Integrated Cognitive Behavioral Therapy Versus Cognitive Processing Therapy for Adults With Depression, Substance Use Disorder, and Trauma.

PubMed

Haller, Moira; Norman, Sonya B; Cummins, Kevin; Trim, Ryan S; Xu, Xiaomin; Cui, Ruifeng; Allard, Carolyn B; Brown, Sandra A; Tate, Susan R

2016-03-01

The comorbidity of substance use disorder (SUD), depression, and PTSD is common among veterans. Prior research has shown that among veterans with SUD and depression, those with PTSD did not maintain cognitive-behavioral treatment gains as well as those without PTSD. Thus, the current study was designed to evaluate whether adding trauma-focused treatment following an initial group-based integrated cognitive behavioral treatment (ICBT) for SUD and depression improved treatment outcomes. Participants were 123 veterans (89% male) recruited from the VA San Diego Healthcare System. All participants received ICBT in twice weekly, group-delivered sessions for 12 weeks (Phase 1). Participants were then randomized to receive 12 sessions of individual follow-up sessions (Phase 2) utilizing either ICBT or cognitive processing therapy that was modified to integrate SUD treatment (CPT-M). Results indicated that PTSD and depression symptoms slightly improved at the end of Phase 1 group ICBT and further improved through Phase 2 individual treatment (except for participants without PTSD who received CPT-M), with treatment gains maintained one year later. Substance use significantly improved at the end of Phase 1 group ICBT and these improvements were maintained through Phase 2 and the one year follow-up. Participants in the trauma-focused Phase 2 treatment (CPT-M) exhibited similar levels of symptom reduction and maintenance of treatment gains as those in the non-trauma-focused Phase 2 treatment (ICBT). However, there was a slight advantage for Phase 2 CPT-M over Phase 2 ICBT with respect to heavy drinking outcomes for individuals with PTSD. Overall, the combination of group ICBT followed by either CPT-M or ICBT individual therapy appears to be effective for veterans with depression, SUD, and trauma history. Copyright © 2015. Published by Elsevier Inc.

Responding to the need for sleep among survivors of interpersonal violence: A randomized controlled trial of a cognitive-behavioral insomnia intervention followed by PTSD treatment.

PubMed

Pigeon, Wilfred R; Heffner, Kathi L; Crean, Hugh; Gallegos, Autumn M; Walsh, Patrick; Seehuus, Martin; Cerulli, Catherine

2015-11-01

Sleep disturbance is a common feature of posttraumatic stress disorder (PTSD), but is not a focus of standard PTSD treatments. Psychological trauma exposure is associated with considerable physical and mental health morbidity, possibly due to the alterations in neuroendocrine function and inflammation observed in trauma exposed individuals. Although PTSD treatments are efficacious, they are associated with high drop-out rates in clinical trials and clinical practice. Finally, individuals with PTSD stemming from exposure to interpersonal violence represent an especially under-treated population with significant sleep disturbance. Community-based participatory research was utilized to design and prepare a clinical trial that randomizes recent survivors of interpersonal violence who have PTSD, depression, and insomnia to receive either: (1) Cognitive Behavioral Therapy for Insomnia (CBTi) followed by Cognitive Processing Therapy (CPT) for trauma, or (2) attention control followed by CPT. Outcome measures include subjective and objective measures of sleep, clinician-administered PTSD and depression scales, inflammatory cytokines, and salivary cortisol. Assessments are conducted at baseline, following the sleep or control intervention, and again following CPT. The design allows for: (1) the first test of a sleep intervention in this population; (2) the comparison of sequenced CBTi and CPT to attention control followed by CPT, and (3) assessing the roles of neuroendocrine function, inflammatory processes, and objective sleep markers in mediating treatment outcomes. The study's overarching hypothesis is that treating insomnia will produce reduction in insomnia, PTSD, and depression severity, allowing patients to more fully engage in, and derive optimal benefits from, cognitive processing therapy. Published by Elsevier Inc.

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

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.

Fidelity to the Cognitive Processing Therapy Protocol: Evaluation of Critical Elements.

PubMed

Farmer, Courtney C; Mitchell, Karen S; Parker-Guilbert, Kelly; Galovski, Tara E

2017-03-01

The contributions of individual therapy elements to the overall efficacy of evidence-based practices for the treatment of posttraumatic stress disorder (PTSD) are not well-understood. This study first examined the extent to which theoretically important treatment components of Cognitive Processing Therapy (CPT; i.e., skill in Socratic questioning; prioritizing assimilation; attention to practice assignments; emphasis on expression of natural affect) were successfully administered across the course of therapy for 68 PTSD-positive survivors of interpersonal trauma. Therapist fidelity in the administration of these four elements was evaluated in 533 taped CPT sessions of study participants included in one of two randomized controlled CPT treatment trials. Second, we examined therapist fidelity to these components as a predictor of session-to-session PTSD and depression symptom change. Third, follow-up analyses examined the influence of high therapist competence for these four components across an entire course of therapy on symptom change from pre- to posttreatment. Results showed consistently high adherence and more variable competence for these four treatment components. There were no significant effects of therapist fidelity on session-to-session symptom change. However, results showed that overall high therapist competence for "skill in Socratic questioning" and "prioritizing assimilation before overaccommodation" were related to greater client improvement in PTSD severity, but "attention to practice assignments" and "emphasis on expression of natural affect" were not. Overall competence ratings for the four components were not significantly associated with improvement in depressive symptoms. Findings contribute to increased understanding of the relationship between the key treatment components of CPT and symptom change. Copyright © 2016. Published by Elsevier Ltd.

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.

Predictors of Initiation and Engagement of Cognitive Processing Therapy Among Veterans With PTSD Enrolled in Collaborative Care.

PubMed

Grubbs, Kathleen M; Fortney, John C; Pyne, Jeffrey M; Hudson, Teresa; Moore, William Mark; Custer, Paul; Schneider, Ronald; Schnurr, Paula P

2015-12-01

Collaborative care (CC) increases access to evidence-based pharmacotherapy and psychotherapy. The study aim was to identify the characteristics of rural veterans receiving a telemedicine-based CC intervention for posttraumatic stress disorder (PTSD) who initiated and engaged in cognitive processing therapy (CPT) delivered via interactive video. Veterans diagnosed with PTSD were recruited from 11 community-based outpatient clinics (N = 133). Chart abstraction identified all mental health encounters received during the 12-month study. General linear mixed models were used to identify characteristics that predicted CPT initiation and engagement (attendance at 8 or more sessions). For initiation, higher PTSD severity according to the Clinician Administered PTSD Scale (d = -0.39, p = .038) and opt-out recruitment (vs. self-referral; d = -0.49, p = .010) were negative predictors. For engagement, major depression (d = -1.32, p = .006) was a negative predictor whereas a pending claim for military service connected disability (d = 2.02, p = .008) was a positive predictor. In general, veterans enrolled in CC initiated and engaged in CPT at higher rates than usual care. Those with more severe symptoms and comorbidity, however, were at risk of not starting or completing CPT. © 2015 International Society for Traumatic Stress Studies.

Augmenting cognitive processing therapy to improve sleep impairment in PTSD: A randomized controlled trial.

PubMed

Galovski, Tara E; Harik, Juliette M; Blain, Leah M; Elwood, Lisa; Gloth, Chelsea; Fletcher, Thomas D

2016-02-01

Despite the success of empirically supported treatments for posttraumatic stress disorder (PTSD), sleep impairment frequently remains refractory after treatment. This single-site, randomized controlled trial examined the effectiveness of sleep-directed hypnosis as a complement to an empirically supported psychotherapy for PTSD (cognitive processing therapy [CPT]). Participants completed either 3 weeks of hypnosis (n = 52) or a symptom monitoring control condition (n = 56) before beginning standard CPT. Multilevel modeling was used to investigate differential patterns of change to determine whether hypnosis resulted in improvements in sleep, PTSD, and depression. An intervening variable approach was then used to determine whether improvements in sleep achieved during hypnosis augmented change in PTSD and depression during CPT. After the initial phase of treatment (hypnosis or symptom monitoring), the hypnosis condition showed significantly greater improvement than the control condition in sleep and depression, but not PTSD. After CPT, both conditions demonstrated significant improvement in sleep and PTSD; however, the hypnosis condition demonstrated greater improvement in depressive symptoms. As sleep improved, there were corresponding improvements in PTSD and depression, with a stronger relationship between sleep and PTSD. Hypnosis was effective in improving sleep impairment, but those improvements did not augment gains in PTSD recovery during the trauma-focused intervention. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Uniformity of Evidence-Based Treatments in Practice? Therapist Effects in the Delivery of Cognitive Processing Therapy for PTSD

ERIC Educational Resources Information Center

Laska, Kevin M.; Smith, Tracey L.; Wislocki, Andrew P.; Minami, Takuya; Wampold, Bruce E.

2013-01-01

Objective: Various factors contribute to the effective implementation of evidence-based treatments (EBTs). In this study, cognitive processing therapy (CPT) was administered in a Veterans Affairs (VA) posttraumatic stress disorder (PTSD) specialty clinic in which training and supervision were provided following VA implementation guidelines. The…

A Randomized Clinical Trial to Dismantle Components of Cognitive Processing Therapy for Posttraumatic Stress Disorder in Female Victims of Interpersonal Violence

ERIC Educational Resources Information Center

Resick, Patricia A.; Galovski, Tara E.; Uhlmansiek, Mary O'Brien; Scher, Christine D.; Clum, Gretchen A.; Young-Xu, Yinong

2008-01-01

The purpose of this experiment was to conduct a dismantling study of cognitive processing therapy in which the full protocol was compared with its constituent components--cognitive therapy only (CPT-C) and written accounts (WA)--for the treatment of posttraumatic stress disorder (PTSD) and comorbid symptoms. The intent-to-treat (ITT) sample…

Pilot Cases of Combined Cognitive Processing Therapy and Smoking Cessation for Smokers With Posttraumatic Stress Disorder.

PubMed

Dedert, Eric A; Resick, Patricia A; McFall, Miles E; Dennis, Paul A; Olsen, Maren; Beckham, Jean C

2016-01-01

Posttraumatic stress disorder (PTSD) and smoking are often comorbid, and both problems are in need of improved access to evidence-based treatment. The combined approach could address two high-priority problems and increase patient access to both treatments, but research is needed to determine whether this is feasible and has promise for addressing both PTSD and smoking. We collected data from 15 test cases that received a treatment combining two evidence-based treatments: cognitive processing therapy-cognitive version (CPT-C) for PTSD and integrated care for smoking cessation (ICSC). We explored two combined treatment protocols including a brief (six-session) CPT-C with five follow-up in-person sessions focused on smoking cessation (n=9) and a full 12-session CPT-C protocol with ICSC (n=6). The combined interventions were feasible and acceptable to patients with PTSD making a quit attempt. Initial positive benefits of the combined treatments were observed. The six-session dose of CPT-C and smoking cessation resulted in 6-month bioverified smoking abstinence in two of nine participants, with clinically meaningful PTSD symptom reduction in three of nine participants. In the second cohort (full CPT-C and smoking treatment), both smoking and PTSD symptoms were improved, with three of six participants abstinent from smoking and four of six participants reporting clinically meaningful reduction in PTSD symptoms. Results suggested that individuals with PTSD who smoke are willing to engage in concurrent treatment of these problems and that combined treatment is feasible. Copyright © 2015. Published by Elsevier Ltd.

Study participant reported outcomes of mental health interventions: results from a randomized controlled trial among survivors of systematic violence in southern Iraq.

PubMed

Mahmooth, Z; Weiss, W M; Zangana, G A S; Bolton, P

2018-01-01

Common mental health problems experienced by survivors of systematic violence include trauma, depression, and anxiety. A trial of mental health interventions by community mental health workers for survivors of systematic violence in southern Iraq showed benefits from two psychotherapies on trauma, depression, anxiety, and function: Common Elements Treatment Approach (CETA) and cognitive processing therapy (CPT). This study assessed whether other non-predetermined changes reported by intervention participants were more common than in the control group. The trial involved 342 participants (CETA: 99 intervention, 50 control; CPT: 129 intervention, 64 control). Sixteen intervention-related changes since enrollment were identified from free-listing interviews of 15 early therapy completers. The changes were then added as a new quantitative module to the follow-up questionnaire. The changes were organized into eight groupings by thematic analysis - family, social standing, anger management, interest in regular activities, optimism, feeling close to God, avoiding smoking and drugs, and physical health. All participants were interviewed with this module and responses were compared between intervention and control participants. Multi-level, multi-variate regression models showed CETA intervention subjects with significant, positive changes relative to CETA controls on most themes. CPT intervention subjects showed little to no change compared with CPT controls in most themes. Participants receiving CETA reported more positive changes from therapy compared with controls than did participants receiving CPT. This study suggests differential effects of psychotherapy beyond the predetermined clinical outcome measures and that identification of these effects should be part of intervention evaluations.

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.

A Quantitative Test of an Implementation Framework in 38 VA Residential PTSD Programs.

PubMed

Cook, Joan M; Dinnen, Stephanie; Thompson, Richard; Ruzek, Josef; Coyne, James C; Schnurr, Paula P

2015-07-01

This study examines the implementation of two evidence-based psychotherapies, Prolonged Exposure (PE) and Cognitive Processing Therapy (CPT), in the Department of Veterans Affairs residential Posttraumatic Stress Disorder treatment programs. Two hundred and one providers from 38 programs completed an online survey concerning implementation of PE delivered on an individual basis and CPT delivered in individual and group formats. For PE, a supportive organizational context (dedicated time and resources, and incentives and mandates) and overall positive view of the treatment were related to its implementation. For both group and individual CPT, only the supportive organizational context was significantly associated with outcome. Implications for implementation efforts are discussed.

The Comparative Effectiveness of Cognitive Processing Therapy for Male Veterans Treated in a VHA Posttraumatic Stress Disorder Residential Rehabilitation Program

ERIC Educational Resources Information Center

Alvarez, Jennifer; McLean, Caitlin; Harris, Alex H. S.; Rosen, Craig S.; Ruzek, Josef I.; Kimerling, Rachel

2011-01-01

Objective: To examine the effectiveness of group cognitive processing therapy (CPT) relative to trauma-focused group treatment as usual (TAU) in the context of a Veterans Health Administration (VHA) posttraumatic stress disorder (PTSD) residential rehabilitation program. Method: Participants were 2 cohorts of male patients in the same program…

An Evaluation of Cognitive Processing Therapy for the Treatment of Posttraumatic Stress Disorder Related to Childhood Sexual Abuse

ERIC Educational Resources Information Center

Chard, Kathleen M.

2005-01-01

This study compared the effectiveness of cognitive processing therapy for sexual abuse survivors (CPT-SA) with that of the minimal attention (MA) given to a wait-listed control group. Seventy-one women were randomly assigned to 1 of the 2 groups. Participants were assessed at pretreatment and 3 times during posttreatment: immediately after…

8-CPT-cAMP/all-trans retinoic acid targets t(11;17) acute promyelocytic leukemia through enhanced cell differentiation and PLZF/RARα degradation

PubMed Central

Jiao, Bo; Ren, Zhi-Hong; Liu, Ping; Chen, Li-Juan; Shi, Jing-Yi; Dong, Ying; Ablain, Julien; Shi, Lin; Gao, Li; Hu, Jun-Pei; Ren, Rui-Bao; de Thé, Hugues; Chen, Zhu; Chen, Sai-Juan

2013-01-01

The refractoriness of acute promyelocytic leukemia (APL) with t(11;17)(q23;q21) to all-trans retinoic acid (ATRA)-based therapy concerns clinicians and intrigues basic researchers. By using a murine leukemic model carrying both promyelocytic leukemia zinc finger/retinoic acid receptor-α (PLZF/RARα) and RARα/PLZF fusion genes, we discovered that 8-chlorophenylthio adenosine-3′, 5′-cyclic monophosphate (8-CPT-cAMP) enhances cellular differentiation and improves gene trans-activation by ATRA in leukemic blasts. Mechanistically, in combination with ATRA, 8-CPT-cAMP activates PKA, causing phosphorylation of PLZF/RARα at Ser765 and resulting in increased dissociation of the silencing mediator for retinoic acid and thyroid hormone receptors/nuclear receptor corepressor from PLZF/RARα. This process results in changes of local chromatin and transcriptional reactivation of the retinoic acid pathway in leukemic cells. Meanwhile, 8-CPT-cAMP also potentiated ATRA-induced degradation of PLZF/RARα through its Ser765 phosphorylation. In vivo treatment of the t(11;17) APL mouse model demonstrated that 8-CPT-cAMP could significantly improve the therapeutic effect of ATRA by targeting a leukemia-initiating cell activity. This combined therapy, which induces enhanced differentiation and oncoprotein degradation, may benefit t(11;17) APL patients. PMID:23382200

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.

A Formative Evaluation of Two Evidence-Based Psychotherapies for PTSD In VA Residential Treatment Programs

PubMed Central

Cook, Joan M.; O’Donnell, Casey; Dinnen, Stephanie; Bernardy, Nancy; Rosenheck, Robert; Desai, Rani

2013-01-01

Thirty-eight U.S. Department of Veterans Affairs (VA) residential treatment programs for posttraumatic stress disorder (PTSD) participated in a formative evaluation of their programmatic services, including evidenced-based treatments (EBTs), between July 2008 and March 2011. Face-to-face qualitative interviews were conducted with over 250 staff by an independent psychologist along with on-site participant observations. This evaluation coincided with a national VA dissemination initiative to train providers in two EBTs for PTSD, Prolonged Exposure (PE) and Cognitive Processing Therapy (CPT). A substantial proportion of eligible (based on professional background) residential treatment providers received training in PE (37.4%) or CPT (64.2%), with 9.5% completing case consultation or becoming national trainers in each therapy respectively. In semi-structured interviews, providers reported that their clinical programs had adopted these EBTs at varying levels ranging from no adoption to every patient receiving the full protocol. Suggestions for improving the adoption of PE and CPT are noted, including distilling manualized treatments to essential common elements. PMID:23417875

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.

Cognitive processing therapy for posttraumatic stress disorder delivered to rural veterans via telemental health: a randomized noninferiority clinical trial.

PubMed

Morland, Leslie A; Mackintosh, Margaret-Anne; Greene, Carolyn J; Rosen, Craig S; Chard, Kathleen M; Resick, Patricia; Frueh, B Christopher

2014-05-01

To compare clinical and process outcomes of cognitive processing therapy-cognitive only version (CPT-C) delivered via videoteleconferencing (VTC) to in-person in a rural, ethnically diverse sample of veterans with posttraumatic stress disorder (PTSD). A randomized clinical trial with a noninferiority design was used to determine if providing CPT-C via VTC is effective and "as good as" in-person delivery. The study took place between March 2009 and June 2013. PTSD was diagnosed per DSM-IV. Participants received 12 sessions of CPT-C via VTC (n = 61) or in-person (n = 64). Assessments were administered at baseline, midtreatment, immediately posttreatment, and 3 and 6 months posttreatment. The primary clinical outcome was posttreatment PTSD severity, as measured by the Clinician-Administered PTSD Scale. Clinical and process outcomes found VTC to be noninferior to in-person treatment. Significant reductions in PTSD symptoms were identified at posttreatment (Cohen d = 0.78, P < .05) and maintained at 3- and 6-month follow-up (d = 0.73, P < .05 and d = 0.76, P < .05, respectively). High levels of therapeutic alliance, treatment compliance, and satisfaction and moderate levels of treatment expectancies were reported, with no differences between groups (for all comparisons, F < 1.9, P > .17). Providing CPT-C to rural residents with PTSD via VTC produced outcomes that were "as good as" in-person treatment. All participants demonstrated significant reductions in PTSD symptoms posttreatment and at follow-up. Results indicate that VTC can offer increased access to specialty mental health care for residents of rural or remote areas. ClinicalTrials.gov identifier: NCT00879255. © Copyright 2014 Physicians Postgraduate Press, Inc.

Treatment adherence in cognitive processing therapy for combat-related PTSD with history of mild TBI.

PubMed

Davis, Jeremy J; Walter, Kristen H; Chard, Kathleen M; Parkinson, R Bruce; Houston, Wes S

2013-02-01

This retrospective study examined treatment adherence in Cognitive Processing Therapy (CPT) for combat-related posttraumatic stress disorder (PTSD) in Veterans of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) with and without history of mild traumatic brain injury (mTBI). Medical record review of consecutive referrals to an outpatient PTSD clinic identified veterans diagnosed with combat-related PTSD who began treatment with CPT. The sample (N = 136) was grouped according to positive (n = 44) and negative (n = 92) mTBI history. Groups were compared in terms of presenting symptoms and treatment adherence. The groups were not different on a pretreatment measure of depression, but self-reported and clinician-rated PTSD symptoms were higher in veterans with history of mTBI. The treatment completion rate was greater than 61% in both groups. The number of sessions attended averaged 9.6 for the PTSD group and 7.9 for the mTBI/PTSD group (p = .05). Given the lack of marked group differences in treatment adherence, these initial findings suggest that standard CPT for PTSD may be a tolerable treatment for OEF/OIF veterans with a history of PTSD and mTBI as well as veterans with PTSD alone.

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.

Long-Term Outcomes of Cognitive-Behavioral Treatments for Posttraumatic Stress Disorder among Female Rape Survivors

ERIC Educational Resources Information Center

Resick, Patricia A.; Williams, Lauren F.; Suvak, Michael K.; Monson, Candice M.; Gradus, Jaimie L.

2012-01-01

Objective: We conducted a long-term follow-up (LTFU) assessment of participants from a randomized controlled trial comparing cognitive processing therapy (CPT) with prolonged exposure (PE) for posttraumatic stress disorder (PTSD). Competing hypotheses for positive outcomes (i.e., additional therapy, medication) were examined. Method:…

Effect of Group vs Individual Cognitive Processing Therapy in Active-Duty Military Seeking Treatment for Posttraumatic Stress Disorder: A Randomized Clinical Trial.

PubMed

Resick, Patricia A; Wachen, Jennifer Schuster; Dondanville, Katherine A; Pruiksma, Kristi E; Yarvis, Jeffrey S; Peterson, Alan L; Mintz, Jim; Borah, Elisa V; Brundige, Antoinette; Hembree, Elizabeth A; Litz, Brett T; Roache, John D; Young-McCaughan, Stacey

2017-01-01

Cognitive processing therapy (CPT), an evidence-based treatment for posttraumatic stress disorder (PTSD), has not been tested as an individual treatment among active-duty military. Group CPT may be an efficient way to deliver treatment. To determine the effects of CPT on PTSD and co-occurring symptoms and whether they differ when administered in an individual or a group format. In this randomized clinical trial, 268 active-duty servicemembers consented to assessment at an army medical center from March 8, 2012, to September 23, 2014, and were randomized to group or individual CPT. Inclusion criteria were PTSD after military deployment and stable medication therapy. Exclusion criteria consisted of suicidal or homicidal intent or psychosis. Data collection was completed on June 15, 2015. Analysis was based on intention to treat. Participants received CPT (the version excluding written accounts) in 90-minute group sessions of 8 to 10 participants (15 cohorts total; 133 participants) or 60-minute individual sessions (135 participants) twice weekly for 6 weeks. The 12 group and individual sessions were conducted concurrently. Primary measures were scores on the Posttraumatic Symptom Scale-Interview Version (PSS-I) and the stressor-specific Posttraumatic Stress Disorder Checklist (PCL-S); secondary measures were scores on the Beck Depression Inventory-II (BDI-II) and the Beck Scale for Suicidal Ideation (BSSI). Assessments were completed by independent evaluators masked to treatment condition at baseline and 2 weeks and 6 months after treatment. Among the 268 participants (244 men [91.0%]; 24 women [9.0%]; mean [SD] age, 33.2 [7.4] years), improvement in PTSD severity at posttreatment was greater when CPT was administered individually compared with the group format (mean [SE] difference on the PSS-I, -3.7 [1.4]; Cohen d = 0.6; P = .006). Significant improvements were maintained with the individual (mean [SE] PSS-I, -7.8 [1.0]; Cohen d = 1.3; mean [SE] PCL-S, -12.6 [1.4]; Cohen d = 1.2) and group (mean [SE] PSS-I, -4.0 [0.97]; Cohen d = 0.7; mean [SE] PCL-S, -6.3 [1.4]; Cohen d = 0.6) formats, with no differences in remission or severity of PTSD at the 6-month follow-up. Symptoms of depression and suicidal ideation did not differ significantly between formats. Individual treatment resulted in greater improvement in PTSD severity than group treatment. Depression and suicidal ideation improved equally with both formats. However, even among those receiving individual CPT, approximately 50% still had PTSD and clinically significant symptoms. In the military population, improving existing treatments such as CPT or developing new treatments is needed. clinicaltrials.gov identifier: NCT02173561.

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.

IN-HOME EXPOSURE THERAPY FOR VETERANS WITH POST TRAUMATIC STRESS DISORDER

DTIC Science & Technology

2016-10-01

study protocol. 5 Our treatment clinicians are providing the manual-guided evidence - based PE PTSD intervention. Therapists attend a weekly PE...with PTSD confirming the noninferiority of using CVT to deliver an evidence - based treatment (EBT) for PTSD, Cognitive Processing Therapy (CPT; Resick...g. Treatment clinicians will conduct a manual-guided evidence based PTSD intervention, Prolonged Exposure Therapy (PE), with approximately 175

Effectiveness of Prolonged Exposure and Cognitive Processing Therapy for U.S. Veterans With a History of Traumatic Brain Injury.

PubMed

Ragsdale, Katie A; Voss Horrell, Sarah C

2016-10-01

This retrospective analysis of previously existing nonrandomized clinical data examined the effectiveness of completing prolonged exposure (PE) or cognitive processing therapy (CPT) in a sample of 41 U.S. veterans at a Veterans Affairs medical center. The sample included 19 veterans with diagnoses of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) and 22 veterans with PTSD only. Diagnostic groups did not significantly differ on PTSD and depression symptom reduction, F(2, 36) = 0.05, p = .951; Pillai's trace = 0.00, partial η 2 = .00. Veterans who completed PE showed greater symptom reduction than those who completed CPT, F(2, 36) = 12.10, p < .001; Pillai's trace = 0.40, partial η 2 = .40, regardless of TBI status. Overall, our results suggested that TBI status should not preclude individuals from being offered trauma-focused PTSD treatment. Copyright © 2016 International Society for Traumatic Stress Studies.

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

Improving Health-care Delivery for Post-Traumatic Stress Disorder: An Interrelated Approach Leveraging Systems Engineering and Optimization

DTIC Science & Technology

2011-09-01

AND EXPERIMENTAL DESIGN ..........................................................................................................31   1...PRIMARY RESERCH QUESTION ............................................................41   C.   OBJECTIVE ACHIEVEMENT...Based Outpatient Clinic CPT Cognitive Processing Therapy DISE Distributed Information Systems Experimentation EBT Evidence-Based Treatment GMC

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

Mechanisms of Change in Cognitive Processing Therapy and Prolonged Exposure Therapy for PTSD: Preliminary Evidence for the Differential Effects of Hopelessness and Habituation

PubMed Central

Resick, Patricia A.

2013-01-01

The present study examined two potential mechanisms of change, hopelessness cognitions and habituation, in a randomized controlled trial of cognitive processing therapy (CPT) and prolonged exposure therapy (PE) for posttraumatic stress disorder (PTSD). Participants were 171 adult women with a current primary diagnosis of sexual assault related PTSD. The potential mechanisms were examined by evaluating the intraindividual change in hopelessness within the course of both treatments and subjective units distress (SUDS) ratings (a proxy for habituation) within the course of PE. The effects of intraindividual change in the proposed mechanisms were then examined on within-treatment changes in PTSD symptoms. Findings indicated that the participants assigned to the CPT treatment had significantly greater pre-post reductions in hopelessness than those assigned to PE and that the changes in hopelessness predicted changes in PTSD symptoms (R2 = .24). Intraindividual changes in SUDS ratings for participants in the PE treatment condition also predicted changes in PTSD symptoms and did so independently of the effect of changes in hopelessness. Future research should examine these mechanisms using more intensive methods of data collection that would permit the demonstration of temporality of change. PMID:24363472

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.

Adherence Rating Scale for Cognitive Processing Therapy - Cognitive Only: Analysis of Psychometric Properties.

PubMed

Dittmann, Clara; Müller-Engelmann, Meike; Resick, Patricia A; Gutermann, Jana; Stangier, Ulrich; Priebe, Kathlen; Fydrich, Thomas; Ludäscher, Petra; Herzog, Julia; Steil, Regina

2017-11-01

The assessment of therapeutic adherence is essential for accurately interpreting treatment outcomes in psychotherapy research. However, such assessments are often neglected. To fill this gap, we aimed to develop and test a scale that assessed therapeutic adherence to Cognitive Processing Therapy - Cognitive Only (CPT), which was adapted for a treatment study targeting patients with post-traumatic stress disorder and co-occurring borderline personality symptoms. Two independent, trained raters assessed 30 randomly selected treatment sessions involving seven therapists and eight patients who were treated in a multicentre randomized controlled trial. The inter-rater reliability for all items and the total score yielded good to excellent results (intraclass correlation coefficient [ICC] = 0.70 to 1.00). Cronbach's α was .56 for the adherence scale. Regarding content validity, three experts confirmed the relevance and appropriateness of each item. The adherence rating scale for the adapted version of CPT is a reliable instrument that can be helpful for interpreting treatment effects, analysing possible relationships between therapeutic adherence and treatment outcomes and teaching therapeutic skills.

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.

Changes in implementation of two evidence-based psychotherapies for PTSD in VA residential treatment programs: a national investigation.

PubMed

Cook, Joan M; Dinnen, Stephanie; Thompson, Richard; Simiola, Vanessa; Schnurr, Paula P

2014-04-01

There has been little investigation of the natural course of evidence-based treatments (EBTs) over time following the draw-down of initial implementation efforts. Thus, we undertook qualitative interviews with the providers at 38 U.S. Department of Veterans Affairs' residential treatment programs for posttraumatic stress disorder (PTSD) to understand implementation and adaptation of 2 EBTs, prolonged exposure (PE), and cognitive processing therapy (CPT), at 2 time points over a 4-year period. The number of providers trained in the therapies and level of training improved over time. At baseline, of the 179 providers eligible per VA training requirements, 65 (36.4%) had received VA training in PE and 111 (62.0%) in CPT with 17 (9.5%) completing case consultation or becoming national trainers in both PE and CPT. By follow-up, of the increased number of 190 eligible providers, 87 (45.8%) had received VA training in PE and 135 (71.1%) in CPT, with 69 (36.3%) and 81 (42.6%) achieving certification, respectively. Twenty-two programs (57.9%) reported no change in PE use between baseline and follow-up, whereas 16 (42.1%) reported an increase. Twenty-four (63.2%) programs reported no change in their use of CPT between baseline and follow-up, 12 (31.6%) programs experienced an increase, and 2 (5.2%) programs experienced a decrease in use. A significant number of providers indicated that they made modifications to the manuals (e.g., tailoring, lengthening). Reasons for adaptations are discussed. The need to dedicate time and resources toward the implementation of EBTs is noted. Published 2014. This article is a US Government work and is in the public domain in the USA.

Developmentally adapted cognitive processing therapy for adolescents and young adults with PTSD symptoms after physical and sexual abuse: study protocol for a randomized controlled trial.

PubMed

Rosner, Rita; König, Hans-Helmut; Neuner, Frank; Schmidt, Ulrike; Steil, Regina

2014-05-29

Although childhood sexual and/or physical abuse (CSA/CPA) is known to have severe psychopathological consequences, there is little evidence on psychotherapeutic interventions for adolescents and young adults suffering from post-traumatic stress disorder (PTSD). Equally sparse are data on moderators of treatment response on PTSD-related epigenetic changes, health care costs and loss of productivity, alterations in cognitive processing, and on how successful interventions affect all of these factors. Early treatment may prevent later (co)morbidity. In this paper, we present a study protocol for the evaluation of a newly developed psychotherapeutic manual for PTSD after CSA/CPA in adolescents and young adults - the Developmentally Adapted Cognitive Processing Therapy (D-CPT). In a multicenter randomized controlled trial (RCT) D-CPT is compared to treatment as usual (TAU). A sample of 90 adolescent outpatients aged 14 to 21 years will be randomized to one of these conditions. Four assessments will be carried out at baseline, at end of treatment, and 3 and 6 months after end of therapy. Each time, patients will be assessed via clinical interviews and a wide range of questionnaires. In addition to PTSD symptoms and comorbidities, we will evaluate moderators of treatment response, epigenetic profiles, direct and indirect costs of this disorder, and neurophysiological processing of threat cues in PTSD and their respective changes in the course of these two treatments (D-CPT and TAU). The study will provide new insights in the understudied field of PTSD in adolescents and young adults. A newly developed intervention will be evaluated in this therapeutically underserved population. Results will provide data on treatment efficacy, direct and indirect treatment costs, as well as on associations of treatment outcome and PTSD intensity both to epigenetic profiles and to the neurobiological processing of threat cues. Besides, they will help to learn more about the psychopathology and possible new objective correlates of PTSD. Germanctr.de identifier: DRKS00004787.

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.

Manualized therapy for PTSD: flexing the structure of cognitive processing therapy.

PubMed

Galovski, Tara E; Blain, Leah M; Mott, Juliette M; Elwood, Lisa; Houle, Timothy

2012-12-01

This study tested a modified cognitive processing therapy (MCPT) intervention designed as a more flexible administration of the protocol. Number of sessions was determined by client progress toward a priori defined end-state criteria, "stressor sessions" were inserted when necessary, and therapy was conducted by novice CPT clinicians. A randomized, controlled, repeated measures, semicrossover design was utilized (a) to test the relative efficacy of the MCPT intervention compared with a symptom-monitoring delayed treatment (SMDT) condition and (b) to assess within-group variation in change with a sample of 100 male and female interpersonal trauma survivors with posttraumatic stress disorder (PTSD). Hierarchical linear modeling analyses revealed that MCPT evidenced greater improvement on all primary (PTSD and depression) and secondary (guilt, quality of life, general mental health, social functioning, and health perceptions) outcomes compared with SMDT. After the conclusion of SMDT, participants crossed over to MCPT, resulting in a combined MCPT sample (n = 69). Of the 50 participants who completed MCPT, 58% reached end-state criteria prior to the 12th session, 8% at Session 12, and 34% between Sessions 12 and 18. Maintenance of treatment gains was found at the 3-month follow-up, with only 2 of the treated sample meeting criteria for PTSD. Use of stressor sessions did not result in poorer treatment outcomes. Findings suggest that individuals respond at a variable rate to CPT, with significant benefit from additional therapy when indicated and excellent maintenance of gains. Insertion of stressor sessions did not alter the efficacy of the therapy.

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

Comparative study of group treatments for posttraumatic stress disorder.

PubMed

Maxwell, Kendal; Callahan, Jennifer L; Holtz, Pamela; Janis, Beth M; Gerber, Monica M; Connor, Dana R

2016-12-01

Presented herein is a comparative study of group treatments for posttraumatic stress disorder (PTSD). In this study, an emerging intervention, memory specificity training (MeST), was compared with cognitive processing therapy (CPT) using standardized outcome measures of target symptoms (i.e., anxiety and depression from client perspective; memory specificity from independent rater perspective) and global functioning (independent rater perspective), as well as a process measure of expectancy (client perspective). Clients were assessed on 3 separate occasions: at baseline, posttreatment, and 3 months posttreatment. Adherence and treatment fidelity (independent rater perspective) were monitored throughout the course of both treatment conditions. Improvement in PTSD symptoms, depressive symptoms, and global functioning were similar between MeST and CPT; an increase in ability to specify memories upon retrieval was also similar between MeST and CPT. Positive reliable change was observed in both groups on all outcome measures. With respect to the primary target of PTSD symptoms, 88% of participants in both treatment groups moved into the functional distribution by posttreatment and maintained these gains at follow-up. Notably, compared with CPT, MeST required only half the dosage (i.e., number of sessions) to accomplish these gains. Illustrative vignettes from client-therapist exchanges are provided, and results are discussed in terms of the potential mechanisms of action. Implications for both clinical practice and clinical research are also included. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Veteran satisfaction and treatment preferences in response to a posttraumatic stress disorder specialty clinic orientation group.

PubMed

Schumm, Jeremiah A; Walter, Kristen H; Bartone, Anne S; Chard, Kathleen M

2015-06-01

To maximize accessibility to evidence-based treatments for posttraumatic stress disorder (PTSD), the United States Department of Veterans Affairs (VA) has widely disseminated cognitive processing therapy (CPT) and prolonged exposure (PE) therapy to VA clinicians. However, there is a lack of research on veteran preferences when presented with a range of psychotherapy and medication options. This study uses a mixed-method approach to explore veteran satisfaction with a VA PTSD specialty clinic pre-treatment orientation group, which provides education about available PTSD treatment options. This study also tested differences in treatment preference in response to the group. Participants were 183 US veterans. Most were White, male, and referred to the clinic by a VA provider. Results indicated high satisfaction with the group in providing an overview of services and helping to inform treatment choice. Most preferred psychotherapy plus medications (63.4%) or psychotherapy only (30.1%). Participants endorsed a significantly stronger preference for CPT versus other psychotherapies. PE was significantly preferred over nightmare resolution therapy and present-centered therapy, and both PE and cognitive-behavioral conjoint therapy were preferred over virtual reality exposure therapy. Results suggest that by informing consumers about evidence-based treatments for PTSD, pre-treatment educational approaches may increase consumer demand for these treatment options. Published by Elsevier Ltd.

Effect of spinal cord stimulation on myocardial perfusion reserve in patients with refractory angina pectoris.

