conflict monitoring (e.g., anterior cingulate cortex). Exploratory examination in a harmonized dataset of both cigarette and alcohol demand (N = 59) suggested common neural activation patterns across commodities, particularly in the anterior insula, caudate, anterior cingulate, medial frontal gyrus, and dorsolateral prefrontal cortex. Collectively, these findings provide initial validation of a CPT fMRI paradigm; reveal the interplay of brain regions associated with executive functioning, incentive salience, and interoceptive processing in cigarette decision making; and add to the literature implicating the insula as a key brain region in addiction. PMID:28157228

The Neuroeconomics of Tobacco Demand: An Initial Investigation of the Neural Correlates of Cigarette Cost-Benefit Decision Making in Male Smokers.

PubMed

Gray, Joshua C; Amlung, Michael T; Owens, Max; Acker, John; Brown, Courtney L; Brody, Gene H; Sweet, Lawrence H; MacKillop, James

2017-02-03

How the brain processes cigarette cost-benefit decision making remains largely unknown. Using functional magnetic resonance imaging (fMRI), this study investigated the neural correlates of decisions for cigarettes (0-10 cigarettes) at varying levels of price during a Cigarette Purchase Task (CPT) in male regular smokers (N = 35). Differential neural activity was examined between choices classified as inelastic, elastic, and suppressed demand, operationalized as consumption unaffected by cost, partially suppressed by cost, and entirely suppressed by cost, respectively. Decisions reflecting elastic demand, putatively the most effortful decisions, elicited greater activation in regions associated with inhibition and planning (e.g., middle frontal gyrus and inferior frontal gyrus), craving and interoceptive processing (anterior insula), and conflict monitoring (e.g., anterior cingulate cortex). Exploratory examination in a harmonized dataset of both cigarette and alcohol demand (N = 59) suggested common neural activation patterns across commodities, particularly in the anterior insula, caudate, anterior cingulate, medial frontal gyrus, and dorsolateral prefrontal cortex. Collectively, these findings provide initial validation of a CPT fMRI paradigm; reveal the interplay of brain regions associated with executive functioning, incentive salience, and interoceptive processing in cigarette decision making; and add to the literature implicating the insula as a key brain region in addiction.

Integrated Advanced Microwave Sounding Unit-A (AMSU-A). Engineering Test Report: AMSU-A1 EOS Instrument, (S/N 202) Qualification Level Vibration Tests of August/September 1998, (S/O 565632, OC-417) Plus Addendum A

NASA Technical Reports Server (NTRS)

Heffer, R.

1998-01-01

The purpose of this report is to present a qualification level vibration testing performed on the S/N 202, EOS AMSU-A1 Instrument was vibration tested to qualification levels per the Ref. 1 shop order. The instrument withstood the 8 g sine sweep test, the 7.5 Grms random vibration test, and the 18.75 g sine burst test in each of the three orthogonal axes. Some loss of transmissibility, however, is seen in the lower reflector after Z-axis random vibration. The test sequence was not without incidence. Failure of Channel 7 in the Limited Performance Test (LPT) performed after completion of the 1 st (X-axis) axis vibration sequence, required replacement of the DRO and subsequent re-testing of the instrument. The post-vibration comprehensive performance test (CPT) was successfully run after completion of the three axes of vibration with the replacement component installed in the instrument. Passing the CPT signified the successful completion of the S/N 202 A1 qualification vibration testing.

Using time-dependent indirect CP asymmetries to measure T and CPT violation in B0-Bbar0 mixing

NASA Astrophysics Data System (ADS)

Karan, Anirban; Nayak, Abinash Kumar; Sinha, Rahul; London, David

2018-06-01

Quantum field theory, which is the basis for all of particle physics, requires that all processes respect CPT invariance. It is therefore of paramount importance to test the validity of CPT conservation. In this Letter, we show that the time-dependent, indirect CP asymmetries involving B decays to a CP eigenstate contain enough information to measure T and CPT violation in B0-Bbar0 mixing, in addition to the standard CP-violating weak phases. Entangled B0Bbar0 states are not required (so that this analysis can be carried out at LHCb, as well as at the B factories), penguin pollution need not be neglected, and the measurements can be made using Bd0 or Bs0 mesons.

Detection of diminished response to cold pressor test in smokers: assessment using phase-contrast cine magnetic resonance imaging of the coronary sinus.

PubMed

Kato, Shingo; Kitagawa, Kakuya; Yoon, Yeonyee E; Nakajima, Hiroshi; Nagata, Motonori; Takase, Shinichi; Nakamori, Shiro; Ito, Masaaki; Sakuma, Hajime

2014-04-01

The purposes of this study were to evaluate the reproducibility for measuring the cold pressor test (CPT)-induced myocardial blood flow (MBF) alteration using phase-contrast (PC) cine MRI, and to determine if this approach could detect altered MBF response to CPT in smokers. After obtaining informed consent, ten healthy male non-smokers (mean age: 28±5 years) and ten age-matched male smokers (smoking duration ≥5 years, mean age: 28±3 years) were examined in this institutional review board approved study. Breath-hold PC cine MR images of the coronary sinus were obtained with a 3T MR imager with 32 channel coils at rest and during a CPT performed after immersing one foot in ice water. MBF was calculated as coronary sinus flow divided by the left ventricular (LV) mass which was given as a total LV myocardial volume measured on cine MRI multiplied by the specific gravity (1.05 g/mL). In non-smokers, MBF was 0.86±0.25 mL/min/g at rest, with a significant increase to 1.20±0.36 mL/min/g seen during CPT (percentage change of MBF (∆MBF (%)); 39.2%±14.4%, p<0.001). Inter-study reproducibility for ∆MBF (%) measurements by different MR technologist was good, as indicated by the intraclass correlation coefficient of 0.93 and reproducibility coefficient of 10.5%. There was no significant difference between smokers and non-smokers for resting MBF (0.85±0.32 mL/min/g, p=0.91). However, ∆MBF (%) in smokers was significantly reduced (-4.0±32.2% vs. 39.2±14.4%, p=0.011). PC cine MRI can be used to reproducibly quantify MBF response to CPT and to detect impaired flow response in smokers. This MR approach may be useful for monitoring the sequential change of coronary blood flow in various potentially pathologic conditions and for investigating its relationship with cardiovascular risk. Copyright © 2014 Elsevier Inc. All rights reserved.

Micropropagation and validation of genetic and biochemical fidelity among regenerants of Nothapodytes nimmoniana (Graham) Mabb. employing ISSR markers and HPLC.

PubMed

Prakash, Lokesh; Middha, Sushil Kumar; Mohanty, Sudipta Kumar; Swamy, Mallappa Kumara

2016-12-01

An in vitro protocol has been established for clonal propagation of Nothapodytes nimmoniana which is an important source of Camptothecin (CPT). Elite source was identified based on the chemical potency to accumulate the optimum level of CPT. Different types and concentrations of plant growth regulators were used to study their effect on inducing multiple shoots from the explants regenerated from embryos of N. nimmoniana. Of these, a combination of N6-benzyladenine (0.2 mg L -1 ) and Indole-3-butyric acid (IBA) (0.1 mg L -1 ) proved optimum for differentiating multiple shoots in 90.6 % of the cultures with an average of 10.24 shoots per explant obtained within 8 weeks of inoculation. Nearly, 92 % of the excised in vitro shoots rooted on half strength Murashige and Skoog (MS) medium containing 0.05 % activated charcoal, supplemented with 1-naphthaleneacetic acid and IBA at 0.1 mg L -1 each. The micropropagated plants were evaluated for their genetic fidelity by employing inter simple sequence repeats (ISSR) markers. Ten individuals, randomly chosen from a population of 145 regenerants, were compared with the donor plant. The regenerated plants were also evaluated for their chemical potency using high-performance liquid chromatography (HPLC) analysis of CPT content. The true-to-type nature of the micropropagated plants was confirmed based on their monomorphic banding profiles with that of the mother plants using ISSR markers. Besides, HPLC evaluation of the CPT content confirmed the existence of chemical uniformity among the regenerated plants and the elite mother plant.

The Stockholm-3 (STHLM3) Model can Improve Prostate Cancer Diagnostics in Men Aged 50-69 yr Compared with Current Prostate Cancer Testing.

PubMed

Eklund, Martin; Nordström, Tobias; Aly, Markus; Adolfsson, Jan; Wiklund, Peter; Brandberg, Yvonne; Thompson, James; Wiklund, Fredrik; Lindberg, Johan; Presti, Joseph C; StLezin, Mark; Clements, Mark; Egevad, Lars; Grönberg, Henrik

2016-11-23

Prostate cancer screening is associated with low specificity, unnecessary biopsies, and overdiagnosis. We have previously shown that the Stockholm-3 model (S3M) can reduce biopsies compared with using prostate-specific antigen (PSA) ≥3ng/ml as an indication for biopsy. Urologists in today's current prostate cancer testing (CPT) have access to numerous variables in addition to PSA (eg, age, ethnicity, family history, free PSA, PSA velocity, digital rectal examination, and prostate volume) to support biopsy decisions. We estimated the number of prostate cancers diagnosed and prostate biopsies performed if S3M replaced CPT in Stockholm, Sweden, by comparing biopsy results in 56 282 men who underwent PSA testing according to CPT in Stockholm in 2011 with the 47 688 men enrolled in the STHLM3 validation cohort 2012-2015. With the same sensitivity as CPT to diagnose Gleason score ≥7 prostate cancer, S3M was estimated to reduce the number of men biopsied by 53% (95% confidence interval [CI]: 41-65%), avoid 76% (95% CI: 67-81%) of negative biopsies, and reduce Gleason score 6 cancers by 23% (95% CI: 6-40%). S3M has the potential to improve prostate cancer diagnostics by better selecting men with high risk of GS ≥7 prostate cancer. We modeled the effect the Stockholm-3 model would have on prostate cancer diagnostics if it replaced current clinical practice. We found that Stockholm-3 model may substantially reduce the number of biopsies, while maintaining the same sensitivity to diagnose clinically significant prostate cancer. Copyright © 2016. Published by Elsevier B.V.

Thermosensitive mPEG-b-PA-g-PNIPAM comb block copolymer micelles: effect of hydrophilic chain length and camptothecin release behavior.

PubMed

Yang, Xiao-Li; Luo, Yan-Ling; Xu, Feng; Chen, Ya-Shao

2014-02-01

Block copolymer micelles are extensively used as drug controlled release carriers, showing promising application prospects. The comb or brush copolymers are especially of great interest, whose densely-grafted side chains may be important for tuning the physicochemical properties and conformation in selective solvents, even in vitro drug release. The purpose of this work was to synthesize novel block copolymer combs via atom transfer radical polymerization, to evaluate its physicochemical features in solution, to improve drug release behavior and to enhance the bioavailablity, and to decrease cytotoxicity. The physicochemical properties of the copolymer micelles were examined by modulating the composition and the molecular weights of the building blocks. A dialysis method was used to load hydrophobic camptothecin (CPT), and the CPT release and stability were detected by UV-vis spectroscopy and high-performance liquid chromatography, and the cytotoxicity was evaluated by MTT assays. The copolymers could self-assemble into well-defined spherical core-shell micelle aggregates in aqueous solution, and showed thermo-induced micellization behavior, and the critical micelle concentration was 2.96-27.64 mg L(-1). The micelles were narrow-size-distribution, with hydrodynamic diameters about 128-193 nm, depending on the chain length of methoxy polyethylene glycol (mPEG) blocks and poly(N-isopropylacrylamide) (PNIPAM) graft chains or/and compositional ratios of mPEG to PNIPAM. The copolymer micelles could stably and effectively load CPT but avoid toxicity and side-effects, and exhibited thermo-dependent controlled and targeted drug release behavior. The copolymer micelles were safe, stable and effective, and could potentially be employed as CPT controlled release carriers.

Monkey Prefrontal Neurons Reflect Logical Operations for Cognitive Control in a Variant of the AX Continuous Performance Task (AX-CPT)

PubMed Central

Blackman, Rachael K.; Crowe, David A.; DeNicola, Adele L.; Sakellaridi, Sofia; MacDonald, Angus W.

2016-01-01

Cognitive control is the ability to modify the behavioral response to a stimulus based on internal representations of goals or rules. We sought to characterize neural mechanisms in prefrontal cortex associated with cognitive control in a context that would maximize the potential for future translational relevance to human neuropsychiatric disease. To that end, we trained monkeys to perform a dot-pattern variant of the AX continuous performance task that is used to measure cognitive control impairment in patients with schizophrenia (MacDonald, 2008; Jones et al., 2010). Here we describe how information processing for cognitive control in this task is related to neural activity patterns in prefrontal cortex of monkeys, to advance our understanding of how behavioral flexibility is implemented by prefrontal neurons in general, and to model neural signals in the healthy brain that may be disrupted to produce cognitive control deficits in schizophrenia. We found that the neural representation of stimuli in prefrontal cortex is strongly biased toward stimuli that inhibit prepotent or automatic responses. We also found that population signals encoding different stimuli were modulated to overlap in time specifically in the case that information from multiple stimuli had to be integrated to select a conditional response. Finally, population signals relating to the motor response were biased toward less frequent and therefore less automatic actions. These data relate neuronal activity patterns in prefrontal cortex to logical information processing operations required for cognitive control, and they characterize neural events that may be disrupted in schizophrenia. SIGNIFICANCE STATEMENT Functional imaging studies have demonstrated that cognitive control deficits in schizophrenia are associated with reduced activation of the dorsolateral prefrontal cortex (MacDonald et al., 2005). However, these data do not reveal how the disease has disrupted the function of prefrontal neurons to produce the observed deficits in cognitive control. Relating cognitive control to neurophysiological signals at a cellular level in prefrontal cortex is a necessary first step toward understanding how disruption of these signals could lead to cognitive control failure in neuropsychiatric disease. To that end, we translated a task that measures cognitive control deficits in patients with schizophrenia to monkeys and describe here how neural signals in prefrontal cortex relate to performance. PMID:27053213

Examining pediatric resuscitation education using simulation and scripted debriefing: a multicenter randomized trial.

PubMed

Cheng, Adam; Hunt, Elizabeth A; Donoghue, Aaron; Nelson-McMillan, Kristen; Nishisaki, Akira; Leflore, Judy; Eppich, Walter; Moyer, Mike; Brett-Fleegler, Marisa; Kleinman, Monica; Anderson, Jodee; Adler, Mark; Braga, Matthew; Kost, Susanne; Stryjewski, Glenn; Min, Steve; Podraza, John; Lopreiato, Joseph; Hamilton, Melinda Fiedor; Stone, Kimberly; Reid, Jennifer; Hopkins, Jeffrey; Manos, Jennifer; Duff, Jonathan; Richard, Matthew; Nadkarni, Vinay M

2013-06-01

Resuscitation training programs use simulation and debriefing as an educational modality with limited standardization of debriefing format and content. Our study attempted to address this issue by using a debriefing script to standardize debriefings. To determine whether use of a scripted debriefing by novice instructors and/or simulator physical realism affects knowledge and performance in simulated cardiopulmonary arrests. DESIGN Prospective, randomized, factorial study design. The study was conducted from 2008 to 2011 at 14 Examining Pediatric Resuscitation Education Using Simulation and Scripted Debriefing (EXPRESS) network simulation programs. Interprofessional health care teams participated in 2 simulated cardiopulmonary arrests, before and after debriefing. We randomized 97 participants (23 teams) to nonscripted low-realism; 93 participants (22 teams) to scripted low-realism; 103 participants (23 teams) to nonscripted high-realism; and 94 participants (22 teams) to scripted high-realism groups. INTERVENTION Participants were randomized to 1 of 4 arms: permutations of scripted vs nonscripted debriefing and high-realism vs low-realism simulators. Percentage difference (0%-100%) in multiple choice question (MCQ) test (individual scores), Behavioral Assessment Tool (BAT) (team leader performance), and the Clinical Performance Tool (CPT) (team performance) scores postintervention vs preintervention comparison (PPC). There was no significant difference at baseline in nonscripted vs scripted groups for MCQ (P = .87), BAT (P = .99), and CPT (P = .95) scores. Scripted debriefing showed greater improvement in knowledge (mean [95% CI] MCQ-PPC, 5.3% [4.1%-6.5%] vs 3.6% [2.3%-4.7%]; P = .04) and team leader behavioral performance (median [interquartile range (IQR)] BAT-PPC, 16% [7.4%-28.5%] vs 8% [0.2%-31.6%]; P = .03). Their improvement in clinical performance during simulated cardiopulmonary arrests was not significantly different (median [IQR] CPT-PPC, 7.9% [4.8%-15.1%] vs 6.7% [2.8%-12.7%], P = .18). Level of physical realism of the simulator had no independent effect on these outcomes. The use of a standardized script by novice instructors to facilitate team debriefings improves acquisition of knowledge and team leader behavioral performance during subsequent simulated cardiopulmonary arrests. Implementation of debriefing scripts in resuscitation courses may help to improve learning outcomes and standardize delivery of debriefing, particularly for novice instructors.

