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Sample records for 90y-sirsphere treatment response

  1. Identifying predictors of treatment response.

    PubMed

    Yoder, Paul; Compton, Don

    2004-01-01

    This article provides a rationale for considering predictors of growth in a treatment group as inadequate to identifying predictors of treatment response. When we interpret predictors of growth in a treatment group as synonymous with predictors of treatment response, we implicitly attribute all of the treated children's growth to the treatment, an untenable assumption under most conditions. We also contend that the use of standard scores in predictors of growth studies does not allow us to differentiate growth from treatment, from growth from other factors. We present two research methodologies that are appropriate methods of identifying predictors of treatment response: (a) single-subject experimental logic utilized to identify the specific participants in which treatment responses (not just growth) were found, combined with follow-up group comparison logic to identify the characteristics on which responders and nonresponders differ, and (b) statistical interactions among child/family/context characteristics and randomly assigned group membership. Principles for selecting potential predictors of treatment response are provided.

  2. Pivotal Response Treatment: Case Reports.

    PubMed

    Ventola, Pamela; Friedman, Hannah; Oosting, Devon

    2015-01-01

    The current paper provides an overview of an evidence-based treatment, Pivotal Response Treatment (PRT), for autism spectrum disorder (ASD). The paper describes PRT principles and then illustrates the approach using two case reports. The children are preschool-aged children with high-functioning ASD. They were participating in a four-month clinical trial of PRT. At the start of treatment, they presented with significant social communication impairments, including a minimal understanding of reciprocity, limited play skills, and repetitive behaviors and speech. The paper outlines how behavioral treatment goals were identified and then how activities were designed, using principles of PRT, to target skill acquisition. Following the treatment course, both children made substantial and meaningful gains in social communication skill development.

  3. Non-response to osteoporosis treatment.

    PubMed

    Francis, Roger M

    2004-06-01

    There are now a number of effective treatments for osteoporosis, which increase bone mineral density (BMD) and decrease the risk of fractures. There is no clear consensus on the optimal method for assessing response to treatment in the individual patient. The goal of osteoporosis treatment is to prevent fractures after minimal trauma, but these are relatively uncommon events and cannot be totally avoided by the use of currently available therapies. Alternative methods of assessing response to treatment include serial measurement of BMD or the biochemical markers of bone turnover, but the observed changes may be misleading if they do not exceed the least significant change. The proportion of patients who fail to respond to osteoporosis treatments is difficult to quantify. Clinical trials show continuing bone loss in up to 15% of participants on hormone replacement therapy or bisphosphonates. Non-response to treatment is probably more common in clinical practice, but may be due to poor adherence to treatment recommendations. Other potential causes of an apparent failure to respond to treatment include the use of a weak antiresorptive agent, differences in bioavailability, low dietary calcium intake, vitamin D insufficiency and underlying causes of secondary osteoporosis. The management of patients who fail to respond to treatment includes confirmation that they are adhering to treatment and have an adequate dietary calcium intake and vitamin D status and excluding causes of secondary osteoporosis. Consideration should also be given to the addition of calcium and vitamin D supplementation and the use of alternative treatments for osteoporosis.

  4. Heterogeneity of neural mechanisms of response to pivotal response treatment

    PubMed Central

    Ventola, Pamela; Yang, Daniel Y. J.; Friedman, Hannah E.; Oosting, Devon; Wolf, Julie; Sukhodolsky, Denis G.; Pelphrey, Kevin A.

    2016-01-01

    We investigated the mechanisms by which Pivotal Response Treatment (PRT) improves social communication in a case series of 10 preschool-aged children with Autism Spectrum Disorder (ASD). Functional magnetic resonance imaging (fMRI) identified brain responses during a biological motion perception task conducted prior to and following 16 weeks of PRT treatment. Overall, the neural systems supporting social perception in these 10 children were malleable through implementation of PRT; following treatment, neural responses were more similar to those of typically developing children (TD). However, at baseline, half of the children exhibited hypoactivation, relative to a group of TD children, in the right posterior superior temporal sulcus (pSTS), and half exhibited hyperactivation in this region. Strikingly, the groups exhibited differential neural responses to treatment: The five children who exhibited hypoactivation at baseline evidenced increased activation in components of the reward system including the ventral striatum and putamen. The five children who exhibited hyperactivation at baseline evidenced decreased activation in subcortical regions critical for regulating the flow of stimulation and conveying signals of salience to the cortex—the thalamus, amygdala, and hippocampus. Our results support further investigation into the differential effects of particular treatment strategies relative to specific neural targets. Identification of treatment strategies that address the patterns of neural vulnerability unique to each patient is consistent with the priority of creating individually tailored interventions customized to the behavioral and neural characteristics of a given person. PMID:25370452

  5. Daily Spiritual Experiences and Adolescent Treatment Response

    PubMed Central

    LEE, MATTHEW T.; VETA, PAIGE S.; JOHNSON, BYRON R.; PAGANO, MARIA E.

    2014-01-01

    The purpose of this study is to explore changes in belief orientation during treatment and the impact of increased daily spiritual experiences (DSE) on adolescent treatment response. One-hundred ninety-five adolescents court-referred to a 2-month residential treatment program were assessed at intake and discharge. Forty percent of youth who entered treatment as agnostic or atheist identified themselves as spiritual or religious at discharge. Increased DSE was associated with greater likelihood of abstinence, increased prosocial behaviors, and reduced narcissistic behaviors. Results indicate a shift in DSE that improves youth self-care and care for others that may inform intervention approaches for adolescents with addiction. PMID:25525291

  6. Stream periphyton responses to mesocosm treatments of ...

    EPA Pesticide Factsheets

    A stream mesocosm experiment was designed to compare biotic responses among streams exposed to an equal excess specific conductivity target of 850 µS/cm relative to a control that was set for 200 µS/cm and three treatments comprised of different major ion contents. Each treatment and the control was replicated 4 times at the mesocosm scale (16 mesocosms total). The treatments were based on dosing the background mesocosm water, a continuous flow-through mixture of natural river water and reverse osmosis treated water, with stock salt solutions prepared from 1) a mixture of sodium chloride and calcium chloride (Na/Cl chloride), 2) sodium bicarbonate, and 3) magnesium sulfate. The realized average specific conductance over the first 28d of continuous dosing was 827, 829, and 847 µS/cm, for the chloride, bicarbonate, and sulfate based treatments, respectively, and did not differ significantly. The controls averaged 183 µS/cm. Here we focus on comparing stream periphyton communities across treatments based on measurements obtained from a Pulse-Amplitude Modulated (PAM) fluorometer. The fluorometer is used in situ and with built in algorithms distributes the total aerial algal biomass (µg/cm2) of the periphyton among cyanobacteria, diatoms, and green algae. A measurement is recorded in a matter of seconds and, therefore, many different locations can be measured with in each mesocosm at a high return frequency. Eight locations within each of the 1 m2 (0.3 m W x 3

  7. Preference for blocking or response redirection during stereotypy treatment.

    PubMed

    Giles, Aimee F; St Peter, Claire C; Pence, Sacha T; Gibson, Alexandra B

    2012-01-01

    Response redirection and response blocking reduce stereotypy maintained by automatic reinforcement. The current study evaluated the effects of redirection and response blocking on the stereotypic responding of three elementary-age children diagnosed with autism. During the treatment evaluation, redirection and response blocking were evaluated using an alternating treatment embedded in a reversal design. Both procedures resulted in comparably low levels of motor stereotypy. Following treatment evaluation, a concurrent chain was conducted to evaluate participant preference for redirection or response blocking. All three participants preferred redirection. Practitioners may wish to consider participant preference when developing and implementing treatments for stereotypy.

  8. Preference for Blocking or Response Redirection during Stereotypy Treatment

    ERIC Educational Resources Information Center

    Giles, Aimee F.; St. Peter, Claire C.; Pence, Sacha T.; Gibson, Alexandra B.

    2012-01-01

    Response redirection and response blocking reduce stereotypy maintained by automatic reinforcement. The current study evaluated the effects of redirection and response blocking on the stereotypic responding of three elementary-age children diagnosed with autism. During the treatment evaluation, redirection and response blocking were evaluated…

  9. Vegetation Response to Western Juniper Slash Treatments

    NASA Astrophysics Data System (ADS)

    O'Connor, Casey; Miller, Rick; Bates, Jonathan D.

    2013-09-01

    The expansion of piñon-juniper woodlands the past 100 years in the western United States has resulted in large scale efforts to kill trees and recover sagebrush steppe rangelands. It is important to evaluate vegetation recovery following woodland control to develop best management practices. In this study, we compared two fuel reduction treatments and a cut-and-leave (CUT) treatment used to control western juniper ( Juniperus occidentalis spp. occidentalis Hook.) of the northwestern United States. Treatments were; CUT, cut-and-broadcast burn (BURN), and cut-pile-and-burn the pile (PILE). A randomized complete block design was used with five replicates of each treatment located in a curl leaf mahogany ( Cercocarpus ledifolius Nutt. ex Torr. & A. Gray)/mountain big sagebrush ( Artemisia tridentata Nutt. spp. vaseyana (Rydb.) Beetle)/Idaho fescue ( Festuca idahoensis Elmer) association. In 2010, 4 years after tree control the cover of perennial grasses (PG) [Sandberg's bluegrass ( Poa secunda J. Pres) and large bunchgrasses] were about 4 and 5 % less, respectively, in the BURN (7.1 ± 0.6 %) than the PILE (11.4 ± 2.3 %) and CUT (12.4 ± 1.7 %) treatments ( P < 0.0015). In 2010, cover of invasive cheatgrass ( Bromus tectorum L.) was greater in the BURN (6.3 ± 1.0 %) and was 50 and 100 % greater than PILE and CUT treatments, respectively. However, the increase in perennial bunchgrass density and cover, despite cheatgrass in the BURN treatment, mean it unlikely that cheatgrass will persist as a major understory component. In the CUT treatment mahogany cover increased 12.5 % and density increased in from 172 ± 25 to 404 ± 123 trees/ha. Burning, killed most or all of the adult mahogany, and mahogany recovery consisted of 100 and 67 % seedlings in the PILE and BURN treatments, respectively. After treatment, juniper presence from untreated small trees (<1 m tall; PILE and CUT treatments) and seedling emergence (all treatments) represented 25-33 % of pre-treatment tree

  10. Rapid Response to Treatment for Binge Eating Disorder

    ERIC Educational Resources Information Center

    Grilo, Carlos M.; Masheb, Robin M.; Wilson, Terence G.

    2006-01-01

    The authors examined rapid response among 108 patients with binge eating disorder (BED) who were randomly assigned to 1 of 4 16-week treatments: fluoxetine, placebo, cognitive-behavioral therapy (CBT) plus fluoxetine, or CBT plus placebo. Rapid response, defined as 65% or greater reduction in binge eating by the 4th treatment week, was determined…

  11. Novel Biomarker for Prognosis, Treatment Response

    Cancer.gov

    An NCI Cancer Currents blog about a study of a new type of cancer biomarker that measures the extent of chromosomal instability as a way to potentially predict patient prognosis and help guide cancer treatment choices.

  12. Mobile Emergency Response Water Treatment Technology Results

    EPA Science Inventory

    When natural disasters like hurricanes, floods and earthquakes occur, safe drinking water can be compromised, limited or unavailable. Under such situations, communities have emergency response plans. One of many options for providing safe drinking water during emergency situati...

  13. Baseline Brain Activity Predicts Response to Neuromodulatory Pain Treatment

    PubMed Central

    Jensen, Mark P.; Sherlin, Leslie H.; Fregni, Felipe; Gianas, Ann; Howe, Jon D.; Hakimian, Shahin

    2015-01-01

    Objectives The objective of this study was to examine the associations between baseline electroencephalogram (EEG)-assessed brain oscillations and subsequent response to four neuromodulatory treatments. Based on available research, we hypothesized that baseline theta oscillations would prospectively predict response to hypnotic analgesia. Analyses involving other oscillations and the other treatments (meditation, neurofeedback, and both active and sham transcranial direct current stimulation) were viewed as exploratory, given the lack of previous research examining brain oscillations as predictors of response to these other treatments. Design Randomized controlled study of single sessions of four neuromodulatory pain treatments and a control procedure. Methods Thirty individuals with spinal cord injury and chronic pain had their EEG recorded before each session of four active treatments (hypnosis, meditation, EEG biofeedback, transcranial direct current stimulation) and a control procedure (sham transcranial direct stimulation). Results As hypothesized, more presession theta power was associated with greater response to hypnotic analgesia. In exploratory analyses, we found that less baseline alpha power predicted pain reduction with meditation. Conclusions The findings support the idea that different patients respond to different pain treatments and that between-person treatment response differences are related to brain states as measured by EEG. The results have implications for the possibility of enhancing pain treatment response by either 1) better patient/treatment matching or 2) influencing brain activity before treatment is initiated in order to prepare patients to respond. Research is needed to replicate and confirm the findings in additional samples of individuals with chronic pain. PMID:25287554

  14. Bench to Bedside: Understanding Symptom Response to Acupuncture Treatment and Designing a Successful Acupuncture Treatment Program

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0533 TITLE: Bench to Bedside: Understanding Symptom Response to Acupuncture Treatment and Designing a Successful... Acupuncture Treatment Program PRINCIPAL INVESTIGATOR: Dr. Lisa Conboy CONTRACTING ORGANIZATION: New England School of Acupuncture ...Understanding Symptom Response to 5a. CONTRACT NUMBER Acupuncture Treatment and Designing a Successful Acupuncture 5b. GRANT NUMBER W81XWH-14-1-0533

  15. Legal and regulatory responses to innovative treatment.

    PubMed

    Chan, Tracey Evans

    2013-01-01

    Developments in medical technology, healthcare delivery, and commercial interests in medicine have increased both the potential for conflicts of interest on the part of physicians, and doubts over the sufficiency of patient autonomy as a justification for administering innovative therapy. The legal and regulatory treatment of innovative therapy is therefore an important question, on which there is a current lack of consensus on a number of issues. This paper discusses recent developments in Singapore and uses them as a springboard to flesh out basic regulatory issues that arise from the deployment of innovative treatment: the distinction between innovative treatment and clinical research, the adequacy of the current post hoc scrutiny of innovative therapy under existing legal principles and the need for further specialised regulatory oversight.

  16. Automated Demand Response Opportunities in Wastewater Treatment Facilities

    SciTech Connect

    Thompson, Lisa; Song, Katherine; Lekov, Alex; McKane, Aimee

    2008-11-19

    Wastewater treatment is an energy intensive process which, together with water treatment, comprises about three percent of U.S. annual energy use. Yet, since wastewater treatment facilities are often peripheral to major electricity-using industries, they are frequently an overlooked area for automated demand response opportunities. Demand response is a set of actions taken to reduce electric loads when contingencies, such as emergencies or congestion, occur that threaten supply-demand balance, and/or market conditions occur that raise electric supply costs. Demand response programs are designed to improve the reliability of the electric grid and to lower the use of electricity during peak times to reduce the total system costs. Open automated demand response is a set of continuous, open communication signals and systems provided over the Internet to allow facilities to automate their demand response activities without the need for manual actions. Automated demand response strategies can be implemented as an enhanced use of upgraded equipment and facility control strategies installed as energy efficiency measures. Conversely, installation of controls to support automated demand response may result in improved energy efficiency through real-time access to operational data. This paper argues that the implementation of energy efficiency opportunities in wastewater treatment facilities creates a base for achieving successful demand reductions. This paper characterizes energy use and the state of demand response readiness in wastewater treatment facilities and outlines automated demand response opportunities.

  17. Predictors of Treatment Response in Pediatric Obsessive-Compulsive Disorder

    ERIC Educational Resources Information Center

    Ginsburg, Golda S.; Kingery, Julie Newman; Drake, Kelly L.; Grados, Marco A.

    2008-01-01

    The study examines predictors of treatment response in pediatric obsessive-compulsive disorder, which is a severe mental illness causing distress and impaired functioning. Summarized findings of psychosocial factors and medication interventions are presented.

  18. A system for identifying and investigating unexpected response to treatment.

    PubMed

    Ozery-Flato, Michal; Ein-Dor, Liat; Neuvirth, Hani; Parush, Naama; Kohn, Martin S; Hu, Jianying; Aharonov, Ranit

    2015-01-01

    The availability of electronic health records creates fertile ground for developing computational models for various medical conditions. Using machine learning, we can detect patients with unexpected responses to treatment and provide statistical testing and visualization tools to help further analysis. The new system was developed to help researchers uncover new features associated with reduced response to treatment, and to aid physicians in identifying patients that are not responding to treatment as expected and hence deserve more attention. The solution computes a statistical score for the deviation of a given patient's response from responses observed individuals with similar characteristics and medication regimens. Statistical tests are then applied to identify clinical features that correlate with cohorts of patients showing deviant responses. The results provide comprehensive visualizations, both at the cohort and the individual patient levels. We demonstrate the utility of this system in a population of diabetic patients.

  19. Pivotal Response Treatments for Autism: Communication, Social, and Academic Development

    ERIC Educational Resources Information Center

    Koegel, Robert L.; Kern Koegel, Lynn

    2006-01-01

    Recognized as one of the top state-of-the-art treatments for autism in the United States, the innovative Pivotal Response Treatment uses natural learning opportunities to target and modify key behaviors in children with autism, leading to widespread positive effects on communication, behavior, and social skills. The product of 20 years of…

  20. Examination of Studies Targeting Social Skills with Pivotal Response Treatment

    ERIC Educational Resources Information Center

    Bozkus Genc, Gulden; Vuran, Sezgin

    2013-01-01

    In early education, especially in effective teaching to children with autism spectrum disorders, the teaching methods which are applicable in natural settings like pivotal response treatment (PRT) are commonly used. It is one of the naturalistic intervention models aiming to facilitate the stimulant-response generalization, decrease the dependency…

  1. Soft-Tissue Abnormalities Associated with Treatment-Resistant and Treatment-Responsive Clubfoot

    PubMed Central

    Moon, Daniel K.; Gurnett, Christina A.; Aferol, Hyuliya; Siegel, Marilyn J.; Commean, Paul K.; Dobbs, Matthew B.

    2014-01-01

    Background: Clubfoot treatment commonly fails and often results in impaired quality of life. An understanding of the soft-tissue abnormalities associated with both treatment-responsive and treatment-resistant clubfoot is important to improving the diagnosis of clubfoot, the prognosis for patients, and treatment. Methods: Twenty patients with clubfoot treated with the Ponseti method were recruited for magnetic resonance imaging (MRI) of their lower extremities. Among these were seven patients (six unilateral cases) with treatment-responsive clubfoot and thirteen patients (five unilateral cases) with treatment-resistant clubfoot. Demographic information and physical examination findings were recorded. A descriptive analysis of the soft-tissue abnormalities was performed for both patient cohorts. For the patients with unilateral clubfoot, we calculated the percentage difference in cross-sectional area between the affected limb and the unaffected limb in terms of muscle, subcutaneous fat, intracompartment fat, and total area. With use of the Wilcoxon signed-rank test, we compared inter-leg differences in cross-sectional areas and the intracompartment adiposity index (IAI) between treatment-responsive and treatment-resistant groups. The IAI characterizes the cross-sectional area of fat within a muscle compartment. Results: Extensive soft-tissue abnormalities were more present in patients with treatment-resistant clubfoot than in patients with treatment-responsive clubfoot. Treatment-resistant clubfoot abnormalities included excess epimysial fat and intramuscular fat replacement as well as unique patterns of hypoplasia in specific muscle groups that were present within a subset of patients. Among the unilateral cases, treatment-resistant clubfoot was associated with a significantly greater difference in muscle area between the affected and unaffected limb (−47.8%) compared with treatment-responsive clubfoot (−26.6%) (p = 0.02), a significantly greater difference in

  2. Patterns of Response After Preoperative Treatment in Gastric Cancer

    SciTech Connect

    Diaz-Gonzalez, Juan A.; Rodriguez, Javier; Hernandez-Lizoain, Jose L.; Ciervide, Raquel; Gaztanaga, Miren; San Miguel, Inigo; Arbea, Leire; Aristu, J. Javier; Chopitea, Ana; Martinez-Regueira, Fernando; Valenti, Victor; Garcia-Foncillas, Jesus; Martinez-Monge, Rafael; Sola, Jesus J.

    2011-07-01

    Purpose: To analyze the rate of pathologic response in patients with locally advanced gastric cancer treated with preoperative chemotherapy with and without chemoradiation at our institution. Methods and Materials: From 2000 to 2007 patients were retrospectively identified who received preoperative treatment for gastric cancer (cT3-4/ N+) with induction chemotherapy (Ch) or with Ch followed by concurrent chemoradiotherapy (45 Gy in 5 weeks) (ChRT). Surgery was planned 4-6 weeks after the completion of neoadjuvant treatment. Pathologic assessment was used to investigate the patterns of pathologic response after neoadjuvant treatment. Results: Sixty-one patients were analyzed. Of 61 patients, 58 (95%) underwent surgery. The R0 resection rate was 87%. Pathologic complete response was achieved in 12% of the patients. A major pathologic response (<10% of residual tumor) was observed in 53% of patients, and T downstaging was observed in 75%. Median follow-up was 38.7 months. Median disease-free survival (DFS) was 36.5 months. The only patient-, tumor-, and treatment-related factor associated with pathologic response was the use of preoperative ChRT. Patients achieving major pathologic response had a 3-year actuarial DFS rate of 63%. Conclusions: The patterns of pathologic response after preoperative ChRT suggest encouraging intervals of DFS. Such a strategy may be of interest to be explored in gastric cancer.

  3. Is the Ultimate Treatment Response Predictable with Early Response in Major Depressive Episode?

    PubMed Central

    ÇİFTÇİ, Aslı; ULAŞ, Halis; TOPUZOĞLU, Ahmet; TUNCA, Zeliha

    2016-01-01

    Introduction New evidence suggests that the efficacy of antidepressants occurs within the first weeks of treatment and this early response predicts the later response. The purpose of the present study was to investigate if the partial response in the first week predicts the response at the end of treatment in patients with major depressive disorder who are treated with either antidepressant medication or electroconvulsive therapy. Methods Inpatients from Dokuz Eylül University Hospital with a major depressive episode, treated with antidepressant medication (n=52) or electroconvulsive therapy (ECT) (n=48), were recruited for the study. The data were retrospectively collected to decide whether a 25% decrease in the Hamilton Depression Rating Scale (HDRS) score at the first week of treatment predicts a 50% decrease at the third week using validity analysis. In addition, the effects of socio-demographic and clinical variables on the treatment response were assessed. Results A 25% decrease in the HDRS score in the first week of treatment predicted a 50% decrease in the HDRS score in the third week with a 78.3% positive predictive value, 62.1% negative predictive value, 62.1% sensitivity, and 78.3% specificity for antidepressant medications and an 88% positive predictive value, 52.2% negative predictive value, 66.7% sensitivity, and 80% specificity for ECT. The number of previous hospitalizations, comorbid medical illnesses, number of depressive episodes, duration of illness, and duration of the current episode were related to the treatment response. Conclusion Treatment response in the first week predicted the response in the third week with a high specificity and a high positive predictive value. Close monitoring of the response from the first week of treatment may thus help the clinician to predict the subsequent response. PMID:28373802

  4. Imaging in evaluation of response to neoadjuvant breast cancer treatment

    PubMed Central

    Ollivier, L; Balu-Maestro, C; Leclère, J

    2005-01-01

    The role of imaging for patients treated with neoadjuvant therapy for breast cancer is not only to evaluate the therapeutic response in terms of tumour shrinkage, but also to predict the histological response to chemotherapy, which is correlated to survival. Surgery and histopathological analysis after neoadjuvant therapy allow for an objective assessment of the accuracy of imaging techniques in evaluating response. The aim of this study is to compare the value of the different conventional and functional imaging techniques for determining response to neoadjuvant chemotherapy in breast cancer treatment. PMID:16154816

  5. Defining Treatment Response in Trichotillomania: A Signal Detection Analysis

    PubMed Central

    Houghton, David C.; Capriotti, Matthew R.; De Nadai, Alessandro S.; Compton, Scott N.; Twohig, Michael P.; Neal-Barnett, Angela M.; Saunders, Stephen M.; Franklin, Martin E.; Woods, Douglas W.

    2015-01-01

    The Massachusetts General Hospital Hairpulling Scale (MGH-HPS) and the NIMH Trichotillomania Severity Scale (NIMH-TSS) are two widely used measures of trichotillomania severity. Despite their popular use, currently no empirically-supported guidelines exist to determine the degrees of change on these scales that best indicate treatment response. Determination of such criteria could aid in clinical decision-making by defining clinically significant treatment response/recovery and producing accurate power analyses for use in clinical trials research. Adults with trichotillomania (N = 69) participated in a randomized controlled trial of psychotherapy and were assessed before and after treatment. Response status was measured via the Clinical Global Impressions-Improvement Scale, and remission status was measured via the Clinical Global Impressions-Severity Scale. For treatment response, a 45% reduction or 7-point raw score change on the MGH-HPS was the best indicator of clinically significant treatment response, and on the NIMH-TSS, a 30–40% reduction or 6-point raw score difference was most effective cutoff. For disorder remission, a 55–60% reduction or 7-point raw score change on the MGH-HPS was the best predictor, and on the NIMH-TSS, a 65% reduction or 6-point raw score change was the best indicator of disorder remission. Implications of these findings are discussed. PMID:26422605

  6. The Impact of PTSD Treatment on the Cortisol Awakening Response

    PubMed Central

    Pacella, Maria L.; Feeny, Norah; Zoellner, Lori; Delahanty, Douglas L.

    2015-01-01

    Background Posttraumatic stress disorder (PTSD) is associated with abnormal functioning of the hypothalamic-pituitary-adrenal (HPA) axis; however, limited research has examined whether cortisol levels change following successful PTSD treatment. The current study examined the impact of successful PTSD treatment on the cortisol awakening response (CAR). Method Twenty-nine adults participating in a treatment trial for chronic PTSD provided saliva samples (upon waking, and 30, 45, and 60-min post-waking) before and after receiving either prolonged exposure therapy or sertraline. PTSD responder status (i.e., loss or retention of a PTSD diagnosis) served as the predictor variable. Outcome measures included area under the curve with respect to ground and increase, reflecting total cortisol output and HPA axis reactivity, respectively. Results A series of hierarchical regressions revealed no significant main effects of PTSD responder status for either CAR outcome. However, a significant gender by treatment response interaction for cortisol reactivity revealed that female treatment non-responders displayed higher cortisol reactivity following treatment than female responders, whereas cortisol reactivity did not change pre- to post-treatment for male responders. Findings remained after controlling for age, trauma history, baseline medication status, baseline PTSD, and baseline depressive symptoms. Conclusion Loss of a PTSD diagnosis may contribute to decreased cortisol reactivity in females. Neuroendocrine changes following treatment may emerge only for specific subgroups, highlighting the importance of exploring treatment moderators. PMID:25327949

  7. Expectation, the placebo effect and the response to treatment.

    PubMed

    Brown, Walter A

    2015-05-01

    What we believe we will experience from a treatment--our expectation--has a substantial impact on what we actually experience. Expectation has been established as a key process behind the placebo effect. Studies in both laboratory and clinical settings consistently show that when people ingest a pharmacologically inert substance (placebo) but believe that it is an active substance, they experience both the subjective sensations and physiologic effects expected from that active substance. Expectation has an important place in the response to "real" treatment as well. This paper provides an overview of the data which point to the role of expectation in both the placebo effect and the response to treatment. These data suggest that clinicians might enhance the benefit of all treatments by promoting patients' positive expectations.

  8. Opportunities for Automated Demand Response in California Wastewater Treatment Facilities

    SciTech Connect

    Aghajanzadeh, Arian; Wray, Craig; McKane, Aimee

    2015-08-30

    Previous research over a period of six years has identified wastewater treatment facilities as good candidates for demand response (DR), automated demand response (Auto-­DR), and Energy Efficiency (EE) measures. This report summarizes that work, including the characteristics of wastewater treatment facilities, the nature of the wastewater stream, energy used and demand, as well as details of the wastewater treatment process. It also discusses control systems and automated demand response opportunities. Furthermore, this report summarizes the DR potential of three wastewater treatment facilities. In particular, Lawrence Berkeley National Laboratory (LBNL) has collected data at these facilities from control systems, submetered process equipment, utility electricity demand records, and governmental weather stations. The collected data were then used to generate a summary of wastewater power demand, factors affecting that demand, and demand response capabilities. These case studies show that facilities that have implemented energy efficiency measures and that have centralized control systems are well suited to shed or shift electrical loads in response to financial incentives, utility bill savings, and/or opportunities to enhance reliability of service. In summary, municipal wastewater treatment energy demand in California is large, and energy-­intensive equipment offers significant potential for automated demand response. In particular, large load reductions were achieved by targeting effluent pumps and centrifuges. One of the limiting factors to implementing demand response is the reaction of effluent turbidity to reduced aeration at an earlier stage of the process. Another limiting factor is that cogeneration capabilities of municipal facilities, including existing power purchase agreements and utility receptiveness to purchasing electricity from cogeneration facilities, limit a facility’s potential to participate in other DR activities.

  9. Peer-nominated deviant talk within residential treatment: individual and group influences on treatment response.

    PubMed

    Zakriski, Audrey L; Wright, Jack C; Cardoos, Stephanie L

    2011-10-01

    This research examined deviant talk during summer residential treatment using peer nominations and extensive field observations. Participants were 239 youth (M (age) = 12.62, SD = 2.60; 67% male), nested in 26 treatment groups. Deviant talk was present in this setting, showed individual differences, and increased over time, especially for younger boys. As expected, its relationship to treatment response was moderated by peer behavior. Initial levels of individual deviant talk were related to clinical improvement, but primarily when peer deviant talk was low. Initial levels of peer deviant talk were related to higher than expected end of treatment aggression, especially for youth who were high in deviant talk. Deviant talk effects were observed for staff impressions of change and observations of aggression and adjustment. Initial antisocial behavior affected whether individual or peer levels of deviant talk more heavily influenced treatment response. Implications for clinical assessment and treatment monitoring are discussed.

  10. The Antidepressant Treatment Response Index as a Predictor of Reboxetine Treatment Outcome in Major Depressive Disorder.

    PubMed

    Caudill, Marissa M; Hunter, Aimee M; Cook, Ian A; Leuchter, Andrew F

    2015-10-01

    Biomarkers to predict clinical outcomes early during the treatment of major depressive disorder (MDD) could reduce suffering and improve outcomes. A quantitative electroencephalogram (qEEG) biomarker, the Antidepressant Treatment Response (ATR) index, has been associated with outcomes of treatment with selective serotonin reuptake inhibitor antidepressants in patients with MDD. Here, we report the results of a post hoc analysis initiated to evaluate whether the ATR index may also be associated with reboxetine treatment outcome, given that its putative mechanism of action is via norepinephrine reuptake inhibition (NRI). Twenty-five adults with MDD underwent qEEG studies during open-label treatment with reboxetine at doses of 8 to 10 mg daily for 8 weeks. The ATR index calculated after 1 week of reboxetine treatment was significantly associated with overall Hamilton Depression Rating Scale (HAM-D) improvement at week 8 (r=0.605, P=.001), even after controlling for baseline depression severity (P=.002). The ATR index predicted response (≥50% reduction in HAM-D) with 70.6% sensitivity and 87.5% specificity, and remission (final HAM-D≤7) with 87.5% sensitivity and 64.7% specificity. These results suggest that the ATR index may be a useful biomarker of clinical response during NRI treatment of adults with MDD. Future studies are warranted to investigate further the potential utility of the ATR index as a predictor of noradrenergic antidepressant treatment response.

  11. Does Temperament Moderate Treatment Response in Adolescent Substance Use Disorders?

    ERIC Educational Resources Information Center

    Burleson, Joseph A.; Kaminer, Yifrah

    2008-01-01

    To assess whether temperament moderates response to treatment for substance use disorders (SUD), n = 88 consecutively referred adolescents with SUD were randomized to cognitive-behavioral (CBT) or psychoeducational (PET) therapies. Principal components analyses reduced the 10-attribute Dimensions of Temperament Revised (DOTS-R) to three factors…

  12. Personality, Stressful Life Events, and Treatment Response in Major Depression

    ERIC Educational Resources Information Center

    Bulmash, Eric; Harkness, Kate L.; Stewart, Jeremy G.; Bagby, R. Michael

    2009-01-01

    The current study examined whether the personality traits of self-criticism or dependency moderated the effect of stressful life events on treatment response. Depressed outpatients (N = 113) were randomized to 16 weeks of cognitive-behavioral therapy, interpersonal psychotherapy, or antidepressant medication (ADM). Stressful life events were…

  13. Parental Marital Discord and Treatment Response in Depressed Adolescents

    ERIC Educational Resources Information Center

    Amaya, Meredith M.; Reinecke, Mark A.; Silva, Susan G.; March, John S.

    2011-01-01

    Evidence suggests that parental marital discord contributes to the development of internalizing and externalizing symptoms in children and adolescents. Few studies, however, have examined the association between parental marital discord and youth's response to treatment. The present study examined the impact of interparental discord on treatment…

  14. Neoadjuvant treatment for advanced esophageal cancer: response assessment before surgery and how to predict response to chemoradiation before starting treatment

    PubMed Central

    Hölscher, Arnulf H.; Schmidt, Matthias; Warnecke-Eberz, Ute

    2015-01-01

    Patients with advanced esophageal cancer (T3-4, N) have a poor prognosis. Chemoradiation or chemotherapy before esophagectomy with adequate lymphadenectomy is the standard treatment for patients with resectable advanced esophageal carcinoma. However, only patients with major histopathologic response (regression to less than 10% of the primary tumor) after preoperative treatment will have a prognostic benefit of preoperative chemoradiation. Using current therapy regimens about 40% to 50% of the patients show major histopathological response. The remaining cohort does not benefit from this neoadjuvant approach but might benefit from earlier surgical resection. Therefore, it is an aim to develop tools for response prediction before starting the treatment and for early response assessment identifying responders. The current review discusses the different imaging techniques and the most recent studies about molecular markers for early response prediction. The results show that [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) has a good sensitivity but the specificity is not robust enough for routine clinical use. Newer positron emission tomography detector technology, the combination of FDG-PET with computed tomography, additional evaluation criteria and standardization of evaluation may improve the predictive value. There exist a great number of retrospective studies using molecular markers for prediction of response. Until now the clinical use is missing. But the results of first prospective studies are promising. A future perspective may be the combination of imaging technics and special molecular markers for individualized therapy. Another aspect is the response assessment after finishing neoadjuvant treatment protocol. The different clinical methods are discussed. The results show that until now no non-invasive method is valid enough to assess complete histopathological response. PMID:26157318

  15. The evolution of the female sexual response concept: treatment implications.

    PubMed

    Damjanović, Aleksandar; Duisin, Dragana; Barisić, Jasmina

    2013-01-01

    Sexual dysfunctions have been the most prevalent group of sexual disorders and include a large number of populations of both sexes.The research of sexual behavior and treatment of women with sexual distress arises many questions related to differences in sexual response of men and women. The conceptualization of this response in modern sexology has changed over time.The objective of our paper was to present the changes and evolution of the female's sexual response concept in a summarized and integrated way, to analyze the expanded and revised definitions of the female sexual response as well as implications and recommendations of new approaches to diagnostics and treatment according to the established changes.The lack of adequate empirical basis of the female sexual response model is a critical question in the literature dealing with this issue. Some articles report that linear models demonstrate more correctly and precisely the sexual response of women with normal sexual functions in relation to women with sexual dysfunction. Modification of this model later resulted in a circular model which more adequately presented the sexual response of women with sexual function disorder than of women with normal sexual function.The nonlinear model of female sexual response constructed by Basson incorporates the value of emotional intimacy, sexual stimulus and satisfaction with the relationship. Female functioning is significantly affected by multiple psychosocial factors such as satisfaction with the relationship, self-image, earlier negative sexual experience, etc. Newly revised, expanded definitions of female sexual dysfunction try to contribute to new knowledge about a highly contextual nature of woman's sexuality so as to enhance clinical treatment of dysfunctions.The definitions emphasize the evaluation of the context of women's problematic sexual experiences.

  16. Rapid Response in Psychological Treatments for Binge-Eating Disorder

    PubMed Central

    Hilbert, Anja; Hildebrandt, Thomas; Agras, W. Stewart; Wilfley, Denise E.; Wilson, G. Terence

    2015-01-01

    Objective Analysis of short- and long-term effects of rapid response across three different treatments for binge-eating disorder (BED). Method In a randomized clinical study comparing interpersonal psychotherapy (IPT), cognitive-behavioral guided self-help (CBTgsh), and behavioral weight loss (BWL) treatment in 205 adults meeting DSM-IV criteria for BED, the predictive value of rapid response, defined as ≥ 70% reduction in binge-eating by week four, was determined for remission from binge-eating and global eating disorder psychopathology at posttreatment, 6-, 12-, 18-, and 24-month follow-up. Results Rapid responders in CBTgsh, but not in IPT or BWL, showed significantly greater rates of remission from binge-eating than non-rapid responders, which was sustained over the long term. Rapid and non-rapid responders in IPT and rapid responders in CBTgsh showed a greater remission from binge-eating than non-rapid responders in CBTgsh and BWL. Rapid responders in CBTgsh showed greater remission from binge-eating than rapid responders in BWL. Although rapid responders in all treatments had lower global eating disorder psychopathology than non-rapid responders in the short term, rapid responders in CBTgsh and IPT were more improved than those in BWL and non-rapid responders in each treatment. Rapid responders in BWL did not differ from non-rapid responders in CBTgsh and IPT. Conclusions Rapid response is a treatment-specific positive prognostic indicator of sustained remission from binge-eating in CBTgsh. Regarding an evidence-based stepped care model, IPT, equally efficacious for rapid and non-rapid responders, could be investigated as a second-line treatment in case of non-rapid response to first-line CBTgsh. PMID:25867446

  17. Poor Response to Periodontal Treatment May Predict Future Cardiovascular Disease.

    PubMed

    Holmlund, A; Lampa, E; Lind, L

    2017-03-01

    Periodontal disease has been associated with cardiovascular disease (CVD), but whether the response to the treatment of periodontal disease affects this association has not been investigated in any large prospective study. Periodontal data obtained at baseline and 1 y after treatment were available in 5,297 individuals with remaining teeth who were treated at a specialized clinic for periodontal disease. Poor response to treatment was defined as having >10% sites with probing pocket depth >4 mm deep and bleeding on probing at ≥20% of the sites 1 y after active treatment. Fatal/nonfatal incidence rate of CVD (composite end point of myocardial infarction, stroke, and heart failure) was obtained from the Swedish cause-of-death and hospital discharge registers. Poisson regression analysis was performed to analyze future risk of CVD. During a median follow-up of 16.8 y (89,719 person-years at risk), those individuals who did not respond well to treatment (13.8% of the sample) had an increased incidence of CVD ( n = 870) when compared with responders (23.6 vs. 15.3%, P < 0.001). When adjusting for calendar time, age, sex, educational level, smoking, and baseline values for bleeding on probing, probing pocket depth >4 mm, and number of teeth, the incidence rate ratio for CVD among poor responders was 1.28 (95% CI, 1.07 to 1.53; P = 0.007) as opposed to good responders. The incidence rate ratio among poor responders increased to 1.39 (95% CI, 1.13 to 1.73; P = 0.002) for those with the most remaining teeth. Individuals who did not respond well to periodontal treatment had an increased risk for future CVD, indicating that successful periodontal treatment might influence progression of subclinical CVD.

  18. Measurement of response to treatment in colorectal liver metastases.

    PubMed Central

    Dworkin, M. J.; Burke, D.; Earlam, S.; Fordy, C.; Allen-Mersh, T. G.

    1995-01-01

    Assessment of tumour response to chemotherapy is important when assessing efficacy of treatment and comparing differing therapeutic regimens. Percentage hepatic replacement (PHR) is commonly used to assess response to treatment of colorectal hepatic metastases. PHR is dependent not only on tumour volume, but also on hepatic parenchymal volume. The effect of tumour growth on hepatic parenchymal volume is unclear but is of importance owing to its effect on PHR. We assessed tumour and hepatic parenchymal weights in an animal tumour model using dissection, and tumour and hepatic parenchymal volumes in patients with colorectal hepatic metastases using CT scanning, in order to establish how hepatic parenchyma varied with change in metastasis size. There was no significant correlation between tumour and liver parenchyma in either the animal model (r = -0.03, P > 0.05) or the patient study (r = 0.3, P < 0.05). This suggests that hepatic parenchymal volume was preserved in the presence of increasing tumour volume. In a further study of computerised tomographic (CT) scans before and after treatment in patients whose tumours either responded to chemotherapy or continued to grow, change in PHR (median proportion of PHR change = 0.40) significantly (P = 0.04) underestimated the change in tumour volume (median proportion of tumour volume change = 0.56), particularly at higher (> 400 ml) volumes. There was good correlation between change in tumour volume and WHO criteria in assigning patients to tumour growth, stable disease or tumour response categories. This study suggests that, in clinical trials comparing colorectal liver metastasis treatments, metastasis volume and not PHR should be used to assess extent of disease and the effect of treatment. PMID:7710957

  19. Response of a seagrass fish assemblage to improved wastewater treatment.

    PubMed

    Ourgaud, M; Ruitton, S; Bell, J D; Letourneur, Y; Harmelin, J G; Harmelin-Vivien, M L

    2015-01-15

    We compared the structure of a seagrass fish assemblage near a sewage outlet before and after improvements to wastewater treatment. To determine whether responses by the fish assemblage were due to changes in water quality or to other factors, comparisons were made with the structure of a fish assemblage from a nearby site unaffected by sewage effluent. Total species richness, density and biomass of fish, decreased at both sites over the 30-year period. An increase in mean trophic level near the sewage outlet following improvements in water quality indicated that wastewater treatment had another important effect. This result is consistent with the reductions in food webs supporting pelagic and benthic fishes that typically accompany decreases in nutrient inputs. Although improvements to wastewater treatment explained much of the variation in the structure of the fish assemblage at PC, our results also suggest that fishing and climate change, at both sites.

  20. Adolescents with Internet Gaming Disorder (IGD): profiles and treatment response.

    PubMed

    Martín-Fernández, María; Matalí, Josep Lluís; García-Sánchez, Sara; Pardo, Marta; Lleras, María; Castellano-Tejedor, Carmina

    2016-10-07

    Demand for treatment for problems related to the use of video games have increased significantly in adolescents. Most cases have a comorbid mental disorder that jeopardises both pathologies. The aim of this study is to describe profiles of adolescents with Internet Gaming Disorder (IGD) according to comorbidity and analyze treatment response at 3 and 6 months. A sample of 86 patients which consulted in the Addictive Behavior Unit of a hospital was assessed with diagnostic criteria for IGD, the interview K-SADS-PL for mental disorders and the Clinical Global Impression (CGI) to treatment progress. Of the initial sample, 68,6% (n = 59) met diagnostic criteria for IGD. Of these, the 45,76% matched an internalizing profile, presenting comorbidity with Mood Disorders (44,4%), Anxiety Disorders (44,4%) and Personality Disorders (11,1%). The externalizing profile would comprise 52,54% of the sample presenting Disruptive Behavior Disorder (48,4%=, ADHD (29%) and Disruptive Behavior Disorders not otherwise specified (22,6%). Unlike externalizing, the internalizing patients had a family history of psychiatric problems (63%), difficulties in social relationships (77,8%) and seemed to use video games preferably to escape discomfort (66,7%). After 3 months the externalizing profile showed improvements. Comorbid disorders allow the discrimination of two IGD profiles in adolescents and these could influence treatment response. Therefore, it is important to assess comorbidities to design a more accurate intervention focused on the specificities of each profile.

  1. Frontocingulate Dysfunction in Depression: Toward Biomarkers of Treatment Response

    PubMed Central

    Pizzagalli, Diego A

    2011-01-01

    Increased rostral anterior cingulate cortex (rACC) activity has emerged as a promising predictor of treatment response in depression, but neither the reliability of this relationship nor the mechanisms supporting it have been thoroughly investigated. This review takes a three-pronged approach to these issues. First, I present a meta-analysis demonstrating that the relationship between resting rACC activity and treatment response is robust. Second, I propose that the rACC plays a key role in treatment outcome because of its ‘hub' position in the default network. Specifically, I hypothesize that elevated resting rACC activity confers better treatment outcomes by fostering adaptive self-referential processing and by helping to recalibrate relationships between the default network and a ‘task-positive network' that comprises dorsolateral prefrontal and dorsal cingulate regions implicated in cognitive control. Third, I support this hypothesis by reviewing neuropsychological, electrophysiological, and neuroimaging data on frontocingulate dysfunction in depression. The review ends with a discussion of the limitations of current work and future directions. PMID:20861828

  2. Electrochemical treatment of deproteinated whey wastewater and optimization of treatment conditions with response surface methodology.

    PubMed

    Güven, Güray; Perendeci, Altunay; Tanyolaç, Abdurrahman

    2008-08-30

    Electrochemical treatment of deproteinated whey wastewater produced during cheese manufacture was studied as an alternative treatment method for the first time in literature. Through the preliminary batch runs, appropriate electrode material was determined as iron due to high removal efficiency of chemical oxygen demand (COD), and turbidity. The electrochemical treatment conditions were optimized through response surface methodology (RSM), where applied voltage was kept in the range, electrolyte concentration was minimized, waste concentration and COD removal percent were maximized at 25 degrees C. Optimum conditions at 25 degrees C were estimated through RSM as 11.29 V applied voltage, 100% waste concentration (containing 40 g/L lactose) and 19.87 g/L electrolyte concentration to achieve 29.27% COD removal. However, highest COD removal through the set of runs was found as 53.32% within 8h. These results reveal the applicability of electrochemical treatment to the deproteinated whey wastewater as an alternative advanced wastewater treatment method.