PubMed

Saraste, Antti; Ukkonen, Heikki; Varis, Antti; Vasankari, Tuija; Tunturi, Satu; Taittonen, Markku; Rautakorpi, Pirkka; Luotolahti, Matti; Airaksinen, K E Juhani; Knuuti, Juhani

2015-04-01

Epidural spinal cord stimulation (SCS) provides symptom relief in refractory angina pectoris, but its mechanism of action remains incompletely understood. We studied effects of short-term SCS therapy on myocardial ischaemia tolerance, myocardial perfusion reserve (MPR), and endothelium-mediated vasodilatation induced by cold pressor test (CPT) in patients with refractory angina pectoris. We prospectively recruited 18 patients with refractory angina pectoris and studied them after implantation of SCS device at baseline before starting the therapy and after 3 weeks of continuous SCS therapy. Myocardial ischaemia was evaluated by dobutamine stress echocardiography. Global and regional myocardial blood flow (MBF) were measured using positron emission tomography and (15)O-water at rest, during adenosine stress, and in response to CPT. Systemic haemodynamics were comparable before and after 3 weeks of SCS at rest, during adenosine stress and during CPT. Appearance of angina pectoris induced by dobutamine stress was delayed after SCS therapy. Global MPR increased (P = 0.02) from 1.7 ± 0.6 at baseline to 2.0 ± 0.6 after 3-week SCS therapy. This was associated with a significant reduction in global MBF at rest and increase in MBF induced by adenosine in the ischaemic regions. Global MBF response to CPT was improved after SCS (0.27 ± 0.20 vs. 0.40 ± 0.15, P = 0.03). Short-term SCS therapy improved myocardial ischaemia tolerance, absolute MPR, and endothelium-mediated vasomotor function in refractory angina pectoris, indicating that this therapy can alleviate myocardial perfusion abnormalities in advanced CAD. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

CPT-11/bevacizumab for the treatment of refractory brain metastases in patients with HER2-neu-positive breast cancer.

PubMed

Sengupta, S; Rojas, R; Mahadevan, A; Kasper, E; Jeyapalan, S

2015-04-01

Nervous system relapse of patients with advanced HER2-neu-positive breast cancer is an increasing problem, with one-third of women developing brain metastases. Standard therapies using steroids, surgery and radiotherapy do not provide a lasting response. We evaluated CPT-11 and bevacizumab, which can both cross the blood-brain barrier, as combination therapy to treat HER2-neu-positive breast cancer with brain metastases.

Examination by EPR spectroscopy of free radicals in melanins isolated from A-375 cells exposed on valproic acid and cisplatin.

PubMed

Chodurek, Ewa; Zdybel, Magdalena; Pilawa, Barbara; Dzierzewicz, Zofia

2012-01-01

Drug binding by melanin biopolymers influence the effectiveness of the chemotherapy, radiotherapy and photodynamic therapy. Free radicals of melanins take part in formation of their complex with drugs. The aim of this work was to determine the effect of the two compounds: valproic acid (VPA) and cisplatin (CPT) on free radicals properties of melanin isolated from A-375 melanoma cells. Free radicals were examined by an X-band (9.3 GHz) electron paramagnetic resonance (EPR) spectroscopy. EPR spectra were measured for the model synthetic eumelanin - DOPA-melanin, the melanin isolated from the control A-375 cells and these cells treated by VPA, CPT and both VPA and CPT. For all the examined samples broad EPR lines (deltaBpp: 0.48-0.68 mT) with g-factors of 2.0045-2.0060 characteristic for o-semiquinone free radicals were observed. Free radicals concentrations (N) in the tested samples, g-factors, amplitudes (A), integral intensities (I) and linewidths (deltaBpp) of the EPR spectra, were analyzed. The EPR lines were homogeneously broadened. Continuous microwave saturation of the EPR spectra indicated that slow spin-lattice relaxation processes existed in all the tested melanin samples. The relatively slowest spin-lattice relaxation processes characterized melanin isolated from A-375 cells treated with both VPA and CPT. The changes of the EPR spectra with increasing microwave power in the range of 2.2-70 mW were evaluated. Free radicals concentrations in the melanin from A-375 cells were higher than in the synthetic DOPA-melanin. The strong increase of free radicals concentration in the melanin from A-375 cells was observed after their treating by VPA. CPT also caused the increase of free radicals concentrations in the examined natural melanin. The free radicals concentration in melanin isolated from A-375 cells treated with both VPA and CPT was slightly higher than those in melanin from the control cells.

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.

CPT-11/bevacizumab for the treatment of refractory brain metastases in patients with HER2–neu-positive breast cancer

PubMed Central

Sengupta, S.; Rojas, R.; Mahadevan, A.; Kasper, E.; Jeyapalan, S.

2015-01-01

Nervous system relapse of patients with advanced HER2–neu-positive breast cancer is an increasing problem, with one-third of women developing brain metastases. Standard therapies using steroids, surgery and radiotherapy do not provide a lasting response. We evaluated CPT-11 and bevacizumab, which can both cross the blood–brain barrier, as combination therapy to treat HER2–neu-positive breast cancer with brain metastases. PMID:26634139

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.

Augmenting CPT to Improve Sleep Impairment in PTSD: A Randomized Clinical Trial

PubMed Central

Galovski, Tara E.; Mott, Juliette; Blain, Leah M.; Elwood, Lisa; Gloth, Chelsea; Fletcher, Thomas

2015-01-01

Objective Despite the success of empirically supported treatments for posttraumatic stress disorder (PTSD), sleep impairment frequently remains refractory following treatment for PTSD. This single-site, randomized controlled trial examined the effectiveness of sleep-directed hypnosis as a complement to an empirically supported psychotherapy for PTSD (cognitive processing therapy; CPT). Method Participants completed either 3 weeks of hypnosis (n = 52) or a symptom monitoring control condition (n = 56) before beginning standard CPT. Multilevel modeling was used to investigate differential patterns of change to determine whether hypnosis resulted in improvements in sleep, PTSD, and depression. An intervening variable approach was then used to determine whether improvements in sleep achieved during hypnosis augmented change in PTSD and depression during CPT. Results After the initial phase of treatment (hypnosis or symptom monitoring), the hypnosis condition showed significantly greater improvement than the control condition in sleep and depression, but not PTSD. After CPT, both conditions demonstrated significant improvement in sleep and PTSD; however, the hypnosis condition demonstrated greater improvement in depressive symptoms. As sleep improved, there were corresponding improvements in PTSD and depression, with a stronger relationship between sleep and PTSD. Conclusion Hypnosis was effective in improving sleep impairment, but those improvements did not augment gains in PTSD recovery during the trauma-focused intervention. Public Health Significance: This study suggests that hypnosis may be a viable treatment option in a stepped-care approach for treating sleep impairment in individuals suffering from PTSD. PMID:26689303

Physical therapy for airway clearance improves cardiac autonomic modulation in children with acute bronchiolitis

PubMed Central

Jacinto, Cynthia P.; Gastaldi, Ada C.; Aguiar, Daniela Y.; Maida, Karina D.; Souza, Hugo C. D.

2013-01-01

Background The effects of physical therapy on heart rate variability (HRV), especially in children, are still inconclusive. Objective We investigated the effects of conventional physical therapy (CPT) for airway clearance and nasotracheal suction on the HRV of pediatric patients with acute bronchiolitis. Method 24 children were divided into two groups: control group (CG, n=12) without respiratory diseases and acute bronchiolitis group (BG, n=12). The heart rate was recorded in the BG at four different moments: basal recording (30 minutes), 5 minutes after the CPT (10 minutes), 5 minutes after nasotracheal suction (10 minutes), and 40 minutes after nasotracheal suction (30 minutes). The CG was subjected to the same protocol, except for nasotracheal suction. To assess the HRV, we used spectrum analysis, which decomposes the heart rate oscillations into frequency bands: low frequency (LF=0.04-0.15Hz), which corresponds mainly to sympathetic modulation; and high frequency (HF=0.15-1.2Hz), corresponding to vagal modulation. Results Under baseline conditions, the BG showed higher values in LF oscillations, lower values in HF oscillations, and increased LF/HF ratio when compared to the CG. After CPT, the values for HRV in the BG were similar to those observed in the CG during basal recording. Five minutes after nasotracheal suction, the BG showed a decrease in LF and HF oscillations; however, after 40 minutes, the values were similar to those observed after application of CPT. Conclusions The CPT and nasotracheal suction, both used for airway clearance, promote improvement in autonomic modulation of HRV in children with acute bronchiolitis. PMID:24271093

Study protocol for a randomised controlled trial of cognitive processing therapy for post-traumatic stress disorder among Japanese patients: the Safety, Power, Intimacy, Esteem, Trust (SPINET) study

PubMed Central

Ito, Masaya; Horikoshi, Masaru; Resick, Patricia A; Katayanagi, Akiko; Miyamae, Mitsuhiro; Takagishi, Yuriko; Takebayashi, Yoshitake; Kanie, Ayako; Hirabayashi, Naotsugu; Furukawa, Toshiaki A

2017-01-01

Introduction Cognitive processing therapy (CPT) is widely regarded as a safe and effective first-line treatment for individuals with post-traumatic stress disorder (PTSD); however, no comparative studies have been conducted to examine the treatment outcomes in an Asian population. The aim of the present trial is to investigate the efficacy of CPT (individual format) as a treatment for PTSD in a population of Japanese patients. Methods and analysis A 16-week, single-centre, assessor-masked, randomised, parallel-group superiority trial has been designed to compare the efficacy of CPT in conjunction with treatment as usual (mostly pharmacotherapy and clinical monitoring) versus treatment as usual alone. The Clinician-Administered PTSD Scale for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) will be our primary outcome measure of the post-traumatic stress symptoms at 17 weeks, whereas the PTSD Checklist for DSM-5 and determination of the operationally defined responder status will be used to assess the secondary outcomes. An estimated sample size of 29 participants in each group will be required to detect an expected effect size of 1.4 (95% CI 0.85 to 1.95). Ethics and dissemination The institutional review board at the National Center of Neurology and Psychiatry in Japan approved this study. The results of this clinical trial will be presented at conferences and disseminated through publication in a peer-reviewed journal. Trial registration number UMIN000021670 (registered on 1 April 2016). PMID:28667201

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

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

Impediments to enhancement of CPT-11 anticancer activity by E. coli directed beta-glucuronidase therapy.

PubMed

Hsieh, Yuan-Ting; Chen, Kai-Chuan; Cheng, Chiu-Min; Cheng, Tian-Lu; Tao, Mi-Hua; Roffler, Steve R

2015-01-01

CPT-11 is a camptothecin analog used for the clinical treatment of colorectal adenocarcinoma. CPT-11 is converted into the therapeutic anti-cancer agent SN-38 by liver enzymes and can be further metabolized to a non-toxic glucuronide SN-38G, resulting in low SN-38 but high SN-38G concentrations in the circulation. We previously demonstrated that adenoviral expression of membrane-anchored beta-glucuronidase could promote conversion of SN-38G to SN-38 in tumors and increase the anticancer activity of CPT-11. Here, we identified impediments to effective tumor therapy with E. coli that were engineered to constitutively express highly active E. coli beta-glucuronidase intracellularly to enhance the anticancer activity of CPT-11. The engineered bacteria, E. coli (lux/βG), could hydrolyze SN-38G to SN-38, increased the sensitivity of cultured tumor cells to SN-38G by about 100 fold and selectively accumulated in tumors. However, E. coli (lux/βG) did not more effectively increase CPT-11 anticancer activity in human tumor xenografts as compared to non-engineered E. coli. SN-38G conversion to SN-38 by E. coli (lux/βG) appeared to be limited by slow uptake into bacteria as well as by segregation of E. coli in necrotic regions of tumors that may be relatively inaccessible to systemically-administered drug molecules. Studies using a fluorescent glucuronide probe showed that significantly greater glucuronide hydrolysis could be achieved in mice pretreated with E. coli (lux/βG) by direct intratumoral injection of the glucuronide probe or by intratumoral lysis of bacteria to release intracellular beta-glucuronidase. Our study suggests that the distribution of beta-glucuronidase, and possibly other therapeutic proteins, in the tumor microenvironment might be an important barrier for effective bacterial-based tumor therapy. Expression of secreted therapeutic proteins or induction of therapeutic protein release from bacteria might therefore be a promising strategy to enhance anti-tumor activity.

Impediments to Enhancement of CPT-11 Anticancer Activity by E. coli Directed Beta-Glucuronidase Therapy

PubMed Central

Hsieh, Yuan-Ting; Chen, Kai-Chuan; Cheng, Chiu-Min; Cheng, Tian-Lu; Tao, Mi-Hua; Roffler, Steve R.

2015-01-01

CPT-11 is a camptothecin analog used for the clinical treatment of colorectal adenocarcinoma. CPT-11 is converted into the therapeutic anti-cancer agent SN-38 by liver enzymes and can be further metabolized to a non-toxic glucuronide SN-38G, resulting in low SN-38 but high SN-38G concentrations in the circulation. We previously demonstrated that adenoviral expression of membrane-anchored beta-glucuronidase could promote conversion of SN-38G to SN-38 in tumors and increase the anticancer activity of CPT-11. Here, we identified impediments to effective tumor therapy with E. coli that were engineered to constitutively express highly active E. coli beta-glucuronidase intracellularly to enhance the anticancer activity of CPT-11. The engineered bacteria, E. coli (lux/βG), could hydrolyze SN-38G to SN-38, increased the sensitivity of cultured tumor cells to SN-38G by about 100 fold and selectively accumulated in tumors. However, E. coli (lux/βG) did not more effectively increase CPT-11 anticancer activity in human tumor xenografts as compared to non-engineered E. coli. SN-38G conversion to SN-38 by E. coli (lux/βG) appeared to be limited by slow uptake into bacteria as well as by segregation of E. coli in necrotic regions of tumors that may be relatively inaccessible to systemically-administered drug molecules. Studies using a fluorescent glucuronide probe showed that significantly greater glucuronide hydrolysis could be achieved in mice pretreated with E. coli (lux/βG) by direct intratumoral injection of the glucuronide probe or by intratumoral lysis of bacteria to release intracellular beta-glucuronidase. Our study suggests that the distribution of beta-glucuronidase, and possibly other therapeutic proteins, in the tumor microenvironment might be an important barrier for effective bacterial-based tumor therapy. Expression of secreted therapeutic proteins or induction of therapeutic protein release from bacteria might therefore be a promising strategy to enhance anti-tumor activity. PMID:25688562

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.

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

Aerosol Therapy for Obstructive Lung Diseases

PubMed Central

2011-01-01

Inhaled aerosol therapies are the mainstay of treatment of obstructive lung diseases. Aerosol devices deliver drugs rapidly and directly into the airways, allowing high local drug concentrations while limiting systemic toxicity. While numerous clinical trials, literature reviews, and expert panel guidelines inform the choice of inhalational drugs, deciding which aerosol device (ie, metered-dose inhaler, nebulizer, or dry powder inhaler) best suits a given patient and clinical setting can seem arbitrary and confusing. Similar confusion regarding Current Procedural Terminology (CPT) coding for administration of aerosol therapies can lead to lost revenue from underbilling and wasted administrative effort handling denied claims. This article reviews the aerosol devices currently available, discusses their relative merits in various clinical settings, and summarizes appropriate CPT coding for aerosol therapy. PMID:21896522

Enhancing Assessments of Mental Health Programs and Program Planning

DTIC Science & Technology

2012-06-01

Eye Movement Desensitization Reprocessing ( EMDR ) 3. Cognitive Processing Therapy (CPT) 4...Department of Defense Instruction EMDR Eye Movement Desensitization Reprocessing FEA Front End Assessment FM Field Manual FOB Forward Operating Base...1.26 N = 47 EMDR 1.04 N = 10 Group .46 N = 6 Other -.53-.78 N = 4 (some ns) Source: Roberts and Schnurr 2012. Slide 64. Large Number of Studies

Mental illness stigma and engagement in an implementation trial for Cognitive Processing Therapy at a diverse community health center: a qualitative investigation.

PubMed

Valentine, Sarah E; Dixon, Louise; Borba, Christina P C; Shtasel, Derri L; Marques, Luana

The present study aimed to describe associations between various types of mental health stigma and help-seeking behaviors among ethnically diverse clients with posttraumatic stress disorder (PTSD) served by an urban community health clinic. The present study draws qualitative data from a parent National Institute of Mental Health Study that aims to identify barriers and facilitators of implementing Cognitive Processing Therapy (CPT) for PTSD. A total of 24 participants from the initial phase of the trial were included in the present study. Mental health stigma emerged as one notable barrier to seeking mental health treatment, as participants described how experiences of environment-level stigma, internalized (self-)stigma and perceived (felt) stigma from their family, friends and previous healthcare providers influenced their decisions to seek care. Despite these barriers to help seeking, many clients also reported that positive interactions with informal and formal support systems, and encouragement from study therapists, helped to combat mental health stigma and facilitate decisions to participate in an implementation trial for CPT. Findings suggest that providers in community health settings may need to attend directly to stigma at the initiation of mental health treatment.

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

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

Examining the effectiveness of an intensive, 2-week treatment program for military personnel and veterans with PTSD: Results of a pilot, open-label, prospective cohort trial.

PubMed

Bryan, Craig J; Leifker, Feea R; Rozek, David C; Bryan, AnnaBelle O; Reynolds, Mira L; Oakey, D Nicolas; Roberge, Erika

2018-06-19

This study aimed to examine the effectiveness of cognitive processing therapy (CPT) for posttraumatic stress disorder (PTSD) when administered on a daily basis during a 2-week period of time. In an open-label, prospective cohort pilot trial, 20 U.S. military personnel and veterans diagnosed with PTSD or subthreshold PTSD participated in 12 daily sessions of CPT. Primary outcomes included Clinician Administered PTSD Scale for DSM-5 and PTSD Checklist for DSM-5 scores. Secondary outcomes included Patient Health Questionnaire-8 and Beck Scale for Suicide Ideation (BSSI) scores. Interviews and self-report scales were completed at pretreatment, posttreatment, and 6 months after the treatment. Relative to baseline, PTSD symptom severity and rates of PTSD diagnosis were significantly reduced at posttreatment and 6-month follow-up. Depression symptom severity did not significantly improve, but suicide ideation significantly decreased at 6-month follow-up. Daily administration of CPT is associated with significant reductions in PTSD and suicide ideation. © 2018 Wiley Periodicals, Inc.

Improving and sustaining delivery of CPT for PTSD in mental health systems: a cluster randomized trial.

PubMed

Wiltsey Stirman, Shannon; Finley, Erin P; Shields, Norman; Cook, Joan; Haine-Schlagel, Rachel; Burgess, James F; Dimeff, Linda; Koerner, Kelly; Suvak, Michael; Gutner, Cassidy A; Gagnon, David; Masina, Tasoula; Beristianos, Matthew; Mallard, Kera; Ramirez, Vanessa; Monson, Candice

2017-03-06

Large-scale implementation of evidence-based psychotherapies (EBPs) such as cognitive processing therapy (CPT) for posttraumatic stress disorder can have a tremendous impact on mental and physical health, healthcare utilization, and quality of life. While many mental health systems (MHS) have invested heavily in programs to implement EBPs, few eligible patients receive EBPs in routine care settings, and clinicians do not appear to deliver the full treatment protocol to many of their patients. Emerging evidence suggests that when CPT and other EBPs are delivered at low levels of fidelity, clinical outcomes are negatively impacted. Thus, identifying strategies to improve and sustain the delivery of CPT and other EBPs is critical. Existing literature has suggested two competing strategies to promote sustainability. One emphasizes fidelity to the treatment protocol through ongoing consultation and fidelity monitoring. The other focuses on improving the fit and effectiveness of these treatments through appropriate adaptations to the treatment or the clinical setting through a process of data-driven, continuous quality improvement. Neither has been evaluated in terms of impact on sustained implementation. To compare these approaches on the key sustainability outcomes and provide initial guidance on sustainability strategies, we propose a cluster randomized trial with mental health clinics (n = 32) in three diverse MHSs that have implemented CPT. Cohorts of clinicians and clinical managers will participate in 1 year of a fidelity oriented learning collaborative or 1 year of a continuous quality improvement-oriented learning collaborative. Patient-level PTSD symptom change, CPT fidelity and adaptation, penetration, and clinics' capacity to deliver EBP will be examined. Survey and interview data will also be collected to investigate multilevel influences on the success of the two learning collaborative strategies. This research will be conducted by a team of investigators with expertise in CPT implementation, mixed method research strategies, quality improvement, and implementation science, with input from stakeholders in each participating MHS. It will have broad implications for supporting ongoing delivery of EBPs in mental health and healthcare systems and settings. The resulting products have the potential to significantly improve efforts to ensure ongoing high quality implementation and consumer access to EBPs. NCT02449421 . Registered 02/09/2015.

Long-term Results of the UCSF-LBNL Randomized Trial: Charged Particle With Helium Ion Versus Iodine-125 Plaque Therapy for Choroidal and Ciliary Body Melanoma

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

Mishra, Kavita K., E-mail: Kavita.mishra@ucsf.edu; Quivey, Jeanne M.; Daftari, Inder K.

Purpose: Relevant clinical data are needed given the increasing national interest in charged particle radiation therapy (CPT) programs. Here we report long-term outcomes from the only randomized, stratified trial comparing CPT with iodine-125 plaque therapy for choroidal and ciliary body melanoma. Methods and Materials: From 1985 to 1991, 184 patients met eligibility criteria and were randomized to receive particle (86 patients) or plaque therapy (98 patients). Patients were stratified by tumor diameter, thickness, distance to disc/fovea, anterior extension, and visual acuity. Tumors close to the optic disc were included. Local tumor control, as well as eye preservation, metastases due tomore » melanoma, and survival were evaluated. Results: Median follow-up times for particle and plaque arm patients were 14.6 years and 12.3 years, respectively (P=.22), and for those alive at last follow-up, 18.5 and 16.5 years, respectively (P=.81). Local control (LC) for particle versus plaque treatment was 100% versus 84% at 5 years, and 98% versus 79% at 12 years, respectively (log rank: P=.0006). If patients with tumors close to the disc (<2 mm) were excluded, CPT still resulted in significantly improved LC: 100% versus 90% at 5 years and 98% versus 86% at 12 years, respectively (log rank: P=.048). Enucleation rate was lower after CPT: 11% versus 22% at 5 years and 17% versus 37% at 12 years, respectively (log rank: P=.01). Using Cox regression model, likelihood ratio test, treatment was the most important predictor of LC (P=.0002) and eye preservation (P=.01). CPT was a significant predictor of prolonged disease-free survival (log rank: P=.001). Conclusions: Particle therapy resulted in significantly improved local control, eye preservation, and disease-free survival as confirmed by long-term outcomes from the only randomized study available to date comparing radiation modalities in choroidal and ciliary body melanoma.« less

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.

Design of VA Cooperative Study #591: CERV-PTSD, comparative effectiveness research in veterans with PTSD.

PubMed

Schnurr, Paula P; Chard, Kathleen M; Ruzek, Josef I; Chow, Bruce K; Shih, Mei-Chiung; Resick, Patricia A; Foa, Edna B; Marx, Brian P; Huang, Grant D; Lu, Ying

2015-03-01

CERV-PTSD is a randomized controlled trial of two of the most effective treatments for PTSD, Prolonged Exposure (PE) and Cognitive Processing Therapy (CPT). Despite solid evidence that both treatments are effective, there is limited evidence about their effectiveness relative to one another. The primary objective is to compare the effectiveness of PE and CPT for reducing PTSD symptom severity in a healthcare system that offers both treatments. The secondary objective is to compare the effectiveness of PE and CPT for reducing the severity of comorbid mental health problems and service utilization as well as improving functioning and quality of life. The tertiary objective is to examine whether discrepancy between patient preferences and treatment assignment reduces the effectiveness of each treatment. Exploratory analyses will examine whether demographic and clinical characteristics predict differential response to PE and CPT. The study is designed to randomize 900 male and female veterans with PTSD due to any traumatic military event to receive PE or CPT. The standard dose of treatment is 12 weekly sessions but veterans who improve more rapidly may finish in fewer sessions and veterans who improve more slowly may have additional sessions. The primary outcome is improvement in PTSD symptoms, measured during and after treatment and then 3 and 6 months later. As a large multi-site trial with men and women, CERV-PTSD is designed to advance the delivery of care for PTSD by providing conclusive information about whether one treatment is better than the other, overall, and for different types of patients. Published by Elsevier Inc.

Study protocol for a randomised controlled trial of cognitive processing therapy for post-traumatic stress disorder among Japanese patients: the Safety, Power, Intimacy, Esteem, Trust (SPINET) study.

PubMed

Ito, Masaya; Horikoshi, Masaru; Resick, Patricia A; Katayanagi, Akiko; Miyamae, Mitsuhiro; Takagishi, Yuriko; Takebayashi, Yoshitake; Kanie, Ayako; Hirabayashi, Naotsugu; Furukawa, Toshiaki A

2017-06-30

Cognitive processing therapy (CPT) is widely regarded as a safe and effective first-line treatment for individuals with post-traumatic stress disorder (PTSD); however, no comparative studies have been conducted to examine the treatment outcomes in an Asian population. The aim of the present trial is to investigate the efficacy of CPT (individual format) as a treatment for PTSD in a population of Japanese patients. A 16-week, single-centre, assessor-masked, randomised, parallel-group superiority trial has been designed to compare the efficacy of CPT in conjunction with treatment as usual (mostly pharmacotherapy and clinical monitoring) versus treatment as usual alone. The Clinician-Administered PTSD Scale for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) will be our primary outcome measure of the post-traumatic stress symptoms at 17 weeks, whereas the PTSD Checklist for DSM-5 and determination of the operationally defined responder status will be used to assess the secondary outcomes. An estimated sample size of 29 participants in each group will be required to detect an expected effect size of 1.4 (95% CI 0.85 to 1.95). The institutional review board at the National Center of Neurology and Psychiatry in Japan approved this study. The results of this clinical trial will be presented at conferences and disseminated through publication in a peer-reviewed journal. UMIN000021670 (registered on 1 April 2016). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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).

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.

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.

Adaptive Disclosure: A Combat Specific PTSD Treatment

DTIC Science & Technology

2017-03-31

to determine whether AD is as least as effective as CPT, cognitive only version (CPT-C), in terms of its impact on deployment-related psychological ...be used to determine treatment efficacy. 15. SUBJECT TERMS Active-duty, Marine Corps, Posttraumatic stress disorder, Cognitive Therapy 16...the early stages of the wars suggest that 10-18% of combat troops experience deployment-related psychological health problems, such as posttraumatic

Fluorescent supramolecular micelles for imaging-guided cancer therapy

NASA Astrophysics Data System (ADS)

Sun, Mengmeng; Yin, Wenyan; Dong, Xinghua; Yang, Wantai; Zhao, Yuliang; Yin, Meizhen

2016-02-01

A novel smart fluorescent drug delivery system composed of a perylene diimide (PDI) core and block copolymer poly(d,l-lactide)-b-poly(ethyl ethylene phosphate) is developed and named as PDI-star-(PLA-b-PEEP)8. The biodegradable PDI-star-(PLA-b-PEEP)8 is a unimolecular micelle and can self-assemble into supramolecular micelles, called as fluorescent supramolecular micelles (FSMs), in aqueous media. An insoluble drug camptothecin (CPT) can be effectively loaded into the FSMs and exhibits pH-responsive release. Moreover, the FSMs with good biocompatibility can also be employed as a remarkable fluorescent probe for cell labelling because the maximum emission of PDI is beneficial for bio-imaging. The flow cytometry and confocal laser scanning microscopy analysis demonstrate that the micelles are easily endocytosed by cancer cells. In vitro and in vivo tumor growth-inhibitory studies reveal a better therapeutic effect of FSMs after CPT encapsulation when compared with the free CPT drug. The multifunctional FSM nanomedicine platform as a nanovehicle has great potential for fluorescence imaging-guided cancer therapy.A novel smart fluorescent drug delivery system composed of a perylene diimide (PDI) core and block copolymer poly(d,l-lactide)-b-poly(ethyl ethylene phosphate) is developed and named as PDI-star-(PLA-b-PEEP)8. The biodegradable PDI-star-(PLA-b-PEEP)8 is a unimolecular micelle and can self-assemble into supramolecular micelles, called as fluorescent supramolecular micelles (FSMs), in aqueous media. An insoluble drug camptothecin (CPT) can be effectively loaded into the FSMs and exhibits pH-responsive release. Moreover, the FSMs with good biocompatibility can also be employed as a remarkable fluorescent probe for cell labelling because the maximum emission of PDI is beneficial for bio-imaging. The flow cytometry and confocal laser scanning microscopy analysis demonstrate that the micelles are easily endocytosed by cancer cells. In vitro and in vivo tumor growth-inhibitory studies reveal a better therapeutic effect of FSMs after CPT encapsulation when compared with the free CPT drug. The multifunctional FSM nanomedicine platform as a nanovehicle has great potential for fluorescence imaging-guided cancer therapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00450d

Proton Radiation Therapy for Pediatric Medulloblastoma and Supratentorial Primitive Neuroectodermal Tumors: Outcomes for Very Young Children Treated With Upfront Chemotherapy

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

Jimenez, Rachel B., E-mail: rbjimenez@partners.org; Sethi, Roshan; Depauw, Nicolas

Purpose: To report the early outcomes for very young children with medulloblastoma or supratentorial primitive neuroectodermal tumor (SPNET) treated with upfront chemotherapy followed by 3-dimensional proton radiation therapy (3D-CPT). Methods and Materials: All patients aged <60 months with medulloblastoma or SPNET treated with chemotherapy before 3D-CPT from 2002 to 2010 at our institution were included. All patients underwent maximal surgical resection, chemotherapy, and adjuvant 3D-CPT with either craniospinal irradiation followed by involved-field radiation therapy or involved-field radiation therapy alone. Results: Fifteen patients (median age at diagnosis, 35 months) were treated with high-dose chemotherapy and 3D-CPT. Twelve of 15 patients hadmore » medulloblastoma; 3 of 15 patients had SPNET. Median time from surgery to initiation of radiation was 219 days. Median craniospinal irradiation dose was 21.6 Gy (relative biologic effectiveness); median boost dose was 54.0 Gy (relative biologic effectiveness). At a median of 39 months from completion of radiation, 1 of 15 was deceased after a local failure, 1 of 15 had died from a non-disease-related cause, and the remaining 13 of 15 patients were alive without evidence of disease recurrence. Ototoxicity and endocrinopathies were the most common long-term toxicities, with 2 of 15 children requiring hearing aids and 3 of 15 requiring exogenous hormones. Conclusions: Proton radiation after chemotherapy resulted in good disease outcomes for a small cohort of very young patients with medulloblastoma and SPNET. Longer follow-up and larger numbers of patients are needed to assess long-term outcomes and late toxicity.« less

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.

Apatinib + CPT-11 + S-1 for treatment of refractory brain metastases in patient with triple-negative breast cancer: Case report and literature review.

PubMed

Hu, Ting; Liu, Cuiwei; Li, Qiuhui; Xiong, Jie; Ma, Yuxi; Wu, Gang; Zhao, Yanxia

2018-04-01

Brain metastasis (BM) is a rising challenge in forward-looking oncology, as its treatment choices are very limited, especially, after the failure of local treatment schemes. We report on a 39-year-old Chinese woman who was diagnosed with stage IV triple-negative breast cancer(TNBC) with multiple brain, lung, and bone metastases. She had previously, undergone whole-brain radiation therapy. Paclitaxel, platinum, UTD1, capecitabine, gemcitabine, vinorelbine, and single-agent apatinib were then administered as first- to fifth-line therapies. She exhibited progression each time after a short period of disease stabilization. Triple-negative breast cancer. The patient chose treatment with apatinib+CPT-11+S-1 as the sixth-line therapy. A remarkable response of the brain, and lung metastases, and alleviation of the brain edema were achieved, and these effects persisted for 7 months. We describe the significant anti-tumor effect of apatinib + CPT-11 + S-1 against BMs from breast cancer. This report is the first to suggest potential approaches to BM treatment using this scheme and describes the effects of an apatinib-containing regimen on BMs.

Apatinib + CPT-11 + S-1 for treatment of refractory brain metastases in patient with triple-negative breast cancer

PubMed Central

Hu, Ting; Liu, Cuiwei; Li, Qiuhui; Xiong, Jie; Ma, Yuxi; Wu, Gang; Zhao, Yanxia

2018-01-01

Abstract Rationale: Brain metastasis (BM) is a rising challenge in forward-looking oncology, as its treatment choices are very limited, especially, after the failure of local treatment schemes. Patient concerns: We report on a 39-year-old Chinese woman who was diagnosed with stage IV triple-negative breast cancer(TNBC) with multiple brain, lung, and bone metastases. She had previously, undergone whole-brain radiation therapy. Paclitaxel, platinum, UTD1, capecitabine, gemcitabine, vinorelbine, and single-agent apatinib were then administered as first- to fifth-line therapies. She exhibited progression each time after a short period of disease stabilization. Diagnoses: Triple-negative breast cancer. Interventions: The patient chose treatment with apatinib+CPT-11+S-1 as the sixth-line therapy. Outcomes: A remarkable response of the brain, and lung metastases, and alleviation of the brain edema were achieved, and these effects persisted for 7 months. Lessons: We describe the significant anti-tumor effect of apatinib + CPT-11 + S-1 against BMs from breast cancer. This report is the first to suggest potential approaches to BM treatment using this scheme and describes the effects of an apatinib-containing regimen on BMs. PMID:29642175

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.

Development and evaluation of camptothecin loaded polymer stabilized nanoemulsion: Targeting potential in 4T1-breast tumour xenograft model.

PubMed

Sugumaran, Abimanyu; Ponnusamy, Chandrasekar; Kandasamy, Palanivel; Krishnaswami, Venkateshwaran; Palanichamy, Rajaguru; Kandasamy, Ruckmani; Lakshmanan, Manikandan; Natesan, Subramanian

2018-04-30

Targeted delivery of anticancer agents is poised to improve cancer therapy, for which polymers can serve as targeting ligands or nanocarriers for chemotherapeutic agents. In this study, we have developed and evaluated the efficacy of a camptothecin (CPT)-loaded polymer stabilized nanoemulsion (PSNE) for the passive targeted delivery to breast cancer. Based on the pseudo-ternary phase diagrams, PSNEs were developed using capmul MCM:poloxamer 407 (4:1), solutol HS 15:simulsol P23 (1:2) and water. CPT polymer mixture was developed by solvent evaporation technique. The PSNEs were characterized for droplet size distribution, plasma protein adsorption, drug release, in-vivo targeting potential, hemolytic potential, cytotoxicity, genotoxicity, in-vivo biodistribution and CPT lactone ring stability. The developed PSNEs showed uniform droplet distribution, extended drug release (76.59±6.12% at 24h), acceptable hemolytic potential, significant cytotoxicity (IC 50 =176±4.3ng/mL) and genotoxicity against MCF-7 cancer cells but low DNA damage potential in human peripheral blood lymphocytes. The efficiency of PSNEs for the targeted delivery of CPT into the tumour regions was documented in 4T1-breast tumour xenografted BALB/c mice. In-vivo biodistribution study shows that 7105.84±568.46ng/g of CPT was passively targeted from PSNE to breast cancer tissue. About 80% of the lactone form was stable for 24h. Taken together, our study provides a promising strategy for developing PSNE-targeted drug delivery system for the breast cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

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.

Acid-activatable oxidative stress-inducing polysaccharide nanoparticles for anticancer therapy.

PubMed

Yoo, Wooyoung; Yoo, Donghyuck; Hong, Eunmi; Jung, Eunkyeong; Go, Yebin; Singh, S V Berwin; Khang, Gilson; Lee, Dongwon

2018-01-10

Drug delivery systems have been extensively developed to enhance the therapeutic efficacy of drugs by altering their pharmacokinetics and biodistribution. However, the use of high quantities of drug delivery systems can cause toxicity due to their poor metabolism and elimination. In this study, we developed polysaccharide-based drug delivery systems which exert potent therapeutic effects and could display synergistic therapeutic effects with drug payloads, leading to dose reduction. Cinnamaldehyde, a major component of cinnamon is known to induce anticancer activity by generating ROS (reactive oxygen species). We developed cinnamaldehyde-conjugated maltodextrin (CMD) as a polymeric prodrug of cinnamaldehyde and a drug carrier. Cinnamaldehyde was conjugated to the hydroxyl groups of maltodextrin via acid-cleavable acetal linkages, allowing facile formulation of nanoparticles and drug encapsulation. CMD nanoparticles induced acid-triggered ROS generation to induce apoptotic cell death. Camptothecin (CPT) was used as a model drug to investigate the potential of CMD nanoparticles as a drug carrier and also evaluate the synergistic anticancer effects with CMD nanoparticles. CPT-loaded CMD nanoparticles exhibited significantly higher anticancer activity than empty CMD nanoparticles and CPT alone in the study of mouse xenograft models, demonstrating the synergistic therapeutic effects of CMD with CPT. Taken together, we believe that CMD nanoparticles hold tremendous potential as a polymeric prodrug of cinnamaldehyde and a drug carrier in anticancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Changes in social adjustment with cognitive processing therapy: effects of treatment and association with PTSD symptom change.

PubMed

Monson, Candice M; Macdonald, Alexandra; Vorstenbosch, Valerie; Shnaider, Philippe; Goldstein, Elizabeth S R; Ferrier-Auerbach, Amanda G; Mocciola, Katharine E

2012-10-01

The current study sought to determine if different spheres of social adjustment, social and leisure, family, and work and income improved immediately following a course of cognitive processing therapy (CPT) when compared with those on a waiting list in a sample of 46 U.S. veterans diagnosed with posttraumatic stress disorder (PTSD). We also sought to determine whether changes in different PTSD symptom clusters were associated with changes in these spheres of social adjustment. Overall social adjustment, extended family relationships, and housework completion significantly improved in the CPT versus waiting-list condition, η(2) = .08 to .11. Hierarchical multiple regression analyses revealed that improvements in total clinician-rated PTSD symptoms were associated with improvements in overall social and housework adjustment. When changes in reexperiencing, avoidance, emotional numbing, and hyperarousal were all in the model accounting for changes in total social adjustment, improvements in emotional numbing symptoms were associated with improvements in overall social, extended family, and housework adjustment (β = .38 to .55). In addition, improvements in avoidance symptoms were associated with improvements in housework adjustment (β = .30), but associated with declines in extended family adjustment (β = -.34). Results suggest that it is important to consider the extent to which PTSD treatments effectively reduce specific types of symptoms, particularly emotional numbing and avoidance, to generally improve social adjustment. Copyright © 2012 International Society for Traumatic Stress Studies.