Antiproton Studies in Penning Traps

DTIC Science & Technology

1993-09-30

applications to MRI imaging. This is by far the most sensitive test of CPT invariance with a baryon system and is one of the most accurate tests of CPT...system which has likely applications to MRI imaging. This is by far the most sensitive test of CPT invariance with a baryon system and is one of the...a thin window of matter . In a second 24 hour demonstration experiment, we managed to capture a few antiprotons in the small volume of an ion trap.1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santos, A.F., E-mail: alesandroferreira@fisica.ufmt.br; Department of Physics and Astronomy, University of Victoria, 3800 Finnerty Road Victoria, BC; Khanna, Faqir C., E-mail: khannaf@uvic.ca

Dynamics between particles is governed by Lorentz and CPT symmetry. There is a violation of Parity (P) and CP symmetry at low levels. The unified theory, that includes particle physics and quantum gravity, may be expected to be covariant with Lorentz and CPT symmetry. At high enough energies, will the unified theory display violation of any symmetry? The Standard Model Extension (SME), with Lorentz and CPT violating terms, has been suggested to include particle dynamics. The minimal SME in the pure photon sector is considered in order to calculate the Casimir effect at finite temperature.

Theoretical Studies of Lorentz and CPT Symmetry

NASA Technical Reports Server (NTRS)

Kostelecky, V. Alan

2005-01-01

The fundamental symmetries studied here are Lorentz and CPT invariance, which form a cornerstone of the relativistic quantum theories used in modern descriptions of nature. The results obtained during the reporting period focus on the idea, originally suggested by the P.I. and his group in the late 1980s, that observable CPT and Lorentz violation in nature might emerge from the qualitatively new physics expected to hold at the Planck scale. What follows is a summary of results obtained during the period of this grant.

76 FR 22081 - North Pacific Fishery Management Council; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-20

... (CPT). SUMMARY: The North Pacific Fishery Management Council's (NPFMC) Crab Plan Team (CPT) will meet.... SUPPLEMENTARY INFORMATION: The Plan Team will discuss: Election of officers, catch accounting for groundfish...

Neuropsychological Effects of Low-Level Manganese Exposure in Welders

PubMed Central

Laohaudomchok, Wisanti; Lin, Xihong; Herrick, Robert F.; Fang, Shona C.; Cavallari, Jennifer M.; Shrairman, Ruth; Landau, Alexander; Christiani, David C.; Weisskopf, Marc G.

2011-01-01

While the neuropsychological effects of high manganese (Mn) exposure in occupational settings are well known, the effects of lower levels of exposure are less understood. In this study, we investigated the neuropsychological effects of lower level occupational Mn exposure in 46 male welders (mean age = 37.4, sd = 11.7 years). Each welders’ cumulative Mn exposure indices (Mn-CEI) for the past 12 months and total work history Mn exposure were constructed based on air Mn measurements and work histories. The association between these exposure indices and performance on cognitive, motor control, and psychological tests was examined. In addition, among a subset of welders (n=24) who completed the tests both before and after a work shift, we examined the association between cross-shift Mn exposure assessed from personal monitoring and acute changes in test scores. Mn exposures in this study (median = 12.9 μg/m3) were much lower, as compared to those observed in other similar studies. Increasing total Mn-CEI was significantly associated with slower reaction time on the continuous performance test (CPT; p<0.01), as well as worse mood for several scales on the Profile of Mood States (POMS; confused, tired, and a composite of tired and energetic, all p≤0.03). Increasing Mn-CEI over the previous 12 months was significantly associated with worse mood on the sad, tense, and confused POMS scales (all p≤0.03) and the association with worse CPT performance approached significance (p=0.10). Higher Mn exposure over the course of a workday was associated with worse performance on the CPT test across the day (p=0.06) as well as declines in fine motor control over the work-shift (p=0.04), adjusting for age and time between the 2 tests. Our study suggests that even at relatively low Mn exposure levels neuropsychological effects may manifest particularly with respect to attention, mood, and fine motor control. PMID:21192973

Differential impact of methylphenidate and atomoxetine on sustained attention in youth with attention-deficit/hyperactivity disorder.

PubMed

Bédard, Anne-Claude V; Stein, Mark A; Halperin, Jeffrey M; Krone, Beth; Rajwan, Estrella; Newcorn, Jeffrey H

2015-01-01

This study examined the effects of atomoxetine (ATX) and OROS methylphenidate (MPH) on laboratory measures of inhibitory control and attention in youth with attention-deficit/hyperactivity disorder (ADHD). It was hypothesized that performance would be improved by both treatments, but response profiles would differ because the medications work via different mechanisms. One hundred and two youth (77 male; mean age = 10.5 ± 2.7 years) with ADHD received ATX (1.4 ± 0.5 mg/kg) and MPH (52.4 ± 16.6 mg) in a randomized, double-blind, crossover design. Medication was titrated in 4-6-week blocks separated by a 2-week placebo washout. Inhibitory control and attention measures were obtained at baseline, following washout, and at the end of each treatment using Conners' Continuous Performance Test II (CPT-II), which provided age-adjusted T-scores for reaction time (RT), reaction time variability (RT variability), and errors. Repeated-measures analyses of variance were performed, with Time (premedication, postmedication) and Treatment type (ATX, MPH) entered as within-subject factors. Data from the two treatment blocks were checked for order effects and combined if order effects were not present. Clinicaltrials.gov: NCT00183391. Main effects for Time on RT (p = .03), RTSD (p = .001), and omission errors (p = .01) were significant. A significant Drug × Time interaction indicated that MPH improved RT, RTSD, and omission errors more than ATX (p < .05). Changes in performance with treatment did not correlate with changes in ADHD symptoms. MPH has greater effects than ATX on CPT measures of sustained attention in youth with ADHD. However, the dissociation of cognitive and behavioral change with treatment indicates that CPT measures cannot be considered proxies for symptomatic improvement. Further research on the dissociation of cognitive and behavioral endpoints for ADHD is indicated. © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.

Improved cognitive functioning in obese adolescents after a 30-week inpatient weight loss program.

PubMed

Vantieghem, Stijn; Bautmans, Ivan; Guchtenaere, Ann De; Tanghe, Ann; Provyn, Steven

2018-06-15

Studies linked obesity with a large number of medical conditions including decreased cognitive functioning. The relation between BMI and cognition was proven in adults, but in adolescents the results are conflicting. Further, limited data are available on the impact of weight loss on cognition. This study analyzed the impact of a 30-week lasting weight loss program on cognition and determined the impact of changes in body composition and self-perceived fatigue on changes in cognition. Sixty-two obese adolescents were evaluated at baseline and after 30 weeks. Stroop test (ST; selective attention), Continuous Performance Test (CPT; sustained attention) and Ray Auditory verbal learning test (RAVLT; short-term memory) were assessed. Additionally, body composition parameters and fatigue (MFI-20) were evaluated. Improved reaction times were found for ST and CPT after the intervention, but were independent for reductions in BMI, fat mass, fat%, and fatigue. Short memory also improved with decreased fatigue as an influencing parameter. Accuracy of ST and CPT showed no significant changes. A 30-week lasting inpatient weight loss program improved selective attention, sustained attention, and short-term memory. Changes in body composition did not explain the improvements in cognitive functioning. Decreased fatigue resulted in improved aspects of cognition.

CPT Special Report: Survey of Ph.D. Programs in Chemistry.

ERIC Educational Resources Information Center

Journal of Chemical Education, 1997

1997-01-01

Presents preliminary results from a survey taken by the American Chemical Society (ACS) Committee on Professional Training (CPT) to determine the current practices among 155 Ph.D. programs in chemistry. (DKM)

Camptothecin prodrug nanomicelle based on a boronate ester-linked diblock copolymer as the carrier of doxorubicin with enhanced cellular uptake.

PubMed

Gao, Ya; Xiao, Yi; Liu, Shiyuan; Yu, Jiahui

2018-02-01

A novel pH-sensitive polymeric prodrug of camptothecin (CPT) by polymerizing γ-camptothecin-glutamate N-carboxyanhydride (Glu (CPT)-NCA) on boronate ester-linked poly (ethyleneglycol) (PEG) directly via the amine-initiated ring open polymerization (ROP) has been developed. The resulting amphiphilic prodrug (mPEG-BC-PGluCPT) could self-assemble into nanoparticles and encapsulate doxorubicin (Dox) simultaneously in aqueous solution for dual-drug delivery. The formation of polymeric prodrug micelles (mPEG-BC@PGluCPT) was confirmed by the measurements of critical aggregation concentration (CAC), particle size, and morphology observations. The mPEG-BC@PGluCPT micelles were colloidally stable in solutions for two weeks. Polymeric prodrug micelles mPEG-BC@PGluCPT and Dox-loaded micelles mPEG-BC@PGluCPT⋅Dox showed sustained drug release profiles over 48 h. As expected, drug release was accelerated by the decreasement of pH value from 7.4 to 6.0, which demonstrated pH-dependent manner of drug release. Additionally, it was found that cellular uptake of mPEG-BC@PGluCPT⋅Dox micelles on HepG2 cells was higher than that on HL-7702 cells, especially in culture medium at pH 6.0. The enhanced cellular uptake of mPEG-BC@PGluCPT⋅Dox micelles under acidic condition on HepG2 cells resulted in the higher cytotoxicity of mPEG-BC@PGluCPT⋅Dox micelles at acidic pH than that at pH 7.4.

Cold Oxygen Plasma Treatments for the Improvement of the Physicochemical and Biodegradable Properties of Polylactic Acid Films for Food Packaging.

PubMed

Song, Ah Young; Oh, Yoon Ah; Roh, Si Hyeon; Kim, Ji Hyeon; Min, Sea C

2016-01-01

The effects of cold plasma (CP) treatment on the physicochemical and biodegradable properties of polylactic acid (PLA) films were studied. The PLA films were exposed to CP for 40 min at 900 W and 667 Pa using oxygen as the plasma-forming gas. The tensile, optical, and dynamic mechanical thermal properties, surface morphology, printability, water contact angle, chemical structure, weight change, and biodegradability properties of the films were evaluated during storage for up to 56 d. The tensile and optical properties of the PLA films were not significantly affected by CP treatment (CPT; P > 0.05). The surface roughness and water contact angle of PLA films increased by CPT and further increased during storage for 56 d. The printability of the PLA films increased following CPT and remained stable throughout the storage period. CP-induced hydrophilicity was also sustained during the storage period. The PLA films lost 1.9% of their weight after CPT, but recovered 99.5% of this loss after 14 d in storage. Photodegradation, thermal, and microbial biodegradable properties of the films were significantly improved by CPT (P < 0.05). Accelerated biodegradation of CP-treated PLA sachets with and without cheese was observed in compost. These results demonstrate the potential of CPT for modifying the stiffness, water contact angle, and chemical structure of PLA films and improving the printability and biodegradability of the films for food packaging. © 2015 Institute of Food Technologists®

Functional characterization of the first filamentous fungal tRNA-isopentenyltransferase and its role in the virulence of Claviceps purpurea.

PubMed

Hinsch, Janine; Galuszka, Petr; Tudzynski, Paul

2016-08-01

In plants, cytokinins (CKs) are synthesized de novo or by the degradation of modified tRNAs. Recently, the first fungal de novo pathway was identified within the plant pathogen Claviceps purpurea. As the deletion of the de novo pathway did not lead to a complete loss of CKs, this work focuses on the tRNA-modifying protein tRNA-isopentenyltransferase (CptRNA-IPT). The contribution of this enzyme to the CK pool of Claviceps and the role of CKs in the host-pathogen interaction are emphasized. The effects of the deletion of cptRNA-ipt and the double deletion of cptRNA-ipt and the key gene of de novo biosynthesis cpipt-log on growth, CK biosynthesis and virulence were analyzed. In addition, the sites of action of CptRNA-IPT were visualized using reporter gene fusions. In addition to CK-independent functions, CptRNA-IPT was essential for the biosynthesis of cis-zeatin (cZ) and contributed to the formation of isopentenyladenine (iP) and trans-zeatin (tZ). Although ΔcptRNA-ipt was reduced in virulence, the 'CK-free' double deletion mutant was nearly apathogenic. The results prove a redundancy of the CK biosynthesis pathway in C. purpurea for iP and tZ formation. Moreover, we show, for the first time, that CKs are required for the successful establishment of a host-fungus interaction. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

The estimation of hemodynamic signals measured by fNIRS response to cold pressor test

NASA Astrophysics Data System (ADS)

Ansari, M. A.; Fazliazar, E.

2018-04-01

The estimation of cerebral hemodynamic signals has an important role for monitoring the stage of neurological diseases. Functional Near-Infrared Spectroscopy (fNIRS) can be used for monitoring of brain activities. fNIRS utilizes light in the near-infrared spectrum (650-1000 nm) to study the response of the brain vasculature to the changes in neural activities, called neurovascular coupling, within the cortex when cognitive activation occurs. The neurovascular coupling may be disrupted in the brain pathological condition. Therefore, we can also use fNIRS to diagnosis brain pathological conditions or to monitor the efficacy of related treatments. The Cold pressor test (CPT), followed by immersion of dominant hand or foot in the ice water, can induce cortical activities. The perception of pain induced by CPT can be related to cortical neurovascular coupling. Hence, the variation of cortical hemodynamic signals during CPT can be an indicator for studying neurovascular coupling. Here, we study the effect of pain induced by CPT on the temporal variation of concentration of oxyhemoglobin [HbO2] and deoxyhemoglobin [Hb] in the healthy brains. We use fNIRS data collected on forehead during a CPT from 11 healthy subjects, and the average data are compared with post-stimulus pain rating scores. The results show that the variation of [Hb] and [HbO2] are positively correlated with self-reported scores during the CPT. These results depict that fNIRS can be potentially applied to study the decoupling of neurovascular process in brain pathological conditions.

Effects of camptothecin or TOP1 overexpression on genetic stability in Saccharomyces cerevisiae.

PubMed

Sloan, Roketa; Huang, Shar-Yin Naomi; Pommier, Yves; Jinks-Robertson, Sue

2017-11-01

Topoisomerase I (Top1) removes DNA torsional stress by nicking and resealing one strand of DNA, and is essential in higher eukaryotes. The enzyme is frequently overproduced in tumors and is the sole target of the chemotherapeutic drug camptothecin (CPT) and its clinical derivatives. CPT stabilizes the covalent Top1-DNA cleavage intermediate, which leads to toxic double-strand breaks (DSBs) when encountered by a replication fork. In the current study, we examined genetic instability associated with CPT treatment or with Top1 overexpression in the yeast Saccharomyces cerevisiae. Two types of instability were monitored: Top1-dependent deletions in haploid strains, which do not require processing into a DSB, and instability at the repetitive ribosomal DNA (rDNA) locus in diploid strains, which reflects DSB formation. Three 2-bp deletion hotspots were examined and mutations at each were elevated either when a wild-type strain was treated with CPT or when TOP1 was overexpressed, with the mutation frequency correlating with the level of TOP1 overexpression. Under both conditions, deletions at novel positions were enriched. rDNA stability was examined by measuring loss-of-heterozygosity and as was observed previously upon CPT treatment of a wild-type strain, Top1 overexpression destabilized rDNA. We conclude that too much, as well as too little of Top1 is detrimental to eukaryotic genomes, and that CPT has destabilizing effects that extend beyond those associated with DSB formation. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of Diurnal Variation and Caffeine Consumption on Test of Variables of Attention (TOVA) Performance in Healthy Young Adults

ERIC Educational Resources Information Center

Hunt, Melissa G.; Momjian, Ani J.; Wong, Keri K.