  3. Enteric microbiome metabolites correlate with response to simvastatin treatment.

    PubMed

    Kaddurah-Daouk, Rima; Baillie, Rebecca A; Zhu, Hongjie; Zeng, Zhao-Bang; Wiest, Michelle M; Nguyen, Uyen Thao; Wojnoonski, Katie; Watkins, Steven M; Trupp, Miles; Krauss, Ronald M

    2011-01-01

    Although statins are widely prescribed medications, there remains considerable variability in therapeutic response. Genetics can explain only part of this variability. Metabolomics is a global biochemical approach that provides powerful tools for mapping pathways implicated in disease and in response to treatment. Metabolomics captures net interactions between genome, microbiome and the environment. In this study, we used a targeted GC-MS metabolomics platform to measure a panel of metabolites within cholesterol synthesis, dietary sterol absorption, and bile acid formation to determine metabolite signatures that may predict variation in statin LDL-C lowering efficacy. Measurements were performed in two subsets of the total study population in the Cholesterol and Pharmacogenetics (CAP) study: Full Range of Response (FR), and Good and Poor Responders (GPR) were 100 individuals randomly selected from across the entire range of LDL-C responses in CAP. GPR were 48 individuals, 24 each from the top and bottom 10% of the LDL-C response distribution matched for body mass index, race, and gender. We identified three secondary, bacterial-derived bile acids that contribute to predicting the magnitude of statin-induced LDL-C lowering in good responders. Bile acids and statins share transporters in the liver and intestine; we observed that increased plasma concentration of simvastatin positively correlates with higher levels of several secondary bile acids. Genetic analysis of these subjects identified associations between levels of seven bile acids and a single nucleotide polymorphism (SNP), rs4149056, in the gene encoding the organic anion transporter SLCO1B1. These findings, along with recently published results that the gut microbiome plays an important role in cardiovascular disease, indicate that interactions between genome, gut microbiome and environmental influences should be considered in the study and management of cardiovascular disease. Metabolic profiles could

  4. The myocardial heat shock response following sodium salicylate treatment

    PubMed Central

    Locke, Marius; Atance, Joel

    2000-01-01

    In cultured cells, salicylate has been shown to potentiate the induction of Hsp72 so that a mild heat stress (40°C) in the presence of salicylate induces an Hsp72 response that is similar to a severe heat stress (42°C). To determine whether salicylate can potentiate the myocardial Hsp70 response in vivo and confer protection from an ischemic stress, male Sprague-Dawley rats (250–300 g) were placed into 5 groups: (1) control, (2) salicylate only (400 mg/kg), (3) mild heat stress (40°C for 15 minutes), (4) mild heat stress plus salicylate, and (5) severe heat stress (42°C for 15 minutes). Twenty-four hours following salicylate treatment and/or heat stress, animals were anesthetized, their hearts rapidly isolated, and hemodynamic function evaluated using the Langendorff technique. Hsp72 content was subsequently assessed by Western blotting. Although salicylate in combination with a mild heat stress induced heat shock factor activation, only the hearts from severely heat-stressed animals (42°C) demonstrated a significantly elevated myocardial Hsp72 content and a significantly enhanced postischemic recovery of left ventricular developed pressure and rates of contraction and relaxation. These results support the role for Hsp72 as a protective protein and suggest that neither salicylate treatment alone nor salicylate in combination with a mild heat stress potentiates the myocardial Hsp72 response. PMID:11048658

  5. Changes in Trypanosoma cruzi-specific immune responses following treatment: surrogate markers of treatment efficacy

    PubMed Central

    Laucella, Susana A.; Mazliah, Damián Pérez; Bertocchi, Graciela; Alvarez, María G.; Cooley, Gretchen; Viotti, Rodolfo; Albareda, María C.; Lococo, Bruno; Postan, Miriam; Armenti, Alejandro; Tarleton, Rick L.

    2009-01-01

    Background As many as 20 million people are living with Trypanosoma cruzi infection in Latin American, yet few receive any treatment. The major limitation in developing and evaluating potential new drugs for their efficacy is the lack of reliable tests to assess parasite burden and elimination. Methods Adults volunteers with chronic T. cruzi infection were evaluated clinically and stratified according to the Kuschnir classification. Individuals in group 0 and group 1 clinical status were treated with 5 mg benznidazole/kg/day for 30 days. The changes in T. cruzi-specific T cell and antibody responses, as well as in clinical status, were measured periodically over the 3-5 year follow-up period and compared to pre-treatment conditions and to an untreated control group. Results The frequency of peripheral IFN- g-producing T cells specific for T. cruzi declined as early as 12 months after BZ treatment and subsequently became undetectable in a substantial proportion of treated subjects. Addtionally decreases in antibody responses to a pool of recombinant T. cruzi proteins also declined in many of these same subjects. The shift to negative IFN- g T cell responses was highly associated with an early increase in IFN- g-producing T cells with phenotypic features of effector/effector memory cells in a subset of subjects. Benznidazole treatment also resulted in an increase in naïve and early differentiated memory-like CD8+ T cells in a majority of subjects. Conclusions BZ treatment during chronic Chagas disease has a substantial impact on parasite-specific immune response that is likely to be indicative of treatment efficacy and cure. PMID:19877967

  6. Chronic Cluster Headache with an Atypical Presentation and Treatment Response

    PubMed Central

    Morais, Hugo

    2016-01-01

    The management of cluster headache (CH) may be challenging. We report a 50-year-old male with recurrent attacks of dull and severe unilateral periorbital pain, lasting 30–45 minutes, twice a day, exclusively during sleep, and accompanied by ipsilateral rhinorrhea and lacrimation. The pain switched sides within every attack. CH treatment was initiated but the patient maintained recurrence rates compatible with chronic CH, even after increasing verapamil to 460 mg/day. Afterwards we decided to add lithium (800 mg/day). With this treatment the severity and recurrence of CH substantially decreased, despite the patient's autonomous decision to take lithium only during the acute phase of the cluster. The exclusively alternating location and the excellent response to short cycles of lithium represent two unique features of CH. PMID:28127484

  7. Transcriptomic Response to Nitric Oxide Treatment in Larix olgensis Henry

    PubMed Central

    Hu, Xiaoqing; Yang, Jingli; Li, Chenghao

    2015-01-01

    Larix olgensis Henry is an important coniferous species found in plantation forests in northeastern China, but it is vulnerable to pathogens. Nitric oxide (NO) is an important molecule involved in plant resistance to pathogens. To study the regulatory role of NO at the transcriptional level, we characterized the transcriptomic response of L. olgensis seedlings to sodium nitroprusside (SNP, NO donor) using Illumina sequencing and de novo transcriptome assembly. A significant number of putative metabolic pathways and functions associated with the unique sequences were identified. Genes related to plant pathogen infection (FLS2, WRKY33, MAPKKK, and PR1) were upregulated with SNP treatment. This report describes the potential contribution of NO to disease resistance in L. olgensis as induced by biotic stress. Our results provide a substantial contribution to the genomic and transcriptomic resources for L. olgensis, as well as expanding our understanding of the involvement of NO in defense responses at the transcriptional level. PMID:26633380

  8. Time to treatment response in first episode schizophrenia: should acute treatment trials last several months?

    PubMed Central

    Gallego, Juan A.; Robinson, Delbert G.; Sevy, Serge M.; Napolitano, Barbara; McCormack, Joanne; Lesser, Martin L.; Kane, John M.

    2010-01-01

    Objectives Response patterns may differ between patients with first episode and multi-episode schizophrenia. This analysis explored trial duration with first episode patients and whether early limited improvement predicts ultimate lack of treatment response with first episode patients as it does with multi-episode patients. Methods 112 subjects (mean age=23.3 years [SD=5.1]) who presented between November 1998 and October 2004 with a first episode of psychosis and had a DSM-IV diagnosis of schizophrenia, schizophreniform or schizoaffective disorder, were randomly assigned to treatment with olanzapine or risperidone for 16 weeks. Treatment response, the primary outcome measure, was defined as a rating of mild or better on all of the positive symptom items on the SADS-C + PD. Response rates were calculated for each study week. A logistic regression analysis examined the association between percent reduction in symptom severity scores from baseline values at weeks 2, 4 or 8 and response by week 16. Results The estimated cumulative response rate by week 8 was 39.59% (95% CI: 29.77% – 49.41%) and 65.19% (95% CI: 55.11% – 75.27%) by week 16. The confidence intervals for estimated response at weeks 10, 12, 14 and 16 were not distinct. Response rates increased approximately 5 to 6 percentage points each 2 week interval between week 10 and 16. Percent reduction in symptom severity score at week 4 (but not 2 or 8) was associated (Chi-square = 3.96; df = 1, p<0.05) with responder status at week 16 (odds ratio: 1.03; 95% CI: 1.00;1.05). However, receiver operating characteristic curves did not suggest any level of percent symptom reduction that would be clinically useful as a predictor of response by week 16. Conclusions Many first episode patients respond between weeks 8 and 16 of treatment with a single antipsychotic medication. Limited early symptom improvement does not identify with enough accuracy to be clinically useful those first episode patients who will not

  9. Rapid acid treatment of Escherichia coli: transcriptomic response and recovery

    PubMed Central

    Kannan, Geetha; Wilks, Jessica C; Fitzgerald, Devon M; Jones, Brian D; BonDurant, Sandra S; Slonczewski, Joan L

    2008-01-01

    Background Many E. coli genes show pH-dependent expression during logarithmic growth in acid (pH 5–6) or in base (pH 8–9). The effect of rapid pH change, however, has rarely been tested. Rapid acid treatment could distinguish between genes responding to external pH, and genes responding to cytoplasmic acidification, which occurs transiently following rapid external acidification. It could reveal previously unknown acid-stress genes whose effects are transient, as well as show which acid-stress genes have a delayed response. Results Microarray hybridization was employed to observe the global gene expression of E. coli K-12 W3110 following rapid acidification of the external medium, from pH 7.6 to pH 5.5. Fluorimetric observation of pH-dependent tetR-YFP showed that rapid external acidification led to a half-unit drop in cytoplasmic pH (from pH 7.6 to pH 6.4) which began to recover within 20 s. Following acid treatment, 630 genes were up-regulated and 586 genes were down-regulated. Up-regulated genes included amino-acid decarboxylases (cadA, adiY, gadA), succinate dehydrogenase (sdhABCD), biofilm-associated genes (bdm, gatAB, and ymgABC), and the Gad, Fur and Rcs regulons. Genes with response patterns consistent with cytoplasmic acid stress were revealed by addition of benzoate, a membrane-permeant acid that permanently depresses cytoplasmic pH without affecting external pH. Several genes (yagU, ygiN, yjeI, and yneI) were up-regulated specifically by external acidification, while other genes (fimB, ygaC, yhcN, yhjX, ymgABC, yodA) presented a benzoate response consistent with cytoplasmic pH stress. Other genes (the nuo operon for NADH dehydrogenase I, and the HslUV protease) showed delayed up-regulation by acid, with expression rising by 10 min following the acid shift. Conclusion Transcriptomic profiling of E. coli K-12 distinguished three different classes of change in gene expression following rapid acid treatment: up-regulation with or without recovery, and

  10. Gastric carcinoma: imaging diagnosis, staging and assessment of treatment response

    PubMed Central

    Hallinan, James Thomas Patrick Decourcy

    2013-01-01

    Abstract Gastric carcinoma (GC) is one of the most common causes of cancer-related death worldwide. Surgical resection is the only cure available and is dependent on the GC stage at presentation, which incorporates depth of tumor invasion, extent of lymph node and distant metastases. Accurate preoperative staging is therefore essential for optimal surgical management with consideration of preoperative and/or postoperative chemotherapy. Multidetector computed tomography (MDCT) with its ability to assess tumor depth, nodal disease and metastases is the preferred technique for staging GC. Endoscopic ultrasonography is more accurate for assessing the depth of wall invasion in early cancer, but is limited in the assessment of advanced local or stenotic cancer and detection of distant metastases. Magnetic resonance imaging (MRI), although useful for staging, is not proven to be effective. Positron emission tomography (PET) is most useful for detecting and characterizing distant metastases. Both MDCT and PET are useful for assessment of treatment response following preoperative chemotherapy and for detection of recurrence after surgical resection. This review article discusses the usefulness of imaging modalities for detecting, staging and assessing treatment response for GC and the potential role of newer applications including CT volumetry, virtual gastroscopy and perfusion CT in the management of GC. PMID:23722535

  11. Genomewide Pharmacogenomic Analysis of Response to Treatment with Antipsychotics

    PubMed Central

    McClay, Joseph L.; Adkins, Daniel E.; Åberg, Karolina; Stroup, Scott; Perkins, Diana O.; Vladimirov, Vladimir I.; Lieberman, Jeffrey A.; Sullivan, Patrick F.; van den Oord, Edwin J.C.G.

    2009-01-01

    Schizophrenia is an often devastating neuropsychiatric illness. Understanding the genetic variation affecting response to antipsychotics is important to develop novel diagnostic tests to match individual schizophrenic patients to the most effective and safe medication. Here we use a genomewide approach to detect genetic variation underlying individual differences in response to treatment with the antipsychotics olanzapine, quetiapine, risperidone, ziprasidone and perphenazine. Our sample consisted of 738 subjects with DSM-IV schizophrenia who took part in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Subjects were genotyped using the Affymetrix 500K genotyping platform plus a custom 164K chip to improve genomewide coverage. Treatment outcome was measured using the Positive and Negative Syndrome Scale (PANSS). Our criterion for genomewide significance was a pre-specified threshold that ensures, on average, only 10% of the significant findings are false discoveries. The top statistical result reached significance at our pre-specified threshold and involved a SNP in an intergenic region on chromosome 4p15. In addition, SNPs in ANKS1B and CNTNAP5 that mediated the effects of olanzapine and risperidone on Negative symptoms were very close to our threshold for declaring significance. The most significant SNP in CNTNAP5 is nonsynonymous, giving rise to an amino acid substitution. In addition to highlighting our top results, we provide all p-values for download as a resource for investigators with the requisite samples to carry out replication. This study demonstrates the potential of GWAS to discover novel genes that mediate effects of antipsychotics, which eventually could help to tailor drug treatment to schizophrenic patients. PMID:19721433

  12. Predicting Treatment Response for Oppositional Defiant and Conduct Disorder Using Pre-treatment Adrenal and Gonadal Hormones.

    PubMed

    Shenk, Chad E; Dorn, Lorah D; Kolko, David J; Susman, Elizabeth J; Noll, Jennie G; Bukstein, Oscar G

    2012-12-01

    Variations in adrenal and gonadal hormone profiles have been linked to increased rates of oppositional defiant disorder (ODD) and conduct disorder (CD). These relationships suggest that certain hormone profiles may be related to how well children respond to psychological treatments for ODD and CD. The current study assessed whether pre-treatment profiles of adrenal and gonadal hormones predicted response to psychological treatment of ODD and CD. One hundred five children, 6 - 11 years old, participating in a randomized, clinical trial provided samples for cortisol, testosterone, dehydroepiandrosterone, and androstenedione. Diagnostic interviews of ODD and CD were administered up to three years post-treatment to track treatment response. Group-based trajectory modeling identified two trajectories of treatment response: 1) a High-response trajectory where children demonstrated lower rates of an ODD or CD diagnosis throughout follow-up, and 2) a Low-response trajectory where children demonstrated higher rates of an ODD or CD diagnosis throughout follow-up. Hierarchical logistic regression predicting treatment response demonstrated that children with higher pre-treatment concentrations of testosterone were four times more likely to be in the Low-response trajectory. No other significant relationship existed between pre-treatment hormone profiles and treatment response. These results suggest that higher concentrations of testosterone are related to how well children diagnosed with ODD or CD respond to psychological treatment over the course of three years.

  13. Pre-treatment high-resolution rectal MRI and treatment response to neoadjuvant chemoradiation

    PubMed Central

    Chang, George J.; You, Y. Nancy; Park, In Ja; Kaur, Harmeet; Hu, Chung-Yuan; Rodriguez-Bigas, Miguel A.; Skibber, John M.; Ernst, Randy D.

    2012-01-01

    Background Use of rectal MRI evaluation of patients with rectal cancer for primary tumor staging and for identification for poor prognostic features is increasing. MR imaging permits precise delineation of tumor anatomy and assessment of mesorectal tumor penetration and radial margin risk. Objective To evaluate the ability of pre-treatment rectal MRI to classify tumor response to neoadjuvant chemoradiation. Design Retrospective, consecutive cohort study, central review. Setting Tertiary academic hospital. Patients 62 consecutive patients with locally advanced (stage cII-cIII)rectal cancer who underwent rectal cancer protocol high resolution MRI prior to surgery(12/09-3/11). Main Outcome Measures Probability of good (ypT0-2N0) vs. poor (≥ypT3N0) response as a function of mesorectal tumor depth, lymph node status, extramural vascular invasion, and grade assessed by uni- and multi-variate logistic regression. Results Tumor response was good in 25, 40.3% and poor in 37, 59.7%.Median interval from MRI to OP was 7.9weeks (IQR: 7.0–9.0). MRI tumor depth was <1 mm in 10 (16.9%), 1–5 mm in 30 (50.8%), and >5 mm in 21(33.9%). LN status was positive in 40 (61.5%) and vascular invasion was present in 16 (25.8%). Tumor response was associated with MRI tumor depth (P=0.001), MRI lymph nodes status (P=<0.001)and vascular invasion (P=0.009). Multivariate regression indicated >5mm MRI tumor depth (OR=0.08, 95% CI=0.01–0.93, p=0.04) and MRI LN positivity (OR=0.12, 95% CI=0.03–0.53, p=0.005) were less likely to achieve a good response to neoadjuvant chemoradiotherapy. Limitations Uncertain generalizability in centers with limited experience with MRI staging for rectal cancer. Conclusion MRI assessment of tumor depth and lymph node status in rectal cancer is associated to tumor response to neoadjuvant chemoradiotherapy. These factors should therefore be considered for stratification of patients for novel treatment strategies reliant on pathologic response to treatment or for

  14. Clinical neuroimaging markers of response to treatment in mood disorders.

    PubMed

    Porcu, Michele; Balestrieri, Antonella; Siotto, Paolo; Lucatelli, Pierleone; Anzidei, Michele; Suri, Jasjit S; Zaccagna, Fulvio; Argiolas, Giovanni Maria; Saba, Luca

    2016-10-11

    Mood disorders (MD) are important and frequent psychiatric pathologies, and the management of the patients affected by thes conditions represent an important factor of disability and a huge problem in socialterms and an economic burden. The "in-vivo" studies can help researchers to understand the first events at the base of the development of the pathology and to identify the molecular and non-molecular targets of therapies, but theyhave strong limitations due to the fact that human brain circuitsthem selvesare difficult to be reproduced in animal models. Besides these challenges, they are difficult to be selectively studied with the modern imaging (such as Magnetic Resonance and Positron Emitted Tomography/Computed Tomography) and non-imaging (such as electroencephalography, magnetoencephalography, transcranial magnetic stimulation and evoked potentials) methods. In comparison with other methods, the "in-vivo" imaging investigations have higher temporal and spatial resolution compared to the "in-vivo" non-imaging techniques.All these factors make difficult to fully understand the aetiology and pathophysiology of these disorders, and consequently make difficult not only in the development, but also the monitoring of the actions of therapies,which according to clinical observations have been demonstrated effective in the treatment. In this review, we will focus our attention on the actual state-of-theart of role of imaging in monitoring of treatment of MD, underlying that up to date there are still not standardized imaging markers available in clinical practice.We will analyse briefly the actual classification of MD; then we will focus on the "in vivo" imaging modalities used in research and clinical activity, the current knowledge about the neural models at the base ofMD. Finally the last part of the review focuses on analysis of the principle markers of response to the treatment according to the type of treatment used and to the imaging techniques adopted.

  15. Proteomic response to acupuncture treatment in spontaneously hypertensive rats.

    PubMed

    Lai, Xinsheng; Wang, Jiayou; Nabar, Neel R; Pan, Sanqiang; Tang, Chunzhi; Huang, Yong; Hao, Mufeng; Yang, Zhonghua; Ma, Chunmei; Zhang, Jin; Chew, Helen; He, Zhenquan; Yang, Junjun; Su, Baogui; Zhang, Jian; Liang, Jun; Sneed, Kevin B; Zhou, Shu-Feng

    2012-01-01

    Previous animal and clinical studies have shown that acupuncture is an effective alternative treatment in the management of hypertension, but the mechanism is unclear. This study investigated the proteomic response in the nervous system to treatment at the Taichong (LR3) acupoint in spontaneously hypertensive rats (SHRs). Unanesthetized rats were subject to 5-min daily acupuncture treatment for 7 days. Blood pressure was monitored over 7 days. After euthanasia on the 7(th) day, rat medullas were dissected, homogenized, and subject to 2D gel electrophoresis and MALDI-TOF analysis. The results indicate that blood pressure stabilized after the 5th day of acupuncture, and compared with non-acupoint treatment, Taichong-acupunctured rat's systolic pressure was reduced significantly (P<0.01), though not enough to bring blood pressure down to normal levels. The different treatment groups also showed differential protein expression: the 2D images revealed 571 ± 15 proteins in normal SD rats' medulla, 576 ± 31 proteins in SHR's medulla, 597 ± 44 proteins in medulla of SHR after acupuncturing Taichong, and 616 ± 18 proteins in medulla of SHR after acupuncturing non-acupoint. In the medulla of Taichong group, compared with non-acupoint group, seven proteins were down-regulated: heat shock protein-90, synapsin-1, pyruvate kinase isozyme, NAD-dependent deacetylase sirtuin-2, protein kinase C inhibitor protein 1, ubiquitin hydrolase isozyme L1, and myelin basic protein. Six proteins were up-regulated: glutamate dehydrogenase 1, aldehyde dehydrogenase 2, glutathione S-transferase M5, Rho GDP dissociation inhibitor 1, DJ-1 protein and superoxide dismutase. The altered expression of several proteins by acupuncture has been confirmed by ELISA, Western blot and qRT-PCR assays. The results indicate an increase in antioxidant enzymes in the medulla of the SHRs subject to acupuncture, which may provide partial explanation for the antihypertensive effect of acupuncture. Further

  16. Factors Affecting Response to Infertility Treatment: Case of Iran

    PubMed Central

    Peyromusavi, Fatemeh; Barouni, Mohsen; Naderi, Tayebeh; Shahravan, Arash

    2016-01-01

    Introduction: Infertility affects both women and men in all the countries. Infertility often has profound long-term or short-term impacts on the people involved and puts them at risk of familial and social pressures. According to WHO estimates, between 8% and 12% of all the couples worldwide experience some form of infertility during their reproductive life, i.e. 50–80 million people are affected. The aim of this study was to evaluate the response to infertility treatment by taking into account factors such as age, hirsutism, menstruation and galactose among women in Kerman. Methodology: Of a total of 300 patient files evaluated 220 cases were flawless, of which the study factors were recorded. These data were estimated by Logit model. The dependent variable was the response to treatment (0 and 1) and the independent variables included age of men and women, hirsutism, menstruation, galactose, duration of the period no preventive measures were used and body mass index. After entering the data, model output was analyzed by using the STATA software. Results: The results showed that of all the model variables, female age (prob=0.0065), menstruation (prob=0.04), hirsutism (prob=0.02), marriage age (in months) (prob=0.02) and BMI were significant and other variables were not significant. McFadden analysis for goodness of fit was 0.92. Conclusion: The study results showed that women should pay more attention to variables such as BMI, menstruation quality (regular and irregular) and aging because clinical disregard of any of the above can have a significant impact on the individual’s fertility. PMID:26234994

  17. [Emotional responsiveness of substance abusers under outpatient treatment].

    PubMed

    Chicharro, Juan; Pérez-García, Ana M; Sanjuán, Pilar

    2012-01-01

    The emotions predispose to action providing information from both internal and external environment. There is evidence indicating that the emotional response in drugdependent patients is different from that of the not consuming population. The present work analyzed the emotions of drugdependent under ambulatory treatment (N=57), following the Lang's theory of emotion, considering the dimensions of valence, arousal and dominance or control, across the International Affective Picture System (IAPS), individually applied. The results were contrasted with a control group of not consuming persons (N=44) of similar age, since this variable concerns emotional experience. The influence of sex was also analyzed, considering the possible differences between men and women in emotional experience. The results can be summarized in the following points: (1) There were significant differences between substance abusers and not consumers in the dimension of valence, valuing the consumers the emotional stimuli of the most extreme form (the agreeable ones as better, and the disagreeable ones as worse); (2) there were no differences between both groups in the arousal and dominance dimensions; and (3) women reported more arousal before aversive images, and less before the sexual ones, than males, independently of they were or not substance abusers. Finally, it is suggested the need to deep into the analysis of sex differences and into the images selected, as well as into the usefulness of the emotion centred therapies for the treatment of drugdependency.

  18. Neurocognitive predictors of treatment response to randomized treatment in adults with tic disorders.

    PubMed

    Abramovitch, Amitai; Hallion, Lauren S; Reese, Hannah E; Woods, Douglas W; Peterson, Alan; Walkup, John T; Piacentini, John; Scahill, Lawrence; Deckersbach, Thilo; Wilhelm, Sabine

    2017-03-06

    Tourette's disorder (TS) and chronic tic disorder (CTD) are neurodevelopmental disorders characterized by involuntary vocal and motor tics. Consequently, TS/CTD have been conceptualized as disorders of cognitive and motor inhibitory control. However, most neurocognitive studies have found comparable or superior inhibitory capacity among individuals with TS/CTD relative to healthy controls. These findings have led to the hypothesis that individuals with TS/CTD develop increased inhibitory control due to the constant need to inhibit tics. However, the role of cognitive control in TS/CTD is not yet understood, particularly in adults. To examine the role of inhibitory control in TS/CTD, the present study investigated this association by assessing the relationship between inhibitory control and treatment response in a large sample of adults with TS/CTD. As part of a large randomized trial comparing behavior therapy versus supportive psychotherapy for TS/CTD, a battery of tests, including tests of inhibitory control was administered to 122 adults with TS/CTD at baseline. We assessed the association between neuropsychological test performance and change in symptom severity, as well as compared the performance of treatment responders and non-responders as defined by the Clinical Global Impression Scale. Results indicated that change in symptoms, and treatment response were not associated with neuropsychological performance on tests of inhibitory control, intellectual ability, or motor function, regardless of type of treatment. The finding that significant change in symptom severity of TS/CTD patients is not associated with impairment or change in inhibitory control regardless of treatment type suggests that inhibitory control may not be a clinically relevant facet of these disorders in adults.

  19. Breaking the DNA damage response to improve cervical cancer treatment.

    PubMed

    Wieringa, Hylke W; van der Zee, Ate G J; de Vries, Elisabeth G E; van Vugt, Marcel A T M

    2016-01-01

    Every year, cervical cancer affects ∼500,000 women worldwide, and ∼275,000 patients die of this disease. The addition of platin-based chemotherapy to primary radiotherapy has increased 5-year survival of advanced-stage cervical cancer patients, which is, however, still only 66%. One of the factors thought to contribute to treatment failure is the ability of tumor cells to repair chemoradiotherapy-induced DNA damage. Therefore, sensitization of tumor cells for chemoradiotherapy via inhibition of the DNA damage response (DDR) as a novel strategy to improve therapy effect, is currently studied pre-clinically as well as in the clinic. Almost invariably, cervical carcinogenesis involves infection with the human papillomavirus (HPV), which inactivates part of the DNA damage response. This HPV-mediated partial inactivation of the DDR presents therapeutic targeting of the residual DDR as an interesting approach to achieve chemoradio-sensitization for cervical cancer. How the DDR can be most efficiently targeted, however, remains unclear. The fact that cisplatin and radiotherapy activate multiple signaling axes within the DDR further complicates a rational choice of therapeutic targets within the DDR. In this review, we provide an overview of the current preclinical and clinical knowledge about targeting the DDR in cervical cancer.

  20. MicroRNAs, DNA Damage Response, and Cancer Treatment

    PubMed Central

    He, Mingyang; Zhou, Weiwei; Li, Chuang; Guo, Mingxiong

    2016-01-01

    As a result of various stresses, lesions caused by DNA-damaging agents occur constantly in each cell of the human body. Generally, DNA damage is recognized and repaired by the DNA damage response (DDR) machinery, and the cells survive. When repair fails, the genomic integrity of the cell is disrupted—a hallmark of cancer. In addition, the DDR plays a dual role in cancer development and therapy. Cancer radiotherapy and chemotherapy are designed to eliminate cancer cells by inducing DNA damage, which in turn can promote tumorigenesis. Over the past two decades, an increasing number of microRNAs (miRNAs), small noncoding RNAs, have been identified as participating in the processes regulating tumorigenesis and responses to cancer treatment with radiation therapy or genotoxic chemotherapies, by modulating the DDR. The purpose of this review is to summarize the recent findings on how miRNAs regulate the DDR and discuss the therapeutic functions of miRNAs in cancer in the context of DDR regulation. PMID:27973455

  1. Potential treatment options and future research to increase hepatitis C virus treatment response rate

    PubMed Central

    TenCate, Veronica; Sainz, Bruno; Cotler, Scott J; Uprichard, Susan L

    2010-01-01

    Hepatitis C virus (HCV) is a liver-tropic blood-borne pathogen that affects more than 170 million people worldwide. Although acute infections are usually asymptomatic, up to 90% of HCV infections persist with the possibility of long-term consequences such as liver fibrosis, cirrhosis, steatosis, insulin resistance, or hepatocellular carcinoma. As such, HCV-associated liver disease is a major public health concern. Although the currently available standard of care therapy of pegylated interferon α plus ribavirin successfully treats infection in a subset of patients, the development of more effective, less toxic HCV antivirals is a health care imperative. This review not only discusses the limitations of the current HCV standard of care but also evaluates upcoming HCV treatment options and how current research elucidating the viral life cycle is facilitating the development of HCV-specific therapeutics that promise to greatly improve treatment response rates both before and after liver transplantation. PMID:21331152

  2. Potential treatment options and future research to increase hepatitis C virus treatment response rate.

    PubMed

    Tencate, Veronica; Sainz, Bruno; Cotler, Scott J; Uprichard, Susan L

    2010-10-01

    Hepatitis C virus (HCV) is a liver-tropic blood-borne pathogen that affects more than 170 million people worldwide. Although acute infections are usually asymptomatic, up to 90% of HCV infections persist with the possibility of long-term consequences such as liver fibrosis, cirrhosis, steatosis, insulin resistance, or hepatocellular carcinoma. As such, HCV-associated liver disease is a major public health concern. Although the currently available standard of care therapy of pegylated interferon α plus ribavirin successfully treats infection in a subset of patients, the development of more effective, less toxic HCV antivirals is a health care imperative. This review not only discusses the limitations of the current HCV standard of care but also evaluates upcoming HCV treatment options and how current research elucidating the viral life cycle is facilitating the development of HCV-specific therapeutics that promise to greatly improve treatment response rates both before and after liver transplantation.

  3. Associations between periodontitis and systemic inflammatory diseases: response to treatment.

    PubMed

    El-Shinnawi, Una; Soory, Mena

    2013-09-01

    There is a significant prevalence of subjects with periodontitis presenting with other inflammatory conditions such as coronary heart disease, insulin resistance and arthritis. This pattern of disease presentation underscores the importance of inflammatory loading from chronic diseases, in driving their pathogeneses in a multidirectional manner. Pro-inflammatory cytokines and other agents play an important role in this process; for example, a single nucleotide polymorphism of the TNF-α gene is associated with significant periodontal attachment loss in patients with coronary heart disease. Changes in gene expression associated with inflammation and lipid metabolism in response to oral infection with the periodontal pathogen Porphyromonas gingivalis (Pg) have been demonstrated in mouse models, independent of the demonstration of atherosclerotic lesions. Insulin resistance is considered to be a chronic low-grade inflammatory condition, associated with altered glucose tolerance, hypertriglyceridemia, central obesity and coronary heart disease. It is accompanied by elevated levels of IL-1, IL-6 and TNF-α also relevant to the progression of periodontitis. There is evidence that uncontrolled periodontal disease contributes to maintenance of systemic diseases, including rheumatoid arthritis (RA), with increased risk of periodontitis in subjects with RA. The periodontal pathogen Pg is significant in contributing to citrullination of proteins resulting in immune dysregulation and autoimmune responses, seen in RA. However, they are both multifactorial chronic diseases with complex etiopathogeneses that affect their presentation. Consistent but weak associations are seen for surrogate markers of periodontitis such as tooth loss, with multiple systemic conditions. Effective treatment of periodontitis would be important in reducing systemic inflammatory loading from chronic local inflammation and in achieving systemic health. Lack of a consistent cause and effect relationship

  4. Transient CNS responses to repeated binge ethanol treatment

    PubMed Central

    Zahr, Natalie M; Rohlfing, Torsten; Mayer, Dirk; Luong, Richard; Sullivan, Edith V; Pfefferbaum, Adolf

    2016-01-01

    Adaptive changes occur in response to repeated exposure to drugs. Although ethanol (EtOH) is known to induce pharmacokinetic tolerance, the effects of EtOH on in vivo, magnetic resonance (MR)-detectable brain measures across repeated exposures have not previously been reported. Of 28 rats weighing 341±22g at baseline, 15 were assigned to the EtOH group and 13 to the control (Ctrl) group. EtOH animals were exposed to 5 cycles of 4-days of EtOH treatment followed by 10 days of recovery. Rats in both groups had structural MR imaging (MRI) scans and whole brain MR spectroscopy (MRS) at baseline, immediately following each binge period, and after each recovery period (total=11 MR scans per rat). Average blood alcohol levels (BALs) across each of the 5, 4-day binge periods were 298, 300, 301, 312, 318 mg/dL. Cerebrospinal fluid (CSF) volumes of the lateral ventricles and cisterns showed enlargement with each binge EtOH exposure but recovery with each abstinence period. Similarly, changes to MRS metabolites were transient: levels of N-acetyl aspartate (NAA) and total creatine (tCr) decreased, while those of choline-containing compounds (Cho) and glutamate/glutamine (Glx) increased with each binge EtOH exposure cycle, but also recovered during each abstinence period. The directionality of changes in response to EtOH were in expected directions based on previous, single-binge EtOH exposure experiments, but the current results do not provide support for accruing pathology with repeated binge EtOH exposure. PMID:26283309

  5. Gender differences in multiple sclerosis epidemiology and treatment response.

    PubMed

    Magyari, Melinda

    2016-03-01

    risk neither in puberty nor in adulthood. The apparent protective effect of childbirth does not appear to reflect postnatal child exposure. The only factor that may show association with a higher MS risk in women is working in agriculture but it was based on very small numbers and cannot contribute quantitatively to the incidence of MS in women. Women are generally more prone to autoimmune diseases than men, but significant increased occurrence of some other autoimmune diseases was only found in male MS cases in the period before clinical onset. None of the investigated autoimmune diseases occurred less frequently in MS patients than in control persons. Treatment response to interferon-β, expressed in relapse rate was independently influenced by gender and the presence of NAbs, but it seems that the presence of NAbs does not affect the treatment effect differently in women and men. The results indicate that men's and women's treatment response to interferon-β is similar. Females had a higher frequency of relapses than males. Our study did not reveal only one reason for the incidence increase, but as MS is multifactorial it is presumed that the incidence increase is caused by more than one factor, because women's lifestyle has undergone tremendous changes in the last half century. Our study contributes to clarification of this issue, with the role of pregnancies on the risk of MS. It is accepted that sex hormones have a clear immunologic involvement in the female predominance in MS, but there is no knowledge yet to explain the changes over time.

  6. Autoimmune hemolytic anemia after nivolumab treatment in Hodgkin lymphoma responsive to immunosuppressive treatment. A case report.

    PubMed

    Tardy, Magalie P; Gastaud, Lauris; Boscagli, Annick; Peyrade, Frederic; Gallamini, Andrea; Thyss, Antoine

    2016-08-19

    The patients with refractory Hodgkin lymphoma have a poor prognosis. The nivolumab, an IgG4 monoclonal antibody inhibiting the program death 1 pathway has recently demonstrated its efficacy and its safety in patients with heavily pretreated refractory Hodgkin lymphoma. The side effects of this immunotherapy include autoimmune-like syndromes. A 75-year-old woman with no significant comorbidities was treated by nivolumab (3 mg/kg every 2 wk) as a third-line treatment for refractory Hodgkin lymphoma. A clinical response was observed with the first injection of nivolumab, with a reduction in superficial lymph nodes. After the second injection, the patient presented an authentic autoimmune hemolytic anemia with a profound anemia at 64 g/L and biologic characteristics of hemolysis (elevated unconjugated bilirubin, lactate dehydrogenase, and reticulocytes). The direct antiglobulin test was strongly positive for IgG antibodies, and the indirect antiglobulin test became positive with a very high level of autoantibodies. After 2 injections of nivolumab, the patient underwent a fluodeoxyglucose F 18 positron emission tomography-computed tomography, showing a partial response according to modified Cheson criteria. A treatment with prednisone (2 mg/kg), initiated after transfusion of 2 units of red blood cells, permitted the complete resolution of this autoimmune reaction after 3 months of corticotherapy. The fluodeoxyglucose F 18 positron emission tomography-computed tomography performed at the end of the corticotherapy showed a clear disease progression. Considering the very good response achieved after only 2 injections of nivolumab, the limited therapeutic resources for this old woman, and the complete resolution of the autoimmune hemolytic anemia, nivolumab was reintroduced at the same dose, with close clinical and biological monitoring. She received 6 more injections of nivolumab without recurrence of hemolysis.

  7. Modulation of Autophagy by Sorafenib: Effects on Treatment Response

    PubMed Central

    Prieto-Domínguez, Nestor; Ordóñez, Raquel; Fernández, Anna; García-Palomo, Andres; Muntané, Jordi; González-Gallego, Javier; Mauriz, José L.

    2016-01-01

    The multikinase inhibitor sorafenib is, at present, the only drug approved for the treatment of hepatocellular carcinoma (HCC), one of the most lethal types of cancer worldwide. However, the increase in the number of sorafenib tumor resistant cells reduces efficiency. A better knowledge of the intracellular mechanism of the drug leading to reduced cell survival could help to improve the benefits of sorafenib therapy. Autophagy is a bulk cellular degradation process activated in a broad range of stress situations, which allows cells to degrade misfolded proteins or dysfunctional organelles. This cellular route can induce survival or death, depending on cell status and media signals. Sorafenib, alone or in combination with other drugs is able to induce autophagy, but cell response to the drug depends on the complex integrative crosstalk of different intracellular signals. In cancerous cells, autophagy can be regulated by different cellular pathways (Akt-related mammalian target of rapamycin (mTOR) inhibition, 5′ AMP-activated protein kinase (AMPK) induction, dissociation of B-cell lymphoma 2 (Bcl-2) family proteins from Beclin-1), or effects of some miRNAs. Inhibition of mTOR signaling by sorafenib and diminished interaction between Beclin-1 and myeloid cell leukemia 1 (Mcl-1) have been related to induction of autophagy in HCC. Furthermore, changes in some miRNAs, such as miR-30α, are able to modulate autophagy and modify sensitivity in sorafenib-resistant cells. However, although AMPK phosphorylation by sorafenib seems to play a role in the antiproliferative action of the drug, it does not relate with modulation of autophagy. In this review, we present an updated overview of the effects of sorafenib on autophagy and its related activation pathways, analyzing in detail the involvement of autophagy on sorafenib sensitivity and resistance. PMID:27375485

  8. Critical incidents and judicial response during medium security treatment.

    PubMed

    Jeandarme, Inge; Wittouck, Ciska; Vander Laenen, Freya; Pouls, Claudia; Heimans, Henri; Oei, T I; Bogaerts, Stefan

    This study examined inpatient incidents in three Flemish forensic medium security units and analyzed the subsequent judicial reactions to these incidents. During medium security treatment, incidents were reported for more than half of the participants. The most frequently registered incidents were non-violent in nature, such as absconding and treatment non-compliance. The base rate for physically violent incidents was low. Although crime-related incidents during medium security treatment were rarely prosecuted and adjudicated, the base rate of revocation - and hence drop-out from treatment - as a result of these incidents was high.

  9. Using host response modifiers in the treatment of periodontal disease.

    PubMed

    Novak, M John; Donley, Timothy G

    2002-01-01

    Periodontal disease is the result of a complex interaction between microbial plaque, the host's inflammatory response to the plaque, and host modifying factors (e.g., smoking, diabetes, genetics) that may have an impact on the disease process. It is known that plaque initiates periodontal disease but that the host response is responsible for the destruction of periodontal tissues. This article describes why host response modifiers may be used to help control inflammation and tissue destruction as part of the initial phase of periodontal therapy in selected patient groups.

  10. Transcriptional profiling of apple fruits in response to heat treatment: involvement of a defense response during P. expansum infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Heat treatment of harvested fruit has been demonstrated to be an effective and safe approach for managing postharvest decay. In the present study, the effect of a hot water treatment (HT) (45 degrees C for 10 minutes) on the response of apple to blue mold infection was investigated. HT was applied...

  11. Effectiveness of Antidepressants and Predictors of Treatment Response for Depressed HIV Patients in Uganda

    PubMed Central

    Ngo, Victoria K.; Wagner, Glenn J.; Nakasujja, Noeline; Dickens, Akena; Aunon, Frances; Musisi, Seggane

    2015-01-01

    Antidepressant medication is well-established for the treatment of depression, but little is known about its effectiveness for HIV populations in sub-Saharan Africa. This study examined the effectiveness of antidepressant treatment and predictors of treatment response among depressed HIV patients in Uganda. Data was obtained from two open label trials in which 184 HIV patients were diagnosed with depression and started on antidepressants. Data at treatment baseline and month 6 were compared to assess treatment response, and baseline predictors of response were assessed. 154 completed Month 6, of whom 122 (79%) had responded to treatment and were no longer depressed (Patient Health Questionnaire-9 score < 5). Bivariate analysis found that education, CD4 count, general health functioning, physical health, pain, quality of life, and social support variables were associated with antidepressant treatment response; however, only secondary education and social support independently predicted treatment response in logistic multiple regression analysis. Baseline depression severity was not associated with treatment response. In conclusion, antidepressants are effective in treating both moderate and more severe depression among persons living with HIV in Uganda, and education [O.R. (95% C.I.) = 4.33 (1.33 – 14.11)] and social support [O.R. (95% C.I.) = 1.54 (1.03 – 2.30)] were most predictive of treatment response. PMID:25525053

  12. Three cases of paraphilias responsive to fluoxetine treatment.

    PubMed

    Perilstein, R D; Lipper, S; Friedman, L J

    1991-04-01

    Three cases are presented in which fluoxetine was employed in the apparently successful treatment of paraphilia, a disorder which has been difficult to treat pharmacologically. Therapeutic benefit may have been related to the efficacy of fluoxetine in the treatment of obsessive compulsive disorders or to direct effects on sexual activity, or both.

  13. Heterogeneity Moderates Treatment Response among Patients with Binge Eating Disorder

    ERIC Educational Resources Information Center

    Sysko, Robyn; Hildebrandt, Tom; Wilson, G. Terence; Wilfley, Denise E.; Agras, W. Stewart

    2010-01-01

    Objective: The purpose of the study was to explore heterogeneity and differential treatment outcome among a sample of patients with binge eating disorder (BED). Method: A latent class analysis was conducted with 205 treatment-seeking, overweight or obese individuals with BED randomized to interpersonal psychotherapy (IPT), behavioral weight loss…

  14. Impact of Physical and Sexual Abuse on Treatment Response in the Treatment of Resistant Depression in Adolescent Study (TORDIA)

    ERIC Educational Resources Information Center

    Shamseddeen, Wael; Asarnow, Joan Rosenbaum; Clarke, Gregory; Vitiello, Benedetto; Wagner, Karen Dineen; Birmaher, Boris; Keller, Martin B.; Emslie, Graham; Iyengar, Satish; Ryan, Neal D.; McCracken, James T.; Porta, Giovanna; Mayes, Taryn; Brent, David A.

    2011-01-01

    Objective: We previously reported that a history of abuse was associated with a poorer response to combination treatment in the Treatment of Resistant Depression in Adolescents study (TORDIA). We now report on the nature and correlates of abuse that might explain these findings. Method: Youth who did not benefit from an adequate selective…

  15. Treatment-Resistant Depressed Youth Show a Higher Response Rate If Treatment Ends during Summer School Break

    ERIC Educational Resources Information Center

    Shamseddeen, Wael; Clarke, Gregory; Wagner, Karen Dineen; Ryan, Neal D.; Birmaher, Boris; Emslie, Graham; Asarnow, Joan Rosenbaum; Porta, Giovanna; Mayes, Taryn; Keller, Martin B.; Brent, David A.

    2011-01-01

    Objective: There is little work on the effect of school on response to treatment of depression, with available research suggesting that children and adolescents with school difficulties are less likely to respond to fluoxetine compared with those with no school difficulties. Method: Depressed adolescents in the Treatment of Resistant Depression in…

  16. An Evaluation of Response Cost in the Treatment of Inappropriate Vocalizations Maintained by Automatic Reinforcement

    ERIC Educational Resources Information Center

    Falcomata, Terry S.; Roane, Henry S.; Hovanetz, Alyson N.; Kettering, Tracy L.; Keeney, Kris M.