Reverse translated and gold standard continuous performance tests predict global cognitive performance in schizophrenia.

PubMed

Bismark, Andrew W; Thomas, Michael L; Tarasenko, Melissa; Shiluk, Alexandra L; Rackelmann, Sonia Y; Young, Jared W; Light, Gregory A

2018-04-12

Attentional dysfunction contributes to functional impairments in schizophrenia (SZ). Sustained attention is typically assessed via continuous performance tasks (CPTs), though many CPTs have limited cross-species translational validity and place demands on additional cognitive domains. A reverse-translated 5-Choice Continuous Performance Task (5C-CPT) for human testing-originally developed for use in rodents-was designed to minimize demands on perceptual, visual learning, processing speed, or working memory functions. To-date, no studies have validated the 5C-CPT against gold standard attentional measures nor evaluated how 5C-CPT scores relate to cognition in SZ. Here we examined the relationship between the 5C-CPT and the CPT-Identical Pairs (CPT-IP), an established and psychometrically robust measure of vigilance from the MATRICS Consensus Cognitive Battery (MCCB) in a sample of SZ patients (n = 35). Relationships to global and individual subdomains of cognition were also assessed. 5C-CPT and CPT-IP measures of performance (d-prime) were strongly correlated (r = 0.60). In a regression model, the 5C-CPT and CPT-IP collectively accounted for 54% of the total variance in MCCB total scores, and 27.6% of overall cognitive variance was shared between the 5C-CPT and CPT-IP. These results indicate that the reverse translated 5C-CPT and the gold standard CPT-IP index a common attentional construct that also significantly overlaps with variance in general cognitive performance. The use of simple, cross-species validated behavioral indices of attentional/cognitive functioning such as the 5C-CPT could accelerate the development of novel generalized pro-cognitive therapeutics for SZ and related neuropsychiatric disorders.

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.

HIV screening among TB patients and co-trimoxazole preventive therapy for TB/HIV patients in Addis Ababa: facility based descriptive study.

PubMed

Denegetu, Amenu Wesen; Dolamo, Bethabile Lovely

2014-01-01

Collaborative TB/HIV management is essential to ensure that HIV positive TB patients are identified and treated appropriately, and to prevent tuberculosis (TB) in HIV positive patients. The purpose of this study was to assess HIV case finding among TB patients and Co-trimoxazole Preventive Therapy (CPT) for HIV/TB patients in Addis Ababa. A descriptive cross-sectional, facility-based survey was conducted between June and July 2011. Data was collected by interviewing 834 TB patients from ten health facilities in Addis Ababa. Both descriptive and inferential statistics were used to summarize and analyze findings. The proportion of TB patients who (self reported) were offered for HIV test, tested for HIV and tested HIV positive during their anti-TB treatment follow-up were; 87.4%, 69.4% and 20.2%; respectively. Eighty seven HIV positive patients were identified, who knew their status before diagnosed for the current TB disease, bringing the cumulative prevalence of HIV among TB patients to 24.5%. Hence, the proportion of TB patients who knew their HIV status becomes 79.9%. The study revealed that 43.6% of those newly identified HIV positives during anti-TB treatment follow-up were actually treated with CPT. However, the commutative proportion of HIV positive TB patients who were ever treated with CPT was 54.4%; both those treated before the current TB disease and during anti-TB treatment follow-up. HIV case finding among TB patients and provision of CPT for TB/HIV co-infected patients needs boosting. Hence, routine offering of HIV test and provision of CPT for PLHIV should be strengthened in-line with the national guidelines.

Errors in the 2017 APA Clinical Practice Guideline for the Treatment of PTSD: What the Data Actually Says.

PubMed

Dominguez, Sarah K; Lee, Christopher W

2017-01-01

The American Psychological Association (APA) Practice Guidelines for the Treatment of Posttraumatic Stress Disorder (PTSD) concluded that there was strong evidence for cognitive behavioral therapy (CBT), cognitive processing therapy (CPT), cognitive therapy (CT), and exposure therapy yet weak evidence for eye movement desensitization and reprocessing (EMDR). This is despite the findings from an associated systematic review which concluded that EMDR leads to loss of PTSD diagnosis and symptom reduction. Depression symptoms were also found to improve more with EMDR than control conditions. In that review, EMDR was marked down on strength of evidence (SOE) for symptom reduction for PTSD. However, there were several problems with the conclusions of that review. Firstly, in assessing the evidence in one of the studies, the reviewers chose an incorrect measure that skewed the data. We recalculated a meta-analysis with a more appropriate measure and found the SOE improved. The resulting effect size for EMDR on PTSD symptom reduction compared to a control condition was large for studies that meet the APA inclusion criteria (SMD = 1.28) and the heterogeneity was low ( I 2 = 43%). Secondly, even if the original measure was chosen, we highlight inconsistencies with the way SOE was assessed for EMDR, CT, and CPT. Thirdly, we highlight two papers that were omitted from the analysis. One of these was omitted without any apparent reason. It found EMDR superior to a placebo control. The other study was published in 2015 and should have been part of APA guidelines since they were published in 2017. The inclusion of either study would have resulted in an improvement in SOE. Including both studies results in standard mean difference and confidence intervals that were better for EMDR than for CPT or CT. Therefore, the SOE should have been rated as moderate and EMDR assessed as at least equivalent to these CBT approaches in the APA guidelines. This would bring the APA guidelines in line with other recent practice guidelines from other countries. Less critical but also important, were several inaccuracies in assessing the risk of bias and the failure to consider studies supporting strong gains of EMDR at follow-up.

Errors in the 2017 APA Clinical Practice Guideline for the Treatment of PTSD: What the Data Actually Says

PubMed Central

Dominguez, Sarah K.; Lee, Christopher W.

2017-01-01

The American Psychological Association (APA) Practice Guidelines for the Treatment of Posttraumatic Stress Disorder (PTSD) concluded that there was strong evidence for cognitive behavioral therapy (CBT), cognitive processing therapy (CPT), cognitive therapy (CT), and exposure therapy yet weak evidence for eye movement desensitization and reprocessing (EMDR). This is despite the findings from an associated systematic review which concluded that EMDR leads to loss of PTSD diagnosis and symptom reduction. Depression symptoms were also found to improve more with EMDR than control conditions. In that review, EMDR was marked down on strength of evidence (SOE) for symptom reduction for PTSD. However, there were several problems with the conclusions of that review. Firstly, in assessing the evidence in one of the studies, the reviewers chose an incorrect measure that skewed the data. We recalculated a meta-analysis with a more appropriate measure and found the SOE improved. The resulting effect size for EMDR on PTSD symptom reduction compared to a control condition was large for studies that meet the APA inclusion criteria (SMD = 1.28) and the heterogeneity was low (I2= 43%). Secondly, even if the original measure was chosen, we highlight inconsistencies with the way SOE was assessed for EMDR, CT, and CPT. Thirdly, we highlight two papers that were omitted from the analysis. One of these was omitted without any apparent reason. It found EMDR superior to a placebo control. The other study was published in 2015 and should have been part of APA guidelines since they were published in 2017. The inclusion of either study would have resulted in an improvement in SOE. Including both studies results in standard mean difference and confidence intervals that were better for EMDR than for CPT or CT. Therefore, the SOE should have been rated as moderate and EMDR assessed as at least equivalent to these CBT approaches in the APA guidelines. This would bring the APA guidelines in line with other recent practice guidelines from other countries. Less critical but also important, were several inaccuracies in assessing the risk of bias and the failure to consider studies supporting strong gains of EMDR at follow-up. PMID:28878718

The Impact of Hypnotic Suggestions on Reaction Times in Continuous Performance Test in Adults with ADHD and Healthy Controls

PubMed Central

Virta, Maarit; Hiltunen, Seppo; Mattsson, Markus; Kallio, Sakari

2015-01-01

Attention is one of the key factors in both hypnotic processes and patients with ADHD. In addition, the brain areas associated with hypnosis and ADHD overlap in many respects. However, the use of hypnosis in ADHD patients has still received only minor attention in research. The main purpose of the present work was to investigate whether hypnosis and hypnotic suggestions influence the performance of adult ADHD (n = 27) and control participants (n = 31) in the continuous performance test (CPT). The hypnotic susceptibility of the participants was measured by the Harvard Group Scale of Hypnotic Susceptibility (HGSHS:A) and the attentional task was a three minute long auditory version of the CPT. The CPT task was administered four times: before hypnosis (CPT1), after a hypnotic induction (CPT2), after suggestions about speed and accuracy (CPT3), and after the termination of hypnosis (CPT4). The susceptibility of the groups measured by HGSHS:A did not differ. There was a statistically significant decrease in reaction times in both ADHD and control groups between CPT2 and CPT3. The differences between CPT1 and CPT2, even though non-significant, were different in the two groups: in the ADHD group reaction times decreased whereas in the control group they increased. Both groups made very few errors in the short CPT. This study indicates that hypnotic suggestions have an effect on reaction times in the sustained attention task both in adult ADHD patients and control subjects. The theoretical and clinical implications are discussed. PMID:25962151

Effects of albendazole combined with TSII-A (a Chinese herb compound) on optic neuritis caused by Angiostrongylus cantonensis in BALB/c mice.

PubMed

Feng, Feng; Feng, Ying; Liu, Zhen; Li, Wei-Hua; Wang, Wen-Cong; Wu, Zhong-Dao; Lv, Zhiyue

2015-11-25

Angiostrongylus cantonensis (A. cantonensis) infection can lead to optic neuritis, retinal inflammation, damage to ganglion cells, demyelination of optic nerve and visual impairment. Combined therapy of albendazole and dexamethasone is a common treatment for the disease in the clinic, but it plays no role in vision recovery. Therefore, it has been necessary to explore alternative therapies to treat this disease. Previous studies reported the neuro-productive effects of two constituents of Danshen (a Chinese herb)-tanshinone II-A (TSII-A) and cryptotanshinone (CPT), and this study aims to evaluate the impacts of TSII-A or CPT combined with albendazole on optic neuritis caused by A. cantonensis infection in a murine model. To assess the effects of TSII-A or CPT combined with albendazole on optic neuritis due to the infection, mice were divided into six groups, including the normal control group, infection group and four treatment groups (albendazole group, albendazole combined with dexamethasone group, albendazole combined with CPT group and albendazole combined with TSII-A group). The infection group and treatment groups were infected with A. cantonensis and the treatment groups received interventions from 14 dpi (days post infection), respectively. At 21 dpi, the visual acuity of mice in each group was examined by visual evoked potential (VEP). The pathologic alteration of the retina and optic nerve were observed by hematoxylin and eosin (H&E) staining and transmission electronic microscopy (TEM). Infection of A. cantonensis caused prolonged VEP latency, obvious inflammatory cell infiltration in the retina, damaged retinal ganglions and retinal swelling, followed by optic nerve fibre demyelination and a decreasing number of axons at 21 dpi. In treatment groups, albendazole could not alleviate the above symptoms; albendazole combined with dexamethasone lessened the inflammation of the retina, but was futile for the other changes; however, albendazole combined with CPT and albendazole combined with TSII-A showed obvious effects on the recovery of prolonged VEP latency, destruction and reduction of ganglion cells, optic nerve demyelination and axon loss. Compared with albendazole-CPT compound, albendazole combined with TSII-A was more effective. The current study demonstrates that albendazole combined with TSII-A plays a more effective role in treating optic neuritis caused by A. cantonensis in mice than with dexamethasone, as applied in conventional treatment, indicating that albendazole combined with TSII-A might be an alternate therapy for this parasitic disease in the clinic.

77 FR 45061 - Hospital Outpatient Prospective and Ambulatory Surgical Center Payment Systems and Quality...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-30

... radiation therapy (IORT), brachytherapy composite APC, multiple imaging composite APCs, cardiac... Outpatient Code Editor IOL Intraocular lens IOM Institute of Medicine IORT Intraoperative radiation treatment... Radiation Therapy (IORT) (APC 0412) a. Background b. CY 2013 Proposals for CPT Codes 77424, 77425, and 77469...

The case for particle therapy.

PubMed

Jones, B

2006-01-01

Among the most important decisions facing the British Government regarding the treatment of cancer in the National Health Service (NHS) is the purchase of charged particle therapy (CPT) centres. CPT is different from conventional radiotherapy: the dose is deposited far more selectively in Bragg Peaks by either protons or "heavy" ions, such as carbon. In this way, it is possible to "dose paint" targets, voxel by voxel, with far less dose to surrounding tissues than with X-ray techniques. At present the UK possesses a 62 MeV cyclotron proton facility at Clatterbridge (Wirral), which provides therapy for intraocular cancers such as melanoma; for deeper situated cancers in the pelvis, chest etc., much higher energies, over 200 MeV are required from a synchrotron facility. There is an impressive expansion in particle beam therapy (PBT) centres worldwide, since they offer good prospects of improved quality of life with enhanced cancer cures in situations where conventional therapy is limited due to radioresistance or by the close proximity of critical normal tissues. There is a threat to UK Oncology, since it is anticipated that several thousand British patients may require referral abroad for therapy; this would severely disrupt their multidisciplinary management and require demanding logistical support.

Modulation of Global and Local Processing Biases in Adults with Autistic-Like Traits

ERIC Educational Resources Information Center

English, Michael C. W.; Maybery, Murray T.; Visser, Troy A. W.

2017-01-01

Previous work shows that doing a continuous performance task (CPT) shifts attentional biases in neurotypical individuals towards global aspects of hierarchical Navon figures by selectively activating right hemisphere regions associated with global processing. The present study examines whether CPT can induce similar modulations of attention in…

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.

ATM Expression Predicts Veliparib and Irinotecan Sensitivity in Gastric Cancer by Mediating P53-Independent Regulation of Cell Cycle and Apoptosis.

PubMed

Subhash, Vinod Vijay; Tan, Shi Hui; Yeo, Mei Shi; Yan, Fui Leng; Peethala, Praveen C; Liem, Natalia; Krishnan, Vaidehi; Yong, Wei Peng

2016-12-01

Identification of synthetically lethal cellular targets and synergistic drug combinations is important in cancer chemotherapy as they help to overcome treatment resistance and increase efficacy. The Ataxia Telangiectasia Mutated (ATM) kinase is a nuclear protein that plays a major role in the initiation of DNA repair signaling and cell-cycle check points during DNA damage. Although ATM was shown to be associated with poor prognosis in gastric cancer, its implications as a predictive biomarker for cancer chemotherapy remain unexplored. The present study evaluated ATM-induced synthetic lethality and its role in sensitization of gastric cancer cells to PARP and TOP1 inhibitors, veliparib (ABT-888) and irinotecan (CPT-11), respectively. ATM expression was detected in a panel of gastric cell lines, and the IC 50 against each inhibitors was determined. The combinatorial effect of ABT-888 and CPT-11 in gastric cancer cells was also determined both in vitro and in vivo ATM deficiency was found to be associated with enhanced sensitivity to ABT-888 and CPT-11 monotherapy, hence suggesting a mechanism of synthetic lethality. Cells with high ATM expression showed reduced sensitivity to monotherapy; however, they showed a higher therapeutic effect with ABT-888 and CPT-11 combinatorial therapy. Furthermore, ATM expression was shown to play a major role in cellular homeostasis by regulating cell-cycle progression and apoptosis in a P53-independent manner. The present study highlights the clinical utility of ATM expression as a predictive marker for sensitivity of gastric cancer cells to PARP and TOP1 inhibition and provides a deeper mechanistic insight into ATM-dependent regulation of cellular processes. Mol Cancer Ther; 15(12); 3087-96. ©2016 AACR. ©2016 American Association for Cancer Research.

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.

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.

Process Pharmacology: A Pharmacological Data Science Approach to Drug Development and Therapy.

PubMed

Lötsch, Jörn; Ultsch, Alfred

2016-04-01

A novel functional-genomics based concept of pharmacology that uses artificial intelligence techniques for mining and knowledge discovery in "big data" providing comprehensive information about the drugs' targets and their functional genomics is proposed. In "process pharmacology", drugs are associated with biological processes. This puts the disease, regarded as alterations in the activity in one or several cellular processes, in the focus of drug therapy. In this setting, the molecular drug targets are merely intermediates. The identification of drugs for therapeutic or repurposing is based on similarities in the high-dimensional space of the biological processes that a drug influences. Applying this principle to data associated with lymphoblastic leukemia identified a short list of candidate drugs, including one that was recently proposed as novel rescue medication for lymphocytic leukemia. The pharmacological data science approach provides successful selections of drug candidates within development and repurposing tasks. © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Single-session manualized ego state therapy (EST) for combat stress injury, PTSD, and ASD, Part 2: the procedure.

PubMed

Barabasz, Arreed F; Barabasz, Marianne; Watkins, John G

2012-01-01

An abbreviated description of our single-session 5- to 6-hour procedure is provided. In contrast to trauma reframing approaches, such as cognitive processing therapy (CPT) or traditional psychoanalytic interventions, our manualized procedure rapidly demystifies subconscious processes, making them accessible and understandable by the patient. The therapist's supportive ego strength is integrated into the intense repeated emotional and physiological releases of the traumatized ego states. The abreactive component of this 5-phase procedure exhausts the bound-up psychological and physiological reactions but also serves to quickly overcome the trauma and to restructure the personality. The patient becomes empowered to release the trauma memories and to emerge with the ability to be adaptive, assertive, giving, strong, and able to express anger appropriately yet be caring with family/friends.

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.

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

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

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

SU-A-210-04: Panel Discussion

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

Stanford, J.

The purpose of this student annual meeting is to address topics that are becoming more relevant to medical physicists, but are not frequently addressed, especially for students and trainees just entering the field. The talk is divided into two parts: medical billing and regulations. Hsinshun Wu – Why should we learn radiation oncology billing? Many medical physicists do not like to be involved with medical billing or coding during their career. They believe billing is not their responsibility and sometimes they even refuse to participate in the billing process if given the chance. This presentation will talk about a physicist’smore » long career and share his own experience that knowing medical billing is not only important and necessary for every young medical physicist, but that good billing knowledge could provide a valuable contribution to his/her medical physics development. Learning Objectives: The audience will learn the basic definition of Current Procedural Terminology (CPT) codes performed in a Radiation Oncology Department. Understand the differences between hospital coding and physician-based or freestanding coding. Apply proper CPT coding for each Radiation Oncology procedure. Each procedure with its specific CPT code will be discussed in detail. The talk will focus on the process of care and use of actual workflow to understand each CPT code. Example coding of a typical Radiation Oncology procedure. Special procedure coding such as brachytherapy, proton therapy, radiosurgery, and SBRT. Maryann Abogunde – Medical physics opportunities at the Nuclear Regulatory Commission (NRC) The NRC’s responsibilities include the regulation of medical uses of byproduct (radioactive) materials and oversight of medical use end-users (licensees) through a combination of regulatory requirements, licensing, safety oversight including inspection and enforcement, operational experience evaluation, and regulatory support activities. This presentation will explore the career options for medical physicists in the NRC, how the NRC interacts with clinical medical physicists, and a physicist’s experience as a regulator. Learning Objectives: Explore non-clinical career pathways for medical physics students and trainees at the Nuclear Regulatory Commission. Overview of NRC medical applications and medical use regulations. Understand the skills needed for physicists as regulators. Abogunde is funded to attend the meeting by her employer, the NRC.« less

SU-A-210-03: Panel Discussion

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

Rodrigues, A.

The purpose of this student annual meeting is to address topics that are becoming more relevant to medical physicists, but are not frequently addressed, especially for students and trainees just entering the field. The talk is divided into two parts: medical billing and regulations. Hsinshun Wu – Why should we learn radiation oncology billing? Many medical physicists do not like to be involved with medical billing or coding during their career. They believe billing is not their responsibility and sometimes they even refuse to participate in the billing process if given the chance. This presentation will talk about a physicist’smore » long career and share his own experience that knowing medical billing is not only important and necessary for every young medical physicist, but that good billing knowledge could provide a valuable contribution to his/her medical physics development. Learning Objectives: The audience will learn the basic definition of Current Procedural Terminology (CPT) codes performed in a Radiation Oncology Department. Understand the differences between hospital coding and physician-based or freestanding coding. Apply proper CPT coding for each Radiation Oncology procedure. Each procedure with its specific CPT code will be discussed in detail. The talk will focus on the process of care and use of actual workflow to understand each CPT code. Example coding of a typical Radiation Oncology procedure. Special procedure coding such as brachytherapy, proton therapy, radiosurgery, and SBRT. Maryann Abogunde – Medical physics opportunities at the Nuclear Regulatory Commission (NRC) The NRC’s responsibilities include the regulation of medical uses of byproduct (radioactive) materials and oversight of medical use end-users (licensees) through a combination of regulatory requirements, licensing, safety oversight including inspection and enforcement, operational experience evaluation, and regulatory support activities. This presentation will explore the career options for medical physicists in the NRC, how the NRC interacts with clinical medical physicists, and a physicist’s experience as a regulator. Learning Objectives: Explore non-clinical career pathways for medical physics students and trainees at the Nuclear Regulatory Commission. Overview of NRC medical applications and medical use regulations. Understand the skills needed for physicists as regulators. Abogunde is funded to attend the meeting by her employer, the NRC.« less

Magnetic Resonance Imaging-Guided Multi-Drug Chemotherapy and Photothermal Synergistic Therapy with pH and NIR-Stimulation Release.

PubMed

Yang, Ji-Chun; Chen, Yang; Li, Yu-Hao; Yin, Xue-Bo

2017-07-12

The combination of multidrug chemotherapy and photothermal therapy (PTT) enhances cancer therapeutic efficacy. Herein, we develop a simple and smart pH/NIR dual-stimulus-responsive degradable mesoporous CoFe 2 O 4 @PDA@ZIF-8 sandwich nanocomposite. The mesoporous CoFe 2 O 4 core acts as T 2 -weighted magnetic resonance (MR) imaging probe, PTT agent, and loading platform of hydrophilic doxorubicin (DOX). A polydopamine (PDA) layer is used to avoid the premature leakage of DOX before arriving at tumor site, enhance PTT efficiency, and facilitate the integration of ZIF-8 (a kind of metal-organic framework). The ZIF-8 shell serves to encapsulate hydrophobic camptothecin (CPT) and as the switch for the pH and NIR stimulation-responsive release of the two drugs. Therefore, T 2 -weighted MR imaging-guided multidrug chemotherapy and PTT synergistic treatment is achieved. Two kinds of anticancer drugs, hydrophilic DOX and hydrophobic CPT, are successfully loaded in CoFe 2 O 4 and ZIF-8, respectively, so no mutual interference between the two drugs exists. A unique two-stage stepwise release process is exhibited for CPT and DOX with an interval of 12 h to improve the anticancer efficacy under the acidic microenvironment of tumor tissue. NIR irradiation achieves the burst drug-release and PTT after laser stimulation, simultaneously. With this smart design, high drug concentration is achieved at the tumor site by quick release, especially for the therapeutic drugs that show nonlinear pharmacokinetics, and PTT is integrated efficiently. Furthermore, negligible biotoxicity and a remarkable synergic antitumor effect of the hybrid nanocomposites are validated by HepG2 cells and tumor-bearing mice as models. Our multidrug delivery-releasing composite improves tumor therapeutic efficiency significantly compared with a single-drug chemotherapy system. The simple multifunctional composite system can be applied as an effective platform for personal nanomedicine with diagnosis, smart drug delivery, and cancer treatment through its remarkable photothermal property and controllable multidrug release.

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.

Carnitine palmitoyltransferase II deficiency

PubMed Central

Roe, C R.; Yang, B-Z; Brunengraber, H; Roe, D S.; Wallace, M; Garritson, B K.

2008-01-01

Background: Carnitine palmitoyltransferase II (CPT II) deficiency is an important cause of recurrent rhabdomyolysis in children and adults. Current treatment includes dietary fat restriction, with increased carbohydrate intake and exercise restriction to avoid muscle pain and rhabdomyolysis. Methods: CPT II enzyme assay, DNA mutation analysis, quantitative analysis of acylcarnitines in blood and cultured fibroblasts, urinary organic acids, the standardized 36-item Short-Form Health Status survey (SF-36) version 2, and bioelectric impedance for body fat composition. Diet treatment with triheptanoin at 30% to 35% of total daily caloric intake was used for all patients. Results: Seven patients with CPT II deficiency were studied from 7 to 61 months on the triheptanoin (anaplerotic) diet. Five had previous episodes of rhabdomyolysis requiring hospitalizations and muscle pain on exertion prior to the diet (two younger patients had not had rhabdomyolysis). While on the diet, only two patients experienced mild muscle pain with exercise. During short periods of noncompliance, two patients experienced rhabdomyolysis with exercise. None experienced rhabdomyolysis or hospitalizations while on the diet. All patients returned to normal physical activities including strenuous sports. Exercise restriction was eliminated. Previously abnormal SF-36 physical composite scores returned to normal levels that persisted for the duration of the therapy in all five symptomatic patients. Conclusions: The triheptanoin diet seems to be an effective therapy for adult-onset carnitine palmitoyltransferase II deficiency. GLOSSARY ALT = alanine aminotransferase; AST = aspartate aminotransferase; ATP = adenosine triphosphate; BHP = β-hydroxypentanoate; BKP = β-ketopentanoate; BKP-CoA = β-ketopentanoyl–coenzyme A; BUN = blood urea nitrogen; CAC = citric acid cycle; CoA = coenzyme A; CPK = creatine phosphokinase; CPT II = carnitine palmitoyltransferase II; LDL = low-density lipoprotein; MCT = medium-chain triglyceride; PCS = physical composite score; SF-36 = 36-item Short-Form Health Status survey. PMID:18645163

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.

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.

Virtual rehabilitation via Nintendo Wii® and conventional physical therapy effectively treat post-stroke hemiparetic patients.

PubMed

da Silva Ribeiro, Nildo Manoel; Ferraz, Daniel Dominguez; Pedreira, Érika; Pinheiro, Ígor; da Silva Pinto, Ana Cláudia; Neto, Mansueto Gomes; Dos Santos, Luan Rafael Aguiar; Pozzato, Michele Gea Guimarães; Pinho, Ricardo Silva; Masruha, Marcelo Rodrigues

2015-08-01

The Nintendo® Wii is a simple and affordable virtual therapy alternative. It may be used at home, and it is a motivating recreational activity that provides continuous feedback. However, studies comparing the use of the Nintendo® Wii to conventional physical therapy are needed. To compare the effect of a rehabilitation treatment using the Nintendo® Wii (NW) with conventional physical therapy (CPT) to improve the sensorimotor function and quality of life for post-stroke hemiparetic patients. The present study applied a randomized, blind, and controlled clinical trial. In total, 30 patients with post-stroke hemiparesis were evaluated. A total of 15 patients were randomly assigned to each group. The SF-36 quality of life and Fugl-Meyer scales were used to evaluate the patients. After treatment, the only variable that differed between the groups was the physical functioning domain of the SF-36 in the group that received conventional physical therapy. A significant difference was observed between both groups before and after treatment in terms of the following Fugl-Meyer scale items: passive movement and pain, motor function of the upper limbs (ULs), and balance. The CPT group also showed a significant difference with regard to their UL and lower limb (LL) coordination. The SF-36 scale analysis revealed a significant difference within both groups with regard to the following domains: physical functioning, role limitation due to physical aspects, vitality, and role limitation due to emotional aspects. The NW group also exhibited a significant difference in the mental health domain. The results indicate that both approaches improved the patients' performance in a similar manner. Virtual rehabilitation using the Nintendo Wii® and CPT both effectively treat post-stroke hemiparetic patients by improving passive movement and pain scores, motor function of the upper limb, balance, physical functioning, vitality, and the physical and emotional aspects of role functioning.

Evaluation of Ambulatory Patient Group (APG) Software Using CHAMPUS professional Services Claims Data (Beta Test)

DTIC Science & Technology

1991-07-15

0.02 73 0.02 261 ELECTROENCEPHALOGRAM 384 0.09 384 0.09 262 ELECTROCONVULSIVE THERAPY 72 0.02 72 0.02 263 NERVE AND MUSCLE TESTS 626 0.15 626 0.14 264...psychotherapy 664 Comprehensive therapy for drug abuse with mental illness 669 Family therapy for drug abuse 670 Group therapy for drug abuse 676...the 1990 CPT codes, but the software was written using the 1989 edition. This difference explained the absence of encounters in APG 131, Chemo- therapy

Chemophototherapy: An Emerging Treatment Option for Solid Tumors

PubMed Central

Luo, Dandan; Carter, Kevin A.; Miranda, Dyego

2016-01-01

Near infrared (NIR) light penetrates human tissues with limited depth, thereby providing a method to safely deliver non‐ionizing radiation to well‐defined target tissue volumes. Light‐based therapies including photodynamic therapy (PDT) and laser‐induced thermal therapy have been validated clinically for curative and palliative treatment of solid tumors. However, these monotherapies can suffer from incomplete tumor killing and have not displaced existing ablative modalities. The combination of phototherapy and chemotherapy (chemophototherapy, CPT), when carefully planned, has been shown to be an effective tumor treatment option preclinically and clinically. Chemotherapy can enhance the efficacy of PDT by targeting surviving cancer cells or by inhibiting regrowth of damaged tumor blood vessels. Alternatively, PDT‐mediated vascular permeabilization has been shown to enhance the deposition of nanoparticulate drugs into tumors for enhanced accumulation and efficacy. Integrated nanoparticles have been reported that combine photosensitizers and drugs into a single agent. More recently, light‐activated nanoparticles have been developed that release their payload in response to light irradiation to achieve improved drug bioavailability with superior efficacy. CPT can potently eradicate tumors with precise spatial control, and further clinical testing is warranted. PMID:28105389

Predicting Treatment Success in Child and Parent Therapy Among Families in Poverty.

PubMed

Mattek, Ryan J; Harris, Sara E; Fox, Robert A

2016-01-01

Behavior problems are prevalent in young children and those living in poverty are at increased risk for stable, high-intensity behavioral problems. Research has demonstrated that participation in child and parent therapy (CPT) programs significantly reduces problematic child behaviors while increasing positive behaviors. However, CPT programs, particularly those implemented with low-income populations, frequently report high rates of attrition (over 50%). Parental attributional style has shown some promise as a contributing factor to treatment attendance and termination in previous research. The authors examined if parental attributional style could predict treatment success in a CPT program, specifically targeting low-income urban children with behavior problems. A hierarchical logistic regression was used with a sample of 425 families to assess if parent- and child-referent attributions variables predicted treatment success over and above demographic variables and symptom severity. Parent-referent attributions, child-referent attributions, and child symptom severity were found to be significant predictors of treatment success. Results indicated that caregivers who viewed themselves as a contributing factor for their child's behavior problems were significantly more likely to demonstrate treatment success. Alternatively, caregivers who viewed their child as more responsible for their own behavior problems were less likely to demonstrate treatment success. Additionally, more severe behavior problems were also predictive of treatment success. Clinical and research implications of these results are discussed.

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.

Spiritually Integrated Cognitive Processing Therapy: A New Treatment for Post-traumatic Stress Disorder That Targets Moral Injury.

PubMed

Pearce, Michelle; Haynes, Kerry; Rivera, Natalia R; Koenig, Harold G

2018-01-01

Post-traumatic stress disorder (PTSD) is a debilitating disorder, and current treatments leave the majority of patients with unresolved symptoms. Moral injury (MI) may be one of the barriers that interfere with recovery from PTSD, particularly among current or former military service members. Given the psychological and spiritual aspects of MI, an intervention that addresses MI using spiritual resources in addition to psychological resources may be particularly effective in treating PTSD. To date, there are no existing empirically based individual treatments for PTSD and MI that make explicit use of a patient's spiritual resources, despite the evidence that spiritual beliefs/activities predict faster recovery from PTSD. To address this gap, we adapted Cognitive Processing Therapy (CPT), an empirically validated treatment for PTSD, to integrate clients' spiritual beliefs, practices, values, and motivations. We call this treatment Spiritually Integrated CPT (SICPT). This article describes this novel manualized therapeutic approach for treating MI in the setting of PTSD for spiritual/religious clients. We provide a description of SICPT and a brief summary of the 12 sessions. Then, we describe a case study in which the therapist helps a client use his spiritual resources to resolve MI and assist in the recovery from PTSD. SICPT may be a helpful way to reduce PTSD by targeting MI, addressing spiritual distress, and using a client's spiritual resources. In addition to the spiritual version (applicable for those of any religion and those who do not identify as religious), we have also developed 5 religion-specific manuals (Christianity, Judaism, Islam, Buddhism, and Hinduism) for clients who desire a more religion-specific approach.

Spiritually Integrated Cognitive Processing Therapy: A New Treatment for Post-traumatic Stress Disorder That Targets Moral Injury

PubMed Central

Pearce, Michelle; Haynes, Kerry; Rivera, Natalia R; Koenig, Harold G.

2018-01-01

Background Post-traumatic stress disorder (PTSD) is a debilitating disorder, and current treatments leave the majority of patients with unresolved symptoms. Moral injury (MI) may be one of the barriers that interfere with recovery from PTSD, particularly among current or former military service members. Objective Given the psychological and spiritual aspects of MI, an intervention that addresses MI using spiritual resources in addition to psychological resources may be particularly effective in treating PTSD. To date, there are no existing empirically based individual treatments for PTSD and MI that make explicit use of a patient’s spiritual resources, despite the evidence that spiritual beliefs/activities predict faster recovery from PTSD. Method To address this gap, we adapted Cognitive Processing Therapy (CPT), an empirically validated treatment for PTSD, to integrate clients’ spiritual beliefs, practices, values, and motivations. We call this treatment Spiritually Integrated CPT (SICPT). Results This article describes this novel manualized therapeutic approach for treating MI in the setting of PTSD for spiritual/religious clients. We provide a description of SICPT and a brief summary of the 12 sessions. Then, we describe a case study in which the therapist helps a client use his spiritual resources to resolve MI and assist in the recovery from PTSD. Conclusion SICPT may be a helpful way to reduce PTSD by targeting MI, addressing spiritual distress, and using a client’s spiritual resources. In addition to the spiritual version (applicable for those of any religion and those who do not identify as religious), we have also developed 5 religion-specific manuals (Christianity, Judaism, Islam, Buddhism, and Hinduism) for clients who desire a more religion-specific approach. PMID:29497585

Glutathione- and pH-responsive nonporous silica prodrug nanoparticles for controlled release and cancer therapy

NASA Astrophysics Data System (ADS)

Xu, Zhigang; Liu, Shiying; Kang, Yuejun; Wang, Mingfeng

2015-03-01

A myriad of drug delivery systems such as liposomes, micelles, polymers and inorganic nanoparticles (NPs) have been developed for cancer therapy. Very few of them, however, have the ability to integrate multiple functionalities such as specific delivery, high circulation stability, controllable release and good biocompatibility and biodegradability in a single system to improve the therapeutic efficacy. Herein, we report two types of stimuli-responsive nonporous silica prodrug NPs towards this goal for controlled release of anticancer drugs and efficient combinatorial cancer therapy. As a proof of concept, anticancer drugs camptothecin (CPT) and doxorubicin (DOX) were covalently encapsulated into silica matrices through glutathione (GSH)-responsive disulfide and pH-responsive hydrazone bonds, respectively, resulting in NPs with sizes tunable in the range of 50-200 nm. Both silica prodrug NPs showed stimuli-responsive controlled release upon exposure to a GSH-rich or acidic environment, resulting in improved anticancer efficacy. Notably, two prodrug NPs simultaneously taken up by HeLa cells showed a remarkable combinatorial efficacy compared to free drug pairs. These results suggest that the stimuli-responsive silica prodrug NPs are promising anticancer drug carriers for efficient cancer therapy.A myriad of drug delivery systems such as liposomes, micelles, polymers and inorganic nanoparticles (NPs) have been developed for cancer therapy. Very few of them, however, have the ability to integrate multiple functionalities such as specific delivery, high circulation stability, controllable release and good biocompatibility and biodegradability in a single system to improve the therapeutic efficacy. Herein, we report two types of stimuli-responsive nonporous silica prodrug NPs towards this goal for controlled release of anticancer drugs and efficient combinatorial cancer therapy. As a proof of concept, anticancer drugs camptothecin (CPT) and doxorubicin (DOX) were covalently encapsulated into silica matrices through glutathione (GSH)-responsive disulfide and pH-responsive hydrazone bonds, respectively, resulting in NPs with sizes tunable in the range of 50-200 nm. Both silica prodrug NPs showed stimuli-responsive controlled release upon exposure to a GSH-rich or acidic environment, resulting in improved anticancer efficacy. Notably, two prodrug NPs simultaneously taken up by HeLa cells showed a remarkable combinatorial efficacy compared to free drug pairs. These results suggest that the stimuli-responsive silica prodrug NPs are promising anticancer drug carriers for efficient cancer therapy. Electronic supplementary information (ESI) available: Experimental details of SSP-CPT and SSP-DOX; 1H NMR and FT-IR spectra; DLS, TEM and SEM images of prodrug NPs; the TEM image, UV-vis absorption and photoluminescence spectra of CPT/DOX NPs; the TEM images of prodrug NPs incubated under physiological conditions; the reaction conditions and structure information of size-controlled prodrug NPs; the IC50 value of free drug and prodrug NPs at different times. See DOI: 10.1039/c5nr00297d

Can an intervention based on a serious videogame prior to cognitive behavioral therapy be helpful in bulimia nervosa? A clinical case study.

PubMed

Giner-Bartolomé, Cristina; Fagundo, Ana B; Sánchez, Isabel; Jiménez-Murcia, Susana; Santamaría, Juan J; Ladouceur, Robert; Menchón, José M; Fernández-Aranda, Fernando

2015-01-01

Several studies have highlighted the implications of impulsivity and novelty seeking for both the maintenance and the process of recovery from bulimia nervosa (BN). Cognitive behavioral therapy (CBT) is the treatment of choice for BN, but for some cases, this treatment alone might not be sufficient for reducing the high levels of impulsivity. The paper presents a case report of a patient with BN, examining the effectiveness of using a videogame (VG; Playmancer) as an additional intervention designed to address impulsivity. Psychometric and neuropsychological measures were collected at baseline. After this assessment, Playmancer was applied prior to CBT, following an "A-B-A-C-A" single case experimental design. Impulsivity levels were assessed with the Conner's Continuous Performance Test II (CPT-II). After the Playmancer treatment, the patient started CBT, and the levels of impulsivity were recorded again. Finally, psychometric and neuropsychological measures were collected after treatment. Weekly frequency of binges and vomiting were also recorded during the entire procedure. After the VG intervention, psychometric measures such as anxiety levels, impulsivity and novelty seeking decreased. Regarding the neuropsychological measures, impulsivity levels (measured with the CPT-II) progressively decreased throughout the intervention, and an improvement in decision making capacities was observed. Furthermore, the frequency of binges also decreased during and after the VG intervention. This case report suggests that using the Playmancer VG to reduce impulsivity prior to CBT may enhance the final results of the treatment for BN.