2011-01-01

The Test of Variables of Attention (TOVA) is a continuous performance test (CPT) that assesses attention, impulsivity, and processing speed. CPTs are used in the assessment of attention-deficit/hyperactivity disorder (ADHD) in children, but more young adults are being assessed for ADHD as well. The TOVA norms are based on a standardization sample…

Coherent population trapping with polarization modulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yun, Peter, E-mail: enxue.yun@obspm.fr; Guérandel, Stéphane; Clercq, Emeric de

Coherent population trapping (CPT) is extensively studied for future vapor cell clocks of high frequency stability. In the constructive polarization modulation CPT scheme, a bichromatic laser field with polarization and phase synchronously modulated is applied on an atomic medium. A high contrast CPT signal is observed in this so-called double-modulation configuration, due to the fact that the atomic population does not leak to the extreme Zeeman states, and that the two CPT dark states, which are produced successively by the alternate polarizations, add constructively. Here, we experimentally investigate CPT signal dynamics first in the usual configuration, a single circular polarization.more » The double-modulation scheme is then addressed in both cases: one pulse Rabi interaction and two pulses Ramsey interaction. The impact and the optimization of the experimental parameters involved in the time sequence are reviewed. We show that a simple seven-level model explains the experimental observations. The double-modulation scheme yields a high contrast similar to the one of other high contrast configurations like push-pull optical pumping or crossed linear polarization scheme, with a setup allowing a higher compactness. The constructive polarization modulation is attractive for atomic clock, atomic magnetometer, and high precision spectroscopy applications.« less

Hypothesis on the Origin of Chaotic Pulse Train in Dart Leader

NASA Astrophysics Data System (ADS)

Pu, Y.; Qie, X.; Sun, Z.; Jiang, R.; Liu, M.; Zhang, H.

2017-12-01

The origin of chaotic pulse train (CPT) during the dart leader propagation remains debatable. Based on previous observations, the `chaotic' dart leader is featured by chaotic electric fields, large charge transfer and high energetic radiation. In some cases, the cause of CPT was attributed to the concurrent branches or upward connecting leader. In this presentation, after carefully examining the simultaneous optical, electrical and VHF location data of triggered lightning in SHATLE and some results in other literature, we found the close relationship between the upper luminous leader segment and CPT. It is hypothesized that the CPT originates from the luminous corona zone around the upper leader channel beyond the leader tip. The fast, sufficient supply of negative charge from the cloud can result in a net negative charge layer around the ionized channel surface. Then new diffuse discharge can make a corona zone outside the channel and radiates in a chaotic way. The cloud charge reservoir and the speed of charge transfer, which can be indicated by the speed of the leader, are determinative to the generation of CPT. Using VHF location technique, we also estimated the speed evolution of the leader and link it with electric field change.

Convection-enhanced delivery of nanoliposomal CPT-11 (irinotecan) and PEGylated liposomal doxorubicin (Doxil) in rodent intracranial brain tumor xenografts

PubMed Central

Krauze, Michal T.; Noble, Charles O.; Kawaguchi, Tomohiro; Drummond, Daryl; Kirpotin, Dmitri B.; Yamashita, Yoji; Kullberg, Erika; Forsayeth, John; Park, John W.; Bankiewicz, Krystof S.

2007-01-01

We have previously shown that convection-enhanced delivery (CED) of highly stable nanoparticle/liposome agents encapsulating chemotherapeutic drugs is effective against intracranial rodent brain tumor xenografts. In this study, we have evaluated the combination of a newly developed nanoparticle/liposome containing the topoisomerase I inhibitor CPT-11 (nanoliposomal CPT-11 [nLs-CPT-11]), and PEGylated liposomal doxorubicin (Doxil) containing the topoisomerase II inhibitor doxorubicin. Both drugs were detectable in the CNS for more than 36 days after a single CED application. Tissue half-life was 16.7 days for nLs-CPT-11 and 10.9 days for Doxil. The combination of the two agents produced synergistic cytotoxicity in vitro. In vivo in U251MG and U87MG intracranial rodent xenograft models, CED of the combination was also more efficacious than either agent used singly. Analysis of the parameters involved in this approach indicated that tissue pharmacokinetics, tumor microanatomy, and biochemical interactions of the drugs all contributed to the therapeutic efficacy observed. These findings have implications for further clinical applications of CED-based treatment of brain tumors. PMID:17652269

Intracellular inhibition of carboxylesterases by benzil: modulation of CPT-11 cytotoxicity.

PubMed

Hyatt, Janice L; Tsurkan, Lyudmila; Wierdl, Monika; Edwards, Carol C; Danks, Mary K; Potter, Philip M

2006-09-01

Carboxylesterases are ubiquitous proteins responsible for the detoxification of xenobiotics. However, these enzymes also activate prodrugs, such as the anticancer agents capecitabine and CPT-11. As a consequence, overexpression of carboxylesterases within tumor cells sensitizes these cells to CPT-11. We have recently identified two classes of carboxylesterase inhibitors based on either a benzil (diphenylethane-1,2-dione) or a benzene sulfonamide scaffold and showed that these compounds inhibit carboxylesterases with Kis in the low nanomolar range. Because both classes of inhibitors show reversible enzyme inhibition, conventional in vitro biochemical assays would not accurately reflect the in situ levels of carboxylesterase activity or inhibition. Therefore, we have developed a novel assay for the determination of intracellular carboxylesterase activity using 4-methylumbelliferone as a substrate. These studies show that benzil and a dimethylbenzil analogue efficiently enter cells and inhibit human intestinal carboxylesterase and rabbit liver carboxylesterase intracellularly. This inhibition results in reduced cytotoxicity to CPT-11 due to the lack of carboxylesterase-mediated conversion of the prodrug to SN-38. These results suggest that intracellular modulation of carboxylesterase activity with benzil or its analogues may be applied to minimize the toxicity of normal cells to CPT-11.

Multi-Method Assessment of ADHD Characteristics in Preschool Children: Relations between Measures

ERIC Educational Resources Information Center

Sims, Darcey M.; Lonigan, Christopher J.

2012-01-01

Several forms of assessment tools, including behavioral rating scales and objective tests such as the Continuous Performance Test (CPT), can be used to measure inattentive and hyperactive/impulsive behaviors associated with Attention-Deficit/Hyperactivity Disorder (ADHD). However, research with school-age children has shown that the correlations…

77 FR 29458 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-17

... excise tax on tobacco products (TP) and cigarette paper and tubes (CP&T) removed from the factory or... collect any unpaid excise tax. Manufactures of TP or CP&T, export warehouse proprietors, and corporate...

75 FR 80849 - Notice of Initial Determination Revising the List of Products Requiring Federal Contractor...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-23

..., Reporter Brasil, the Citizens' Charcoal Institute (ICC), and the Pastoral Land Commission (CPT), indicate... Brasil, the Citizens' Charcoal Institute (ICC), and the Pastoral Land Commission (CPT), indicate that...

[Autobiographical memory of depressed patients].

PubMed

Yao, Shuqiao; Liu, Xianhua; Zhao, Weifeng; Yang, Wenhui; Tan, Furong

2010-07-01

To explore the autobiographical memory characteristics in depressed patients and their influence factors. Autobiographical memory, emotion and cognitive executive function of 60 depressed patients and 60 healthy controls were assessed with autobiographical memory test (AMT), Hamilton depression scale (HAMD), Beck depression inventory (BDI), Beck anxiety inventory (BAI), hospital anxiety and depression scale (HAD), arrow-task stroop test (ATST), Wisconsin card sorting test (WCST), Backward masking test (BMT) and continuous performance test (CPT). The specific memory of the depressed group was significantly less than that of the control group, and was negatively related with the negative emotion score, the time of anterograde and retrograde reading of ATST, and the time difference of ATST. The overgeneral memory increased and the latency to response of ATST was significantly longer than that of the control group. The two factors were positively related with the negative emotion score, the time of anterograde and retrograde reading of ATST, and the time difference of ATST. The autobiographical memory of the depressed patients is overgeneralized and retarded. These characteristics are related with negative emotion and impairment of cognitive executive function.

The pro-apoptotic protein Bim is a convergence point for cAMP/protein kinase A- and glucocorticoid-promoted apoptosis of lymphoid cells.

PubMed

Zhang, Lingzhi; Insel, Paul A

2004-05-14

The mechanisms by which cAMP mediates apoptosis are not well understood. In the current studies, we used wild-type (WT) S49 T-lymphoma cells and the kin(-) variant (which lacks protein kinase A (PKA)) to examine cAMP/PKA-mediated apoptosis. The cAMP analog, 8-CPT-cAMP, increased phosphorylation of the cAMP response element-binding protein (CREB), activated caspase-3, and induced apoptosis in WT but not in kin(-) S49 cells. Using an array of 96 apoptosis-related genes, we found that treatment of WT cells with 8-CPT-cAMP for 24 h induced expression of mRNA for the pro-apoptotic gene, Bim. Real-time PCR analysis indicated that 8-CPT-cAMP increased Bim RNA in WT cells in <2 h and maintained this increase for >24 h. Bim protein expression increased in WT but not kin(-) cells treated with 8-CPT-cAMP or with the beta-adrenergic receptor agonist isoproterenol. Both apoptosis and Bim expression were reversible with removal of 8-CPT-cAMP after <6 h. The glucocorticoid dexamethasone also promoted apoptosis and Bim expression in S49 cells. In contrast, both UV light and anti-mouse Fas monoclonal antibody promoted apoptosis in S49 cells but did not induce Bim expression. 8-CPT-cAMP also induced Bim expression and enhanced dexamethasone-promoted apoptosis in human T-cell leukemia CEM-C7-14 (glucocorticoid-sensitive) and CEM-C1-15 (glucocorticoid-resistant) cells; increased Bim expression in 8-CPT-cAMP-treated CEM-C1-15 cells correlated with conversion of the cells from resistance to sensitivity to glucocorticoid-promoted apoptosis. Induction of Bim appears to be a key event in cAMP-promoted apoptosis in both murine and human T-cell lymphoma and leukemia cells and thus appears to be a convergence point for the killing of such cells by glucocorticoids and agents that elevate cAMP.

Hyposensitivity of C-fiber Afferents at the Distal Extremities as an Indicator of Early Stages Diabetic Bladder Dysfunction in Type 2 Diabetic Women

PubMed Central

Lee, Wei-Chia; Wu, Han-Ching; Huang, Kuo-How; Wu, Huey-Peir; Yu, Hong-Jeng; Wu, Chia-Ching

2014-01-01

Purpose To investigate the relationship between distal symmetric peripheral neuropathy and early stages of autonomic bladder dysfunction in type 2 diabetic women. Materials and Methods A total of 137 diabetic women with minimal coexisting confounders of voiding dysfunction followed at a diabetes clinic were subject to the following evaluations: current perception threshold (CPT) tests on myelinated and unmyelinated nerves at the big toe for peroneal nerve and middle finger for median nerve, uroflowmetry, post-void residual urine volume, and overactive bladder (OAB) symptom score questionnaire. Patients presenting with voiding difficulty also underwent urodynamic studies and intravesical CPT tests. Results Based on the OAB symptom score and urodynamic studies, 19% of diabetic women had the OAB syndrome while 24.8% had unrecognized urodynamic bladder dysfunction (UBD). The OAB group had a significantly greater mean 5 Hz CPT test value at the big toe by comparison to those without OAB. When compared to diabetic women without UBD, those with UBD showed greater mean 5 Hz CPT test values at the middle finger and big toe. The diabetic women categorized as C-fiber hyposensitivity at the middle finger or big toe by using CPT test also had higher odds ratios of UBD. Among diabetic women with UBD, the 5 Hz CPT test values at the big toe and middle finger were significantly associated with intravesical 5 Hz CPT test values. Conclusions Using electrophysiological evidence, our study revealed that hyposensitivity of unmyelinated C fiber afferents at the distal extremities is an indicator of early stages diabetic bladder dysfunction in type 2 diabetic women. The C fiber dysfunction at the distal extremities seems concurrent with vesical C-fiber neuropathy and may be a sentinel for developing early diabetic bladder dysfunction among female patients. PMID:24466107

Association between genetic variants of the ADD1 and GNB3 genes and blood pressure response to the cold pressor test in a Chinese Han population: the GenSalt Study.

PubMed

Wang, Laiyuan; Chen, Shufeng; Zhao, Qi; Hixson, James E; Rao, Dabeeru C; Jaquish, Cashell E; Huang, Jianfeng; Lu, Xiangfeng; Chen, Jichun; Cao, Jie; Li, Jianxin; Li, Hongfan; He, Jiang; Liu, De-Pei; Gu, Dongfeng

2012-08-01

Genetic factors influence blood pressure (BP) response to the cold pressor test (CPT), which is a phenotype related to hypertension risk. We examined the association between variants of the α-adducin (ADD1) and guanine nucleotide binding protein (G protein) β-polypeptide 3 (GNB3) genes and BP response to the CPT. A total of 1998 Han Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity completed the CPT. The area under the curve (AUC) above the baseline BP during the CPT was used to measure the BP response. Twelve single-nucleotide polymorphisms (SNPs) of the ADD1 and GNB3 genes were selected and genotyped. Both single-marker and haplotype association analyses were conducted using linear mixed models. The rs17833172 and rs3775067 SNPs of the ADD1 gene and the rs4963516 SNP of the GNB3 gene were significantly associated with the BP response to CPT, even after adjusting for multiple testing. For the ADD1 gene, the AA genotype of SNP rs17833172 was associated with lower systolic BP (SBP) reactivity (P<0.0001) and faster BP recovery (P=0.0003). The TT genotype of rs3775067 was associated with slower SBP recovery (P=0.004). For the GNB3 gene, the C allele of SNP rs4963516 was associated with faster diastolic BP recovery (P=0.002) and smaller overall AUC (P=0.003). Haplotype analysis indicated that the CCGC haplotype of ADD1 constructed by rs1263359, rs3775067, rs4961 and rs4963 was significantly associated with the BP response to CPT. These data suggest that genetic variants of the ADD1 and GNB3 genes may have important roles in BP response to the CPT. Future studies aimed at replicating these novel findings are warranted.

The impact of Cognitive Processing Therapy on stigma among survivors of sexual violence in eastern Democratic Republic of Congo: results from a cluster randomized controlled trial.

PubMed

Murray, S M; Augustinavicius, J; Kaysen, D; Rao, D; Murray, L K; Wachter, K; Annan, J; Falb, K; Bolton, P; Bass, J K

2018-01-01

Sexual violence is associated with a multitude of poor physical, emotional, and social outcomes. Despite reports of stigma by sexual violence survivors, limited evidence exists on effective strategies to reduce stigma, particularly in conflict-affected settings. We sought to assess the effect of group Cognitive Processing Therapy (CPT) on stigma and the extent to which stigma might moderate the effectiveness of CPT in treating mental health problems among survivors of sexual violence in the Democratic Republic of Congo. Data were drawn from 405 adult female survivors of sexual violence reporting mental distress and poor functioning in North and South Kivu. Women were recruited through organizations providing psychosocial support and then cluster randomized to group CPT or individual support. Women were assessed at baseline, the end of treatment, and again six months later. Assessors were masked to women's treatment assignment. Linear mixed-effect regression models were used to estimate (1) the effect of CPT on feelings of perceived and internalized (felt) stigma, and (2) whether felt stigma and discrimination (enacted stigma) moderated the effects of CPT on combined depression and anxiety symptoms, posttraumatic stress, and functional impairment. Participants receiving CPT experienced moderate reductions in felt stigma relative to those in individual support (Cohen's D = 0.44, p  = value = 0.02) following the end of treatment, though this difference was no longer significant six-months later (Cohen's D = 0.45, p  = value = 0.12). Neither felt nor enacted stigma significantly moderated the effect of CPT on mental health symptoms or functional impairment. Group cognitive-behavioral based therapies may be an effective stigma reduction tool for survivors of sexual violence. Experiences and perceptions of stigma did not hinder therapeutic effects of group psychotherapy on survivors' mental health. ClinicalTrials.gov NCT01385163.