    2004-01-01

    In the current study, we examined the utility of a procedure consisting of noncontingent reinforcement with and without response cost in the treatment of inappropriate vocalizations maintained by automatic reinforcement. Results are discussed in terms of examining the variables that contribute to the effectiveness of response cost as treatment for…

  17. An evaluation of response cost in the treatment of inappropriate vocalizations maintained by automatic reinforcement.

    PubMed

    Falcomata, Terry S; Roane, Henry S; Hovanetz, Alyson N; Kettering, Tracy L; Keeney, Kris M

    2004-01-01

    In the current study, we examined the utility of a procedure consisting of noncontingent reinforcement with and without response cost in the treatment of inappropriate vocalizations maintained by automatic reinforcement. Results are discussed in terms of examining the variables that contribute to the effectiveness of response cost as treatment for problem behavior maintained by automatic reinforcement.

  18. Neural Mechanisms of Improvements in Social Motivation after Pivotal Response Treatment: Two Case Studies

    ERIC Educational Resources Information Center

    Voos, Avery C.; Pelphrey, Kevin A.; Tirrell, Jonathan; Bolling, Danielle Z.; Vander Wyk, Brent; Kaiser, Martha D.; McPartland, James C.; Volkmar, Fred R.; Ventola, Pamela

    2013-01-01

    Pivotal response treatment (PRT) is an empirically validated behavioral treatment that has widespread positive effects on communication, behavior, and social skills in young children with autism spectrum disorder (ASD). For the first time, functional magnetic resonance imaging was used to identify the neural correlates of successful response to…

  19. Rapid Response Predicts Treatment Outcomes in Binge Eating Disorder: Implications for Stepped Care

    ERIC Educational Resources Information Center

    Masheb, Robin M.; Grilo, Carlos M.

    2007-01-01

    The authors examined rapid response in 75 overweight patients with binge eating disorder (BED) who participated in a randomized clinical trial of guided self-help treatments (cognitive-behavioral therapy [CBTgsh] and behavioral weight loss [BWLgsh]). Rapid response, defined as a 65% or greater reduction in binge eating by the 4th treatment week,…

  20. Response of postharvest tree nut lepidopteran pests to vacuum treatments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Industry concerns over insect resistance, regulatory action, and the needs of organic processors have renewed interest in nonchemical alternative postharvest treatments to fumigants used for California tree nuts. The development of inexpensive polyvinyl chloride containers capable of holding low pre...

  1. Multimodal treatment of unresectable hepatocellular carcinoma to achieve complete response results in improved survival

    PubMed Central

    Newell, Pippa H; Wu, YingXing; Hoen, Helena; Uppal, Richa; Thiesing, John Tyler; Sasadeusz, Kevin; Cassera, Maria A; Wolf, Ronald F; Hansen, Paul; Hammill, Chet W

    2015-01-01

    Introduction With technological advances, questions arise regarding how to best fit newer treatment modalities, such as transarterial therapies, into the treatment algorithm for patients with hepatocellular carcinoma (HCC). Methods Between 2005 and 2011, 128 patients initially treated with transarterial radioembolization or chemoembolization using drug-eluting beads were identified. The response was graded retrospectively. Toxicity was measured 1, 3, and 6 months after the first and last treatments. Results Sixty-five patients (53%) were advanced stage. Twenty patients (16%) had an initial complete response, but with additional treatments, this was increased to 46 (36%). Patients with a complete response as their best response to treatment had a median survival [95% confidence interval (CI)] of 5.77 (2.58, upper limit not yet reached) years, significantly longer than those whose best response was a partial response, 1.22 (0.84, 2.06) years and those with stable disease as their best response, 0.34 (0.29, 0.67) years. Repeated treatments did not increase toxicity. Discussion This retrospective review of patients treated for intermediate and advanced stage HCC revealed a significant survival advantage in patients who achieved a complete response. These data support use of a multi-modality approach to intermediate and advanced stage HCC, combining liver-directed treatments as necessary to achieve a complete response. PMID:25580988

  2. Multidimensional prediction of treatment response to antidepressants with cognitive control and functional MRI.

    PubMed

    Crane, Natania A; Jenkins, Lisanne M; Bhaumik, Runa; Dion, Catherine; Gowins, Jennifer R; Mickey, Brian J; Zubieta, Jon-Kar; Langenecker, Scott A

    2017-02-01

    Predicting treatment response for major depressive disorder can provide a tremendous benefit for our overstretched health care system by reducing number of treatments and time to remission, thereby decreasing morbidity. The present study used neural and performance predictors during a cognitive control task to predict treatment response (% change in Hamilton Depression Rating Scale pre- to post-treatment). Forty-nine individuals diagnosed with major depressive disorder were enrolled with intent to treat in the open-label study; 36 completed treatment, had useable data, and were included in most data analyses. Participants included in the data analysis sample received treatment with escitalopram (n = 22) or duloxetine (n = 14) for 10 weeks. Functional MRI and performance during a Parametric Go/No-go test were used to predict per cent reduction in Hamilton Depression Rating Scale scores after treatment. Haemodynamic response function-based contrasts and task-related independent components analysis (subset of sample: n = 29) were predictors. Independent components analysis component beta weights and haemodynamic response function modelling activation during Commission errors in the rostral and dorsal anterior cingulate, mid-cingulate, dorsomedial prefrontal cortex, and lateral orbital frontal cortex predicted treatment response. In addition, more commission errors on the task predicted better treatment response. Together in a regression model, independent component analysis, haemodynamic response function-modelled, and performance measures predicted treatment response with 90% accuracy (compared to 74% accuracy with clinical features alone), with 84% accuracy in 5-fold, leave-one-out cross-validation. Convergence between performance markers and functional magnetic resonance imaging, including novel independent component analysis techniques, achieved high accuracy in prediction of treatment response for major depressive disorder. The strong link to a task paradigm

  3. Pivotal Response Treatment Parent Training for Autism: Findings from a 3-Month Follow-Up Evaluation

    ERIC Educational Resources Information Center

    Gengoux, Grace W.; Berquist, Kari L.; Salzman, Emma; Schapp, Salena; Phillips, Jennifer M.; Frazier, Thomas W.; Minjarez, Mendy B.; Hardan, Antonio Y.

    2015-01-01

    This study's objective was to assess maintenance of treatment effects 3 months after completion of a 12-week Pivotal Response Treatment (PRT) parent education group. Families who completed the active treatment (N = 23) were followed for an additional 12 weeks to measure changes in language and cognitive skills. Results indicated a significant…

  4. Life Stress and Treatment Course of Recurrent Depression: 1. Response during Index Episode.

    ERIC Educational Resources Information Center

    Monroe, Scott M.; And Others

    1992-01-01

    Conducted prospective study of 91 individuals treated for recurrent depression. Specific forms of stress occurring before treatment entry or during first 6 weeks of treatment predicted poor clinical response both after 16 weeks and after more extended intervention period. Severe stress occurring early in treatment predicted loner time to attain…

  5. Brief Parent Training in Pivotal Response Treatment for Preschoolers with Autism

    ERIC Educational Resources Information Center

    Coolican, Jamesie; Smith, Isabel M.; Bryson, Susan E.

    2010-01-01

    Background: Evidence of improved outcomes with early behavioural intervention has placed the early treatment of autism as a health priority. However, long waiting lists for treatment often preclude timely access, raising the question of whether parents could be trained in the interim. Parent training in pivotal response treatment (PRT) has been…

  6. Adolescent eating disorders: treatment and response in a naturalistic study.

    PubMed

    Thompson-Brenner, Heather; Boisseau, Christina L; Satir, Dana A

    2010-03-01

    This naturalistic study investigated the treatment and outcome of adolescents with eating disorders (EDs) in the community. Clinicians from a practice-research network provided data on ED symptoms, global functioning, comorbidity, treatment, and outcome for 120 adolescents with EDs. ED "not otherwise specified" was the most common ED diagnosed. After an average of 8 months of treatment, about one third of patients had recovered, with patients with anorexia nervosa showing the most improvement. Clinicians utilized a range of psychotherapy interventions and two thirds of the patients had received adjunct psychoactive medication. Although CBT showed the strongest association with outcome in a subsample characterized by poor relational/personality functioning, dynamic therapy was associated with better global outcome in the overall sample.

  7. Adolescent Eating Disorders: Treatment and Response in a Naturalistic Study

    PubMed Central

    Thompson-Brenner, Heather; Boisseau, Christina L.; Satir, Dana A.

    2014-01-01

    This naturalistic study investigated the treatment and outcome of adolescents with eating disorders (EDs) in the community. Clinicians from a practice-research network provided data on ED symptoms, global functioning, comorbidity, treatment, and outcome for 120 adolescents with EDs. ED “not otherwise specified” was the most common ED diagnosed. After an average of 8 months of treatment, about one third of patients had recovered, with patients with anorexia nervosa showing the most improvement. Clinicians utilized a range of psychotherapy interventions and two thirds of the patients had received adjunct psychoactive medication. Although CBT showed the strongest association with outcome in a subsample characterized by poor relational/personality functioning, dynamic therapy was associated with better global outcome in the overall sample. PMID:19938166

  8. Inflammatory response in heroin addicts undergoing methadone maintenance treatment.

    PubMed

    Chan, Yuan-Yu; Yang, Szu-Nian; Lin, Jyh-Chyang; Chang, Junn-Liang; Lin, Jaung-Geng; Lo, Wan-Yu

    2015-03-30

    Opioid addiction influences many physiological functions including reactions of the immune system. The objective of this study was to investigate the immune system function in heroin addicted patients undergoing methadone maintenance treatment (MMT) compared to healthy controls. We tested the cytokine production of IL-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α from a group of heroin addicts (n=34) and healthy controls (n=20). The results show that production of IL-1β, IL-6 and IL-8 was significantly higher in the group of methadone-maintained patients than in the healthy control group. Plasma TNF-α and IL-6 levels were significantly correlated with the dairy methadone dosage administered, and the IL-1β level was significantly correlated with the duration of methadone maintenance treatment. These findings suggest that methadone maintenance treatment influences the immune system functions of opioid-dependent patients and may also induce long-term systemic inflammation.

  9. Genetic factors affecting patient responses to pancreatic cancer treatment

    PubMed Central

    Fotopoulos, George; Syrigos, Konstantinos; Saif, Muhammad Wasif

    2016-01-01

    Cancer of the exocrine pancreas is a malignancy with a high lethal rate. Surgical resection is the only possible curative mode of treatment. Metastatic pancreatic cancer is incurable with modest results from the current treatment options. New genomic information could prove treatment efficacy. An independent review of PubMed and ScienceDirect databases was performed up to March 2016, using combinations of terms such pancreatic exocrine cancer, chemotherapy, genomic profile, pancreatic cancer pharmacogenomics, genomics, molecular pancreatic pathogenesis, and targeted therapy. Recent genetic studies have identified new markers and therapeutic targets. Our current knowledge of pancreatic cancer genetics must be further advanced to elucidate the molecular basis and pathogenesis of the disease, improve the accuracy of diagnosis, and guide tailor-made therapies. PMID:27708512

  10. Loss of Response to Melatonin Treatment Is Associated with Slow Melatonin Metabolism

    ERIC Educational Resources Information Center

    Braam, W.; van Geijlswijk, I.; Keijzer, Henry; Smits, Marcel G.; Didden, Robert; Curfs, Leopold M. G.

    2010-01-01

    Background: In some of our patients with intellectual disability (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment, while the good response returned only after considerable dose reduction. The cause for this loss of response to melatonin is yet unknown. We hypothesise that this…

  11. Perceptions of the Causes of Obesity and Responsiveness to Treatment.

    ERIC Educational Resources Information Center

    Hartigan, Kevin J.; And Others

    1982-01-01

    Examined whether obese subjects' causal attributions of their weight problems to ability, effort, task difficulty, and luck affect how much weight they lose as a function of treatment. Results indicated the most powerful predictor of positive weight status was subjects' perception that they had the ability to lose weight. (Author)

  12. Association between gene variants and response to buprenorphine maintenance treatment.

    PubMed

    Gerra, Gilberto; Somaini, Lorenzo; Leonardi, Claudio; Cortese, Elena; Maremmani, Icro; Manfredini, Matteo; Donnini, Claudia

    2014-01-30

    A variety of studies were addressed to differentiate responders and non-responders to substitution treatment among heroin dependent patients, without conclusive findings. In particular, preliminary pharmacogenetic findings have been reported to predict treatment effectiveness in mental health and substance use disorders. Aim of the present study was to investigate the possible association of buprenorphine (BUP) treatment outcome with gene variants that may affect kappa-opioid receptors and dopamine system function. One hundred and seven heroin addicts (West European, Caucasians) who underwent buprenorphine maintenance treatment were genotyped and classified into two groups (A and B) on the basis of treatment outcome. Non-responders to buprenorphine (group B) have been identified taking into account early drop out, continuous use of heroin, severe behavioral or psychiatric problems, misbehavior and diversion during the 6 months treatment period. No difference was evidenced between responders and non-responders to BUP in the frequency of kappa opioid receptor (OPRK1) 36G>T SNP. The frequency of dopamine transporter (DAT) gene polymorphism (SLC6A3/DAT1), allele 10, was evidently much higher in "non-responder" than in "responder" individuals (64.9% vs. 55.93%) whereas the frequency of the category of other alleles (6, 7 and 11) was higher in responder than in non-responder individuals (11.02% vs. 2.13% respectively). On one hand, the hypothesis that possible gene-related changes in kappa-opioid receptor could consistently affect buprenorphine pharmacological action and clinical effectiveness was not confirmed in our study, at least in relation to the single nucleotide polymorphism 36G>T. On the other hand, the possibility that gene-related dopamine changes could have reduced BUP effectiveness and impaired maintenance treatment outcome was cautiously supported by our findings. DAT1 gene variants such as allele 10, previously reported in association with personality and

  13. Neurobiology of Sleep and Sleep Treatment Response in PTSD

    DTIC Science & Technology

    2009-10-01

    nightmares, dreaming and REM sleep may provide a unique psychophvsiological milieu dur- lllg which traumatic memories can he reexperienced in the absence of...physioiogiccli arousal. This process could f,lCilitate the attenuation of emotional and physio- logical responses associated with these memories ...subserving emotional processing and integration of trauma- related memories . Specifically, it is suggested that REM sleep provides a unique

  14. Mitochondria in the striatum of subjects with schizophrenia: relationship to treatment response.

    PubMed

    Somerville, Shahza M; Lahti, Adrienne C; Conley, Robert R; Roberts, Rosalinda C

    2011-03-01

    Schizophrenia (SZ) is a severe mental illness with neuropathology in many regions, including the striatum. The typical symptoms of this disease are psychosis (such as hallucinations and delusions), cognitive impairments, and the deficit syndrome. Not all patients respond to treatment and, in those who do, only psychotic symptoms are improved. Imaging studies support a biological distinction between treatment response and resistance, but postmortem examinations of this issue are rare. This study tests the hypotheses that abnormalities in mitochondria, the energy producing organelles in the cell, may correlate with treatment response. Postmortem striatal tissue was obtained from the Maryland Brain Collection. The density of mitochondria (in various neuropil compartments) and the number of mitochondria per synapse (all types of synapses combined) were tallied using electron microscopy and stereology in striatum from SZ subjects (rated treatment responsive or not) and normal controls. The number of mitochondria per synapse was significantly different among groups for both the caudate nucleus (P < 0.025) and putamen (P < 0.002). Compared to controls, treatment-responsive SZ subjects had a 37-43% decrease in the number of mitochondria per synapse in the caudate nucleus and putamen. In the putamen, treatment-responsive subjects also had decreases in this measure compared to treatment-resistant subjects (34%). Our results provide further support for a biological distinction between treatment response and treatment resistance in SZ. Because treatment responders have fewer mitochondria per synapse than controls, although the treatment-resistant subjects have similar results to that of controls, fewer mitochondria per synapse may be related to treatment response.

  15. Treatment Response to an Intensive Summer Treatment Program for Adolescents with ADHD

    ERIC Educational Resources Information Center

    Sibley, Margaret H.; Smith, Bradley H.; Evans, Steven W.; Pelham, William E.; Gnagy, Elizabeth M.

    2012-01-01

    Objective: There are presently almost no empirically validated treatments for adolescents with ADHD. However, in childhood, behavioral treatments for ADHD typically include behavioral parent training, classroom interventions, and intensive child-directed interventions. Method: The present investigation examines treatment gains following an 8-week…

  16. Determinants of Pain Treatment Response and Non-Response: Identification of TMD Patient Subgroups

    PubMed Central

    Litt, Mark D.; Porto, Felipe B.

    2013-01-01

    The purpose of the present study was to determine if we could identify a specific subtype of temporomandibular disorder (TMD) pain patients that does not respond to treatment. Patients were 101 men and women with chronic TMD pain recruited from the community and randomly assigned to one of two treatment conditions: a standard conservative care (STD) condition or a standard care plus cognitive-behavioral treatment condition (STD+CBT) in which patients received all elements of STD, but also received cognitive-behavioral coping skills training. Growth mixture modeling, incorporating a series of treatment-related predictors, was used to distinguish several distinct classes of responders or non-responders to treatment based on reported pain over a one-year follow-up period. Results indicated that treatment non-responders accounted for 16% of the sample, and did not differ from treatment responders on demographics or temporomandibular joint pathology, but that they reported more psychiatric symptoms, poorer coping, and higher levels of catastrophizing. Treatment-related predictors of membership in treatment responder groups versus the non-responder group included the addition of CBT to standard treatment, treatment attendance, and decreasing catastrophization. It was concluded that CBT may be made more efficacious for TMD patients by placing further emphasis on decreasing catastrophization and on individualizing care. PMID:24094979

  17. White-matter connectivity related to paliperidone treatment response in patients with schizophrenia.

    PubMed

    Kim, Min-Kyoung; Kim, Borah; Lee, Kang Soo; Kim, Chan Mo; Bang, Seong Yun; Choi, Tai Kiu; Lee, Sang-Hyuk

    2016-03-01

    The objective of this study was to examine whether white-matter (WM) connectivity of patients with schizophrenia at early stage of treatment is related to treatment response after paliperidone extended-release (ER) treatment. Forty-one patients with schizophrenia and 17 age- and sex-matched healthy control subjects were included in this study. Brain magnetic resonance scans at 3 Tesla were conducted at early stage of treatment. Voxel-wise statistical analysis of the fractional anisotropy (FA) data was performed using Tract-Based Spatial Statistics. At baseline and eight weeks after paliperidone treatment, patients were assessed using the Positive and Negative Syndrome Scale, the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. Among the patients with schizophrenia, the FA values of the corpus callosum, corona radiata, internal capsule, external capsule, superior longitudinal fasciculus and fronto-temporal WM regions showed significant negative correlations with scores of the treatment response. The current study suggests that the treatment response after paliperidone ER treatment may be associated with the fronto-temporo-limbic WM connectivity at early stage of treatment in patients with schizophrenia, and it could be used as a predictor of treatment response to paliperidone ER treatment after studies with large samples verify these results.

  18. Managing inadequate responses to frontline treatment of chronic myeloid leukemia: a case-based review.

    PubMed

    Bixby, Dale L

    2013-05-01

    The tyrosine kinase inhibitors (TKIs) imatinib, nilotinib, and dasatinib are the standard of care for treating patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML). Compared with interferon-based treatment, the previous standard of care, imatinib is associated with significantly higher cytogenetic response rates and prolonged overall survival. Nilotinib and dasatinib, both newer and more potent TKIs, significantly improve cytogenetic and molecular response rates compared with imatinib. Despite significant advances in CML treatment enabled by the TKIs, a fraction of patients who receive frontline treatment with a TKI demonstrate inadequate response. The reasons for this vary, but in many cases, inadequate response can be attributed to non-adherence to the treatment regimen, intolerance to the drug, intrinsic or acquired resistance to the drug, or a combination of reasons. More often than not, strategies to improve response necessitate a change in treatment plan, either a dose adjustment or a switch to an alternate drug, particularly in the case of drug intolerance or drug resistance. Improved physician-patient communication and patient education are effective strategies to address issues relating to adherence and intolerance. Because inadequate response to TKI treatment correlates with poor long-term outcomes, it is imperative that patients who experience intolerance or who fail to achieve appropriate responses are carefully evaluated so that appropriate treatment modifications can be made to maximize the likelihood of positive long-term outcome.

  19. Significance of "Deqi" response in acupuncture treatment: myth or reality.

    PubMed

    Zhou, Wei; Benharash, Peyman

    2014-08-01

    Acupuncture has been practiced in China for over 2000 years to treat a variety of diseases based on the "meridian theory," as described in the "Yellow Emperor's Classics of Internal Medicine." Deqi refers to the excitation of qi or vital energy inside meridians by acupuncture needle stimulation. Patients often experience multidimensional and intense needling sensations such as numbness, soreness, distention, heaviness, dull pain, and sharp pain during acupuncture stimulation. Deqi is considered as an important parameter in the process of achieving therapeutic effectiveness in acupuncture treatment. Understanding this phenomenon from neurophysiological aspects is important for clinical practice and enables practitioners to perform quantitative acupuncture evaluation to obtain a reliable prognosis of acupuncture treatment. This review paper describes our current knowledge and understanding of Deqi from a physiological aspect.

  20. Parsing placebo treatments: a response to Barnhill and Miller.

    PubMed

    Glackin, Shane Nicholas

    2016-10-01

    Anne Barnhill and Franklin Miller dispute my claim that the prescriptions of placebo treatments to patients are not typically deceptive, and do not typically violate the patients' informed consent. However, Barnhill and Miller seriously mischaracterise my position in two ways, as well as failing to show that the procedure I discuss requires a physician to act wrongfully in deceiving her patient. Accordingly, I find their argument unpersuasive.

  1. Temetex in the treatment of steroid-responsive dermatoses.

    PubMed

    Bergson, V S; Franklin, W H

    1977-01-01

    Five hundred and seventy-five patients with various steroid-responsive dermatoses were studied for up to six weeks in eighty-eight separate general practices using a new topical corticosteroid. Temetex (diflucortolone valerate 0-1%). It was concluded that Temetex is both effective and well tolerated in a wide variety of conditions, especially eczema and psoriasis. It was also shown that a large-scale general practice trial can be carried out efficiently with a very high compliance rate.

  2. Temporal Treatment of a Thermal Response for Defect Depth Estimation

    NASA Technical Reports Server (NTRS)

    Plotnikov, Y. A.; Winfree, W. P.

    2004-01-01

    Transient thermography, which employs pulse surface heating of an inspected component followed by acquisition of the thermal decay stage, is gaining wider acceptance as a result of its remoteness and rapidness. Flaws in the component s material may induce a thermal contrast in surface thermograms. An important issue in transient thermography is estimating the depth of a subsurface flaw from the thermal response. This improves the quantitative ability of the thermal evaluation: from one scan it is possible to locate regions of anomalies in thickness (caused by corrosion) and estimate the implications of the flaw on the integrity of the structure. Our research focuses on thick composite aircraft components. A long square heating pulse and several minutes observation period are required to receive an adequate thermal response from such a component. Application of various time-related informative parameters of the thermal response for depth estimation is discussed. A three-dimensional finite difference model of heat propagation in solids in Cartesian coordinates is used to simulate the thermographic process. Typical physical properties of polymer graphite composites are assumed for the model.

  3. Acclimation responses of Arabidopsis thaliana to sustained phosphite treatments

    PubMed Central

    Berkowitz, Oliver

    2013-01-01

    Phosphite () induces a range of physiological and developmental responses in plants by disturbing the homeostasis of the macronutrient phosphate. Because of its close structural resemblance to phosphate, phosphite impairs the sensing, membrane transport, and subcellular compartmentation of phosphate. In addition, phosphite induces plant defence responses by an as yet unknown mode of action. In this study, the acclimation of Arabidopsis thaliana plants to a sustained phosphite supply in the growth medium was investigated and compared with plants growing under varying phosphate supplies. Unlike phosphate, phosphite did not suppress the formation of lateral roots in several Arabidopsis accessions. In addition, the expression of well-documented phosphate-starvation-induced genes, such as miRNA399d and At4, was not repressed by phosphite accumulation, whilst the induction of PHT1;1 and PAP1 was accentuated. Thus, a mimicking of phosphate by phosphite was not observed for these classical phosphate-starvation responses. Metabolomic analysis of phosphite-treated plants showed changes in several metabolite pools, most prominently those of aspartate, asparagine, glutamate, and serine. These alterations in amino acid pools provide novel insights for the understanding of phosphite-induced pathogen resistance. PMID:23404904

  4. Atypical depressive symptoms as a predictor of treatment response to exercise in Major Depressive Disorder.

    PubMed

    Rethorst, Chad D; Tu, Jian; Carmody, Thomas J; Greer, Tracy L; Trivedi, Madhukar H

    2016-08-01

    Effective treatment of Major Depressive Disorder (MDD) will require the development of alternative treatments and the ability for clinicians to match patients with the treatment likely to produce the greatest effect. We examined atypical depression subtype as a predictor of treatment response to aerobic exercise augmentation in persons with non-remitted MDD. Our results revealed a small-to-moderate effect, particularly in a group assigned to high-dose exercise (semi-partial eta-squared =0.0335, p=0.0735), indicating that those with atypical depression tended to have larger treatment response to exercise. Through this hypothesis-generating analysis, we indicate the need for research to examine depression subtype, along with other demographic, clinical and biological factors as predictors of treatment response to exercise.

  5. Drinking water treatment response following a Colorado wildfire.

    PubMed

    Hohner, Amanda K; Cawley, Kaelin; Oropeza, Jill; Summers, R Scott; Rosario-Ortiz, Fernando L

    2016-11-15

    Wildfires can greatly alter the vegetation, soils, and hydrologic processes of watersheds serving as drinking water supplies, which may negatively influence source water quality and treatment. To address wildfire impacts on treatment, a drinking water intake below a burned watershed and an upstream, unburned reference site were monitored following the High Park wildfire (2012) in the Cache la Poudre watershed of northern Colorado, USA. Turbidity, nutrients, dissolved organic matter (DOM) character, coagulation treatability, and disinfection byproduct formation were evaluated and compared to pre-fire data. Post-fire paired spatial differences between the treatment plant intake and reference site for turbidity, nitrogen, and phosphorus increased by an order of magnitude compared to pre-fire differences. Fluorescence index (FI) values were significantly higher at the intake compared to the reference site (Δ = 0.04), and higher than pre-fire years, suggesting the wildfire altered the DOM character of the river. Total trihalomethane (TTHM) and haloacetonitrile (HAN4) formation at the intake were 10.1 μg L(-1) and 0.91 μg L(-1) higher than the reference site. Post-fire water was amenable to conventional treatment at a 10 mg L(-1) higher average alum dose than reference samples. The intake was also monitored following rainstorms. Post-rainstorm samples showed the maximum observed FI values (1.52), HAN4 (3.4 μg mgC(-1)) and chloropicrin formation yields (3.6 μg mgC(-1)), whereas TTHM and haloacetic acid yields were not elevated. Several post-rainstorm samples presented treatment challenges, and even at high alum doses (65 mg L(-1)), showed minimal dissolved organic carbon removal (<10%). The degraded water quality of the post-rainstorm samples is likely attributed to the combined effects of runoff from precipitation and greater erosion following wildfire. Wildfire impacts cannot be separated from rainfall effects due to the lack of post-rainstorm samples from

  6. Stereotactic body radiation therapy of liver tumors: post-treatment appearances and evaluation of treatment response: a pictorial review.

    PubMed

    Haddad, Mustafa M; Merrell, Kenneth W; Hallemeier, Christopher L; Johnson, Geoffrey B; Mounajjed, Taofic; Olivier, Kenneth R; Fidler, Jeff L; Venkatesh, Sudhakar K

    2016-10-01

    Stereotactic body radiation therapy (SBRT) is a noninvasive treatment technique for selected patients with primary liver tumors and liver-confined oligometastatic disease. Recently, SBRT has emerged as an alternative treatment option in non-surgical candidates and in whom percutaneous treatment methods are not possible or contraindicated. The experience with SBRT continues to grow. There are currently no imaging guidelines for assessment of tumor response and follow-up schedule following SBRT. SBRT produces characteristic radiation-induced changes in the treated tumor and surrounding liver parenchyma. Knowledge of these changes is essential in the interpretation of follow-up imaging and assessment of treatment response. In this review, we will describe the CT, MRI, and PET imaging findings following SBRT of both the targeted liver tumor and surrounding hepatic parenchyma.

  7. Dispositional optimism, trait anxiety, and coping: unique or shared effects on biological response to fertility treatment?

    PubMed

    Lancastle, Deborah; Boivin, Jacky

    2005-03-01

    The aim of this study was to examine the unique and shared predictive power of psychological variables on reproductive physical health. Three months before fertility treatment, 97 women completed measures of dispositional optimism, trait anxiety, and coping. Information about biological response to treatment (e.g., estradiol level) was collected from medical charts after treatment. Structural equation modeling showed that measured psychological variables were all significant indicators of a single latent construct and that this construct was a better predictor of biological response to treatment than was any individual predictor. This research contributes to evidence suggesting that the health benefits of dispositional optimism are due to its shared variance with neuroticism.

  8. Acute promyelocytic leukemia: new issues on pathogenesis and treatment response.

    PubMed

    Vitoux, Dominique; Nasr, Rihab; de The, Hugues

    2007-01-01

    Pathogenesis of acute promyelocytic leukemia appears to be one of the best understood among human malignancies. The ability of retinoic acid (RA) and arsenic trioxide to directly target the oncogenic promyelocytic leukemia-retinoic receptor A (PML-RARA) fusion protein also made this disease the first model for oncogene-targeted therapies. A set of recent data has significantly increased the complexity of our view of acute promyelocytic leukemia pathogenesis, as well as of therapeutic response. This review summarizes and discusses these findings, which yield novels questions and models.

  9. Wood preserving waste-contaminated soil: Treatment and toxicity response

    SciTech Connect

    Huling, S.G.; Pope, D.F.; Matthews, J.E.; Sims, J.L.; Sims, R.C.; Sorensen, D.L.

    1995-12-31

    Soils contaminated with pentachlorophenol (PCP) and creosote were treated without bioaugmentation at field scale in tow 1-acre land treatment units (LTUs) at Libby, Montana. The concentration of indicator compounds of treatment performance, i.e., PCP, pyrene, total carcinogenic polycyclic aromatic hydrocarbons (TCPAHs) were monitored in the soil by taking both composited and discrete soil samples. A statistically significant decrease in PCP, pyrene, and TCPAH concentration occurred at field scale, and first-order degradation rate kinetics, from discrete and composited soil samples, satisfactorily represented the chemical loss for these compounds. Detoxification, as measured by the Microtox{trademark} assay, occurred in the soil; and toxicity reduction corresponded with PCP, pyrene, and TCPAH disappearance. No increase in toxicity in the lower treated soil layers (lifts) of the LTUs was observed with time, while the upper, more recently applied lifts were highly contaminated and toxic. This indicated that vertical migration of soluble contaminants had little effect on microbial activity in lower lifts of treated soil.

  10. A thermo-responsive protein treatment for dry eyes

    PubMed Central

    Wang, Wan; Jashnani, Aarti; Aluri, Suhaas R.; Gustafson, Joshua A.; Hsueh, Pang-Yu; Yarber, Frances; McKown, Robert L.; Laurie, Gordon W.; Hamm-Alvarez, Sarah F.; MacKay, J. Andrew

    2015-01-01

    Millions of Americans suffer from dry eye disease, and there are few effective therapies capable of treating these patients. A decade ago, an abundant protein component of human tears was discovered and named lacritin(Lacrt). Lacrt has prosecretory activity in the lacrimal gland and mitogenic activity at the corneal epithelium. Similar to other proteins placed on the ocular surface, the durability of its effect is limited by rapid tear turnover. Motivated by the rationale that a thermo-responsive coacervate containing Lacrt would have better retention upon administration, we have constructed and tested the activity of a thermo-responsive Lacrt fused to an Elastin-like polypeptide (ELP). Inspired from the human tropoelastin protein, ELP protein polymers reversibly phase separate into viscous coacervates above a tunable transition temperature. This fusion construct exhibited the prosecretory function of native Lacrt as illustrated by its ability to stimulate β-hexosaminidase secretion from primary rabbit lacrimal gland acinar cells. It also increased tear secretion from non-obese diabetic (NOD) mice, a model of autoimmune dacryoadenitis, when administered via intra-lacrimal injection. Lacrt ELP fusion proteins undergo temperature-mediated assembly to form a depot inside the lacrimal gland. We propose that these Lacrt ELP fusion proteins represent a potential therapy for dry eye disease and the strategy of ELP-mediated phase separation may have applicability to other diseases of the ocular surface. PMID:25481446

  11. Upper esophageal sphincter abnormalities are strongly predictive of treatment response in patients with achalasia

    PubMed Central

    Mathews, Simon C; Ciarleglio, Maria; Chavez, Yamile Haito; Clarke, John O; Stein, Ellen; Chander Roland, Bani

    2014-01-01

    AIM: To investigate the relationship between upper esophageal sphincter abnormalities achalasia treatment METHODS: We performed a retrospective study of 41 consecutive patients referred for high resolution esophageal manometry with a final manometric diagnosis of achalasia. Patients were sub-divided by presence or absence of Upper esophageal sphincter (UES) abnormality, and clinical and manometric profiles were compared. Correlation between UES abnormality and sub-type (i.e., hypertensive, hypotensive or impaired relaxation) and a number of variables, including qualitative treatment response, achalasia sub-type, co-morbid medical illness, psychiatric illness, surgical history, dominant presenting symptom, treatment type, age and gender were also evaluated. RESULTS: Among all 41 patients, 24 (58.54%) had a UES abnormality present. There were no significant differences between the groups in terms of age, gender or any other clinical or demographic profiles. Among those with UES abnormalities, the majority were either hypertensive (41.67%) or had impaired relaxation (37.5%) as compared to hypotensive (20.83%), although this did not reach statistical significance (P = 0.42). There was no specific association between treatment response and treatment type received; however, there was a significant association between UES abnormalities and treatment response. In patients with achalasia and concomitant UES abnormalities, 87.5% had poor treatment response, while only 12.5% had favorable response. In contrast, in patients with achalasia and no UES abnormalities, the majority (78.57%) had good treatment response, as compared to 21.43% with poor treatment response (P = 0.0001). After controlling for achalasia sub-type, those with UES abnormality had 26 times greater odds of poor treatment response than those with no UES abnormality (P = 0.009). Similarly, after controlling for treatment type, those with UES abnormality had 13.9 times greater odds of poor treatment response

  12. Clinical utility of C-reactive protein to predict treatment response during cystic fibrosis pulmonary exacerbations

    PubMed Central

    Sharma, Ashutosh; Kirkpatrick, Gordon; Chen, Virginia; Skolnik, Kate; Hollander, Zsuzsanna; Wilcox, Pearce; Quon, Bradley S.

    2017-01-01

    Rationale C-reactive protein (CRP) is a systemic marker of inflammation that correlates with disease status in cystic fibrosis (CF). The clinical utility of CRP measurement to guide pulmonary exacerbation (PEx) treatment decisions remains uncertain. Objectives To determine whether monitoring CRP during PEx treatment can be used to predict treatment response. We hypothesized that early changes in CRP can be used to predict treatment response. Methods We reviewed all PEx events requiring hospitalization for intravenous (IV) antibiotics over 2 years at our institution. 83 PEx events met our eligibility criteria. CRP levels from admission to day 5 were evaluated to predict treatment non-response, using a modified version of a prior published composite definition. CRP was also evaluated to predict time until next exacerbation (TUNE). Measurements and main results 53% of 83 PEx events were classified as treatment non-response. Paradoxically, 24% of PEx events were characterized by a ≥ 50% increase in CRP levels within the first five days of treatment. Absolute change in CRP from admission to day 5 was not associated with treatment non-response (p = 0.58). Adjusted for FEV1% predicted, admission log10 CRP was associated with treatment non-response (OR: 2.39; 95% CI: 1.14 to 5.91; p = 0.03) and shorter TUNE (HR: 1.60; 95% CI: 1.13 to 2.27; p = 0.008). The area under the receiver operating characteristics (ROC) curve of admission CRP to predict treatment non-response was 0.72 (95% CI 0.61–0.83; p<0.001). 23% of PEx events were characterized by an admission CRP of > 75 mg/L with a specificity of 90% for treatment non-response. Conclusions Admission CRP predicts treatment non-response and time until next exacerbation. A very elevated admission CRP (>75mg/L) is highly specific for treatment non-response and might be used to target high-risk patients for future interventional studies aimed at improving exacerbation outcomes. PMID:28178305

  13. Interpersonal impacts mediate the association between personality and treatment response in major depression.

    PubMed

    Dermody, Sarah S; Quilty, Lena C; Bagby, R Michael

    2016-07-01

    Personality, as characterized by the Five-Factor Model, predicts response to psychotherapy for depression. To explain how personality impacts treatment response, the present study investigated patient and therapist interpersonal processes in treatment sessions as an explanatory pathway. A clinical trial was conducted in which 103 outpatients (mean age: 41.17 years, 65% female) with primary major depressive disorder completed 16-20 weeks of cognitive-behavioral or interpersonal therapy. Before treatment, patients completed the Revised NEO Personality Inventory to assess personality domains (neuroticism, extraversion, openness-to-experience, agreeableness, and conscientiousness). After 3 and 13 weeks, patient interpersonal behavior was rated by the therapist and vice versa to determine levels of patient and therapist communal and agentic behaviors. Depression levels were measured before and after treatment. Structural equation modeling supported that patients' interpersonal behavior during therapy mediated the associations between pretreatment personality and depression treatment outcome. Specifically, extraversion, conscientiousness, and neuroticism (inverse) predicted higher levels of patient communion throughout treatment, which was in turn associated with improved treatment outcomes. Furthermore, patient agreeableness was inversely associated with agency throughout treatment, which was linked to poorer treatment response. Therapist interpersonal behavior was not a significant mediator. Results suggest that patient interpersonal behavior during treatment may be one way that patient personality impacts clinical outcomes in depression. Results underscore the clinical utility of Five-Factor Model domains in treatment process and outcome. (PsycINFO Database Record

  14. Peer-Nominated Deviant Talk within Residential Treatment: Individual and Group Influences on Treatment Response

    ERIC Educational Resources Information Center

    Zakriski, Audrey L.; Wright, Jack C.; Cardoos, Stephanie L.

    2011-01-01

    This research examined deviant talk during summer residential treatment using peer nominations and extensive field observations. Participants were 239 youth (M age = 12.62, SD = 2.60; 67% male), nested in 26 treatment groups. Deviant talk was present in this setting, showed individual differences, and increased over time, especially for younger…

  15. Treatment responsive Holmes tremor: case report and literature review

    PubMed Central

    Alqwaifly, Mohammed

    2016-01-01

    Holmes tremor is a rare symptomatic movement disorder, characterized by a combination of resting, postural, and action tremors. It is usually caused by lesions involving the brainstem, thalamus, and cerebellum. It is often difficult to treat, many medications have been used with varying degrees of success. It may respond to stereotactic thalamotomy and deep brain stimulation in ventralis intermedius nucleus. Here I report a case of Holmes tremor secondary to multiple sclerosis that treated with L-dopa/carpidopa and showed marked improvement. A relevant literature search was performed, using PubMed for Holmes tremor as labelled in the literature. I included all patients diagnosed with Holmes tremor who responded to medical treatment. I found 27 cases, which are summarized in this review. This report describes a patient with Holmes tremor, who responded very well to Levodopa. This outcome suggests that Levodopa should be considered in the initial management of Holmes tremor. PMID:27833521

  16. Novel Approaches to Thyroid Cancer Treatment and Response Assessment

    PubMed Central

    Grewal, Ravinder K.; Ho, Alan; Schöder, Heiko

    2015-01-01

    The incidence of thyroid cancer has been on the rise. After total thyroidectomy of well differentiated thyroid tumors with intermediate or high-risk features on pathology, radioiodine remains one of the mainstays as the standard therapy for thyroid remnant ablation as well as treatment of metastatic disease. SPECT/CT, a relatively newer modality, has shown to play a pivotal role predominantly in the post-therapy setting by changing the risk stratification of patients with thyroid cancer. In the case of radioiodine failure, other modalities such as FDG PET/CT have been shown to provide prognostic information in terms of metabolic activity and external beam radiation therapy, thereby playing a role in disease management. The role of newer redifferentiation drugs has been evaluated with the use of I-124 PET/CT. PMID:26897715

  17. Subjective response as a consideration in the pharmacogenetics of alcoholism treatment.

    PubMed

    Roche, Daniel Jo; Ray, Lara A

    2015-01-01

    Currently available pharmacological treatments for alcoholism have modest efficacy and high individual variability in treatment outcomes, both of which have been partially attributed to genetic factors. One path to reducing the variability and improving the efficacy associated with these pharmacotherapies may be to identify overlapping genetic contributions to individual differences in both subjective responses to alcohol and alcoholism pharmacotherapy outcomes. As acute subjective response to alcohol is highly predictive of future alcohol related problems, identifying such shared genetic mechanisms may inform the development of personalized treatments that can effectively target converging pathophysiological mechanisms that convey risk for alcoholism. The focus of this review is to revisit the association between subjective response to alcohol and the etiology of alcoholism while also describing genetic contributions to this relationship, discuss potential pharmacogenetic approaches to target subjective response to alcohol in order to improve the treatment of alcoholism and examine conceptual and methodological issues associated with these topics, and outline future approaches to overcome these challenges.

  18. Response to Stimulant Drug Treatment in Hyperactive Children: Prediction from EEG and Neurological Findings

    ERIC Educational Resources Information Center

    Satterfield, James H.; And Others

    1973-01-01

    A study of neurological examinations, electroencephalographic findings, and behavioral responses to methylphenidate treatment in 57 hyperactive boys, 5 to 10 years of age, is reported and discussed. (Author/MC)

  19. Do Processing Patterns of Strengths and Weaknesses Predict Differential Treatment Response?

    ERIC Educational Resources Information Center

    Miciak, Jeremy; Williams, Jacob L.; Taylor, W. Pat; Cirino, Paul T.; Fletcher, Jack M.; Vaughn, Sharon

    2016-01-01

    No previous empirical study has investigated whether the learning disabilities (LD) identification decisions of proposed methods to operationalize processing strengths and weaknesses approaches for LD identification are associated with differential treatment response. We investigated whether the identification decisions of the…

  20. Site-Specific Seismic Site Response Model for the Waste Treatment Plant, Hanford, Washington

    SciTech Connect

    Rohay, Alan C.; Reidel, Steve P.

    2005-02-24

    This interim report documents the collection of site-specific geologic and geophysical data characterizing the Waste Treatment Plant site and the modeling of the site-specific structure response to earthquake ground motions.

  1. MicroRNAs as putative mediators of treatment response in prostate cancer.

    PubMed

    O'Kelly, Fardod; Marignol, Laure; Meunier, Armelle; Lynch, Thomas H; Perry, Antoinette S; Hollywood, Donal

    2012-05-22

    MicroRNAs (miRNAs) are an abundant class of noncoding RNAs that function to regulate post-transcriptional gene expression, predominantly by translational repression. In addition to their role in prostate cancer initiation and progression, recent evidence suggests that miRNAs might also participate in treatment response across a range of therapies including radiation treatment, chemotherapy and androgen suppression. The mechanism of this regulation is thought to be multifactorial and is currently poorly understood. To date, only a small number of studies have examined the functional role of miRNAs in response to prostate cancer treatment. Elucidating the role of miRNAs in treatment response following radiotherapy, chemotherapy and androgen suppression will provide new avenues of investigation for the development of novel therapies for the treatment of prostate cancer.

  2. The role of p53 in treatment responses of lung cancer

    SciTech Connect

    Viktorsson, Kristina; Lewensohn, Rolf . E-mail: Rolf.Lewensohn@cck.ki.se

    2005-06-10

    Resistance to radio- and chemotherapy is a major problem in treatment responses of lung cancer. In this disease, biological markers, that can be predictive of response to treatment for guiding clinical practice, still need to be validated. Radiotherapy and most chemotherapeutic agents directly target DNA and in response to such therapies, p53 functions as a coordinator of the DNA repair process, cell cycle arrest, and apoptosis. In fact, it participates in the main DNA repair systems operative in cells, including NHEJ, HRR, NER, BER, and MMR. Given the high p53 mutation frequency in lung cancer which likely impairs some of the p53-mediated functions, a role of p53 as a predictive marker for treatment responses has been suggested. In this review, we summarize the conflicting results coming from preclinical and clinical studies on the role of p53 as a predictive marker of responses to chemotherapy or radiotherapy in lung cancer.

  3. Using biomarkers to predict treatment response in major depressive disorder: evidence from past and present studies.

    PubMed

    Thase, Michael E

    2014-12-01

    Major depressive disorder (MDD) is a heterogeneous condition with a variable response to a wide range of treatments. Despite intensive efforts, no biomarker has been identified to date that can reliably predict response or non-response to any form of treatment, nor has one been identified that can be used to identify those at high risk of developing treatment-resistant depression (ie, non-response to a sequence of treatments delivered for adequate duration and intensity). This manuscript reviews some past areas of research that have proved informative, such as studies using indexes of hypercortisolism or sleep disturbance, and more recent research findings using measures of inflammation and different indicators of regional cortical activation to predict treatment response. It is concluded that, although no method has yet been demonstrated to be sufficiently accurate to be applied in clinical practice, progress has been made. It thus seems likely that--at some point in the not-too-distant future--it will be possible to prospectively identify, at least for some MDD patients, the likelihood of response or non-response to cognitive therapy or various antidepressant medications.