Differences in Visuo-Motor Control in Skilled vs. Novice Martial Arts Athletes during Sustained and Transient Attention Tasks: A Motor-Related Cortical Potential Study

PubMed Central

Sanchez-Lopez, Javier; Fernandez, Thalia; Silva-Pereyra, Juan; Martinez Mesa, Juan A.; Di Russo, Francesco

2014-01-01

Cognitive and motor processes are essential for optimal athletic performance. Individuals trained in different skills and sports may have specialized cognitive abilities and motor strategies related to the characteristics of the activity and the effects of training and expertise. Most studies have investigated differences in motor-related cortical potential (MRCP) during self-paced tasks in athletes but not in stimulus-related tasks. The aim of the present study was to identify the differences in performance and MRCP between skilled and novice martial arts athletes during two different types of tasks: a sustained attention task and a transient attention task. Behavioral and electrophysiological data from twenty-two martial arts athletes were obtained while they performed a continuous performance task (CPT) to measure sustained attention and a cued continuous performance task (c-CPT) to measure transient attention. MRCP components were analyzed and compared between groups. Electrophysiological data in the CPT task indicated larger prefrontal positive activity and greater posterior negativity distribution prior to a motor response in the skilled athletes, while novices showed a significantly larger response-related P3 after a motor response in centro-parietal areas. A different effect occurred in the c-CPT task in which the novice athletes showed strong prefrontal positive activity before a motor response and a large response-related P3, while in skilled athletes, the prefrontal activity was absent. We propose that during the CPT, skilled athletes were able to allocate two different but related processes simultaneously according to CPT demand, which requires controlled attention and controlled motor responses. On the other hand, in the c-CPT, skilled athletes showed better cue facilitation, which permitted a major economy of resources and “automatic” or less controlled responses to relevant stimuli. In conclusion, the present data suggest that motor expertise enhances neural flexibility and allows better adaptation of cognitive control to the requested task. PMID:24621480

Differences in visuo-motor control in skilled vs. novice martial arts athletes during sustained and transient attention tasks: a motor-related cortical potential study.

PubMed

Sanchez-Lopez, Javier; Fernandez, Thalia; Silva-Pereyra, Juan; Martinez Mesa, Juan A; Di Russo, Francesco

2014-01-01

Cognitive and motor processes are essential for optimal athletic performance. Individuals trained in different skills and sports may have specialized cognitive abilities and motor strategies related to the characteristics of the activity and the effects of training and expertise. Most studies have investigated differences in motor-related cortical potential (MRCP) during self-paced tasks in athletes but not in stimulus-related tasks. The aim of the present study was to identify the differences in performance and MRCP between skilled and novice martial arts athletes during two different types of tasks: a sustained attention task and a transient attention task. Behavioral and electrophysiological data from twenty-two martial arts athletes were obtained while they performed a continuous performance task (CPT) to measure sustained attention and a cued continuous performance task (c-CPT) to measure transient attention. MRCP components were analyzed and compared between groups. Electrophysiological data in the CPT task indicated larger prefrontal positive activity and greater posterior negativity distribution prior to a motor response in the skilled athletes, while novices showed a significantly larger response-related P3 after a motor response in centro-parietal areas. A different effect occurred in the c-CPT task in which the novice athletes showed strong prefrontal positive activity before a motor response and a large response-related P3, while in skilled athletes, the prefrontal activity was absent. We propose that during the CPT, skilled athletes were able to allocate two different but related processes simultaneously according to CPT demand, which requires controlled attention and controlled motor responses. On the other hand, in the c-CPT, skilled athletes showed better cue facilitation, which permitted a major economy of resources and "automatic" or less controlled responses to relevant stimuli. In conclusion, the present data suggest that motor expertise enhances neural flexibility and allows better adaptation of cognitive control to the requested task.

SU-A-210-01: Why Should We Learn Radiation Oncology Billing?

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

Wu, H.

The purpose of this student annual meeting is to address topics that are becoming more relevant to medical physicists, but are not frequently addressed, especially for students and trainees just entering the field. The talk is divided into two parts: medical billing and regulations. Hsinshun Wu – Why should we learn radiation oncology billing? Many medical physicists do not like to be involved with medical billing or coding during their career. They believe billing is not their responsibility and sometimes they even refuse to participate in the billing process if given the chance. This presentation will talk about a physicist’smore » long career and share his own experience that knowing medical billing is not only important and necessary for every young medical physicist, but that good billing knowledge could provide a valuable contribution to his/her medical physics development. Learning Objectives: The audience will learn the basic definition of Current Procedural Terminology (CPT) codes performed in a Radiation Oncology Department. Understand the differences between hospital coding and physician-based or freestanding coding. Apply proper CPT coding for each Radiation Oncology procedure. Each procedure with its specific CPT code will be discussed in detail. The talk will focus on the process of care and use of actual workflow to understand each CPT code. Example coding of a typical Radiation Oncology procedure. Special procedure coding such as brachytherapy, proton therapy, radiosurgery, and SBRT. Maryann Abogunde – Medical physics opportunities at the Nuclear Regulatory Commission (NRC) The NRC’s responsibilities include the regulation of medical uses of byproduct (radioactive) materials and oversight of medical use end-users (licensees) through a combination of regulatory requirements, licensing, safety oversight including inspection and enforcement, operational experience evaluation, and regulatory support activities. This presentation will explore the career options for medical physicists in the NRC, how the NRC interacts with clinical medical physicists, and a physicist’s experience as a regulator. Learning Objectives: Explore non-clinical career pathways for medical physics students and trainees at the Nuclear Regulatory Commission. Overview of NRC medical applications and medical use regulations. Understand the skills needed for physicists as regulators. Abogunde is funded to attend the meeting by her employer, the NRC.« less

SU-A-210-02: Medical Physics Opportunities at the NRC

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

Abogunde, M.

The purpose of this student annual meeting is to address topics that are becoming more relevant to medical physicists, but are not frequently addressed, especially for students and trainees just entering the field. The talk is divided into two parts: medical billing and regulations. Hsinshun Wu – Why should we learn radiation oncology billing? Many medical physicists do not like to be involved with medical billing or coding during their career. They believe billing is not their responsibility and sometimes they even refuse to participate in the billing process if given the chance. This presentation will talk about a physicist’smore » long career and share his own experience that knowing medical billing is not only important and necessary for every young medical physicist, but that good billing knowledge could provide a valuable contribution to his/her medical physics development. Learning Objectives: The audience will learn the basic definition of Current Procedural Terminology (CPT) codes performed in a Radiation Oncology Department. Understand the differences between hospital coding and physician-based or freestanding coding. Apply proper CPT coding for each Radiation Oncology procedure. Each procedure with its specific CPT code will be discussed in detail. The talk will focus on the process of care and use of actual workflow to understand each CPT code. Example coding of a typical Radiation Oncology procedure. Special procedure coding such as brachytherapy, proton therapy, radiosurgery, and SBRT. Maryann Abogunde – Medical physics opportunities at the Nuclear Regulatory Commission (NRC) The NRC’s responsibilities include the regulation of medical uses of byproduct (radioactive) materials and oversight of medical use end-users (licensees) through a combination of regulatory requirements, licensing, safety oversight including inspection and enforcement, operational experience evaluation, and regulatory support activities. This presentation will explore the career options for medical physicists in the NRC, how the NRC interacts with clinical medical physicists, and a physicist’s experience as a regulator. Learning Objectives: Explore non-clinical career pathways for medical physics students and trainees at the Nuclear Regulatory Commission. Overview of NRC medical applications and medical use regulations. Understand the skills needed for physicists as regulators. Abogunde is funded to attend the meeting by her employer, the NRC.« less

SU-A-210-00: AAPM Medical Physics Student Meeting: Medical Billing and Regulations: Everything You Always Wanted To Know, But Were Too Afraid To Ask

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

NONE

The purpose of this student annual meeting is to address topics that are becoming more relevant to medical physicists, but are not frequently addressed, especially for students and trainees just entering the field. The talk is divided into two parts: medical billing and regulations. Hsinshun Wu – Why should we learn radiation oncology billing? Many medical physicists do not like to be involved with medical billing or coding during their career. They believe billing is not their responsibility and sometimes they even refuse to participate in the billing process if given the chance. This presentation will talk about a physicist’smore » long career and share his own experience that knowing medical billing is not only important and necessary for every young medical physicist, but that good billing knowledge could provide a valuable contribution to his/her medical physics development. Learning Objectives: The audience will learn the basic definition of Current Procedural Terminology (CPT) codes performed in a Radiation Oncology Department. Understand the differences between hospital coding and physician-based or freestanding coding. Apply proper CPT coding for each Radiation Oncology procedure. Each procedure with its specific CPT code will be discussed in detail. The talk will focus on the process of care and use of actual workflow to understand each CPT code. Example coding of a typical Radiation Oncology procedure. Special procedure coding such as brachytherapy, proton therapy, radiosurgery, and SBRT. Maryann Abogunde – Medical physics opportunities at the Nuclear Regulatory Commission (NRC) The NRC’s responsibilities include the regulation of medical uses of byproduct (radioactive) materials and oversight of medical use end-users (licensees) through a combination of regulatory requirements, licensing, safety oversight including inspection and enforcement, operational experience evaluation, and regulatory support activities. This presentation will explore the career options for medical physicists in the NRC, how the NRC interacts with clinical medical physicists, and a physicist’s experience as a regulator. Learning Objectives: Explore non-clinical career pathways for medical physics students and trainees at the Nuclear Regulatory Commission. Overview of NRC medical applications and medical use regulations. Understand the skills needed for physicists as regulators. Abogunde is funded to attend the meeting by her employer, the NRC.« less

Investigating the Role of Hypothalamic Tumor Involvement in Sleep and Cognitive Outcomes Among Children Treated for Craniopharyngioma.

PubMed

Jacola, Lisa M; 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

2016-07-01

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. 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. 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. Routine screening for sleep problems during therapy is indicated for children with craniopharyngioma, to optimize the timing of interventions and reduce long-term morbidity. © The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A case report of metastatic neuroendocrine carcinoma of the right adrenal gland successfully treated with chemotherapy and surgery.

PubMed

Ochiai, Toshiya; Komiyama, Sosuke; Ikoma, Hisashi; Kubota, Takeshi; Nakanishi, Masayoshi; Ichikawa, Daisuke; Kikuchi, Shojiro; Fujiwara, Hitoshi; Sakakura, Chohei; Kokuba, Yukihito; Sonoyama, Teruhisa; Otsuji, Eigo

2010-08-01

Poorly differentiated neuroendocrine carcinoma has a poor prognosis, especially when associated with distant metastasis. A 60-year-old man was admitted to a private hospital because of dyspnea at work in 2007. Computed tomography revealed lung infarction and a right adrenal tumor sized 12 cm in diameter that was tightly compressed against the inferior vena cava (IVC). Moreover, multiple lymph node metastases around the celiac axis and a solitary liver metastasis at the lateral segment were observed. Thus, we planned chemotherapy without surgery. We selected a combination therapy of irinotecan (CPT-11) and cisplatin (CDDP) (i.e., IP therapy): administration of CDDP [60 mg/m(2) body surface area (BSA)] on day 1 plus CPT-11 (80 mg/m(2)) BSA on days 1 and 8. Thereafter, this protocol was repeated at 3-week intervals. After 15 months of this chemotherapy strategy, the whole lesions showed a partial response by RECIST. The primary tumor had shrunk to 4.2 cm in diameter. In November 2008, we planned surgery to perform resection of the whole lesions. Histological diagnosis of the specimen was a poorly differentiated neuroendocrine carcinoma based on the immunostaining features, i.e., synaptophysin- and chromogranin positive. There were no viable tumor cells at the dissected lymph nodes or at the liver tumor. After surgery, CPT-11 administration was continued. The patient has remained well for 9 months without recurrence.

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.

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.

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.

Image cloning beyond diffraction based on coherent population trapping in a hot rubidium vapor.

PubMed

Ding, Dong-Sheng; Zhou, Zhi-Yuan; Shi, Bao-Sen

2014-01-15

Following recent theoretical predictions, we report on an experimental realization of image cloning beyond usual diffraction, through the coherent population trapping (CPT) effect in a hot rubidium vapor. In our experiment, an alphabet letter image was transferred from a coupling field to a probe field, based on the CPT effect. Furthermore, we demonstrate that the cloned probe field carrying the image is transmitted without the usual diffraction. To our best knowledge, this is the first experimental report about image cloning beyond diffraction. We believe this mechanism, based on CPT, has definite and important applications in image metrology, image processing, and biomedical imaging.

Cryptotanshinone exhibits therapeutical effects on cerebral stroke through the PI3K/AKT‑eNOS signaling pathway.

PubMed

Zhu, Weixin; Qiu, Weihong; Lu, Ailan

2017-12-01

Cerebral stroke is a kind of acute cerebrovascular disease with high incidence, morbidity and disability. Treatments against various types of cerebral stroke are limited at preventive measurements due to the lack of effective therapeutic method. The present study aimed to investigate the protective effect of cryptotanshinone (CPT) on cerebral stroke, and investigate the possible mechanism involved in order to develop a novel therapy against stoke. The phosphoinositide 3‑kinase membrane translocation of cerebral stroke rats pretreated with CPT at various concentrations were measured, as well as the phosphorylation of protein kinase B (AKT) and endothelial nitric oxide synthase (eNOS). Additionally, the expression level of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) and vascular endothelial growth factor were also assessed using western blotting and reverse transcription‑quantitative polymerase chain reaction. Furthermore, biochemical tests were used to measure the activity of superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) in both the cerebral cortex and peripheral blood. As a result, CPT‑pretreated rats presented declined phosphoinositide 3‑kinase (PI3K) and AKT expression levels, indicating that the PI3K/AKT signaling pathway was inhibited. Increased Bcl‑2 and NO levels in both the cerebral cortex and peripheral blood demonstrated the anti‑apoptosis and blood vessel protection effect of CPT. Furthermore, increased SOD activity and declined MDA levels demonstrated suppressed lipid peroxidation. In conclusion, CPT exhibited a protective effect against cerebral stroke through inhibition of the PI3K/AKT‑eNOS signaling pathway. These results suggested the potential of CPT as a promising agent in the treatment of cerebral stroke.

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

Review of LOGEX. Main Report and Appendixes A-I

DTIC Science & Technology

1975-05-23

been developed on an RCA Spectra 70 machine located at the Army Logistics Management Center, Fort Lee, Virginia. This was undoubtedly an outstanding...Control Number ADP - Automatic Data Processing ACT - Active Duty for Training ALMC - US Army Logistics Management Center AMO - Ammunition AR - Amy...Directorate CPT McClellan, LOGEX Directorate CPT Weaver, LOGEX Directorate United States Army Logistics Management Center Mr. Loper Mr. Ross United States

Can an intervention based on a serious videogame prior to cognitive behavioral therapy be helpful in bulimia nervosa? A clinical case study

PubMed Central

Giner-Bartolomé, Cristina; Fagundo, Ana B.; Sánchez, Isabel; Jiménez-Murcia, Susana; Santamaría, Juan J.; Ladouceur, Robert; Menchón, José M.; Fernández-Aranda, Fernando

2015-01-01

Background: Several studies have highlighted the implications of impulsivity and novelty seeking for both the maintenance and the process of recovery from bulimia nervosa (BN). Cognitive behavioral therapy (CBT) is the treatment of choice for BN, but for some cases, this treatment alone might not be sufficient for reducing the high levels of impulsivity. The paper presents a case report of a patient with BN, examining the effectiveness of using a videogame (VG; Playmancer) as an additional intervention designed to address impulsivity. Design: Psychometric and neuropsychological measures were collected at baseline. After this assessment, Playmancer was applied prior to CBT, following an “A-B-A-C-A” single case experimental design. Impulsivity levels were assessed with the Conner’s Continuous Performance Test II (CPT-II). After the Playmancer treatment, the patient started CBT, and the levels of impulsivity were recorded again. Finally, psychometric and neuropsychological measures were collected after treatment. Weekly frequency of binges and vomiting were also recorded during the entire procedure. Results: After the VG intervention, psychometric measures such as anxiety levels, impulsivity and novelty seeking decreased. Regarding the neuropsychological measures, impulsivity levels (measured with the CPT-II) progressively decreased throughout the intervention, and an improvement in decision making capacities was observed. Furthermore, the frequency of binges also decreased during and after the VG intervention. Discussion: This case report suggests that using the Playmancer VG to reduce impulsivity prior to CBT may enhance the final results of the treatment for BN. PMID:26236261

In rape trauma PTSD, patient characteristics indicate which trauma-focused treatment they are most likely to complete.

PubMed

Keefe, John R; Wiltsey Stirman, Shannon; Cohen, Zachary D; DeRubeis, Robert J; Smith, Brian N; Resick, Patricia A

2018-04-01

Dropout rates for effective therapies for posttraumatic stress disorder (PTSD) can be high, especially in practice settings. Although clinicians have intuitions regarding what treatment patients may complete, there are few systematic data to drive those judgments. A multivariable model of dropout risk was constructed with randomized clinical trial data (n = 160) comparing prolonged exposure (PE) and cognitive processing therapy (CPT) for rape-induced PTSD. A two-step bootstrapped variable selection algorithm was applied to identify moderators of dropout as a function of treatment condition. Employing identified moderators in a model, fivefold cross-validation yielded estimates of dropout probability for each patient in each condition. Dropout rates between patients who did and did not receive their model-indicated treatment were compared. Despite equivalent dropout rates across treatments, patients assigned to their model-indicated treatment were significantly less likely to drop out relative to patients who did not (relative risk = 0.49 [95% CI: 0.29-0.82]). Moderators included in the model were: childhood physical abuse, current relationship conflict, anger, and being a racial minority, all of which were associated with higher likelihood of dropout in PE than CPT. Individual differences among patients affect the likelihood they will complete a particular treatment, and clinicians can consider these moderators in treatment planning. In the future, treatment selection models could be used to increase the percentage of patients who will receive a full course of treatment, but replication and extension of such models, and consideration of how best to integrate them into routine practice, are needed. © 2018 Wiley Periodicals, Inc.

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.

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.

Role of the protein in the DNA sequence specificity of the cleavage site stabilized by the camptothecin topoisomerase IB inhibitor: a metadynamics study

PubMed Central

Coletta, Andrea; Desideri, Alessandro

2013-01-01

Camptothecin (CPT) is a topoisomerase IB (TopIB) selective inhibitor whose derivatives are currently used in cancer therapy. TopIB cleaves DNA at any sequence, but in the presence of CPT the only stabilized protein–DNA covalent complex is the one having a thymine in position −1 with respect to the cleavage site. A metadynamics simulation of two TopIB–DNA–CPT ternary complexes differing for the presence of a thymine or a cytosine in position −1 indicates the occurrence of two different drug’s unbinding pathways. The free-energy difference between the bound state and the transition state is large when a thymine is present in position −1 and is strongly reduced in presence of a cytosine, in line with the different drug stabilization properties of the two systems. Such a difference is strictly related to the changes in the hydrogen bond network between the protein, the DNA and the drug in the two systems, indicating a direct role of the protein in determining the specificity of the cleavage site sequence stabilized by the CPT. Calculations carried out in presence of one compound of the indenoisoquinoline family (NSC314622) indicate a comparable energy difference between the bound and the transition state independently of the presence of a thymine or a cytosine in position −1, in line with the experimental results. PMID:24003027

Delivering TB/HIV services in Ghana: a comparative study of service delivery models.

PubMed

Ansa, Gloria A; Walley, John D; Siddiqi, Kamran; Wei, Xiaolin

2014-09-01

TB and HIV interaction increases TB incidence and HIV adverse outcomes. Integration improves patients' access to comprehensive care. This paper compares the impact of increasing integration on TB/HIV service delivery. Three hospitals with different delivery models were identified and a survey of TB cases registered between June 2007 and December 2008 conducted. HIV screening, co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) uptake for HIV-positive TB patients were compared. Of the 590 TB patients, 85.9% (507/590) knew their HIV status. HIV screening was highest (98.6% [95%CI: 97.6-99.5%]) at the one-stop shop (OSS) and lowest (72.5% [71.9-73.9%]) at the referral site (RS). CPT was highest [(93.8% [91.0-96.7%]) at the RS and least (74.7% [72.8-76.5%]) at the partially-integrated site (PIS). At the OSS it was 82.3% (80.6-84.0%). ART was highest (59.5% [58.0-61.0%]) at the PIS, and 10.8% (10.4-11.1%) at the RS. No ART records existed at the OSS. Increasing integration improved HIV screening but not CPT or ART uptake. There was insufficient evidence to identify the most effective model due to design limitations and health system barriers. More research and training is needed to improve uptake, data completeness and accuracy. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

Fatty acid carbon is essential for dNTP synthesis in endothelial cells

PubMed Central

Missiaen, Rindert; Queiroz, Karla CS; Borgers, Gitte; Elia, Ilaria; Zecchin, Annalisa; Cantelmo, Anna Rita; Christen, Stefan; Goveia, Jermaine; Heggermont, Ward; Goddé, Lucica; Vinckier, Stefan; Van Veldhoven, Paul P.; Eelen, Guy; Schoonjans, Luc; Gerhardt, Holger; Dewerchin, Mieke; Baes, Myriam; De Bock, Katrien; Ghesquière, Bart; Lunt, Sophia Y.; Fendt, Sarah-Maria; Carmeliet, Peter

2015-01-01

The metabolism of endothelial cells (ECs) during vessel sprouting remains poorly studied. Here, we report that endothelial loss of CPT1a, a rate-limiting enzyme of fatty acid oxidation (FAO), caused vascular sprouting defects due to impaired proliferation, not migration of ECs. Reduction of FAO in ECs did not cause energy depletion or disturb redox homeostasis, but impaired de novo nucleotide synthesis for DNA replication. Isotope labeling studies in control ECs showed that fatty acid carbons substantially replenished the Krebs cycle, and were incorporated into aspartate (a nucleotide precursor), uridine monophosphate (a precursor of pyrimidine nucleoside triphosphates) and DNA. CPT1a silencing reduced these processes and depleted EC stores of aspartate and deoxyribonucleoside triphosphates. Acetate (metabolized to acetyl-CoA, thereby substituting for the depleted FAO-derived acetyl-CoA) or a nucleoside mix rescued the phenotype of CPT1a-silenced ECs. Finally, CPT1 blockade inhibited pathological ocular angiogenesis, suggesting a novel strategy for blocking angiogenesis. PMID:25830893

Controlled release of silyl ether camptothecin from thiol-ene click chemistry-functionalized mesoporous silica nanoparticles.

PubMed

Yan, Yue; Fu, Jie; Wang, Tianfu; Lu, Xiuyang

2017-03-15

As efficient drug carriers, stimuli-responsive mesoporous silica nanoparticles are at the forefront of research on drug delivery systems. An acid-responsive system based on silyl ether has been applied to deliver a hybrid prodrug. Thiol-ene click chemistry has been successfully utilized for tethering this prodrug to mesoporous silica nanoparticles. Here, by altering the steric bulk of the substituent on the silicon atom, the release rate of a model drug, camptothecin, was controlled. The synthesized drug delivery system was investigated by analytical methods to confirm the functionalization and conjugation of the mesoporous silica nanoparticles. Herein, trimethyl silyl ether and triethyl silyl ether were selected to regulate the release rate. Under normal plasma conditions (pH 7.4), both types of camptothecin-loaded mesoporous silica nanoparticles (i.e., MSN-Me-CPT and MSN-Et-CPT) did not release the model drug. However, under in vitro acidic conditions (pH 4.0), based on a comparison of the release rates, camptothecin was released from MSN-Me-CPT more rapidly than from MSN-Et-CPT. To determine the biocompatibility of the modified mesoporous silica nanoparticles and the in vivo camptothecin uptake behavior, MTT assays with cancer cells and confocal microscopy observations were conducted, with positive results. These functionalized nanoparticles could be useful in clinical treatments requiring controlled drug release. As the release rate of drug from drug-carrier plays important role in therapy effects, trimethyl silyl ether (TMS) and triethyl silyl ether (TES) were selected as acid-sensitive silanes to control the release rates of model drugs conjugated from MSNs by thiol-ene click chemistry. The kinetic profiles of TMS and TES materials have been studied. At pH 4.0, the release of camptothecin from MSN-Et-CPT occurred after 2h, whereas MSN-Me-CPT showed immediate drug release. The results showed that silyl ether could be used to control release rates of drugs from MSNs under acid environment, which could be useful in clinical treatments requiring controlled drug release. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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.

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

Proton Radiotherapy for High-Risk Pediatric Neuroblastoma: Early Outcomes and Dose Comparison

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

Hattangadi, Jona A.; Rombi, Barbara; Provincial Agency for Proton Therapy, Trento

2012-07-01

Purpose: To report the early outcomes for children with high-risk neuroblastoma treated with proton radiotherapy (RT) and to compare the dose distributions for intensity-modulated photon RT (IMRT), three-dimensional conformal proton RT (3D-CPT), and intensity-modulated proton RT to the postoperative tumor bed. Methods and Materials: All patients with high-risk (International Neuroblastoma Staging System Stage III or IV) neuroblastoma treated between 2005 and 2010 at our institution were included. All patients received induction chemotherapy, surgical resection of residual disease, high-dose chemotherapy with stem cell rescue, and adjuvant 3D-CPT to the primary tumor sites. The patients were followed with clinical examinations, imaging, andmore » laboratory testing every 6 months to monitor disease control and side effects. IMRT, 3D-CPT, and intensity-modulated proton RT plans were generated and compared for a representative case of adjuvant RT to the primary tumor bed followed by a boost. Results: Nine patients were treated with 3D-CPT. The median age at diagnosis was 2 years (range 10 months to 4 years), and all patients had Stage IV disease. All patients had unfavorable histologic characteristics (poorly differentiated histologic features in 8, N-Myc amplification in 6, and 1p/11q chromosomal abnormalities in 4). The median tumor size at diagnosis was 11.4 cm (range 7-16) in maximal dimension. At a median follow-up of 38 months (range 11-70), there were no local failures. Four patients developed distant failure, and, of these, two died of disease. Acute side effects included Grade 1 skin erythema in 5 patients and Grade 2 anorexia in 2 patients. Although comparable target coverage was achieved with all three modalities, proton therapy achieved substantial normal tissue sparing compared with IMRT. Intensity-modulated proton RT allowed additional sparing of the kidneys, lungs, and heart. Conclusions: Preliminary outcomes reveal excellent local control with proton therapy for high-risk neuroblastoma, although distant failures continu to occur. Dosimetric comparisons demonstrate the advantage of proton RT compared with IMRT in this setting, allowing more conformal treatment and better normal tissue sparing.« less

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.

Exoskeleton-assisted gait training to improve gait in individuals with spinal cord injury: a pilot randomized study.

PubMed

Chang, Shuo-Hsiu; Afzal, Taimoor; Berliner, Jeffrey; Francisco, Gerard E

2018-01-01

Robotic wearable exoskeletons have been utilized as a gait training device in persons with spinal cord injury. This pilot study investigated the feasibility of offering exoskeleton-assisted gait training (EGT) on gait in individuals with incomplete spinal cord injury (iSCI) in preparation for a phase III RCT. The objective was to assess treatment reliability and potential efficacy of EGT and conventional physical therapy (CPT). Forty-four individuals were screened, and 13 were eligible to participate in the study. Nine participants consented and were randomly assigned to receive either EGT or CPT with focus on gait. Subjects received EGT or CPT, five sessions a week (1 h/session daily) for 3 weeks. American Spinal Injury Association (ASIA) Lower Extremity Motor Score (LEMS), 10-Meter Walk Test (10MWT), 6-Minute Walk Test (6MWT), Timed Up and Go (TUG) test, and gait characteristics including stride and step length, cadence and stance, and swing phase durations were assessed at the pre- and immediate post- training. Mean difference estimates with 95% confidence intervals were used to analyze the differences. After training, improvement was observed in the 6MWT for the EGT group. The CPT group showed significant improvement in the TUG test. Both the EGT and the CPT groups showed significant increase in the right step length. EGT group also showed improvement in the stride length. EGT could be applied to individuals with iSCI to facilitate gait recovery. The subjects were able to tolerate the treatment; however, exoskeleton size range may be a limiting factor in recruiting larger cohort of patients. Future studies with larger sample size are needed to investigate the effectiveness and efficacy of exoskeleton-assisted gait training as single gait training and combined with other gait training strategies. Clinicaltrials.org, NCT03011099, retrospectively registered on January 3, 2017.

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.

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.

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:

[Chemotherapy-induced diarrhea].

PubMed

Kobayashi, Kunihiko

2003-06-01

Chemotherapy-induced diarrhea is a well-documented side effect of many cancer treatments and is associated with increased morbidity and mortality. Chemotherapy-induced diarrhea negatively impacts patient quality of life and treatment outcome by requiring dose limitations or treatment interruption. The chemotherapeutic agent CPT-11 (irinotecan) has shown promising results as a single agent and in combination chemotherapy for the treatment of colorectal and small cell lung cancer. However, delayed onset diarrhea is considered to be its major dose-limiting toxicity. In some cases, it can be life threatening. To prevent CPT-11-induced delayed diarrhea, oral alkalization (OA) and control of defecation (CD) [Int J Cancer 92: 269-275, 2001] were developed based on fundamental studies [Int J Cancer 83: 491-496, 1999; Cancer Res 62: 179-187, 2002]. Oral administration of antibiotics [Cancer Res 56: 3752-3757, 1996; Clin Cancer Res 7: 1136-1141, 2001] or kampo medicine [Jpn J Cancer Res 86: 978-984, 1995; Jpn J Cancer Res 86: 985-989, 1995] to decrease beta-glucuronidase activity derived from bacteria in the large intestine was also reported to be successful in preventing delayed diarrhea. When CPT-11-induced delayed diarrhea occurs, the conventional treatment is loperamide [J Natl Cancer Inst 86: 446-449, 1994], and the early recognition and treatment of diarrhea with this opioid has reduced, although not entirely eliminated, patient morbidity. Other therapies are needed to treat patients with loperamide-refractory CPT-11 induced diarrhea, and the successful use of the somatostatin analogue octreotide has been reported [Support Care Cancer 9: 258-260, 2001; Ann Oncol 12: 227-229, 2001; Proc Am Soc Clin Oncol 21: 387a, 2002].

Sustained and transient attention in the continuous performance task.

PubMed

Smid, H G O M; de Witte, M R; Homminga, I; van den Bosch, R J

2006-08-01

One of the most frequently applied methods to study abnormal cognition is the Continuous Performance Task (CPT). It is unclear, however, which cognitive functions are engaged in normal CPT performance. The aims of the present study were to identify the neurocognitive functions engaged in the main variants of the CPT and to determine to what extent these variants differentially engage these functions. We hypothesized that the main CPT versions (CPT-X, CPT-AX, CPT-Identical Pairs) can be distinguished by whether they demand sustained or transient attention and sustained or transient response preparation. Transient attention to objects like letters or digits, that is, the need to switch attention to different objects from trial to trial, impairs target detection accuracy relative to sustained attention to a single object. Transient response preparation, that is, the possibility to switch response preparation on and off from trial to trial, improves response speed relative to having to sustain response preparation across all trials. Comparison of task performance and Event-Related brain Potentials (ERPs) of healthy participants obtained in the main CPT variants confirmed these hypotheses. Behavioral and ERP measures indicated worse target detection in the CPT-AX than in the CPT-X, consistent with a higher demand on transient attention in that task. In contrast, behavioral and ERP measures indicated higher response speed in the CPT-AX than in the CPT-X, associated with more response preparation in advance of the targets. This supports the idea of increased transient response preparation in the CPT-AX. We conclude that CPTs differ along at least two task variables that each influences a different cognitive function.

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.

Effects of organic solvents on drug incorporation into polymeric carriers and morphological analyses of drug-incorporated polymeric micelles.

PubMed

Harada, Yoshiko; Yamamoto, Tatsuhiro; Sakai, Masaru; Saiki, Toshiharu; Kawano, Kumi; Maitani, Yoshie; Yokoyama, Masayuki

2011-02-14

We incorporated an anticancer agent, camptothecin (CPT), into polymeric micelle carriers by using two different solvents (TFE and chloroform) in the solvent-evaporation drug incorporation process. We observed significant differences in the drug-incorporation behaviors, in the morphologies of the incorporated drug and the polymeric micelles, and in the pharmacokinetic behaviors between the two solvents' cases. In particular, the CPT-incorporated polymeric micelles prepared with TFE as the incorporation solvent exhibited more stable circulation in blood than those prepared with chloroform. This contrast indicates a novel technological perspective regarding the drug incorporation into polymeric micelle carriers. Morphological analyses of the inner core have revealed the presence of the directed alignment of the CPT molecules and CPT crystals in the micelle inner core. This is the first report of the morphologies of the drug incorporated into the polymeric micelle inner cores. We believe these analyses are very important for further pharmaceutical developments of polymeric micelle drug-carrier systems. Copyright © 2010 Elsevier B.V. All rights reserved.

The use of response surface methodology in the evaluation of captopril microparticles manufactured using an oil in oil solvent evaporation technique.

PubMed

Khamanga, Sandile Maswazi; Walker, Roderick B

2012-01-01

Captopril (CPT) microparticles were manufactured by solvent evaporation using acetone (dispersion phase) and liquid paraffin (manufacturing phase) with Eudragit® and Methocel® as coat materials. Design of experiments and response surface methodology (RSM) approaches were used to optimize the process. The microparticles were characterized based on the percent of drug released and yield, microcapsule size, entrapment efficiency and Hausner ratio. Differential scanning calorimetry (DSC), Infrared (IR) spectroscopy, scanning electron microscopy (SEM) and in vitro dissolution studies were conducted. The microcapsules were spherical, free-flowing and IR and DSC thermograms revealed that CPT was stable. The percent drug released was investigated with respect to Eudragit® RS and Methocel® K100M, Methocel® K15M concentrations and homogenizing speed. The optimal conditions for microencapsulation were 1.12 g Eudragit® RS, 0.67 g Methocel® K100M and 0.39 g Methocel® K15M at a homogenizing speed of 1643 rpm and 89% CPT was released. The value of RSM-mediated microencapsulation of CPT was elucidated.

Magnetic graphene oxide as a carrier for targeted delivery of chemotherapy drugs in cancer therapy

NASA Astrophysics Data System (ADS)

Huang, Ya-Shu; Lu, Yu-Jen; Chen, Jyh-Ping

2017-04-01

A magnetic targeted functionalized graphene oxide (GO) complex is constituted as a nanocarrier for targeted delivery and pH-responsive controlled release of chemotherapy drugs to cancer cells. Magnetic graphene oxide (mGO) was prepared by chemical co-precipitation of Fe3O4 magnetic nanoparticles on GO nano-platelets. The mGO was successively modified by chitosan and mPEG-NHS through covalent bindings to synthesize mGOC-PEG. The polyethylene glycol (PEG) moiety is expected to prolong the circulation time of mGO by reducing the reticuloendothelial system clearance. Irinotecan (CPT-11) or doxorubicin (DOX) was loaded to mGOC-PEG through π-π stacking interactions for magnetic targeted delivery of the cancer chemotherapy drug. The best values of loading efficiency and loading content of CPT-11 were 54% and 2.7% respectively; whereas for DOX, they were 65% and 393% The pH-dependent drug release profile was further experimented at different pHs, in which 60% of DOX was released at pH 5.4 and 10% was released at pH 7.4. In contrast, 90% CPT-11 was released at pH 5.4 and 70% at pH 7.4. Based on the drug loading and release characteristics, mGOC-PEG/DOX was further chosen for in vitro cytotoxicity tests against U87 human glioblastoma cell line. The IC50 value of mGOC-PEG/DOX was found to be similar to that of free DOX but was reduced dramatically when subject to magnetic targeting. It is concluded that with the high drug loading and pH-dependent drug release properties, mGOC-PEG will be a promising drug carrier for targeted delivery of chemotherapy drugs in cancer therapy.

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.

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.

[Assessment of therapeutic passive hypothermia in newborns with hypoxic-ischemic encephalopathy that need interhospital transport].

PubMed

Fuentes-Ruiz, José A; Lagares-Franco, Carolina; Rodríguez-Molina, Óscar; Cordero-Cañas, Enrique; Benavente-Fernández, Isabel

2015-04-01

Induced hypothermia for the first hours of life in a newborn is an effective treatment to reduce mortality and serious effects in neonates that had suffered a hypoxia episode. This method needs an universal attendance independently of the place of birth being usually necessary a transfer to the reference hospital. To analyze the efficacy of the newborn with hypoxic-ischemic encephalopathy transfer in passive hypothermia. Descriptive study of series of cases with retrospective character of newborn from Cadiz's province that need induced hypothermia. 46 newborn were included in the study: 33 of them (71.74%) needed being transfer by the Critical Patients Transport service (CPT group), the rest (28.26%) were born into the reference hospital. Both groups are similar in age gestational at birth, sex, weight and hypoxic-ischemic encephalopathy degree. It analyzed variables related to hypothermia therapy and in addition in CPT group transfer specific variables. At discharge, it does not exist significant differences between groups in the efficiency-consequence of neuroprotection therapy with hypothermia (p = 0.159). It does not find complications derived from the interhospital move. Neonatal inter-hospital transfer in passive therapeutic hypothermia is effective, safe and necessary for the therapy compliance. It is required reach an agreement between the attendance and the reference service, setting up guides for the support and suitable range of temperature.

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

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.