Association between Blood Pressure Responses to Cold Pressor Test and Dietary Sodium Intervention in the Chinese Population

PubMed Central

Chen, Jing; Gu, Dongfeng; Jaquish, Cashell E.; Chen, Chung-Shiuan; Rao, DC; Liu, Depei; Hixson, James E.; Hamm, L. Lee; Gu, C. Charles; Whelton, Paul K.; He, Jiang

2008-01-01

Background Blood pressure (BP) responses to the cold pressor test (CPT) and to dietary sodium intake might be related to the risk of hypertension. We examined the association between BP responses to the CPT and to dietary sodium and potassium interventions. Methods The CPT and dietary intervention were conducted among 1,906 study participants in rural China. The dietary intervention included three 7-day periods of low-sodium-feeding (51.3 mmol/day), high-sodium-feeding (307.8 mmol/day), and high-sodium-feeding plus potassium-supplementation (60 mmol/day). A total of 9 BP measurements were obtained during the 3-day baseline observation and the last 3 days of each intervention using a random-zero sphygmomanometer. Results BP response to the CPT was significantly associated with BP changes during the sodium and potassium interventions (all p<0.0001). Compared to the lowest quartile of BP response to the CPT, systolic BP changes (95% confident interval) for the top 3 quartiles, respectively, were −2.02 (−2.87, −1.16), −3.17 (−4.05, −2.28), and −5.98 (−6.89, −5.08) mm Hg during the low-sodium intervention. Corresponding systolic BP changes during the high-sodium intervention were 0.40 (−0.36, 1.16), 0.44 (−0.35, 1.22), and 2.30 (1.50, 3.10) mm Hg, and during the potassium-supplementation were −0.26 (−0.99, 0.46), −0.95 (−1.70, −0.20), and −1.59 (−2.36, −0.83) mm Hg, respectively. Conclusions These results indicated that BP response to the CPT was associated with salt-sensitivity and potassium-sensitivity. Furthermore, a low-sodium or high-potassium diet might be more effective to lower BP among individuals with high responses to the CPT. PMID:18779460

8-pCPT-cGMP prevents mitochondrial depolarization and improves the outcome of steatotic partial liver transplantation

PubMed Central

Liu, Qinlong; Rehman, Hasibur; Krishnasamy, Yasodha; Lemasters, John J; Zhong, Zhi

2017-01-01

Permeant cGMP analogs prevent the mitochondria permeability transition (MPT) in vitro. In this study, we explored whether 8-pCPT-cGMP prevents the MPT and decreases post-transplant damage to fatty partial liver grafts (FPG) in vivo. Rats were fed a control or high-fat, high-fructose diet for 2-week. Lean and fatty liver explants were reduced in size ex vivo to ~35% and stored in the University of Wisconsin solution with and without 8-pCPT-cGMP (300 µM) for 2 h. After transplantation, alanine aminotransferase release (indicator of hepatocellular injury), hyperbilirubinemia (indicator of poor liver function), and cell death were all higher in FPG than in lean partial grafts (LPG). Liver regeneration increased in LPG but was suppressed in FPG. 8-pCPT-cGMP blunted graft injury, improved liver regeneration and function, and increased survival of FPG. Hepatic mitochondrial depolarization detected by intravital multiphoton microscopy of rhodamine 123 in living rats was ~3.5-fold higher in FPG than in LPG. 8-pCPT-cGMP decreased mitochondrial depolarization in FPG almost to the level of LPG. Activation of mammalian target of rapamycin (mTOR), an energy sensitive kinase that stimulates cell proliferation and growth, and p70S6 kinase, a downstream signaling molecule of mTOR, was increased in LPG but suppressed in FPG. 8-pCPT-cGMP restored the activity of mTOR and p70S6 kinase in FPG. 8-pCPT-cGMP also increased activation of cAMP response element-binding protein (CREB) and expression of cyclins D1 and E in FPG. Non-alcoholic steatosis increases injury and suppresses regeneration after partial liver transplantation, at least in part, due to more severe mitochondrial dysfunction. Protection of mitochondria with a cGMP analog effectively improves outcomes of FPG transplantation. PMID:28694919

Biliary transport of irinotecan and metabolites in normal and P-glycoprotein-deficient mice.

PubMed

Iyer, Lalitha; Ramírez, Jacqueline; Shepard, Dale R; Bingham, Christopher M; Hossfeld, Dieter-Kurt; Ratain, Mark J; Mayer, Ulrich

2002-04-01

The extensive and unpredictable biliary excretion of CPT-11 and its metabolites, SN-38 and SN-38 glucuronide (SN-38G) may contribute to the wide interpatient variability reported in the disposition and gastrointestinal toxicity of CPT-11. We studied the role of P-glycoprotein (P-gp) in in vivo biliary excretion of CPT-11, SN-38 and SN-38G in mice lacking mdr1-type P-gp [ mdr1a/1b(-/-)] in the presence of the multidrug resistance (MDR) reversal agent, PSC833. Wild-type (Wt) and mdr1a/1b(-/-) mice ( n=3 or 4) were treated intragastrically with PSC833 (50 mg/kg) or vehicle 2 h prior to i.v. CPT-11 dosing (10 mg/kg), and bile samples were collected. P-gp was found to play an important role in CPT-11 biliary excretion, as there was a significant (40%, P<0.05) decrease in its biliary recovery in 90 min in mdr1a/1b(-/-) mice (6.6+/-0.6% dose) compared with Wt mice (11+/-1.2%). This also implied a major role of other undetermined non-P-gp-mediated mechanism(s) for hepatic transport of CPT-11, which was inhibited by PSC833 (1.8+/-0.8% with PSC833, 6.6+/-0.6% without PSC833) in mdr1a/1b(-/-) mice. SN-38 and SN-38G biliary transport was unchanged in mice lacking P-gp after vehicle treatment, indicating a lack of P-gp mediation in their transport. PSC833 significantly reduced (56-89%) SN-38 and SN-38G biliary transport in Wt and mdr1a/1b(-/-) mice, suggesting that PSC833 may be a candidate to modulate biliary excretion of SN-38 with potential use in reducing CPT-11 toxicity.

Microcomputer Processing of LANDSAT Thematic Mapper Data for the Acquisition of Military Tactical Terrain Data.

DTIC Science & Technology

1985-04-12

12 9 5 VPV TiTAY T,%. T , TiRAiU A ~ 6. PERFORMING ORG. REPORT NUMBER 7. AUTHOR(.) 6. CONTRACT OR GRANT NUMBER(a) .-- CPT zi 0 9. PERFORMING ...of period covered, such as the life of a contract covered in a final contractor report. Block 6. Performing Organization Report Number. Only numbers...affiliation of an author if it differs from that of the performing organization. Block 8. Contract or grant Number(s). For a contractor or grantee

Search for Violation of $CPT$ and Lorentz Invariance in $${B_s^0}$$ Meson Oscillations

DOE PAGES

Abazov, Victor Mukhamedovich

2015-06-12

We present the first search for CPT-violating effects in the mixing of B 0 s mesons using the full Run II data set with an integrated luminosity of 10.4 fb -1 of proton-antiproton collisions collected using the D0 detector at the Fermilab Tevatron Collider. We measure the CPT-violating asymmetry in the decay B 0 s → µ ±D ± s as a function of celestial direction and sidereal phase. We find no evidence for CPT-violating effects and place limits on the direction and magnitude of flavor-dependent CPTand Lorentz-invariance violating coupling coefficients. We find 95% confidence intervals of Δa⊥ < 1.2more » × 10 -12 GeV and (-0.8 < ΔaT - 0.396Δa Z < 3.9) × 10 -13 GeV.« less

Search for Violation of CPT and Lorentz Invariance in B-s(0) Meson Oscillations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abazov, V. M.

2015-10-14

We present the first search for CPT-violating effects in the mixing of B 0 s mesons using the full Run II data set with an integrated luminosity of 10.4 fb -1 of proton-antiproton collisions collected using the D0 detector at the Fermilab Tevatron Collider. We measure the CPT-violating asymmetry in the decay B 0 s → µ ±D ± s as a function of celestial direction and sidereal phase. We find no evidence for CPT-violating effects and place limits on the direction and magnitude of flavor-dependent CPTand Lorentz-invariance violating coupling coefficients. We find 95% confidence intervals of Δa⊥ < 1.2more » × 10 -12 GeV and (-0.8 < ΔaT - 0.396Δa Z < 3.9) × 10 -13 GeV.« less

A novel coumarin-pyrazole-triazine based fluorescence chemosensor for fluoride detection via deprotonation process: Experimental and theoretical studies

NASA Astrophysics Data System (ADS)

Yalçın, Ergin; Alkış, Meltem; Seferoğlu, Nurgül; Seferoğlu, Zeynel

2018-03-01

A novel fluorescence coumarin-pyrazole-triazine based chemosensor (CPT) bearing 5-hydroxypyrazole as a receptoric part was synthesized and characterized by using IR, 1H/13C NMR and HRMS for the purpose of recognition of anions in DMSO. The most stable tautomeric form of CPT was determined by experimental techniques and theoretical calculations. The selectivity and sensitivity of CPT towards anions (CN-, F-, Cl-, Br-, I-, AcO-, HSO4-, H2PO4- and ClO4-) were determined using spectrophotometric and 1H NMR titration techniques as the experimental approach, and the results were explained by employing theoretical calculations. It was found to be suitable for the selective detection of F- in the presence of CN- and AcO- as competing anions. In addition, CPT exhibits significant "light-up" effect after interaction with TFA in CH2Cl2.

CPT-hole closure

USGS Publications Warehouse

Noce, T.E.; Holzer, T.L.

2003-01-01

The long-term stability of deep holes 1.75 inches. (4.4 cm) in diameter by 98.4 feet (30 m) created by cone penetration testing (CPT) was monitored at a site in California underlain by Holocene and Pleistocene age alluvial fan deposits. Portions of the holes remained open both below and above the 28.6-foot (8.7 m)-deep water table for approximately three years, when the experiment was terminated. Hole closure appears to be a very slow process that may take decades in the stiff soils studied here. Other experience suggests holes in softer soils may also remain open. Thus, despite their small diameter, CPT holes may remain open for years and provide paths for rapid migration of contaminants. The observations confirm the need to grout holes created by CPT soundings as well as other direct-push techniques in areas where protection of shallow ground water is important.

Communicated Sense-making After Miscarriage: A Dyadic Analysis of Spousal Communicated Perspective-Taking, Well-being, and Parenting Role Salience.

PubMed

Horstman, Haley Kranstuber; Holman, Amanda

2017-08-28

Grounded in communicated sense-making (CSM) theorizing, we investigated communicated perspective-taking (CPT; i.e., conversational partners' attendance to and confirmation of each other's views) in association with individual and relational well-being in married couples who had miscarried (n = 183; N = 366). Actor-partner interdependence modeling revealed husbands' perceptions of wives' CPT were positively related to husbands' positive affect about the miscarriage and both spouses' relational satisfaction, as well as negatively associated with wives' positive affect. Wives' perceptions of husbands' CPT related positively to their own relational satisfaction and negatively to husbands' negative affect. Analyses revealed identification as a parent to the miscarried child (i.e., "parenting role salience") positively moderated the relationship between CPT and relational satisfaction. Implications for advancing CSM theorizing in health contexts and practical applications are explored.

Coherent Population Trapping in a Superconducting Phase Qubit

NASA Astrophysics Data System (ADS)

Kelly, William R.; Dutton, Zachary; Ohki, Thomas A.; Schlafer, John; Mookerji, Bhaskar; Kline, Jeffery S.; Pappas, David P.

2010-03-01

The phenomenon of Coherent Population Trapping (CPT) of an atom (or solid state ``artificial atom''), and the associated effect of Electromagnetically Induced Transparency (EIT), are clear demonstrations of quantum interference due to coherence in multi-level quantum systems. We report observation of CPT in a superconducting phase qubit by simultaneously driving two coherent transitions in a λ-type configuration, utilizing the three lowest lying levels of a local minimum of the phase qubit. We observe ˜60% suppression of excited state population under conditions of two-photon resonance, where EIT and CPT are expected to occur. We present data and matching theoretical simulations showing the development of CPT in time. We also used the observed time dependence of the excited state population to characterize quantum dephasing times of the system, as predicted in [1]. [1] K.V. Murali, Z. Dutton, W.D. Oliver, D.S. Crankshaw, and T.P.Orlando, Phys. Rev. Lett. 93, 087003 (2004).

Protein arginine (N)-methyl transferase 7 (PRMT7) as a potential target for the sensitization of tumor cells to camptothecins.

PubMed

Verbiest, Vincent; Montaudon, Danièle; Tautu, Michel T; Moukarzel, Joyce; Portail, Jean-Pierre; Markovits, Judith; Robert, Jacques; Ichas, François; Pourquier, Philippe

2008-04-30

PRMT7 belongs to the protein arginine methyl-transferases family. We show that downregulation of PRMT7alpha and beta isoforms in DC-3F hamster cells was associated with increased sensitivity to the Top1 inhibitor camptothecin (CPT). This effect was not due to a change in Top1 contents or catalytic activity, or to a difference in the reversal of DNA breaks. Overexpression of PRMT7alpha and beta in DC-3F cells had no effect on CPT sensitivity, whereas it conferred a resistance to DC-3F/9-OH-E cells for which both isoforms are reduced by two- to three-fold as compared to DC-3F parental cells. Finally, downregulation of the human PRMT7 could also sensitize HeLa cells to CPT, suggesting that it could be used as a target to potentiate CPT derivatives.

Camptothecin Attenuates Cytochrome P450 3A4 Induction by Blocking the Activation of Human Pregnane X ReceptorS⃞

PubMed Central

Chen, Yakun; Tang, Yong; Robbins, Gregory T.

2010-01-01

Differential regulation of drug-metabolizing enzymes (DMEs) is a common cause of adverse drug effects in cancer therapy. Due to the extremely important role of cytochrome P450 3A4 (CYP3A4) in drug metabolism and the dominant regulation of human pregnane X receptor (hPXR) on CYP3A4, finding inhibitors for hPXR could provide a unique tool to control drug efficacies in cancer therapy. Camptothecin (CPT) was demonstrated as a novel and potent inhibitor (IC50 = 0.58 μM) of an hPXR-mediated transcriptional regulation on CYP3A4 in this study. In contrast, one of its analogs, irinotecan (CPT-11), was found to be an hPXR agonist in the same tests. CPT disrupted the interaction of hPXR with steroid receptor coactivator-1 but had effects on neither the competition of ligand binding nor the formation of the hPXR and retinoid X receptor α heterodimer, nor the interaction between the regulatory complex and DNA-responsive elements. CPT treatment resulted in delayed metabolism of nifedipine in human hepatocytes treated with rifampicin, suggesting a potential prevention of drug-drug interactions between CYP3A4 inducers and CYP3A4-metabolized drugs. Because CPT is the leading compound of topoisomerase I inhibitors, which comprise a quickly developing class of anticancer agents, the findings indicate the potential of a new class of compounds to modify hPXR activity as agonists/inhibitors and are important in the development of CPT analogs. PMID:20504912

Atomic clocks based on extened-cavity diode laser in multimode operation

NASA Astrophysics Data System (ADS)

Yim, Sin; Cho, D.

2011-05-01

We demonstrated the possibilities to develope an atomic clock based on coherent population trapping (CPT) without using a local oscillator and a modulator. Instead of using a modulator, we use two modes from a single extended-cavity diode laser in multimode operation. Two different types of feedback system are applied to stabilize a difference frequency between the two modes and eliminate the need for an extra frequency modulation. In the first type, we employ an electronic feedback using dispersion of the CPT resonance as an error signal. The two modes are phase locked with reference to a dispersion signal from a CPT resonance of 85Rb at 3.036 GHz ground hyperfine splitting. We use D1 transition at 794.8 nm with lin ⊥lin polarizations to obtain large-contrast CPT signal. Allan deviation of the beat frequency between the two modes is 1 ×10-10 at 200-s integration time. In the second type, we employ optoelectronic feedback to construct an opto-electronic oscillator (OEO). In an OEO, the beating signal between two modes is recovered by a fast photodiode, and its output is amplified and fed back to the laser diode by using a direct modulation of an injection current. When the OEO loop is closed, oscillation frequency depends on variations of the loop length. In order to stabilize an OEO loop length and thereby its oscillation frequency, CPT cell is inserted to play a role of microwave band pass filter. Allan deviation of the CPT-stabilized OEO is 2 ×10-10 at 100-s integration time.