  4. Evaluating and monitoring treatment response in depression using measurement-based assessment and rating scales.

    PubMed

    Trivedi, Madhukar H

    2013-07-01

    Even with many treatment options available for major depressive disorder, many patients fail to achieve remission and return to their presymptomatic levels of functioning at work, in leisure activities, and in relationships. Throughout treatment, clinicians should implement measurement-based care by systematically monitoring patients' response using self-rated scales, such as the PHQ-9, QIDS-SR, or BDI. By tracking depressive symptoms, as well as suicidality, treatment adherence, and side effects, clinicians can adjust treatment to help patients achieve the best outcomes. Measurement-based care enables clinicians to make informed decisions at critical points throughout the treatment process and to involve patients in making those decisions.

  5. Impact of Physical and Sexual Abuse on Treatment Response in the Treatment of Resistant Depression in Adolescent Study (TORDIA)

    PubMed Central

    Shamseddeen, Wael; Asarnow, Joan Rosenbaum; Clarke, Gregory; Vitiello, Benedetto; Wagner, Karen Dineen; Birmaher, Boris; Keller, Martin B.; Emslie, Graham; Iyengar, Satish; Ryan, Neal D.; McCracken, James T.; Porta, Giovanna; Mayes, Taryn; Brent, David A.

    2010-01-01

    Objective We previously reported that a history of abuse was associated with a poorer response to combination treatment in the Treatment of Resistant Depression in Adolescents study (TORDIA). We now report on the nature and correlates of abuse that might explain these findings. Method Youth who did not benefit from an adequate selective serotonin re-uptake inhibitor (SSRI) trial (N=334) were randomized to: an alternative SSRI; an alternative SSRI plus cognitive behavior therapy (CBT); venlafaxine; or venlafaxine plus CBT. Analyses examined the effect of history of abuse on response to the pharmacotherapy and combination therapy. Results Those without a history of physical abuse (PA) or sexual abuse (SA) had a higher 12-week response rate to combination therapy compared to medication mono-therapy (62.8% vs. 37.6%; OR=2.8, 95% CI: 1.6–4.7, p<0.001). Those with a history of SA had similar response rates to combination vs. medication monotherapy (48.3% vs. 42.3%; OR=1.3, 95% CI: 0.4–3.7; p=0.66), while those with history of PA had a much lower rate of response to combination therapy (18.4% vs. 52.4%, OR=0.1; 95% CI: 0.02–0.43). Even after adjusting for other clinical predictors, a history of PA moderated treatment outcome. Conclusion These results should be considered within the limitations of a post-hoc analysis, lack of detailed assessment of abuse and other forms of trauma, and neuropsychological status. Depressed patients with history of abuse, especially PA may require specialized clinical approaches. Further work is needed to understand by what mechanisms a history of abuse affects treatment response. PMID:21334569

  6. Validation of functional imaging as a biomarker for radiation treatment response.

    PubMed

    Jentsch, C; Beuthien-Baumann, B; Troost, E G C; Shakirin, G

    2015-07-01

    Major advances in radiotherapy techniques, increasing knowledge of tumour biology and the ability to translate these advances into new therapeutic approaches are important goals towards more individualized cancer treatment. With the development of non-invasive functional and molecular imaging techniques such as positron emission tomography (PET)-CT scanning and MRI, there is now a need to evaluate potential new biomarkers for tumour response prediction, for treatment individualization is not only based on morphological criteria but also on biological tumour characteristics. The goal of individualization of radiotherapy is to improve treatment outcome and potentially reduce chronic treatment toxicity. This review gives an overview of the molecular and functional imaging modalities of tumour hypoxia and tumour cell metabolism, proliferation and perfusion as predictive biomarkers for radiation treatment response in head and neck tumours and in lung tumours. The current status of knowledge on integration of PET/CT/MRI into treatment management and bioimage-guided adaptive radiotherapy are discussed.

  7. Inmate responses to prison-based drug treatment: a repeated measures analysis.

    PubMed

    Welsh, Wayne N

    2010-06-01

    Using a sample of 347 prison inmates and general linear modeling (GLM) repeated measures analyses, this paper examined during-treatment responses (e.g., changes in psychological and social functioning) to prison-based TC drug treatment. These effects have rarely been examined in previous studies, and never with a fully multivariate model accounting for within-subjects effects (changes over time), between-subjects effects (e.g., levels of risk and motivation), and within/between-subjects interactions (timexriskxmotivation). The results provide evidence of positive inmate change in response to prison TC treatment, but the patterns of results varied depending upon: (a) specific indicators of psychological and social functioning, motivation, and treatment process; (b) the time periods examined (1, 6, and 12 months during treatment); and (c) baseline levels of risk and motivation. Significant interactions between time and type of inmate suggest important new directions for research, theory, and practice in offender-based substance abuse treatment.

  8. Diagnosis of response and non-response to dry eye treatment using infrared thermography images

    NASA Astrophysics Data System (ADS)

    Acharya, U. Rajendra; Tan, Jen Hong; Vidya, S.; Yeo, Sharon; Too, Cheah Loon; Lim, Wei Jie Eugene; Chua, Kuang Chua; Tong, Louis

    2014-11-01

    The dry eye treatment outcome depends on the assessment of clinical relevance of the treatment effect. The potential approach to assess the clinical relevance of the treatment is to identify the symptoms responders and non-responders to the given treatments using the responder analysis. In our work, we have performed the responder analysis to assess the clinical relevance effect of the dry eye treatments namely, hot towel, EyeGiene®, and Blephasteam® twice daily and 12 min session of Lipiflow®. Thermography is performed at week 0 (baseline), at weeks 4 and 12 after treatment. The clinical parameters such as, change in the clinical irritations scores, tear break up time (TBUT), corneal staining and Schirmer's symptoms tests values are used to obtain the responders and non-responders groups. We have obtained the infrared thermography images of dry eye symptoms responders and non-responders to the three types of warming treatments. The energy, kurtosis, skewness, mean, standard deviation, and various entropies namely Shannon, Renyi and Kapoor are extracted from responders and non-responders thermograms. The extracted features are ranked based on t-values. These ranked features are fed to the various classifiers to get the highest performance using minimum features. We have used decision tree (DT), K nearest neighbour (KNN), Naves Bayesian (NB) and support vector machine (SVM) to classify the features into responder and non-responder classes. We have obtained an average accuracy of 99.88%, sensitivity of 99.7% and specificity of 100% using KNN classifier using ten-fold cross validation.

  9. Examining Heterogeneity in Residual Variance to Detect Differential Response to Treatments

    ERIC Educational Resources Information Center

    Kim, Jinok; Seltzer, Michael

    2011-01-01

    Individual differences in response to treatments have been a long-standing interest in education, psychology, and related fields. This article presents a conceptual framework and hierarchical modeling strategies that may help identify the subgroups for whom, or the conditions under which, a particular treatment is associated with better outcomes.…

  10. Large Scale Dissemination and Community Implementation of Pivotal Response Treatment: Program Description and Preliminary Data

    ERIC Educational Resources Information Center

    Bryson, Susan E.; Koegel, Lynn K.; Koegel, Robert L.; Openden, Daniel; Smith, Isabel M.; Nefdt, Nicolette

    2007-01-01

    This paper describes a collaborative effort aimed at province-wide dissemination and implementation of pivotal response treatment (PRT) for young children with autism spectrum disorder (ASD) in Nova Scotia, Canada. Three critical components of the associated training model are described: (1) direct training of treatment teams (parents, one-to-one…

  11. The PRT Pocket Guide: Pivotal Response Treatment for Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Koegel, Robert L.; Koegel, Lynn Kern

    2012-01-01

    What is Pivotal Response Treatment? What's the research behind it, what does it look like in practice, and what are some good examples of how to use it? Now one concise book gives professionals and parents all the basics of the widely used PRT--one of a select group of highly effective, evidence-based treatments for autism. great resource for…

  12. Treatment Response in CP/ADHD Children with Callous/Unemotional Traits

    ERIC Educational Resources Information Center

    Haas, Sarah M.; Waschbusch, Daniel A.; Pelham, William E.; King, Sara; Andrade, Brendan F.; Carrey, Normand J.

    2011-01-01

    The current study examines the role of callous/unemotional (CU) traits in response to treatment among children with conduct problems (CP) and attention-deficit/hyperactivity disorder (ADHD). Fifty-four children with CP/ADHD and 16 controls (age = 9.48, SD = 1.58) took part in a summer treatment and research program. Simple correlations showed that…

  13. Childhood Maltreatment and Differential Treatment Response and Recurrence in Adult Major Depressive Disorder

    ERIC Educational Resources Information Center

    Harkness, Kate L.; Bagby, R. Michael; Kennedy, Sidney H.

    2012-01-01

    Objective: A substantial number of patients with major depressive disorder (MDD) do not respond to treatment, and recurrence rates remain high. The purpose of this study was to examine a history of severe childhood abuse as a moderator of response following a 16-week acute treatment trial, and of recurrence over a 12-month follow-up. Method:…

  14. Thermal treatment for increasing magnetostrictive response of rare earth-iron alloy rods

    DOEpatents

    Verhoeven, John D.; McMasters, O. D.

    1989-07-18

    Magnetostrictive rods formed from rare earth-iron alloys are subjected to a short time heat treatment to increase their Magnetostrictive response under compression. The heat treatment is preferably carried out at a temperature of from 900.degree. to 1000.degree. C. for 20 minutes to six hours.

  15. Thermal treatment for increasing magnetostrictive response of rare earth-iron alloy rods

    DOEpatents

    Verhoeven, J.D.; McMasters, O.D.

    1989-07-18

    Magnetostrictive rods formed from rare earth-iron alloys are subjected to a short time heat treatment to increase their magnetostrictive response under compression. The heat treatment is preferably carried out at a temperature of from 900 to 1,000 C for 20 minutes to six hours.

  16. Effectiveness of Community-Based Early Intervention Based on Pivotal Response Treatment

    ERIC Educational Resources Information Center

    Smith, Isabel M.; Flanagan, Helen E.; Garon, Nancy; Bryson, Susan E.

    2015-01-01

    Preschoolers (n = 118) with autism spectrum disorder (ASD) participated in this prospective effectiveness study of an early intervention program. Treatment entailed parent training and therapist-implemented components, incorporating Pivotal Response Treatment and Positive Behaviour Support. Standardized ability and behavioural measures were…

  17. Brief Report: Reduced Restricted and Repetitive Behaviors after Pivotal Response Treatment

    ERIC Educational Resources Information Center

    Ventola, Pamela E.; Yang, Daniel; Abdullahi, Sebiha M.; Paisley, Courtney A.; Braconnier, Megan L.; Sukhodolsky, Denis G.

    2016-01-01

    Children with ASD show high frequency of restricted and repetitive behaviors (RRBs); however, higher-order RRBs, such as restricted interests, have remained largely resistant to treatment. This study evaluated change in severity of RRBs following a 16-weeks open trial of Pivotal Response Treatment (PRT). Participants included 15 children with ASD…

  18. Predicting Response of ADHD Symptoms to Methylphenidate Treatment Based on Comorbid Anxiety

    ERIC Educational Resources Information Center

    Blouin, Brittany; Maddeaux, Cindy; Stanley Firestone, Jill; van Stralen, Judy

    2010-01-01

    Objective: In this small pilot study, the association of comorbid anxiety with the treatment of ADHD is studied. Methods: Eighteen volunteers from a pediatric clinic are tested for ADHD and anxiety and assessed for behavioral and cognitive ADHD symptomology. Response to methylphenidate as treatment for ADHD symptoms is measured 2 to 3 weeks, and…

  19. Empirically and Clinically Useful Decision Making in Psychotherapy: Differential Predictions with Treatment Response Models

    ERIC Educational Resources Information Center

    Lutz, Wolfgang; Saunders, Stephen M.; Leon, Scott C.; Martinovich, Zoran; Kosfelder, Joachim; Schulte, Dietmar; Grawe, Klaus; Tholen, Sven

    2006-01-01

    In the delivery of clinical services, outcomes monitoring (i.e., repeated assessments of a patient's response to treatment) can be used to support clinical decision making (i.e., recurrent revisions of outcome expectations on the basis of that response). Outcomes monitoring can be particularly useful in the context of established practice research…

  20. Prediction of Response to Medication and Cognitive Therapy in the Treatment of Moderate to Severe Depression

    ERIC Educational Resources Information Center

    Fournier, Jay C.; DeRubeis, Robert J.; Shelton, Richard C.; Hollon, Steven D.; Amsterdam, Jay D.; Gallop, Robert

    2009-01-01

    A recent randomized controlled trial found nearly equivalent response rates for antidepressant medications and cognitive therapy in a sample of moderate to severely depressed outpatients. In this article, the authors seek to identify the variables that were associated with response across both treatments as well as variables that predicted…

  1. Placebo response in the treatment of women's sexual dysfunctions: a review and commentary.

    PubMed

    Bradford, Andrea; Meston, Cindy M

    2009-01-01

    We reviewed the literature to determine the nature and magnitude of therapeutic response associated with placebo treatment in clinical trials for women's sexual dysfunction. We abstracted data from 16 articles to record the effect size associated with placebo treatment. In most of these studies, placebo recipients reported statistically significant improvements on one or more major endpoints relative to baseline. Although placebo responses varied across study populations and methodologies, within-group effect sizes were predominantly in the moderate range. Our findings suggest that post-menopausal women and women with hypoactive sexual desire disorder may be more likely to respond to placebo treatment.

  2. Prognostic factors versus markers of response to treatment versus surrogate endpoints: Three different concepts.

    PubMed

    Sormani, Maria Pia

    2017-03-01

    Multiple sclerosis is a highly heterogeneous disease; the quantitative assessment of disease progression is problematic for many reasons, including the lack of objective methods to measure disability and the long follow-up times needed to detect relevant and stable changes. For these reasons, the importance of prognostic markers, markers of response to treatments and of surrogate endpoints, is crucial in multiple sclerosis research. Aim of this report is to clarify some basic definitions and methodological issues about baseline factors to be considered prognostic markers or markers of response to treatment; to define the dynamic role that variables must have to be considered surrogate markers in relation to specific treatments.

  3. ¹⁸F-FDG PET/CT for Monitoring of Treatment Response in Breast Cancer.

    PubMed

    Avril, Stefanie; Muzic, Raymond F; Plecha, Donna; Traughber, Bryan J; Vinayak, Shaveta; Avril, Norbert

    2016-02-01

    Changes in tumor metabolic activity have been shown to be an early indicator of treatment effectiveness for breast cancer, mainly in the neoadjuvant setting. The histopathologic response at the completion of chemotherapy has been used as the reference standard for assessment of the accuracy of (18)F-FDG PET in predicting a response during systemic treatment. Although a pathologic complete response (pCR) remains an important positive prognostic factor for an individual patient, a recent metaanalysis could validate pCR as a surrogate marker for patient outcomes only in aggressive breast cancer subtypes. For establishment of the clinical application of metabolic treatment response studies, larger series of specific breast cancer subtypes-including hormone receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative breast cancers-are necessary. In addition, thresholds for relative changes in (18)F-FDG uptake to distinguish between responding and nonresponding tumors need to be validated for different systemic treatment approaches, with progression-free survival and overall survival as references. A PET-based treatment stratification is applicable clinically only if valid alternative therapies are available. Of note, patients who do not achieve a pCR might still benefit from neoadjuvant therapy enabling breast-conserving surgery. In the metastatic setting, residual tumor metabolic activity after the initiation of systemic therapy is an indicator of active disease, whereas a complete resolution of metabolic activity is predictive of a successful treatment response.

  4. 18F-FDG PET/CT for Monitoring of Treatment Response in Breast Cancer

    PubMed Central

    Avril, Stefanie; Muzic, Raymond F.; Plecha, Donna; Traughber, Bryan J.; Vinayak, Shaveta; Avril, Norbert

    2016-01-01

    Changes in tumor metabolic activity have been shown to be an early indicator of treatment effectiveness for breast cancer, mainly in the neoadjuvant setting. The histopathologic response at the completion of chemotherapy has been used as the reference standard for assessment of the accuracy of 18F-FDG PET in predicting a response during systemic treatment. Although a pathologic complete response (pCR) remains an important positive prognostic factor for an individual patient, a recent metaanalysis could validate pCR as a surrogate marker for patient outcomes only in aggressive breast cancer subtypes. For establishment of the clinical application of metabolic treatment response studies, larger series of specific breast cancer subtypes—including hormone receptor–positive, human epidermal growth factor receptor 2–positive, and triple-negative breast cancers—are necessary. In addition, thresholds for relative changes in 18F-FDG uptake to distinguish between responding and nonresponding tumors need to be validated for different systemic treatment approaches, with progression-free survival and overall survival as references. A PET-based treatment stratification is applicable clinically only if valid alternative therapies are available. Of note, patients who do not achieve a pCR might still benefit from neoadjuvant therapy enabling breast-conserving surgery. In the metastatic setting, residual tumor metabolic activity after the initiation of systemic therapy is an indicator of active disease, whereas a complete resolution of metabolic activity is predictive of a successful treatment response. PMID:26834099

  5. A systematic method for estimating individual responses to treatment with antipsychotics in CATIE

    PubMed Central

    Adkins, Daniel E.; McClay, Joseph; Lieberman, Jeffrey; Sullivan, Patrick F.

    2009-01-01

    Objective In addition to comparing drug treatment groups, the wealth of genetic and clinical data collected in the Clinical Antipsychotic Trials of Intervention Effectiveness study offers tremendous opportunities to study individual differences in response to treatment with antipsychotics. A major challenge, however, is how to estimate the individual responses to treatments. For this purpose, we propose a systematic method that condenses all information collected during the trials in an optimal, empirical fashion. Method Our method comprises three steps. First, we test how to best model treatment effects over time. Next, we screen many covariates to select those that will further improve the precision of the individual treatment effect estimates which, for example, improves power to detect predictors of individual treatment response. Third, Best Linear Unbiased Predictors (BLUPs) of the random effects are used to estimate for each individual a treatment effect based on the model empirically indicated to best fit the data. We illustrate our method for the Positive and Negative Syndrome Scale (PANSS). Results A model assuming it takes on average about 30 days for a treatment to exert an effect that will then remain about the same for the rest of the trial showed the best fit to the data. Of all screened covariates, only two improved the precision of the individual treatment effect estimates. A comparison with more traditional post- minus pre-treatment symptom scores showed that our model based treatment effect estimates were a) more precise because they use all data collected during the trial rather than just two data points, and b) less sensitive to biases created by using the same baseline to calculate multiple treatment effects in CATIE. Conclusions We demonstrate that treatment effects can be estimated in a way that condenses all information collected in an optimal, empirical fashion. We expect the proposed method to be valuable for other clinical outcomes in

  6. Activation of Phenotypic Subpopulations in Response to Ciprofloxacin Treatment in Acinetobacter baumannii

    PubMed Central

    MacGuire, Ashley E.; Ching, Meining Carly; Diamond, Brett H.; Kazakov, Alexey; Novichkov, Pavel; Godoy, Veronica G.

    2014-01-01

    Summary The multidrug-resistant, opportunistic pathogen, Acinetobacter baumannii, has spread swiftly through hospitals worldwide. Previously, we demonstrated that A. baumannii regulates the expression of various genes in response to DNA damage. Some of these regulated genes, especially those encoding the multiple error-prone DNA polymerases, can be implicated in induced mutagenesis, leading to antibiotic resistance. Here, we further explore the DNA damage-inducible system at the single cell level using chromosomal transcriptional reporters for selected DNA damage response genes. We found the genes examined respond in a bimodal fashion to ciprofloxacin treatment, forming two phenotypic subpopulations: induced and uninduced. This bimodal response to ciprofloxacin treatment in A. baumannii is unique and quite different than the Escherichia coli paradigm. The subpopulations are not genetically different, with each subpopulation returning to a starting state and differentiating with repeated treatment. We then identified a palindromic motif upstream of certain DNA damage response genes, and have shown alterations to this sequence to diminish the bimodal induction in response to DNA damaging treatment. Lastly, we are able to show a biological advantage for a bimodal response, finding that one subpopulation survives ciprofloxacin treatment better than the other. PMID:24612352

  7. Purine and pyrimidine metabolism: Convergent evidence on chronic antidepressant treatment response in mice and humans

    PubMed Central

    Park, Dong Ik; Dournes, Carine; Sillaber, Inge; Uhr, Manfred; Asara, John M.; Gassen, Nils C.; Rein, Theo; Ising, Marcus; Webhofer, Christian; Filiou, Michaela D.; Müller, Marianne B.; Turck, Christoph W.

    2016-01-01

    Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used drugs for the treatment of psychiatric diseases including major depressive disorder (MDD). For unknown reasons a substantial number of patients do not show any improvement during or after SSRI treatment. We treated DBA/2J mice for 28 days with paroxetine and assessed their behavioral response with the forced swim test (FST). Paroxetine-treated long-time floating (PLF) and paroxetine-treated short-time floating (PSF) groups were stratified as proxies for drug non-responder and responder mice, respectively. Proteomics and metabolomics profiles of PLF and PSF groups were acquired for the hippocampus and plasma to identify molecular pathways and biosignatures that stratify paroxetine-treated mouse sub-groups. The critical role of purine and pyrimidine metabolisms for chronic paroxetine treatment response in the mouse was further corroborated by pathway protein expression differences in both mice and patients that underwent chronic antidepressant treatment. The integrated -omics data indicate purine and pyrimidine metabolism pathway activity differences between PLF and PSF mice. Furthermore, the pathway protein levels in peripheral specimens strongly correlated with the antidepressant treatment response in patients. Our results suggest that chronic SSRI treatment differentially affects purine and pyrimidine metabolisms, which may explain the heterogeneous antidepressant treatment response and represents a potential biosignature. PMID:27731396

  8. TPH-2 Polymorphisms Interact with Early Life Stress to Influence Response to Treatment with Antidepressant Drugs

    PubMed Central

    Reynolds, Gavin P.; Yuan, Yonggui; Shi, Yanyan; Pu, Mengjia; Zhang, Zhijun

    2016-01-01

    Background: Variation in genes implicated in monoamine neurotransmission may interact with environmental factors to influence antidepressant response. We aimed to determine how a range of single nucleotide polymorphisms in monoaminergic genes influence this response to treatment and how they interact with childhood trauma and recent life stress in a Chinese sample. An initial study of monoaminergic coding region single nucleotide polymorphisms identified significant associations of TPH2 and HTR1B single nucleotide polymorphisms with treatment response that showed interactions with childhood and recent life stress, respectively (Xu et al., 2012). Methods: A total of 47 further single nucleotide polymorphisms in 17 candidate monoaminergic genes were genotyped in 281 Chinese Han patients with major depressive disorder. Response to 6 weeks’ antidepressant treatment was determined by change in the 17-item Hamilton Depression Rating Scale score, and previous stressful events were evaluated by the Life Events Scale and Childhood Trauma Questionnaire-Short Form. Results: Three TPH2 single nucleotide polymorphisms (rs11178998, rs7963717, and rs2171363) were significantly associated with antidepressant response in this Chinese sample, as was a haplotype in TPH2 (rs2171363 and rs1487278). One of these, rs2171363, showed a significant interaction with childhood adversity in its association with antidepressant response. Conclusions: These findings provide further evidence that variation in TPH2 is associated with antidepressant response and may also interact with childhood trauma to influence outcome of antidepressant treatment. PMID:27521242

  9. Sex differences in associations between cannabis craving and neural responses to cannabis cues: Implications for treatment.

    PubMed

    Wetherill, Reagan R; Jagannathan, Kanchana; Hager, Nathan; Childress, Anna Rose; Franklin, Teresa R

    2015-08-01

    Preclinical and clinical research indicates that there are sex differences in how men and women initiate, progress, respond to, and withdraw from cannabis use; however, neurophysiological differences, such as neural responses to cannabis cues, are not well understood. Using functional MRI and an event-related blood oxygen level-dependent backward-masking task, we compared neural responses to backward-masked cannabis cues to neutral cues in treatment-seeking, cannabis-dependent adults (N = 44; 27 males) and examined whether sex differences exist. In addition, functional MRI findings were correlated with cannabis craving. Backward-masked cannabis cues elicited greater neural responses than neutral cues in reward-related brain regions, including the striatum, hippocampus/amygdala, insula, anterior cingulate cortex, and lateral orbitofrontal cortex, p < .01, k > 121 voxels. Although no significant sex differences in neural responses to cannabis cues emerged, women showed a positive correlation between neural responses to cannabis cues in the bilateral insula and cannabis craving and an inverse correlation between neural responses to cannabis cues in the left lateral orbitofrontal cortex and cannabis craving. Men, however, showed a positive correlation between neural responses to cannabis cues in the striatum and cannabis craving. Given that cues and craving are important triggers and the focus on many behavioral treatment approaches, these findings suggest that treatment-seeking, cannabis-dependent men and women may benefit from sex-specific and tailored cannabis use disorder treatments.

  10. Body mass index and response to a multidisciplinary treatment of fibromyalgia.

    PubMed

    Castel, Antoni; Castro, Sonia; Fontova, Ramon; Poveda, Maria José; Cascón-Pereira, Rosalia; Montull, Salvador; Padrol, Anna; Qanneta, Rami; Rull, Maria

    2015-02-01

    The purpose of this study is to determine whether there are some differences in the treatment responses to a multidisciplinary fibromyalgia (FM) treatment related with the baseline body mass index (BMI) of the participants. Inclusion criteria consisted of female sex, a diagnosis of FM (American College of Rheumatology criteria), age between 18 and 60 years, and between 3 and 8 years of schooling. Baseline BMI was determined, and patients were randomly assigned to one of the two treatment conditions: conventional pharmacologic treatment or multidisciplinary treatment. Outcome measures were pain intensity, functionality, catastrophizing, psychological distress, health-related quality of life, and sleep disturbances. One hundred thirty patients participated in the study. No statistical significant differences regarding pre-treatment outcomes were found among the different BMI subgroups, and between the two experimental conditions for each BMI category. General linear model analysis showed a significant interaction group treatment × time in pain intensity (p < .01), functionality (p < .0001), catastrophizing (p < .01), psychological distress (p < .0001), sleep index problems (p < .0001), and health-related quality of life (p < .05). No significant interactions were found in BMI × time, and in BMI × group treatment × time. There are not differences among normal weight, overweight and obese patients with FM regarding their response to a multidisciplinary treatment programme for FM which combines pharmacological treatment, education, physical therapy and cognitive behavioural therapy.

  11. Artificial neural network model for the prediction of obsessive-compulsive disorder treatment response.

    PubMed

    Salomoni, Giuliana; Grassi, Massimiliano; Mosini, Paola; Riva, Patrizia; Cavedini, Paolo; Bellodi, Laura

    2009-08-01

    Several patients with obsessive-compulsive disorder (OCD) who are refractory to adequate treatment with first-line treatments are considered treatment-resistant. Further surveys were to be implemented to explore the outcome predictors of the antiobsessional response. Such study was aimed at building a model suitable to predict the final outcome of a mixed OCD pharmacologic and nonpharmacologic treatment approaches. We studied 130 subjects with OCD who underwent pharmacologic (with selective serotonin reuptake inhibitors alone or with selective serotonin reuptake inhibitors and risperidone at low dosage) and/or behavioral therapy (using exposure and response prevention techniques). The following variables were used as predictors: symptoms dimension, as resulting from the Yale-Brown Obsessive-Compulsive Scale items factor analysis; neuropsychologic performances; and epidemiologic variables. The treatment response arising from 3 to 6 months of therapy was used as dependent variable. A conventional logistic regression was used to define a previsional model of treatment response and multilayer perceptrons and to supervise an artificial neural network technique. The 46.9% of the sample resulted to be refractory to treatment. Results obtained with the logistic regression model showed that the only predictors of treatment outcome are hoarding symptoms, repeating rituals, and counting compulsions. Furthermore, using all the variables considered in the models, multilayer perceptrons showed highly better predictive performance as compared with the logistic regression models (93.3% vs 61.5%, respectively, of correct classification of cases). Complex interactions between different clinical and neuropsychologic variables are involved in defining OCD treatment response profile, and nonlinear and interactive modeling strategies, that is, supervised artificial neural networks, seem to be more suitable to investigate this complexity than linear techniques.

  12. Immune response profiling in early rheumatoid arthritis: discovery of a novel interaction of treatment response with viral immunity

    PubMed Central

    2013-01-01

    Introduction It remains challenging to predict the outcomes of therapy in patients with rheumatoid arthritis (RA). The objective of this study was to identify immune response signatures that correlate with clinical treatment outcomes in patients with RA. Methods A cohort of 71 consecutive patients with early RA starting treatment with disease-modifying antirheumatic drugs (DMARDs) was recruited. Disease activity at baseline and after 21 to 24 weeks of follow-up was measured using the Disease Activity Score in 28 joints (DAS28). Immune response profiling was performed by analyzing multi-cytokine production from peripheral blood cells following incubation with a panel of stimuli, including a mixture of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) lysates. Profiles identified via principal components analysis (PCA) for each stimulus were then correlated with the ΔDAS28 from baseline to follow-up. A clinically meaningful improvement in the DAS28 was defined as a decrease of ≥1.2. Results A profile of T-cell cytokines (IL-13, IL-4, IL-5, IL-2, IL-12, and IFN-γ) produced in response to CMV/EBV was found to correlate with the ΔDAS28 from baseline to follow-up. At baseline, a higher magnitude of the CMV/EBV immune response profile predicted inadequate DAS28 improvement (mean PCA-1 scores: 65.6 versus 50.2; P = 0.029). The baseline CMV/EBV response was particularly driven by IFN-γ (P = 0.039) and IL-4 (P = 0.027). Among patients who attained clinically meaningful DAS28 improvement, the CMV/EBV PCA-1 score increased from baseline to follow-up (mean +11.6, SD 25.5), whereas among patients who responded inadequately to DMARD therapy, the CMV/EBV PCA-1 score decreased (mean -12.8, SD 25.4; P = 0.002). Irrespective of the ΔDAS28, methotrexate use was associated with up-regulation of the CMV/EBV response. The CMV/EBV profile was associated with positive CMV IgG (P <0.001), but not EBV IgG (P = 0.32), suggesting this response was related to

  13. Immediate skin responses to laser and light treatments: Warning endpoints: How to avoid side effects.

    PubMed

    Wanner, Molly; Sakamoto, Fernanda H; Avram, Mathew M; Anderson, R Rox

    2016-05-01

    Lasers are versatile, commonly used treatment tools in dermatology. While it is tempting to follow manufacturer's guidelines or other "recipes" for laser treatment, this approach alone can be a recipe for disaster. Specific and immediate skin responses or endpoints exist and are clinically useful because they correlate with underlying mechanisms that are either desirable (ie, therapeutic), undesirable (ie, warning signs of injury or side effects), or incidental. The observation of clinical endpoints is a safe and reliable guide for appropriate treatment. This article presents the warning endpoints during specific dermatologic laser treatments, and the accompanying article presents the therapeutic endpoints, their underlying mechanisms, and the utility of these endpoints.

  14. Clinical and immunological response to photodynamic therapy in the treatment of vulval intraepithelial neoplasia.

    PubMed

    Daayana, S; Winters, U; Stern, P L; Kitchener, H C

    2011-05-01

    Vulval intraepithelial neoplasia (VIN) is a premalignant condition of the vulva and its incidence is increasing. The common type of VIN is associated with oncogenic types of human papilloma virus (HPV) infection. The standard modalities of treatment for VIN, surgical excision and laser ablation, are both sub-optimal, associated with high rates of disease recurrence. There is a need for non-surgical treatment options for VIN and photodynamic therapy (PDT), by altering the local immunological parameters, has the potential to clear both VIN and HPV. This article reviews the studies of PDT treatment for VIN and discusses the clinical and immunological responses to PDT treatment in the various studies.

  15. Oral Appliance Treatment Response and Polysomnographic Phenotypes of Obstructive Sleep Apnea

    PubMed Central

    Sutherland, Kate; Takaya, Hisashi; Qian, Jin; Petocz, Peter; Ng, Andrew T.; Cistulli, Peter A.

    2015-01-01

    Study Objectives: Mandibular advancement splints (MAS) are an effective treatment for obstructive sleep apnea (OSA); however, therapeutic response is variable. Younger age, female gender, less obesity, and milder and supine-dependent OSA have variably been associated with treatment success in relatively small samples. Our objective was to utilize a large cohort of MAS treated patients (1) to compare efficacy across patients with different phenotypes of OSA and (2) to assess demographic, anthropometric, and polysomnography variables as treatment response predictors. Methods: Retrospective analysis of MAS-treated patients participating in clinical trials in sleep centers in Sydney, Australia between years 2000–2013. All studies used equivalent customized two-piece MAS devices and treatment protocols. Treatment response was defined as (1) apnea-hypopnea index (AHI) < 5/h, (2) AHI < 10/h and ≥ 50% reduction, and (3) ≥ 50% AHI reduction. Results: A total of 425 patients (109 female) were included (age 51.2 ± 10.9 years, BMI 29.2 ± 5.0 kg/m2). MAS reduced AHI by 50.3% ± 50.7% across the group. Supine-predominant OSA patients had lower treatment response rates than non-positional OSA (e.g., 36% vs. 59% for AHI < 10/h). REM-predominant OSA showed a lower response rate than either NREM or non-stage dependent OSA. In prediction modelling, age, baseline AHI, and anthropometric variables were predictive of MAS treatment outcome but not OSA phenotype. Gender was not associated with treatment outcome. Conclusions: Lower MAS treatment response rates were observed in supine and REM sleep. In a large sample, we confirm that demographic, anthropometric, and polysomnographic data only weakly inform about MAS efficacy, supporting the need for alternative objective prediction methods to reliably select patients for MAS treatment. Citation: Sutherland K, Takaya H, Qian J, Petocz P, Ng AT, Cistulli PA. Oral appliance treatment response and polysomnographic phenotypes of

  16. Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B.

    PubMed Central

    Boni, C; Bertoletti, A; Penna, A; Cavalli, A; Pilli, M; Urbani, S; Scognamiglio, P; Boehme, R; Panebianco, R; Fiaccadori, F; Ferrari, C

    1998-01-01

    High viral and/or antigen load may be an important cause of the T cell hyporesponsiveness to hepatitis B virus (HBV) antigens that is often observed in patients with chronic HBV infection. Reduction of viral and antigen load by lamivudine treatment represents an ideal model for investigating this hypothesis. HLA class II restricted T cell responses and serum levels of HBV-DNA, HBsAg, and HBeAg were studied before and during lamivudine treatment in 12 patients with hepatitis B e antigen positive chronic active hepatitis B to assess possible correlations between viral and/or antigen load and vigor of the T cell response. Cell proliferation to HBV nucleocapsid antigens and peptides and frequency of circulating HBV nucleocapsid-specific T cells were assessed to characterize CD4-mediated responses. A highly significant enhancement of the CD4-mediated response to HBV nucleocapsid antigens was already detectable in most patients 7-14 d after the start of lamivudine treatment. This effect was dramatic and persistent in 10 patients but undetectable in 2. It occurred concomitant with a rapid and marked reduction of viremia. Interestingly, lamivudine also enhanced the responses to mitogens and recall antigens, showing that its effect was not limited to HBV-specific T cells. In conclusion, an efficient antiviral T cell response can be restored by lamivudine treatment in patients with chronic hepatitis B concurrently with reduction of viremia, indicating the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients. Since lamivudine treatment can overcome T cell hyporeactivity, combining lamivudine with treatments directed to stimulate the T cell response may represent an effective strategy to induce eradication of chronic HBV infection. PMID:9727065

  17. Serial diffusion MRI to monitor and model treatment response of the targeted nanotherapy CRLX101

    PubMed Central

    Ng, Thomas S.C.; Wert, David; Sohi, Hargun; Procissi, Daniel; Colcher, David; Raubitschek, Andrew A.; Jacobs, Russell E.

    2013-01-01

    Purpose Targeted nanotherapies are being developed to improve tumor drug delivery and enhance therapeutic response. Techniques that can predict response will facilitate clinical translation and may help define optimal treatment strategies. We evaluated the efficacy of diffusion-weighted magnetic resonance imaging to monitor early response to CRLX101 nanotherapy (formerly IT-101), and explored its potential as a therapeutic response predictor using a mechanistic model of tumor cell-proliferation. Experimental Design Diffusion MRI was serially performed following CRLX101 administration in a mouse lymphoma model. Apparent diffusion coefficients (ADC) extracted from the data were used as treatment response biomarkers. Animals treated with irinotecan (CPT-11) and saline were imaged for comparison. ADC data were also input into a mathematical model of tumor growth. Histological analysis using cleaved-caspase 3, TUNEL, Ki-67 and H&E were conducted on tumor samples for correlation with imaging results. Results CRLX101 treated tumors at day 2, 4, 7 post-treatment exhibited changes in mean ADC=16 ± 9%, 24 ± 10% 49 ± 17% and size (TV)=−5 ± 3%, −30 ± 4% and −45 ± 13% respectively. Both parameters were statistically greater than controls (p(ADC) ≤ 0.02, and p(TV) ≤ 0.01 at day 4 and 7), and noticeably greater than CPT-11 treated tumors (ADC=5 ± 5%, 14 ± 7% and 18 ± 6%, TV=−15 ± 5%, −22 ± 13% and −26 ± 8%). Model-derived parameters for cell-proliferation obtained using ADC data distinguished CRLX101 treated tumors from controls (p = 0.02). Conclusions Temporal changes in ADC specified early CRLX101 treatment response and could be used to model image-derived cell-proliferation rates following treatment. Comparisons of targeted and non-targeted treatments highlight the utility of non-invasive imaging and modeling to evaluate, monitor and predict responses to targeted nanotherapeutics. PMID:23532891

  18. CT contrast predicts pancreatic cancer treatment response to verteporfin-based photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Jermyn, Michael; Davis, Scott C.; Dehghani, Hamid; Huggett, Matthew T.; Hasan, Tayyaba; Pereira, Stephen P.; Bown, Stephen G.; Pogue, Brian W.

    2014-04-01

    The goal of this study was to determine dominant factors affecting treatment response in pancreatic cancer photodynamic therapy (PDT), based on clinically available information in the VERTPAC-01 trial. This trial investigated the safety and efficacy of verteporfin PDT in 15 patients with locally advanced pancreatic adenocarcinoma. CT scans before and after contrast enhancement from the 15 patients in the VERTPAC-01 trial were used to determine venous-phase blood contrast enhancement and this was correlated with necrotic volume determined from post-treatment CT scans, along with estimation of optical absorption in the pancreas for use in light modeling of the PDT treatment. Energy threshold contours yielded estimates for necrotic volume based on this light modeling. Both contrast-derived venous blood content and necrotic volume from light modeling yielded strong correlations with observed necrotic volume (R2 = 0.85 and 0.91, respectively). These correlations were much stronger than those obtained by correlating energy delivered versus necrotic volume in the VERTPAC-01 study and in retrospective analysis from a prior clinical study. This demonstrates that contrast CT can provide key surrogate dosimetry information to assess treatment response. It also implies that light attenuation is likely the dominant factor in the VERTPAC treatment response, as opposed to other factors such as drug distribution. This study is the first to show that contrast CT provides needed surrogate dosimetry information to predict treatment response in a manner which uses standard-of-care clinical images, rather than invasive dosimetry methods.

  19. Genetic polymorphisms, their allele combinations and IFN-β treatment response in Irish multiple sclerosis patients

    PubMed Central

    O’Doherty, Catherine; Favorov, Alexander; Heggarty, Shirley; Graham, Colin; Favorova, Olga; Ochs, Michael; Hawkins, Stanley; Hutchinson, Michael; O’Rourke, Killian; Vandenbroeck, Koen

    2009-01-01

    Introduction IFN-β is widely used as first-line immunomodulatory treatment for multiple sclerosis. Response to treatment is variable (30–50% of patients are nonresponders) and requires a long treatment duration for accurate assessment to be possible. Information about genetic variations that predict responsiveness would allow appropriate treatment selection early after diagnosis, improve patient care, with time saving consequences and more efficient use of resources. Materials & methods We analyzed 61 SNPs in 34 candidate genes as possible determinants of IFN-β response in Irish multiple sclerosis patients. Particular emphasis was placed on the exploration of combinations of allelic variants associated with response to therapy by means of a Markov chain Monte Carlo-based approach (APSampler). Results The most significant allelic combinations, which differed in frequency between responders and nonresponders, included JAK2–IL10RB–GBP1–PIAS1 (permutation p-value was pperm = 0.0008), followed by JAK2–IL10–CASP3 (pperm = 0.001). Discussion The genetic mechanism of response to IFN-β is complex and as yet poorly understood. Data mining algorithms may help in uncovering hidden allele combinations involved in drug response versus nonresponse. PMID:19604093

  20. Breeding bird responses to three silvicultural treatments in the Oregon Coast Range

    USGS Publications Warehouse

    Chambers, C.L.; McComb, W.C.; Tappeiner, J. C.

    1999-01-01

    Silvicultural alternatives to clear-cutting have been suggested to promote development, retention, or creation of late-successional features such as large trees, multilayered canopies, snags, and logs. We assessed bird response to three silvicultural alternatives to clear-cutting that retained structural features found in old Douglas-fir (Pseudotsuga menziesii) forests and that imitated natural disturbance regimes more closely than did traditional clear-cutting: (1) small-patch group selection treatment representing a low-intensity disturbance; (2) two-story treatment, representing a moderate to high-intensity disturbance; and (3) modified clear-cut treatment, representing a high-intensity disturbance. We counted diurnal breeding birds 1 yr prior to and 2 yr after harvest to estimate effects of the silvicultural treatments on bird communities compared with uncut controls. The small-patch group selection treatment was most similar in species composition to control stands. The two-story treatment was more similar to the modified clear-cut treatment. Ten bird species remained abundant following the small-patch group selection treatment. They declined in abundance in modified clearcuts and two-story stands. These species included four neotropical migratory species and five species with restricted geographic ranges and habitat associations. Nine species increased in response to moderate and/or high-intensity disturbances. This group included a larger proportion of species that were habitat generalists. Silvicultural treatments imitating low-intensity disturbances were most effective in retaining bird communities associated with mature forest; high-intensity disturbances such as the two-story and modified clear-cut treatments greatly altered bird community composition. Bird responses to the silvicultural treatments that we studied indicate that a variety of stand types is needed to meet needs of all species.

  1. Relationship satisfaction as a predictor of treatment response during cognitive behavioral sex therapy.

    PubMed

    Stephenson, Kyle R; Rellini, Alessandra H; Meston, Cindy M

    2013-01-01

    Although recent research suggests that individual cognitive behavioral therapy (CBT) may be an effective treatment for female sexual dysfunctions, we have little information regarding predictors of treatment response. The goal of the current study was to assess the degree to which pre-treatment relationship satisfaction predicted treatment response to cognitive behavioral sex therapy. Women with sexual dysfunction (n = 31, M age = 28 years, 77.4 % Caucasian) receiving cognitive-behavioral sex therapy with or without ginkgo biloba, as part of a wider randomized clinical trial, were assessed pre- and post-treatment using validated self-report measures of sexual satisfaction, sexual distress, sexual functioning, and relationship satisfaction. Pre-treatment relationship satisfaction predicted changes in sexual satisfaction and distress, but not sexual functioning. Women with higher relationship satisfaction at intake experienced larger gains in sexual satisfaction and distress over the course of treatment. Pre-treatment relationship satisfaction also moderated the association between changes in sexual functioning and changes in sexual distress, such that improved functioning was associated with decreased distress only for women entering therapy with high relationship satisfaction. These findings suggest that, for women with low relationship satisfaction before entering treatment, improvement in sexual functioning may not be enough to alleviate their sexual distress.