Effectiveness of Commercial Gaming-Based Virtual Reality Movement Therapy on Functional Recovery of Upper Extremity in Subacute Stroke Patients

PubMed Central

Choi, Jun Hwan; Kim, Bo Ryun; Kim, Sun Mi; Im, Sang Hee; Lee, So Young; Hyun, Chul Woong

2014-01-01

Objective To investigate the effectiveness of commercial gaming-based virtual reality (VR) therapy on the recovery of paretic upper extremity in subacute stroke patients. Methods Twenty patients with the first-onset subacute stroke were enrolled and randomly assigned to the case group (n=10) and the control group (n=10). Primary outcome was measured by the upper limb score through the Fugl-Meyer Assessment (FMA-UL) for the motor function of both upper extremities. Secondary outcomes were assessed for motor function of both upper extremities including manual function test (MFT), box and block test (BBT), grip strength, evaluated for activities of daily living (Korean version of Modified Barthel Index [K-MBI]), and cognitive functions (Korean version of the Mini-Mental State Examination [K-MMSE] and continuous performance test [CPT]). The case group received commercial gaming-based VR therapy using Wii (Nintendo, Tokyo, Japan), and the control group received conventional occupational therapy (OT) for 30 minutes a day during the period of 4 weeks. All patients were evaluated before and after the 4-week intervention. Results There were no significant differences in the baseline between the two groups. After 4 weeks, both groups showed significant improvement in the FMA-UL, MFT, BBT, K-MBI, K-MMSE, and correct detection of auditory CPT. However, grip strength was improved significantly only in the case group. There were no significant intergroup differences before and after the treatment. Conclusion These findings suggested that the commercial gaming-based VR therapy was as effective as conventional OT on the recovery of upper extremity motor and daily living function in subacute stroke patients. PMID:25229027

Effectiveness of commercial gaming-based virtual reality movement therapy on functional recovery of upper extremity in subacute stroke patients.

PubMed

Choi, Jun Hwan; Han, Eun Young; Kim, Bo Ryun; Kim, Sun Mi; Im, Sang Hee; Lee, So Young; Hyun, Chul Woong

2014-08-01

To investigate the effectiveness of commercial gaming-based virtual reality (VR) therapy on the recovery of paretic upper extremity in subacute stroke patients. Twenty patients with the first-onset subacute stroke were enrolled and randomly assigned to the case group (n=10) and the control group (n=10). Primary outcome was measured by the upper limb score through the Fugl-Meyer Assessment (FMA-UL) for the motor function of both upper extremities. Secondary outcomes were assessed for motor function of both upper extremities including manual function test (MFT), box and block test (BBT), grip strength, evaluated for activities of daily living (Korean version of Modified Barthel Index [K-MBI]), and cognitive functions (Korean version of the Mini-Mental State Examination [K-MMSE] and continuous performance test [CPT]). The case group received commercial gaming-based VR therapy using Wii (Nintendo, Tokyo, Japan), and the control group received conventional occupational therapy (OT) for 30 minutes a day during the period of 4 weeks. All patients were evaluated before and after the 4-week intervention. There were no significant differences in the baseline between the two groups. After 4 weeks, both groups showed significant improvement in the FMA-UL, MFT, BBT, K-MBI, K-MMSE, and correct detection of auditory CPT. However, grip strength was improved significantly only in the case group. There were no significant intergroup differences before and after the treatment. These findings suggested that the commercial gaming-based VR therapy was as effective as conventional OT on the recovery of upper extremity motor and daily living function in subacute stroke patients.

[A case of cytology-positive, stage IV gastric cancer, alive with no recurrence for 4 years, curatively treated with combination chemotherapy using S-1, CPT-11 and subsequent total gastrectomy].

PubMed

Kubo, Naoshi; Nobuhara, Yasuyuki; Kanemura, Mizuyuki; Sunami, Takeshi; Nishimura, Shigehiko; Ako, Eiji; Yo, Taiho

2007-11-01

A 68-year-old man was admitted to another hospital because of progressive weight decrease and appetite loss. Endoscopic examination revealed type 4 advanced gastric cancer at the upper body of the stomach. In February, 2003, he patient had probe laparotomy because there was a small amount of ascites in his peritoneal cavity, and intraoperative washing cytology revealed cancer cells in ascites.Subsequently, we started chemotherapy using S-1 and CPT-11. S-1 at a dose of 100 mg/day was orally administered for 2 weeks, and CPT-11 at a dose of 90 mg/body was intravenously administered once a week for 2 weeks followed by a 2-week drug-free period as 1 course. After 7 courses of the chemotherapy, the main lesion endoscopically vanished.Subsequently, the patient underwent curative total gastrectomy together with D2 lymph node dissection. Intraoperative cytology revealed no cancer cells, and histological examination of the primary lesion showed cancer cells invading the subserosa with no metastasis to any dissected lymph nodes. This therapy induced Grade 2 effect on cancer cells.Postoperatively, only S-1 was administered to the patient, who has remained alive with no recurrence for 4 years as of January, 2007.

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.

Effectiveness of manual therapy versus surgery in pain processing due to carpal tunnel syndrome: A randomized clinical trial.

PubMed

Fernández-de-Las-Peñas, C; Cleland, J; Palacios-Ceña, M; Fuensalida-Novo, S; Alonso-Blanco, C; Pareja, J A; Alburquerque-Sendín, F

2017-08-01

People with carpal tunnel syndrome (CTS) exhibit widespread pressure pain and thermal pain hypersensitivity as a manifestation of central sensitization. The aim of our study was to compare the effectiveness of manual therapy versus surgery for improving pain and nociceptive gain processing in people with CTS. The trial was conducted at a local regional Hospital in Madrid, Spain from August 2014 to February 2015. In this randomized parallel-group, blinded, clinical trial, 100 women with CTS were randomly allocated to either manual therapy (n = 50), who received three sessions (once/week) of manual therapies including desensitization manoeuvres of the central nervous system, or surgical intervention (n = 50) group. Outcomes including pressure pain thresholds (PPT), thermal pain thresholds (HPT or CPT), and pain intensity which were assessed at baseline, and 3, 6, 9 and 12 months after the intervention by an assessor unaware of group assignment. Analysis was by intention to treat with mixed ANCOVAs adjusted for baseline scores. At 12 months, 95 women completed the follow-up. Patients receiving manual therapy exhibited higher increases in PPT over the carpal tunnel at 3, 6 and 9 months (all, p < 0.01) and higher decrease of pain intensity at 3 month follow-up (p < 0.001) than those receiving surgery. No significant differences were observed between groups for the remaining outcomes. Manual therapy and surgery have similar effects on decreasing widespread pressure pain sensitivity and pain intensity in women with CTS. Neither manual therapy nor surgery resulted in changes in thermal pain sensitivity. The current study found that manual therapy and surgery exhibited similar effects on decreasing widespread pressure pain sensitivity and pain intensity in women with carpal tunnel syndrome at medium- and long-term follow-ups investigating changes in nociceptive gain processing after treatment in carpal tunnel syndrome. © 2017 European Pain Federation - EFIC®.

Pegaptanib sodium as maintenance therapy in neovascular age-related macular degeneration: the LEVEL study.

PubMed

Friberg, Thomas R; Tolentino, Michael; Weber, Pamela; Patel, Sunil; Campbell, Scott; Goldbaum, Mauro

2010-12-01

To assess the efficacy of pegaptanib as maintenance therapy in neovascular age-related macular degeneration (NV-AMD) patients after induction therapy. A phase IV, prospective, open-label, uncontrolled exploratory study including subjects with subfoveal NV-AMD who had had one to three induction treatments 30-120 days before entry and showed investigator-determined clinical/anatomical NV-AMD improvement. Lesions in the study eye were: any subtype, 12 or fewer disc areas; postinduction centre point thickness (CPT) 275 μm or less or thinning of 100 μm or more (optical coherence tomography); visual acuity (VA) 20/20-20/400. Intravitreal pegaptanib 0.3 mg was administered as maintenance every 6 weeks for 48 weeks with follow-up to week 54. Booster treatment additional unscheduled treatment for wet age-related macular degeneration, was allowed in the study eye at the investigators' discretion for clinical deterioration. Of 568 enrolled subjects, 86% completed 1 year of pegaptanib. Mean VA improvement during induction (49.6 to 65.5 letters) was well preserved (54-week mean 61.8 letters). Mean CPT was relatively stable during maintenance (20 μm increase during the study). Fifty per cent did not receive unscheduled booster treatment to week 54; 46% did have one such booster (mean 147 days after maintenance initiation). An induction-maintenance strategy, using non-selective then selective vascular endothelial growth factor (VEGF) inhibitors, could be considered for NV-AMD. This approach may have particular relevance for patients with systemic comorbidities who require long-term anti-VEGF therapy for NV-AMD.

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.

High expression of sphingosine kinase 1 and S1P receptors in chemotherapy-resistant prostate cancer PC3 cells and their camptothecin-induced up-regulation

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

Akao, Yukihiro; Banno, Yoshiko; Nakagawa, Yoshihito

2006-04-21

Although most of pharmacological therapies for cancer utilize the apoptotic machinery of the cells, the available anti-cancer drugs are limited due to the ability of prostate cancer cells to escape from the anti-cancer drug-induced apoptosis. A human prostate cancer cell line PC3 is resistant to camptothecin (CPT). To elucidate the mechanism of this resistance, we have examined the involvement of sphingosine kinase (SPHK) and sphingosine 1-phosphate (S1P) receptor in CPT-resistant PC3 and -sensitive LNCaP cells. PC3 cells exhibited higher activity accompanied with higher expression levels of protein and mRNA of SPHK1, and also elevated expression of S1P receptors, S1P{sub 1}more » and S1P{sub 3}, as compared with those of LNCaP cells. The knockdown of SPHK1 by small interfering RNA and inhibition of S1P receptor signaling by pertussis toxin in PC3 cells induced significant inhibition of cell growth, suggesting implication of SPHK1 and S1P receptors in cell proliferation in PC3 cells. Furthermore, the treatment of PC3 cells with CPT was found to induce up-regulation of the SPHK1/S1P signaling by induction of both SPHK1 enzyme and S1P{sub 1}/S1P{sub 3} receptors. These findings strongly suggest that high expression and up-regulation of SPHK1 and S1P receptors protect PC3 cells from the apoptosis induced by CPT.« less

Synthesis and Applications of Multimodal Hybrid Albumin Nanoparticles for Chemotherapeutic Drug Delivery and Photothermal Therapy Platforms

NASA Astrophysics Data System (ADS)

Peralta, Donna V.

Progress has been made in using human serum albumin nanoparticles (HSAPs) as carrier systems for targeted treatment of cancer. Human serum albumin (HSA), the most abundant human blood protein, can form HSAPs via a desolvation and crosslinking method, with the size of the HSAPs having crucial importance for drug loading and in vivo performance. Gold nanoparticles have also gained medicinal attention due to their ability to absorb near-infrared (NIR) light. These relatively non-toxic particles offer combinational therapy via imaging and photothermal therapy (PPTT) capabilities. A desolvation and crosslinking approach was employed to encapsulate gold nanoparticles (AuNPs), hollow gold nanoshells (AuNSs), and gold nanorods (AuNRs), into efficiently sized HSAPs for future tumor heat ablation via PPTT. The AuNR-HSAPs, AuNP-HSAPs and AuNS-HSAPs had average particle diameters of 222 +/- 5, 195 +/- 9 and 156 +/- 15, respectively. We simultaneously encapsulated AuNRs and the anticancer drug paclitaxel (PAC), forming PAC-AuNR-HSAPs with overall average particle size of 299 +/- 6 nm. Loading of paclitaxel into PAC-AuNR-HSAPs reached 3microg PAC/mg HSA. PAC-AuNR-HSAPs experienced photothermal heating of 46 °C after 15 minutes of NIR laser exposure; the temperature necessary to cause severe cellular hyperthermia. There was a burst release of paclitaxel up to 188 ng caused by the irradiation session, followed by a temporal drug release. AuNR-HSAPs were tested for ablation of renal cell carcinoma using NIR irradiation in vitro. Particles created with the same amount of AuNRs, but varying HSA (1, 5 or 20 mg) showed overall particle size diameters 409 +/- 224, 294 +/- 83 and 167 +/- 4 nm, respectively. Increasing HSAPs causes more toxicity under non-irradiated treatment conditions: AuNR-HSAPs with 20 mg versus 5 mg HSA caused cell viability of 64.5% versus 87%, respectively. All AuNR-HSAPs batches experienced photothermal heating above 42 °C. Coumarin-6, was used to visualize the cellular uptake of AuNR-HSAPs via fluorescence microscopy. Finally, camptothecin (CPT) an antineoplastic agent and BACPT (7-butyl-10-aminocamptothecin) were loaded into HSAPs to combat their aqueous insolubility. BACPT-HSAPs loaded up to 5.25 micrograms BACPT/ mg of HSA. CPT encapsulation could not be determined. BACPT-HSAPs and CPT-HSAPs showed cytotoxicity to human sarcoma cells in vitro. Key words: Hybrid Nanoparticles, Photothermal Therapy, Gold Nanomaterials, Drug Delivery, Combinational Cancer Therapies, Materials, Human Serum Albumin, Colloidal Carriers.

Annual Research Progress Report for Department of Clinical Investigation (Madigan Army Medical Center), October 1990 - September 1991

DTIC Science & Technology

1991-09-01

approach ethically difficult to justify. Untreated observation until 2 years post injury follows for both groups. Information pertaining to seizure ...completing adjuvant therapy, except for tamoxifen and DES. Patients with a history of deep vein thrombosis, cerebral embolus, stroke , congestive heart...Controlled Hypertensive Patients Arthur Herpolsheimer Pulmonary Function of Preeclamptic Women CPT, MC Receiving Intravenous Magnesium Sulfate Seizure

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.

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 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

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...

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.

A Clinician’s Guide to PTSD Treatments for Returning Veterans

PubMed Central

Sharpless, Brian A.; Barber, Jacques P.

2011-01-01

What options are available to mental health providers helping clients with posttraumatic stress disorder (PTSD)? In this paper we review many of the current pharmacological and psychological interventions available to help prevent and treat PTSD with an emphasis on combat-related traumas and Veteran populations. There is strong evidence supporting the use of several therapies including prolonged exposure (PE), eye movement desensitization and reprocessing (EMDR), and cognitive processing therapies (CPT), with PE possessing the most empirical evidence in favor of its efficacy. There have been relatively fewer studies of non-exposure based modalities (e.g., psychodynamic, interpersonal, and dialectical behavior therapy perspectives), but there is no evidence that these treatments are less effective. Pharmacotherapy is promising (especially paroxetine, sertraline, and venlafaxine), but more research comparing the relative merits of medication vs. psychotherapy and the efficacy of combined treatments is needed. Given the recent influx of combat-related traumas due to ongoing conflicts in Iraq and Afghanistan, there is clearly an urgent need to conduct more randomized clinical trials research and effectiveness studies in military and Department of Veterans Affairs PTSD samples. Finally, we provide references to a number of PTSD treatment manuals and propose several recommendations to help guide clinicians’ treatment selections. PMID:21475611

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.

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.

Attention/Vigilance in Schizophrenia: Performance Results from a Large Multi-Site Study of the Consortium on the Genetics of Schizophrenia (COGS)

PubMed Central

Nuechterlein, Keith H.; Green, Michael F.; Calkins, Monica E.; Greenwood, Tiffany A.; Gur, Raquel E.; Gur, Ruben C.; Lazzeroni, Laura C.; Light, Gregory A.; Radant, Allen D.; Seidman, Larry J.; Siever, Larry J.; Silverman, Jeremy M.; Sprock, Joyce; Stone, William S.; Sugar, Catherine A.; Swerdlow, Neal R.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Braff, David L.

2015-01-01

Attention/vigilance impairments are present in individuals with schizophrenia across psychotic and remitted states and in their first-degree relatives. An important question is whether deficits in attention/vigilance can be consistently and reliably measured across sites varying in many participant demographic, clinical, and functional characteristics, as needed for large-scale genetic studies of endophenotypes. We examined Continuous Performance Test (CPT) data from Phase 2 of the Consortium on the Genetics of Schizophrenia (COGS-2), the largest-scale assessment of cognitive and psychophysiological endophenotypes relevant to schizophrenia. CPT data from 2251 participants from five sites were examined. A perceptual-load vigilance task (the Degraded Stimulus CPT or DS-CPT) and a memory-load vigilance task (CPT - Identical Pairs or CPT-IP) were utilized. Schizophrenia patients performed more poorly than healthy comparison subjects (HCS) across sites, despite significant site differences in participant age, sex, education, and racial distribution. Patient-HCS differences in signal/noise discrimination (d’) in the DS-CPT varied significantly across sites, but averaged a medium effect size. CPT-IP performance showed large patient-HCS differences across sites. Poor CPT performance was independent of or weakly correlated with symptom severity, but was significantly associated with lower educational achievement and functional capacity. Current smoking was associated with poorer CPT-IP d’. Patients taking both atypical and typical antipsychotic medication performed more poorly than those on no or atypical antipsychotic medications, likely reflecting their greater severity of illness. We conclude that CPT deficits in schizophrenia can be reliably detected across sites, are relatively independent of current symptom severity, and are related to functional capacity. PMID:25749017

Attention/vigilance in schizophrenia: performance results from a large multi-site study of the Consortium on the Genetics of Schizophrenia (COGS).

PubMed

Nuechterlein, Keith H; Green, Michael F; Calkins, Monica E; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Light, Gregory A; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Stone, William S; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Braff, David L

2015-04-01

Attention/vigilance impairments are present in individuals with schizophrenia across psychotic and remitted states and in their first-degree relatives. An important question is whether deficits in attention/vigilance can be consistently and reliably measured across sites varying in many participant demographic, clinical, and functional characteristics, as needed for large-scale genetic studies of endophenotypes. We examined Continuous Performance Test (CPT) data from phase 2 of the Consortium on the Genetics of Schizophrenia (COGS-2), the largest-scale assessment of cognitive and psychophysiological endophenotypes relevant to schizophrenia. The CPT data from 2251 participants from five sites were examined. A perceptual-load vigilance task (the Degraded Stimulus CPT or DS-CPT) and a memory-load vigilance task (CPT-Identical Pairs or CPT-IP) were utilized. Schizophrenia patients performed more poorly than healthy comparison subjects (HCS) across sites, despite significant site differences in participant age, sex, education, and racial distribution. Patient-HCS differences in signal/noise discrimination (d') in the DS-CPT varied significantly across sites, but averaged a medium effect size. CPT-IP performance showed large patient-HCS differences across sites. Poor CPT performance was independent of or weakly correlated with symptom severity, but was significantly associated with lower educational achievement and functional capacity. Current smoking was associated with poorer CPT-IP d'. Patients taking both atypical and typical antipsychotic medication performed more poorly than those on no or atypical antipsychotic medications, likely reflecting their greater severity of illness. We conclude that CPT deficits in schizophrenia can be reliably detected across sites, are relatively independent of current symptom severity, and are related to functional capacity. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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.

Fatty acid oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C.

PubMed

Lin, Zhaoyu; Liu, Fei; Shi, Peiliang; Song, Anying; Huang, Zan; Zou, Dayuan; Chen, Qin; Li, Jianxin; Gao, Xiang

2018-02-26

Changes in metabolic pathway preferences are key events in the reprogramming process of somatic cells to induced pluripotent stem cells (iPSCs). The optimization of metabolic conditions can enhance reprogramming; however, the detailed underlying mechanisms are largely unclear. By comparing the gene expression profiles of somatic cells, intermediate-phase cells, and iPSCs, we found that carnitine palmitoyltransferase (Cpt)1b, a rate-limiting enzyme in fatty acid oxidation, was significantly upregulated in the early stage of the reprogramming process. Mouse embryonic fibroblasts isolated from transgenic mice carrying doxycycline (Dox)-inducible Yamanaka factor constructs were used for reprogramming. Various fatty acid oxidation-related metabolites were added during the reprogramming process. Colony counting and fluorescence-activated cell sorting (FACS) were used to calculate reprogramming efficiency. Fatty acid oxidation-related metabolites were measured by liquid chromatography-mass spectrometry. Seahorse was used to measure the level of oxidative phosphorylation. We found that overexpression of cpt1b enhanced reprogramming efficiency. Furthermore, palmitoylcarnitine or acetyl-CoA, the primary and final products of Cpt1-mediated fatty acid oxidation, also promoted reprogramming. In the early reprogramming process, fatty acid oxidation upregulated oxidative phosphorylation and downregulated protein kinase C activity. Inhibition of protein kinase C also promoted reprogramming. We demonstrated that fatty acid oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C activity in the early stage of the reprogramming process. This study reveals that fatty acid oxidation is crucial for the reprogramming efficiency.

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.

Behavioral and neurophysiological study of attentional and inhibitory processes in ADHD-combined and control children.

PubMed

Baijot, S; Deconinck, N; Slama, H; Massat, I; Colin, C

2013-12-01

This study compares behavioral and electrophysiological (P300) responses recorded in a cued continuous performance task (CPT-AX) performed by children with attention deficit hyperactivity disorder-combined subtype (ADHD-com) and age-matched healthy controls. P300 cognitive-evoked potentials and behavioral data were recorded in eight children with ADHD (without comorbidity) and nine control children aged 8-12 years while performing a CPT-AX task. Such task enables to examine several kinds of false alarms and three different kinds of P300 responses: the "Cue P300", the "Go P300" and the "NoGo P300", respectively, associated with preparatory processing/attentional orienting, motor/response execution and motor/response inhibition. Whereas hit rates were about 95% in each group, ADHD children made significantly more false alarm responses (inattention- and inhibition-related) than control children. ADHD children had a marginally smaller Cue P300 than the control children. Behavioral and electrophysiological findings both highlighted inhibition and attention deficits in ADHD-com children in the CPT-AX task. A rarely studied kind of false alarm, the "Other" FA, seems to be a sensitive FA to take into account, even if its interpretation remains unclear.

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

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.

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.

Higher body fat percentage is associated with enhanced temperature perception in NAFLD: results from the randomised Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy trial (WELCOME) trial.

PubMed

Clough, Geraldine F; McCormick, Keith G; Scorletti, Eleonora; Bhatia, Lokpal; Calder, Philip C; Griffin, Michael J; Byrne, Christopher D

2016-07-01

The effect of n-3 fatty acid treatment on temperature perception as a sensory nerve function modality is uncertain. In patients with non-alcoholic fatty liver disease (NAFLD) both with and without type 2 diabetes, we: (1) tested whether 15-18 months' treatment with 4 g/day of docosahexaenoic plus eicosapentaenoic acid (DHA+EPA) improved hot (HPT) and cold (CPT) temperature perception thresholds and (2) explored factors associated with HPT and CPT, in a randomised, double-blind, placebo-controlled trial. The effect of treatment (n = 44) on HPT, CPT and temperature perception index (TPI: difference between HPT and CPT) was measured at the big toe in 90 individuals without neuropathy (type 2 diabetes; n = 30). Participants were randomised 1:1, using sequential numbering, by personnel independent from the trial team. All participants and all members of the research team were blinded to group assignment. Data were collected in the Southampton National Institute for Health Research Biomedical Research Centre. Treatment effects and the independence of associations were testing by regression modelling. Mean ± SD age was 50.9 ± 10.6 years. In men (n = 53) and women (n = 37), HPTs (°C) were 46.1 ± 5.1 and 43.1 ± 6.4 (p = 0.02), CPTs (°C) were 22.7 ± 3.4 and 24.5 ± 3.6 (p = 0.07) and TPIs (°C) were 23.4 ± 7.4 and 18.7 ± 9.5 (p = 0.008), respectively. In univariate analyses, total body fat percentage (measured by dual-energy x-ray absorptiometry [DXA]) was associated with HPT (r = -0.36 p = 0.001), CPT (r = 0.35 p = 0.001) and TPI (r = 0.39 p = 0.0001). In multivariable-adjusted regression models, adjusting for age, sex and other potential confounders, only body fat percentage was independently associated with HPT, CPT or TPI (p = 0.006, p = 0.006 and p = 0.002, respectively). DHA+EPA treatment did not modify HPT, CPT or TPI (p = 0.93, p = 0.44 and p = 0.67, respectively). There were no important adverse effects or side effects reported. Higher body fat percentage is associated with enhanced temperature perception. There was no benefit of treatment with high-dose n-3 fatty acids on the thresholds to detect hot or cold stimuli. ClinicalTrials.gov NCT00760513 FUNDING: This work was supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Unit grant and by a Diabetes UK allied health research training fellowship awarded to KMcC (Diabetes UK. BDA 09/0003937).

A CPT for Improving Turbulence and Cloud Processes in the NCEP Global Models

NASA Astrophysics Data System (ADS)

Krueger, S. K.; Moorthi, S.; Randall, D. A.; Pincus, R.; Bogenschutz, P.; Belochitski, A.; Chikira, M.; Dazlich, D. A.; Swales, D. J.; Thakur, P. K.; Yang, F.; Cheng, A.

2016-12-01

Our Climate Process Team (CPT) is based on the premise that the NCEP (National Centers for Environmental Prediction) global models can be improved by installing an integrated, self-consistent description of turbulence, clouds, deep convection, and the interactions between clouds and radiative and microphysical processes. The goal of our CPT is to unify the representation of turbulence and subgrid-scale (SGS) cloud processes and to unify the representation of SGS deep convective precipitation and grid-scale precipitation as the horizontal resolution decreases. We aim to improve the representation of small-scale phenomena by implementing a PDF-based SGS turbulence and cloudiness scheme that replaces the boundary layer turbulence scheme, the shallow convection scheme, and the cloud fraction schemes in the GFS (Global Forecast System) and CFS (Climate Forecast System) global models. We intend to improve the treatment of deep convection by introducing a unified parameterization that scales continuously between the simulation of individual clouds when and where the grid spacing is sufficiently fine and the behavior of a conventional parameterization of deep convection when and where the grid spacing is coarse. We will endeavor to improve the representation of the interactions of clouds, radiation, and microphysics in the GFS/CFS by using the additional information provided by the PDF-based SGS cloud scheme. The team is evaluating the impacts of the model upgrades with metrics used by the NCEP short-range and seasonal forecast operations.

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.

A quantitative systems physiology model of renal function and blood pressure regulation: Model description.

PubMed

Hallow, K M; Gebremichael, Y

2017-06-01

Renal function plays a central role in cardiovascular, kidney, and multiple other diseases, and many existing and novel therapies act through renal mechanisms. Even with decades of accumulated knowledge of renal physiology, pathophysiology, and pharmacology, the dynamics of renal function remain difficult to understand and predict, often resulting in unexpected or counterintuitive therapy responses. Quantitative systems pharmacology modeling of renal function integrates this accumulated knowledge into a quantitative framework, allowing evaluation of competing hypotheses, identification of knowledge gaps, and generation of new experimentally testable hypotheses. Here we present a model of renal physiology and control mechanisms involved in maintaining sodium and water homeostasis. This model represents the core renal physiological processes involved in many research questions in drug development. The model runs in R and the code is made available. In a companion article, we present a case study using the model to explore mechanisms and pharmacology of salt-sensitive hypertension. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

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.

HIV-infected adolescents have low adherence to antiretroviral therapy: a cross-sectional study in Addis Ababa, Ethiopia.

PubMed

Firdu, Naod; Enquselassie, Fikre; Jerene, Degu

2017-01-01

For antiretroviral therapy (ART) to work effectively, adherence is very crucial. However, most studies done on ART adherence are either on children or on adults. There is limited information on the level of adherence among adolescents. Using a cross-sectional study design, we interviewed 273 HIV-infected adolescents receiving ART from three hospitals in Addis Ababa. We used a structured questionnaire to measure adherence levels using patient self-reports. Bivariate and multivariate methods were used for analysis. We interviewed 273 adolescents aged 13 to 19 years, and 144 (52.7%) of the participants were girls. Their mean age was 15.4 years (SD± 1.75). The self-reported adherence rate of the respondents was 79.1% (216/273). On bivariate analysis, variables like WHO clinical stage, being on Cotrimoxazole Prophylactic Therapy (CPT), marital and living status of the parent, whether parent was on ART or not and having special instructions for ART medications were associated with optimum adherence. However of those, only WHO stage IV (adjusted OR, 12.874 95% CI, 2.079-79.706), being on CPT (adjusted OR, 0.339 95% CI, 0.124-0.97) and adolescents with widowed parent (adjusted OR, 0.087 with 95% CI, 0.021-0.359) were found to be significantly associated with optimum ART adherence. The level of self-reported ART adherence among HIV-infected adolescents at the three hospitals was below the recommended threshold. Though earlier presentation of adolescents to care should be encouraged, more targeted adherence support should be planned for those who present at an early stage of their illness.

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

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.

Use of the Cone Penetration Testing (CPT) method to interpret late Quaternary tide-dominated successions: A case study from the eastern China coastal plain

NASA Astrophysics Data System (ADS)

Zhang, Xia; Lin, Chun-Ming; Dalrymple, Robert W.; Gao, Shu; Canas, Daniel T.

2018-06-01

We evaluate the applicability of cone penetration testing (CPT), calibrated using adjacent cores, as a tool for the sedimentological and stratigraphic examination of late Quaternary tide-dominated successions in the eastern China coastal plain. The results indicate that the sedimentary facies and sequence-stratigraphic surfaces can be readily distinguished using CPT profiles in the Qiantang River incised-valley system because of their distinctive mechanical behavior. The lithologic character of the various facies, which is controlled mainly by sediment supply, dynamic processes and post-depositional diagenesis, is the key factor affecting how well the CPT technique works. Within this particular macrotidal environment, which is dominated by non-cohesive sand and silt in the tidal channels, the accumulation of fluid mud is rare. Consequently, the tidal-channel deposits exhibit the geotechnical properties of coarse-grained sediments, and can be easily distinguished from the mud-dominated facies. However, in the nearby Changjiang delta system which is characterized by very high suspended-sediment concentrations and an abundance of fine-grained cohesive sediments, the presence of channel-bottom fluid muds makes it difficult to recognize channel deposits, because of the lack of a sharp lithologic contrast at their base. Consequently, the CPT method might not be as universally effective in tide-dominated systems as it appears to be in wave-dominated settings. Care is needed in the interpretation of the results from tide-dominated successions because of the widespread presence of fluid muds, the heterolithic nature of tidal deposits, the rheological similarity between adjacent facies, and the averaging of geotechnical properties between the alternating finer and coarser layers.

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

Activation of exchange protein activated by cAMP in the rat basolateral amygdala impairs reconsolidation of a memory associated with self-administered cocaine.

PubMed

Wan, Xun; Torregrossa, Mary M; Sanchez, Hayde; Nairn, Angus C; Taylor, Jane R

2014-01-01

The intracellular mechanisms underlying memory reconsolidation critically involve cAMP signaling. These events were originally attributed to PKA activation by cAMP, but the identification of Exchange Protein Activated by cAMP (Epac), as a distinct mediator of cAMP signaling, suggests that cAMP-regulated processes that subserve memory reconsolidation are more complex. Here we investigated how activation of Epac with 8-pCPT-cAMP (8-CPT) impacts reconsolidation of a memory that had been associated with cocaine self-administration. Rats were trained to lever press for cocaine on an FR-1 schedule, in which each cocaine delivery was paired with a tone+light cue. Lever pressing was then extinguished in the absence of cue presentations and cocaine delivery. Following the last day of extinction, rats were put in a novel context, in which the conditioned cue was presented to reactivate the cocaine-associated memory. Immediate bilateral infusions of 8-CPT into the basolateral amygdala (BLA) following reactivation disrupted subsequent cue-induced reinstatement in a dose-dependent manner, and modestly reduced responding for conditioned reinforcement. When 8-CPT infusions were delayed for 3 hours after the cue reactivation session or were given after a cue extinction session, no effect on cue-induced reinstatement was observed. Co-administration of 8-CPT and the PKA activator 6-Bnz-cAMP (10 nmol/side) rescued memory reconsolidation while 6-Bnz alone had no effect, suggesting an antagonizing interaction between the two cAMP signaling substrates. Taken together, these studies suggest that activation of Epac represents a parallel cAMP-dependent pathway that can inhibit reconsolidation of cocaine-cue memories and reduce the ability of the cue to produce reinstatement of cocaine-seeking behavior.

Activation of Exchange Protein Activated by cAMP in the Rat Basolateral Amygdala Impairs Reconsolidation of a Memory Associated with Self-Administered Cocaine

PubMed Central

Sanchez, Hayde; Nairn, Angus C.; Taylor, Jane R.

2014-01-01

The intracellular mechanisms underlying memory reconsolidation critically involve cAMP signaling. These events were originally attributed to PKA activation by cAMP, but the identification of Exchange Protein Activated by cAMP (Epac), as a distinct mediator of cAMP signaling, suggests that cAMP-regulated processes that subserve memory reconsolidation are more complex. Here we investigated how activation of Epac with 8-pCPT-cAMP (8-CPT) impacts reconsolidation of a memory that had been associated with cocaine self-administration. Rats were trained to lever press for cocaine on an FR-1 schedule, in which each cocaine delivery was paired with a tone+light cue. Lever pressing was then extinguished in the absence of cue presentations and cocaine delivery. Following the last day of extinction, rats were put in a novel context, in which the conditioned cue was presented to reactivate the cocaine-associated memory. Immediate bilateral infusions of 8-CPT into the basolateral amygdala (BLA) following reactivation disrupted subsequent cue-induced reinstatement in a dose-dependent manner, and modestly reduced responding for conditioned reinforcement. When 8-CPT infusions were delayed for 3 hours after the cue reactivation session or were given after a cue extinction session, no effect on cue-induced reinstatement was observed. Co-administration of 8-CPT and the PKA activator 6-Bnz-cAMP (10 nmol/side) rescued memory reconsolidation while 6-Bnz alone had no effect, suggesting an antagonizing interaction between the two cAMP signaling substrates. Taken together, these studies suggest that activation of Epac represents a parallel cAMP-dependent pathway that can inhibit reconsolidation of cocaine-cue memories and reduce the ability of the cue to produce reinstatement of cocaine-seeking behavior. PMID:25259911

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

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

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

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.

An Aggressive Signet Ring Cell Carcinoma of the Prostate in a Japanese Man

PubMed Central

Hashimoto, Yasuhiro; Imanishi, Kengo; Okamoto, Akiko; Sasaki, Atsushi; Saitoh, Hisao; Wada, Ryuichi; Yamamoto, Hayato; Koie, Takuya; Ohyama, Chikara

2011-01-01

Signet ring cell carcinoma (SRCC) of the prostate is rare, with approximately 100 case reports to date. Here we report a very aggressive case of SRCC of the prostate in a Japanese man. The patient received estramustine, docetaxel, and carboplatin combination chemotherapy, followed by TS-1 and CPT-11 combination therapy. Unfortunately, the disease progressed, and he died of general metastatic disease treated over 16 month with systemic chemotherapy. PMID:22114579

Visible light-induced crosslinking and physiological stabilization of diselenide-rich nanoparticles for redox-responsive drug release and combination chemotherapy.

PubMed

Zhai, Shaodong; Hu, Xianglong; Hu, Yongjun; Wu, Baoyan; Xing, Da

2017-03-01

Undesired physiological instability of nanocarriers and premature drug leakage during blood circulation result in compromised therapeutic efficacy and severe side effects, which have significantly impeded the development of nanomedicine. Facile crosslinking of drug-loaded nanocarriers while keeping the potency of site-specific degradation and drug release has emerged as a viable strategy to overcome these drawbacks. Additionally, combination therapy has already shown advantages in inhibiting advanced tumors and life extension than single drug therapy. Herein, three kinds of diselenide-rich polymers were fabricated with distinct hydrophobic side chains. The component effect was interrogated to screen out PEG-b-PBSe diblock copolymer due to its favorable self-assembly controllability and high drug loading of camptothecin (CPT) and doxorubicin (DOX) that had synergistic antitumor property. Facile visible light-induced diselenide metathesis and regeneration was employed to crosslink nanocarriers for the first time. The dual drug-loaded crosslinked micelles (CPT/DOX-CCM) were stable in physiological conditions with minimal drug leakage, possessing extended blood circulation, whereas hand-in-hand dual drug release was significantly accelerated in tumor's redox microenvironments. In vitro cytotoxicity evaluation and in vivo tumor suppression with low dosage drugs further demonstrated the favorable potency of the redox-responsive nanoplatform in tumor combination chemotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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.

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.

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

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.

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).

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

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.

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.

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.

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.

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.

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.

Unified study of Quality of Service (QoS) in OPS/OBS networks

NASA Astrophysics Data System (ADS)

Hailu, Dawit Hadush; Lema, Gebrehiwet Gebrekrstos; Yekun, Ephrem Admasu; Kebede, Samrawit Haylu

2017-07-01

With the growth of Internet traffic, an inevitable use of optical networks provide a large bandwidth, fast data transmission rates and Quality of Service (QoS) support. Currently, Optical Burst Switched (OBS)/Optical Packet Switched (OPS) networks are under study as future solutions for addressing the increase demand of Internet traffic. However, due to their high blocking probability in the intermediate nodes they have been delayed in the industries. Packet loss in OBS/OPS networks is mainly occur due to contention. Hence, the contribution of this study is to analyze the file loss ratio (FLR), packet overhead and number of disjoint paths, and processing delay over Coded Packet Transport (CPT) scheme for OBS/OPS network using simulation. The simulations show that CPT scheme reduces the FLR in OBS/OPS network for the evaluated scenarios since the data packets are chopped off into blocks of the data packet for transmission over a network. Simulation results for secrecy and survivability are verified with the help of the analytical model to define the operational range of CPT scheme.

Neutral Porphyrin Derivative Exerts Anticancer Activity by Targeting Cellular Topoisomerase I (Top1) and Promotes Apoptotic Cell Death without Stabilizing Top1-DNA Cleavage Complexes

PubMed Central

2017-01-01

Camptothecin (CPT) selectively traps topoisomerase 1-DNA cleavable complexes (Top1cc) to promote anticancer activity. Here, we report the design and synthesis of a new class of neutral porphyrin derivative 5,10-bis(4-carboxyphenyl)-15, 20-bis(4-dimethylaminophenyl)porphyrin (compound 8) as a potent catalytic inhibitor of human Top1. In contrast to CPT, compound 8 reversibly binds with the free enzyme and inhibits the formation of Top1cc and promotes reversal of the preformed Top1cc with CPT. Compound 8 induced inhibition of Top1cc formation in live cells was substantiated by fluorescence recovery after photobleaching (FRAP) assays. We established that MCF7 cells treated with compound 8 trigger proteasome-mediated Top1 degradation, accumulate higher levels of reactive oxygen species (ROS), PARP1 cleavage, oxidative DNA fragmentation, and stimulate apoptotic cell death without stabilizing apoptotic Top1-DNA cleavage complexes. Finally, compound 8 shows anticancer activity by targeting cellular Top1 and preventing the enzyme from directly participating in the apoptotic process. PMID:29290109

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.