Proton Radiotherapy for Pediatric Central Nervous System Germ Cell Tumors: Early Clinical Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacDonald, Shannon M., E-mail: smacdonald@partners.or; Trofimov, Alexei; Safai, Sairos

Purpose: To report early clinical outcomes for children with central nervous system (CNS) germ cell tumors treated with protons; to compare dose distributions for intensity-modulated photon radiotherapy (IMRT), three-dimensional conformal proton radiation (3D-CPT), and intensity-modulated proton therapy with pencil beam scanning (IMPT) for whole-ventricular irradiation with and without an involved-field boost. Methods and Materials: All children with CNS germinoma or nongerminomatous germ cell tumor who received treatment at the Massachusetts General Hospital between 1998 and 2007 were included in this study. The IMRT, 3D-CPT, and IMPT plans were generated and compared for a representative case. Results: Twenty-two patients were treatedmore » with 3D-CPT. At a median follow-up of 28 months, there were no CNS recurrences; 1 patient had a recurrence outside the CNS. Local control, progression-free survival, and overall survival rates were 100%, 95%, and 100%, respectively. Comparable tumor volume coverage was achieved with IMRT, 3D-CPT, and IMPT. Substantial normal tissue sparing was seen with any form of proton therapy as compared with IMRT. The use of IMPT may yield additional sparing of the brain and temporal lobes. Conclusions: Preliminary disease control with proton therapy compares favorably to the literature. Dosimetric comparisons demonstrate the advantage of proton radiation over IMRT for whole-ventricle radiation. Superior dose distributions were accomplished with fewer beam angles utilizing 3D-CPT and scanned protons. Intensity-modulated proton therapy with pencil beam scanning may improve dose distribution as compared with 3D-CPT for this treatment.« less

Neonatal carnitine palmitoyltransferase II deficiency associated with Dandy-Walker syndrome and sudden death.

PubMed

Yahyaoui, Raquel; Espinosa, María Gracia; Gómez, Celia; Dayaldasani, Anita; Rueda, Inmaculada; Roldán, Ana; Ugarte, Magdalena; Lastra, Gonzalo; Pérez, Vidal

2011-11-01

Neonatal onset of carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive, often lethal disorder of the mitochondrial beta-oxidation of long-chain fatty acids. It is a rare multiorgan disease which includes hypoketotic hypoglycemia, severe hepatomuscular symptoms, cardiac abnormalities, seizures and lethargy, as well as dysmorphic features. Until now, only 22 affected families have been described in the literature. An increasing number of mutations are being identified in the CPT2 gene, with a distinct genotype-phenotype correlation in most cases. Herein we report a new case of neonatal CPT II deficiency associated with Dandy-Walker syndrome and sudden death at 13 days of life. CPT II deficiency was suggested by acylcarnitine analysis of dried-blood on filter paper in the expanded newborn screening. Genetic analysis of the CPT2 gene identified the presence of a previously described mutation in homozygosity (c.534_558del25bpinsT). All lethal neonatal CPT II deficiency patients previously described presented severe symptoms during the first week of life, although this was not the case in our patient, who remained stable and without apparent vital risk during the first 11 days of life. The introduction of tandem mass spectrometry to newborn screening has substantially improved our ability to detect metabolic diseases in the newborn period. This case illustrates the value of expanded newborn screening in a neonate with an unusual clinical presentation, combining hydrocephalus and sudden death, that might not commonly lead to the suspicion of an inborn error of metabolism. Copyright © 2011 Elsevier Inc. All rights reserved.

Old drug new use--amoxapine and its metabolites as potent bacterial β-glucuronidase inhibitors for alleviating cancer drug toxicity.

PubMed

Kong, Ren; Liu, Timothy; Zhu, Xiaoping; Ahmad, Syed; Williams, Alfred L; Phan, Alexandria T; Zhao, Hong; Scott, John E; Yeh, Li-An; Wong, Stephen T C

2014-07-01

Irinotecan (CPT-11) induced diarrhea occurs frequently in patients with cancer and limits its usage. Bacteria β-glucuronidase (GUS) enzymes in intestines convert the nontoxic metabolite of CPT-11, SN-38G, to toxic SN-38, and finally lead to damage of intestinal epithelial cells and diarrhea. We previously reported amoxapine as a potent GUS inhibitor in vitro. To further understand the molecular mechanism of amoxapine and its potential for treatment of CPT-11-induced diarrhea, we studied the binding modes of amoxapine and its metabolites by docking and molecular dynamics simulation, and tested the in vivo efficacy on mice in combination with CPT-11. The binding of amoxapine, its metabolites, 7-hydroxyamoxapine and 8-hydroxyamoxapine, and a control drug loxapine with GUS was explored by computational protocols. The in vitro potencies of metabolites were measured by Escherichia coli GUS enzyme and cell-based assay. Low-dosage daily oral administration was designed to use along with CPT-11 to treat tumor-bearing mice. Computational modeling results indicated that amoxapine and its metabolites bound in the active site of GUS and satisfied critical pharmacophore features: aromatic features near bacterial loop residue F365' and hydrogen bond toward E413. Amoxapine and its metabolites were demonstrated as potent in vitro. Administration of low dosages of amoxapine with CPT-11 in mice achieved significant suppression of diarrhea and reduced tumor growth. Amoxapine has great clinical potential to be rapidly translated to human subjects for irinotecan-induced diarrhea. ©2014 American Association for Cancer Research.

Old drug new use - Amoxapine and its metabolites as potent bacterial β-glucuronidase inhibitors for alleviating cancer drug toxicity

PubMed Central

Kong, Ren; Liu, Timothy; Zhu, Xiaoping; Ahmad, Syed; Williams, Alfred L.; Phan, Alexandria T; Zhao, Hong; Scott, John E.; Yeh, Li-An; Wong, Stephen TC

2014-01-01

Purpose Irinotecan (CPT-11) induced diarrhea occurs frequently in cancer patients and limits its usage. Bacteria β-glucuronidase (GUS) enzymes in intestines convert the non-toxic metabolite of CPT-11, SN-38G, to toxic SN-38, and finally lead to damage of intestinal epithelial cells and diarrhea. We previously reported amoxapine as potent GUS inhibitor in vitro. To further understand the molecular mechanism of amoxapine and its potential for treatment of CPT-11 induced diarrhea, we studied the binding modes of amoxapine and its metabolites by docking and molecular dynamics simulation, and tested the in vivo efficacy on mice in combination with CPT-11. Experimental Design The binding of amoxapine, its metabolites, 7-hydroxyamoxapine and 8-hydroxyamoxapine, and a control drug loxapine with GUS was explored by computational protocols. The in vitro potencies of metabolites were measured by E. Coli GUS enzyme and cell-based assay. Low dosage daily oral administration was designed to use along with CPT-11 to treat tumor-bearing mice. Results Computational modeling results indicated that amoxapine and its metabolites bound in the active site of GUS and satisfied critical pharmacophore features: aromatic features near bacterial loop residue F365’ and hydrogen bond toward E413. Amoxapine and its metabolites were demonstrated as potent in vitro. Administration of low dosages of amoxapine with CPT-11 in mice achieved significant suppression of diarrhea and reduced tumor growth. Conclusions Amoxapine has great clinical potential to be rapidly translated to human subjects for irinotecan induced diarrhea. PMID:24780296

Identification of a novel malonyl-CoA IC(50) for CPT-I: implications for predicting in vivo fatty acid oxidation rates.

PubMed

Smith, Brennan K; Perry, Christopher G R; Koves, Timothy R; Wright, David C; Smith, Jeffrey C; Neufer, P Darrell; Muoio, Deborah M; Holloway, Graham P

2012-11-15

Published values regarding the sensitivity (IC(50)) of CPT-I (carnitine palmitoyltransferase I) to M-CoA (malonyl-CoA) inhibition in isolated mitochondria are inconsistent with predicted in vivo rates of fatty acid oxidation. Therefore we have re-examined M-CoA inhibition kinetics under various P-CoA (palmitoyl-CoA) concentrations in both isolated mitochondria and PMFs (permeabilized muscle fibres). PMFs have an 18-fold higher IC(50) (0.61 compared with 0.034 μM) in the presence of 25 μM P-CoA and a 13-fold higher IC(50) (6.3 compared with 0.49 μM) in the presence of 150 μM P-CoA compared with isolated mitochondria. M-CoA inhibition kinetics determined in PMFs predicts that CPT-I activity is inhibited by 33% in resting muscle compared with >95% in isolated mitochondria. Additionally, the ability of M-CoA to inhibit CPT-I appears to be dependent on P-CoA concentration, as the relative inhibitory capacity of M-CoA is decreased with increasing P-CoA concentrations. Altogether, the use of PMFs appears to provide an M-CoA IC(50) that better reflects the predicted in vivo rates of fatty acid oxidation. These findings also demonstrate that the ratio of [P-CoA]/[M-CoA] is critical for regulating CPT-I activity and may partially rectify the in vivo disconnect between M-CoA content and CPT-I flux within the context of exercise and Type 2 diabetes.

Exploring the effect of Vitamin E in Cancer Chemotherapy- A Biochemical and Biophysical Insight.

PubMed

Bhori, Mustansir; Singh, Kanchanlata; Marar, Thankamani; MuraliKrishna, C

2018-05-16

Many oncologists contend that patient undergoing chemotherapy must avoid antioxidant supplementation as it may interfere with the activity of the drug. In the present investigation, we have explored the influence of vitamin E, a well known antioxidant on Camptothecin (CPT), a potent anti-cancer drug induced cell apoptosis and death of cervical cancer cells. HeLa cells were treated with different concentrations of CPT in presence and absence of 100μm vitamin E. Treated cells were subjected to cytotoxicity studies, catalase assay, DNA fragmentation assay, clonogenic assay and flow cytometry based apoptosis detection. Also, Raman spectroscopy a label free technique which provides global information in conjunction with multivariate tools like PCA, PCLDA and FDA, was investigated to explore vitamin E supplementation induced alterations. Our data based on biochemical and biophysical experimental analysis reveals that CPT causes DNA damage along with protein and lipid alteration culminating in cell death. Importantly, Raman spectroscopic analysis could uniquely differentiate the cluster of control and vitamin E control from CPT and CPT+Vit E treated cells. We conclusively prove that presence of vitamin E at 100μM concentration shows promising antioxidant activity and displays no modulatory role on CPT induced effect, thereby causing no possible hindrance with the efficacy of the drug. Vitamin E may prove beneficial to alleviate chemotherapy associated side effects in patients during clinical settings which may open the doors further for subsequent exploration in in vivo pre clinical studies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Glomeruloid Microvascular Proliferation, Desmoplasia, and High Proliferative Index as Potential Indicators of High Grade Canine Choroid Plexus Tumors.

PubMed

Muscatello, Luisa Vera; Avallone, Giancarlo; Serra, Fabienne; Seuberlich, Torsten; Mandara, Maria Teresa; Sisó, Silvia; Brunetti, Barbara; Oevermann, Anna

2018-05-01

Choroid plexus tumors (CPT) are intraventricular neoplasms accounting for 10% of all primary central nervous system tumors in dogs. They are frequently classified according to the human WHO classification into choroid plexus papilloma (CPP, grade I), atypical CPP (aCPP, grade II), and choroid plexus carcinoma (CPC, grade III). Histological features observed in canine CPT such as increased vascular density (IVD) and glomeruloid microvascular proliferation (GMVP) are not part of the WHO classification. This multi-centric study aimed to investigate tumor-associated vascular hyperplasia in dogs by determining the prevalence of GMVP and IVD in 52 canine CPT and their association with tumor grade. In addition, the expression of angiogenic factors was assessed by immunohistochemistry in 25 tumors to investigate the pathogenesis of tumor-associated vascular hyperplasia. Based on the classical histological hallmarks, this study of 52 CPT identified 22 (42%) CPP (grade I) and 30 of (58%) CPC (grade III). GMVP was more prevalent in CPC (13/30; 43%) than CPP (1/22; 4%), whereas IVD occurred to a similar extent in CPP and CPC. Desmoplasia was more common in CPC (19/30; 63%) than CPP (2/22; 9%), and similarly, the proliferative index (PI) of neoplastic epithelium was significantly higher in CPC (5.14%) than CPP (0.94%). The majority of CPT expressed platelet-derived growth factor (PDGF), PDGFRα, PDGFRβ, and vascular endothelial growth factor (VEGF) irrespective of tumor grade or tumor-associated vascular hyperplasia. These results suggest that tumor-associated GMVP, desmoplasia, and PI may serve as histological indicators of malignancy in CPT.

Effects of depletion of dihydropyrimidine dehydrogenase on focus formation and RPA phosphorylation.

PubMed

Someya, Masanori; Sakata, Koh-ichi; Matsumoto, Yoshihisa; Tauchi, Hiroshi; Kai, Masahiro; Hareyama, Masato; Fukushima, Masakazu

2012-01-01

Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase (DPYD), partially inhibits homologous recombination (HR) repair and has a radiosensitizing effect as well as enhanced sensitivity to Camptothecin (CPT). DPYD is the target protein for radiosensitization by Gimeracil. We investigated the mechanisms of sensitization of radiation and CPT by DPYD inhibition using DLD-1 cells treated with siRNA for DPYD. We investigated the focus formation of various kinds of proteins involved in HR and examined the phosphorylation of RPA by irradiation using Western blot analysis. DPYD depletion by siRNA significantly restrained the formation of radiation-induced foci of Rad51 and RPA, whereas it increased the number of foci of NBS1. The numbers of colocalization of NBS1 and RPA foci in DPYD-depleted cells after radiation were significantly smaller than in the control cells. These results suggest that DPYD depletion is attributable to decreased single-stranded DNA generated by the Mre11/Rad50/NBS1 complex-dependent resection of DNA double-strand break ends. The phosphorylation of RPA by irradiation was partially suppressed in DPYD-depleted cells, suggesting that DPYD depletion may partially inhibit DNA repair with HR by suppressing phosphorylation of RPA. DPYD depletion showed a radiosensitizing effect as well as enhanced sensitivity to CPT. The radiosensitizing effect of DPYD depletion plus CPT was the additive effect of DPYD depletion and CPT. DPYD depletion did not have a cell-killing effect, suggesting that DPYD depletion may not be so toxic. Considering these results, the combination of CPT and drugs that inhibit DPYD may prove useful for radiotherapy as a method of radiosensitization.

Benefits of music therapy as an adjunct to chest physiotherapy in infants and toddlers with cystic fibrosis.

PubMed

Grasso, M C; Button, B M; Allison, D J; Sawyer, S M

2000-05-01

Routine chest physiotherapy (CPT) is an important component of prophylactic therapy in children with cystic fibrosis (CF) and requires a significant commitment of time and energy. It is important, therefore, to establish CPT as a positive experience. In this study, we evaluated the effect of recorded music as an adjunct to CPT. Specifically, we compared the use of newly composed music, familiar music, and the family's usual routine on children's and parents' enjoyment of CPT and the parents' perception of time taken to complete CPT. Enjoyment and perception of time were evaluated via questionnaires designed specifically for this study. Participants were caregivers of one or more children with CF who were aged between 4(1/2) months and 24 months at the commencement of the clinical trial and required CPT on a daily basis. Participants were randomly allocated into control and treatment groups. Control group participants experienced two conditions consecutively: no audiotape (NT; control) and familiar music tape (FT; placebo control). Treatment group participants were given the treatment music tape (TT), which was composed and compiled by a music therapist. After baseline assessment, evaluation occurred at two 6-weekly intervals. Children's enjoyment increased significantly after use of the TT (+1. 25 units) compared to NT (-0.5 units; P = 0.03), as did parents' enjoyment (+1.0 vs. 0.0 units, P = 0.02). Children's enjoyment did not change significantly after use of the FT (+0.75 units) compared to NT (n.s.). Likewise, parents' enjoyment did not change significantly after use of the FT (+1.0 units, n.s.). There was no change in perception of time after use of the TT (-4.5 vs. +0.2 min, n.s.) or the FT (+3.3 min, n.s.). These results indicate that children's and parents' enjoyment of CPT significantly increased after the use of specifically composed and recorded music as an adjunct. We therefore recommend that recorded music, such as that provided in this study, be given to parents to use as an adjunct to CPT when their young children are diagnosed with CF, in order to assist the establishment of a positive routine. Copyright 2000 Wiley-Liss, Inc.