  2. The Promise of Biological Markers for Treatment Response in First-Episode Psychosis: A Systematic Review

    PubMed Central

    Fond, Guillaume; d’Albis, Marc-Antoine; Jamain, Stéphane; Tamouza, Ryad; Arango, Celso; Fleischhacker, W. Wolfgang; Glenthøj, Birte; Leweke, Markus; Lewis, Shôn; McGuire, Phillip; Meyer-Lindenberg, Andreas; Sommer, Iris E.; Winter-van Rossum, Inge; Kapur, Shitij; Kahn, René S.; Rujescu, Dan; Leboyer, Marion

    2015-01-01

    Successful treatment of first-episode psychosis is one of the major factors that impacts long-term prognosis. Currently, there are no satisfactory biological markers (biomarkers) to predict which patients with a first-episode psychosis will respond to which treatment. In addition, a non-negligible rate of patients does not respond to any treatment or may develop side effects that affect adherence to the treatments as well as negatively impact physical health. Thus, there clearly is a pressing need for defining biomarkers that may be helpful to predict response to treatment and sensitivity to side effects in first-episode psychosis. The present systematic review provides (1) trials that assessed biological markers associated with antipsychotic response or side effects in first-episode psychosis and (2) potential biomarkers associated with biological disturbances that may guide the choice of conventional treatments or the prescription of innovative treatments. Trials including first-episode psychoses are few in number. Most of the available data focused on pharmacogenetics markers with so far only preliminary results. To date, these studies yielded—beside markers for metabolism of antipsychotics—no or only a few biomarkers for response or side effects, none of which have been implemented in daily clinical practice. Other biomarkers exploring immunoinflammatory, oxidative, and hormonal disturbances emerged as biomarkers of first-episode psychoses in the last decades, and some of them have been associated with treatment response. In addition to pharmacogenetics, further efforts should focus on the association of emergent biomarkers with conventional treatments or with innovative therapies efficacy, where some preliminary data suggest promising results. PMID:25759473

  3. Impact of Interleukin 28B Genotype on the Virological Responses in Chronic Hepatitis C Treatment

    PubMed Central

    Aygen, Bilgehan; Yildiz, Orhan; Akhan, Sila; Gunal, Ozgur; Taheri, Serpil; Zararsiz, Gokmen; Sayan, Murat; Rustemoglu, Aydin; Altinok, Elif Sargin

    2014-01-01

    Background Interleukin (IL) 28B single nucleotide polymorphisms may play a role in the clearance of hepatitis C virus (HCV). We aimed to evaluate the treatment response of chronic HCV infection patients to pegile interferon (pegIFN) and ribavirin treatment with regard to IL28B rs12979860 C/T polymorphism. Methods A total of 186 patients (mean age, 55.6 ± 10 years; 65.1% female) who underwent pegIFN and ribavirin treatment for chronic HCV infection were studied. We analyzed demographics, HCV genotype, baseline alanine aminotransferase (ALT) levels, histopathological data, viral load before treatment and at 4, 12, 24, 48, and 72 weeks from the treatment start, and IL28B genotype. IL28B polymorphism was genotyped using polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) in all the subjects. Results One hundred forty-five (86.8%) patients were infected with viral genotype 1b, and 13.2% were infected with viral genotype 4. The rates of C/C, C/T, and T/T genotypes were 22.6%, 52.7%, and 24.7% respectively. The percentage of patients with a viral load over 400,000 IU/mL was higher in the C/T group (P = 0.020). Of the patients, 44.6% provided sustained virological response (SVR) to pegIFN and ribavirin combination treatment. The frequency of T allele was 41% in patients with SVR, whereas 59% patients provided no response (P < 0.001). SVR was obtained in 66.7%, 42.9%, and 28.3% of CC, CT, and TT groups (P = 0.001). The rates of rapid virological response (RVR), early virological response (EVR), end-of-treatment response (ETR), and SVR were higher in the CC group than other groups (P = 0.216, P < 0.001, P = 0.001, P = 0.001, respectively). The relapse and null response (NR) rates were higher in TT group and partial response rate (PR) was higher in CT group. Conclusions IL28B rs12979860 C/T gene polymorphism affects the response to antiviral treatment in the patients with chronic HCV genotypes 1b and 4 infections. PMID:27785282

  4. Treatment response, safety, and tolerability of paliperidone extended release treatment in patients recently diagnosed with schizophrenia

    PubMed Central

    Peuskens, Joseph; Vauth, Roland; Sacchetti, Emilio; bij de Weg, Haye; Herken, Hasan; Lahaye, Marjolein; Schreiner, Andreas

    2015-01-01

    Objective: This study was designed to explore the efficacy and tolerability of oral paliperidone extended release (ER) in a sample of patients who were switched to flexible doses within the crucial first 5 years after receiving a diagnosis of schizophrenia. Methods: Patients were recruited from 23 countries. Adults with nonacute but symptomatic schizophrenia, previously unsuccessfully treated with other oral antipsychotics, were transitioned to paliperidone ER (3–12 mg/day) and prospectively treated for up to 6 months. The primary efficacy outcome for patients switching for the main reason of lack of efficacy with their previous antipsychotic was at least 20% improvement in Positive and Negative Syndrome Scale (PANSS) total scores. For patients switching for other main reasons, such as lack of tolerability, compliance or ‘other’, the primary outcome was non-inferiority in efficacy compared with the previous oral antipsychotic. Results: For patients switching for the main reason of lack of efficacy, 63.1% achieved an improvement of at least 20% in PANSS total scores from baseline to endpoint. For each reason for switching other than lack of efficacy, efficacy maintenance after switching to paliperidone ER was confirmed. Statistically significant improvement in patient functioning from baseline to endpoint, as assessed by the Personal and Social Performance scale, was observed (p < 0.0001). Treatment satisfaction with prior antipsychotic treatment at baseline was rated ‘good’ to ‘very good’ by 16.8% of patients, and at endpoint by 66.0% of patients treated with paliperidone ER. Paliperidone ER was generally well tolerated, with frequently reported treatment-emergent adverse events being insomnia, anxiety and somnolence. Conclusions: Flexibly dosed paliperidone ER was associated with clinically relevant symptomatic and functional improvement in recently diagnosed patients with non-acute schizophrenia previously unsuccessfully treated with other oral

  5. Smoking cessation and adolescent treatment response with comorbid ADHD☆,☆☆,★

    PubMed Central

    Pagano, Maria E.; Delos-Reyes, Christina M.; Wasilow, Sherry; Svala, Kathleen M.; Kurtz, Steven P.

    2016-01-01

    Minors entering treatment for alcohol and other drug (AOD) use disorders tend to smoke at high rates, and many have comorbid attention deficit hyperactivity disorder (ADHD). Clear-air laws force patients to refrain from smoking on the premises of AOD treatment facilities, which may hinder the progress of treatment-seeking populations who smoke and struggle with ADHD comorbidity in particular. This study explores clinical characteristics associated with smoking among youths presenting for residential treatment, clinical characteristics associated with smoking cessation, and the impact of smoking cessation with ADHD comorbidity on AOD treatment response. Participants were 195 adolescents (52% female, aged 14–18 years) court-referred to residential treatment. Data were collected at intake, prospectively each week for the 10-week treatment period, and at discharge. Two-thirds (67%) of the enrollment sample entered treatment smoking half a pack a day on average, a large proportion (50%) of which did not smoke during treatment. ADHD patients were more likely to smoke before and during treatment except for those who got active in service and step-work. Quitting smoking did not adversely affect AOD outcomes and was associated with better prognosis of lowered AOD cravings for youths with and without ADHD. Smoking cessation during adolescent AOD treatment is recommended with provision of pharmaceutical and/or behavioral modalities that reduce nicotine withdrawal. PMID:27692184

  6. Drawing Sound Inferences Concerning the Effects of Treatment on Dispersion in Outcomes: Bringing to Light Individual Differences in Response to Treatment. CSE Technical Report 710

    ERIC Educational Resources Information Center

    Seltzer, Michael; Kim, Jinok

    2007-01-01

    Individual differences in response to a given treatment have been a longstanding interest in education. While many evaluation studies focus on average treatment effects (i.e., the effects of treatments on the levels of outcomes of interest), this paper additionally considers estimating the effects of treatments on the dispersion in outcomes.…

  7. Comparative effectiveness of imaging modalities to determine metastatic breast cancer treatment response.

    PubMed

    Lee, Christoph I; Gold, Laura S; Nelson, Heidi D; Chou, Roger; Ramsey, Scott D; Sullivan, Sean D

    2015-02-01

    We performed a systematic review to address the comparative effectiveness of different imaging modalities in evaluating treatment response among metastatic breast cancer patients. We searched seven multidisciplinary electronic databases for relevant publications (January 2003-December 2013) and performed dual abstraction of details and results for all clinical studies that involved stage IV breast cancer patients and evaluated imaging for detecting treatment response. Among 159 citations reviewed, 17 single-institution, non-randomized, observational studies met our inclusion criteria. Several studies demonstrate that changes in PET/CT standard uptake values are associated with changes in tumor volume as determined by bone scan, MRI, and/or CT. However, no studies evaluated comparative test performance between modalities or determined relationships between imaging findings and subsequent clinical decisions. Evidence for imaging's effectiveness in determining treatment response among metastatic breast cancer patients is limited. More rigorous research is needed to address imaging's value in this patient population.

  8. Response of Human Prostate Cancer Cells to Mitoxantrone Treatment in Simulated Microgravity Environment

    NASA Astrophysics Data System (ADS)

    Zhang, Ye; Wu, Honglu

    2012-07-01

    RESPONSE OF HUMAN PROSTATE CANCER CELLS TO MITOXANTRONE TREATMENT IN SIMULATED MICROGRAVITY ENVIRONMENT Ye Zhang1,2, Christopher Edwards3, and Honglu Wu1 1 NASA-Johnson Space Center, Houston, TX 2 Wyle Integrated Science and Engineering Group, Houston, TX 3 Oregon State University, Corvallis, OR This study explores the changes in growth of human prostate cancer cells (LNCaP) and their response to the treatment of an antineoplastic agent, mitoxantrone, under the simulated microgravity condition. In comparison to static 1g, microgravity and simulated microgravity have been shown to alter global gene expression patterns and protein levels in various cultured cell models or animals. However, very little is known about the effect of altered gravity on the responses of cells to the treatment of drugs, especially chemotherapy drugs. To test the hypothesis that zero gravity would result in altered regulations of cells in response to antineoplastic agents, we cultured LNCaP cells in either a High Aspect Ratio Vessel (HARV) bioreactor at the rotating condition to model microgravity in space or in the static condition as control, and treated the cells with mitoxantrone. Cell growth, as well as expressions of oxidative stress related genes, were analyzed after the drug treatment. Compared to static 1g controls, the cells cultured in the simulated microgravity environment did not present significant differences in cell viability, growth rate, or cell cycle distribution. However, after mitoxantrone treatment, a significant proportion of bioreactor cultured cells became apoptotic or was arrested in G2. Several oxidative stress related genes also showed a higher expression level post mitoxantrone treatment. Our results indicate that simulated microgravity may alter the response of LNCaP cells to mitoxantrone treatment. Understanding the mechanisms by which cells respond to drugs differently in an altered gravity environment will be useful for the improvement of cancer treatment on

  9. HIV treatment as prevention in Jamaica and Barbados: magic bullet or sustainable response?

    PubMed

    Barrow, Geoffrey; Barrow, Christine

    2015-01-01

    This discursive article introduces HIV treatment as prevention (TasP) and identifies various models for its extrapolation to wider population levels. Drawing on HIV surveillance data for Jamaica and Barbados, the article identifies significant gaps in HIV response programming in relation to testing, antiretroviral treatment coverage, and treatment adherence, thereby highlighting the disparity between assumptions and prerequisites for TasP success. These gaps are attributable, in large part, to sociocultural impediments and structural barriers, severe resource constraints, declining political will, and the redefinition of HIV as a manageable, chronic health issue. Antiretroviral treatment and TasP can realize success only within a combination prevention frame that addresses structural factors, including stigma and discrimination, gender inequality and gender-based violence, social inequality, and poverty. The remedicalization of the response compromises outcomes and undermines the continued potential of HIV programming as an entry point for the promotion of sexual, health, and human rights.

  10. Discordant Treatment Responses to Combination Antiretroviral Therapy in Rwanda: A Prospective Cohort Study

    PubMed Central

    Kayigamba, Felix R.; Franke, Molly F.; Bakker, Mirjam I.; Rodriguez, Carly A.; Bagiruwigize, Emmanuel; Wit, Ferdinand WNM; Rich, Michael L.; Schim van der Loeff, Maarten F.

    2016-01-01

    Introduction Some antiretroviral therapy naïve patients starting combination antiretroviral therapy (cART) experience a limited CD4 count rise despite virological suppression, or vice versa. We assessed the prevalence and determinants of discordant treatment responses in a Rwandan cohort. Methods A discordant immunological cART response was defined as an increase of <100 CD4 cells/mm3 at 12 months compared to baseline despite virological suppression (viral load [VL] <40 copies/mL). A discordant virological cART response was defined as detectable VL at 12 months with an increase in CD4 count ≥100 cells/mm3. The prevalence of, and independent predictors for these two types of discordant responses were analysed in two cohorts nested in a 12-month prospective study of cART-naïve HIV patients treated at nine rural health facilities in two regions in Rwanda. Results Among 382 patients with an undetectable VL at 12 months, 112 (29%) had a CD4 rise of <100 cells/mm3. Age ≥35 years and longer travel to the clinic were independent determinants of an immunological discordant response, but sex, baseline CD4 count, body mass index and WHO HIV clinical stage were not. Among 326 patients with a CD4 rise of ≥100 cells/mm3, 56 (17%) had a detectable viral load at 12 months. Male sex was associated with a virological discordant treatment response (P = 0.05), but age, baseline CD4 count, BMI, WHO HIV clinical stage, and travel time to the clinic were not. Conclusions Discordant treatment responses were common in cART-naïve HIV patients in Rwanda. Small CD4 increases could be misinterpreted as a (virological) treatment failure and lead to unnecessary treatment changes. PMID:27438000

  11. Success rates and immunologic responses of autogenic, allogenic, and xenogenic treatments to repair articular cartilage defects.

    PubMed

    Revell, Christopher M; Athanasiou, Kyriacos A

    2009-03-01

    This review examines current approaches available for articular cartilage repair, not only in terms of their regeneration potential, but also as a function of immunologic response. Autogenic repair techniques, including osteochondral plug transplantation, chondrocyte implantation, and microfracture, are the most widely accepted clinical treatment options due to the lack of immunogenic reactions, but only moderate graft success rates have been reported. Although suspended allogenic chondrocytes are shown to evoke an immune response upon implantation, allogenic osteochondral plugs and tissue-engineered grafts using allogenic chondrocytes exhibit a tolerable immunogenic response. Additionally, these repair techniques produce neotissue with success rates approaching those of currently available autogenic repair techniques, while simultaneously obviating their major hindrance of donor tissue scarcity. To date, limited research has been performed with xenogenic tissue, although several studies demonstrate the potential for its long-term success. This article focuses on the various treatment options for cartilage repair and their associated success rates and immunologic responses.

  12. Success Rates and Immunologic Responses of Autogenic, Allogenic, and Xenogenic Treatments to Repair Articular Cartilage Defects

    PubMed Central

    Revell, Christopher M.

    2009-01-01

    This review examines current approaches available for articular cartilage repair, not only in terms of their regeneration potential, but also as a function of immunologic response. Autogenic repair techniques, including osteochondral plug transplantation, chondrocyte implantation, and microfracture, are the most widely accepted clinical treatment options due to the lack of immunogenic reactions, but only moderate graft success rates have been reported. Although suspended allogenic chondrocytes are shown to evoke an immune response upon implantation, allogenic osteochondral plugs and tissue-engineered grafts using allogenic chondrocytes exhibit a tolerable immunogenic response. Additionally, these repair techniques produce neotissue with success rates approaching those of currently available autogenic repair techniques, while simultaneously obviating their major hindrance of donor tissue scarcity. To date, limited research has been performed with xenogenic tissue, although several studies demonstrate the potential for its long-term success. This article focuses on the various treatment options for cartilage repair and their associated success rates and immunologic responses. PMID:19063664

  13. Standardization of terminology of virological response in the treatment of chronic hepatitis C: panel recommendations.

    PubMed

    Jacobson, I M; Poordad, F; Brown, R S; Kwo, P Y; Reddy, K R; Schiff, E

    2012-04-01

    The treatment paradigm for hepatitis C virus (HCV) infection is at a critical point in its evolution. The addition of a protease inhibitor to peginterferon plus ribavirin has become the new standard-of-care treatment for most patients. Data from clinical trials of new antivirals have been difficult to interpret and compare, partly because of heterogeneity in trial design, and partly because of inconsistencies in terminology used to define viral responses and the populations evaluated. Present definitions of viral responses for treatment with peginterferon and ribavirin are insufficient for novel treatment paradigms. Further, categorization of prior patient treatment experience in clinical trials, particularly of nonresponders to prior therapy, is inconsistent. Existing terms and definitions must be updated, standardized and/or redefined for easier interpretation of data and effective communication among clinicians. A panel of experts in HCV infection treatment met on 3 December 2009. Goals of the panel were to evaluate terms and definitions used traditionally in treatment with peginterferon and ribavirin, to refine and clarify definitions of existing terms that have varying meanings and to propose new terms and definitions appropriate for novel treatment paradigms emerging with development of new agents. A number of recommendations were accepted unanimously by the panel. Adoption of these terms would improve communication among investigators, enhance comparability among clinical trials, facilitate development of therapeutic guidelines and provide a standardized terminology for use in clinical practice.

  14. Decreased Total Antioxidant Activity in Major Depressive Disorder Patients Non-Responsive to Antidepressant Treatment

    PubMed Central

    Baek, Song-Eun; Lee, Gyoung-Ja; Rhee, Chang-Kyu; Rho, Dae-Young; Kim, Do-Hoon; Huh, Sun

    2016-01-01

    Objective This study aimed to evaluate the total antioxidant activity (TAA) in patients with major depressive disorder (MDD) and the effect of antidepressants on TAA using a novel potentiometric method. Methods Twenty-eight patients with MDD and thirty-one healthy controls were enrolled in this study. The control group comprised 31 healthy individuals matched for gender, drinking and smoking status. We assessed symptoms of depression using the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). We measured TAA using potentiometry. All measurements were made at baseline and four and eight weeks later. Results There was a significant negative correlation between BDI scores and TAA. TAA was significantly lower in the MDD group than in controls. When the MDD group was subdivided into those who showed clinical response to antidepressant therapy (response group) and those who did not (non-response group), only the non-response group showed lower TAA, while the response group showed no significant difference to controls at baseline. After eight weeks of antidepressant treatment, TAA in both the response and non-response groups was similar, and there was no significant difference among the three groups. Conclusion These results suggest that the response to antidepressant treatment in MDD patients might be predicted by measuring TAA. PMID:27081384

  15. Varying responses of insect herbivores to altered plant chemistry under organic and conventional treatments

    PubMed Central

    Staley, Joanna T.; Stewart-Jones, Alex; Pope, Tom W.; Wright, Denis J.; Leather, Simon R.; Hadley, Paul; Rossiter, John T.; van Emden, Helmut F.; Poppy, Guy M.

    2010-01-01

    The hypothesis that plants supplied with organic fertilizers are better defended against insect herbivores than those supplied with synthetic fertilizers was tested over two field seasons. Organic and synthetic fertilizer treatments at two nitrogen concentrations were supplied to Brassica plants, and their effects on the abundance of herbivore species and plant chemistry were assessed. The organic treatments also differed in fertilizer type: a green manure was used for the low-nitrogen treatment, while the high-nitrogen treatment contained green and animal manures. Two aphid species showed different responses to fertilizers: the Brassica specialist Brevicoryne brassicae was more abundant on organically fertilized plants, while the generalist Myzus persicae had higher populations on synthetically fertilized plants. The diamondback moth Plutella xylostella (a crucifer specialist) was more abundant on synthetically fertilized plants and preferred to oviposit on these plants. Glucosinolate concentrations were up to three times greater on plants grown in the organic treatments, while foliar nitrogen was maximized on plants under the higher of the synthetic fertilizer treatments. The varying response of herbivore species to these strong differences in plant chemistry demonstrates that hypotheses on defence in organically grown crops have over-simplified the response of phytophagous insects. PMID:19906673

  16. Varying responses of insect herbivores to altered plant chemistry under organic and conventional treatments.

    PubMed

    Staley, Joanna T; Stewart-Jones, Alex; Pope, Tom W; Wright, Denis J; Leather, Simon R; Hadley, Paul; Rossiter, John T; van Emden, Helmut F; Poppy, Guy M

    2010-03-07

    The hypothesis that plants supplied with organic fertilizers are better defended against insect herbivores than those supplied with synthetic fertilizers was tested over two field seasons. Organic and synthetic fertilizer treatments at two nitrogen concentrations were supplied to Brassica plants, and their effects on the abundance of herbivore species and plant chemistry were assessed. The organic treatments also differed in fertilizer type: a green manure was used for the low-nitrogen treatment, while the high-nitrogen treatment contained green and animal manures. Two aphid species showed different responses to fertilizers: the Brassica specialist Brevicoryne brassicae was more abundant on organically fertilized plants, while the generalist Myzus persicae had higher populations on synthetically fertilized plants. The diamondback moth Plutella xylostella (a crucifer specialist) was more abundant on synthetically fertilized plants and preferred to oviposit on these plants. Glucosinolate concentrations were up to three times greater on plants grown in the organic treatments, while foliar nitrogen was maximized on plants under the higher of the synthetic fertilizer treatments. The varying response of herbivore species to these strong differences in plant chemistry demonstrates that hypotheses on defence in organically grown crops have over-simplified the response of phytophagous insects.

  17. An imaging-based tumour growth and treatment response model: Investigating the effect of tumour oxygenation on radiation therapy response

    PubMed Central

    Jeraj, Robert

    2010-01-01

    A multiscale tumour simulation model employing cell-line-specific biological parameters and functional information derived from pre-therapy PET/CT imaging data was developed to investigate effects of different oxygenation levels on the response to radiation therapy. For each tumour voxel, stochastic simulations were performed to model cellular growth and therapeutic response. Model parameters were fitted to published preclinical experiments of head and neck squamous cell carcinoma (HNSCC). Using the obtained parameters, the model was applied to a human HNSCC case to investigate effects of different uniform and non-uniform oxygenation levels and results were compared for treatment efficacy. Simulations of the preclinical studies showed excellent agreement with published data and underlined the model’s ability to quantitatively reproduce tumour behaviour within experimental uncertainties. When using a simplified transformation to derive non-uniform oxygenation levels from molecular imaging data, simulations of the clinical case showed heterogeneous tumour response and variability in radioresistance with decreasing oxygen levels. Once clinically validated, this model could be used to transform patient-specific data into voxel-based biological objectives for treatment planning and to investigate biologically optimized dose prescriptions. PMID:18677042

  18. Hemisphere Asymmetry of Response to Pharmacologic Treatment in an Alzheimer’s Disease Mouse Model

    PubMed Central

    Manousopoulou, Antigoni; Saito, Satoshi; Yamamoto, Yumi; Al-Daghri, Nasser M.; Ihara, Masafumi; Carare, Roxana O.; Garbis, Spiros D.

    2016-01-01

    The aim of this study was to examine hemisphere asymmetry of response to pharmacologic treatment in an Alzheimer’s disease mouse model using cilostazol as a chemical stimulus. Eight-month-old mice were assigned to vehicle or cilostazol treatment for three months and hemispheres were analyzed using quantitative proteomics. Bioinformatics interpretation showed that following treatment, aggregation of blood platelets significantly decreased in the right hemisphere whereas neurodegeneration significantly decreased and synaptic transmission increased in the left hemisphere only. Our study provides novel evidence on cerebral laterality of pharmacologic activity, with important implications in deciphering regional pharmacodynamic effects of existing drugs thus uncovering novel hemisphere-specific therapeutic targets. PMID:26836196

  19. Association between bevacizumab-related hypertension and response to treatment in patients with metastatic colorectal cancer

    PubMed Central

    Dionísio de Sousa, Isabel José; Ferreira, Joana; Rodrigues, Joana; Bonito, Nuno; Jacinto, Paula; Marques, Mariela; Ribeiro, João; Pais, Ana; Gervásio, Helena

    2016-01-01

    Background Bevacizumab has become standard of care as first-line treatment of metastatic colorectal cancer (mCRC), after proving increased response rates and improvement in survival outcomes. Hypertension (HTN) is a common complication of the treatment with bevacizumab and, owing to its close relation with antiangiogenic mechanism, may represent a clinical biomarker to predict the efficacy of the treatment. The aim of this study was to retrospectively evaluate if HTN grades 2 to 3 were correlated with response to treatment with bevacizumab in first line, as well as with improved progression-free survival (PFS) and overall survival (OS), in a series of patients with mCRC. Methods Retrospective evaluation of clinical records of patients with histologically proven mCRC, treated with bevacizumab as first-line treatment, between January 2008 and December 2013. Results 79 patients were evaluated. 51.9% of patients developed HTN G2-G3 during chemotherapy-bevacizumab treatment. In the group of patients who developed bevacizumab-related HTN, 73.2% showed response to treatment (complete response (CR)+ partial response (PR)) and 97.6% achieved disease control (CR, PR or stable disease) compared to 18.4% of patients with response and 63.2% with disease control in the group that did not (OR 12.08; 95% CI 4.13 to 35.29; p<0.001 responders vs non-responders; OR 20.8; 95% CI 2.56 to 168.91; p 0.005 controlled vs non controlled disease). The median OS was 28 months (22.7–33.3). Significant statistical difference was obtained in PFS between the two groups (p<0.001). In the group that developed bevacizumab-related HTN, the median OS was 33 months (25.7–40.3), and in the group that did not, it was 21 months (16.5–25.5) with no significant statistical difference between the two groups (p 0.114). Conclusions In this subset of patients, HTN G2-3 was predictive of response to treatment with bevacizumab and of PFS but not of OS. PMID:27843607

  20. Early changes in emotional processing as a marker of clinical response to SSRI treatment in depression.

    PubMed

    Godlewska, B R; Browning, M; Norbury, R; Cowen, P J; Harmer, C J

    2016-11-22

    Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the selective serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment. The neural response to fearful and happy emotional facial expressions was assessed before and after 7 days of treatment using functional magnetic resonance imaging. Changes in the neural response to these facial cues after 7 days of escitalopram were compared in patients as a function of later clinical response. A sample of healthy controls was also assessed. At baseline, depressed patients showed greater activation to fear versus happy faces than controls in the insula and dorsal anterior cingulate. Depressed patients who went on to respond to the SSRI had a greater reduction in neural activity to fearful versus happy facial expressions after just 7 days of escitalopram across a network of regions including the anterior cingulate, insula, amygdala and thalamus. Mediation analysis confirmed that the direct effect of neural change on symptom response was not mediated by initial changes in depressive symptoms. These results support the hypothesis that early changes in emotional processing with antidepressant treatment are the basis of later clinical improvement. As such, early correction of negative bias may be a key mechanism of antidepressant drug action and a potentially useful predictor of therapeutic response.

  1. Early changes in emotional processing as a marker of clinical response to SSRI treatment in depression

    PubMed Central

    Godlewska, B R; Browning, M; Norbury, R; Cowen, P J; Harmer, C J

    2016-01-01

    Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the selective serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment. The neural response to fearful and happy emotional facial expressions was assessed before and after 7 days of treatment using functional magnetic resonance imaging. Changes in the neural response to these facial cues after 7 days of escitalopram were compared in patients as a function of later clinical response. A sample of healthy controls was also assessed. At baseline, depressed patients showed greater activation to fear versus happy faces than controls in the insula and dorsal anterior cingulate. Depressed patients who went on to respond to the SSRI had a greater reduction in neural activity to fearful versus happy facial expressions after just 7 days of escitalopram across a network of regions including the anterior cingulate, insula, amygdala and thalamus. Mediation analysis confirmed that the direct effect of neural change on symptom response was not mediated by initial changes in depressive symptoms. These results support the hypothesis that early changes in emotional processing with antidepressant treatment are the basis of later clinical improvement. As such, early correction of negative bias may be a key mechanism of antidepressant drug action and a potentially useful predictor of therapeutic response. PMID:27874847

  2. Comparison of treatment response in second-episode versus first-episode schizophrenia.

    PubMed

    Emsley, Robin; Oosthuizen, Petrus; Koen, Liezl; Niehaus, Dana; Martinez, Lupe

    2013-02-01

    This study investigated whether illness progression and treatment refractoriness emerge after relapse in schizophrenia. We compared outcomes in a cohort treated with a standardized protocol for the first and second episodes of illness. The sample comprised 31 participants who (1) had successfully completed a 2-year open-label treatment phase with risperidone long-acting injection (RLAI) for a first episode of schizophrenia; (2) underwent an intermittent treatment extension phase up to 3 years or until recurrence, and (3) entered a further 2-year treatment phase with RLAI for a recurrence episode. For the patients who remained in treatment (n = 14 [45%]), Positive and Negative Syndrome Scale score reductions, response rates, remission rates, time to response, time to remission, functional outcome scores, and modal RLAI doses were similar for the 2 treatment periods. However, 17 (55 %) of the 31 patients discontinued the study in the second episode compared with 14 (28%) of 50 patients in the first episode, suggesting reduced effectiveness of antipsychotics when reintroduced after illness recurrence. Most notably, emergent treatment nonresponsiveness was observed in 5 participants (16%), consistent with the hypothesis that relapse may be biologically harmful in a subset of patients.

  3. Prediction of Response to Treatment in a Randomized Clinical Trial of Marital Therapy

    ERIC Educational Resources Information Center

    Atkins, David C.; Berns, Sara B.; George, William H.; Doss, Brian D.; Gattis, Krista; Christensen, Andrew

    2005-01-01

    This study investigated demographic, intrapersonal, and interpersonal predictors of treatment response in a randomized clinical trial of 134 distressed married couples, which examined traditional (N. S. Jacobson & G. Margolin, 1979) and integrative (N. S. Jacobson & A. Christensen, 1996) behavioral couple therapy. Results based on hierarchical…

  4. Mediation and Moderation of Psychological Pain Treatments: Response Expectancies and Hypnotic Suggestibility

    ERIC Educational Resources Information Center

    Milling, Leonard S.; Reardon, John M.; Carosella, Gina M.

    2006-01-01

    The mediator role of response expectancies and the moderator role of hypnotic suggestibility were evaluated in the analogue treatment of pain. Approximately 1,000 participants were assessed for hypnotic suggestibility. Later, as part of a seemingly unrelated experiment, 188 of these individuals were randomly assigned to distraction,…

  5. Peer-Mediated Pivotal Response Treatment for Young Children with Autism Spectrum Disorders: A Systematic Review

    ERIC Educational Resources Information Center

    Boudreau, Ainsley M.; Corkum, Penny; Meko, Katelyn; Smith, Isabel M.

    2015-01-01

    This review examined the effectiveness of peer-mediated pivotal response treatment (PM-PRT) to increase social-communication skills for children with autism spectrum disorders (ASD). A systematic review was conducted of all published studies examining PM-PRT in school-aged children with ASD, based on an established rubric. Five PM-PRT studies…

  6. Pivotal Response Treatment for Children with Autism: Core Principles and Applications for School Psychologists

    ERIC Educational Resources Information Center

    Renshaw, Tyler L.; Kuriakose, Sarah

    2011-01-01

    During the past 2 decades, pivotal response treatment (PRT) has emerged as an evidence-based methodology for intervening with the behavioral, communicative, social, and academic impairments of children with autism. Unlike other highly structured behavioral interventions for autism, PRT emphasizes principles over procedures and focuses on enhancing…

  7. Pivotal Response Treatment for Infants At-Risk for Autism Spectrum Disorders: A Pilot Study

    ERIC Educational Resources Information Center

    Steiner, Amanda Mossman; Gengoux, Grace W.; Klin, Ami; Chawarska, Katarzyna

    2013-01-01

    Presently there is limited research to suggest efficacious interventions for infants at-risk for autism. Pivotal response treatment (PRT) has empirical support for use with preschool children with autism, but there are no reports in the literature utilizing this approach with infants. In the current study, a developmental adaptation of PRT was…

  8. [The responsibility of the emergency service physician and patient consent to treatment and hospitalization].

    PubMed

    Wiernikowski, A; Szczepanek, M

    1997-01-01

    Amenability of emergency service physician for the treatment given without patient consent has been presented in the study. Depending on circumstances it can be penal, civil, disciplinary and professional responsibility. The study has been annotated with current legal and ethical rules, which should be not only commonly known to physicians but also respected to avoid legal consequences.

  9. The Effects of a Response Cost Treatment Tactic on Hyperactive Children.

    ERIC Educational Resources Information Center

    Rapport, Mark D.; And Others

    1980-01-01

    Tested a response cost procedure, compared with Ritalin treatment, on hyperactive elementary school children to determine effectiveness in reducing hyperactive behavior and in increasing academic performance. The cost program alone and combined with medication were effective in reducing off-task behavior and in increasing academic performance.…

  10. Molecular Targeted Therapy in Modern Oncology: Imaging Assessment of Treatment Response and Toxicities

    PubMed Central

    Braschi-Amirfarzan, Marta; DiPiro, Pamela J.; Jagannathan, Jyothi P.; Shinagare, Atul B.

    2017-01-01

    Oncology is a rapidly evolving field with a shift toward personalized cancer treatment. The use of therapies targeted to the molecular features of individual tumors and the tumor microenvironment has become much more common. In this review, anti-angiogenic and other molecular targeted therapies are discussed, with a focus on typical and atypical response patterns and imaging manifestations of drug toxicities. PMID:28096716

  11. Primary non-small cell lung cancer response upon treatment with denosumab.

    PubMed

    Curioni-Fontecedro, A; Husmann, L; Soldini, D; Stahel, R A

    2013-12-01

    Here we report the case of a patient with metastatic adenocarcinoma of the lung harboring an ALK gene translocation. In this patient a response of the primary tumor and metastases has been detected upon treatment with denosumab. A possible link between ALK and RANK is postulated.

  12. How Attendance and Quality of Participation Affect Treatment Response to Parent Management Training

    ERIC Educational Resources Information Center

    Nix, Robert L.; Bierman, Karen L.; McMahon, Robert J.

    2009-01-01

    This study examined whether attendance and quality of participation in parent management training predicted treatment response. Data were from 445 parents (55% minority, 62% single; almost all of low socioeconomic status) who had 1st-grade children with severe conduct problems. Quality of participation in weekly parent groups was based on group…

  13. Acute Time to Response in the Treatment for Adolescents with Depression Study (TADS)

    ERIC Educational Resources Information Center

    Kratochvil, Christopher; Emslie, Graham; Silva, Susan; McNulty, Steve; Walkup, John; Curry, John; Reinecke, Mark; Vitiello, Benedetto; Rohde, Paul; Feeny, Nora; Casat, Charles; Pathak, Sanjeev; Weller, Elizabeth; May, Diane; Mayes, Taryn; Robins, Michele; March, John

    2006-01-01

    Objective: To examine the time to response for both pharmacotherapy and psychotherapy in the Treatment for Adolescents with Depression Study (TADS). Method: Adolescents (N = 439, ages 12 to 17 years) with major depressive disorder were randomized to fluoxetine (FLX), cognitive-behavioral therapy (CBT), their combination (COMB), or pill placebo…

  14. Dose Response Effects of Lisdexamfetamine Dimesylate Treatment in Adults with ADHD: An Exploratory Study

    ERIC Educational Resources Information Center

    Faraone, Stephen V.; Spencer, Thomas J.; Kollins, Scott H.; Glatt, Stephen J.; Goodman, David

    2012-01-01

    Objective: To explore dose-response effects of lisdexamfetamine dimesylate (LDX) treatment for ADHD. Method: This was a 4-week, randomized, double-blinded, placebo-controlled, parallel-group, forced-dose titration study in adult participants, aged 18 to 55 years, meeting "Diagnostic and Statistical Manual of Mental Disorders" (4th ed., text rev.)…

  15. Expression of Interferon Effector Gene SART1 Correlates with Interferon Treatment Response against Hepatitis B Infection

    PubMed Central

    Li, Yong; Zhu, Chuanlong; Wang, Faxi; Zhu, Tiantian; Liu, Shufeng

    2016-01-01

    Interferon-α (IFN-α) has limited response rate in the treatment of chronic hepatitis B (CHB). The underlying mechanism of differential responsiveness to IFN remains elusive. It has been recently reported that SART1 mediates antiviral effects of IFN-α in the hepatitis C virus (HCV) cell culture model. In this study, we investigated the role of SART1 in antiviral activity of IFN-α against hepatitis B virus (HBV) using blood and liver biopsy samples from chronic hepatitis B patients treated with pegylated IFN-α and HepG2 cells transfected with cloned HBV DNA. We observed that the basal SART1 expression in liver and PBMCs before IFN treatment was significantly higher in responders than in nonresponders. Furthermore, baseline SART1 expression level positively correlated with the degree of HBV DNA and HBeAg decline after IFN treatment. Mechanistically, silencing SART1 abrogated the antiviral activity of IFN-α, reduced the expression of IFN-stimulated genes (ISGs) Mx, OAS, and PKR, and attenuated JAK-STAT signaling in HepG2 cells, suggesting that SART1 regulates IFN-mediated antiviral activity through JAK-STAT signaling and ISG expression. Our study elucidates the important role of SART1 in IFN-mediated anti-HBV response and provides new insights into understanding variation of IFN treatment response in CHB patients. PMID:28077916

  16. 21 CFR 1230.15 - Responsibility for labeling directions for treatment.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Responsibility for labeling directions for treatment. 1230.15 Section 1230.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND...

  17. Improving Question-Asking Initiations in Young Children with Autism Using Pivotal Response Treatment

    ERIC Educational Resources Information Center

    Koegel, Robert L.; Bradshaw, Jessica L.; Ashbaugh, Kristen; Koegel, Lynn Kern

    2014-01-01

    Social initiations make up a core deficit for children with autism spectrum disorder (ASD). In particular, initiated questions during social interactions are often minimal or absent in this population. In the context of a multiple baseline design, the efficacy of using the motivational procedures of Pivotal Response Treatment to increase social…

  18. Therapeutic Responses of Psychopathic Sexual Offenders: Treatment Attrition, Therapeutic Change, and Long-Term Recidivism

    ERIC Educational Resources Information Center

    Olver, Mark E.; Wong, Stephen C. P.

    2009-01-01

    The authors examined the therapeutic responses of psychopathic sex offenders (greater than or equal to 25 Psychopathy Checklist-Revised; PCL-R) in terms of treatment dropout and therapeutic change, as well as sexual and violent recidivism over a 10-year follow-up among 156 federally incarcerated sex offenders treated in a high-intensity inpatient…

  19. Predictors of Treatment Response to Cognitive-Behavioral Therapy for Depression in Parkinson's Disease

    ERIC Educational Resources Information Center

    Dobkin, Roseanne D.; Rubino, Jade Tiu; Allen, Lesley A.; Friedman, Jill; Gara, Michael A.; Mark, Margery H.; Menza, Matthew

    2012-01-01

    Objective: The purpose of this study was to examine predictors of treatment response to cognitive-behavioral therapy (CBT) for depression in Parkinson's disease (PD). Method: The sample comprised 80 depressed ("DSM-IV" criteria) adults with PD (60% male) and their caregivers who participated in an National Institutes of Health-sponsored…

  20. Habituation of Premonitory Sensations during Exposure and Response Prevention Treatment in Tourette's Syndrome

    ERIC Educational Resources Information Center

    Verdellen, Cara W. J.; Hoogduin, Cees A. L.; Kato, Bernet S.; Keijsers, Ger P. J.; Cath, Danielle C.; Hoijtink, Herbert B.

    2008-01-01

    Exposure to premonitory sensations and response prevention of tics (ER) has been shown to be a promising new treatment for Tourette's syndrome (TS). The present study tested the hypothesis that habituation to unpleasant premonitory sensations associated with the tic is an underlying mechanism of change in ER. Patients rated the severity of…

  1. Time to response to citalopram treatment for agitation in Alzheimer's disease

    PubMed Central

    Weintraub, Daniel; Drye, Lea T.; Porsteinsson, Anton P.; Rosenberg, Paul B.; Pollock, Bruce G.; Devanand, D.P.; Frangakis, Constantine; Ismail, Zahinoor; Marano, Christopher; Meinert, Curtis L.; Mintzer, Jacobo E.; Munro, Cynthia A.; Pelton, Gregory; Rabins, Peter V.; Schneider, Lon S.; Shade, David M.; Yesavage, Jerome; Lyketsos, Constantine G.

    2015-01-01

    Background Agitation is a common and significant problem in Alzheimer’s disease (AD). In the recent Citalopram for Agitation in Alzheimer’s Disease (CitAD) study, citalopram was efficacious for the treatment of AD agitation. Here we examined the time course and predictors of response to treatment. Methods Response in CitAD was defined as a modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC) score of 1 or 2, or a Neurobehavioral Rating Scale agitation subscale (NBRS-A) score reduction ≥50% from baseline. “Stable early response” was defined as meeting the aforementioned criteria at both weeks 3 and 9, “late response” was response at week 9 but not at week 3, and “unstable response” was response at week 3 but not at week 9. Results In the primary analyses, citalopram was superior to placebo on both the CGIC and the NBRS-A response measures. There were little between-group differences in response rates in the first three weeks of the study (21% vs 19% on the CGIC). Citalopram patients were more likely than placebo patients to be a late responder (18% vs. 8% on CGIC, Fisher’s exact p=0.09; 31% vs. 15% on NBRS-A, Fisher’s exact p=0.02). Approximately half (45–56%) of citalopram responders at end-of-study achieved response later in the study, compared with 30–44% of placebo responders. Discussion Treatment with citalopram for agitation in AD needs to be at least nine weeks in duration to allow sufficient time for full response, and study duration is an important factor to consider in the design of clinical trials for agitation in Alzheimer’s disease. PMID:26238225

  2. Dissociation predicts treatment response in eye-movement desensitization and reprocessing for posttraumatic stress disorder.

    PubMed

    Bae, Hwallip; Kim, Daeho; Park, Yong Chon

    2016-01-01

    Using clinical data from a specialized trauma clinic, this study investigated pretreatment clinical factors predicting response to eye-movement desensitization and reprocessing (EMDR) among adult patients diagnosed with posttraumatic stress disorder (PTSD). Participants were evaluated using the Clinician-Administered PTSD Scale (CAPS), the Symptom Checklist-90-Revised, the Beck Depression Inventory, and the Dissociative Experiences Scale before treatment and were reassessed using the CAPS after treatment and at 6-month follow-up. A total of 69 patients underwent an average of 4 sessions of EMDR, and 60 (87%) completed the posttreatment evaluation, including 8 participants who terminated treatment prematurely. Intent-to-treat analysis revealed that 39 (65%) of the 60 patients were classified as responders and 21 (35%) as nonresponders when response was defined as more than a 30% decrease in total CAPS score. The nonresponders had higher levels of dissociation (depersonalization and derealization) and numbing symptoms, but other PTSD symptoms, such as avoidance, hyperarousal, and intrusion, were not significantly different. The number of psychiatric comorbidities was also associated with treatment nonresponse. The final logistic regression model yielded 2 significant variables: dissociation (p < .001) and more than 2 comorbidities compared to none (p < .05). These results indicate that complex symptom patterns in PTSD may predict treatment response and support the inclusion of the dissociative subtype of PTSD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

  3. Genomic Profiling of the Response of Candida albicans to Itraconazole Treatment Using a DNA Microarray

    PubMed Central

    De Backer, Marianne D.; Ilyina, Tatiana; Ma, Xiao-Jun; Vandoninck, Sandy; Luyten, Walter H. M. L.; Vanden Bossche, Hugo

    2001-01-01

    The application of genome-wide expression profiling to determine how drugs achieve their therapeutic effect has provided the pharmaceutical industry with an exciting new tool for drug mode-of-action studies. We used DNA chip technology to study cellular responses to perturbations of ergosterol biosynthesis caused by the broad-spectrum antifungal agent itraconazole. Simultaneous examination of over 6,600 Candida albicans gene transcript levels, representing the entire genome, upon treatment of cells with 10 μM itraconazole revealed that 296 genes were responsive. For 116 genes transcript levels were decreased at least 2.5-fold, while for 180 transcript levels were similarly increased. A global upregulation of ERG genes in response to azole treatment was observed. ERG11 and ERG5 were found to be upregulated approximately 12-fold. In addition, a significant upregulation was observed for ERG6, ERG1, ERG3, ERG4, ERG10, ERG9, ERG26, ERG25, ERG2, IDII, HMGS, NCP1, and FEN2, all of which are genes known to be involved in ergosterol biosynthesis. The effects of itraconazole on a wide variety of known metabolic processes are discussed. As over 140 proteins with unknown function were responsive to itraconazole, our analysis might provide—in combination with phenotypic data—first hints of their potential function. The present report is the first to describe the application of DNA chip technology to study the response of a major human fungal pathogen to drug treatment. PMID:11353609

  4. Magnetic Resonance Imaging Predictors of Treatment Response in First-Episode Schizophrenia

    PubMed Central

    Szeszko, Philip R.; Narr, Katherine L.; Phillips, Owen R.; McCormack, Joanne; Sevy, Serge; Gunduz-Bruce, Handan; Kane, John M.; Bilder, Robert M.; Robinson, Delbert G.

    2012-01-01

    Identifying neurobiological predictors of response to antipsychotics in patients with schizophrenia is a critical goal of translational psychiatry. Few studies, however, have investigated the relationship between indices of brain structure and treatment response in the context of a controlled clinical trial. In this study, we sought to identify magnetic resonance (MR) imaging measures of the brain that predict treatment response in patients experiencing a first-episode of schizophrenia. Structural MR imaging scans were acquired in 39 patients experiencing a first-episode of schizophrenia with minimal or no prior exposure to antipsychotics participating in a double-blind 16-week clinical trial comparing the efficacy of risperidone vs olanzapine. Twenty-five patients were classified as responders by meeting operationally defined treatment response criteria on 2 consecutive study visits. Fourteen patients never responded to antipsychotic medication at any point during the clinical trial. MR imaging scans were also acquired in 45 age- and sex-matched healthy volunteers. Cortical pattern matching methods were used to compare cortical thickness and asymmetry measures among groups. Statistical mapping results, confirmed by permutation testing, indicated that responders had greater cortical thickness in occipital regions and greater frontal cortical asymmetry compared with nonresponders. Moreover, among responders, greater thickness in temporal regions was associated with less time to respond. Our findings are consistent with the hypothesis that plasticity and cortical thickness may be more preserved in responders and that MR imaging may assist in the prediction of antipsychotic drug response in patients experiencing a first-episode of schizophrenia. PMID:21084552

  5. Magnetic resonance imaging predictors of treatment response in first-episode schizophrenia.

    PubMed

    Szeszko, Philip R; Narr, Katherine L; Phillips, Owen R; McCormack, Joanne; Sevy, Serge; Gunduz-Bruce, Handan; Kane, John M; Bilder, Robert M; Robinson, Delbert G

    2012-05-01

    Identifying neurobiological predictors of response to antipsychotics in patients with schizophrenia is a critical goal of translational psychiatry. Few studies, however, have investigated the relationship between indices of brain structure and treatment response in the context of a controlled clinical trial. In this study, we sought to identify magnetic resonance (MR) imaging measures of the brain that predict treatment response in patients experiencing a first-episode of schizophrenia. Structural MR imaging scans were acquired in 39 patients experiencing a first-episode of schizophrenia with minimal or no prior exposure to antipsychotics participating in a double-blind 16-week clinical trial comparing the efficacy of risperidone vs olanzapine. Twenty-five patients were classified as responders by meeting operationally defined treatment response criteria on 2 consecutive study visits. Fourteen patients never responded to antipsychotic medication at any point during the clinical trial. MR imaging scans were also acquired in 45 age- and sex-matched healthy volunteers. Cortical pattern matching methods were used to compare cortical thickness and asymmetry measures among groups. Statistical mapping results, confirmed by permutation testing, indicated that responders had greater cortical thickness in occipital regions and greater frontal cortical asymmetry compared with nonresponders. Moreover, among responders, greater thickness in temporal regions was associated with less time to respond. Our findings are consistent with the hypothesis that plasticity and cortical thickness may be more preserved in responders and that MR imaging may assist in the prediction of antipsychotic drug response in patients experiencing a first-episode of schizophrenia.