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

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

Tracking coherent population transfer and thermal population relaxation in condensed system by broad-band transient grating spectroscopy

NASA Astrophysics Data System (ADS)

Zhang, Wei; Liu, Xiaosong; Wu, Honglin; Song, Yunfei; Liu, Weilong; Yang, Yanqiang

2018-04-01

Broad-band transient grating (BB-TG) spectroscopy was proposed to track both coherent population transfer (CPT) and thermal population relaxation processes in a condensed system of solvated molecules in solution (Rhodamine101 in methanol). A broad band around 1500 cm‑1 and a relative narrow band near 2900 cm‑1 emerge in TG and transient absorption contour plots when pump and probe pulses overlap in the sample. The experimental results matched well with the vibrational modes of Rhodamine101 that were obtained by theoretical calculation. In addition, it was found that the population of CPT particles can be evaluated quantitatively through the intensity of the TG signal.

Blockade of beta-adrenoceptors enhances cAMP signal transduction in vivo

NASA Technical Reports Server (NTRS)

Whalen, E. J.; Johnson, A. K.; Lewis, S. J.

1998-01-01

The aim of this study was to determine whether the blockade of beta-adrenoceptors would enhance cAMP-mediated signal transduction processes in vivo. The administration of the membrane permeable cAMP analogue, 8-(4-chlorophenylthiol)-cAMP (8-CPT-cAMP, 10 micromol/kg, i.v.) produced an increase in heart rate (+27 +/- 2%, P < 0.05), a fall in mean arterial blood pressure (-21 +/- 3%, P < 0.05) and falls in hindquarter (-12 +/- 3%, P < 0.05) and mesenteric (-32 +/- 3%, P < 0.05) vascular resistances in pentobarbital-anesthetized rats. The beta-adrenoceptor antagonist, propranolol (1 mg/kg, i.v.) lowered heart rate (-12 +/- 3%, P < 0.05) but did not affect mean arterial blood pressure or vascular resistances. The tachycardia, hypotension and vasodilation produced by 8-CPT-cAMP were exaggerated after administration of propranolol (P < 0.05 for all comparisons). The nitric oxide-donor, sodium nitroprusside (2 microg/kg, i.v.), produced falls in mean arterial blood pressure and vascular resistances of similar magnitude to those produced by 8-CPT-cAMP. These sodium nitroprusside-induced responses were unaffected by propranolol (P < 0.05 for all comparisons). Sodium nitroprusside also produced a minor increase in heart rate (+5 +/- 1%, P < 0.05) which was abolished by propranolol. These findings suggest that 8-CPT-cAMP directly increases heart rate and that blockade of beta-adrenoceptors enhances the potency of cAMP within the heart and vasculature.

The downregulation of the RNA-binding protein Staufen2 in response to DNA damage promotes apoptosis

PubMed Central

Zhang, Xin; Trépanier, Véronique; Beaujois, Remy; Viranaicken, Wildriss; Drobetsky, Elliot; DesGroseillers, Luc

2016-01-01

Staufen2 (Stau2) is an RNA-binding protein involved in cell fate decision by controlling several facets of mRNA processing including localization, splicing, translation and stability. Herein we report that exposure to DNA-damaging agents that generate replicative stress such as camptothecin (CPT), 5-fluoro-uracil (5FU) and ultraviolet radiation (UVC) causes downregulation of Stau2 in HCT116 colorectal cancer cells. In contrast, other agents such as doxorubicin and ionizing radiation had no effect on Stau2 expression. Consistently, Stau2 expression is regulated by the ataxia telangiectasia and Rad3-related (ATR) signaling pathway but not by the DNA-PK or ataxia telangiectasia mutated/checkpoint kinase 2 pathways. Stau2 downregulation is initiated at the level of transcription, independently of apoptosis induction. Promoter analysis identified a short 198 bp region which is necessary and sufficient for both basal and CPT-regulated Stau2 expression. The E2F1 transcription factor regulates Stau2 in untreated cells, an effect that is abolished by CPT treatment due to E2F1 displacement from the promoter. Strikingly, Stau2 downregulation enhances levels of DNA damage and promotes apoptosis in CPT-treated cells. Taken together our results suggest that Stau2 is an anti-apoptotic protein that could be involved in DNA replication and/or maintenance of genome integrity and that its expression is regulated by E2F1 via the ATR signaling pathway. PMID:26843428

Bioresponsive polymer coated drug nanorods for breast cancer treatment

NASA Astrophysics Data System (ADS)

Laemthong, Tunyaboon; Kim, Hannah H.; Dunlap, Kelly; Brocker, Caitlin; Barua, Dipak; Forciniti, Daniel; Huang, Yue-Wern; Barua, Sutapa

2017-01-01

Ineffective drug release at the target site is among the top challenges for cancer treatment. This reflects the facts that interaction with the physiological condition can denature active ingredients of drugs, and low delivery to the disease microenvironment leads to poor therapeutic outcomes. We hypothesize that depositing a thin layer of bioresponsive polymer on the surface of drug nanoparticles would not only protect drugs from degradation but also allow the release of drugs at the target site. Here, we report a one-step process to prepare bioresponsive polymer coated drug nanorods (NRs) from liquid precursors using the solvent diffusion method. A thin layer (10.3 ± 1.4 nm) of poly(ε-caprolactone) (PCL) polymer coating was deposited on the surface of camptothecin (CPT) anti-cancer drug NRs. The mean size of PCL-coated CPT NRs was 500.9 ± 91.3 nm length × 122.7 ± 10.1 nm width. The PCL polymer coating was biodegradable at acidic pH 6 as determined by Fourier transform infrared spectroscopy. CPT drugs were released up to 51.5% when PCL coating dissolved into non-toxic carboxyl and hydroxyl groups. Trastuzumab (TTZ), a humanized IgG monoclonal antibody, was conjugated to the NR surface for breast cancer cell targeting. Combination treatments using CPT and TTZ decreased the HER-2 positive BT-474 breast cancer cell growth by 66.9 ± 5.3% in vitro. These results suggest effective combination treatments of breast cancer cells using bioresponsive polymer coated drug delivery.

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.

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

Measuring Use of Evidence-Based Psychotherapy for PTSD in VA Residential Treatment Settings with Clinician Survey and Electronic Medical Record Templates.

PubMed

Shiner, Brian; Leonard Westgate, Christine; Simiola, Vanessa; Thompson, Richard; Schnurr, Paula P; Cook, Joan M

2018-03-14

Available studies on implementation of evidence-based psychotherapy (EBP) for patients attending Department of Veterans Affairs (VA) residential post-traumatic stress disorder (PTSD) programs rely on therapist self-report of EBP delivery. Patient-level data on receipt of EBP are needed both to corroborate therapist self-report and to understand patient factors that predict receipt of EBPs for PTSD. We identified 159 therapists from 38 VA residential PTSD programs who responded to a survey about EBP implementation during the 2015 fiscal year (FY15). Therapists self-reported their use of two EBPs, including prolonged exposure delivered in an individual format (PE-I) and cognitive processing therapy delivered in individual and group formats (CPT-I and CPT-G). Using electronic medical record (EMR) templates mandated for EBP documentation in FY15, we measured contemporaneous patient-level receipt of EBPs for PTSD. We assessed the degree of correlation between therapist self-reported EBP delivery and patient receipt of EBT as measured by EMR templates using polychoric correlation coefficients. We determined patient and therapist factors that predicted the receipt of EBPs with multivariable logistic regression, using random effects and robust standard error estimation, and controlling for site. The Veterans IRB of Northern New England provided a waiver of informed consent; as this was a retrospective review, no patients or therapists were contacted, and all data were stored, transmitted, and analyzed on secure VA servers. The VA Connecticut Health Care System Human Research Protection Program approved secondary use of therapist survey data for this project. When EMR template use became mandated in FY15, the proportion of patients in residential PTSD programs who received at least one EBP session that was recorded with an EMR template increased dramatically from 8.8% to 33.9%. There was adequate correlation and between survey-based and EMR-based measures of EBP receipt, with polychoric correlation values of 0.77 for PE-I, 0.69 for CPT-I, and 0.82 for CPT-G. Multiple patient factors were positive (e.g., female gender) and negative (e.g., depressive disorders) predictors of receipt of EBPs, even after controlling for site. Among therapist factors, only EBP consultant or trainer status was a positive predictor of EBP provision and only therapist race was a negative predictor of EBT provision after controlling for site. Following a FY15 mandate, EMR templates documenting EBP delivery were widely used by therapists working in VA residential PTSD programs. EBP receipt measured using EMR templates was consistent with therapist self-report of EBT delivery. There were several patient-level predictors of EBP receipt and therapist-level predictors of EBP delivery. However, therapists most likely to deliver EBPs were clustered at a limited number of sites.

Essential competencies in prescribing: A first european cross-sectional study among 895 final-year medical students.

PubMed

Brinkman, D J; Tichelaar, J; Schutte, T; Benemei, S; Böttiger, Y; Chamontin, B; Christiaens, T; Likic, R; Maˇiulaitis, R; Marandi, T; Monteiro, E C; Papaioannidou, P; Pers, Y M; Pontes, C; Raskovic, A; Regenthal, R; Sanz, E J; Tamba, B I; Wilson, K; Vries, Tp de; Richir, M C; Agtmael, Ma van

2017-02-01

European medical students should have acquired adequate prescribing competencies before graduation, but it is not known whether this is the case. In this international multicenter study, we evaluated the essential knowledge, skills, and attitudes in clinical pharmacology and therapeutics (CPT) of final-year medical students across Europe. In a cross-sectional design, 26 medical schools from 17 European countries were asked to administer a standardized assessment and questionnaire to 50 final-year students. Although there were differences between schools, our results show an overall lack of essential prescribing competencies among final-year students in Europe. Students had a poor knowledge of drug interactions and contraindications, and chose inappropriate therapies for common diseases or made prescribing errors. Our results suggest that undergraduate teaching in CPT is inadequate in many European schools, leading to incompetent prescribers and potentially unsafe patient care. A European core curriculum with clear learning outcomes and assessments should be urgently developed. © 2016 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of The American Society for Clinical Pharmacology and Therapeutics.

Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss.

PubMed

Halassa, Michael M; Florian, Cedrick; Fellin, Tommaso; Munoz, James R; Lee, So-Young; Abel, Ted; Haydon, Philip G; Frank, Marcos G

2009-01-29

Astrocytes modulate neuronal activity by releasing chemical transmitters via a process termed gliotransmission. The role of this process in the control of behavior is unknown. Since one outcome of SNARE-dependent gliotransmission is the regulation of extracellular adenosine and because adenosine promotes sleep, we genetically inhibited the release of gliotransmitters and asked if astrocytes play an unsuspected role in sleep regulation. Inhibiting gliotransmission attenuated the accumulation of sleep pressure, assessed by measuring the slow wave activity of the EEG during NREM sleep, and prevented cognitive deficits associated with sleep loss. Since the sleep-suppressing effects of the A1 receptor antagonist CPT were prevented following inhibition of gliotransmission and because intracerebroventricular delivery of CPT to wild-type mice mimicked the transgenic phenotype, we conclude that astrocytes modulate the accumulation of sleep pressure and its cognitive consequences through a pathway involving A1 receptors.

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.

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.

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.

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

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.

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.

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.

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.

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

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.

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.

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.

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

CPT site characterization for seismic hazards in the New Madrid seismic zone

USGS Publications Warehouse

Liao, T.; Mayne, P.W.; Tuttle, M.P.; Schweig, E.S.; Van Arsdale, R.B.

2002-01-01

A series of cone penetration tests (CPTs) were conducted in the vicinity of the New Madrid seismic zone in central USA for quantifying seismic hazards, obtaining geotechnical soil properties, and conducting studies at liquefaction sites related to the 1811-1812 and prehistoric New Madrid earthquakes. The seismic piezocone provides four independent measurements for delineating the stratigraphy, liquefaction potential, and site amplification parameters. At the same location, two independent assessments of soil liquefaction susceptibility can be made using both the normalized tip resistance (qc1N) and shear wave velocity (Vs1). In lieu of traditional deterministic approaches, the CPT data can be processed using probability curves to assess the level and likelihood of future liquefaction occurrence. ?? 2002 Elsevier Science Ltd. All rights reserved.

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.

Reaction time, processing speed and sustained attention in schizophrenia: impact on social functioning.

PubMed

Lahera, Guillermo; Ruiz, Alicia; Brañas, Antía; Vicens, María; Orozco, Arantxa

Previous studies have linked processing speed with social cognition and functioning of patients with schizophrenia. A discriminant analysis is needed to determine the different components of this neuropsychological construct. This paper analyzes the impact of processing speed, reaction time and sustained attention on social functioning. 98 outpatients between 18 and 65 with DSM-5 diagnosis of schizophrenia, with a period of 3 months of clinical stability, were recruited. Sociodemographic and clinical data were collected, and the following variables were measured: processing speed (Trail Making Test [TMT], symbol coding [BACS], verbal fluency), simple and elective reaction time, sustained attention, recognition of facial emotions and global functioning. Processing speed (measured only through the BACS), sustained attention (CPT) and elective reaction time (but not simple) were associated with functioning. Recognizing facial emotions (FEIT) correlated significantly with scores on measures of processing speed (BACS, Animals, TMT), sustained attention (CPT) and reaction time. The linear regression model showed a significant relationship between functioning, emotion recognition (P=.015) and processing speed (P=.029). A deficit in processing speed and facial emotion recognition are associated with worse global functioning in patients with schizophrenia. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

The downregulation of the RNA-binding protein Staufen2 in response to DNA damage promotes apoptosis.

PubMed

Zhang, Xin; Trépanier, Véronique; Beaujois, Remy; Viranaicken, Wildriss; Drobetsky, Elliot; DesGroseillers, Luc

2016-05-05

Staufen2 (Stau2) is an RNA-binding protein involved in cell fate decision by controlling several facets of mRNA processing including localization, splicing, translation and stability. Herein we report that exposure to DNA-damaging agents that generate replicative stress such as camptothecin (CPT), 5-fluoro-uracil (5FU) and ultraviolet radiation (UVC) causes downregulation of Stau2 in HCT116 colorectal cancer cells. In contrast, other agents such as doxorubicin and ionizing radiation had no effect on Stau2 expression. Consistently, Stau2 expression is regulated by the ataxia telangiectasia and Rad3-related (ATR) signaling pathway but not by the DNA-PK or ataxia telangiectasia mutated/checkpoint kinase 2 pathways. Stau2 downregulation is initiated at the level of transcription, independently of apoptosis induction. Promoter analysis identified a short 198 bp region which is necessary and sufficient for both basal and CPT-regulated Stau2 expression. The E2F1 transcription factor regulates Stau2 in untreated cells, an effect that is abolished by CPT treatment due to E2F1 displacement from the promoter. Strikingly, Stau2 downregulation enhances levels of DNA damage and promotes apoptosis in CPT-treated cells. Taken together our results suggest that Stau2 is an anti-apoptotic protein that could be involved in DNA replication and/or maintenance of genome integrity and that its expression is regulated by E2F1 via the ATR signaling pathway. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

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.

Soil classification based on cone penetration test (CPT) data in Western Central Java

NASA Astrophysics Data System (ADS)

Apriyono, Arwan; Yanto, Santoso, Purwanto Bekti; Sumiyanto

2018-03-01

This study presents a modified friction ratio range for soil classification i.e. gravel, sand, silt & clay and peat, using CPT data in Western Central Java. The CPT data was obtained solely from Soil Mechanic Laboratory of Jenderal Soedirman University that covers more than 300 sites within the study area. About 197 data were produced from data filtering process. IDW method was employed to interpolated friction ratio values in a regular grid point for soil classification map generation. Soil classification map was generated and presented using QGIS software. In addition, soil classification map with respect to modified friction ratio range was validated using 10% of total measurements. The result shows that silt and clay dominate soil type in the study area, which is in agreement with two popular methods namely Begemann and Vos. However, the modified friction ratio range produces 85% similarity with laboratory measurements whereby Begemann and Vos method yields 70% similarity. In addition, modified friction ratio range can effectively distinguish fine and coarse grains, thus useful for soil classification and subsequently for landslide analysis. Therefore, modified friction ratio range proposed in this study can be used to identify soil type for mountainous tropical region.

Biocleavable graphene oxide based-nanohybrids synthesized via ATRP for gene/drug delivery.

PubMed

Yang, Xinchao; Zhao, Nana; Xu, Fu-Jian

2014-06-07

Graphene oxide (GO) has been proven to be promising in many biomedical fields due to its biocompatibility, unique conjugated structure, easily tunable surface functionalization and facile synthesis. In this work, a flexible two-step method was first developed to introduce the atom transfer radical polymerization (ATRP) initiation sites containing disulfide bonds onto GO surfaces. Surface-initiated ATRP of (2-dimethyl amino)ethyl methacrylate (DMAEMA) was then employed to tailor the GO surfaces in a well-controlled manner, producing a series of organic-inorganic hybrids (termed as SS-GPDs) for highly efficient gene delivery. Under reducible conditions, the PDMAEMA side chains can be readily cleavable from the GO backbones, benefiting the resultant gene delivery process. Moreover, due to the conjugated structure of the graphene basal plane, SS-GPD can attach and absorb aromatic, water insoluble drugs, such as 10-hydroxycamptothecin (CPT), producing SS-GPD-CPT. The MTT assay and the simultaneous double-staining procedure revealed that SS-GPD-CPT possessed a high potency of killing cancer cells in vitro. With a high aqueous solubility and coulombic interaction with cell membrane, SS-GPDs may have great potential in gene/drug delivery fields.

[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.

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

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.

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.

Cerebral networks of sustained attention and working memory: a functional magnetic resonance imaging study based on the Continuous Performance Test.

PubMed

Bartés-Serrallonga, M; Adan, A; Solé-Casals, J; Caldú, X; Falcón, C; Pérez-Pàmies, M; Bargalló, N; Serra-Grabulosa, J M

2014-04-01

One of the most used paradigms in the study of attention is the Continuous Performance Test (CPT). The identical pairs version (CPT-IP) has been widely used to evaluate attention deficits in developmental, neurological and psychiatric disorders. However, the specific locations and the relative distribution of brain activation in networks identified with functional imaging, varies significantly with differences in task design. To design a task to evaluate sustained attention using functional magnetic resonance imaging (fMRI), and thus to provide data for research concerned with the role of these functions. Forty right-handed, healthy students (50% women; age range: 18-25 years) were recruited. A CPT-IP implemented as a block design was used to assess sustained attention during the fMRI session. The behavioural results from the CPT-IP task showed a good performance in all subjects, higher than 80% of hits. fMRI results showed that the used CPT-IP task activates a network of frontal, parietal and occipital areas, and that these are related to executive and attentional functions. In relation to the use of the CPT to study of attention and working memory, this task provides normative data in healthy adults, and it could be useful to evaluate disorders which have attentional and working memory deficits.

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.

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.

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.

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.

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.

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.

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

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.

Medication Effects on Periurethral Sensation and Urethral Sphincter Activity

PubMed Central

Greer, W. Jerod; Gleason, Jonathan L.; Kenton, Kimberly; Szychowski, Jeff M.; Goode, Patricia S; Richter, Holly E

2014-01-01

Aim To characterize urethral neuromuscular function before and 2 weeks after medication therapy. Methods Premenopausal women without lower urinary tract symptoms were randomly allocated to one of six medications for 2 weeks (pseudoephedrine ER 120mg, imipramine 25mg, cyclobenzaprine 10mg, tamsulosin 0.4mg, solifenacin 5mg or placebo). At baseline and after medication, participants underwent testing: quantitative concentric needle EMG (CNE) of the urethral sphincter using automated Multi-Motor Unit Action Potential (MUP) software; current perception threshold (CPT) testing to measure periurethral sensation; and standard urodynamic pressure flow studies (PFS). Nonparametric tests were used to compare pre-post differences. Results 56 women had baseline testing; 48 (85.7%) completed follow-up CNE, and 49 (87.5%) completed follow-up CPT and PFS testing. Demographics showed no significant differences among medication groups with respect to age (mean 34.3 ± 10.1), BMI (mean 31.8 ± 7.5), parity (median 1, range 0–7), or race (14% Caucasian, 80% African American). PFS parameters were not significantly different within medication groups. No significant pre-post changes in CNE values were noted; however, trends in amplitudes were in a direction consistent with the expected physiologic effect of the medications. With CPT testing, a trend toward increased urethral sensation at the 5 Hz stimulation level, was observed following treatment with pseudoephedrine (0.15 to 0.09 mA at 5Hz; P=0.03). Conclusion In women without LUTS, pseudoephedrine improved urethral sensation, but not urethral neuromuscular function on CNE or pressure flow studies. Imipramine, cyclobenzaprine, tamsulosin, solifenacin, and placebo did not change urethral sensation or neuromuscular function. PMID:25185603

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.

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.

Situating Cyberzone: Black lesbian identity in comics.

PubMed

Howard, Sheena C

2018-04-25

Cyberzone is a fitting place to start any discussion around Black lesbian identity in comics, as it is the first comic book that this researcher could find which features a Black lesbian female lead superheroine. Cyberzone was self-published by Jimmie Robinson in 1994 and later re-vamped into a mini-comic series called Amanda and Gunn with Image Comics. First, this article deconstructs Cyberzone through the lens of Cultural Prism Theory (CPT). Second, this article situates Cyberzone within the framework of CPT to address Cyberzone's place within the comic book ecosystem. Finally, this essay offers a close reading of Cyberzone, issues #1-#4, against the backdrop of the intersectional framework Black Queer Identity Matrix. During this process, the researcher demonstrates how Cyberzone is a powerful site of resistant cultural commentary.

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.

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

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.

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.

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

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.

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

Continuous performance task in ADHD: Is reaction time variability a key measure?

PubMed

Levy, Florence; Pipingas, Andrew; Harris, Elizabeth V; Farrow, Maree; Silberstein, Richard B

2018-01-01

To compare the use of the Continuous Performance Task (CPT) reaction time variability (intraindividual variability or standard deviation of reaction time), as a measure of vigilance in attention-deficit hyperactivity disorder (ADHD), and stimulant medication response, utilizing a simple CPT X-task vs an A-X-task. Comparative analyses of two separate X-task vs A-X-task data sets, and subgroup analyses of performance on and off medication were conducted. The CPT X-task reaction time variability had a direct relationship to ADHD clinician severity ratings, unlike the CPT A-X-task. Variability in X-task performance was reduced by medication compared with the children's unmedicated performance, but this effect did not reach significance. When the coefficient of variation was applied, severity measures and medication response were significant for the X-task, but not for the A-X-task. The CPT-X-task is a useful clinical screening test for ADHD and medication response. In particular, reaction time variability is related to default mode interference. The A-X-task is less useful in this regard.

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.

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.

Adaptation of community health worker-delivered behavioral activation for torture survivors in Kurdistan, Iraq.

PubMed

Magidson, J F; Lejuez, C W; Kamal, T; Blevins, E J; Murray, L K; Bass, J K; Bolton, P; Pagoto, S

2015-12-01

Growing evidence supports the use of Western therapies for the treatment of depression, trauma, and stress delivered by community health workers (CHWs) in conflict-affected, resource-limited countries. A recent randomized controlled trial (Bolton et al . 2014 a ) supported the efficacy of two CHW-delivered interventions, cognitive processing therapy (CPT) and brief behavioral activation treatment for depression (BATD), for reducing depressive symptoms and functional impairment among torture survivors in the Kurdish region of Iraq. This study describes the adaptation of the CHW-delivered BATD approach delivered in this trial (Bolton et al .2014 a ), informed by the Assessment-Decision-Administration-Production-Topical experts-Integration-Training-Testing (ADAPT-ITT) framework for intervention adaptation (Wingood & DiClemente, 2008). Cultural modifications, adaptations for low-literacy, and tailored training and supervision for non-specialist CHWs are presented, along with two clinical case examples to illustrate delivery of the adapted intervention in this setting. Eleven CHWs, a study psychiatrist, and the CHW clinical supervisor were trained in BATD. The adaptation process followed the ADAPT-ITT framework and was iterative with significant input from the on-site supervisor and CHWs. Modifications were made to fit Kurdish culture, including culturally relevant analogies, use of stickers for behavior monitoring, cultural modifications to behavioral contracts, and including telephone-delivered sessions to enhance feasibility. BATD was delivered by CHWs in a resource-poor, conflict-affected area in Kurdistan, Iraq, with some important modifications, including low-literacy adaptations, increased cultural relevancy of clinical materials, and tailored training and supervision for CHWs. Barriers to implementation, lessons learned, and recommendations for future efforts to adapt behavioral therapies for resource-limited, conflict-affected areas are discussed.

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.

Analyzing nearly four decades of historical radiosonde observations of tropical tropopause layer and cold-point temperatures

NASA Astrophysics Data System (ADS)

Gilford, D.; Randel, W. J.

2017-12-01

An understanding of historical trends and variability in the thermal structure of the tropical tropopause layer (TTL) is important for assessing climate and investigating TTL processes. In particular, the cold-point tropopause (CPT) plays an important role in stratospheric dehydration, the potential intensities of tropical cyclones, and other forms of stratospheric-tropospheric coupling. Uncertainties and biases of in-situ observations, however, make long-term estimation of TTL temperatures challenging, especially in the early decades of the satellite era. The goal of this study is to construct and analyze a long-term record of radiosondes temperatures with minimal biases. Temperature observations from 1979-present are drawn from the Integrated Global Radiosonde Archive version 2 (IGRA2). Vertically integrated radiosonde temperatures are compared with brightness temperatures from the Microwave Sounding Units (MSU) Lower Stratosphere channel to identify the radiosonde stations with the smallest temporal discontinuities. Insights from this comparison highlight the importance of independent measurements when evaluating TTL temperatures. The 38-year dataset constructed from IGRA2 stations with the smallest biases spans the tropics and has high vertical resolution, permitting reasonable estimates of the CPT temperature. Radiosonde temperatures show good agreement with GPS radio occultation measurements over the past decade. A multivariate regression model incorporating the Quasi-Biennial Oscillation and the El Nino Southern Oscillation is fit to the deseasonalized data to evaluate the spatial and temporal structures in its variability. Long-term trends in CPT temperatures are considered in the context of historical estimates from climate models. Correlations with TTL water vapor concentrations from the Stratospheric Water and OzOne Satellite Homogenized (SWOOSH) data set suggest a strong relationship between the historically observed CPT temperatures and dehydration.

Evaluation of pitting corrosion resistance of high-alloyed stainless steels welds for FGD plants in Korea

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

Baek, K.K.; Sung, H.J.; Im, C.S.

1998-12-31

For successful application of high-alloyed stainless steels for Flue Gas Desulfurization (FGD) plants, pitting corrosion resistance of arc welds of N-added 6%Mo austenitic stainless steels (UNS N 08367) and super duplex stainless steels (UNS S 32550) made with various filler metals were evaluated using the Green Death solution. For Gas Tungsten Arc (GTA) and Gas Metal Arc (GMA) welds of N 08367, Critical Pitting Temperature (CPT) of base metal was 65--70 C, whereas weld made by ERNiCrMo-3 filler metal yielded CPT of 50 C. Welds made by ERNiCrMo-10 or ERNiCrMo-4 filler metals showed CPT of 60--65 C and 65--70C, respectively.more » For GTA and GMA welds of S 32550, CPT of welds made by ERNiCrMo-3 was 45--50 C, indicating that the filler metal can provide pitting corrosion resistance matching the S 32550 alloy. Thus, a proper pitting corrosion resistance of weldments of high-alloy stainless steels can be achieved by selecting filler metals having at least +10 higher Pitting Resistance Equivalent Number (PRE{sub N}) value than the base metal regardless of the type of arc welding process. The over-alloyed filler metals would compensate preferential segregation of Cr, MO along the dendrite boundary, which made the dendrite core more susceptible to pitting. Nitrogen addition to the GTA welds of N 08367 made with ERNiCrMo-3 failed to improve pitting corrosion resistance, which was attributed to the precipitation of nitrogen in the weld metal in the form of Nb-nitride.« less

SU-F-J-202: Secondary Radiation Measurements for Charged Particle Therapy Monitoring: Fragmentation of Therapeutic He, C and O Ion Beams Impinging On a PMMA Target

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

Rucinski, A; Mancini-Terracciano, C; Paramatti, R

Purpose: In Charged Particle Therapy (CPT), besides protons, there has been recently a growing interest in 4He, 12C and 16O beams. The secondary radiation produced in the interaction of those beams with a patient could be potentially used for on-line monitoring of range uncertainties in order to fully exploit the advantages of those light ions resulting from increased Radio Biological Effectiveness, reduced multiple scattering and Oxygen Enhancement Ratio. The study and precise characterization of secondary radiation (beta+, prompt gamma, charged fragments) is the cornerstone of any R&D activity aiming for online monitoring development and purpose of the analysis presented here.more » Methods: We present the measurements of the secondary radiation generated by He, C and O beams impinging on a beam stopping PMMA target. The data has been collected at the Heidelberg Ionbeam Therapy center (HIT), where several millions of collisions were recorded at different energies, relevant for therapeutical applications. Results: The experimental setup, as well as the analysis strategies will be reviewed. The detected particle fluxes as a function of the primary beam energy and the emission angle with respect to the beam direction will be presented and compared to the results of other available measurements. In addition, the energy spectra and emission shapes of charged secondary particles will be shown and discussed in the context of the primary beam range monitoring technique that is being developed by the ARPG collaboration, within the INSIDE project funded by the Italian research ministry. The implications for dose monitoring applications will be discussed, in the context of the current (or planned) state-of- the-art detector solutions. Conclusion: The characterization of the radiation produced by 12C, 4He and 16O beams fully supports the feasibility of on-line range monitoring in the clinical practice of CPT by means of secondary particles detection.« less

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

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.

Effect of convection on the thermal structure of the troposphere and lower stratosphere including the tropical tropopause layer in the South Asian monsoon region

NASA Astrophysics Data System (ADS)

Muhsin, M.; Sunilkumar, S. V.; Venkat Ratnam, M.; Parameswaran, K.; Krishna Murthy, B. V.; Emmanuel, Maria

2018-04-01

Influence of convection on the thermal structure of Troposphere and Lower Stratosphere (TLS) is investigated using radiosonde data, obtained from Trivandrum (8.5°N, 76.9°E), Gadanki (13.5°N, 79.2°E), Bhubaneswar (20.25°N, 85.83°E), Kolkata (22.65°N, 88.45°E) and Singapore (1.37°N, 103.98°E), collected during different convective categories classified based on the altitude of deep convective cloud tops (CT) in the period 2008-2014. During deep convective events, the temperature showed lower tropospheric cooling, an upper tropospheric warming and an anomalous cooling (warming) below (above) the cold point tropopause (CPT) with respect to the clear-sky value. While warming in the upper troposphere is strongest (∼2-4 K) around 10-12 km, anomalous cooling (warming) below (above) the CPT is maximum around 15.5 km (17.5 km) with values in the range of-2 to -4 K (3-6 K). These temperature perturbations are observed 5-6 days prior to the convective events. In response to deep convection, surface cooling up to ∼ -4 K is also observed. This study showed that the magnitude of cold and warm anomalies increases with strength of convection. During deep convection, the potential temperature (θ) shows a decrease (<5 K) in the tropical tropopause layer (TTL) from the TTL-base up to CPT compared to that on clear-sky days, confirming the vertical mixing of convective air from the lower atmosphere to the TTL-levels. Correlation analysis between different TTL parameters suggests that, as the cloud top altitude increases, along with the adiabatic process, diabatic process also plays a major role in the TTL. An interesting feature observed during deep convection is the ascent of TTL-base by ∼1.5 km and descent of CPT and TTL-top by 0.5 km, which effectively thins the TTL by ∼2 km.

An aggregate method to calibrate the reference point of cumulative prospect theory-based route choice model for urban transit network

NASA Astrophysics Data System (ADS)

Zhang, Yufeng; Long, Man; Luo, Sida; Bao, Yu; Shen, Hanxia

2015-12-01

Transit route choice model is the key technology of public transit systems planning and management. Traditional route choice models are mostly based on expected utility theory which has an evident shortcoming that it cannot accurately portray travelers' subjective route choice behavior for their risk preferences are not taken into consideration. Cumulative prospect theory (CPT), a brand new theory, can be used to describe travelers' decision-making process under the condition of uncertainty of transit supply and risk preferences of multi-type travelers. The method to calibrate the reference point, a key parameter to CPT-based transit route choice model, determines the precision of the model to a great extent. In this paper, a new method is put forward to obtain the value of reference point which combines theoretical calculation and field investigation results. Comparing the proposed method with traditional method, it shows that the new method can promote the quality of CPT-based model by improving the accuracy in simulating travelers' route choice behaviors based on transit trip investigation from Nanjing City, China. The proposed method is of great significance to logical transit planning and management, and to some extent makes up the defect that obtaining the reference point is solely based on qualitative analysis.

tLyP-1-conjugated mesoporous silica nanoparticles for tumor targeting and penetrating hydrophobic drug delivery

NASA Astrophysics Data System (ADS)

Xu, Baiyao; Ju, Yang; Song, Guanbin; Cui, Yanbin

2013-12-01

Mesoporous silica nanoparticles (MSNs) are among the most appealing candidates for targeted drug delivery, a process for which it is essential that nanoparticles be internalized into targeted cells with high speed and efficiency. Therefore, it is necessary to conjugate a targeting ligand to the surface of a nanocarrier in order to trigger rapid receptor-mediated endocytosis and effective cellular uptake, which occurs following recognition and selective binding to a target cell's membrane receptor. Here, a tumor targeting and penetrating drug delivery system (DDS) based on MSNs ( 100 nm in size) is described. The MSNs were functionalized by engrafting with the tumor-homing and penetrating peptide tLyP-1. The fabricated MSN-tLyP-1 loaded with camptothecin (CPT) showed a robust targeting and penetrating efficiency to HeLa cells and MCF-7 cells and induced the death of these cells. Moreover, the adverse side effect of CPT on human mesenchymal stem cells (hMSCs) was minimized, because the nanoparticles were selectively targeted to the tumor cells, and little hydrophobic CPT was released into the culture medium or blood. The results indicate that the MSN-tLyP-1 DDS has great potential for the delivery of hydrophobic anticancer drugs to target tumors.

Measurements of Masses with the Canadian Penning Trap

NASA Astrophysics Data System (ADS)

Kuta, Trenton; Nystrom, Andrew; Aprahamian, Ani; Brodeur, Maxime; Burdette, Daniel; Buchinger, Fritz; Orford, Rodney; Clark, Jason; Hirsh, Tsviki; Ling-Ying, Lin; Savard, Guy; Burkey, Mary; Klimes, Jeffery; Dwaipayan, Ray; Sharma, Kumar; Morgan, Graeme

2016-09-01

The primary focus of the Canadian Penning Trap (CPT) located at Argonne National Laboratory is to determine the masses of various isotopes relevant to the rprocess, an astrophysical process thought to be responsible for the creation of half the elements heavier than iron. Currently, the CPT is operating in conjunction with the CAlifornium Rare Isotope Breeder Upgrade (CARIBU) at Argonne National Laboratory's ATLAS facility in an attempt to measure neutron-rich nuclei produced by a 1.0 Curie source of 252Cf. The mass measurements of these nuclei are accomplished by measuring the cyclotron frequency of the isotopes captured in the trap. This frequency is measured with a position-sensitive microchannel plate (MCP), which records the relative position of the isotope in the trap for different phase accumulation times. This summer, the CPT group was able to successfully measure to a precision of 10 keV/c2 the masses of 142I and 156 , 158 , 159Nd, which are key nuclei needed to more accurately model the rprocess. This also marks the first time that any of these nuclei had ever been measured. This work was supported by the National Science Foundation under Contract PHY-1205412, the University of Notre Dame, and the U.S. Department of Energy, Office of Nuclear Physics, under Contract No. DE-AC02-06CH11357.

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...

Using network biology to bridge pharmacokinetics and pharmacodynamics in oncology.

PubMed

Kirouac, D C; Onsum, M D

2013-09-04

If mathematical modeling is to be used effectively in cancer drug development, future models must take into account both the mechanistic details of cellular signal transduction networks and the pharmacokinetics (PK) of drugs used to inhibit their oncogenic activity. In this perspective, we present an approach to building multiscale models that capture systems-level architectural features of oncogenic signaling networks, and describe how these models can be used to design combination therapies and identify predictive biomarkers in silico.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e71; doi:10.1038/psp.2013.38; published online 4 September 2013.

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)

Sustaining visual attention in the face of distraction: a novel gradual-onset continuous performance task.

PubMed

Rosenberg, Monica; Noonan, Sarah; DeGutis, Joseph; Esterman, Michael

2013-04-01

Sustained attention is a fundamental aspect of human cognition and has been widely studied in applied and clinical contexts. Despite a growing understanding of how attention varies throughout task performance, moment-to-moment fluctuations are often difficult to assess. In order to better characterize fluctuations in sustained visual attention, in the present study we employed a novel continuous performance task (CPT), the gradual-onset CPT (gradCPT). In the gradCPT, a central face stimulus gradually transitions between individuals at a constant rate (1,200 ms), and participants are instructed to respond to each male face but not to a rare target female face. In the distractor-present version, the background distractors consist of scene images, and in the distractor-absent condition, of phase-scrambled scene images. The results confirmed that the gradCPT taxes sustained attention, as vigilance decrements were observed over the task's 12-min duration: Participants made more commission errors and showed increasingly variable response latencies (RTs) over time. Participants' attentional states also fluctuated from moment to moment, with periods of higher RT variability being associated with increased likelihood of errors and greater speed-accuracy trade-offs. In addition, task performance was related to self-reported mindfulness and the propensity for attention lapses in everyday life. The gradCPT is a useful tool for studying both low- and high-frequency fluctuations in sustained visual attention and is sensitive to individual differences in attentional ability.