Delivering Cognitive Processing Therapy in a Community Health Setting: The Influence of Latino Culture and Community Violence on Posttraumatic Cognitions

PubMed Central

Marques, Luana; Eustis, Elizabeth H.; Dixon, Louise; Valentine, Sarah E.; Borba, Christina; Simon, Naomi; Kaysen, Debra; Wiltsey-Stirman, Shannon

2015-01-01

Despite the applicability of Cognitive Processing Therapy (CPT) for Posttraumatic Stress Disorder (PTSD) to addressing sequelae of a range of traumatic events, few studies have evaluated whether the treatment itself is applicable across diverse populations. The present study examined differences and similarities amongst non-Latino, Latino Spanish-speaking, and Latino English-speaking clients in rigid beliefs – or “stuck points” – associated with PTSD symptoms in a sample of community mental health clients. We utilized the procedures of content analysis to analyze stuck point logs and impact statements of 29 participants enrolled in a larger implementation trial for CPT. Findings indicated that the content of stuck points was similar across Latino and non-Latino clients, although fewer total stuck points were identified for Latino clients compared to non-Latino clients. Given that identification of stuck points is central to implementing CPT, difficulty identifying stuck points could pose significant challenges for implementing CPT among Latino clients and warrants further examination. Thematic analysis of impact statements revealed the importance of family, religion, and the urban context (e.g., poverty, violence exposure) in understanding how clients organize beliefs and emotions associated with trauma. Clinical recommendations for implementing CPT in community settings and the identification of stuck points are provided. PMID:25961865

Delivering cognitive processing therapy in a community health setting: The influence of Latino culture and community violence on posttraumatic cognitions.

PubMed

Marques, Luana; Eustis, Elizabeth H; Dixon, Louise; Valentine, Sarah E; Borba, Christina P C; Simon, Naomi; Kaysen, Debra; Wiltsey-Stirman, Shannon

2016-01-01

Despite the applicability of cognitive processing therapy (CPT) for posttraumatic stress disorder (PTSD) to addressing sequelae of a range of traumatic events, few studies have evaluated whether the treatment itself is applicable across diverse populations. The present study examined differences and similarities among non-Latino, Latino Spanish-speaking, and Latino English-speaking clients in rigid beliefs-or "stuck points"-associated with PTSD symptoms in a sample of community mental health clients. We utilized the procedures of content analysis to analyze stuck point logs and impact statements of 29 participants enrolled in a larger implementation trial for CPT. Findings indicated that the content of stuck points was similar across Latino and non-Latino clients, although fewer total stuck points were identified for Latino clients compared to non-Latino clients. Given that identification of stuck points is central to implementing CPT, difficulty identifying stuck points could pose significant challenges for implementing CPT among Latino clients and warrants further examination. Thematic analysis of impact statements revealed the importance of family, religion, and the urban context (e.g., poverty, violence exposure) in understanding how clients organize beliefs and emotions associated with trauma. Clinical recommendations for implementing CPT in community settings and the identification of stuck points are provided. (c) 2016 APA, all rights reserved).

Maps and documentation of seismic CPT soundings in the central, eastern, and western United States

USGS Publications Warehouse

Holzer, Thomas L.; Noce, Thomas E.; Bennett, Michael J.

2010-01-01

Nine hundred twenty seven seismic cone penetration tests (CPT) in a variety of geologic deposits and geographic locations were conducted by the U.S. Geological Survey (USGS) primarily between 1998 and 2008 for the purpose of collecting penetration test data to evaluate the liquefaction potential of different types of surficial geologic deposits (table 1). The evaluation is described in Holzer and others (in press). This open-file report summarizes the seismic CPT and geotechnical data that were collected for the evaluation, outlines the general conditions under which the data were acquired, and briefly describes the geographic location of each study area and local geologic conditions. This report also describes the field methods used to obtain the seismic CPT data and summarizes the results of shear-wave velocities measurements at 2-m intervals in each sounding. Although the average depth of the 927 soundings was 18.5 m, we estimated a time-averaged shear-wave velocity to depths of 20 m and 30 m, VS20 and VS30, respectively, for soundings deeper than 10 m and 20 m. Soil sampling also was selectively conducted in many of the study areas at representative seismic CPT soundings. These data are described and laboratory analyses of geotechnical properties of these samples are summarized in table 2.

The diagnostic utility of behavioral checklists in identifying children with ADHD and children with working memory deficits.

PubMed

Alloway, Tracy Packiam; Gathercole, Susan E; Holmes, Joni; Place, Maurice; Elliott, Julian G; Hilton, Kerry

2009-09-01

The present study investigated whether children with ADHD and those with working memory impairments have a common behavioral profile in the classroom. Three teacher checklists were used: the Conners' teacher rating scale (CTRS), the behavior rating inventory of executive function (BRIEF), and the working memory rating scale. The Conners' continuous performance test (CPT) was also included to determine whether there is a correspondence between performance on this widely used cognitive measure of attention deficits and teacher ratings of classroom behavior. All three behavior scales, but not the CPT, were able to successfully discriminate children with ADHD and those with working memory deficits from typically-developing children. Both the CTRS and the BRIEF discriminated a significant proportion of the children with ADHD from those with working memory deficits, indicating that while both groups exhibit behavioral problems in the classroom, they are characterized by differential attention profiles. The children with ADHD were identified on the basis of oppositional and hyperactive behavior, while those with working memory deficits were more inattentive.

Development and validation of an HPLC method to quantify camptothecin in polymeric nanocapsule suspensions.

PubMed

Granada, Andréa; Murakami, Fabio S; Sartori, Tatiane; Lemos-Senna, Elenara; Silva, Marcos A S

2008-01-01

A simple, rapid, and sensitive reversed-phase column high-performance liquid chromatographic method was developed and validated to quantify camptothecin (CPT) in polymeric nanocapsule suspensions. The chromatographic separation was performed on a Supelcosil LC-18 column (15 cm x 4.6 mm id, 5 microm) using a mobile phase consisting of methanol-10 mM KH2PO4 (60 + 40, v/v; pH 2.8) at a flow rate of 1.0 mL/min and ultraviolet detection at 254 nm. The calibration graph was linear from 0.5 to 3.0 microg/mL with a correlation coefficient of 0.9979, and the limit of quantitation was 0.35 microg/mL. The assay recovery ranged from 97.3 to 105.0%. The intraday and interday relative standard deviation values were < 5.0%. The validation results confirmed that the developed method is specific, linear, accurate, and precise for its intended use. The current method was successfully applied to the evaluation of CPT entrapment efficiency and drug content in polymeric nanocapsule suspensions during the early stage of formulation development.

Sex differences in how social networks and relationship quality influence experimental pain sensitivity.

PubMed

Vigil, Jacob M; Rowell, Lauren N; Chouteau, Simone; Chavez, Alexandre; Jaramillo, Elisa; Neal, Michael; Waid, David

2013-01-01

This is the first study to examine how both structural and functional components of individuals' social networks may moderate the association between biological sex and experimental pain sensitivity. One hundred and fifty-two healthy adults (mean age = 22yrs., 53% males) were measured for cold pressor task (CPT) pain sensitivity (i.e., intensity ratings) and core aspects of social networks (e.g., proportion of friends vs. family, affection, affirmation, and aid). Results showed consistent sex differences in how social network structures and intimate relationship functioning modulated pain sensitivity. Females showed higher pain sensitivity when their social networks consisted of a higher proportion of intimate types of relationship partners (e.g., kin vs. non kin), when they had known their network partners for a longer period of time, and when they reported higher levels of logistical support from their significant other (e.g., romantic partner). Conversely, males showed distinct patterns in the opposite direction, including an association between higher levels of logistical support from one's significant other and lower CPT pain intensity. These findings show for the first time that the direction of sex differences in exogenous pain sensitivity is likely dependent on fundamental components of the individual's social environment. The utility of a social-signaling perspective of pain behaviors for examining, comparing, and interpreting individual and group differences in experimental and clinical pain reports is discussed.

Since surgery isn't getting any easier, why is reimbursement going down? An update from the SGO taskforce on coding and reimbursement.

PubMed

Uppal, Shitanshu; Shahin, Mark S; Rathbun, Jill A; Goff, Barbara A

2017-02-01

In 2015, there was an 18% reduction in the Relative Value Units (RVUs) that the Center for Medicare and Medicaid Services (CMS) assigned to the Current Procedural Terminology (CPT) code 58571 (Laparoscopy, surgical, with total hysterectomy, for uterus 250g or less; with removal of tube(s) and/or ovary(s)→TLH+BSO). The other CPT codes for laparoscopic hysterectomy and laparoscopic supracervical hysterectomy (58541-58544 and 58570-58573) lost between 12 and 23% of their assigned RVUs. In 2016, the laparoscopic lymph node dissection codes 38570 (Laparoscopy, surgical; with retroperitoneal lymph node sampling (biopsy), single or multiple), 38571 (Laparoscopy, surgical; with bilateral total pelvic lymphadenectomy), and 38572 (Laparoscopy, surgical; with bilateral total pelvic lymphadenectomy and para-aortic lymph node sampling (biopsy), single or multiple) lost between 5.5 and 16.3% of their RVU's. The goals of this article from the Society of Gynecologic Oncology (SGO) Task force on Coding and Reimbursement are 1) to inform the SGO members on why CMS identified these codes as a part of their misvalued services screening program and then finalized a reduction in their payment levels; and 2) outline the role individual providers have in CMS' methodology used to determine the reimbursement of a surgical procedure. Copyright © 2016 Elsevier Inc. All rights reserved.

Sex Differences in How Social Networks and Relationship Quality Influence Experimental Pain Sensitivity

PubMed Central

Vigil, Jacob M.; Rowell, Lauren N.; Chouteau, Simone; Chavez, Alexandre; Jaramillo, Elisa; Neal, Michael; Waid, David

2013-01-01

This is the first study to examine how both structural and functional components of individuals’ social networks may moderate the association between biological sex and experimental pain sensitivity. One hundred and fifty-two healthy adults (mean age = 22yrs., 53% males) were measured for cold pressor task (CPT) pain sensitivity (i.e., intensity ratings) and core aspects of social networks (e.g., proportion of friends vs. family, affection, affirmation, and aid). Results showed consistent sex differences in how social network structures and intimate relationship functioning modulated pain sensitivity. Females showed higher pain sensitivity when their social networks consisted of a higher proportion of intimate types of relationship partners (e.g., kin vs. non kin), when they had known their network partners for a longer period of time, and when they reported higher levels of logistical support from their significant other (e.g., romantic partner). Conversely, males showed distinct patterns in the opposite direction, including an association between higher levels of logistical support from one’s significant other and lower CPT pain intensity. These findings show for the first time that the direction of sex differences in exogenous pain sensitivity is likely dependent on fundamental components of the individual’s social environment. The utility of a social-signaling perspective of pain behaviors for examining, comparing, and interpreting individual and group differences in experimental and clinical pain reports is discussed. PMID:24223836

The Full Scope of Family Physicians' Work Is Not Reflected by Current Procedural Terminology Codes.

PubMed

Young, Richard A; Burge, Sandy; Kumar, Kaparaboyna Ashok; Wilson, Jocelyn

2017-01-01

The purpose of this study was to characterize the content of family physician (FP) clinic encounters, and to count the number of visits in which the FPs addressed issues not explicitly reportable by 99211 to 99215 and 99354 Current Procedural Terminology (CPT) codes with current reimbursement methods and based on examples provided in the CPT manual. The data collection instrument was modeled on the National Ambulatory Medical Care Survey. Trained assistants directly observed every other FP-patient encounter and recorded every patient concern, issue addressed by the physician (including care barriers related to health care systems and social determinants), and treatment ordered in clinics affiliated with 10 residencies of the Residency Research Network of Texas. A visit was deemed to include physician work that was not explicitly reportable if the number or nature of issues addressed exceeded the definitions or examples for 99205/99215 or 99214 + 99354 or a preventive service code, included the physician addressing health care system or social determinant issues, or included the care of a family member. In 982 physician-patient encounters, patients raised 517 different reasons for visit (total, 5278; mean, 5.4 per visit; range, 1 to 16) and the FPs addressed 509 different issues (total issues, 3587; mean, 3.7 per visit; range, 1 to 10). FPs managed 425 different medications, 18 supplements, and 11 devices. A mean of 3.9 chronic medications were continued per visit (range, 0 to 21) and 4.6 total medications were managed (range, 0 to 22). In 592 (60.3%) of the visits the FPs did work that was not explicitly reportable with available CPT codes: 582 (59.3%) addressed more numerous issues than explicitly reportable, 64 (6.5%) addressed system barriers, and 13 (1.3%) addressed concerns for other family members. FPs perform cognitive work in a majority of their patient encounters that are not explicitly reportable, either by being higher than the CPT example number of diagnoses per code or the type of problems addressed, which has implications for the care of complex multi-morbid patients and the growth of the primary care workforce. To address these limitations, either the CPT codes and their associated rules should be updated to reflect the realities of family physicians' practices or new billing and coding approaches should be developed. © Copyright 2017 by the American Board of Family Medicine.

Low Baseline Sympathetic Tone Correlates to a Greater Blood Pressure Change in the Cold Pressor Test.

PubMed

Youssef, Marylen; Ghassemi, Azadeh; Carvajal Gonczi, Catalina Marysol; Kugathasan, Thiffya Arabi; Kilgour, Robert D; Darlington, Peter J

2018-06-01

The cold pressor test (CPT) involves acute hand or foot exposure to cold water. CPT hyper-responders have unique traits, including risk of hypertension and a greater vasoconstrictor reserve and g force tolerance compared to hypo-responders. The purpose of this study was to uncover differences in cardiovascular and sympathetic biomarkers between responder types. Healthy volunteers (N = 30) submerged one hand into cold water (3.3 ± 0.8°C) for 5 min. Blood pressure, heart rate, cardiac output, and cardiac parameters were recorded using an automated monitor, impedance cardiography, and a beat-to-beat monitoring system. We analyzed for salivary α-amylase (SαA), which is a convenient biomarker of the sympathetic nervous system. Subjects were stratified post hoc into hyper-responders (≥ 22 mmHg) and hypo-responders (< 22 mmHg) based on change in systolic blood pressure during CPT. Hyper-responders had a significantly lower baseline heart rate (64 ± 7 bpm), cardiac output (5.6 ± 0.9 L · min-1), and SαA (60 ± 37 U · mL-1) compared to hypo-responders (73 ± 9 bpm, 6.9 ± 1.3 L · min-1, 165 ± 122 U · mL-1). During the cold immersion, hyper-responders had significantly higher systolic blood pressure (150 ± 14 mmHg), diastolic blood pressure (91 ± 10 mmHg), mean arterial pressure (129 ± 17 mmHg), and systemic vascular resistance (1780 ± 640 dyn · s-1 · cm-5) than hypo-responders (130 ± 14 mmHg, 81 ± 10 mmHg, 110 ± 9 mmHg, 1290 ± 220 dyn · s-1 · cm-5). The change in systolic blood pressure correlated with baseline SαA (r = -0.455, P = 0.011) and baseline heart rate (r = -0.374, P = 0.042). Baseline characteristics influenced by sympathetic tone such as SαA, heart rate, and cardiac output are indicative of responses to CPT. Our data supports the use of baseline values to predict blood pressure response to acute cold exposure and indicates an intrinsic difference between CPT responder phenotypes.Youssef M, Ghassemi A, Carvajal Gonczi CM, Kugathasan TA, Kilgour RD, Darlington PJ. Low baseline sympathetic tone correlates to a greater blood pressure change in the cold pressor test. Aerosp Med Hum Perform. 2018; 89(6):503-509.