  6. Effect of nabumetone treatment on vascular responses of the thoracic aorta in rat experimental arthritis.

    PubMed

    Ulker, S; Onal, A; Hatip, F B; Sürücü, A; Alkanat, M; Koşay, S; Evinç, A

    2000-04-01

    Nabumetone is a nonsteroidal anti-inflammatory (NSAI) drug which is known to cause less gastrointestinal damage than other NSAI drugs. This study was performed to evaluate whether nabumetone treatment might alter the vascular aberrations related to inflammation in a rat model of adjuvant-induced arthritis. Nabumetone treatment (120 or 240 mg x kg(-1) x day(-1), orally) was initiated on the 15th day of adjuvant inoculation and continued for 14 days. Arthritic lesions, vascular contractile and relaxant responses and gastroduodenal histopathological preparations were evaluated 29 days after adjuvant inoculation. The contractile responses of aortic rings to phenylephrine and KCl were increased in grade 2 arthritic rats. In grade 3 arthritis only the phenylephrine contractility was decreased. The relaxant responses to acetylcholine and sodium nitroprusside were decreased in grades 2 and 3. In healthy rats, nabumetone did not change the vascular responses. After treatment of arthritic rats with nabumetone, both the contractile and relaxant response of the aortic rings returned to normal, and arthritic score and paw swelling were reduced. Gastroduodenal histopathology did not show erosions or ulcers in any of the groups. In conclusion, nabumetone improved the systemic signs and vascular alterations in experimental arthritis without showing any gastrointestinal side effects.

  7. Sex influences immune responses to viruses, and efficacy of prophylaxis and treatments for viral diseases.

    PubMed

    Klein, Sabra L

    2012-12-01

    The intensity and prevalence of viral infections are typically higher in males, whereas disease outcome can be worse for females. Females mount higher innate and adaptive immune responses than males, which can result in faster clearance of viruses, but also contributes to increased development of immunopathology. In response to viral vaccines, females mount higher antibody responses and experience more adverse reactions than males. The efficacy of antiviral drugs at reducing viral load differs between the sexes, and the adverse reactions to antiviral drugs are typically greater in females than males. Several variables should be considered when evaluating male/female differences in responses to viral infection and treatment: these include hormones, genes, and gender-specific factors related to access to, and compliance with, treatment. Knowledge that the sexes differ in their responses to viruses and to treatments for viral diseases should influence the recommended course of action differently for males and females. Editor's suggested further reading in BioEssays X-chromosome-located microRNAs in immunity: Might they explain male/female differences Abstract.

  8. Response of the dropped head/bent spine syndrome to treatment with intravenous immunoglobulin.

    PubMed

    Dominick, Justin; Sheean, Geoffrey; Schleimer, Jonathan; Wixom, Christopher

    2006-06-01

    Weakness of neck extension causing a dropped head may result from many neuromuscular disorders. One etiology is isolated neck extensor myopathy. A similar focal myopathy of the lower axial muscles may cause the bent spine syndrome, which manifests as flexion of the trunk and inability to stand upright. Combination of both dropped head and bent spine myopathies is uncommon. Inflammation is usually not pronounced in these conditions and response to immunosuppressive treatment is rare. We present an 81-year-old man who developed progressive weakness of neck and trunk extension over several months, with a prominent inflammatory process in the thoracic paraspinal muscles, which responded dramatically to treatment with intravenous immunoglobulin (IVIg). This case, together with other rare reports, suggests that the presence of inflammation in the biopsy of an affected muscle may predict treatment response.

  9. Computerized EEG as a predictor of drug response in treatment resistant schizophrenics.

    PubMed

    Itil, T M; Shapiro, D; Schneider, S J; Francis, I B

    1981-10-01

    Thirteen chronic schizophrenics were identified who failed to improve with physician's choice medication and 1 year of systematic treatment with a long acting phenothiazine. These patients were considered to be treatment resistant. Computer analyzed electroencephalogram (CEEG) or these treatment resistant schizophrenics was characterized by a large amount of alpha activity and less fast activity, in comparison with previous results from therapy responsive schizophrenics. The therapy resistant subjects did not display the typical neuroleptic CEEG profile following test dosages of four neuroleptics, and instead displayed CEEG profiles which more closely resembled the typical profile for psychostimulants. These findings may point to an altered metabolism, neurotransmitter defect, or other problem which alters the physiological and clinical response of therapy resistant schizophrenics to neuroleptic medication.

  10. Testing Equality of Treatments under an Incomplete Block Crossover Design with Ordinal Responses.

    PubMed

    Lui, Kung-Jong

    2017-02-03

    The generalized odds ratio (GOR) for paired sample is considered to measure the relative treatment effect on patient responses in ordinal data. Under a three-treatment two-period incomplete block crossover design, both asymptotic and exact procedures are developed for testing equality between treatments with ordinal responses. Monte Carlo simulation is employed to evaluate and compare the finite-sample performance of these test procedures. A discussion on advantages and disadvantages of the proposed test procedures based on the GOR versus those based on Wald's tests under the normal random effects proportional odds model is provided. The data taken as a part of a crossover trial studying the effects of low and high doses of an analgesic versus a placebo for the relief of pain in primary dysmenorrhea over the first two periods are applied to illustrate the use of these test procedures.

  11. Genetic predictors of the response to the treatment of hepatitis C virus infection

    PubMed Central

    Dzekova-Vidimliski, Pavlina; Nikolov, Igor G.; Matevska-Geshkovska, Nadica; Boyanova, Yana; Nikolova, Nina; Romanciuc, Grigore; Dumitrascu, Dan; Caloska-Ivanova, Viktorija; Joksimovic, Nenad; Antonov, Krasimir; Mateva, Lyudmila; Rostaing, Lionel; Dimovski, Aleksandar; Sikole, Aleksandar

    2015-01-01

    The genome-wide association studies have identified a strong association between interleukin 28B (IL28B) gene polymorphisms and the response to treatment in patients with hepatitis C virus (HCV) infection. The aim of the study was to evaluate the association between three most widely studied IL28B gene polymorphisms and the response to antiviral treatment of chronic hepatitis C. We performed the genotyping of the three IL28B gene polymorphisms: rs12979860, rs8099917, and rs12980275 in 72 Caucasian patients with chronic hepatitis C, previously treated with the combination therapy of pegylated interferon alpha (PEGIFN α) and ribavirin (RBV). The patients included in the study had finished the treatment regimen at least 6 months before enrolling in the study. We used the sustained viral response (SVR) for the evaluation of the effectiveness of the antiviral treatment, and it was tested with an assay with a sensitivity of 20 IU/mL. An SVR was achieved in 59.7% (43/72) of the treated patients. The three IL28B gene polymorphisms (CC genotype of rs12979860, TT genotype of rs8099917, and AA genotype of rs12980275) were associated with the SVR (p = 0.029, p = 0.016, and p = 0.028, respectively) in the study patients with chronic hepatitis C treated with the combination therapy of PEGIFN α and RBV. The association of IL28B gene polymorphisms with the treatment response points to the possibility of personalized medicine for the treatment of HCV infection. PMID:26614853

  12. Differences in maintenance of response upon discontinuation across medication treatments in attention-deficit/hyperactivity disorder.

    PubMed

    Buitelaar, Jan; Asherson, Philip; Soutullo, Cesar; Colla, Michael; Adams, David H; Tanaka, Yoko; Haynes, Virginia S; Escobar, Rodrigo; Upadhyaya, Himanshu

    2015-10-01

    The attention-deficit/hyperactivity disorder (ADHD) treatment literature has been focused on onset-of-effect and short-term effect size, with little exploration of ADHD symptoms upon medication discontinuation. The objective of this narrative review and analysis was to better understand the relapse of ADHD symptoms upon discontinuation of medication treatment in children, adolescents, and adults with ADHD who have responded to medication treatment and to explore differences among different medications in maintaining treatment response. Randomized withdrawal studies of dexmethylphenidate hydrochloride (d-MPH), methylphenidate modified-release (MPH-LA), lisdexamphetamine dimesylate (LDX), guanfacine extended-release (GXR), and atomoxetine (ATX) in both children/adolescents and adults with ADHD were reviewed. The percentage of relapse was significantly higher and the time-to-relapse significantly shorter with placebo compared to active treatment in patients who were previously stable on 5 weeks to 1 year of active treatment, suggesting clinically significant benefit with continued long-term pharmacotherapy. However, percentage of relapse at each time point studied after discontinuing stimulants and GXR appears substantially higher than observed when discontinuing ATX, suggesting longer maintenance of response after discontinuing ATX than after stimulants and GXR. Additionally, slope of relapse percentages over time appears to be more rapid with stimulants or GXR than with ATX. These differences in maintenance of response among ATX, GXR, and stimulants may reflect differences in mechanisms of action and persistence of the medication effect. Alternatively, they may be due to methodological differences, including study design and response/relapse definitions. Continued investigation is needed regarding factors that affect risk of symptom relapse upon discontinuation of pharmacotherapy.

  13. Race, genetic ancestry and response to antidepressant treatment for major depression.

    PubMed

    Murphy, Eleanor; Hou, Liping; Maher, Brion S; Woldehawariat, Girma; Kassem, Layla; Akula, Nirmala; Laje, Gonzalo; McMahon, Francis J

    2013-12-01

    The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study revealed poorer antidepressant treatment response among black compared with white participants. This racial disparity persisted even after socioeconomic and baseline clinical factors were taken into account. Some studies have suggested genetic contributions to this disparity, but none have attempted to disentangle race and genetic ancestry. Here we used genome-wide single-nucleotide polymorphism (SNP) data to examine independent contributions of race and genetic ancestry to citalopram response. Secondary data analyses included 1877 STAR*D participants who completed an average of 10 weeks of citalopram treatment and provided DNA samples. Participants reported their race as White (n=1464), black (n=299) or other/mixed (n=114). Genetic ancestry was estimated by multidimensional scaling (MDS) analyses of about 500 000 SNPs. Ancestry proportions were estimated by STRUCTURE. Structural equation modeling was used to examine the direct and indirect effects of observed and latent predictors of response, defined as change in the Quick Inventory of Depressive Symptomatology (QIDS) score from baseline to exit. Socioeconomic and baseline clinical factors, race, and anxiety significantly predicted response, as previously reported. However, direct effects of race disappeared in all models that included genetic ancestry. Genetic African ancestry predicted lower treatment response in all models. Although socioeconomic and baseline clinical factors drive racial differences in antidepressant response, genetic ancestry, rather than self-reported race, explains a significant fraction of the residual differences. Larger samples would be needed to identify the specific genetic mechanisms that may be involved, but these findings underscore the importance of including more African-American patients in drug trials.

  14. Avian community responses to juniper woodland structure and thinning treatments on the Colorado Plateau

    USGS Publications Warehouse

    Crow, Claire; van Riper, Charles

    2011-01-01

    We also studied responses of breeding birds to mechanical reduction of pinyon-juniper woodlands scattered across sagebrush steppe in 11 control and 9 treatment plots at Grand Staircase-Escalante National Monument, Utah, in 2005 and 2006. We surveyed birds in 3.1-ha (7.6-acre) plots during the breeding season before and following treatment. Thinning in April 2006 removed a mean of 92 percent (standard error = 6.4 percent) of the live trees from treatment plots. Two of 14 species, Gray Vireo (Vireo vicinior) and Brown-headed Cowbird (Molothrus ater), were not detected after thinning. Shrub-nesting birds, including sagebrush specialist Brewer's Sparrow (Spizella breweri), increased in relative abundance in treatment areas compared to controls. However, some species may exhibit a time lag in response, and further changes in community composition and abundance could result. Our findings lend support to the concept that multiple small-scale fuels-reduction treatments, applied over the landscape, may provide the variety of successional stages needed to support a full assemblage of avian species in pinyon-juniper woodlands on the Colorado Plateau. Limiting scale and increasing precision of fuels-reduction projects in pinyon-juniper vegetation communities may maximize the benefits of management to both the pinyon-juniper and sagebrush steppe avian communities. We conclude that small-scale fuels-reduction treatments can benefit many bird species while reducing fire risk and restoring an ecological balance.

  15. The role of readiness to change in response to treatment of adolescent depression.

    PubMed

    Lewis, Cara C; Simons, Anne D; Silva, Susan G; Rohde, Paul; Small, David M; Murakami, Jessica L; High, Robin R; March, John S

    2009-06-01

    The effect of readiness to change on treatment outcome was examined among 332 adolescents (46% male, 74% Caucasian), ages 12 through 17 years (M = 14.6, SD = 1.5), with major depressive disorder who were participating in the Treatment for Adolescents With Depression Study (TADS). TADS is a randomized clinical trial comparing the effectiveness of fluoxetine (an antidepressant medication), cognitive-behavioral therapy, their combination, and a pill placebo. An abbreviated Stages of Change Questionnaire was used to obtain 4 readiness to change scores: precontemplation, contemplation, action, and maintenance. The association between each readiness score and depression severity across 12 weeks of acute treatment for depression, as measured by the Children's Depression Rating Scale--Revised, was examined. Although treatment response was not moderated by any of the readiness scores, baseline action scores predicted outcome: Higher action scores were associated with better outcome regardless of treatment modality. Furthermore, treatment effects were mediated by change in action scores during the first 6 weeks of treatment, with increases in action scores related to greater improvement in depression. Assessing readiness to change may have implications for tailoring treatments for depressed adolescents.

  16. Assessment and monitoring of treatment response in adult ADHD patients: current perspectives

    PubMed Central

    Ramsay, J Russell

    2017-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome that emerges in childhood or early adolescence and persists into adulthood for a majority of individuals. There are many other adults with ADHD who may not seek out evaluation and treatment until adulthood, having been able to “get by” before struggling with inattention, hyperactivity, and/or impulsivity in adulthood, in addition to facing the associated features of disorganization, poor time management, and procrastination among many others. A lifetime diagnosis of ADHD is associated with a wide range of life impairments, which makes a comprehensive and accurate diagnostic assessment essential in order to obtain appropriate treatment. Moreover, while there are effective medical and psychosocial treatments for ADHD, it is important to be able to track treatment response in order to evaluate whether adjustments in specific interventions are needed or referrals for adjunctive treatments and supports are indicated to facilitate optimal therapeutic outcomes. The goal of this article is to provide a clinically useful review of the various measures that practicing clinicians can use to aid in the diagnostic assessment and monitoring of psychosocial and medical treatment of ADHD in adult patients. This review includes various structured interviews, screening scales, adult ADHD symptom inventories, measures of associated features of ADHD, as well as ratings of impairment and functioning which can be adapted to clinicians’ practice needs in order to track treatment progress and optimize treatments for adults with ADHD. PMID:28184164

  17. A responsive evaluation of mental health treatment in Cambodia: Intentionally addressing poverty to increase cultural responsiveness in therapy.

    PubMed

    Seponski, Desiree M; Lewis, Denise C; Megginson, Maegan C

    2014-01-01

    Mental health issues are significant contributors to the global burden of disease with the highest incidence in resource poor countries; 90% of those in need of mental health treatment reside in low resource countries but receive only 10% of the world's resources. Cambodia, the eighth least developed country in the world, serves as one example of the need to address mental health concerns in low-income, resource poor countries. The current study utilises responsive evaluation methodology to explore how poverty-stricken Cambodian clients, therapists and supervisors experience Western models of therapy as culturally responsive to their unique needs. Quantitative and qualitative data were triangulated across multiple stakeholders using numerous methods including a focus group, interviews, surveys, case illustrations and live supervision observation and analysed using constant comparative analysis. Emerging findings suggest that poverty, material needs, therapy location and financial situations greatly impact the daily lives and mental health conditions of Cambodians and hinder clients' therapeutic progress. The local community needs and context of poverty greatly hinder clients' therapeutic progress in therapy treatment and when therapy does not directly address the culture of poverty, clients did not experience therapy as valuable despite some temporary decreases in mental health symptoms.

  18. The impact of melanoma genetics on treatment response and resistance in clinical and experimental studies.

    PubMed

    Kunz, M; Hölzel, M

    2017-02-16

    Recent attempts to characterize the melanoma mutational landscape using high-throughput sequencing technologies have identified new genes and pathways involved in the molecular pathogenesis of melanoma. Apart from mutated BRAF, NRAS, and KIT, a series of new recurrently mutated candidate genes with impact on signaling pathways have been identified such as NF1, PTEN, IDH1, RAC1, ARID2, and TP53. Under targeted treatment using BRAF and MEK1/2 inhibitors either alone or in combination, a majority of patients experience recurrences, which are due to different genetic mechanisms such as gene amplifications of BRAF or NRAS, MEK1/2 and PI3K mutations. In principle, resistance mechanisms converge on two signaling pathways, MAPK and PI3K-AKT-mTOR pathways. Resistance may be due to small subsets of resistant cells within a heterogeneous tumor mass not identified by sequencing of the bulk tumor. Future sequencing studies addressing tumor heterogeneity, e.g., by using single-cell sequencing technology, will most likely improve this situation. Gene expression patterns of metastatic lesions were also shown to predict treatment response, e.g., a MITF-low/NF-κB-high melanoma phenotype is resistant against classical targeted therapies. Finally, more recent treatment approaches using checkpoint inhibitors directed against PD-1 and CTLA-4 are very effective in melanoma and other tumor entities. Here, the mutational and neoantigen load of melanoma lesions may help to predict treatment response. Taken together, the new sequencing, molecular, and bioinformatic technologies exploiting the melanoma genome for treatment decisions have significantly improved our understanding of melanoma pathogenesis, treatment response, and resistance for either targeted treatment or immune checkpoint blockade.

  19. PET-Based Treatment Response Evaluation in Rectal Cancer: Prediction and Validation

    SciTech Connect

    Janssen, Marco H.M.; Oellers, Michel C.; Stiphout, Ruud G.P.M. van; Riedl, Robert G.; Bogaard, Jorgen van den; Buijsen, Jeroen; Lambin, Philippe; Lammering, Guido

    2012-02-01

    Purpose: To develop a positron emission tomography (PET)-based response prediction model to differentiate pathological responders from nonresponders. The predictive strength of the model was validated in a second patient group, treated and imaged identical to the patients on which the predictive model was based. Methods and Materials: Fifty-one rectal cancer patients were prospectively included in this study. All patients underwent fluorodeoxyglucose (FDG) PET-computed tomography (CT) imaging both before the start of chemoradiotherapy (CRT) and after 2 weeks of treatment. Preoperative treatment with CRT was followed by a total mesorectal excision. From the resected specimen, the tumor regression grade (TRG) was scored according to the Mandard criteria. From one patient group (n = 30), the metabolic treatment response was correlated with the pathological treatment response, resulting in a receiver operating characteristic (ROC) curve based cutoff value for the reduction of maximum standardized uptake value (SUV{sub max}) within the tumor to differentiate pathological responders (TRG 1-2) from nonresponders (TRG 3-5). The applicability of the selected cutoff value for new patients was validated in a second patient group (n = 21). Results: When correlating the metabolic and pathological treatment response for the first patient group using ROC curve analysis (area under the curve = 0.98), a cutoff value of 48% SUV{sub max} reduction was selected to differentiate pathological responders from nonresponders (specificity of 100%, sensitivity of 64%). Applying this cutoff value to the second patient group resulted in a specificity and sensitivity of, respectively, 93% and 83%, with only one of the pathological nonresponders being false positively predicted as pathological responding. Conclusions: For rectal cancer, an accurate PET-based prediction of the pathological treatment response is feasible already after 2 weeks of CRT. The presented predictive model could be used to

  20. Pivotal Response Treatment Parent Training for Autism: Findings from a 3-Month Follow-Up Evaluation.

    PubMed

    Gengoux, Grace W; Berquist, Kari L; Salzman, Emma; Schapp, Salena; Phillips, Jennifer M; Frazier, Thomas W; Minjarez, Mendy B; Hardan, Antonio Y

    2015-09-01

    This study's objective was to assess maintenance of treatment effects 3 months after completion of a 12-week Pivotal Response Treatment (PRT) parent education group. Families who completed the active treatment (N = 23) were followed for an additional 12 weeks to measure changes in language and cognitive skills. Results indicated a significant improvement in frequency of functional utterances, with maintenance at 3-month follow-up [F(2, 21): 5.9, p = .009]. Children also made significant gains on the Vineland Communication Domain Standard Score [F(2, 12):11.74, p = .001] and the Mullen Scales of Early Learning Composite score [F(1, 20) = 5.43, p = .03]. These results suggest that a brief PRT parent group intervention can lead to improvements in language and cognitive functioning that are maintained 12 weeks post treatment.

  1. Treatment of cockroach allergen asthma model with imatinib attenuates airway responses.

    PubMed

    Berlin, Aaron A; Lukacs, Nicholas W

    2005-01-01

    In the present study it was determined whether a pharmacologic approach to blocking receptor tyrosine kinase-mediated activation during allergic airway responses could be beneficial. To examine these responses, allergic mice were given a single oral dose of imatinib at clinically relevant concentrations, ranging from 0.05 to 50 mg/kg, by oral gavages just before allergen challenge. The reduction in the allergen-induced responses was significant and centered on reducing overall inflammation as well as pulmonary cytokine levels. In particular, the treatment of the mice with imatinib significantly attenuated airway hyperreactivity and peribronchial eosinophil accumulation, and significantly reduced Th2 cytokines, interleukin-4 and interleukin-13. In addition, chemokines previously associated with allergen-induced pulmonary disease, CCL2, CCL5, and CCL6, were significantly reduced in the lungs of the imatinib-treated animals. Together these data demonstrate that the pharmacologic inhibitor imatinib may provide a clinically attractive therapy for allergic, asthmatic responses.

  2. Brain responses to biological motion predict treatment outcome in young children with autism

    PubMed Central

    Yang, D; Pelphrey, K A; Sukhodolsky, D G; Crowley, M J; Dayan, E; Dvornek, N C; Venkataraman, A; Duncan, J; Staib, L; Ventola, P

    2016-01-01

    Autism spectrum disorders (ASDs) are common yet complex neurodevelopmental disorders, characterized by social, communication and behavioral deficits. Behavioral interventions have shown favorable results—however, the promise of precision medicine in ASD is hampered by a lack of sensitive, objective neurobiological markers (neurobiomarkers) to identify subgroups of young children likely to respond to specific treatments. Such neurobiomarkers are essential because early childhood provides a sensitive window of opportunity for intervention, while unsuccessful intervention is costly to children, families and society. In young children with ASD, we show that functional magnetic resonance imaging-based stratification neurobiomarkers accurately predict responses to an evidence-based behavioral treatment—pivotal response treatment. Neural predictors were identified in the pretreatment levels of activity in response to biological vs scrambled motion in the neural circuits that support social information processing (superior temporal sulcus, fusiform gyrus, amygdala, inferior parietal cortex and superior parietal lobule) and social motivation/reward (orbitofrontal cortex, insula, putamen, pallidum and ventral striatum). The predictive value of our findings for individual children with ASD was supported by a multivariate pattern analysis with cross validation. Predicting who will respond to a particular treatment for ASD, we believe the current findings mark the very first evidence of prediction/stratification biomarkers in young children with ASD. The implications of the findings are far reaching and should greatly accelerate progress toward more precise and effective treatments for core deficits in ASD. PMID:27845779

  3. Age and sex differences in immune response following LPS treatment in mice.

    PubMed

    Cai, Kyle Chiman; van Mil, Spencer; Murray, Emma; Mallet, Jean-François; Matar, Chantal; Ismail, Nafissa

    2016-11-01

    Puberty is an important developmental event that is marked by the reorganizing and remodeling of the brain. Exposure to stress during this critical period of development can have enduring effects on both reproductive and non-reproductive behaviors. The purpose of this study was to investigate age and sex differences in immune response by examining sickness behavior, body temperature changes, and serum cytokine levels following an immune challenge. The effects of circulating gonadal hormones on age and sex differences in immune response were also examined. Results showed that male mice display more sickness behavior and greater fluctuations in body temperature following LPS treatment than female mice. Moreover, adult male mice display more sickness behavior and a greater drop in body temperature following LPS treatment compared to pubertal male mice. Following gonadectomy, pubertal and adult males displayed steeper and prolonged drops in body temperature compared to sham-operated counterparts. Gonadectomy did not eliminate sex differences in LPS-induced body temperature changes, suggesting that additional factors contribute to the observed differences. LPS treatment increased cytokine levels in all mice. However, the increase in pro-inflammatory cytokines was higher in adult compared to pubertal mice, while the increase in anti-inflammatory cytokines was greater in pubertal than in adult mice. Our findings contribute to a better understanding of age and sex differences in acute immune response following LPS treatment and possible mechanisms involved in the enduring alterations in behavior and brain function following pubertal exposure to LPS.

  4. Akt inhibition improves irinotecan treatment and prevents cell emergence by switching the senescence response to apoptosis

    PubMed Central

    Vétillard, Alexandra; Jonchère, Barbara; Moreau, Marie; Toutain, Bertrand; Henry, Cécile; Fontanel, Simon; Bernard, Anne-Charlotte; Campone, Mario; Guette, Catherine; Coqueret, Olivier

    2015-01-01

    Activated in response to chemotherapy, senescence is a tumor suppressive mechanism that induces a permanent loss of proliferation. However, in response to treatment, it is not really known how cells can escape senescence and how irreversible or incomplete this pathway is. We have recently described that cells that escape senescence are more transformed than non-treated parental cells, they resist anoikis and rely on Mcl-1. In this study, we further characterize this emergence in response to irinotecan, a first line treatment used in colorectal cancer. Our results indicate that Akt was activated as a feedback pathway during the early step of senescence. The inhibition of the kinase prevented cell emergence and improved treatment efficacy, both in vitro and in vivo. This improvement was correlated with senescence inhibition, p21waf1 downregulation and a concomitant activation of apoptosis due to Noxa upregulation and Mcl-1 inactivation. The inactivation of Noxa prevented apoptosis and increased the number of emergent cells. Using either RNA interference or p21waf1-deficient cells, we further confirmed that an intact p53-p21-senescence pathway favored cell emergence and that its downregulation improved treatment efficacy through apoptosis induction. Therefore, although senescence is an efficient suppressive mechanism, it also generates more aggressive cells as a consequence of apoptosis inhibition. We therefore propose that senescence-inducing therapies should be used sequentially with drugs favoring cell death such as Akt inhibitors. This should reduce cell emergence and tumor relapse through a combined induction of senescence and apoptosis. PMID:26485768

  5. Subtyping Schizophrenia by Treatment Response: Antipsychotic Development and the Central Role of Positive Symptoms.

    PubMed

    Lee, Jimmy; Takeuchi, Hiroyoshi; Fervaha, Gagan; Sin, Gwen Li; Foussias, George; Agid, Ofer; Farooq, Saeed; Remington, Gary

    2015-11-01

    We have recently proposed a model for subtyping schizophrenia based on antipsychotic (AP) treatment response. Evidence suggests that APs, both old and new, are comparable in terms of efficacy; however, one AP, clozapine, is uniquely effective in one subgroup of patients (that is, those with treatment-resistant schizophrenia [TRS]). This permits us to subdivide schizophrenia into 3 specific groups: AP responsive, clozapine responsive, and clozapine resistant. Here, we integrate this model with current criteria related to TRS and ultraresistant schizophrenia, the latter referred to in our model as clozapine resistant. We suggest several modifications to existing criteria, in line with current evidence and practice patterns, particularly emphasizing the need to focus on positive symptoms. While APs can favourably impact numerous dimensions related to schizophrenia, it is their effect on positive symptoms that distinguishes them from other psychotropics. Further, it is positive symptoms that are central to AP and clozapine resistance, and it is these people that place the greatest demands on acute and long-term inpatient resources. In moving AP development forward, we advocate specifically focusing on positive symptoms and capitalizing on the evidence we have of 3 subtypes of psychosis (that is, positive symptoms) based on treatment response, implicating 3 distinguishable forms of underlying pathophysiology. Conversely, pooling these groups risks obfuscating potentially identifiable differences. Such a position does not challenge the importance of dopamine D2 receptor blockade, but rather highlights the need to better isolate those other subgroups that require something more or entirely different.

  6. Markers of Differential Response to Inhaled Corticosteroid Treatment among Children with Mild Persistent Asthma

    PubMed Central

    Gerald, Joe K.; Gerald, Lynn B.; Vasquez, Monica M.; Morgan, Wayne J; Boehmer, Susan J; Lemanske, Robert F; Mauger, David T.; Strunk, Robert C.; Szefler, Stanley J; Zeiger, Robert S; Bacharier, Leonard B.; Bade, Elizabeth; Covar, Ronina A.; Guilbert, Theresa W; Heidarian-Raissy, Hengameh; Kelly, H William; Malka-Rais, Jonathan; Sorkness, Christine A.; Taussig, Lynn; Chinchilli, Vernon M.; Martinez, Fernando D.

    2015-01-01

    Background Inhaled corticosteroids (ICSs) are recommended as first-line therapy for children with mild persistent asthma; however, specific patient characteristics may modify the treatment response. Objective Identify demographic, clinical, and atopic characteristics that may modify the ICS treatment response among children enrolled in the Treating Children to Prevent Exacerbations of Asthma (TREXA) trial. Methods Children age 6-18 years with mild persistent asthma were randomized to 44 weeks of combined, daily, rescue, or placebo treatment. Daily treatment consisted of 40 mcg of beclomethasone twice daily. Rescue treatment consisted of 40 mcg beclomethasone accompanying each symptom-driven albuterol actuation. Combined treatment consisted of both. Outcomes included time to first exacerbation and proportion of asthma control days. Fourteen baseline characteristics were selected for interaction testing based on their clinical relevance. Results Two-hundred-eighty-eight children were randomized. Seventy-five percent were white and 55% were male. As measured by time to first exacerbation, 4 characteristics identified children who received greater benefit from treatment: non-Hispanic ethnicity, positive aeroallergen skin test, serum immunoglobulin E level ≥350 K/μL, and history of oral corticosteroid use in the year prior to enrollment. As measured by asthma control days, 4 characteristics identified children who received greater benefit from treatment: male sex, positive aeroallergen skin test, serum immunoglobulin E level ≥350 K/μL, and incomplete run-in asthma control. Conclusions Children with mild persistent asthma who have markers of atopic asthma or who have greater asthma burden may obtain greater benefit from beclomethasone therapy. Additional study is needed to confirm whether these markers can guide individualized therapy. PMID:25783161

  7. Glucocorticoid Genes and the Developmental Origins of Asthma Susceptibility and Treatment Response

    PubMed Central

    Kho, Alvin T.; Chhabra, Divya; Qiu, Weiliang; Gaedigk, Roger; Vyhlidal, Carrie A.; Leeder, J. Steven; Barraza-Villarreal, Albino; London, Stephanie J.; Gilliland, Frank; Raby, Benjamin A.; Weiss, Scott T.; Tantisira, Kelan G.

    2015-01-01

    Antenatal corticosteroids enhance lung maturation. However, the importance of glucocorticoid genes on early lung development, asthma susceptibility, and treatment response remains unknown. We investigated whether glucocorticoid genes are important during lung development and their role in asthma susceptibility and treatment response. We identified genes that were differentially expressed by corticosteroids in two of three genomic datasets: lymphoblastoid cell lines of participants in the Childhood Asthma Management Program, a glucocorticoid chromatin immunoprecipitation/RNA sequencing experiment, or a murine model; these genes made up the glucocorticoid gene set (GCGS). Using gene expression profiles from 38 human fetal lungs and C57BL/6J murine fetal lungs, we identified developmental genes that were in the top 5% of genes contributing to the top three principal components (PCs) most highly associated with post-conceptional age. Glucocorticoid genes that were enriched in this set of developmental genes were then included in the developmental glucocorticoid gene set (DGGS). We then investigated whether glucocorticoid genes are important during lung development, and their role in asthma susceptibility and treatment response. A total of 232 genes were included in the GCGS. Analysis of gene expression demonstrated that glucocorticoid genes were enriched in lung development (P = 7.02 × 10−26). The developmental GCGS was enriched for genes that were differentially expressed between subjects with asthma and control subjects (P = 4.26 × 10−3) and were enriched after treatment of subjects with asthma with inhaled corticosteroids (P < 2.72 × 10−4). Our results show that glucocorticoid genes are overrepresented among genes implicated in fetal lung development. These genes influence asthma susceptibility and treatment response, suggesting their involvement in the early ontogeny of asthma. PMID:25192440

  8. Metabolic Imaging to Assess Treatment Response to Cytotoxic and Cytostatic Agents

    PubMed Central

    Serkova, Natalie J.; Eckhardt, S. Gail

    2016-01-01

    For several decades, cytotoxic chemotherapeutic agents were considered the basis of anticancer treatment for patients with metastatic tumors. A decrease in tumor burden, assessed by volumetric computed tomography and magnetic resonance imaging, according to the response evaluation criteria in solid tumors (RECIST), was considered as a radiological response to cytotoxic chemotherapies. In addition to RECIST-based dimensional measurements, a metabolic response to cytotoxic drugs can be assessed by positron emission tomography (PET) using 18F-fluoro-thymidine (FLT) as a radioactive tracer for drug-disrupted DNA synthesis. The decreased 18FLT-PET uptake is often seen concurrently with increased apparent diffusion coefficients by diffusion-weighted imaging due to chemotherapy-induced changes in tumor cellularity. Recently, the discovery of molecular origins of tumorogenesis led to the introduction of novel signal transduction inhibitors (STIs). STIs are targeted cytostatic agents; their effect is based on a specific biological inhibition with no immediate cell death. As such, tumor size is not anymore a sensitive end point for a treatment response to STIs; novel physiological imaging end points are desirable. For receptor tyrosine kinase inhibitors as well as modulators of the downstream signaling pathways, an almost immediate inhibition in glycolytic activity (the Warburg effect) and phospholipid turnover (the Kennedy pathway) has been seen by metabolic imaging in the first 24 h of treatment. The quantitative imaging end points by magnetic resonance spectroscopy and metabolic PET (including 18F-fluoro-deoxy-glucose, FDG, and total choline) provide an early treatment response to targeted STIs, before a reduction in tumor burden can be seen. PMID:27471678

  9. EEG biomarkers in major depressive disorder: discriminative power and prediction of treatment response.

    PubMed

    Olbrich, Sebastian; Arns, Martijn

    2013-10-01

    Major depressive disorder (MDD) has high population prevalence and is associated with substantial impact on quality of life, not least due to an unsatisfactory time span of sometimes several weeks from initiation of treatment to clinical response. Therefore extensive research focused on the identification of cost-effective and widely available electroencephalogram (EEG)-based biomarkers that not only allow distinguishing between patients and healthy controls but also have predictive value for treatment response for a variety of treatments. In this comprehensive overview on EEG research on MDD, biomarkers that are either assessed at baseline or during the early course of treatment and are helpful in discriminating patients from healthy controls and assist in predicting treatment outcome are reviewed, covering recent decades up to now. Reviewed markers include quantitative EEG (QEEG) measures, connectivity measures, EEG vigilance-based measures, sleep-EEG-related measures and event-related potentials (ERPs). Further, the value and limitations of these different markers are discussed. Finally, the need for integrated models of brain function and the necessity for standardized procedures in EEG biomarker research are highlighted to enhance future research in this field.

  10. Immune Responses to Epidermal Growth Factor Receptor (EGFR) and Their Application for Cancer Treatment.

    PubMed

    Sasada, Tetsuro; Azuma, Koichi; Ohtake, Junya; Fujimoto, Yuki

    2016-01-01

    Epidermal growth factor receptor (EGFR) is a prototypic cell-surface receptor belonging to the ErbB/HER onocogene family. Overexpression or somatic mutations of EGFR have been reported to play an important role in tumorigenesis in various types of epithelial cancers. Therefore, targeting of EGFR with specific blocking antibodies or inhibitors have been developing for treatment for EGFR-associated tumors. Immune responses to HER2, another molecule of the ErbB/HER onocogene family, have been well studied, but only limited information on the immune responses to EGFR in cancer has been currently available. In this review, we have summarized the available data and discussed potential clinical importance of the anti-EGFR immune responses and EGFR-mediated immune regulation in cancer. Several lines of evidence suggest that cellular and humoral immune responses to EGFR might be useful as a marker and/or target for cancer therapy against EGFR-associated tumors. In addition, recent studies suggest the critical roles of EGFR-mediated signaling in regulation of expression of an immune checkpoint molecule, programmed death-ligand 1 (PD-L1) in tumor cells. Further studies are warranted to clarify the impact of the anti-EGFR immune responses and EGFR-mediated immunomodulation for clinical application for cancer treatment.

  11. Treatment with the selective serotonin reuptake inhibitor, fluoxetine, attenuates the fish hypoxia response.

    PubMed

    Panlilio, Jennifer M; Marin, Sara; Lobl, Marissa B; McDonald, M Danielle

    2016-08-08

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX), the active ingredient of the antidepressant drug Prozac, inhibits reuptake of the neurotransmitter, serotonin (5-HT; 5-hydroxytryptamine), into cells by the 5-HT transporter (SERT). Given the role of 5-HT in oxygen detection and the cardiovascular and ventilatory responses of fish to hypoxia, we hypothesized that treatment of the Gulf toadfish, Opsanus beta, with FLX would interfere with their response to hypoxia. Toadfish treated intra-arterially with 3.4 μg.g(-1) FLX under normoxic conditions displayed a transient tachycardia and a biphasic caudal arterial blood pressure (PCA) response that are in direct conflict with the typical hypoxia response. Fish injected intraperitoneally with FLX under normoxia had resting cardiovascular and ventilatory parameters similar to controls. Upon exposure to hypoxia, control toadfish exhibit a significant bradycardia, reduction in PCA and an increase in ventilatory amplitude (VAMP) without any changes in ventilatory frequency (fV). Fish treated IP with 10 μg.g(-1) FLX showed an interference in the cardiovascular and ventilatory response to hypoxia. Interestingly, when treated with 25 μg.g(-1) FLX, the bradycardia and VAMP response to hypoxia were similar to control fish while the PCA response to hypoxia was further inhibited. These results suggest that SERT inhibition by FLX may hinder survival in hypoxia.

  12. Treatment with the selective serotonin reuptake inhibitor, fluoxetine, attenuates the fish hypoxia response

    PubMed Central

    Panlilio, Jennifer M.; Marin, Sara; Lobl, Marissa B.; McDonald, M. Danielle

    2016-01-01

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX), the active ingredient of the antidepressant drug Prozac, inhibits reuptake of the neurotransmitter, serotonin (5-HT; 5-hydroxytryptamine), into cells by the 5-HT transporter (SERT). Given the role of 5-HT in oxygen detection and the cardiovascular and ventilatory responses of fish to hypoxia, we hypothesized that treatment of the Gulf toadfish, Opsanus beta, with FLX would interfere with their response to hypoxia. Toadfish treated intra-arterially with 3.4 μg.g−1 FLX under normoxic conditions displayed a transient tachycardia and a biphasic caudal arterial blood pressure (PCA) response that are in direct conflict with the typical hypoxia response. Fish injected intraperitoneally with FLX under normoxia had resting cardiovascular and ventilatory parameters similar to controls. Upon exposure to hypoxia, control toadfish exhibit a significant bradycardia, reduction in PCA and an increase in ventilatory amplitude (VAMP) without any changes in ventilatory frequency (fV). Fish treated IP with 10 μg.g−1 FLX showed an interference in the cardiovascular and ventilatory response to hypoxia. Interestingly, when treated with 25 μg.g−1 FLX, the bradycardia and VAMP response to hypoxia were similar to control fish while the PCA response to hypoxia was further inhibited. These results suggest that SERT inhibition by FLX may hinder survival in hypoxia. PMID:27499056

  13. Behavioural treatment of tics: habit reversal and exposure with response prevention.

    PubMed

    van de Griendt, J M T M; Verdellen, C W J; van Dijk, M K; Verbraak, M J P M

    2013-07-01

    Behaviour therapy has been shown to be an effective strategy in treating tics; both habit reversal (HR) and exposure and response prevention (ER) are recommended as first-line interventions. This review provides an overview of the history, theoretical concepts and evidence at present for HR and ER. In addition, treatment manuals for HR and ER are described. Despite the evidence and availability of treatment manuals, many patients do not receive a first-line psychological intervention for tics. Barriers to the acceptance and dissemination of behaviour therapy are discussed as are ways to overcome these barriers, such as the use of E-health and E-learning.

  14. Ovarian response to gonadotropin treatment initiated relative to wave emergence in ultrasonographically monitored ewes.

    PubMed

    Rubianes, E; Ungerfeld, R; Viñoles, C; Rivero, A; Adams, G P

    1997-06-01

    Follicular recruitment and luteal response to superovulatory treatment initiated relative to the status of the first wave of the ovine estrous cycle (Wave 1) were studied. All ewes (n = 25) received an intravaginal progestagen sponge to synchronize estrous cycles, and ewes were monitored daily by transrectal ultrasonography. Multiple-dose FSH treatment (total dose = 100 mg NIH-FSH-P1) was initiated on the day of ovulation (Day 0 group) in 16 ewes. In the remaining 9 ewes, FSH treatment was started 3 d after emergence of the largest follicle of Wave 1 (Day 3 group). Ewes received PGF(2alpha) with the last 2 FSH treatments to induce luteolysis. Daily blood samples were taken to determine progesterone profiles and to evaluate the luteal response subsequent to superovulation. The ovulation rate was determined by ultrasonography and correlated with direct observation of the ovaries during laparotomy 5 to 6 d after superovulatory estrus when the uterus was flushed to collect embryos. Results confirmed that follicular recruitment was suppressed by the presence of a large, growing follicle. In the Day 0 and Day 3 groups, respectively, mean numbers (+/- SEM) of large follicles (>/= 4 mm) recruited were 6.4 +/- 0.6 and 2.7 +/- 0.7 (P < 0.01) at 48 h after the onset of treatment, and 6.7 +/- 0.5 and 5.1 +/- 0.6 (P = 0.08) at 72 h after the onset of treatment. Ovulation rates were 5.6 +/- 0.8 and 3.3 +/- 0.8 in the respective groups (P < 0.05). The number of transferable embryos was 1.8 +/- 0.5 and 0.3 +/- 0.2 in the respective groups (P < 0.05). Short luteal phases (treatment initiated at the time of emergence of Wave 1 induced a superovulatory response in ewes. Response was influenced by the status of the follicular wave. The presence of a large growing follicle

  15. Responses to hexyl 5-aminolevulinate-induced photodynamic treatment in rat bladder cancer model

    NASA Astrophysics Data System (ADS)

    Arum, Carl-Jørgen; Gederas, Odrun; Larsen, Eivind; Randeberg, Lise; Zhao, Chun-Mei

    2010-02-01

    OBJECTIVES: In this study, we evaluated histologically the effects of hexyl 5-aminolevulinateinduced photodynamic treatment in the AY-27 tumor cell induced rat bladder cancer model. MATERIAL & METHODS: The animals (fischer-344 female rats) were divided into 2 groups, half of which were orthotopically implanted with 400,000 syngeniec AY-27 urothelia1 rat bladder cancer cells and half sham implanted. 14 days post implantation 6 rats from each group were treated with hexyl 5-aminolevulinate-induced photodynamic treatment (8mM HAL and light fluence of 20 J/cm2). Additional groups of animals were only given HAL instillation, only light treatment, or no treatment. All animals were sacrificed 7 days after the PDT/only HAL/only light or no treatment. Each bladder was removed, embedded in paraffin and stained with hematoxylin, eosin, and saferin for histological evaluation at high magnification for features of tissue damage by a pathologist blinded to the sample source. RESULTS: In all animals that were AY-27 implanted and not given complete PDT treatment, viable tumors were found in the bladder mucosa and wall. In the animals treated with complete HAL-PDT only 3 of 6 animals had viable tumor. In the 3 animals with viable tumor it was significantly reduced in volume compared to the untreated animals. It was also noted that in the PDT treated animals there was a significantly increased inflammatory response (lymphocytic and mononuclear cell infiltration) in the peri-tumor area compared to implanted animals without complete HAL-PDT. CONCLUSION: Our results suggest that hexyl 5-aminolevulinate-induced photodynamic treatment in a rat bladder cancer model involves both direct effects on cell death (necrosis and apoptosis) and indirect effects to evoke the host immune-response, together contributing to tumor eradication.