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.

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.).

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.

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.

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.

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...

[Cognitive therapy of trauma related guilt in patients with PTSD].

PubMed

Popiel, Agnieszka

2014-01-01

Various aspects of guilt are frequent problems of patients suffering from PTSD, though they have been included into the diagnostic criteria for PTSD just in the present version DSM-5. Some studies indicate limitation of effectiveness of exposure therapy in PTSD patients with predominant emotions of anger or guilt. The aim of this paper is to present cognitive conceptualization of guilt in PTSD proposed by Kubany, and a treatment protocol resulting from this conceptualization. The clinical application of the protocol is illustrated with preliminary results of systematic observation of 8 patients with moderate to severe PTSD who were treated with cognitive therapy for guilt followed by a standard prolonged exposure protocol. The cognitive therapy of guilt can be a valuable supplement for treatment of PTSD. This protocol can also be an inspiration for therapists working with patients with dysfunctional guilt as a problem in other than PTSD disorders--like depression or adjustment disorders. In discussion the place of guilt in treatment according to different (PE-Foa et al.; CPT-Resick et al.; CT-Ehlers and Clark) trauma focused therapy approaches is addressed, and the need for further studies is underlined.

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.

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.

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

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.

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…

MO-G-BRE-05: Clinical Process Improvement and Billing in Radiation Oncology: A Case Study of Applying FMEA for CPT Code 77336 (continuing Medical Physics Consultation)

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

Spirydovich, S; Huq, M

2014-06-15

Purpose: The improvement of quality in healthcare can be assessed by Failure Mode and Effects Analysis (FMEA). In radiation oncology, FMEA, as applied to the billing CPT code 77336, can improve both charge capture and, most importantly, quality of the performed services. Methods: We created an FMEA table for the process performed under CPT code 77336. For a given process step, each member of the assembled team (physicist, dosimetrist, and therapist) independently assigned numerical values for: probability of occurrence (O, 1–10), severity (S, 1–10), and probability of detection (D, 1–10) for every failure mode cause and effect combination. The riskmore » priority number, RPN, was then calculated as a product of O, S and D from which an average RPN was calculated for each combination mentioned above. A fault tree diagram, with each process sorted into 6 categories, was created with linked RPN. For processes with high RPN recommended actions were assigned. 2 separate R and V systems (Lantis and EMR-based ARIA) were considered. Results: We identified 9 potential failure modes and corresponding 19 potential causes of these failure modes all resulting in unjustified 77336 charge and compromised quality of care. In Lantis, the range of RPN was 24.5–110.8, and of S values – 2–10. The highest ranking RPN of 110.8 came from the failure mode described as “end-of-treatment check not done before the completion of treatment”, and the highest S value of 10 (RPN=105) from “overrides not checked”. For the same failure modes, within ARIA electronic environment with its additional controls, RPN values were significantly lower (44.3 for end-of-treatment missing check and 20.0 for overrides not checked). Conclusion: Our work has shown that when charge capture was missed that also resulted in some services not being performed. Absence of such necessary services may result in sub-optimal quality of care rendered to patients.« less

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.

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.

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.

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.

Surgical management of failed endoscopic treatment of pancreatic disease.

PubMed

Evans, Kimberly A; Clark, Colby W; Vogel, Stephen B; Behrns, Kevin E

2008-11-01

Endoscopic therapy of acute and chronic pancreatitis has decreased the need for operative intervention. However, a significant proportion of patients treated endoscopically require definitive surgical management for persistent symptoms. Our aim was to determine which patients are likely to fail with endoscopic therapy, and to assess the clinical outcome of surgical management. Patients were identified using ICD-9 codes for pancreatic disease as well as CPT codes for endoscopic therapy followed by surgery. Patients with documented acute or chronic pancreatitis treated endoscopically prior to surgical therapy were included (N = 88). The majority of patients (65%) exhibited chronic pancreatitis due to alcohol abuse. Common indicators for surgery were: persistent symptoms, anatomy not amenable to endoscopic treatment and unresolved common bile duct or pancreatic duct strictures. Surgical salvage procedures included internal drainage of a pseudocyst or an obstructed pancreatic duct (46%), debridement of peripancreatic fluid collections (25%), and pancreatic resection (31%). Death occurred in 3% of patients. The most common complications were hemorrhage (16%), wound infection (13%), and pulmonary complications (11%). Chronic pancreatitis with persistent symptoms is the most common reason for pancreatic surgery following endoscopic therapy. Surgical salvage therapy can largely be accomplished by drainage procedures, but pancreatic resection is common. These complex procedures can be performed with acceptable mortality but also with significant risk for morbidity.

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.

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

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.

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.

Effects of Neurofeekback Training on EEG, Continuous Performance Task (CPT), and ADHD Symptoms in ADHD-prone College Students.

PubMed

Ryoo, Manhee; Son, Chongnak

2015-12-01

This study explored the effects of neurofeedback training on Electroencephalogram (EEG), Continuous Performance Task (CPT) and ADHD symptoms in ADHD prone college students. Two hundred forty seven college students completed Korean Version of Conners' Adult ADHD Rating Scales (CAARS-K) and Korean Version of Beck Depression Inventory (K-BDI). The 16 participants who ranked in the top 25% of CAARS-K score and had 16 less of K-BDI score participated in this study. Among them, 8 participants who are fit for the research schedule were assigned to neurofeedback training group and 8 not fit for the research schedule to the control group. All participants completed Adult Attention Deficiency Questionnaire, CPT and EEG measurement at pretest. The neurofeedback group received 15 neurofeedback training sessions (5 weeks, 3 sessions per week). The control group did not receive any treatment. Four weeks after completion of the program, all participants completed CAARS-K, Adult Attention Deficiency Questionnaire, CPT and EEG measurement for post-test. The neurofeedback group showed more significant improvement in EEG, CPT performance and ADHD symptoms than the control group. The improvements were maintained at follow up. Neurofeedback training adjusted abnormal EEG and was effective in improving objective and subjective ADHD symptoms in ADHD prone college students.

Forensic surface metrology: tool mark evidence.

PubMed

Gambino, Carol; McLaughlin, Patrick; Kuo, Loretta; Kammerman, Frani; Shenkin, Peter; Diaczuk, Peter; Petraco, Nicholas; Hamby, James; Petraco, Nicholas D K

2011-01-01

Over the last several decades, forensic examiners of impression evidence have come under scrutiny in the courtroom due to analysis methods that rely heavily on subjective morphological comparisons. Currently, there is no universally accepted system that generates numerical data to independently corroborate visual comparisons. Our research attempts to develop such a system for tool mark evidence, proposing a methodology that objectively evaluates the association of striated tool marks with the tools that generated them. In our study, 58 primer shear marks on 9 mm cartridge cases, fired from four Glock model 19 pistols, were collected using high-resolution white light confocal microscopy. The resulting three-dimensional surface topographies were filtered to extract all "waviness surfaces"-the essential "line" information that firearm and tool mark examiners view under a microscope. Extracted waviness profiles were processed with principal component analysis (PCA) for dimension reduction. Support vector machines (SVM) were used to make the profile-gun associations, and conformal prediction theory (CPT) for establishing confidence levels. At the 95% confidence level, CPT coupled with PCA-SVM yielded an empirical error rate of 3.5%. Complementary, bootstrap-based computations for estimated error rates were 0%, indicating that the error rate for the algorithmic procedure is likely to remain low on larger data sets. Finally, suggestions are made for practical courtroom application of CPT for assigning levels of confidence to SVM identifications of tool marks recorded with confocal microscopy. Copyright © 2011 Wiley Periodicals, Inc.

Fatty acid metabolism in CD8+ T cell memory: Challenging current concepts.

PubMed

Raud, Brenda; McGuire, Peter J; Jones, Russell G; Sparwasser, Tim; Berod, Luciana

2018-05-01

CD8 + T cells are key members of the adaptive immune response against infections and cancer. As we discuss in this review, these cells can present diverse metabolic requirements, which have been intensely studied during the past few years. Our current understanding suggests that aerobic glycolysis is a hallmark of activated CD8 + T cells, while naive and memory (T mem ) cells often rely on oxidative phosphorylation, and thus mitochondrial metabolism is a crucial determinant of CD8 + T mem cell development. Moreover, it has been proposed that CD8 + T mem cells have a specific requirement for the oxidation of long-chain fatty acids (LC-FAO), a process modulated in lymphocytes by the enzyme CPT1A. However, this notion relies heavily on the metabolic analysis of in vitro cultures and on chemical inhibition of CPT1A. Therefore, we introduce more recent studies using genetic models to demonstrate that CPT1A-mediated LC-FAO is dispensable for the development of CD8 + T cell memory and protective immunity, and question the use of chemical inhibitors to target this enzyme. We discuss insights obtained from those and other studies analyzing the metabolic characteristics of CD8 + T mem cells, and emphasize how T cells exhibit flexibility in their choice of metabolic fuel. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Magnetic and thermodynamic properties of Heusler alloys Ni55Mn26Al19

NASA Astrophysics Data System (ADS)

Ito, Masakazu; Onda, Keijiro; Taira, Atsushi; Sonoda, Kazuki; Hiroi, Masahiko; Uwatoko, Yoshiya

2018-05-01

The temperature dependence of magnetization, M(T), specific heat, Cp(T), and thermal expansion, ΔL/L300K(T) were investigated for the Heusler compound Ni55Mn26Al19 with B2 structure. M(T) has a cusp-type anomaly for the antiferromagnetic (AF) transition at the Néel temperature TN = 280 K that is irreversible between the field-cooled and zero-field-cooled processes below Tf ˜ 60 K, which is characteristic of spin glass. Cp(T) also has an anomaly at TN = 280 K. For temperatures T < 280 K, Cp(T) shows no anomaly without indicating any phase transition. These results mean that with decreasing T Ni55Mn26Al19 has a reentrant spin glass below Tf from the AF state. ΔL/L300K(T) shows no discontinuity indicating a structural transition in the range 5 < T < 300 K, i.e., Ni55Mn26Al19 has no martensitic transformation. TN increases proportionally with pressure, P, because of the enhancement of the AF interaction. The value of its initial rate is estimated to be d/TN d P = 5.25 K/GPa. Tf also increases proportionally with P with d/Tf d P = 2.21 K/GPa, and hence magnetic frustration, which promotes the spin glass system, is enhanced under pressurization.

[A recent trial of chemo-radiation with S-1 against gastric cancer].

PubMed

Saikawa, Yoshiro; Kiyota, Tsuyoshi; Nakamura, Rieko; Wada, Norihito; Yoshida, Masashi; Kubota, Tetsuro; Kumai, Koichiro; Shigematsu, Naoyuki; Kubo, Atsushi; Kitajima, Masaki

2006-06-01

A recent development of novel anticancer agents like S-1, CPT-11 or taxanes has improved a therapeutic outcome for advanced gastric cancer, while conventional anticancer agents showed less anticancer effect against gastric cancer. The present main drug in Japan is S-1, which is easily used for outpatient with a high efficacy rate and low toxicity, also shows better effect in combination with other anticancer drugs than S-1 alone. In the present article, we demonstrated significant meaning of additional radiation therapy with anticancer drugs like S-1. With novel anticancer drugs like S-1, we will expose a clinical advantage and appropriateness for chemo-radiation therapy against gastric cancer discussed in the present references according to chemo-radiation therapy. Although chemo-radiation therapy has been recognized as one of the standard therapies for gastric cancer in Western countries, radiation therapy was selected in Japan for palliation therapy of recurrent disease or a terminal cancer to improve patients' QOL. On the other hand, we demonstrated in our trial of chemo-radiation therapy with S-1/low-dose CDDP/radiation (TSLDR), which was applied to initial treatment against highly advanced Stage IV gastric cancer and revealed the usefulness of the regimen in anticancer effect and toxicity. In addition, chemo-radiation therapy including novel anticancer agents like S-1 will be discussed based on various kinds of view points, expecting a better clinical outcome of multimodal therapies against advanced gastric cancer.

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

Organic Anion Transporting Polypeptide (OATP)2B1 Contributes to Gastrointestinal Toxicity of Anticancer Drug SN-38, Active Metabolite of Irinotecan Hydrochloride.

PubMed

Fujita, Daichi; Saito, Yoshimasa; Nakanishi, Takeo; Tamai, Ikumi

2016-01-01

Gastrointestinal toxicity, such as late-onset diarrhea, is a significant concern in irinotecan hydrochloride (CPT-11)-containing regimens. Prophylaxis of late-onset diarrhea has been reported with use of Japanese traditional (Kampo) medicine containing baicalin and with the antibiotic cefixime, and this has been explained in terms of inhibition of bacterial deconjugation of SN-38-glucuronide since unconjugated SN-38 (active metabolite of CPT-11) is responsible for the gastrointestinal toxicity. It is also prerequisite for SN-38 to be accumulated in intestinal tissues to exert toxicity. Based on the fact that liver-specific organic anion transporting polypeptide (OATP)1B1, a member of the same family as OATP2B1, is known to be involved in hepatic transport of SN-38, we hypothesized that intestinal transporter OATP2B1 contributes to the accumulation of SN-38 in gastrointestinal tissues, and its inhibition would help prevent associated toxicity. We found that uptake of SN-38 by OATP2B1-expressing Xenopus oocytes was significantly higher than that by control oocytes. OATP2B1-mediated uptake of SN-38 was saturable, pH dependent, and decreased in the presence of baicalin, cefixime, or fruit juices such as apple juice. In vivo gastrointestinal toxicity of SN-38 in mice caused by oral administration for consecutive 5 days was prevented by coingestion of apple juice. Thus, OATP2B1 contributes to the uptake of SN-38 by intestinal tissues, triggering gastrointestinal toxicity. So, in addition to the reported inhibition of bacterial β-glucuronidase by cefixime or baicalin, inhibition of OATP2B1 may also contribute to prevention of gastrointestinal toxicity. Apple juice may be helpful for prophylaxis of late-onset diarrhea observed in CPT-11 therapy without disturbance of the intestinal microflora. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

A conjugate of camptothecin and a somatostatin analog against prostate cancer cell invasion via a possible signaling pathway involving PI3K/Akt, alphaVbeta3/alphaVbeta5 and MMP-2/-9.

PubMed

Sun, Li-Chun; Luo, Jing; Mackey, L Vienna; Fuselier, Joseph A; Coy, David H

2007-02-08

Camptothecin (CPT) was conjugated to the N-terminal of a somatostatin analog (SSA) directly via a carbamate group and a basic N-terminal linking motif, D-Lys-D-Tyr-Lys-D-Tyr-D-Lys. This new CPT-SSA conjugate termed JF-10-81 was evaluated as a receptor-specific delivery system for its anti-invasive and anti-angiogenic activities. It was found that, in addition to blocking migration and invasion of highly invasive prostate cancer PC-3 cells, this conjugate also inhibited in vitro capillary-like tube formation of endothelial cells and in vivo angiogenesis in C57B1/6N female mice. JF-10-81 was found to block PC-3 cell attachment to various extracellular matrix components, mainly to vitronectin, the ligand of cell surface receptors integrin alphaVbeta3 and alphaVbeta5. Additionally, JF-10-81 reduced expression of integrins alphaVbeta3 and alphaVbeta5 on PC-3 cell surfaces, without effects on beta1 or any alphabeta1 heterodimers. This conjugate also inactivated phosphorylation of protein kinase B (PKB/Akt), down-regulated the expression of latent matrix metalloproteinase (MMP) -2 and MMP-9, but had little effect on MMP-3/-10. Meanwhile, membrane type-1 matrix metalloproteinase (MT1-MMP) and the tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) were not detectable in PC-3 cells. alphaVbeta3/alphaVbeta5 and MMP-2/-9 are known to be highly expressed in many tumor cells and play an important role in tumor progression. Our results support that this conjugate could possibly inhibit prostate cancer PC-3 cell invasion through a signaling pathway involving PI3K/Akt, alphaVbeta3/alphaVbeta5 and MMP-2/-9, and this SSA could be used as an efficient vector to deliver CPT or other cytotoxic agents to target sites for cancer therapy.

Modelling carcinogenesis after radiotherapy using Poisson statistics: implications for IMRT, protons and ions.

PubMed

Jones, Bleddyn

2009-06-01

Current technical radiotherapy advances aim to (a) better conform the dose contours to cancers and (b) reduce the integral dose exposure and thereby minimise unnecessary dose exposure to normal tissues unaffected by the cancer. Various types of conformal and intensity modulated radiotherapy (IMRT) using x-rays can achieve (a) while charged particle therapy (CPT)-using proton and ion beams-can achieve both (a) and (b), but at greater financial cost. Not only is the long term risk of radiation related normal tissue complications important, but so is the risk of carcinogenesis. Physical dose distribution plans can be generated to show the differences between the above techniques. IMRT is associated with a dose bath of low to medium dose due to fluence transfer: dose is effectively transferred from designated organs at risk to other areas; thus dose and risk are transferred. Many clinicians are concerned that there may be additional carcinogenesis many years after IMRT. CPT reduces the total energy deposition in the body and offers many potential advantages in terms of the prospects for better quality of life along with cancer cure. With C ions there is a tail of dose beyond the Bragg peaks, due to nuclear fragmentation; this is not found with protons. CPT generally uses higher linear energy transfer (which varies with particle and energy), which carries a higher relative risk of malignant induction, but also of cell death quantified by the relative biological effect concept, so at higher dose levels the frank development of malignancy should be reduced. Standard linear radioprotection models have been used to show a reduction in carcinogenesis risk of between two- and 15-fold depending on the CPT location. But the standard risk models make no allowance for fractionation and some have a dose limit at 4 Gy. Alternatively, tentative application of the linear quadratic model and Poissonian statistics to chromosome breakage and cell kill simultaneously allows estimation of relative changes in carcinogenesis that incorporate fractionation and relative biological effects (RBE). This alternative modelling approach allows absolute and relative risk estimations per cell and can be extended to tissues. The classical turnover point in carcinogenesis occurring after a single exposure is a feature of the model; also, the dose-response relationship becomes pseudo-linear with extended fractionation and when heterogeneity of the radiosensitivity parameters is introduced; there is also an inverse relationship between dose per fraction and cancer induction. In principle, this new approach might influence the conduct of proton and ion beam therapy, particularly beam placements and fractionation policies. The theoretical implications for future radiotherapy are considerable, but these predictions should be subjected to cellular and tissue experiments that simulate these forms of treatment, including any secondary neutron production in some cases depending on the beam delivery technique, e.g. in tissue equivalent humanoid phantoms using cell transformation techniques. Since the UK has no working high energy particle beam facility over 100 MeV, British scientists would require use of particle beam facilities in Europe, USA or Japan to perform experiments.

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.

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.

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.

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.

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

A conservation planning tool for Greater Sage-grouse using indices of species distribution, resilience, and resistance.

PubMed

Ricca, Mark A; Coates, Peter S; Gustafson, K Benjamin; Brussee, Brianne E; Chambers, Jeanne C; Espinosa, Shawn P; Gardner, Scott C; Lisius, Sherri; Ziegler, Pilar; Delehanty, David J; Casazza, Michael L

2018-06-01

Managers require quantitative yet tractable tools that identify areas for restoration yielding effective benefits for targeted wildlife species and the ecosystems they inhabit. As a contemporary example of high national significance for conservation, the persistence of Greater Sage-grouse (Centrocercus urophasianus) in the Great Basin is compromised by strongly interacting stressors of conifer expansion, annual grass invasion, and more frequent wildfires occurring in sagebrush ecosystems. Associated restoration treatments to a sagebrush-dominated state are often costly and may yield relatively little ecological benefit to sage-grouse if implemented without estimating how Sage-grouse may respond to treatments, or do not consider underlying processes influencing sagebrush ecosystem resilience to disturbance and resistance to invasive species. Here, we describe example applications of a spatially explicit conservation planning tool (CPT) to inform prioritization of: (1) removal of conifers (i.e., pinyon-juniper); and (2) wildfire restoration aimed at improving habitat conditions for the Bi-State Distinct Population Segment of Sage-grouse along the California-Nevada state line. The CPT measures ecological benefits to sage-grouse for a given management action through a composite index comprised of resource selection functions and estimates of abundance and space use. For pinyon-juniper removal, we simulated changes in land-cover composition following the removal of sparse trees with intact understories, and ranked treatments on the basis of changes in ecological benefits per dollar-unit of cost. For wildfire restoration, we formulated a conditional model to simulate scenarios for land cover changes (e.g., sagebrush to annual grass) given estimated fire severity and underlying ecosystem processes influencing resilience to disturbance and resistance to invasion by annual grasses. For both applications, we compared CPT rankings to land cover changes along with sagebrush resistance and resilience metrics. Model results demonstrated how the CPT can be an important step in identifying management projects that yield the highest quantifiable benefit to Sage-grouse while avoiding costly misallocation of resources, and highlight the importance of considering changes in sage-grouse ecological response and factors influencing sagebrush ecosystem resilience to disturbance and resistance to invasion. This unique framework can be adopted to help inform other management questions aimed at improving habitat for other species across sagebrush and other ecosystems. © 2018 The Authors. Ecological Applications published by Wiley Periodicals, Inc. on behalf of Ecological Society of America.

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.

Models & Searches of CPT Violation: a personal, very partial, list

NASA Astrophysics Data System (ADS)

Mavromatos, Nick E.

2018-01-01

In this talk, first I motivate theoretically, and then I review the phenomenology of, some models entailing CPT Violation (CPTV). The latter is argued to be responsible for the observed matter-antimatter asymmetry in the Cosmos, and may owe its origin to either Lorentz-violating background geometries, whose effects are strong in early epochs of the Universe but very weak today, being temperature dependent in general, or to an ill-defined CPT generator in some quantum gravity models entailing decoherence of quantum matter as a result of quantum degrees of freedom in the gravity sector that are inaccessible to the low-energy observers. In particular, for the latter category of CPTV, I argue that entangled states of neutral mesons (Kaons or B-systems), of central relevance to KLOE-2 experiment, 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, which I only briefly touch upon.

Intrabilayer 64Cu Labeling of Photoactivatable, Doxorubicin-Loaded Stealth Liposomes.

PubMed

Luo, Dandan; Goel, Shreya; Liu, Hai-Jun; Carter, Kevin A; Jiang, Dawei; Geng, Jumin; Kutyreff, Christopher J; Engle, Jonathan W; Huang, Wei-Chiao; Shao, Shuai; Fang, Chao; Cai, Weibo; Lovell, Jonathan F

2017-12-26

Doxorubicin (Dox)-loaded stealth liposomes (similar to those in clinical use) can incorporate small amounts of porphyrin-phospholipid (PoP) to enable chemophototherapy (CPT). PoP is also an intrinsic and intrabilayer 64 Cu chelator, although how radiolabeling impacts drug delivery has not yet been assessed. Here, we show that 64 Cu can radiolabel the stable bilayer of preformed Dox-loaded PoP liposomes with inclusion of 1% ethanol without inducing drug leakage. Dox-PoP liposomes labeled with intrabilayer copper behaved nearly identically to unlabeled ones in vitro and in vivo with respect to physical parameters, pharmacokinetics, and CPT efficacy. Positron emission tomography and near-infrared fluorescence imaging visualized orthotopic mammary tumors in mice with passive liposome accumulation following administration. A single CPT treatment with 665 nm light (200 J/cm 2 ) strongly inhibited primary tumor growth. Liposomes accumulated in lung metastases, based on NIR imaging. These results establish the feasibility of CPT interventions guided by intrinsic multimodal imaging of Dox-loaded stealth PoP liposomes.

Modulation of irinotecan-induced diarrhea by cotreatment with neomycin in cancer patients.

PubMed

Kehrer, D F; Sparreboom, A; Verweij, J; de Bruijn, P; Nierop, C A; van de Schraaf, J; Ruijgrok, E J; de Jonge, M J

2001-05-01

This study was designed to evaluate irinotecan (CPT-11) disposition and pharmacodynamics in the presence and absence of the broad-spectrum antibiotic neomycin. Seven evaluable cancer patients experiencing diarrhea graded > or =2 after receiving CPT-11 alone (350 mg/m(2) i.v. once every 3 weeks) received the same dose combined with oral neomycin at 1000 mg three times per day (days -2 to 5) in the second course. Neomycin had no effect on the systemic exposure of CPT-11 and its major metabolites (P > or = 0.22). However, it changed fecal beta-glucuronidase activity from 7.03 +/- 1.76 microg/h/mg (phenolphthalein assay) to undetectable levels and decreased fecal concentrations of the pharmacologically active metabolite SN-38. Although neomycin had no significant effect on hematological toxicity (P > 0.05), diarrhea ameliorated in six of seven patients (P = 0.033). Our findings indicate that bacterial beta-glucuronidase plays a crucial role in CPT-11-induced diarrhea without affecting enterocycling and systemic SN-38 levels.

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

Current Perception Threshold for Assessment of the Neurological Components of Hand-Arm Vibration Syndrome: A Review

PubMed Central

Kurozawa, Youichi; Hosoda, Takenobu; Nasu, Yoshiro

2010-01-01

Current perception threshold (CPT) has been proposed as a quantitative method for assessment of peripheral sensory nerve function. The aim of this review of selected reports is to provide an overview of CPT measurement for the assessment of the neurological component of hand-arm vibration syndrome (HAVS). The CPT values at 2000 Hz significantly increased for patients with HAVS. This result supports the previous histological findings that demyelination is found predominantly in the peripheral nerves in the hands of men exposed to hand-arm vibration. Diagnostic sensitivity and specificity were high for severe cases of Stockholm sensorineural (SSN) stage 3 compared with non-exposed controls, but not high for mild cases of SSN stage 1 or 2 and for carpal tunnel syndrome associated with HAVS. However, there are only a few studies on the diagnostic validity of the CPT test for the neurological components of HAVS. Further research is needed and should include diagnostic validity and standardizing of measurement conditions such as skin temperature. PMID:24031119

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.

Treatment of neonatal jaundice with filtered sunlight in Nigerian neonates: study protocol of a non-inferiority, randomized controlled trial.

PubMed

Slusher, Tina M; Olusanya, Bolajoko O; Vreman, Hendrik J; Wong, Ronald J; Brearley, Ann M; Vaucher, Yvonne E; Stevenson, David K

2013-12-28

Severe neonatal jaundice and its progression to kernicterus is a leading cause of death and disability among newborns in poorly-resourced countries, particularly in sub-Saharan Africa. The standard treatment for jaundice using conventional phototherapy (CPT) with electric artificial blue light sources is often hampered by the lack of (functional) CPT devices due either to financial constraints or erratic electrical power. In an attempt to make phototherapy (PT) more readily available for the treatment of pathologic jaundice in underserved tropical regions, we set out to test the hypothesis that filtered sunlight phototherapy (FS-PT), in which potentially harmful ultraviolet and infrared rays are appropriately screened, will be as efficacious as CPT. This prospective, non-blinded randomized controlled non-inferiority trial seeks to enroll infants with elevated total serum/plasma bilirubin (TSB, defined as 3 mg/dl below the level recommended by the American Academy of Pediatrics for high-risk infants requiring PT) who will be randomly and equally assigned to receive FS-PT or CPT for a total of 616 days at an inner-city maternity hospital in Lagos, Nigeria. Two FS-PT canopies with pre-tested films will be used. One canopy with a film that transmits roughly 33% blue light (wavelength range: 400 to 520 nm) will be used during sunny periods of a day. Another canopy with a film that transmits about 79% blue light will be used during overcast periods of the day. The infants will be moved from one canopy to the other as needed during the day with the goal of keeping the blue light irradiance level above 8 μW/cm²/nm. FS-PT will be as efficacious as CPT in reducing the rate of rise in bilirubin levels. Secondary outcome: The number of infants requiring exchange transfusion under FS-PT will not be more than those under CPT. This novel study offers the prospect of an effective treatment for infants at risk of severe neonatal jaundice and avoidable exchange transfusion in poorly-resourced settings without access to (reliable) CPT in the tropics. ClinicalTrials.gov Identifier: NCT01434810.

Quality improvement in neurology: AAN Parkinson disease quality measures

PubMed Central

Cheng, E.M.; Tonn, S.; Swain-Eng, R.; Factor, S.A.; Weiner, W.J.; Bever, C.T.

2010-01-01

Background: Measuring the quality of health care is a fundamental step toward improving health care and is increasingly used in pay-for-performance initiatives and maintenance of certification requirements. Measure development to date has focused on primary care and common conditions such as diabetes; thus, the number of measures that apply to neurologic care is limited. The American Academy of Neurology (AAN) identified the need for neurologists to develop measures of neurologic care and to establish a process to accomplish this. Objective: To adapt and test the feasibility of a process for independent development by the AAN of measures for neurologic conditions for national measurement programs. Methods: A process that has been used nationally for measure development was adapted for use by the AAN. Topics for measure development are chosen based upon national priorities, available evidence base from a systematic literature search, gaps in care, and the potential impact for quality improvement. A panel composed of subject matter and measure development methodology experts oversees the development of the measures. Recommendation statements and their corresponding level of evidence are reviewed and considered for development into draft candidate measures. The candidate measures are refined by the expert panel during a 30-day public comment period and by review by the American Medical Association for Current Procedural Terminology (CPT) II codes. All final AAN measures are approved by the AAN Board of Directors. Results: Parkinson disease (PD) was chosen for measure development. A review of the medical literature identified 258 relevant recommendation statements. A 28-member panel approved 10 quality measures for PD that included full specifications and CPT II codes. Conclusion: The AAN has adapted a measure development process that is suitable for national measurement programs and has demonstrated its capability to independently develop quality measures. GLOSSARY AAN = American Academy of Neurology; ABPN = American Board of Psychiatry and Neurology; AMA = American Medical Association; CPT II = Current Procedural Terminology; PCPI = Physician Consortium for Performance Improvement; PD = Parkinson disease; PMAG = Performance Measurement Advisory Group; PQRI = Physician Quality Reporting Initiative; QMR = Quality Measurement and Reporting Subcommittee. PMID:21115958

Neutrino-antineutrino oscillations as a possible solution for the LSND and MiniBooNE anomalies?

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

Hollenberg, Sebastian; Micu, Octavian; Paes, Heinrich

2009-09-01

We investigate resonance structures in CPT and Lorentz symmetry-violating neutrino-antineutrino oscillations in a two generation framework. The neutrino-antineutrino oscillations are induced by Lorentz- and CPT-violating terms in the Hamiltonian. The resonances are suitably described in terms of charge conjugation eigenstates of the system. The relations among the flavor, charge conjugation and mass eigenbasis of neutrino-antineutrino oscillations are examined along with the interplay between the available CPT-violating parameter space and possible resonance structures. Eventually we remark on the consequences of such scenarios for neutrino oscillation experiments, namely, possible solutions for the LSND and MiniBooNE anomalies.

Lorentz- and CPT-symmetry studies in subatomic physics

NASA Astrophysics Data System (ADS)

Lehnert, Ralf

2016-12-01

Subatomic systems provide an exquisite test bench for spacetime symmetries. This work motivates such measurements, reviews the effective field theory test framework for the description of Lorentz and CPT violation, and employs this framework to study the phenomenology of spacetime-symmetry breaking in various subatomic systems.

Association between the low-dose irinotecan regimen-induced occurrence of grade 4 neutropenia and genetic variants of UGT1A1 in patients with gynecological cancers

PubMed Central

MORIYA, HIROYUKI; SAITO, KATSUHIKO; HELSBY, NUALA; SUGINO, SHIGEKAZU; YAMAKAGE, MICHIAKI; SAWAGUCHI, TAKERU; TAKASAKI, MASAHIKO; KATO, HIDENORI; KUROSAWA, NAHOKO

2014-01-01

The occurrence of severe neutropenia during treatment with irinotecan (CPT-11) is associated with the *6 and *28 alleles of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). However, the correlation between these variants and the occurrence of severe neutropenia in a low-dose CPT-11 regimen for the treatment of gynecological cancers has not been extensively studied. There are also no studies regarding the association between the 421C>A mutation in ATP-binding cassette sub-family G member 2 (ABCG2) and the occurrence of severe neutropenia in CPT-11-treated patients with gynecological cancers. The present study was designed to determine the factors associated with the occurrence of grade 4 neutropenia during chemotherapy for gynecological cancers with combinations of CPT-11 and cisplatin or mitomycin C. In total, 44 patients with gynecological cancer were enrolled in the study. The association between the absolute neutrophil count (ANC) nadir values, the total dose of CPT-11 and the genotypes of UGT1A1 or ABCG2 was studied. No correlation was observed between the ANC nadir values and the total dose of CPT-11. The ANC nadir values in the UGT1A1*6/*28 and *6/*6 groups were significantly lower compared with those in the *1/*1 group (P<0.01). Univariate analysis showed no association between the occurrence of grade 4 neutropenia and the ABCG2 421C>A mutation. Subsequent to narrowing the factors by univariate analysis, multivariate logistic regression analysis only detected significant correlations between the occurrence of grade 4 neutropenia and the UGT1A1*6/*6 and *6/*28 groups (P=0.029; odds ratio, 6.90; 95% confidence interval, 1.22–38.99). No associations were detected between the occurrence of grade 4 neutropenia and the heterozygous variant (*1/*6 or *1/*28) genotype, type of regimen or age. In conclusion, the UGT1A1*6/*28 and *6/*6 genotypes were found to be associated with the occurrence of severe neutropenia in the low-dose CPT-11 regimen for gynecological cancers. This finding indicates that the determination of UGT1A1 variants may be as useful in CPT-11 chemotherapy for gynecological conditions as it is in colorectal and lung cancer patients treated with this drug. PMID:24932285

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.

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.

A kinetic clutch governs uncoiling by type IB topoisomerases

NASA Astrophysics Data System (ADS)

Neuman, Keir

2013-03-01

Type IB topoisomerases (Top1B) are essential enzymes that relax excessive DNA supercoiling associated with replication and transcription and are important drug targets for cancer chemotherapy. The natural compound camptothecin (CPT) and the cancer chemotherapeutics derived from it, irinotecan and topotecan, are highly specific inhibitors of human nuclear Type IB topoisomerase (nTop1). We employed a magnetic-tweezers based single-molecule DNA supercoil relaxation assay to measure the torque dependence of human nuclear Top1 relaxation (nTop1) and inhibition by CPT. For comparison, we examined the human mitochondrial (Top1mt) topoisomerase and an N-terminal deletion mutant of nTop1 (Top68). Despite substantial sequence homology in their core domains, nTop1 and Top1mt exhibit dramatic differences in sensitivity to torque and CPT, with Top68 betraying intermediate characteristics. In particular, nTop1 displays nearly torque-independent religation probability, distinguishing it from other Top1B enzymes studied to date. Kinetic modeling reveals a hitherto unobserved torque-independent transition linking the DNA rotation and religation phases of the enzymatic cycle. The parameters of this transition determine the torque sensitivity of religation, and the efficiency of CPT binding. This ``kinetic clutch'' mechanism explains the molecular basis of CPT sensitivity and more generally provides a framework with which to interpret Top1B activity and inhibition.

Long-term increased carnitine palmitoyltransferase 1A expression in ventromedial hypotalamus causes hyperphagia and alters the hypothalamic lipidomic profile.

PubMed

Mera, Paula; Mir, Joan Francesc; Fabriàs, Gemma; Casas, Josefina; Costa, Ana S H; Malandrino, Maria Ida; Fernández-López, José-Antonio; Remesar, Xavier; Gao, Su; Chohnan, Shigeru; Rodríguez-Peña, Maria Sol; Petry, Harald; Asins, Guillermina; Hegardt, Fausto G; Herrero, Laura; Serra, Dolors

2014-01-01

Lipid metabolism in the ventromedial hypothalamus (VMH) has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT) 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH), long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT) and reduced vesicular glutamate transporter 2 (VGLUT2) expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH.

Long-Term Increased Carnitine Palmitoyltransferase 1A Expression in Ventromedial Hypotalamus Causes Hyperphagia and Alters the Hypothalamic Lipidomic Profile

PubMed Central

Fabriàs, Gemma; Casas, Josefina; Costa, Ana S. H.; Malandrino, Maria Ida; Fernández-López, José-Antonio; Remesar, Xavier; Gao, Su; Chohnan, Shigeru; Rodríguez-Peña, Maria Sol; Petry, Harald; Asins, Guillermina; Hegardt, Fausto G.; Herrero, Laura; Serra, Dolors

2014-01-01

Lipid metabolism in the ventromedial hypothalamus (VMH) has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT) 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH), long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT) and reduced vesicular glutamate transporter 2 (VGLUT2) expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH. PMID:24819600

Laticifer-specific cis-prenyltransferase silencing affects the rubber, triterpene, and inulin content of Taraxacum brevicorniculatum.

PubMed

Post, Janina; van Deenen, Nicole; Fricke, Julia; Kowalski, Natalie; Wurbs, David; Schaller, Hubert; Eisenreich, Wolfgang; Huber, Claudia; Twyman, Richard M; Prüfer, Dirk; Gronover, Christian Schulze

2012-03-01

Certain Taraxacum species, such as Taraxacum koksaghyz and Taraxacum brevicorniculatum, produce large amounts of high-quality natural rubber in their latex, the milky cytoplasm of specialized cells known as laticifers. This high-molecular mass biopolymer consists mainly of poly(cis-1,4-isoprene) and is deposited in rubber particles by particle-bound enzymes that carry out the stereospecific condensation of isopentenyl diphosphate units. The polymer configuration suggests that the chain-elongating enzyme (rubber transferase; EC 2.5.1.20) is a cis-prenyltransferase (CPT). Here, we present a comprehensive analysis of transgenic T. brevicorniculatum plants in which the expression of three recently isolated CPTs known to be associated with rubber particles (TbCPT1 to -3) was heavily depleted by laticifer-specific RNA interference (RNAi). Analysis of the CPT-RNAi plants by nuclear magnetic resonance, size-exclusion chromatography, and gas chromatography-mass spectrometry indicated a significant reduction in rubber biosynthesis and a corresponding 50% increase in the levels of triterpenes and the main storage carbohydrate, inulin. Transmission electron microscopy revealed that the laticifers in CPT-RNAi plants contained fewer and smaller rubber particles than wild-type laticifers. We also observed lower activity of hydroxymethylglutaryl-coenzyme A reductase, the key enzyme in the mevalonate pathway, reflecting homeostatic control of the isopentenyl diphosphate pool. To our knowledge, this is the first in planta demonstration of latex-specific CPT activity in rubber biosynthesis.