The effect of prenatal methamphetamine exposure on attention as assessed by continuous performance tests: results from the Infant Development, Environment, and Lifestyle study.

PubMed

Kiblawi, Zeina N; Smith, Lynne M; LaGasse, Linda L; Derauf, Chris; Newman, Elana; Shah, Rizwan; Arria, Amelia; Huestis, Marilyn; DellaGrotta, Sheri; Dansereau, Lynne M; Neal, Charles; Lester, Barry

2013-01-01

To assess for the increased risk of attention-deficit hyperactivity disorder (ADHD) in young children with prenatal methamphetamine exposure from the multicenter, longitudinal Infant Development, Environment, and Lifestyle (IDEAL) study. The IDEAL study enrolled 412 mother-infant pairs at 4 sites (Tulsa, OK; Des Moines, IA; Los Angeles, CA; and Honolulu, HI). Methamphetamine-exposed subjects (n = 204) were identified by self-report and/or gas chromatography/mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Matched subjects (n = 208) denied methamphetamine use and had a negative meconium screen. This analysis included a subsample of 301 subjects who were administered the Conners' Kiddie Continuous Performance Test (K-CPT) at 5.5 years of age (153 exposed and 148 comparison). Hierarchical linear models adjusted for covariates tested exposure effects on K-CPT measures. Using the same covariates, logistic regression was used to determine the effect of exposure on the incidence of a positive ADHD confidence index score, defined as greater than 50%. There were no differences between the groups in omission or commission errors or reaction time for correct trials. However, methamphetamine exposure was associated with subtle differences in other outcomes predictive of ADHD, including increased slope of reaction time across blocks (p < .001), increased variability in reaction time with longer interstimulus intervals (p < .01), and increased likelihood of greater than 50% on the ADHD confidence index (odds ratio, 3.1; 95% confidence interval, 1.2-7.8; p = .02). Prenatal methamphetamine exposure was associated with subtle differences in K-CPT scores at 5.5 years of age. Even at this relatively young age, these children exhibit indicators of risk for ADHD and warrant monitoring.

The 22-Modifier in Reimbursement for Orthopedic Procedures: Hip Arthroplasty and Obesity Are Worth the Effort.

PubMed

Smith, Eric L; Tybor, David J; Daniell, Hayley D; Naccarato, Laura A; Pevear, Mary E; Cassidy, Charles

2018-02-21

Orthopedic surgeons utilize the 22-modifier when billing for complex procedures under the American Medical Association's Current Procedural Terminology (CPT) for reasons such as excessive blood loss, anatomic abnormality, and morbid obesity, cases that would ideally be reimbursed at a higher rate to compensate for additional physician work and time. We investigated how the 22-modifier affects physician reimbursement in knee and hip arthroplasty. We queried hospital billing data from 2009 to 2016, identifying all cases performed at our urban tertiary care orthopedic center for knee arthroplasty (CPT codes 27438, 27447, 27487, and 27488) and hip arthroplasty (CPT codes 27130, 27132, 27134, 27236). We extracted patient insurance status and reimbursement data to compare the average reimbursement between cases with and without the 22-modifier. We analyzed data from 2605 procedures performed by 10 providers. There were 136 cases with 22-modifiers. For knee arthroplasty (n = 1323), the 22-modifier did not significantly increase reimbursement after adjusting for insurer, provider, and fiscal year (4.2% dollars higher on average, P = .159). For hip arthroplasty (n = 1282), cases with a 22-modifier had significantly higher reimbursement than those without the 22-modifier (6.2% dollars more, P = .049). For hip arthroplasty cases with a 22-modifier, those noting morbid obesity were reimbursed 29% higher than those cases with other etiology. The effect of the 22-modifier on reimbursement amount is differential between knee and hip arthroplasty. Hip arthroplasty procedures coded as 22-modifier are reimbursed more than those without the 22-modifier. Providers should consider these potential returns when considering submitting a 22-modifier. Copyright © 2018 Elsevier Inc. All rights reserved.

Exchange protein activated by cAMP (Epac) induces vascular relaxation by activating Ca2+-sensitive K+ channels in rat mesenteric artery

PubMed Central

Roberts, Owain Llŷr; Kamishima, Tomoko; Barrett-Jolley, Richard; Quayle, John M; Dart, Caroline

2013-01-01

Vasodilator-induced elevation of intracellular cyclic AMP (cAMP) is a central mechanism governing arterial relaxation but is incompletely understood due to the diversity of cAMP effectors. Here we investigate the role of the novel cAMP effector exchange protein directly activated by cAMP (Epac) in mediating vasorelaxation in rat mesenteric arteries. In myography experiments, the Epac-selective cAMP analogue 8-pCPT-2′-O-Me-cAMP-AM (5 μm, subsequently referred to as 8-pCPT-AM) elicited a 77.6 ± 7.1% relaxation of phenylephrine-contracted arteries over a 5 min period (mean ± SEM; n= 6). 8-pCPT-AM induced only a 16.7 ± 2.4% relaxation in arteries pre-contracted with high extracellular K+ over the same time period (n= 10), suggesting that some of Epac's relaxant effect relies upon vascular cell hyperpolarization. This involves Ca2+-sensitive, large-conductance K+ (BKCa) channel opening as iberiotoxin (100 nm) significantly reduced the ability of 8-pCPT-AM to reverse phenylephrine-induced contraction (arteries relaxed by only 35.0 ± 8.5% over a 5 min exposure to 8-pCPT-AM, n= 5; P < 0.05). 8-pCPT-AM increased Ca2+ spark frequency in Fluo-4-AM-loaded mesenteric myocytes from 0.045 ± 0.008 to 0.103 ± 0.022 sparks s-1μm-1 (P < 0.05) and reversibly increased both the frequency (0.94 ± 0.25 to 2.30 ± 0.72 s−1) and amplitude (23.9 ± 3.3 to 35.8 ± 7.7 pA) of spontaneous transient outward currents (STOCs) recorded in isolated mesenteric myocytes (n= 7; P < 0.05). 8-pCPT-AM-activated STOCs were sensitive to iberiotoxin (100 nm) and to ryanodine (30 μm). Current clamp recordings of isolated myocytes showed a 7.9 ± 1.0 mV (n= 10) hyperpolarization in response to 8-pCPT-AM that was sensitive to iberiotoxin (n= 5). Endothelial disruption suppressed 8-pCPT-AM-mediated relaxation in phenylephrine-contracted arteries (24.8 ± 4.9% relaxation after 5 min of exposure, n= 5; P < 0.05), as did apamin and TRAM-34, blockers of Ca2+-sensitive, small- and intermediate-conductance K+ (SKCa and IKCa) channels, respectively, and NG-nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthase (NOS). In Fluo-4-AM-loaded mesenteric endothelial cells, 8-pCPT-AM induced a sustained increase in global Ca2+. Our data suggest that Epac hyperpolarizes smooth muscle by (1) increasing localized Ca2+ release from ryanodine receptors (Ca2+ sparks) to activate BKCa channels, and (2) endothelial-dependent mechanisms involving the activation of SKCa/IKCa channels and NOS. Epac-mediated smooth muscle hyperpolarization will limit Ca2+ entry via voltage-sensitive Ca2+ channels and represents a novel mechanism of arterial relaxation. PMID:23959673

Contribution of the polarization moments of different rank to the integral CPT signal

NASA Astrophysics Data System (ADS)

Taskova, E.; Alipieva, E.; Todorov, G.

2016-01-01

In the present work we investigate the relation of the polarization moments having different ranks with the tensor components which form the observable integral CPT signal, in the presence of a stray magnetic field. A numerical experiment with parameters close to the real ones is performed, using a program based on the irreducible tensor operator formalism1. The integral fluorescent signal is calculated for the non-polarized fluorescence at different laser power excitation. Detailed analysis of the numerical solutions for all tensor components which describe population and alignment allows visualizing the dynamics of their behavior in dependence on the experimental geometry and laboratory magnetic field B'. The dependence of population f00, longitudinal f02 and transverse f22 alignment in the presence of transverse magnetic field is investigated. The shape and sign of the resonance change with laser power.

Quantitative EEG features selection in the classification of attention and response control in the children and adolescents with attention deficit hyperactivity disorder.

PubMed

Bashiri, Azadeh; Shahmoradi, Leila; Beigy, Hamid; Savareh, Behrouz A; Nosratabadi, Masood; N Kalhori, Sharareh R; Ghazisaeedi, Marjan

2018-06-01

Quantitative EEG gives valuable information in the clinical evaluation of psychological disorders. The purpose of the present study is to identify the most prominent features of quantitative electroencephalography (QEEG) that affect attention and response control parameters in children with attention deficit hyperactivity disorder. The QEEG features and the Integrated Visual and Auditory-Continuous Performance Test ( IVA-CPT) of 95 attention deficit hyperactivity disorder subjects were preprocessed by Independent Evaluation Criterion for Binary Classification. Then, the importance of selected features in the classification of desired outputs was evaluated using the artificial neural network. Findings uncovered the highest rank of QEEG features in each IVA-CPT parameters related to attention and response control. Using the designed model could help therapists to determine the existence or absence of defects in attention and response control relying on QEEG.

Sleep, attention, and executive functioning in children with attention-deficit/hyperactivity disorder.

PubMed

Moreau, Vincent; Rouleau, Nancie; Morin, Charles M

2013-11-01

The objective of this study was to investigate potential relationships between two measures of sleep impairments (i.e., sleep duration and sleep efficiency [SE]) and attention and executive functioning in children with attention-deficit/hyperactivity disorder (ADHD). Parents of 43 children (mean age = 10 ± 1.8 years) with ADHD completed sleep and behavioral questionnaires. Children also wore a wrist actigraph for seven nights and were subsequently assessed with the Conners' continuous performance test (CPT)-2. A significant relationship was found between lower SE and increased variability in reaction time on the CPT. Shorter sleep duration was associated with a range of executive functioning problems as reported by the parents. The relationships between sleep duration and the executive functioning measures held even after controlling for age, gender, and use of medication, but not the relationships with SE. These results suggest that sleep quantity is an important correlate of executive functioning in children with ADHD.

Assessing medication effects in the MTA study using neuropsychological outcomes.

PubMed

Epstein, Jeffery N; Conners, C Keith; Hervey, Aaron S; Tonev, Simon T; Arnold, L Eugene; Abikoff, Howard B; Elliott, Glen; Greenhill, Laurence L; Hechtman, Lily; Hoagwood, Kimberly; Hinshaw, Stephen P; Hoza, Betsy; Jensen, Peter S; March, John S; Newcorn, Jeffrey H; Pelham, William E; Severe, Joanne B; Swanson, James M; Wells, Karen; Vitiello, Benedetto; Wigal, Timothy

2006-05-01

While studies have increasingly investigated deficits in reaction time (RT) and RT variability in children with attention deficit/hyperactivity disorder (ADHD), few studies have examined the effects of stimulant medication on these important neuropsychological outcome measures. 316 children who participated in the Multimodal Treatment Study of Children with ADHD (MTA) completed the Conners' Continuous Performance Test (CPT) at the 24-month assessment point. Outcome measures included standard CPT outcomes (e.g., errors of commission, mean hit reaction time (RT)) and RT indicators derived from an Ex-Gaussian distributional model (i.e., mu, sigma, and tau). Analyses revealed significant effects of medication across all neuropsychological outcome measures. Results on the Ex-Gaussian outcome measures revealed that stimulant medication slows RT and reduces RT variability. This demonstrates the importance of including analytic strategies that can accurately model the actual distributional pattern, including the positive skew. Further, the results of the study relate to several theoretical models of ADHD.

The Relation Between Inattentive and Hyperactive/Impulsive Behaviors and Early Mathematics Skills.

PubMed

Sims, Darcey M; Purpura, David J; Lonigan, Christopher J

2016-08-01

Despite strong evidence that inattentive and hyperactive/impulsive behaviors are associated with mathematical difficulties in school-age children, little research has been conducted to examine the link between these constructs before the start of formal education. The purpose of this study was to examine how different manifestations of inattentive and hyperactive/impulsive behaviors, as measured by different assessment tools, are related to early mathematics skills in preschoolers. Eighty-two preschool children completed a measure of early mathematics and the Continuous Performance Test (CPT). Teachers rated children's behaviors using the Conners' Teacher Rating Scale-15 Item. Sixty-five of these children completed mathematics assessments 1 year later. Teacher ratings of inattention were uniquely related to concurrent early mathematics skills, whereas CPT errors were uniquely predictive of early mathematics skills 1 year later. Findings have implications for the understanding and assessment of behavior problems that are associated with early mathematics difficulties. © The Author(s) 2012.

Enhanced Intratumoral Delivery of SN38 as a Tocopherol Oxyacetate Prodrug Using Nanoparticles in a Neuroblastoma Xenograft Model.

PubMed

Nguyen, Ferro; Alferiev, Ivan; Guan, Peng; Guerrero, David T; Kolla, Venkatadri; Moorthy, Ganesh S; Chorny, Michael; Brodeur, Garrett M

2018-06-01

Purpose: Currently, <50% of high-risk pediatric solid tumors like neuroblastoma can be cured, and many survivors experience serious or life-threatening toxicities, so more effective, less toxic therapy is needed. One approach is to target drugs to tumors using nanoparticles, which take advantage of the enhanced permeability of tumor vasculature. Experimental Design: SN38, the active metabolite of irinotecan (CPT-11), is a potent therapeutic agent that is readily encapsulated in polymeric nanoparticles. Tocopherol oxyacetate (TOA) is a hydrophobic mitocan that was linked to SN38 to significantly increase hydrophobicity and enhance nanoparticle retention. We treated neuroblastomas with SN38-TOA nanoparticles and compared the efficacy with the parent prodrug CPT-11 using a mouse xenograft model. Results: Nanoparticle treatment induced prolonged event-free survival (EFS) in most mice, compared with CPT-11. This was shown for both SH-SY5Y and IMR-32 neuroblastoma xenografts. Enhanced efficacy was likely due to increased and sustained drug levels of SN38 in the tumor compared with conventional CPT-11 delivery. Interestingly, when recurrent CPT-11-treated tumors were re-treated with SN38-TOA nanoparticles, the tumors transformed from undifferentiated neuroblastomas to maturing ganglioneuroblastomas. Furthermore, these tumors were infiltrated with Schwann cells of mouse origin, which may have contributed to the differentiated histology. Conclusions: Nanoparticle delivery of SN38-TOA produced increased drug delivery and prolonged EFS compared to conventional delivery of CPT-11. Also, lower total dose and drug entrapment in nanoparticles during circulation should decrease toxicity. We propose that nanoparticle-based delivery of a rationally designed prodrug is an attractive approach to enhance chemotherapeutic efficacy in pediatric and adult tumors. Clin Cancer Res; 24(11); 2585-93. ©2018 AACR . ©2018 American Association for Cancer Research.

Overexpression of Nitrogen Permease Regulator Like-2 (NPRL2) Enhances Sensitivity to Irinotecan (CPT-11) in Colon Cancer Cells by Activating the DNA Damage Checkpoint Pathway.

PubMed

Liu, Shasha; Liu, Bingrong

2018-03-09

BACKGROUND Colorectal cancer (CRC) is the third most common cancer worldwide, making it is a serious threat to human health. It is imperative to develop new therapeutics to improve the CRC treatment efficiency. The aim of this study was to investigate the role of NPRL2 in improving sensitivity to CPT-11 in colon cancer cells. MATERIAL AND METHODS NPRL2 overexpression was established by transfecting the recombinant lentivirus-encoding NPRL2 gene into HCT116 colon cancer cells. Cell proliferation was identified using Cell Counting Kit-8 (CCK8) assay. Cell cycle and apoptosis were examined by flow cytometry. An immunofluorescence staining assay was conducted to examine the expression of γ-H2AX. Wound-healing and Transwell assays were utilized to show cell migration and invasion capability. The expression of apoptosis-related proteins (cleaved caspase-3, caspase-9, cleaved PARP, BAX, and Bcl-2), invasion-related proteins (MMP2, MMP9, p-PI3K, and p-AKT), and DNA damage checkpoint pathway proteins (p-ATM, p-Chk2, Cdc25C, Cdc2, and Cyclin B1) were quantified by Western blotting. RESULTS A CCK8 assay revealed that the overexpression of NPRL2 improved the sensitivity of CPT-11 in HCT116 cells (P<0.05). Functionally, NPRL2 overexpression elevated the sensitivity of CPT-11 by preventing colon cancer cell proliferation, cell movement, and invasion, and promoting cell apoptosis and G2/M cell cycle arrest. Mechanistically, NPRL2 overexpression enhanced CPT-11 sensitivity by activating the DNA damage checkpoint pathway. CONCLUSIONS NPRL2 overexpression enhances sensitivity to CPT-11 treatment in colon cancer cells, and it may serve as a molecular therapeutic agent to treat patients with CRC.