  16. Antiparasitic Treatment Induces an Improved CD8(+) T Cell Response in Chronic Chagasic Patients.

    PubMed

    Mateus, Jose; Pérez-Antón, Elena; Lasso, Paola; Egui, Adriana; Roa, Nubia; Carrilero, Bartolomé; González, John M; Thomas, M Carmen; Puerta, Concepción J; López, Manuel C; Cuéllar, Adriana

    2017-04-15

    Chagas disease is a chronic infection caused by Trypanosoma cruzi, an intracellular protozoan parasite. Chronic chagasic patients (CCPs) have dysfunctional CD8(+) T cells that are characterized by impaired cytokine production, high coexpression of inhibitory receptors, and advanced cellular differentiation. Most patients diagnosed in the chronic phase of Chagas disease already exhibit heart involvement, and there is no vaccination that protects against the disease. Antiparasitic treatment is controversial as to its indication for this stage of the disease. There is a lack of biological markers to evaluate the effectiveness of antiparasitic treatment, and little is known about the effect of the treatment on CD8(+) T cells. Thus, the aim of the current study was to analyze the early effects of antiparasitic treatment on CD8(+) T cells from CCPs with asymptomatic clinical forms of disease. To evaluate the CD8(+) T cell subsets, expression of inhibitory receptors, and functionality of T cells in CCPs, PBMCs were isolated. The results showed that treatment of CCPs with the asymptomatic form of the disease induces an increase in the frequency of CD8(+) central memory T cells and terminal effector T cells, a decrease in the coexpression of inhibitory receptors, an improved Ag-specific CD8(+) T cell response exhibited by the individual production of IFN-γ or IL-2, and a multifunctional CD8(+) T cell profile of up to four functions (IFN-γ(+)IL-2(+)Perforin(+)Granzyme B(+)). These findings suggest that, in CCPs, antiparasitic treatment improved the quality of Ag-specific CD8(+) T cell responses associated with a decrease in inhibitory receptor coexpression, which could serve as biomarkers for monitoring the effectiveness of antiparasitic treatment.

  17. Community occupancy responses of small mammals to restoration treatments in ponderosa pine forests, northern Arizona, USA.

    PubMed

    Kalies, E L; Dickson, B G; Chambers, C L; Covington, W W

    2012-01-01

    In western North American conifer forests, wildfires are increasing in frequency and severity due to heavy fuel loads that have accumulated after a century of fire suppression. Forest restoration treatments (e.g., thinning and/or burning) are being designed and implemented at large spatial and temporal scales in an effort to reduce fire risk and restore forest structure and function. In ponderosa pine (Pinus ponderosa) forests, predominantly open forest structure and a frequent, low-severity fire regime constituted the evolutionary environment for wildlife that persisted for thousands of years. Small mammals are important in forest ecosystems as prey and in affecting primary production and decomposition. During 2006-2009, we trapped eight species of small mammals at 294 sites in northern Arizona and used occupancy modeling to determine community responses to thinning and habitat features. The most important covariates in predicting small mammal occupancy were understory vegetation cover, large snags, and treatment. Our analysis identified two generalist species found at relatively high occupancy rates across all sites, four open-forest species that responded positively to treatment, and two dense-forest species that responded negatively to treatment unless specific habitat features were retained. Our results indicate that all eight small mammal species can benefit from restoration treatments, particularly if aspects of their evolutionary environment (e.g., large trees, snags, woody debris) are restored. The occupancy modeling approach we used resulted in precise species-level estimates of occupancy in response to habitat attributes for a greater number of small mammal species than in other comparable studies. We recommend our approach for other studies faced with high variability and broad spatial and temporal scales in assessing impacts of treatments or habitat alteration on wildlife species. Moreover, since forest planning efforts are increasingly focusing on

  18. Racial and ethnic differences in response to medicines: towards individualized pharmaceutical treatment.

    PubMed Central

    Burroughs, Valentine J.; Maxey, Randall W.; Levy, Richard A.

    2002-01-01

    It is now well documented that substantial disparities exist in the quality and quantity of medical care received by minority Americans, especially those of African, Asian and Hispanic heritage. In addition, the special needs and responses to pharmaceutical treatment of these groups have been undervalued or ignored. This article reviews the genetic factors that underlie varying responses to medicines observed among different ethnic and racial groups. Pharmacogenetic research in the past few decades has uncovered significant differences among racial and ethnic groups in the metabolism, clinical effectiveness, and side-effect profiles of many clinically important drugs. These differences must be taken into account in the design of cost management policies such as formulary implementation, therapeutic substitution and step-care protocols. These programs should be broad and flexible enough to enable rational choices and individualized treatment for all patients, regardless of race or ethnic origin. Images Figure 3 PMID:12401060

  19. Management of proton pump inhibitor responsive-esophageal eosinophilia and eosinophilic esophagitis: controversies in treatment approaches.

    PubMed

    Kochar, Bharati; Dellon, Evan S

    2015-01-01

    Eosinophilic esophagitis (EoE) is a chronic immune-mediated clinicopathologic disease. The prevalence of EoE is approximately 1/2000 persons, EoE is now the most common cause of food impactions, with healthcare expenditures approaching US$ 1 billion annually. This article will discuss challenges related to proton pump inhibitor responsive esophageal eosinophilia, including distinguishing this condition from EoE and understanding the mechanisms behind the PPI response. For EoE, we will review multiple ongoing debates about treatment and monitoring strategies, including selecting treatment outcomes, optimizing medication formulations, approaching the steroid-refractory patient, conducting dietary elimination, prescribing long-term maintenance therapy and performing esophageal dilation.

  20. Pulmonary Tuberculosis in Mumbai, India: Factors Responsible for Patient and Treatment Delays

    PubMed Central

    Tamhane, Ashutosh; Ambe, Girish; Vermund, Sten H; Kohler, Connie L; Karande, Alka; Sathiakumar, Nalini

    2012-01-01

    Purpose: To determine the factors responsible for patient delay and treatment delay in newly diagnosed sputum smear-positive pulmonary tuberculosis (TB) patients. Methods: Study subjects (N = 150) were randomly selected from municipal health centers in Mumbai, India. Duration of symptoms, treatment, and reason for delay were assessed using interviews and medical records. We defined patient delay as presentation to a health care provider (HCP) >20 days of the onset of TB-related symptoms and treatment delay as therapy initiated more than 14 days after the first consultation (for TB-related symptoms) with an HCP. Results: Of the 150 subjects, 29% had patient delays and 81% had treatment delays. In multivariable analysis, patient delay was significantly associated with the self-perception that initial symptoms were due to TB [odds ratio (OR) = 3.8, 95% confidence interval (CI) = 1.1–12.6] and perceived inability to pay for care (OR = 2.9, 95% CI = 1.2–7.1). Treatment delay was significantly associated with consulting a non-allopathic provider (OR = 12.3, 95% CI = 1.4–105) and consulting >3 providers (OR = 5.0, 95% CI = 1.4–17.4). Patient interval was half the treatment interval (median days: 15 vs. 31). Women were slightly more likely to experience patient and treatment delays than men. For two-thirds of the patients, another TB patient was a source of TB-related knowledge, while health education material (16%) and television (10%) played a smaller role. Conclusion: Treatment delay, primarily due to diagnosis delay, was a greater problem than patient delay. Expanding public–public and public–private partnerships and regular training sessions for HCPs might decrease treatment delay. Media coverage and cured TB patients as peer advocates may help to reinforce TB-related health education messages. PMID:22973488

  1. Predictors of anti-VEGF treatment response in neovascular age-related macular degeneration.

    PubMed

    Finger, Robert P; Wickremasinghe, Sanjeewa S; Baird, Paul N; Guymer, Robyn H

    2014-01-01

    Currently available evidence on predictors of anti-vascular endothelial growth factor (VEGF) treatment response in neovascular age-related macular degeneration was reviewed. No meta-analysis of results is possible because of a lack of controlled and randomized trials, varying treatment regimes and outcome measures used, as well as suboptimal reporting. For genetic factors, most evidence to date has been generated for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), and VEGF-A genes. Just under half of the SNPs assessed in the CFH gene and 15% of the SNPs assessed in the VEGF gene were found to be associated with visual outcomes or the number of injections required during follow-up. Some evidence suggests association of worse treatment outcomes as well as a younger age at treatment onset with an increasing number of risk alleles in known risk genes (CFH and ARMS2/HTRA1) and polymorphisms in the VEGF-A gene. Clinical factors such as higher age, a better visual acuity (VA), a larger choroidal neovascularization (CNV) lesion at baseline, and a delay between symptom onset and initiation of treatment of more than 3 weeks also impact outcomes. Conversely, a worse acuity at baseline predicted more gain in vision. Overall, patients presenting with good acuity at baseline were more likely to have good VA at follow up, but the gain afforded by treatment was impacted by a ceiling effect. Most available evidence suggests a strong association of clinical factors such as age, baseline VA, and CNV lesion size with anti-VEGF treatment outcomes. No behavioral factors such as smoking influence treatment outcomes. Based on the studies conducted so far, the evidence suggests that underlying genotype of known AMD risk associated genes or of the VEGF-A gene have a limited effect, whereas presenting clinical factors appear to be more important in determining treatment outcomes.

  2. Response of Human Prostate Cancer Cells to Mitoxantrone Treatment in Simulated Microgravity Environment

    NASA Technical Reports Server (NTRS)

    Zhang, Ye; Edwards, Christopher; Wu, Honglu

    2011-01-01

    This study explores the changes in growth of human prostate cancer cells (LNCaP) and their response to the treatment of antineoplastic agent, mitoxantrone, under the simulated microgravity condition. In comparison to static 1g, microgravity and simulated microgravity have been shown to alter global gene expression patterns and protein levels in various cultured cell models or animals. However, very little is known about the effect of altered gravity on the responses of cells to drugs, especially chemotherapy drugs. To test the hypothesis that zero gravity would result in altered regulation of cells in response to antineoplastic agents, we cultured LNCaP cells for 96 hr either in a High Aspect Ratio Vessel (HARV) bioreactor at the rotating condition to model microgravity in space or in the static condition as a control. 24 hr after the culture started, mitoxantrone was introduced to the cells at a final concentration of 1 M. The mitoxantrone treatment lasted 72 hr and then the cells were collected for various measurements. Compared to static 1g controls, the cells cultured in the simulated microgravity environment did not show significant differences in cell viability, growth rate, or cell cycle distribution. However, in response to mitoxantrone (1uM), a significant proportion of bioreactor cultured cells (30%) was arrested at G2 phase and a significant number of these cells were apoptotic in comparison to their static controls. The expressions of 84 oxidative stress related genes were analyzed using Qiagen PCR array to identify the possible mechanism underlying the altered responses of bioreactor culture cells to mitoxantrone. Nine out of 84 genes showed higher expression at four hour post mitoxantrone treatment in cells cultured at rotating condition compared to those at static. Taken together, the results reported here indicate that simulated microgravity may alter the responses of LNCaP cells to mitoxantrone treatment. The alteration of oxidative stress pathways

  3. Incorporating Cancer Stem Cells in Radiation Therapy Treatment Response Modeling and the Implication in Glioblastoma Multiforme Treatment Resistance

    SciTech Connect

    Yu, Victoria Y.; Nguyen, Dan; Pajonk, Frank; Kupelian, Patrick; Kaprealian, Tania; Selch, Michael; Low, Daniel A.; Sheng, Ke

    2015-03-15

    Purpose: To perform a preliminary exploration with a simplistic mathematical cancer stem cell (CSC) interaction model to determine whether the tumor-intrinsic heterogeneity and dynamic equilibrium between CSCs and differentiated cancer cells (DCCs) can better explain radiation therapy treatment response with a dual-compartment linear-quadratic (DLQ) model. Methods and Materials: The radiosensitivity parameters of CSCs and DCCs for cancer cell lines including glioblastoma multiforme (GBM), non–small cell lung cancer, melanoma, osteosarcoma, and prostate, cervical, and breast cancer were determined by performing robust least-square fitting using the DLQ model on published clonogenic survival data. Fitting performance was compared with the single-compartment LQ (SLQ) and universal survival curve models. The fitting results were then used in an ordinary differential equation describing the kinetics of DCCs and CSCs in response to 2- to 14.3-Gy fractionated treatments. The total dose to achieve tumor control and the fraction size that achieved the least normal biological equivalent dose were calculated. Results: Smaller cell survival fitting errors were observed using DLQ, with the exception of melanoma, which had a low α/β = 0.16 in SLQ. Ordinary differential equation simulation indicated lower normal tissue biological equivalent dose to achieve the same tumor control with a hypofractionated approach for 4 cell lines for the DLQ model, in contrast to SLQ, which favored 2 Gy per fraction for all cells except melanoma. The DLQ model indicated greater tumor radioresistance than SLQ, but the radioresistance was overcome by hypofractionation, other than the GBM cells, which responded poorly to all fractionations. Conclusion: The distinct radiosensitivity and dynamics between CSCs and DCCs in radiation therapy response could perhaps be one possible explanation for the heterogeneous intertumor response to hypofractionation and in some cases superior outcome from

  4. Globally Efficient Brain Organization and Treatment Response in Psychosis: A Connectomic Study of Gyrification

    PubMed Central

    Palaniyappan, Lena; Marques, Tiago Reis; Taylor, Heather; Mondelli, Valeria; Reinders, A. A. T. Simone; Bonaccorso, Stefania; Giordano, Annalisa; DiForti, Marta; Simmons, Andrew; David, Anthony S.; Pariante, Carmine M.; Murray, Robin M.; Dazzan, Paola

    2016-01-01

    Background: Converging evidence suggests that patients with first-episode psychosis who show a poor treatment response may have a higher degree of neurodevelopmental abnormalities than good Responders. Characterizing the disturbances in the relationship among brain regions (covariance) can provide more information on neurodevelopmental integrity than searching for localized changes in the brain. Graph-based connectomic approach can measure structural covariance thus providing information on the maturational processes. We quantified the structural covariance of cortical folding using graph theory in first-episode psychosis, to investigate if this systems-level approach would improve our understanding of the biological determinants of outcome in psychosis. Methods: Magnetic Resonance Imaging data were acquired in 80 first-episode psychosis patients and 46 healthy controls. Response to treatment was assessed after 12 weeks of naturalistic follow-up. Gyrification-based connectomes were constructed to study the maturational organization of cortical folding. Results: Nonresponders showed a reduction in the distributed relationship among brain regions (high segregation, poor integration) when compared to Responders and controls, indicating a higher burden of aberrant neurodevelopment. They also showed reduced centrality of key regions (left insula and anterior cingulate cortex) indicating a marked reconfiguration of gyrification. Nonresponders showed a vulnerable pattern of covariance that disintegrated when simulated lesions removed high-degree hubs, indicating an abnormal dependence on highly central hub regions in Nonresponders. Conclusions: These findings suggest that a perturbed maturational relationship among brain regions underlies poor treatment response in first-episode psychosis. The information obtained from gyrification-based connectomes can be harnessed for prospectively predicting treatment response and prognosis in psychosis. PMID:27352783

  5. Serotonin 1A receptor binding and treatment response in late-life depression.

    PubMed

    Meltzer, Carolyn Cidis; Price, Julie C; Mathis, Chester A; Butters, Meryl A; Ziolko, Scott K; Moses-Kolko, Eydie; Mazumdar, Sati; Mulsant, Benoit H; Houck, Patricia R; Lopresti, Brian J; Weissfeld, Lisa A; Reynolds, Charles F

    2004-12-01

    Depression in late life carries an increased risk of dementia and brittle response to treatment. There is growing evidence to support a key role of the serotonin type 1A (5-HT(1A)) receptor as a regulator of treatment response, particularly the 5-HT(1A) autoreceptor in the dorsal raphe nucleus (DRN). We used [11C]WAY 100635 and positron emission tomography (PET) to test our hypothesis that 5-HT(1A) receptor binding in the DRN and prefrontal cortex is altered in elderly depressives and that these measures relate to treatment responsivity. We studied 17 elderly subjects with untreated (nonpsychotic, nonbipolar) major depression (four men, 13 women; mean age: 71.4+/-5.9) and 17 healthy control subjects (eight men, nine women; mean age: 70.0+/-6.7). Patients were subsequently treated with paroxetine as part of a clinical trial of maintenance therapies in geriatric depression. [11C]WAY 100635 PET imaging was acquired and binding potential (BP) values derived using compartmental modeling. We observed significantly diminished [11C]WAY 100635 binding in the DRN in depressed (BP = 2.31+/-0.90) relative to control (BP = 3.69+/-1.56) subjects (p = 0.0016). Further, the DRN BP was correlated with pretreatment Hamilton Depression Rating Scores (r = 0.60, p = 0.014) in the depressed cohort. A trend level correlation between DRN binding and time to remission (r = 0.52, p = 0.067) was observed in the 14 depressed patients for whom these data were available. Our finding of decreased [11C]WAY 100635 binding in the brainstem region of the DRN in elderly depressed patients supports evidence of altered 5-HT(1A) autoreceptor function in depression. Further, this work indicates that dysfunction in autoreceptor activity may play a central role in the mechanisms underlying treatment response to selective serotonin reuptake inhibitors in late-life depression.

  6. Low Dose Iron Treatments Induce a DNA Damage Response in Human Endothelial Cells within Minutes

    PubMed Central

    Mollet, Inês G.; Giess, Adam; Paschalaki, Koralia; Periyasamy, Manikandan; Lidington, Elaine C.; Mason, Justin C.; Jones, Michael D.; Game, Laurence; Ali, Simak; Shovlin, Claire L.

    2016-01-01

    Background Spontaneous reports from patients able to report vascular sequelae in real time, and recognition that serum non transferrin bound iron may reach or exceed 10μmol/L in the blood stream after iron tablets or infusions, led us to hypothesize that conventional iron treatments may provoke acute vascular injury. This prompted us to examine whether a phenotype could be observed in normal human endothelial cells treated with low dose iron. Methodology Confluent primary human endothelial cells (EC) were treated with filter-sterilized iron (II) citrate or fresh media for RNA sequencing and validation studies. RNA transcript profiles were evaluated using directional RNA sequencing with no pre-specification of target sequences. Alignments were counted for exons and junctions of the gene strand only, blinded to treatment types. Principal Findings Rapid changes in RNA transcript profiles were observed in endothelial cells treated with 10μmol/L iron (II) citrate, compared to media-treated cells. Clustering for Gene Ontology (GO) performed on all differentially expressed genes revealed significant differences in biological process terms between iron and media-treated EC, whereas 10 sets of an equivalent number of randomly selected genes from the respective EC gene datasets showed no significant differences in any GO terms. After 1 hour, differentially expressed genes clustered to vesicle mediated transport, protein catabolism, and cell cycle (Benjamini p = 0.0016, 0.0024 and 0.0032 respectively), and by 6 hours, to cellular response to DNA damage stimulus most significantly through DNA repair genes FANCG, BLM, and H2AFX. Comet assays demonstrated that 10μM iron treatment elicited DNA damage within 1 hour. This was accompanied by a brisk DNA damage response pulse, as ascertained by the development of DNA damage response (DDR) foci, and p53 stabilization. Significance These data suggest that low dose iron treatments are sufficient to modify the vascular endothelium

  7. THE EFFECTS OF RESPONSE EFFORT ON SAFE PERFORMANCE BY THERAPISTS AT AN AUTISM TREATMENT FACILITY

    PubMed Central

    Casella, Sarah E; Wilder, David A; Neidert, Pamela; Rey, Catalina; Compton, Megan; Chong, Ivy

    2010-01-01

    The effects of response effort on safe behaviors (i.e., glove wearing, hand sanitizing, and electrical outlet replacement) exhibited by therapists at an autism treatment center were examined. Participants were exposed to 2 or 3 levels of effort (i.e., high, medium, low) for each dependent variable. Results showed increased safe performance during the low-effort conditions relative to other conditions across all dependent variables for all participants. PMID:21541157

  8. Response to Microneedling Treatment in Men with Androgenetic Alopecia Who Failed to Respond to Conventional Therapy

    PubMed Central

    Dhurat, Rachita; Mathapati, Sukesh

    2015-01-01

    Introduction: The efficacy of conventional therapy viz. finasteride and minoxidil in androgenetic alopecia (AGA) that is based on both preventing hair loss and promoting new hair growth, varies between 30% and 60%. This has led to a large number of patients unsatisfied who demand for a better cosmetic coverage over the scalp. Microneedling has recently been reported to be promising, effective and a safe treatment modality in the treatment of AGA. This augments the response of conventional therapy. Materials and Methods: Four men with AGA were on finasteride and 5% minoxidil solution since 2 to 5 years. Though there was no worsening in their respective AGA stages with the therapy, they showed no new hair growth. They were subjected to microneedling procedure over a period of 6 months along with their ongoing therapy. Patients were assessed with the use of the standardized 7-point evaluation scale and patients’ subjective hair growth assessment scale. The patients were followed up for 18 months post microneedling procedure to assess the sustainability of the response. Results: All patients showed a response of + 2 to + 3 on standardized 7-point evaluation scale. The response in the form of new hair growth started after 8-10 sessions. The patients’ satisfaction was more than 75% in three patients and more 50% in one patient, on patients’ subjective hair growth assessment scale. The obtained results were sustained post procedure during 18 months follow-up period. Conclusion Treatment with microneedling showed an accelerated response with addition of microneedling procedure leading to significant scalp density. This is the first case series to report the boosting effect of microneedling with respect to new hair follicle stimulation in patients with androgenetic alopecia who were poor responders to conventional therapy. PMID:26120151

  9. Cellular response of the amoeba Acanthamoeba castellanii to chlorine, chlorine dioxide, and monochloramine treatments.

    PubMed

    Mogoa, Emerancienne; Bodet, Charles; Morel, Franck; Rodier, Marie-Hélène; Legube, Bernard; Héchard, Yann

    2011-07-01

    Acanthamoeba castellanii is a free-living amoebae commonly found in water systems. Free-living amoebae might be pathogenic but are also known to bear phagocytosis-resistant bacteria, protecting these bacteria from water treatments. The mode of action of these treatments is poorly understood, particularly on amoebae. It is important to examine the action of these treatments on amoebae in order to improve them. The cellular response to chlorine, chlorine dioxide, and monochloramine was tested on A. castellanii trophozoites. Doses of disinfectants leading to up to a 3-log reduction were compared by flow cytometry and electron microscopy. Chlorine treatment led to size reduction, permeabilization, and retraction of pseudopods. In addition, treatment with chlorine dioxide led to a vacuolization of the cytoplasm. Monochloramine had a dose-dependent effect. At the highest doses monochloramine treatment resulted in almost no changes in cell size and permeability, as shown by flow cytometry, but the cell surface became smooth and dense, as seen by electron microscopy. We show that these disinfectants globally induced size reduction, membrane permeabilization, and morphological modifications but that they have a different mode of action on A. castellanii.

  10. Cellular Response of the Amoeba Acanthamoeba castellanii to Chlorine, Chlorine Dioxide, and Monochloramine Treatments

    PubMed Central

    Mogoa, Emerancienne; Bodet, Charles; Morel, Franck; Rodier, Marie-Hélène; Legube, Bernard; Héchard, Yann

    2011-01-01

    Acanthamoeba castellanii is a free-living amoebae commonly found in water systems. Free-living amoebae might be pathogenic but are also known to bear phagocytosis-resistant bacteria, protecting these bacteria from water treatments. The mode of action of these treatments is poorly understood, particularly on amoebae. It is important to examine the action of these treatments on amoebae in order to improve them. The cellular response to chlorine, chlorine dioxide, and monochloramine was tested on A. castellanii trophozoites. Doses of disinfectants leading to up to a 3-log reduction were compared by flow cytometry and electron microscopy. Chlorine treatment led to size reduction, permeabilization, and retraction of pseudopods. In addition, treatment with chlorine dioxide led to a vacuolization of the cytoplasm. Monochloramine had a dose-dependent effect. At the highest doses monochloramine treatment resulted in almost no changes in cell size and permeability, as shown by flow cytometry, but the cell surface became smooth and dense, as seen by electron microscopy. We show that these disinfectants globally induced size reduction, membrane permeabilization, and morphological modifications but that they have a different mode of action on A. castellanii. PMID:21602398

  11. Identification of Differentially Expressed Proteins and Phosphorylated Proteins in Rice Seedlings in Response to Strigolactone Treatment

    PubMed Central

    Chen, Fangyu; Jiang, Liangrong; Zheng, Jingsheng; Huang, Rongyu; Wang, Houcong; Hong, Zonglie; Huang, Yumin

    2014-01-01

    Strigolactones (SLs) are recently identified plant hormones that inhibit shoot branching and control various aspects of plant growth, development and interaction with parasites. Previous studies have shown that plant D10 protein is a carotenoid cleavage dioxygenase that functions in SL biosynthesis. In this work, we used an allelic SL-deficient d10 mutant XJC of rice (Oryza sativa L. spp. indica) to investigate proteins that were responsive to SL treatment. When grown in darkness, d10 mutant seedlings exhibited elongated mesocotyl that could be rescued by exogenous application of SLs. Soluble protein extracts were prepared from d10 mutant seedlings grown in darkness in the presence of GR24, a synthetic SL analog. Soluble proteins were separated on two-dimensional gels and subjected to proteomic analysis. Proteins that were expressed differentially and phosphoproteins whose phosphorylation status changed in response to GR24 treatment were identified. Eight proteins were found to be induced or down-regulated by GR24, and a different set of 8 phosphoproteins were shown to change their phosphorylation intensities in the dark-grown d10 seedlings in response to GR24 treatment. Analysis of these proteins revealed that they are important enzymes of the carbohydrate and amino acid metabolic pathways and key components of the cellular energy generation machinery. These proteins may represent potential targets of the SL signaling pathway. This study provides new insight into the complex and negative regulatory mechanism by which SLs control shoot branching and plant development. PMID:24699514

  12. TGFβ Treatment Enhances Glioblastoma Virotherapy by Inhibiting the Innate Immune Response.

    PubMed

    Han, Jianfeng; Chen, Xilin; Chu, Jianhong; Xu, Bo; Meisen, Walter H; Chen, Lichao; Zhang, Lingling; Zhang, Jianying; He, Xiaoming; Wang, Qi-En; Chiocca, E Antonio; Kaur, Balveen; Caligiuri, Michael A; Yu, Jianhua

    2015-12-15

    Oncolytic viruses, including oncolytic herpes simplex virus (oHSV), have produced provocative therapeutic responses in patients with glioblastoma, the most aggressive brain tumor. Paradoxically, innate immune responses mediated by natural killer (NK) cells and macrophages/microglia appear to limit oHSV efficacy. Therefore, we investigated whether pretreatment with an immunosuppressive cytokine, TGFβ, might reverse these effects and thereby potentiate oHSV efficacy. TGFβ treatment of NK cells rendered them less cytolytic against oHSV-infected glioblastoma cells and stem-like cells in vitro. Furthermore, TGFβ treatment of NK cells, macrophages, or microglia increased viral titers of oHSV in cocultures with glioblastoma cells. In a syngeneic mouse model of glioblastoma, administering TGFβ prior to oHSV injection inhibited intracranial infiltration and activation of NK cells and macrophages. Notably, a single administration of TGFβ prior to oHSV therapy was sufficient to phenocopy NK-cell depletion and suppress tumor growth and prolong survival in both xenograft and syngeneic models of glioblastoma. Collectively, our findings show how administering a single dose of TGFβ prior to oncolytic virus treatment of glioblastoma can transiently inhibit innate immune cells that limit efficacy, thereby improving therapeutic responses and survival outcomes.

  13. Effect of HLA-DPA1 alleles on chronic hepatitis B prognosis and treatment response

    PubMed Central

    Katrinli, Seyma; Enc, Feruze Yilmaz; Ozdil, Kamil; Ozturk, Oguzhan; Tuncer, Ilyas; Doganay, Gizem Dinler; Doganay, Levent

    2016-01-01

    OBJECTIVE: Chronic hepatitis B (CHB) is a major health problem. The outcome of hepatitis B virus (HBV) infection is associated with variations in HLA-DPA1 alleles. The aim of this study was to investigate possible associations of HLA-DPA1 alleles with treatment response and with hepatitis B virus e antigen (HBeAg) seroconversion. METHODS: Eight different HLA-DPA1 alleles from 246 CHB patients were genotyped by polymerase chain reaction with sequence-specific primers at high resolution to investigate the association of HLA-DPA1 alleles with treatment response, development of cirrhosis, HBeAg seroconversion, and disease reoccurrence upon HBeAg loss. RESULTS: There was no significant association between HLA-DPA1 alleles and treatment response, development of cirrhosis, or HBeAg seroconversion. However, HLA-DPA1*04:01 allele was significantly more frequently found in patients who redeveloped disease upon HBeAg seroconversion (100% vs 36.8%: p=0.037; Fisher’s exact test). CONCLUSION: HLA-DPA1*04:01 allele may be a risk factor for reoccurrence of CHB after HBeAg seroconversion. PMID:28275747

  14. Rad51-mediated replication fork reversal is a global response to genotoxic treatments in human cells

    PubMed Central

    Zellweger, Ralph; Dalcher, Damian; Mutreja, Karun; Berti, Matteo; Schmid, Jonas A.; Herrador, Raquel; Vindigni, Alessandro

    2015-01-01

    Replication fork reversal protects forks from breakage after poisoning of Topoisomerase 1. We here investigated fork progression and chromosomal breakage in human cells in response to a panel of sublethal genotoxic treatments, using other topoisomerase poisons, DNA synthesis inhibitors, interstrand cross-linking inducers, and base-damaging agents. We used electron microscopy to visualize fork architecture under these conditions and analyzed the association of specific molecular features with checkpoint activation. Our data identify replication fork uncoupling and reversal as global responses to genotoxic treatments. Both events are frequent even after mild treatments that do not affect fork integrity, nor activate checkpoints. Fork reversal was found to be dependent on the central homologous recombination factor RAD51, which is consistently present at replication forks independently of their breakage, and to be antagonized by poly (ADP-ribose) polymerase/RECQ1-regulated restart. Our work establishes remodeling of uncoupled forks as a pivotal RAD51-regulated response to genotoxic stress in human cells and as a promising target to potentiate cancer chemotherapy. PMID:25733714

  15. Molecular and Cellular Responses to Interleukin-4 Treatment in a Rat Model of Transient Ischemia

    PubMed Central

    Lively, Starlee; Hutchings, Sarah

    2016-01-01

    Within hours after stroke, potentially cytotoxic pro-inflammatory mediators are elevated within the brain; thus, one potential therapeutic strategy is to reduce them and skew the brain toward an anti-inflammatory state. Because interleukin-4 (IL-4) treatment induces an anti-inflammatory, “alternative-activation” state in microglia and macrophages in vitro, we tested the hypothesis that early supplementation of the brain with IL-4 can shift it toward an anti-inflammatory state and reduce damage after transient focal ischemia. Adult male rat striata were injected with endothelin-1, with or without co-injection of IL-4. Inflammation, glial responses and damage to neurons and white matter were quantified from 1 to 7 days later. At 1 day, IL-4 treatment increased striatal expression of several anti-inflammatory markers (ARG1, CCL22, CD163, PPARγ), increased phagocytic (Iba1-positive, CD68-positive) microglia/macrophages, and increased VEGF-A-positive infiltrating neutrophils in the infarcts. At 7 days, there was evidence of sustained, propagating responses. IL-4 increased CD206, CD200R1, IL-4Rα, STAT6, PPARγ, CD11b, and TLR2 expression and increased microglia/macrophages in the infarct and astrogliosis outside the infarct. Neurodegeneration and myelin damage were not reduced, however. The sustained immune and glial responses when resolution and repair processes have begun warrant further studies of IL-4 treatment regimens and long-term outcomes. PMID:27634961

  16. A novel approach to assess the treatment response using Gaussian random field in PET

    PubMed Central

    Wang, Mengdie; Guo, Ning; Hu, Guangshu; El Fakhri, Georges; Zhang, Hui; Li, Quanzheng

    2016-01-01

    Purpose: The assessment of early therapeutic response to anticancer therapy is vital for treatment planning and patient management in clinic. With the development of personal treatment plan, the early treatment response, especially before any anatomically apparent changes after treatment, becomes urgent need in clinic. Positron emission tomography (PET) imaging serves an important role in clinical oncology for tumor detection, staging, and therapy response assessment. Many studies on therapy response involve interpretation of differences between two PET images, usually in terms of standardized uptake values (SUVs). However, the quantitative accuracy of this measurement is limited. This work proposes a statistically robust approach for therapy response assessment based on Gaussian random field (GRF) to provide a statistically more meaningful scale to evaluate therapy effects. Methods: The authors propose a new criterion for therapeutic assessment by incorporating image noise into traditional SUV method. An analytical method based on the approximate expressions of the Fisher information matrix was applied to model the variance of individual pixels in reconstructed images. A zero mean unit variance GRF under the null hypothesis (no response to therapy) was obtained by normalizing each pixel of the post-therapy image with the mean and standard deviation of the pretherapy image. The performance of the proposed method was evaluated by Monte Carlo simulation, where XCAT phantoms (1282 pixels) with lesions of various diameters (2–6 mm), multiple tumor-to-background contrasts (3–10), and different changes in intensity (6.25%–30%) were used. The receiver operating characteristic curves and the corresponding areas under the curve were computed for both the proposed method and the traditional methods whose figure of merit is the percentage change of SUVs. The formula for the false positive rate (FPR) estimation was developed for the proposed therapy response assessment

  17. Withholding and withdrawing life-sustaining treatment: criminal responsibility for established medical practice?

    PubMed

    White, Ben; Willmott, Lindy; Allen, John

    2010-05-01

    The law recognises the right of a competent adult to refuse medical treatment even if this will lead to death. Guardianship and other legislation also facilitates the making of decisions to withhold or withdraw life-sustaining treatment in certain circumstances. Despite this apparent endorsement that such decisions can be lawful, doubts have been raised in Queensland about whether decisions to withhold or withdraw life-sustaining treatment would contravene the criminal law, and particularly the duty imposed by the Criminal Code (Qld) to provide the "necessaries of life". This article considers this tension in the law and examines various arguments that might allow for such decisions to be made lawfully. It ultimately concludes, however, that criminal responsibility may still arise and so reform is needed.

  18. The Role of Cetuximab in the Induction of Anticancer Immune Response in Colorectal Cancer Treatment.

    PubMed

    Holubec, Lubos; Polivka, Jiri; Safanda, Martin; Karas, Michal; Liska, Vaclav

    2016-09-01

    Monoclonal antibodies binding the epidermal growth factor receptor (EGFR), such as cetuximab or panitumumab, are widely used targeted therapeutics for the treatment of patients with colorectal cancer. The clinical significance of these drugs has so far been associated with combined chemotherapy or radiation. It has been shown that these treatment strategies have their clinical limitations and do not fully exploit the immunomodulatory effect of these drugs. In this review, we discuss the mechanisms of immunomodulation together with the anticancer immune response to the monoclonal antibodies targeted to the EGFR. The combination of anti-EGFR monoclonal antibodies with other immunotherapeutic treatment modalities certainly brings new opportunities for targeted therapy in patients with colorectal cancer.

  19. Pivotal response group treatment program for parents of children with autism.

    PubMed

    Minjarez, Mendy Boettcher; Williams, Sharon E; Mercier, Emma M; Hardan, Antonio Y

    2011-01-01

    The number of children diagnosed with autism spectrum disorders is increasing, necessitating the development of efficient treatment models. Research has demonstrated that parent-delivered behavioral interventions are a viable treatment model; however, little research has focused on teaching parents in groups. The aim of this study was to demonstrate that parents can learn Pivotal Response Training (PRT) in group therapy, resulting in correlated gains in children's language. Baseline and post-treatment data were obtained and examined for changes in (a) parent fidelity of PRT implementation, and (b) child functional verbal utterances. Significant differences were observed for both variables. These findings suggest that parents can learn PRT in a group format, resulting in correlated child language gains, thus future controlled studies are warranted.

  20. Verbal memory functioning moderates psychotherapy treatment response for PTSD-Related nightmares.

    PubMed

    Scott, J Cobb; Harb, Gerlinde; Brownlow, Janeese A; Greene, Jennifer; Gur, Ruben C; Ross, Richard J

    2017-04-01

    Posttraumatic stress disorder (PTSD) is associated with cognitive deficits in attention, executive control, and memory, although few studies have investigated the relevance of cognitive difficulties for treatment outcomes. We examined whether cognitive functioning and history of traumatic brain injury (TBI) were associated with response to cognitive-behavioral therapy (CBT) for PTSD-related sleep problems. In a randomized controlled trial of Imagery Rehearsal (IR) added to components of CBT for Insomnia (IR + cCBT-I) compared to cCBT-I alone for PTSD-related recurrent nightmares, 94 U.S. veterans completed a battery of cognitive tests. TBI was assessed via structured clinical interview. Mixed-effects models examined main effects of cognitive functioning and interactions with time on primary sleep and nightmare outcomes. Significant verbal immediate memory by time interactions were found for nightmare distress, nightmare frequency, and sleep quality, even after controlling for overall cognitive performance and depression. TBI exhibited main effects on outcomes but no interactions with time. Findings indicated that individuals with lower verbal memory performance were less likely to respond to treatment across two sleep interventions. Veterans with TBI displayed greater symptoms but no altered trajectories of treatment response. Together with prior literature, findings suggest that verbal memory functioning may be important to consider in PTSD treatment implementation.

  1. Histogram-based classification with Gaussian mixture modeling for GBM tumor treatment response using ADC map

    NASA Astrophysics Data System (ADS)

    Huo, Jing; Kim, Hyun J.; Pope, Whitney B.; Okada, Kazunori; Alger, Jeffery R.; Wang, Yang; Goldin, Jonathan G.; Brown, Matthew S.

    2009-02-01

    This study applied a Gaussian Mixture Model (GMM) to apparent diffusion coefficient (ADC) histograms to evaluate glioblastoma multiforme (GBM) tumor treatment response using diffusion weighted (DW) MR images. ADC mapping, calculated from DW images, has been shown to reveal changes in the tumor's microenvironment preceding morphologic tumor changes. In this study, we investigated the effectiveness of features that represent changes from pre- and post-treatment tumor ADC histograms to detect treatment response. The main contribution of this work is to model the ADC histogram as the composition of two components, fitted by GMM with expectation maximization (EM) algorithm. For both pre- and post-treatment scans taken 5-7 weeks apart, we obtained the tumor ADC histogram, calculated the two-component features, as well as the other standard histogram-based features, and applied supervised learning for classification. We evaluated our approach with data from 85 patients with GBM under chemotherapy, in which 33 responded and 52 did not respond based on tumor size reduction. We compared AdaBoost and random forests classification algorithms, using ten-fold cross validation, resulting in a best accuracy of 69.41%.

  2. Impact of Helicobacter pylori infection on severity of psoriasis and response to treatment.

    PubMed

    Onsun, Nahide; Arda Ulusal, Hande; Su, Ozlem; Beycan, Ismet; Biyik Ozkaya, Dilek; Senocak, Mustafa

    2012-01-01

    The aims of this study were to determine the prevalence of H. pylori seropositivity in patients with psoriasis, to evaluate the relationship between PASI (Psoriasis Area and Severity Index) scores and H. pylori infection, and to assess the impact of H. pylori infection on the response to treatment. A total of 300 patients with psoriasis and 150 non-psoriatic healthy controls were enrolled in the study. Patient PASI scores were recorded and H. pylori stool antigen tests performed in both patients and controls. Fifty patients with H. pylori infections were randomly assigned to one of two groups, one of which received acitretin with H. pylori treatment and the other acitretin alone. Statistical analyses were performed using chi-square and logistic regression tests. PASI scores were significantly higher in patients with H. pylori infections. Treatment aimed at eradicating H. pylori infection enhanced the effectiveness of acitretin therapy and shortened response times. Our results suggest that H. pylori infection plays a role in the severity of psoriasis, and that eradicating such infections enhances the effectiveness of psoriasis treatment.

  3. In vivo growth and responses to treatment of renal cell carcinoma in different environments

    PubMed Central

    Alhamhoom, Yahya; Zhang, Guisheng; Gao, Mingming; Cai, Houjian; Liu, Dexi

    2017-01-01

    Renal cell carcinoma is the most common type of kidney cancer in adults and is associated with poor prognosis. The hydrodynamic cell delivery technique was employed in this study to establish tumor growth in mouse lung, liver and kidneys. We demonstrate that RencaLuc cells exhibit different growth rates and responses to the cancer treatment of 5-florouracil and cytokine gene therapy when growing in different organs. The tumor growth rate was faster in the kidneys compared to that in the lung and liver. The liver is the second-best organ in support of tumor growth. Tumors in the liver and lung respond to 5-florouracil treatment but are less responsive in the kidneys. IL-12 gene therapy resulted in whole-body tumor suppression and prolonged animal survival. IFN-β gene therapy was effective in suppressing tumor growth in the liver but not effective for those in the lung and kidneys. These results suggest that kidney cancer cells, once metastasized in different organs, show different growth patterns and respond differently to treatment. Our data also imply that an animal model with multi-organ tumor growth is critical for development of a new strategy for treatment of tumors when metastasis is suspected. At the same time, the results also provide direct evidence in support of the usefulness of the hydrodynamic tail vein injection as a tool for establishment of tumor growth in the lung, liver and kidneys. PMID:28337378

  4. Role of WW domain proteins WWOX in development, prognosis, and treatment response of glioma

    PubMed Central

    Liu, Shin-Yi; Chen, Yu-Jen

    2015-01-01

    Glioblastoma multiforme (GBM) is the most aggressive and malignant brain tumor. Delicate microenvironment and lineage heterogeneity of GBM cells including infiltration, hypoxia, angiogenesis, and stemness make them highly resistant to current conventional therapies, with an average life expectancy for GBM patients of less than 15 months. Poor response to cytotoxic agents of GBM cells remains the major challenge of GBM treatment. Resistance of GBM to clinical treatment is a result of genomic alternation and deregulated signaling pathways, such as p53 mutation and apoptosis signaling blockage, providing cancer cells more opportunities for survival rather than cell death. WW domain-containing oxidoreductase (WWOX) is a tumor suppressor gene, commonly downregulated in various types of tumors, including GBM. It has been found that the reintroduction of WWOX induced p53-mutant GBM cells to undergo apoptosis, but not in p53 wild-type GBM cells, indicating WWOX is likely to reopen apoptosis pathways in a p53-independent manner in GBM. Identifying the crucial target modulated by WWOX deficiency provides a potential therapeutic target for GBM treatment. Here, we have reviewed the literatures about the role of WWOX in development, signaling pathway, prognosis, and treatment response in malignant glioma. PMID:25432984

  5. A Novel Methodology to Estimate the Treatment Effect in Presence of Highly Variable Placebo Response

    PubMed Central

    Gomeni, Roberto; Goyal, Navin; Bressolle, Françoise; Fava, Maurizio

    2015-01-01

    One of the main reasons for the inefficiency of multicenter randomized clinical trials (RCTs) in depression is the excessively high level of placebo response. The aim of this work was to propose a novel methodology to analyze RCTs based on the assumption that centers with high placebo response are less informative than the other centers for estimating the ‘true' treatment effect (TE). A linear mixed-effect modeling approach for repeated measures (MMRM) was used as a reference approach. The new method for estimating TE was based on a nonlinear longitudinal modeling of clinical scores (NLMMRM). NLMMRM estimates TE by associating a weighting factor to the data collected in each center. The weight was defined by the posterior probability of detecting a clinically relevant difference between active treatment and placebo at that center. Data from five RCTs in depression were used to compare the performance of MMRM with NLMMRM. The results of the analyses showed an average improvement of ~15% in the TE estimated with NLMMRM when the center effect was included in the analyses. Opposite results were observed with MMRM: TE estimate was reduced by ~4% when the center effect was considered as covariate in the analysis. The novel NLMMRM approach provides a tool for controlling the confounding effect of high placebo response, to increase signal detection and to provide a more reliable estimate of the ‘true' TE by controlling false negative results associated with excessively high placebo response. PMID:25895454

  6. Response of autochthonous microbiota of diesel polluted soils to land-farming treatments.

    PubMed

    Silva-Castro, Gloria Andrea; Uad, Imane; Rodríguez-Calvo, Alfonso; González-López, Jesús; Calvo, Concepción

    2015-02-01

    This study investigated the response of autochthonous microorganisms of diesel polluted soils to land-farming treatments. Inorganic NPK (nitrogen, phosphorous, and potassium) fertilizer and Ivey surfactant were applied alone or in combination as biostimulating agents. The study was carried out in experimental separated land-farming plots performed with two soils: a sandy clay soil with low biological activity and a sandy clay soil with higher biological activity, contaminated with two concentrations of diesel: 10,000 and 20,000mgkg(-1). Bacterial growth, dehydrogenase activity and CO2 production were the biological parameters evaluated. Non-metric multidimensional scaling analysis proved that moisture content showed a tendency related to microbial growth and that heterotrophic and degrading microorganisms had the best relationship. Initial biological activity of soil influenced the response with 11.1% of variability attributed to this parameter. Soils with low activity had higher degree of response to nutrient addition.