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

Compassionate Use of Triheptanoin (C7) for Inherited Disorders of Energy Metabolism

ClinicalTrials.gov

2018-05-02

Very Long-chain acylCoA Dehydrogenase (VLCAD) Deficiency; Carnitine Palmitoyltransferase Deficiencies (CPT1, CPT2); Mitochondrial Trifunctional Protein Deficiency; Long-chain Hydroxyacyl-CoA Dehydrogenase Deficiency; Glycogen Storage Disorders; Pyruvate Carboxylase Deficiency Disease; ACYL-CoA DEHYDROGENASE FAMILY, MEMBER 9, DEFICIENCY of; Barth Syndrome

Anomalous visual experiences, negative symptoms, perceptual organization and the magnocellular pathway in schizophrenia: a shared construct?

PubMed

Kéri, Szabolcs; Kiss, Imre; Kelemen, Oguz; Benedek, György; Janka, Zoltán

2005-10-01

Schizophrenia is associated with impaired visual information processing. The aim of this study was to investigate the relationship between anomalous perceptual experiences, positive and negative symptoms, perceptual organization, rapid categorization of natural images and magnocellular (M) and parvocellular (P) visual pathway functioning. Thirty-five unmedicated patients with schizophrenia and 20 matched healthy control volunteers participated. Anomalous perceptual experiences were assessed with the Bonn Scale for the Assessment Basic Symptoms (BSABS). General intellectual functions were evaluated with the revised version of the Wechsler Adult Intelligence Scale. The 1-9 version of the Continuous Performance Test (CPT) was used to investigate sustained attention. The following psychophysical tests were used: detection of Gabor patches with collinear and orthogonal flankers (perceptual organization), categorization of briefly presented natural scenes (rapid visual processing), low-contrast and frequency-doubling vernier threshold (M pathway functioning), isoluminant colour vernier threshold and high spatial frequency discrimination (P pathway functioning). The patients with schizophrenia were impaired on test of perceptual organization, rapid visual processing and M pathway functioning. There was a significant correlation between BSABS scores, negative symptoms, perceptual organization, rapid visual processing and M pathway functioning. Positive symptoms, IQ, CPT and P pathway measures did not correlate with these parameters. The best predictor of the BSABS score was the perceptual organization deficit. These results raise the possibility that multiple facets of visual information processing deficits can be explained by M pathway dysfunctions in schizophrenia, resulting in impaired attentional modulation of perceptual organization and of natural image categorization.

Infant Malnutrition Is Associated with Persisting Attention Deficits in Middle Adulthood123

PubMed Central

Galler, Janina R.; Bryce, Cyralene P.; Zichlin, Miriam L.; Fitzmaurice, Garrett; Eaglesfield, G. David; Waber, Deborah P.

2012-01-01

Infantile malnutrition is known to be associated with cognitive and behavioral impairment during childhood and adolescence. Data pertaining to longer-term effects on behavioral outcomes in adulthood are limited. In this study, we report associations between infantile malnutrition and attention problems in adults at midlife. Attention problems were assessed by the Conners Adult ADHD Rating Scales (CAARS) and the Conners Continuous Performance Test (CPT) in 145 Barbadian adults (aged 37–43 y) who had been followed longitudinally since childhood. Previously malnourished participants (n = 80) had experienced moderate to severe protein-energy malnutrition in the first year of life and were successfully rehabilitated thereafter. They were compared with healthy adults (n = 65) who were former classmates of the index cases and who had been matched for age, sex, and handedness in childhood. Multiple regression analyses showed persisting effects of childhood malnutrition on both the CAARS and the CPT, independent of effects of household standard of living assessed in childhood. The malnutrition effect on the CAARS ratings was independent of IQ, whereas this effect was attenuated for the CPT after adjustment for IQ. Teacher-reported attention problems in childhood predicted attention problems in adulthood, indicating continuity over the life span. Infantile malnutrition may have long-term effects on attentional processes nearly 40 y after the episode, even with excellent long-term nutritional rehabilitation and independent of socioeconomic conditions in childhood and adolescence. This finding has major public health implications for populations exposed to early childhood malnutrition. PMID:22378333

Infant malnutrition is associated with persisting attention deficits in middle adulthood.

PubMed

Galler, Janina R; Bryce, Cyralene P; Zichlin, Miriam L; Fitzmaurice, Garrett; Eaglesfield, G David; Waber, Deborah P

2012-04-01

Infantile malnutrition is known to be associated with cognitive and behavioral impairment during childhood and adolescence. Data pertaining to longer-term effects on behavioral outcomes in adulthood are limited. In this study, we report associations between infantile malnutrition and attention problems in adults at midlife. Attention problems were assessed by the Conners Adult ADHD Rating Scales (CAARS) and the Conners Continuous Performance Test (CPT) in 145 Barbadian adults (aged 37-43 y) who had been followed longitudinally since childhood. Previously malnourished participants (n = 80) had experienced moderate to severe protein-energy malnutrition in the first year of life and were successfully rehabilitated thereafter. They were compared with healthy adults (n = 65) who were former classmates of the index cases and who had been matched for age, sex, and handedness in childhood. Multiple regression analyses showed persisting effects of childhood malnutrition on both the CAARS and the CPT, independent of effects of household standard of living assessed in childhood. The malnutrition effect on the CAARS ratings was independent of IQ, whereas this effect was attenuated for the CPT after adjustment for IQ. Teacher-reported attention problems in childhood predicted attention problems in adulthood, indicating continuity over the life span. Infantile malnutrition may have long-term effects on attentional processes nearly 40 y after the episode, even with excellent long-term nutritional rehabilitation and independent of socioeconomic conditions in childhood and adolescence. This finding has major public health implications for populations exposed to early childhood malnutrition.

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

Product-sum universality and Rushbrooke inequality in explosive percolation

NASA Astrophysics Data System (ADS)

Sabbir, M. M. H.; Hassan, M. K.

2018-05-01

We study explosive percolation (EP) on an Erdös-Rényi network for product rule (PR) and sum rule (SR). Initially, it was claimed that EP describes discontinuous phase transition; now it is well accepted as a probabilistic model for thermal continuous phase transition (CPT). However, no model for CPT is complete unless we know how to relate its observable quantities with those of thermal CPT. To this end, we define entropy and specific heat, redefine susceptibility, and show that they behave exactly like their thermal counterparts. We obtain the critical exponents ν ,α ,β , and γ numerically and find that both PR and SR belong to the same universality class and obey Rushbrooke inequality.

Lineshape asymmetry for joint coherent population trapping and three-photon N resonances

NASA Astrophysics Data System (ADS)

Hancox, Cindy; Hohensee, Michael; Crescimanno, Michael; Phillips, David F.; Walsworth, Ronald L.

2008-06-01

We show that a characteristic two photon lineshape asymmetry arises in coherent population trapping (CPT) and three photon (N) resonances because both resonances are simultaneously induced by modulation sidebands in the interrogating laser light. The N resonance is a three-photon resonance in which a two-photon Raman excitation is combined with a resonant optical pumping field. This joint CPT and N resonance can be the dominant source of lineshape distortion, with direct relevance for the operation of miniaturized atomic frequency standards. We present the results of both an experimental study and theoretical treatment of the asymmetry of the joint CPT and N resonance under conditions typical to the operation of an N resonance clock.

A CEFR-Based Computerized Adaptive Testing System for Chinese Proficiency

ERIC Educational Resources Information Center

Wang, Hsuan-Po; Kuo, Bor-Chen; Tsai, Ya-Hsun; Liao, Chen-Huei

2012-01-01

In the era of globalization, the trend towards learning Chinese as a foreign language (CFL) has become increasingly popular worldwide. The increasing demand in learning CFL has raised the profile of the Chinese proficiency test (CPT). This study will analyze in depth the inadequacy of current CPT's utilizing the common European framework of…

Does Curriculum Practical Training Affect Engineers' Workplace Outcomes? Evidence from an Engineer Survey in China

ERIC Educational Resources Information Center

Li, Jing; Zhang, Yu; Tsang, Mun; Li, Manli

2015-01-01

With the increasing attention to STEM (Science, Technology, Engineering, and Math), hands-on Curriculum Practical Training (CPT) has been expanding rapidly worldwide as a requirement of the undergraduate engineering education. In China, a typical CPT for undergraduate engineering students requires several weeks of hands-on training in the…

Relationships between Continuous Performance Task Scores and Other Cognitive Measures: Causality or Commonality?

ERIC Educational Resources Information Center

Aylward, Glen P.; Gordon, Michael; Verhulst, Steven J.

1997-01-01

Relationships among continuous performance test (CPT), IQ, achievement, and memory/learning scores were explored for 1,280 children about 9 years old. Associations among the CPT measures and various cognitive/academic tasks suggest that all require attention and inhibition. The importance of assessing attention and disinhibition in psychological…

76 FR 53416 - North Pacific Fishery Management Council; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-26

... North Pacific Fishery Management Council's (NPFMC) Crab Plan Team (CPT). SUMMARY: The CPT will meet September 19-22, 2011 at the Alaska Fishery Science Center, 7600 Sand Point Way, NE., Building 4, Traynor.... ADDRESSES: The meeting will be held at the Alaska Fishery Science Center, 7600 Sand Point Way, NE., Building...

75 FR 52511 - North Pacific Fishery Management Council; Notice of Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-26

...; review Bristol Bay red king crab CIE report, review and recommend approaches for Tanner crab model, review and recommend approaches for Pribilof Islands blue king crab and red king crab models, receive an... Fishery Management Council's Crab Plan Team (CPT). SUMMARY: The CPT will meet September 13-16, 2010, at...

Affordability Constraints in Major Defense Acquisitions

DTIC Science & Technology

2016-11-01

Fence Inc 1 30-May-2014 4-Oct-2012 4-Nov-2015 32 SSC 5-Jul-2012 33 VH-92A (VXX) 5-Apr-2013 17-Apr-2014 34 FAB -T CPT 26-Oct...Development EPAWSS Eagle Passive/Active Warning and Survivability System EPP Extended Planning Period EPS Enhanced Polar System FAB -T CPT Family of

Feasibility of using cone penetrometer truck (CPT) to install time domain reflectometry (TDR) and fiber optic slope failure detectors in pavement structures.

DOT National Transportation Integrated Search

2011-02-01

A new method of cable installation using a heavy-duty Cone Penetration Test : (CPT) truck was developed and practiced successfully in this study. The coaxial and fiber : optic cables were pushed along with the cone rods by the hydraulic system integr...

Constraints on relativity violations from gamma-ray bursts.

PubMed

Kostelecký, V Alan; Mewes, Matthew

2013-05-17

Tiny violations of the Lorentz symmetry of relativity and the associated discrete CPT symmetry could emerge in a consistent theory of quantum gravity such as string theory. Recent evidence for linear polarization in gamma-ray bursts improves existing sensitivities to Lorentz and CPT violation involving photons by factors ranging from ten to a million.

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.

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.

Identification and reconstitution of the rubber biosynthetic machinery on rubber particles from Hevea brasiliensis

PubMed Central

Yamashita, Satoshi; Yamaguchi, Haruhiko; Waki, Toshiyuki; Aoki, Yuichi; Mizuno, Makie; Yanbe, Fumihiro; Ishii, Tomoki; Funaki, Ayuta; Tozawa, Yuzuru; Miyagi-Inoue, Yukino; Fushihara, Kazuhisa; Nakayama, Toru; Takahashi, Seiji

2016-01-01

Natural rubber (NR) is stored in latex as rubber particles (RPs), rubber molecules surrounded by a lipid monolayer. Rubber transferase (RTase), the enzyme responsible for NR biosynthesis, is believed to be a member of the cis-prenyltransferase (cPT) family. However, none of the recombinant cPTs have shown RTase activity independently. We show that HRT1, a cPT from Heveabrasiliensis, exhibits distinct RTase activity in vitro only when it is introduced on detergent-washed HeveaRPs (WRPs) by a cell-free translation-coupled system. Using this system, a heterologous cPT from Lactucasativa also exhibited RTase activity, indicating proper introduction of cPT on RP is the key to reconstitute active RTase. RP proteomics and interaction network analyses revealed the formation of the protein complex consisting of HRT1, rubber elongation factor (REF) and HRT1-REF BRIDGING PROTEIN. The RTase activity enhancement observed for the complex assembled on WRPs indicates the HRT1-containing complex functions as the NR biosynthetic machinery. DOI: http://dx.doi.org/10.7554/eLife.19022.001 PMID:27790974

Predicting the spatial distribution of soil profile in Adapazari/Turkey by artificial neural networks using CPT data

NASA Astrophysics Data System (ADS)

Arel, Ersin

2012-06-01

The infamous soils of Adapazari, Turkey, that failed extensively during the 46-s long magnitude 7.4 earthquake in 1999 have since been the subject of a research program. Boreholes, piezocone soundings and voluminous laboratory testing have enabled researchers to apply sophisticated methods to determine the soil profiles in the city using the existing database. This paper describes the use of the artificial neural network (ANN) model to predict the complex soil profiles of Adapazari, based on cone penetration test (CPT) results. More than 3236 field CPT readings have been collected from 117 soundings spread over an area of 26 km2. An attempt has been made to develop the ANN model using multilayer perceptrons trained with a feed-forward back-propagation algorithm. The results show that the ANN model is fairly accurate in predicting complex soil profiles. Soil identification using CPT test results has principally been based on the Robertson charts. Applying neural network systems using the chart offers a powerful and rapid route to reliable prediction of the soil profiles.

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

Cognitive and motor dual task gait training improve dual task gait performance after stroke - A randomized controlled pilot trial.

PubMed

Liu, Yan-Ci; Yang, Yea-Ru; Tsai, Yun-An; Wang, Ray-Yau

2017-06-22

This study investigated effects of cognitive and motor dual task gait training on dual task gait performance in stroke. Participants (n = 28) were randomly assigned to cognitive dual task gait training (CDTT), motor dual task gait training (MDTT), or conventional physical therapy (CPT) group. Participants in CDTT or MDTT group practiced the cognitive or motor tasks respectively during walking. Participants in CPT group received strengthening, balance, and gait training. The intervention was 30 min/session, 3 sessions/week for 4 weeks. Three test conditions to evaluate the training effects were single walking, walking while performing cognitive task (serial subtraction), and walking while performing motor task (tray-carrying). Parameters included gait speed, dual task cost of gait speed (DTC-speed), cadence, stride time, and stride length. After CDTT, cognitive-motor dual task gait performance (stride length and DTC-speed) was improved (p = 0.021; p = 0.015). After MDTT, motor dual task gait performance (gait speed, stride length, and DTC-speed) was improved (p = 0.008; p = 0.008; p = 0.008 respectively). It seems that CDTT improved cognitive dual task gait performance and MDTT improved motor dual task gait performance although such improvements did not reach significant group difference. Therefore, different types of dual task gait training can be adopted to enhance different dual task gait performance in stroke.

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

The rational status of quantum cognition.

PubMed

Pothos, Emmanuel M; Busemeyer, Jerome R; Shiffrin, Richard M; Yearsley, James M

2017-07-01

Classic probability theory (CPT) is generally considered the rational way to make inferences, but there have been some empirical findings showing a divergence between reasoning and the principles of classical probability theory (CPT), inviting the conclusion that humans are irrational. Perhaps the most famous of these findings is the conjunction fallacy (CF). Recently, the CF has been shown consistent with the principles of an alternative probabilistic framework, quantum probability theory (QPT). Does this imply that QPT is irrational or does QPT provide an alternative interpretation of rationality? Our presentation consists of 3 parts. First, we examine the putative rational status of QPT using the same argument as used to establish the rationality of CPT, the Dutch Book (DB) argument, according to which reasoners should not commit to bets guaranteeing a loss. We prove the rational status of QPT by formulating it as a particular case of an extended form of CPT, with separate probability spaces produced by changing context. Second, we empirically examine the key requirement for whether a CF can be rational or not; the results show that participants indeed behave rationally, at least relative to the representations they employ. Finally, we consider whether the conditions for the CF to be rational are applicable in the outside (nonmental) world. Our discussion provides a general and alternative perspective for rational probabilistic inference, based on the idea that contextuality requires either reasoning in separate CPT probability spaces or reasoning with QPT principles. (PsycINFO Database Record (c) 2017 APA, 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.

Laticifer-Specific cis-Prenyltransferase Silencing Affects the Rubber, Triterpene, and Inulin Content of Taraxacum brevicorniculatum12[C][W

PubMed Central

Post, Janina; van Deenen, Nicole; Fricke, Julia; Kowalski, Natalie; Wurbs, David; Schaller, Hubert; Eisenreich, Wolfgang; Huber, Claudia; Twyman, Richard M.; Prüfer, Dirk; Gronover, Christian Schulze

2012-01-01

Certain Taraxacum species, such as Taraxacum koksaghyz and Taraxacum brevicorniculatum, produce large amounts of high-quality natural rubber in their latex, the milky cytoplasm of specialized cells known as laticifers. This high-molecular mass biopolymer consists mainly of poly(cis-1,4-isoprene) and is deposited in rubber particles by particle-bound enzymes that carry out the stereospecific condensation of isopentenyl diphosphate units. The polymer configuration suggests that the chain-elongating enzyme (rubber transferase; EC 2.5.1.20) is a cis-prenyltransferase (CPT). Here, we present a comprehensive analysis of transgenic T. brevicorniculatum plants in which the expression of three recently isolated CPTs known to be associated with rubber particles (TbCPT1 to -3) was heavily depleted by laticifer-specific RNA interference (RNAi). Analysis of the CPT-RNAi plants by nuclear magnetic resonance, size-exclusion chromatography, and gas chromatography-mass spectrometry indicated a significant reduction in rubber biosynthesis and a corresponding 50% increase in the levels of triterpenes and the main storage carbohydrate, inulin. Transmission electron microscopy revealed that the laticifers in CPT-RNAi plants contained fewer and smaller rubber particles than wild-type laticifers. We also observed lower activity of hydroxymethylglutaryl-coenzyme A reductase, the key enzyme in the mevalonate pathway, reflecting homeostatic control of the isopentenyl diphosphate pool. To our knowledge, this is the first in planta demonstration of latex-specific CPT activity in rubber biosynthesis. PMID:22238421

Influence of a high-intensity interval training session on peripheral and central blood pressure at rest and during stress testing in healthy individuals.

PubMed

Ketelhut, Sascha; Milatz, Florian; Heise, Walter; Ketelhut, Reinhard G

2016-09-01

Regular physical activity is known to reduce arterial pressure (BP). In a previous investigation, we could prove that even a single bout of moderate-intensity continuous exercise (MICE) causes a prolonged reduction in BP. Whether high-intensity interval training (HIIT) has a favourable influence on BP, and therefore may be followed subjects and methods by a prolonged BP reduction, should be examined on the basis of blood pressure response after exercise and during a subsequent stress test. In 39 healthy men (aged 34 ± 8 years, BMI 24 ± 2), peripheral and central BP were measured noninvasively at rest and at the end of a 2-min cold pressor test (CPT) using a Mobil-O-Graph (24 PWA monitor, IEM). Following HIIT (6 x 1 min at 98% of the previously determined maximum wattage, 4-min rest between intervals) BP was measured again throughout 60 min of rest and thereafter during a CPT. The results were compared with those obtained before HIIT. Similar to MICE, peripheral and central BPs were significantly (p < 0.05) lower 45 min after HIIT. When analysing peripheral BP during a CPT before and after exercise, significantly lower systolic (p < 0.001) and diastolic (p = 0.008) pressures were established after HIIT. This was true for systolic (p = 0.002) and diastolic (p = 0.006) central BP as well. Although there were no more significant differences between pressures at rest before and 60 min after exercise, the increase in peripheral systolic pressure due to CPT was significantly slower after HIIT (p = 0.019) when compared with BP during CPT before exercise. This was true for central systolic BP as well (p = 0.017). HIIT leads to a BP reduction, which can still be detected up to 45 min after completion of the training. Even 60 min after exercise, pressures during a CPT showed a reduced augmentation, indicating an attenuated hemodynamic response to stress testing after HIIT.

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).

Mild dehydration modifies the cerebrovascular response to the cold pressor test.

PubMed

Perry, Blake G; Bear, Tracey L K; Lucas, Samuel J E; Mündel, Toby

2016-01-01

The cold pressor test (CPT) is widely used in clinical practice and physiological research. It is characterized by a robust autonomic response, with associated increases in heart rate (HR), mean arterial pressure (MAP) and mean middle cerebral artery blood flow velocity (MCAv(mean)). Hydration status is not commonly reported when conducting this test, yet blood viscosity alone can modulate MCAv(mean), potentially modifying the MCAv(mean) response to the CPT. We investigated the effect of mild dehydration on the physiological response to the CPT in 10 healthy men (mean ± SD: age 28 ± 5 years; body mass 83 ± 5 kg). All participants completed two CPTs, cold water (0°C) immersion of both feet for 90 s, with the order of the euhydration and dehydration trials counterbalanced. Beat-to-beat MCAv, MAP, HR and breath-by-breath partial pressure of end-tidal CO2 (P(ET,CO2)) were measured continuously. Participants' pain perception was measured 1 min into the CPT using a visual analog scale (no pain = 0; maximal pain = 10). Dehydration significantly elevated plasma osmolality and urine specific gravity and reduced body mass (all P < 0.01). The MAP and HR responses were not different between treatments (both P > 0.05). After 90 s of immersion, the change in MCAv(mean) from baseline was less in the dehydration compared with the euhydration trial (change 0 ± 5 versus 7 ± 7 cm s(-1), P = 0.01), as was P(ET,CO2) (change -3 ± 2 versus 0 ± 3 mmHg, P = 0.02). Dehydration was associated with greater relative pain sensation during the CPT (7.0 ± 1.3 vs 5.8 ± 1.8, P = 0.02). Our results demonstrate that mild dehydration can modify the cerebrovascular response to the CPT, with dehydration increasing perceived pain, lowering P ET ,CO2 and, ultimately, blunting the MCAv(mean) response. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Phase 2 trial of BCNU plus irinotecan in adults with malignant glioma1

PubMed Central

Reardon, David A.; Quinn, Jennifer A.; Rich, Jeremy N.; Gururangan, Sridharan; Vredenburgh, James; Sampson, John H.; Provenzale, James M.; Walker, Amy; Badruddoja, Michael; Tourt-Uhlig, Sandra; Herndon, James E.; Dowell, Jeannette M.; Affronti, Mary Lou; Jackson, Susanne; Allen, Deborah; Ziegler, Karen; Silverman, Steven; Bohlin, Cindy; Friedman, Allan H.; Bigner, Darell D.; Friedman, Henry S.

2004-01-01

In preclinical studies, BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, plus CPT-11 (irinotecan) exhibits schedule-dependent, synergistic activity against malignant glioma (MG). We previously established the maximum tolerated dose of CPT-11 when administered for 4 consecutive weeks in combination with BCNU administered on the first day of each 6-week cycle. We now report a phase 2 trial of BCNU plus CPT-11 for patients with MG. In the current study, BCNU (100 mg/m2) was administered on day 1 of each 6-week cycle. CPT-11 was administered on days 1, 8, 15, and 22 at 225 mg/m2 for patients receiving CYP3A1- or CYP3A4-inducing anticonvulsants and at 125 mg/m2 for those not on these medications. Newly diagnosed patients received up to 3 cycles before radiotherapy, while recurrent patients received up to 8 cycles. The primary end point of this study was radiographic response, while time to progression and overall survival were also assessed. Seventy-six patients were treated, including 37 with newly diagnosed tumors and 39 with recurrent disease. Fifty-six had glioblastoma multiforme, 18 had anaplastic astrocytoma, and 2 had anaplastic oligodendroglioma. Toxicities (grade ⩾3) included infections (13%), thromboses (12%), diarrhea (10%), and neutropenia (7%). Interstitial pneumonitis developed in 4 patients. Five newly diagnosed patients (14%; 95% CI, 5%–29%) achieved a radiographic response (1 complete response and 4 partial responses). Five patients with recurrent MG also achieved a response (1 complete response and 4 partial responses; 13%; 95% CI, 4%–27%). More than 40% of both newly diagnosed and recurrent patients achieved stable disease. Median time to progression was 11.3 weeks for recurrent glioblastoma multiforme patients and 16.9 weeks for recurrent anaplastic astrocytoma/anaplastic oligodendroglioma patients. We conclude that the activity of BCNU plus CPT-11 for patients with MG appears comparable to that of CPT-11 alone and may be more toxic. PMID:15134628

Effects of tumor necrosis factor-related apoptosis-inducing ligand alone and in combination with chemotherapeutic agents on patients' colon tumors grown in SCID mice.

PubMed

Naka, Takuji; Sugamura, Kenji; Hylander, Bonnie L; Widmer, Michael B; Rustum, Youcef M; Repasky, Elizabeth A

2002-10-15

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to induce apoptosis in a variety of malignant cell lines, but it shows little or no toxicity in most normal cells. We examined the response of three human colon tumors to TRAIL alone and in combination with chemotherapy, using SCID mice engrafted with intact patient surgical specimens. These tumors, taken from fresh surgical specimens, contained the heterogeneous tumor cell population characteristic of patient tumors and showed differential sensitivity to TRAIL alone. We also investigated the effect of TRAIL in combination with chemotherapy, using one tumor that showed moderate sensitivity to TRAIL alone. Combining TRAIL with either 5-fluorouracil (5-FU) or CPT-11 (irinotecan hydrochloride) produced a greatly enhanced antitumor effect over that of either agent alone, with 50% of the animals achieving complete tumor regression with a combination of TRAIL and CPT-11. By histological analysis, tumors treated with TRAIL plus either 5-FU or CPT-11 were seen to consist mainly of connective tissue and fibrotic areas with only a few scattered tumor cells encapsulated in the connective tissue. Several markers were assessed to investigate the basis for the observed therapeutic effect, and significant induction of apoptosis was observed in tumors treated with curative combinations. Cytoplasmic and cell surface expression of the TRAIL receptors DR4 and DR5 was observed in this patient's tumor by immunohistochemistry. Tumors treated with CPT-11 showed increased membrane expression of DR5, suggesting that CPT-11 may increase sensitivity to TRAIL by up-regulation of DR5. These results obtained in a relevant preclinical model support the idea that the use of TRAIL in combination with either 5-FU or CPT-11 may be an effective strategy in controlling human colon cancer.

Variants in CPT1A, FADS1, and FADS2 are Associated with Higher Levels of Estimated Plasma and Erythrocyte Delta-5 Desaturases in Alaskan Eskimos.

PubMed

Voruganti, V Saroja; Higgins, Paul B; Ebbesson, Sven O E; Kennish, John; Göring, Harald H H; Haack, Karin; Laston, Sandra; Drigalenko, Eugene; Wenger, Charlotte R; Harris, William S; Fabsitz, Richard R; Devereux, Richard B; Maccluer, Jean W; Curran, Joanne E; Carless, Melanie A; Johnson, Matthew P; Moses, Eric K; Blangero, John; Umans, Jason G; Howard, Barbara V; Cole, Shelley A; Comuzzie, Anthony Gean

2012-01-01

The delta-5 and delta-6 desaturases (D5D and D6D), encoded by fatty acid desaturase 1 (FADS1) and 2 (FADS2) genes, respectively, are rate-limiting enzymes in the metabolism of ω-3 and ω-6 fatty acids. The objective of this study was to identify genes influencing variation in estimated D5D and D6D activities in plasma and erythrocytes in Alaskan Eskimos (n = 761) participating in the genetics of coronary artery disease in Alaska Natives (GOCADAN) study. Desaturase activity was estimated by product: precursor ratio of polyunsaturated fatty acids. We found evidence of linkage for estimated erythrocyte D5D (eD5D) on chromosome 11q12-q13 (logarithm of odds score = 3.5). The confidence interval contains candidate genes FADS1, FADS2, 7-dehydrocholesterol reductase (DHCR7), and carnitine palmitoyl transferase 1A, liver (CPT1A). Measured genotype analysis found association between CPT1A, FADS1, and FADS2 single-nucleotide polymorphisms (SNPs) and estimated eD5D activity (p-values between 10(-28) and 10(-5)). A Bayesian quantitative trait nucleotide analysis showed that rs3019594 in CPT1A, rs174541 in FADS1, and rs174568 in FADS2 had posterior probabilities > 0.8, thereby demonstrating significant statistical support for a functional effect on eD5D activity. Highly significant associations of FADS1, FADS2, and CPT1A transcripts with their respective SNPs (p-values between 10(-75) and 10(-7)) in Mexican Americans of the San Antonio Family Heart Study corroborated our results. These findings strongly suggest a functional role for FADS1, FADS2, and CPT1A SNPs in the variation in eD5D activity.

Characterization of mutant tobacco mosaic virus coat protein that interferes with virus cell-to-cell movement.

PubMed

Bendahmane, Mohammed; Szecsi, Judit; Chen, Iju; Berg, R Howard; Beachy, Roger N

2002-03-19

Expression of tobacco mosaic virus (TMV) coat protein (CP) in plants confers resistance to infection by TMV and related tobamoviruses. Certain mutants of the CP (CP(T42W)) provide much greater levels of resistance than wild-type (wt) CP. In the present work, infection induced by RNA transcripts of TMV clones that contain wt CP or mutant CP(T42W) fused to the green fluorescent protein (GFP) (TMV-CP:GFP, TMV-CP(T42W):GFP) and clones harboring TMV movement protein (MP):GFP were followed in nontransgenic and transgenic tobacco BY-2 protoplasts and Nicotiana tabaccum Xanthi-nn plants that express wt CP or CP(T42W). On nontransgenic and wt CP transgenic plants, TMV-CP:GFP produced expanding, highly fluorescent disk-shaped areas. On plants expressing CP(T42W), infection by TMV-CP:GFP or TMV-MP:GFP-CP produced infection sites of smaller size that were characterized by low fluorescence, reflecting reduced levels of virus spread and reduced accumulation of both CP:GFP and MP:GFP. TMV-CP(T42W):GFP failed to produce visible infection sites on nontransgenic plants, yet produced normal infection sites on MP-transgenic plants that produce MP. TMV infection of transgenic BY-CP(T42W) protoplasts resulted in very low levels of MP accumulation, whereas on BY-CP protoplasts (containing wt CP), infection produced higher levels of MP than in nontransgenic BY-2 cells. The results suggest that wt CP has a positive effect on the production of MP, whereas the CP(T42W) has a negative effect on MP accumulation and/or function. This effect results in very high levels of resistance to TMV infection in plants containing CP(T42W). This report shows that the CP of a plant virus regulates production of the MP, and that a mutant CP interferes with MP accumulation and cell-to-cell movement of infection.

The concept of a marine Free-fall CPT systems revisited

NASA Astrophysics Data System (ADS)

Kopf, A.; Stegmann, S.

2005-12-01

Cone Penetration Tests (CPT) are a widely used method for the geotechnical in situ characterisation of sediments in onshore settings. In the course of enhanced use of the continental shelf and slope by humans impact, the need for time- and cost-efficient solutions in the marine realm is emerging. In order to avoid the challenges of lowering heavy gear to the seafloor for the penetration tests, free drop devices have been developed since the 1970s, however, the use of the majority of them was discontinued owing to technical difficulties in measurement and data interpretation caused by the impact. Based on those experiences, two different free-fall CPT lances were designed for the in situ measurement of strength (tip resistance, sleeve friction), pore pressure and temperature. In addition, deceleration and tilt are monitored for vertical profiling of the penetrated sediment column. Both CPT systems rely on an industry 15 cm2 piezocone with the sensors at the tip and a pressure housing containing a microprocessor at the top. The lightweight (40-100 kg), shallow water (200 m depth) lance works completely autonomous with a volatile memory and battery package, and can be deployed from any platform, even without a winch. The sturdier, deeper water (2500 m depth) system uses both power and telemetry for data transmission from the research vessel. The length and weight of either system can be varied according to the sediment stiffness and hence allow variable penetration depth (usually less than 5 m). Initial use of the CPT systems attests their efficiency and reliability in the measurement of sediment physical properties. While most of the data are collected within the first seconds of the CPT experiments, long term (pore pressure dissipation tests have also been successfully carried out for durations in excess of 6 hours. In a variety of estuarine and marine settings, our studies served objectives such as the assessment of slope stability, navigability of harbours/estuaries, consultancy for cable laying and trenching, or ground-truthing of geophysical data.

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.

Arrhythmic effects of Epac-mediated ryanodine receptor activation in Langendorff-perfused murine hearts are associated with reduced conduction velocity.

PubMed

Li, Mengye; Hothi, Sandeep S; Salvage, Samantha C; Jeevaratnam, Kamalan; Grace, Andrew A; Huang, Christopher L-H

2017-06-01

Recent papers have attributed arrhythmic substrate in murine RyR2-P2328S hearts to reduced action potential (AP) conduction velocities (CV), reflecting acute functional inhibition and/or reduced expression of sodium channels. We explored for acute effects of direct exchange protein directly activated by cAMP (Epac)-mediated ryanodine receptor-2 (RyR2) activation on arrhythmic substrate and CV. Monophasic action potential (MAP) recordings demonstrated that initial steady (8 Hz) extrinsic pacing elicited ventricular tachycardia (VT) in 0 of 18 Langendorff-perfused wild-type mouse ventricles before pharmacological intervention. The Epac activator 8-CPT (8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate) (VT in 1 of 7 hearts), and the RyR2 blocker dantrolene, either alone (0 of 11) or with 8-CPT (0 of 9) did not then increase VT incidence (P>.05). Both progressively increased pacing rates and programmed extrasystolic (S2) stimuli similarly produced no VT in untreated hearts (n=20 and n=9 respectively). 8-CPT challenge then increased VT incidences (5 of 7 and 4 of 8 hearts respectively; P<.05). However, dantrolene, whether alone (0 of 10 and 1 of 13) or combined with 8-CPT (0 of 10 and 0 of 13) did not increase VT incidence relative to those observed in untreated hearts (P>.05). 8-CPT but not dantrolene, whether alone or combined with 8-CPT, correspondingly increased AP latencies (1.14±0.04 (n=7), 1.04±0.03 (n=10), 1.09±0.05 (n=8) relative to respective control values). In contrast, AP durations, conditions for 2:1 conduction block and ventricular effective refractory periods remained unchanged throughout. We thus demonstrate for the first time that acute RyR2 activation reversibly induces VT in specific association with reduced CV. © 2017 The Authors. Clinical and Experimental Pharmacology and Physiology Published by John Wiley & Sons Australia, Ltd.

Interns' knowledge of clinical pharmacology and therapeutics after undergraduate and on-going internship training in Nigeria: a pilot study

PubMed Central

Oshikoya, Kazeem A; Senbanjo, Idowu O; Amole, Olufemi O

2009-01-01

Background A sound knowledge of pathophysiology of a disease and clinical pharmacology and therapeutics (CPT) of a drug is required for safe and rational prescribing. The aim of this study was therefore to assess how adequately the undergraduate CPT teaching had prepared interns in Nigeria for safe and rational prescribing and retrospectively, to know how they wanted the undergraduate curriculum to be modified so as to improve appropriate prescribing. The effect of internship training on the prescribing ability of the interns was also sought. Methods A total of 100 interns were randomly selected from the Lagos State University Teaching Hospital (LASUTH), Ikeja; Lagos University Teaching Hospital (LUTH), Idiaraba; General Hospital Lagos (GHL); the EKO Hospital, Ikeja; and Havana Specialist Hospital, Surulere. A structured questionnaire was the instrument of study. The questionnaire sought information about the demographics of the interns, their undergraduate CPT teaching, experience of adverse drug reactions (ADRs) and drug interactions since starting work, confidence in drug usage and, in retrospect; any perceived deficiencies in their undergraduate CPT teaching. Results The response rate was 81%. All the respondents graduated from universities in Nigeria. The ability of the interns to prescribe rationally (66, 81.4%) and safely (47, 58%) was provided by undergraduate CPT teaching. Forty two (51.8%) respondents had problems with prescription writing. The interns would likely prescribe antibiotics (71, 87.6%), nonsteroidal analgesics (66, 81.4%), diuretics (55, 67.9%), sedatives (52, 62.9%), and insulin and oral hypoglycaemics (43, 53%) with confidence and unsupervised. The higher the numbers of clinical rotations done, the more confident were the respondents to prescribe unsupervised (χ2 = 19.98, P < 0.001). Similarly, respondents who had rotated through the four major clinical rotations and at least a special posting (χ2 = 11.57, P < 0.001) or four major clinical rotations only (χ2 = 11.25, P < 0.001) were significantly more confident to prescribe drugs unsupervised. Conclusion Undergraduate CPT teaching in Nigeria appears to be deficient. Principles of rational prescribing, drug dose calculation in children and pharmacovigilance should be the focus of undergraduate CPT teaching and should be taught both theoretically and practically. Medical students and interns should be periodically assessed on prescribing knowledge and skills during their training as a means of minimizing prescribing errors. PMID:19638199

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.

The Role of Aspiration Level in Risky Choice: A Comparison of Cumulative Prospect Theory and SP/A Theory.

PubMed

Lopes; Oden

1999-06-01

In recent years, descriptive models of risky choice have incorporated features that reflect the importance of particular outcome values in choice. Cumulative prospect theory (CPT) does this by inserting a reference point in the utility function. SP/A (security-potential/aspiration) theory uses aspiration level as a second criterion in the choice process. Experiment 1 compares the ability of the CPT and SP/A models to account for the same within-subjects data set and finds in favor of SP/A. Experiment 2 replicates the main finding of Experiment 1 in a between-subjects design. The final discussion brackets the SP/A result by showing the impact on fit of both decreasing and increasing the number of free parameters. We also suggest how the SP/A approach might be useful in modeling investment decision making in a descriptively more valid way and conclude with comments on the relation between descriptive and normative theories of risky choice. Copyright 1999 Academic Press.

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