Altered coronary endothelial function in young smokers detected by magnetic resonance assessment of myocardial blood flow during the cold pressor test.

PubMed

Ichikawa, Yasutaka; Kitagawa, Kakuya; Kato, Shingo; Dohi, Kaoru; Hirano, Tadanori; Ito, Masaaki; Sakuma, Hajime

2014-06-01

Endothelial dysfunction is a key element in early atherogenesis. The purposes of this study were to evaluate the feasibility of magnetic resonance (MR) assessment of altered myocardial blood flow (MBF) in response to the cold pressor test (CPT) and to determine if coronary endothelial dysfunction in young smokers can be detected with this noninvasive approach. Fourteen healthy non-smokers (31 ± 6 years) and 12 smokers (34 ± 8 years) were studied. Breath-hold phase-contrast cine MR imaging (PC-MRI) of the coronary sinus (CS) were obtained at rest and during the CPT. MBF was measured as CS flow divided by left ventricle mass and the rate pressure product. In non-smokers, MBF was 0.88 ± 0.19 ml/min/g at rest and significantly increased to 1.13 ± 0.26 ml/min/g during the CPT (P = 0.0001). In smokers, MBF was 0.94 ± 0.26 ml/min/g at rest and 0.96 ± 0.30 ml/min/g during the CPT (P = 0.73). ΔMBF (MBF during the CPT-MBF at rest) was significantly reduced in smokers compared with non-smokers (0.02 ± 0.20 vs. 0.26 ± 0.18 ml/min/g, P = 0.005). The intra-class correlation coefficient between measurements by two observers was 0.90 for ΔMBF. A significant reduction in MBF response to CPT was demonstrated in young smokers with PC-MRI at 1.5 T. This noninvasive method has great potential for assessment of coronary endothelial function.

An alternative to the traditional cold pressor test: the cold pressor arm wrap.

PubMed

Porcelli, Anthony John

2014-01-16

Recently research on the relationship between stress and cognition, emotion, and behavior has greatly increased. These advances have yielded insights into important questions ranging from the nature of stress' influence on addiction(1) to the role of stress in neural changes associated with alterations in decision-making(2,3). As topics being examined by the field evolve, however, so too must the methodologies involved. In this article a practical and effective alternative to a classic stress induction technique, the cold pressor test (CPT), is presented: the cold pressor arm wrap (CPAW). CPT typically involves immersion of a participant's dominant hand in ice-cold water for a period of time(4). The technique is associated with robust activation of the sympatho-adrenomedullary (SAM) axis (and release of catecholamines; e.g. adrenaline and noradrenaline) and mild-to-moderate activation of the hypothalamic-pituitary-adrenal (HPA) axis with associated glucocorticoid (e.g. cortisol) release. While CPT has been used in a wide range of studies, it can be impractical to apply in some research environments. For example use of water during, rather than prior to, magnetic resonance imaging (MRI) has the potential to damage sensitive and expensive equipment or interfere with acquisition of MRI signal. The CPAW is a practical and effective alternative to the traditional CPT. Composed of a versatile list of inexpensive and easily acquired components, CPAW makes use of MRI-safe gelpacs cooled to a temperature similar to CPT rather than actual water. Importantly CPAW is associated with levels of SAM and HPA activation comparable to CPT, and can easily be applied in a variety of research contexts. While it is important to maintain specific safety protocols when using the technique, these are easy to implement if planned for. Creation and use of the CPAW will be discussed.

Brain Delivery of Drug and MRI Contrast Agent: Detection and Quantitative Determination of Brain Deposition of CPT-Glu Using LC-MS/MS and Gd-DTPA Using Magnetic Resonance Imaging.

PubMed

Tabanor, Kayann; Lee, Phil; Kiptoo, Paul; Choi, In-Young; Sherry, Erica B; Eagle, Cheyenne Sun; Williams, Todd D; Siahaan, Teruna J

2016-02-01

Successful treatment and diagnosis of neurological diseases depend on reliable delivery of molecules across the blood-brain barrier (BBB), which restricts penetration of pharmaceutical drugs and diagnostic agents into the brain. Thus, developing new noninvasive strategies to improve drug delivery across the BBB is critically needed. This study was aimed at evaluating the activity of HAV6 peptide (Ac-SHAVSS-NH2) in improving brain delivery of camptothecin-glutamate (CPT-Glu) conjugate and gadolinium-diethylenetriaminepentaacetate (Gd-DTPA) contrast agent in Sprague-Dawley rats. Brain delivery of both CPT-Glu and Gd-DTPA was evaluated in an in situ rat brain perfusion model in the presence and absence of HAV6 peptide (1.0 mM). Gd-DTPA (0.6 mmol/kg) was intravenously (iv) administered with and without HAV6 peptide (0.019 mmol/kg) in rats. The detection and quantification of CPT-Glu and Gd-DTPA in the brain were carried out by LC-MS/MS and quantitative magnetic resonance imaging (MRI), respectively. Rats perfused with CPT-Glu in combination with HAV6 had significantly higher deposition of drug in the brain compared to CPT-Glu alone. MRI results also showed that administration of Gd-DTPA in the presence of HAV6 peptide led to significant accumulation of Gd-DTPA in various regions of the brain in both the in situ rat brain perfusion and in vivo studies. All observations taken together indicate that HAV6 peptide can disrupt the BBB and enhance delivery of small molecules into the brain.

Hepatic β-Oxidation and Regulation of Carnitine Palmitoyltransferase (CPT) I in Blunt Snout Bream Megalobrama amblycephala Fed a High Fat Diet

PubMed Central

Lu, Kang-Le; Xu, Wei-Na; Wang, Li-Na; Zhang, Ding-Dong; Zhang, Chun-Nuan; Liu, Wen-Bin

2014-01-01

High-fat diets may promote growth, partly through their protein-sparing effects. However, high-fat diets often lead to excessive fat deposition, which may have a negative impact on fish such as poor growth and suppressive immune. Therefore, this study investigated the effects of a fat-rich diet on the mechanisms of fat deposition in the liver. Three-hundred blunt snout bream (Megalobrama amblycephala) juveniles (initial mass 18.00±0.05 g) were fed with one of two diets (5% or 15% fat) for 8 weeks. β-Oxidation capacity and regulation of rate-limiting enzymes were assessed. Large fat droplets were present in hepatocytes of fish fed the high-fat diet. This observation is thought to be largely owing to the reduced capacity for mitochondrial and peroxisomal β-oxidation in the livers of fish fed the high-fat diet, as well as the decreased activities of carnitine palmitoyltransferase (CPT) I and acyl-CoA oxidase (ACO), which are enzymes involved in fatty-acid metabolism. Study of CPT I kinetics showed that CPT I had a low affinity for its substrates and a low catalytic efficiency in fish fed the high-fat diet. Expression of both CPT I and ACO was significantly down-regulated in fish fed the high-fat diet. Moreover, the fatty-acid composition of the mitochondrial membrane varied between the two groups. In conclusion, the attenuated β-oxidation capacity observed in fish fed a high-fat diet is proposed to be owing to decreased activity and/or catalytic efficiency of the rate-limiting enzymes CPT I and ACO, via both genetic and non-genetic mechanisms. PMID:24676148

Brain Delivery of Drug and MRI Contrast Agent: Detection and Quantitative Determination of Brain Deposition of CPT-Glu Using LC-MS/MS and Gd-DTPA Using Magnetic Resonance Imaging

PubMed Central

Tabanor, Kayann; Lee, Phil; Kiptoo, Paul; Choi, In-Young; Sherry, Erica B.; Eagle, Cheyenne Sun; Williams, Todd D.; Siahaan, Teruna J.

2015-01-01

Successful treatment and diagnosis of neurological diseases depend on reliable delivery of molecules across the blood-brain barrier (BBB), which restricts penetration of pharmaceutical drugs and diagnostic agents into the brain. Thus, developing new non-invasive strategies to improve drug delivery across the BBB is critically needed. This study was aimed at evaluating the activity of HAV6 peptide (Ac-SHAVSS-NH2) in improving brain delivery of camptothecin-glutamate (CPT-Glu) conjugate and gadolinium-diethylenetriaminepentaacetate (Gd-DTPA) contrast agent in Sprague-Dawley rats. Brain delivery of both CPT-Glu and Gd-DTPA was evaluated in an in situ rat brain perfusion model in the presence and absence of HAV6 peptide (1.0 mM). Gd-DTPA (0.6 mmol/kg) was intravenously (i.v.) administered with and without HAV6 peptide (0.019 mmol/kg) in rats. The detection and quantification of CPT-Glu and Gd-DTPA in the brain were carried out by LC-MS/MS and quantitative magnetic resonance imaging (MRI), respectively. Rats perfused with CPT-Glu in combination with HAV6 had significantly higher deposition of drug in the brain compared to CPT-Glu alone. MRI results also showed that administration of Gd-DTPA in the presence of HAV6 peptide led to significant accumulation of Gd-DTPA in various regions of the brain in both the in situ rat brain perfusion and in vivo studies. All observations taken together indicate that HAV6 peptide can disrupt the BBB and enhance delivery of small molecules into the brain. PMID:26705088

Predicting hydrofacies and hydraulic conductivity from direct-push data using a data-driven relevance vector machine approach: Motivations, algorithms, and application

NASA Astrophysics Data System (ADS)

Paradis, Daniel; Lefebvre, René; Gloaguen, Erwan; Rivera, Alfonso

2015-01-01

The spatial heterogeneity of hydraulic conductivity (K) exerts a major control on groundwater flow and solute transport. The heterogeneous spatial distribution of K can be imaged using indirect geophysical data as long as reliable relations exist to link geophysical data to K. This paper presents a nonparametric learning machine approach to predict aquifer K from cone penetrometer tests (CPT) coupled with a soil moisture and resistivity probe (SMR) using relevance vector machines (RVMs). The learning machine approach is demonstrated with an application to a heterogeneous unconsolidated littoral aquifer in a 12 km2 subwatershed, where relations between K and multiparameters CPT/SMR soundings appear complex. Our approach involved fuzzy clustering to define hydrofacies (HF) on the basis of CPT/SMR and K data prior to the training of RVMs for HFs recognition and K prediction on the basis of CPT/SMR data alone. The learning machine was built from a colocated training data set representative of the study area that includes K data from slug tests and CPT/SMR data up-scaled at a common vertical resolution of 15 cm with K data. After training, the predictive capabilities of the learning machine were assessed through cross validation with data withheld from the training data set and with K data from flowmeter tests not used during the training process. Results show that HF and K predictions from the learning machine are consistent with hydraulic tests. The combined use of CPT/SMR data and RVM-based learning machine proved to be powerful and efficient for the characterization of high-resolution K heterogeneity for unconsolidated aquifers.

Wireless, accelerometry-triggered functional electrical stimulation of the peroneal nerve in spastic paresis: A randomized, controlled pilot study.

PubMed

Ghédira, Mouna; Albertsen, Inke Marie; Mardale, Valentina; Gracies, Jean-Michel; Bayle, Nicolas; Hutin, Émilie

2017-01-01

In hemiparesis, Wireless, Accelerometry-Triggered Functional Electrical Stimulation (WAFES) of the common peroneal nerve may hold intrinsic rehabilitative properties. The present pilot study analyzes WAFES against conventional therapy. Twenty adults with chronic hemiparesis (time since lesion 7(6) years; median (interquartile range)) were randomized into 2 10-week rehabilitation programs: a 45-minute (min) daily walk using WAFES (n = 10) and conventional physical therapy (CPT), 3 × 45 min per week (n = 10). The outcomes were 3D sagittal speed measurements, step length, cadence, maximal amplitude and velocity of hip, knee, and ankle during gait at free and fast speed without WAFES and clinical assessments of plantar flexor angles of shortening, spasticity, and weakness, before (D1) and after the program (W10). Kinematic and spasticity improvements occurred in the WAFES group only: (i) ankle dorsiflexion velocity (D1 versus W10, free speed, WAFES, +4(5)°/sec, p = 0.002; CPT, -3(8)°/sec, p = 0.007; fast, WAFES, +8(6)°/sec, p = 0.03; CPT, -1(4)°/sec, NS); (ii) maximal passive ankle dorsiflexion (WAFES,+26(85)%; CPT,+0(27)%; group-visit, p = 0.007) and knee flexion (WAFES, +13(17)%; CPT, -1(11)%; group-visit, p = 0.006) at fast speed only; (iii) 15% plantar flexor spasticity grade reduction with WAFES. Over 10 weeks, gait training using WAFES improved ankle and knee kinematics and reduced plantar flexor spasticity compared with CPT. Studies with longer WAFES use should explore functional effects.

HIV screening among TB patients and level of antiretroviral therapy and co-trimoxazole preventive therapy for TB/HIV patients in Hawassa University Referral Hospital: a five year retrospective study.

PubMed

Simieneh, Asnake; Hailemariam, Mengistu; Amsalu, Anteneh

2017-01-01

Initiation of antiretroviral therapy (ART) and co-trimoxazole preventive therapy (CPT) is recommended for tuberculosis (TB)/human immunodeficiency virus (HIV) co-infected patients to prevent opportunistic infection. The aim of this study was to assess the prevalence of HIV among TB patients and initiation of ART and provision of CPT for TB/HIV co-infected patients in Hawassa university referral hospital. A five year document review was done on 1961 TB patients who are registered at TB clinic of Hawassa university referral hospital from September 2009 to august 2014. Data were collected using checklist. Data analysis was done by using SPSS version 20 software. Bivariate and multivariate logistic regression analysis was used to determine the predictors of TB/HIV co-infection. Among 1961 TB patients diagnosed in the hospital, 95% (1765) were screened for HIV. Of these, 13.9% (246) were HIV positive. Out of 246 TB/HIV co-infected patients 31.7% (78/246) and 37.4% (92/246) were enrolled to start ART and CPT respectively. Roughly the trends of TB/HIV co-infection decreased with increased linkage to CPT, while linkage to ART was not regular across the year. The rate of TB/HIV co-infection was significantly associated with type of TB. Although, trend of HIV among TB patients has decreased across the year, only a minority of co-infected patients was linked to start ART and CPT. Therefore, screening of all TB patients for HIV and linkage of co-infected patients to HIV care to start ART and CPT should be strengthened in-line with the national guidelines.

Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) Extension Study for Subjects Previously Enrolled in Triheptanoin Studies.

ClinicalTrials.gov

2018-06-19

Carnitine Palmitoyltransferase (CPT I or CPT II) Deficiency; Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency; Long-chain 3-hydroxy-acyl-CoA Dehydrogenase (LCHAD) Deficiency; Trifunctional Protein (TFP) Deficiency; Carnitine-acylcarnitine Translocase (CACT) Deficiency

Update of correlations between cone penetration and boring log data : technical summary report.

DOT National Transportation Integrated Search

2009-12-01

The main objective of this project is to update the correlations that are currently used to interpret : Cone Penetration Test (CPT) data for engineering design purposes and to assess the reliability of : using CPT data to predict soil shear strength....

Evaluation of bearing capacity of piles from cone penetration test data : technical summary.

DOT National Transportation Integrated Search

1999-11-01

Among the different in situ tests, cone penetration test (CPT) is considered the most frequently used method for characterization of geomedia. Due to the soft nature of soil deposits in Louisiana, the CPT is considered a perfect tool for characteriza...

Evaluation of Cone Penetrometer Data for Permeability Correlation at the Savannah River Site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, M.K.

1997-02-01

This report documents the results of an assessment of cone penetrometer technology (CPT) use at the Savannah River Site. The study is intended to provide valuable insight into methods of increasing the utility of CPT data for site characterization.