  7. A village treatment center for malaria: community response in Sri Lanka.

    PubMed

    Konradsen, F; Amerasinghe, P H; Perera, D; Van der Hoek, W; Amerasinghe, F P

    2000-03-01

    Early diagnosis and treatment of malaria cases is one of the basic elements of the current global malaria control strategy. In order to provide this service to people in rural areas there is a need for new cost-effective approaches. To ensure that such new approaches are acceptable to the target communities, it is important to know the rationale for people's malaria treatment-seeking behavior. The present study provides insights into the reasons for people's preferences for different types of healthcare facilities and describes variation of these preferences within a rural community in Sri Lanka. The study reports on the experiences with the establishment of a village health facility and its effect on the treatment-seeking behavior of the population. After the introduction of the village treatment center it quickly took over the role of main provider for diagnosis and treatment of malaria from the government facilities. The treatment center did not improve the response time in seeking treatment for young children, but the delay for adults was reduced by 1-2 days. Mothers with small children often preferred the government facilities since they wanted a more qualified opinion than available from the locally recruited staff of the village treatment center. The treatment center significantly reduced the stress and discomfort experienced by the elderly and handicapped segment of the community. The study indicated that the effective catchment area of a village treatment center will be influenced by the degree of initial support from key individuals in the communities, the selection procedure and training of assistants, and the history of the relationships between different villages to be served by the center. The government health services and communities across the dry zone of Sri Lanka could benefit substantially from the establishment of more village treatment centers. To ensure the long-term sustainability of these type of facilities it is necessary to assess the

  8. FERTILITY TREATMENT RESPONSE: IS IT BETTER TO BE MORE OPTIMISTIC OR LESS PESSIMISTIC?

    PubMed Central

    Bleil, Maria E.; Pasch, Lauri A.; Gregorich, Steven E.; Millstein, Susan G.; Katz, Patricia P.; Adler, Nancy E.

    2011-01-01

    Objective To evaluate the prospective relation between dispositional traits of optimism and pessimism and IVF treatment failure among women seeking medical intervention for infertility. Methods Among 198 women (ages 24-45, M=35.1[4.1]; 77% white), the outcome of each participant’s first IVF treatment cycle was examined. Treatment outcome was classified as being successful (vs. failed) if the woman either delivered a baby or was pregnant as a result of the cycle by the end of the 18-month study period. At baseline, optimism and pessimism were measured as a single bipolar dimension and as separate unipolar dimensions according to the Life Orientation Test (LOT) total score and the optimism and pessimism subscale scores, respectively. Results Optimism/pessimism, measured as a single bipolar dimension, predicted IVF treatment failure initially (B = -.09; p = .02; OR = 0.917; 95% CI = 0.851 – 0.988), but this association attenuated following statistical control for trait negative affect (B = -.06; p = .13; OR = 0.938; 95% CI = 0.863 – 1.020). When examined as separate unipolar dimensions, pessimism (B = .14; p = .04; OR = 1.146; 95% CI = 1.008 – 1.303), but not optimism (B = -.09; p = .12; OR = 0.912; 95% CI = 0.813 – 1.023), predicted IVF treatment failure independently of risk factors for poor IVF treatment response as well as trait negative affect. Conclusions Being pessimistic may be a risk factor for IVF treatment failure. Future research should attempt to delineate the biological and behavioral mechanisms by which pessimism may negatively affect treatment outcomes. PMID:22286845

  9. Treatment Response, Symptom Remission and Wellness in Obsessive-Compulsive Disorder

    PubMed Central

    Farris, Samantha G.; McLean, Carmen P.; Van Meter, Page E.; Simpson, H. Blair; Foa, Edna B.

    2014-01-01

    Objective Obsessive-compulsive disorder (OCD) is defined both by intrusive, unwanted thoughts, images or impulses and by repetitive behavioral or mental acts that are often performed to try to alleviate anxiety. The ultimate goal of treatment for OCD is to reduce the symptoms, as well as help patients achieve “wellness”, however currently there are no widely accepted, empirically supported criteria for determining wellness in OCD. Method Building on previous research, the current study pooled data from four OCD treatment trials (N = 288) that took place between 1990–2011to examine the Yale-Brown Obsessive Compulsive Disorder Scale (Y-BOCS) score that most reliably identified patients who responded to treatment, those who achieved symptom remission and those who achieved wellness. Results Signal detection analyses showed that a pre- to post-treatment reduction of ≥ 35% on the Y-BOCS was most predictive of treatment response, as defined by the Clinical Global Impressions (CGI-Improvement). A post-treatment Y-BOCS score of ≤ 14 was the best predictor of symptom remission, where a score of ≤ 12 was the best predictor of wellness, as defined by symptom remission defined by the CGI-Severity, good quality of life as measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (QLES-Q) and a high-level of adaptive function as assessed by the Social Adjustment Scale (SAS-SR). Conclusions Empirically supported criteria for defining wellness in OCD can facilitate comparisons across treatment outcome studies and inform clinical treatment planning. PMID:23945445

  10. Whole-Exome Sequencing of Metastatic Cancer and Biomarkers of Treatment Response

    PubMed Central

    Beltran, Himisha; Eng, Kenneth; Mosquera, Juan Miguel; Sigaras, Alexandros; Romanel, Alessandro; Rennert, Hanna; Kossai, Myriam; Pauli, Chantal; Faltas, Bishoy; Fontugne, Jacqueline; Park, Kyung; Banfelder, Jason; Prandi, Davide; Madhukar, Neel; Zhang, Tuo; Padilla, Jessica; Greco, Noah; McNary, Terra J.; Herrscher, Erick; Wilkes, David; MacDonald, Theresa Y.; Xue, Hui; Vacic, Vladimir; Emde, Anne-Katrin; Oschwald, Dayna; Tan, Adrian Y.; Chen, Zhengming; Collins, Colin; Gleave, Martin E.; Wang, Yuzhuo; Chakravarty, Dimple; Schiffman, Marc; Kim, Robert; Campagne, Fabien; Robinson, Brian D.; Nanus, David M.; Tagawa, Scott T.; Xiang, Jenny Z.; Smogorzewska, Agata; Demichelis, Francesca; Rickman, David S.; Sboner, Andrea; Elemento, Olivier; Rubin, Mark A.

    2015-01-01

    Importance Understanding molecular mechanisms of response and resistance to anticancer therapies requires prospective patient follow-up and clinical and functional validation of both common and low-frequency mutations. We describe a whole-exome sequencing (WES) precision medicine trial focused on patients with advanced cancer. Objective To understand how WES data affect therapeutic decision making in patients with advanced cancer and to identify novel biomarkers of response. Design, Setting, and Patients Patients with metastatic and treatment-resistant cancer were prospectively enrolled at a single academic center for paired metastatic tumor and normal tissue WES during a 19-month period (February 2013 through September 2014). A comprehensive computational pipeline was used to detect point mutations, indels, and copy number alterations. Mutations were categorized as category 1, 2, or 3 on the basis of actionability; clinical reports were generated and discussed in precision tumor board. Patients were observed for 7 to 25 months for correlation of molecular information with clinical response. Main Outcomes and Measures Feasibility, use of WES for decision making, and identification of novel biomarkers. Results A total of 154 tumor-normal pairs from 97 patients with a range of metastatic cancers were sequenced, with a mean coverage of 95× and 16 somatic alterations detected per patient. In total, 16 mutations were category 1 (targeted therapy available), 98 were category 2 (biologically relevant), and 1474 were category 3 (unknown significance). Overall, WES provided informative results in 91 cases (94%), including alterations for which there is an approved drug, there are therapies in clinical or preclinical development, or they are considered drivers and potentially actionable (category 1-2); however, treatment was guided in only 5 patients (5%) on the basis of these recommendations because of access to clinical trials and/or off-label use of drugs. Among

  11. Autoimmune response in MRL+/+ mice following treatment with dichloroacetyl chloride or dichloroacetic anhydride

    SciTech Connect

    Cai Ping; Koenig, Rolf; Khan, M. Firoze; Qiu, Suimin; Kaphalia, Bhupendra S.; Ansari, G.A.S. . E-mail: sansari@utmb.edu

    2006-10-15

    Dichloroacetyl chloride (DCAC) is formed from trichloroethene (TCE), which is implicated in inducing/accelerating autoimmune response. Due to its potent acylating activity, DCAC may convert proteins to neo-antigens and thus could induce autoimmune responses. Dichloroacetic anhydride (DCAA), which is a similar acylating agent, might also induce autoimmune responses. To evaluate if chloroacylation plays a role in the induction of autoimmunity, we have measured the autoimmune responses following treatment with DCAC or DCAA in autoimmune-prone MRL+/+ mice. Five-week-old female mice were injected intraperitoneally (twice weekly) with 0.2 mmol/kg of DCAC or DCAA in corn oil for 6 weeks. Total serum IgG, IgG1, and IgE levels were significantly increased in DCAC-treated mice as compared to controls. These increases corresponded with increases in DCAC-specific IgG and IgG1 levels. Total serum IgM was decreased in both DCAC- and DCAA-treated mice. Antinuclear antibodies, measured as an indication of systemic autoimmune responses, were increased in both DCAC- and DCAA-treated mice. Of eight Th1/Th2 cytokines measured in the serum, only IL-5 was significantly decreased in both treatment groups. The cytokine secretion patterns of splenic lymphocytes after stimulation with antibodies against CD3 (T cell receptor-mediated signal) and CD28 (costimulatory signal) differed between treatment and control groups. Levels of IL-1, IL-3, IL-6, IFN-{gamma}, G-CSF, and KC were higher in cultures of stimulated splenocytes from either DCAC- or DCAA-treated mice than from controls. The level of IL-17 was only increased in cultures from DCAC-treated mice. Increased lymphocytic populations were found in the red pulp of spleens following treatment with either DCAC or DCAA. In addition, thickening of the alveolar septa in the lungs of DCAC- or DCAA-treated mice was observed. The lung histopathology in exposed mice was consistent with the symptomology observed in welders exposed to DCAC

  12. Methods to assess the biodistribution of radiolabelled somatostatin analogues and treatment response of neuroendocrine tumours

    NASA Astrophysics Data System (ADS)

    Gnanasegaran, Gopinath

    Introduction: During the past decade, proof of the principle that somatostatin receptors can be successfully used for in vivo targeting of neuroendocrine tumours (NETs) has been provided. These tumours are imaged with 111Indium-pentetreotide and treated with 90Yttrium labeled somatostatin analogues. The aim of this study was to assess (a) the biodistribution and residency of 90Y labelled agents using the brehmsstrahlung imaging technique (b) the tumour response to various treatment modalities using a simplified scintigraphic method [Functional SPECT tumour volume (STV)]. Material and methods: 1) 19 patients with NETs were imaged with 111In-pentetreotide and 14 of them underwent treatment with 90Y-lanreotide. The rest underwent treatment with 90Y-SMT. All the patients were imaged 24 hours post-therapy. Brehmsstrahlung images obtained post therapies were used to assess the 90Y-lanreotide biodistribution in 14 patients and the 5 patients treated with 90Y-SMT, comparing them with 111In-pentetreotide. 2) In 42 patients with NETs a retrospective analysis was performed of the 111In-pentetreotide imaging and CT scan in patients treated with different therapies. A simplified scintigraphic method using 111In-pentetreotide SPECT liver imaging was used to monitor changes in tumour response and to determine how this correlates with CT scan and clinical response. Results: 1) 90Y-lanreotide and 90Y-SMT (with amino acids) have much lower uptake in the kidney (p 0.000 and 0.041 respectively) than 111In-pentetreotide. G Gnanasegaran MD 2 2) 22/42 patients had a good clinical response. A mean fall in total functional STV of 37% was seen in patients with symptomatic relief and a mean increase of 72 % was seen in patients with no symptomatic relief STV predicted the clinical outcome in 34 patients (81%) and CT predicted the outcome in 21 (50%) patients. Conclusion: There was a difference in biodistribution between 111In-pentetreotide and 90Y-lanreotide/ 90Y-SMT, especially in the

  13. Targeting Tumor Metabolism to Enhance the Effectiveness of Antitumor Immune Response in the Treatment of Breast Cancer

    DTIC Science & Technology

    2013-11-01

    the effectiveness of antitumor immune response in the treatment of breast cancer PRINCIPAL INVESTIGATOR: Shanmugasundaram Ganapathy-Kanniappan...the effectiveness of antitumor immune response in the treatment of breast cancer 5b. GRANT NUMBER W81XWH-11-1-0343 5c. PROGRAM ELEMENT NUMBER 6...response. Data from the current research investigation demonstrate that human breast cancer cells pre-treated with low, non-toxic dose of the

  14. Response to Early Intensive Behavioral Intervention for autism--an umbrella approach to issues critical to treatment individualization.

    PubMed

    Fava, Leonardo; Strauss, Kristin

    2014-12-01

    Integrating knowledge across the disciplines of genetics, neurological, and behavioral science targets, so far, early identification of children with autism and thus early access to intervention. Cross-discipline collaboration might be substantially improve treatment efficacy via individualized treatment based on the child and family needs, consistency across treatment providers and careful planning of skill curricula, setting and techniques. This paper documents the current state of five main issues critical to treatment individualization where cross-discipline collaboration is warranted: (1) developmental timing, (2) treatment intensity, (3) heterogeneity in treatment response, (4) program breath and flexibility, and (5) formats of treatment provision.

  15. Post-treatment Vascular Leakage and Inflammatory Responses around Brain Cysts in Porcine Neurocysticercosis

    PubMed Central

    Mahanty, Siddhartha; Orrego, Miguel Angel; Mayta, Holger; Marzal, Miguel; Cangalaya, Carla; Paredes, Adriana; Gonzales-Gustavson, Eloy; Arroyo, Gianfranco; Gonzalez, Armando E.; Guerra-Giraldez, Cristina; García, Hector H.; Nash, Theodore E.

    2015-01-01

    Cysticidal treatment of neurocysticercosis, an infection of humans and pig brains with Taenia solium, results in an early inflammatory response directed to cysts causing seizures and focal neurological manifestations. Treatment-induced pericystic inflammation and its association with blood brain barrier (BBB) dysfunction, as determined by Evans blue (EB) extravasation, was studied in infected untreated and anthelmintic-treated pigs. We compared the magnitude and extent of the pericystic inflammation, presence of EB-stained capsules, the level of damage to the parasite, expression of genes for proinflammatory and regulatory cytokines, chemokines, and tissue remodeling by quantitative PCR assays between treated and untreated infected pigs and between EB-stained (blue) and non stained (clear) cysts. Inflammatory scores were higher in pericystic tissues from EB-stained cysts compared to clear cysts from untreated pigs and also from anthelmintic-treated pigs 48 hr and 120 hr after treatment. The degree of inflammation correlated with the severity of cyst wall damage and both increased significantly at 120 hours. Expression levels of the proinflammatory genes for IL-6, IFN-γ, TNF-α were higher in EB-stained cysts compared to clear cysts and unaffected brain tissues, and were generally highest at 120 hr. Additionally, expression of some markers of immunoregulatory activity (IL-10, IL-2Rα) were decreased in EB-stained capsules. An increase in other markers for regulatory T cells (CTLA4, FoxP3) was found, as well as significant increases in expression of two metalloproteases, MMP1 and MMP2 at 48 hr and 120 hr post-treatment. We conclude that the increase in severity of the inflammation caused by treatment is accompanied by both a proinflammatory and a complex regulatory response, largely limited to pericystic tissues with compromised vascular integrity. Because treatment induced inflammation occurs in porcine NCC similar to that in human cases, this model can be used to

  16. SIRT1 as a potential biomarker of response to treatment with glatiramer acetate in multiple sclerosis.

    PubMed

    Hewes, Daniel; Tatomir, Alexandru; Kruszewski, Adam M; Rao, Gautam; Tegla, Cosmin A; Ciriello, Jonathan; Nguyen, Vingh; Royal, Walter; Bever, Christopher; Rus, Violeta; Rus, Horea

    2017-01-19

    SIRT1, a NAD dependent histone and protein deacetylase, is a member of the histone deacetylase class III family. We previously showed that SIRT1 mRNA expression is significantly lower in peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients during relapses than in stable patients. We have now investigated SIRT1 as a possible biomarker to predict relapse as well as responsiveness to glatiramer acetate (GA) treatment in relapsing-remitting MS (RRMS) patients. Over the course of 2years, a cohort of 15 GA-treated RRMS patients were clinically monitored using the Expanded Disability Status Scale and assessed for MS relapses. Blood samples collected from MS patients were analyzed for levels of SIRT1 and histone H3 lysine 9 (H3K9) acetylation and dimethylation. During relapses, MS patients had a lower expression of SIRT1 mRNA than did stable MS patients. In addition, there was a significant decrease in H3K9 dimethylation (H3K9me2) during relapses in MS patients when compared to stable patients (p=0.01). Responders to GA treatment had significantly higher SIRT1 mRNA (p=0.01) and H3K9me2 levels than did non-responders (p=0.018). Receiver operating characteristic analysis was used to assess the predictive power of SIRT1 and H3K9me2 as putative biomarkers: for SIRT1 mRNA, the predictive value for responsiveness to GA treatment was 70% (p=0.04) and for H3K9me2 was 71% (p=0.03). Our data suggest that SIRT1 and H3K9me2 could serve as potential biomarkers for evaluating patients' responsiveness to GA therapy in order to help guide treatment decisions in MS.

  17. Evaluation of chemotherapy response in ovarian cancer treatment using quantitative CT image biomarkers: a preliminary study

    NASA Astrophysics Data System (ADS)

    Qiu, Yuchen; Tan, Maxine; McMeekin, Scott; Thai, Theresa; Moore, Kathleen; Ding, Kai; Liu, Hong; Zheng, Bin

    2015-03-01

    The purpose of this study is to identify and apply quantitative image biomarkers for early prediction of the tumor response to the chemotherapy among the ovarian cancer patients participated in the clinical trials of testing new drugs. In the experiment, we retrospectively selected 30 cases from the patients who participated in Phase I clinical trials of new drug or drug agents for ovarian cancer treatment. Each case is composed of two sets of CT images acquired pre- and post-treatment (4-6 weeks after starting treatment). A computer-aided detection (CAD) scheme was developed to extract and analyze the quantitative image features of the metastatic tumors previously tracked by the radiologists using the standard Response Evaluation Criteria in Solid Tumors (RECIST) guideline. The CAD scheme first segmented 3-D tumor volumes from the background using a hybrid tumor segmentation scheme. Then, for each segmented tumor, CAD computed three quantitative image features including the change of tumor volume, tumor CT number (density) and density variance. The feature changes were calculated between the matched tumors tracked on the CT images acquired pre- and post-treatments. Finally, CAD predicted patient's 6-month progression-free survival (PFS) using a decision-tree based classifier. The performance of the CAD scheme was compared with the RECIST category. The result shows that the CAD scheme achieved a prediction accuracy of 76.7% (23/30 cases) with a Kappa coefficient of 0.493, which is significantly higher than the performance of RECIST prediction with a prediction accuracy and Kappa coefficient of 60% (17/30) and 0.062, respectively. This study demonstrated the feasibility of analyzing quantitative image features to improve the early predicting accuracy of the tumor response to the new testing drugs or therapeutic methods for the ovarian cancer patients.

  18. Opiate Analgesia Treatment Reduced Early Inflammatory Response After Severe Chest Injuries

    PubMed Central

    Krdzalic, Goran; Musanovic, Nermin; Krdzalic, Alisa; Mehmedagic, Indira; Kesetovic, Amar

    2016-01-01

    Background: The frequency of severe chest injuries are increased. Their high morbidity is followed by systemic inflammatory response. The efficacy of pharmacological blockade of the response could prevent complications after chest injures. Aim: The aim of the study was to show an inflammatory response level, its prognostic significant and length of hospital stay after chest injures opiate analgesia treatment. Methods: Sixty patients from Department of Thoracic Surgery with severe chest injures were included in the prospective study. With respect of non opiate or opiate analgesia treatment, the patients were divided in two groups consisted of 30 patients. As a inflammatory markers, serum values of leukocytes, neutrophils, C-reactive protein (CRP) and fibrinogen in three measurements: at the time of admission, 24hours and 48 hours after admission, were followed. Results: Statistically significant differences were found between the examined groups in mean serum values of neutrophils (p=0.026 and p=0.03) in the second and the third measurement, CRP (p=0.05 and 0.25) in the second and the third measurement and leukocytes in the third measurement (p=0.016). 6 patients in group I and 3 in group II had initial stage of pneumonia, 13 patients in group I and 6 in group II had atelectasis and 7 patients from group I and 4 from group II had pleural effusion. The rate of complications was lower in group of patient who were under opiate analgesia treatment but without significant difference. The length of hospital stay for the patients in group I was 7.3±1.15 days and for the patients in group II it was 6.1±0.87 days with statistically significant difference p=0.017. Conclusion: The opiate analgesia in patients with severe chest injures reduced level of early inflammatory response, rate of intra hospital complications and length of hospital stay. PMID:28210021

  19. Endophenotypes and serotonergic polymorphisms associated with treatment response in obsessive-compulsive disorder

    PubMed Central

    Corregiari, Fábio M; Bernik, Márcio; Cordeiro, Quirino; Vallada, Homero

    2012-01-01

    OBJECTIVES: Approximately 40-60% of obsessive-compulsive disorder patients are nonresponsive to serotonin reuptake inhibitors. Genetic markers associated with treatment response remain largely unknown. We aimed (1) to investigate a possible association of serotonergic polymorphisms in obsessive-compulsive disorder patients and therapeutic response to selective serotonin reuptake inhibitors and (2) to examine the relationship between these polymorphisms and endocrine response to intravenous citalopram challenge in responders and non-responders to serotonin reuptake inhibitors and in healthy volunteers. METHODS: Patients with obsessive-compulsive disorder were classified as either responders or non-responders after long-term treatment with serotonin reuptake inhibitors, and both groups were compared with a control group of healthy volunteers. The investigated genetic markers were the G861C polymorphism of the serotonin receptor 1Dβ gene and the T102C and C516T polymorphisms of the serotonin receptor subtype 2A gene. RESULTS: The T allele of the serotonin receptor subtype 2A T102C polymorphism was more frequent among obsessive-compulsive disorder patients (responders and non-responders) than in the controls (p<0.01). The CC genotype of the serotonin receptor subtype 2A C516T polymorphism was more frequent among the non-responders than in the responders (p<0.01). The CC genotype of the serotonin receptor subtype 1Dβ G681C polymorphism was associated with higher cortisol and prolactin responses to citalopram (p<0.01 and p<0.001, respectively) and with a higher platelet-rich plasma serotonin concentration among the controls (p<0.05). However, this pattern was not observed in the non-responders with the same CC genotype after chronic treatment with serotonin reuptake inhibitors. This CC homozygosity was not observed in the responders. PMID:22522758

  20. Symptom predictors of response to electroconvulsive therapy in older patients with treatment-resistant depression

    PubMed Central

    Tominaga, Keiichiro; Okazaki, Mioto; Higuchi, Hisashi; Utagawa, Itaru; Nakamura, Etsuko; Yamaguchi, Noboru

    2011-01-01

    Background: Electroconvulsive therapy (ECT) has been used for treatment-resistant depression. However, predictors of response to ECT have not been adequately studied using the Montgomery and Åsberg Depression Rating Scale, especially in older patients with treatment-resistant depression. Methods: This study included 18 Japanese patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision criteria for a diagnosis of major depressive disorder or bipolar disorder with a current major depressive episode, and met the definition of treatment-resistant depression outlined by Thase and Rush, scoring ≥21 on the Montgomery and Åsberg Depression Rating Scale. The three-factor model of the Montgomery and Åsberg Depression Rating Scale was used for analysis. Factor 1 was defined by three items, factor 2 by four items, and factor 3 by three items, representing dysphoria, retardation, and vegetative symptoms, respectively. ECT was performed twice a week for a total of six sessions using a Thymatron System IV device with the brief pulse technique. Clinical responses were defined on the basis of a ≥50% decrease in total pretreatment Montgomery and Åsberg Depression Rating Scale scores. Results: The mean pretreatment factor 2 score for responders (n = 7) was significantly lower than that for nonresponders (n = 11). Furthermore, a significant difference in mean factor 3 score between responders and nonresponders was observed one week after six sessions of ECT, indicating a time lag of response. No significant differences were observed for age, number of previous episodes, and duration of the current episode between responders and nonresponders. Conclusion: This study suggests that a low pretreatment factor 2 score is a good predictor of response to ECT in older patients with major depression. PMID:21845058

  1. Homer-1 polymorphisms are associated with psychopathology and response to treatment in schizophrenic patients.

    PubMed

    Spellmann, Ilja; Rujescu, Dan; Musil, Richard; Mayr, Andreas; Giegling, Ina; Genius, Just; Zill, Peter; Dehning, Sandra; Opgen-Rhein, Markus; Cerovecki, Anja; Hartmann, Annette M; Schäfer, Martin; Bondy, Brigitta; Müller, Norbert; Möller, Hans-Jürgen; Riedel, Michael

    2011-02-01

    The HOMER 1 protein plays a crucial role in mediating glutamatergic neurotransmission. It has previously shown to be a candidate gene for etiology and pathophysiology of different psychiatric diseases such as schizophrenia. To identify genes involved in response to antipsychotics, subgroups of animals were treated with haloperidol (1 mg/kg, n = 11) or saline (n = 12) for one week. By analyzing microarray data, we replicated the observed increase of Homer 1 gene expression. Furthermore, we genotyped 267 schizophrenic patients, who were treated monotherapeutically with different antipsychotics within randomized-controlled trials. Psychopathology was measured weekly using the PANSS for a minimum of four and a maximum of twelve weeks. Correlations between PANSS subscale scores at baseline and PANSS improvement scores after four weeks of treatment and genotypes were calculated by using a linear model for all investigated SNP's. We found an association between two HOMER 1 polymorphisms (rs2290639 and rs4704560) and different PANSS subscales at baseline. Furthermore all seven investigated polymorphisms were found to be associated with therapy response in terms of a significant correlation with different PANSS improvement subscores after four weeks of antipsychotic treatment. Most significant associations have been shown between the rs2290639 HOMER 1 polymorphism and PANSS subscales both at baseline conditions and after four weeks of antipsychotic treatment. This is the first study which shows an association between HOMER 1 polymorphisms and psychopathology data at baseline and therapy response in a clinical sample of schizophrenic patients. Thus, these data might further help in detecting differential therapy response in individuals with schizophrenia.

  2. Substance Abuse Treatment, HIV/AIDS, and the Continuum of Response for People Who Inject Drugs

    PubMed Central

    Kresina, Thomas F.; Lubran, Robert; Clark, H. Westley; Cheever, Laura W.

    2012-01-01

    The continuum of response (CoR) to HIV/AIDS is a framework for implementation of HIV prevention, care, and treatment programs based on a national strategic plan for HIV/AIDS services. The CoR for people who inject drugs (PWID) is an important extension of the developed CoR to HIV/AIDS. The CoR-PWID employs stakeholders who together plan, develop, pilot, and provide a full range of services that address the various prevention, care/support, and treatment needs of people, families, and communities infected or affected by HIV/AIDS and injection drug use. The CoR-PWID comprises a broad range of services that include but are not limited to the World Health Organization priority interventions for HIV/AIDS prevention, treatment, and care in the health sector and the package of essential interventions for the prevention, treatment, and care of HIV for people who inject drugs. Implementation of these well-defined, essential prevention, care/support, and treatment services, in addition to locally defined needed services, in a coordinated fashion is important to clients, their families, and communities. The CoR-PWID is, therefore, a necessary framework essential for service development for countries that address HIV/AIDS in populations of PWID. PMID:23243517

  3. Liquid biopsy and therapeutic response: Circulating tumor cell cultures for evaluation of anticancer treatment.

    PubMed

    Khoo, Bee Luan; Grenci, Gianluca; Jing, Tengyang; Lim, Ying Bena; Lee, Soo Chin; Thiery, Jean Paul; Han, Jongyoon; Lim, Chwee Teck

    2016-07-01

    The lack of a robust anticancer drug screening system to monitor patients during treatment delays realization of personalized treatment. We demonstrate an efficient approach to evaluate drug response using patient-derived circulating tumor cell (CTC) cultures obtained from liquid biopsy. Custom microfabricated tapered microwells were integrated with microfluidics to allow robust formation of CTC clusters without pre-enrichment and subsequent drug screening in situ. Rapid feedback after 2 weeks promotes immediate intervention upon detection of drug resistance or tolerance. The procedure was clinically validated with blood samples (n = 73) from 55 patients with early-stage, newly diagnosed, locally advanced, or refractory metastatic breast cancer. Twenty-four of these samples were used for drug evaluation. Cluster formation potential correlated inversely with increased drug concentration and therapeutic treatment. This new and robust liquid biopsy technique can potentially evaluate patient prognosis with CTC clusters during treatment and provide a noninvasive and inexpensive assessment that can guide drug discovery development or therapeutic choices for personalized treatment.

  4. Liquid biopsy and therapeutic response: Circulating tumor cell cultures for evaluation of anticancer treatment

    PubMed Central

    Khoo, Bee Luan; Grenci, Gianluca; Jing, Tengyang; Lim, Ying Bena; Lee, Soo Chin; Thiery, Jean Paul; Han, Jongyoon; Lim, Chwee Teck

    2016-01-01

    The lack of a robust anticancer drug screening system to monitor patients during treatment delays realization of personalized treatment. We demonstrate an efficient approach to evaluate drug response using patient-derived circulating tumor cell (CTC) cultures obtained from liquid biopsy. Custom microfabricated tapered microwells were integrated with microfluidics to allow robust formation of CTC clusters without pre-enrichment and subsequent drug screening in situ. Rapid feedback after 2 weeks promotes immediate intervention upon detection of drug resistance or tolerance. The procedure was clinically validated with blood samples (n = 73) from 55 patients with early-stage, newly diagnosed, locally advanced, or refractory metastatic breast cancer. Twenty-four of these samples were used for drug evaluation. Cluster formation potential correlated inversely with increased drug concentration and therapeutic treatment. This new and robust liquid biopsy technique can potentially evaluate patient prognosis with CTC clusters during treatment and provide a noninvasive and inexpensive assessment that can guide drug discovery development or therapeutic choices for personalized treatment. PMID:27453941

  5. Differences in Phyllotreta cruciferae and Phyllotreta striolata (Coleoptera: Chrysomelidae) responses to neonicotinoid seed treatments.

    PubMed

    Tansey, J A; Dosdall, L M; Keddie, B A; Sarfraz, R M

    2008-02-01

    Insecticidal seed treatments are used commonly throughout the Northern Great Plains of North America to systemically protect seedlings of canola (Brassica napus L. and Brassica rapa L.) from attack by the flea beetles Phyllotreta cruciferae (Goeze) and Phyllotreta striolata (F.) (Coleoptera: Chrysomelidae). Here, we investigated differential responses by the two flea beetle species to the neonicotinoid seed treatments thiamethoxam (Helix and Helix XTra) and clothianidin (Prosper 400) in greenhouse experiments. P. cruciferae experienced higher mortality and fed less when exposed to these compounds than did P. striolata. Beetles of the overwintered and the summer generations responded differently when feeding on seedlings that developed with insecticidal seed treatments, with mortality higher for P. cruciferae in May than in August. When the two flea beetle species were held together at equal densities and allowed to feed on seedlings affected by the seed treatments, mortality of P. cruciferae significantly exceeded that of P. striolata. Differences in efficacies of these compounds for these beetles have ramifications for management strategies in regions where these insects occur sympatrically. Competitive release of P. striolata was previously reported to occur when P. cruciferae was excluded from brassicaceous crops; consequently, the consistent use of these seed treatments over millions of hectares of canola cropland may be a factor that contributes to a shift in prevalence of flea beetle pest species from P. cruciferae toward P. striolata.

  6. Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis

    PubMed Central

    Sieberts, Solveig K.; Zhu, Fan; García-García, Javier; Stahl, Eli; Pratap, Abhishek; Pandey, Gaurav; Pappas, Dimitrios; Aguilar, Daniel; Anton, Bernat; Bonet, Jaume; Eksi, Ridvan; Fornés, Oriol; Guney, Emre; Li, Hongdong; Marín, Manuel Alejandro; Panwar, Bharat; Planas-Iglesias, Joan; Poglayen, Daniel; Cui, Jing; Falcao, Andre O.; Suver, Christine; Hoff, Bruce; Balagurusamy, Venkat S. K.; Dillenberger, Donna; Neto, Elias Chaibub; Norman, Thea; Aittokallio, Tero; Ammad-ud-din, Muhammad; Azencott, Chloe-Agathe; Bellón, Víctor; Boeva, Valentina; Bunte, Kerstin; Chheda, Himanshu; Cheng, Lu; Corander, Jukka; Dumontier, Michel; Goldenberg, Anna; Gopalacharyulu, Peddinti; Hajiloo, Mohsen; Hidru, Daniel; Jaiswal, Alok; Kaski, Samuel; Khalfaoui, Beyrem; Khan, Suleiman Ali; Kramer, Eric R.; Marttinen, Pekka; Mezlini, Aziz M.; Molparia, Bhuvan; Pirinen, Matti; Saarela, Janna; Samwald, Matthias; Stoven, Véronique; Tang, Hao; Tang, Jing; Torkamani, Ali; Vert, Jean-Phillipe; Wang, Bo; Wang, Tao; Wennerberg, Krister; Wineinger, Nathan E.; Xiao, Guanghua; Xie, Yang; Yeung, Rae; Zhan, Xiaowei; Zhao, Cheng; Calaza, Manuel; Elmarakeby, Haitham; Heath, Lenwood S.; Long, Quan; Moore, Jonathan D.; Opiyo, Stephen Obol; Savage, Richard S.; Zhu, Jun; Greenberg, Jeff; Kremer, Joel; Michaud, Kaleb; Barton, Anne; Coenen, Marieke; Mariette, Xavier; Miceli, Corinne; Shadick, Nancy; Weinblatt, Michael; de Vries, Niek; Tak, Paul P.; Gerlag, Danielle; Huizinga, Tom W. J.; Kurreeman, Fina; Allaart, Cornelia F.; Louis Bridges Jr., S.; Criswell, Lindsey; Moreland, Larry; Klareskog, Lars; Saevarsdottir, Saedis; Padyukov, Leonid; Gregersen, Peter K.; Friend, Stephen; Plenge, Robert; Stolovitzky, Gustavo; Oliva, Baldo; Guan, Yuanfang; Mangravite, Lara M.

    2016-01-01

    Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h2=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data. PMID:27549343

  7. Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis.

    PubMed

    Sieberts, Solveig K; Zhu, Fan; García-García, Javier; Stahl, Eli; Pratap, Abhishek; Pandey, Gaurav; Pappas, Dimitrios; Aguilar, Daniel; Anton, Bernat; Bonet, Jaume; Eksi, Ridvan; Fornés, Oriol; Guney, Emre; Li, Hongdong; Marín, Manuel Alejandro; Panwar, Bharat; Planas-Iglesias, Joan; Poglayen, Daniel; Cui, Jing; Falcao, Andre O; Suver, Christine; Hoff, Bruce; Balagurusamy, Venkat S K; Dillenberger, Donna; Neto, Elias Chaibub; Norman, Thea; Aittokallio, Tero; Ammad-Ud-Din, Muhammad; Azencott, Chloe-Agathe; Bellón, Víctor; Boeva, Valentina; Bunte, Kerstin; Chheda, Himanshu; Cheng, Lu; Corander, Jukka; Dumontier, Michel; Goldenberg, Anna; Gopalacharyulu, Peddinti; Hajiloo, Mohsen; Hidru, Daniel; Jaiswal, Alok; Kaski, Samuel; Khalfaoui, Beyrem; Khan, Suleiman Ali; Kramer, Eric R; Marttinen, Pekka; Mezlini, Aziz M; Molparia, Bhuvan; Pirinen, Matti; Saarela, Janna; Samwald, Matthias; Stoven, Véronique; Tang, Hao; Tang, Jing; Torkamani, Ali; Vert, Jean-Phillipe; Wang, Bo; Wang, Tao; Wennerberg, Krister; Wineinger, Nathan E; Xiao, Guanghua; Xie, Yang; Yeung, Rae; Zhan, Xiaowei; Zhao, Cheng; Greenberg, Jeff; Kremer, Joel; Michaud, Kaleb; Barton, Anne; Coenen, Marieke; Mariette, Xavier; Miceli, Corinne; Shadick, Nancy; Weinblatt, Michael; de Vries, Niek; Tak, Paul P; Gerlag, Danielle; Huizinga, Tom W J; Kurreeman, Fina; Allaart, Cornelia F; Louis Bridges, S; Criswell, Lindsey; Moreland, Larry; Klareskog, Lars; Saevarsdottir, Saedis; Padyukov, Leonid; Gregersen, Peter K; Friend, Stephen; Plenge, Robert; Stolovitzky, Gustavo; Oliva, Baldo; Guan, Yuanfang; Mangravite, Lara M; Bridges, S Louis; Criswell, Lindsey; Moreland, Larry; Klareskog, Lars; Saevarsdottir, Saedis; Padyukov, Leonid; Gregersen, Peter K; Friend, Stephen; Plenge, Robert; Stolovitzky, Gustavo; Oliva, Baldo; Guan, Yuanfang; Mangravite, Lara M

    2016-08-23

    Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h(2)=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data.

  8. Training motor responses to food: A novel treatment for obesity targeting implicit processes.

    PubMed

    Stice, Eric; Lawrence, Natalia S; Kemps, Eva; Veling, Harm

    2016-11-01

    The present review first summarizes results from prospective brain imaging studies focused on identifying neural vulnerability factors that predict excessive weight gain. Next, findings from cognitive psychology experiments evaluating various interventions involving food response inhibition training or food response facilitation training are reviewed that appear to target these neural vulnerability factors and that have produced encouraging weight loss effects. Findings from both of these reviewed research fields suggest that interventions that reduce reward and attention region responses to high calorie food cues and increase inhibitory region responses to high calorie food cues could prove useful in the treatment of obesity. Based on this review, a new conceptual model is presented to describe how different cognitive training procedures may contribute to modifying eating behavior and important directions for future research are offered. It is concluded that there is a need for evaluating the effectiveness of more intensive food response training interventions and testing whether adding such training to extant weight loss interventions increases their efficacy.

  9. Posttraumatic and postsurgical neuropathic pain responsive to treatment with capsaicin 8% topical patch.

    PubMed

    Zis, Panagiotis; Apsokardos, Alexandros; Isaia, Christina; Sykioti, Panagiota; Vadalouca, Athina

    2014-01-01

    Capsaicin 8% patch (Qutenza) is mainly used to treat postherpetic neuralgia and human immunodeficiency virus-associated neuropathy. However, evidence of the efficacy of Qutenza in other forms of neuropathic pain is lacking. A 24-year old Libyan man, with no previous medical history, sustained multiple wounds in the right side of the chest and back after a bomb explosion. The patient experienced pain, which persisted in a wide location around the surgical intervention for a long time, beyond the usual course of natural healing of an acute pain and was different from that suffered preoperatively. The characteristics of the pain included burning, electric shock-like sensation, tingling, and numbness, and it was paroxysmal. The pain was associated with hyperalgesia and intense allodynia in a wide area, approximately of 1,100 cm2. Our initial treatment strategy included pregabalin, tramadol, and duloxetine. However, our patient's pain responded to treatment with capsaicin 8% patch when the initial treatments showed only minimal effectiveness regarding the intensity of pain. Interestingly, the most important finding was that capsaicin 8% patch showed a more than 80% reduction of the area of allodynia associated with the pain, when other treatments failed. Moreover, although recent data showed that in patients who respond to Qutenza, analgesia starts within a few days of treatment and lasts on average 5 months, our patient showed an initial response within 7 days of treatment but a longer duration of more than 18 months. Although further controlled studies are needed to explore the efficacy of the capsaicin 8% patch in patients who experience posttraumatic neuropathic pain, we encourage clinicians to try the capsaicin 8% patch when alternative treatments fail.

  10. Favorable Growth Hormone Treatment Response in a Young Boy with Achondroplasia

    PubMed Central

    Krstevska-Konstantinova, Marina; Stamatova, Ana; Gucev, Zoran

    2016-01-01

    Background: Achondroplasia is a skeletal dysplasia, the most common cause of rhizomelic dwarfism. Case presentation: This is a ten year old boy who was first diagnosed prenatally. He had a mutation c1138G>A in the gene FGFR3 in a heterozygotic constellation. His IGF1 and IGFBP3 levels were normal. Two stimulation tests for growth hormone were performed with values within the reference range. His psychomotor development was adequate for his age except for speech difficulty. He started with recombinant hGH (r-hGH) at the age of 3.4 years in a dose of 0.06 mg/kg. His mean Height SDS (HtSDS) was -2.2. Results: The growth increased to 10 cm/year in the first year of therapy (HtSDS -1.1). It decreased during the second year to 4 cm (HtSDS -1.7) and again increased during the third year to 8 cm/year (HtSDS–1.3). In the next years the growth was constant (6.5, 2.3, 3.5 cm / year). He is still growing in the 3rd percentile of the growth curve (HtSDS – 1.2) under GH treatment. The body disproportion remained the same. Conclusion: The growth response on GH treatment was satisfactory in the first 4 years of treatment, and the boy still continued to grow. The young age at the start of treatment was also of importance. Our other patients with achondroplasia who started treatment older had a poor response to growth hormone. PMID:27147792

  11. Neurocognitive Predictors of Response in Treatment Resistant Depression to Subcallosal Cingulate Gyrus Deep Brain Stimulation.

    PubMed

    McInerney, Shane J; McNeely, Heather E; Geraci, Joseph; Giacobbe, Peter; Rizvi, Sakina J; Ceniti, Amanda K; Cyriac, Anna; Mayberg, Helen S; Lozano, Andres M; Kennedy, Sidney H

    2017-01-01

    Background: Deep brain stimulation (DBS) is a neurosurgical intervention with demonstrated effectiveness for treatment resistant depression (TRD), but longitudinal studies on the stability of cognitive parameters following treatment are limited. The objectives of this study are to (i) identify baseline cognitive predictors of treatment response to subcallosal cingulate gyrus (SCG) DBS for unipolar TRD and (ii) compare neurocognitive performance prior to and 12 months after DBS implantation. Methods: Twenty unipolar TRD patients received SCG DBS for 12 months. A standardized neuropsychological battery was used to assess a range of neurocognitive abilities at baseline and after 12 months. Severity of depression was evaluated using the 17 item Hamilton Rating Scale for Depression. Results: Finger Tap-Dominant Hand Test and total number of errors made on the Wisconsin Card Sorting Test predicted classification of patients as treatment responders or non-responders, and were independent of improvement in mood. Change in verbal fluency was the only neuropsychological test that correlated with change in mood from baseline to the follow up period. None of the neuropsychological measures displayed deterioration in cognitive functioning from baseline to repeat testing at 12 months. Limitations: This was an open label study with a small sample size which limits predictive analysis. Practice effects of the neuropsychological testing could explain the improvement from baseline to follow up on some tasks. Replication using a larger sample of subjects who received neuropsychological testing before and at least 12 months after DBS surgery is required. Conclusion: These preliminary results (i) suggest that psychomotor speed may be a useful baseline predictor of response to SCG DBS treatment and (ii) support previous suggestions that SCG DBS has no deleterious effects on cognition.

  12. Neurocognitive Predictors of Response in Treatment Resistant Depression to Subcallosal Cingulate Gyrus Deep Brain Stimulation

    PubMed Central

    McInerney, Shane J.; McNeely, Heather E.; Geraci, Joseph; Giacobbe, Peter; Rizvi, Sakina J.; Ceniti, Amanda K.; Cyriac, Anna; Mayberg, Helen S.; Lozano, Andres M.; Kennedy, Sidney H.

    2017-01-01

    Background: Deep brain stimulation (DBS) is a neurosurgical intervention with demonstrated effectiveness for treatment resistant depression (TRD), but longitudinal studies on the stability of cognitive parameters following treatment are limited. The objectives of this study are to (i) identify baseline cognitive predictors of treatment response to subcallosal cingulate gyrus (SCG) DBS for unipolar TRD and (ii) compare neurocognitive performance prior to and 12 months after DBS implantation. Methods: Twenty unipolar TRD patients received SCG DBS for 12 months. A standardized neuropsychological battery was used to assess a range of neurocognitive abilities at baseline and after 12 months. Severity of depression was evaluated using the 17 item Hamilton Rating Scale for Depression. Results: Finger Tap-Dominant Hand Test and total number of errors made on the Wisconsin Card Sorting Test predicted classification of patients as treatment responders or non-responders, and were independent of improvement in mood. Change in verbal fluency was the only neuropsychological test that correlated with change in mood from baseline to the follow up period. None of the neuropsychological measures displayed deterioration in cognitive functioning from baseline to repeat testing at 12 months. Limitations: This was an open label study with a small sample size which limits predictive analysis. Practice effects of the neuropsychological testing could explain the improvement from baseline to follow up on some tasks. Replication using a larger sample of subjects who received neuropsychological testing before and at least 12 months after DBS surgery is required. Conclusion: These preliminary results (i) suggest that psychomotor speed may be a useful baseline predictor of response to SCG DBS treatment and (ii) support previous suggestions that SCG DBS has no deleterious effects on cognition. PMID:28286473

  13. The evaluation of risk factors for failed response to conservative treatment in tubo-ovarian abscesses

    PubMed Central

    Akkurt, Mehmet Özgür; Yalçın, Serenat Eris; Akkurt, İltaç; Tatar, Burak; Yavuz, And; Yalçın, Yakup; Akgül, Mehmet Akif; Kayıkçıoğlu, Fulya

    2015-01-01

    Objective The aim of our study is to assess the risk factors for medical treatment failure and to predict the patients who will require the surgical therapy as well as to predict the factors affecting treatment success. Material and Methods This was a cross-sectional study including 76 women with tubo-ovarian abscesses (TOA) who were either conservatively or surgically treated and were admitted to two gynecology units over a 4-year period. The demographic characteristics of the patients, gynecologic and obstetric histories, size and localization of abscesses were recorded. Gentamicin plus clindamycin treatment protocol was implemented for all patients. Ampicillin treatment was added in three patients with the positive culture of Actinomyces. Response to treatment was evaluated after 48–72 h. Patients who fail to respond to medical treatment required surgery or percutaneous drainage. We compared clinical and laboratory factors between the groups. Results In surgery group, patients were significantly older than the others (44.9±5.4 versus 39.1±7.6 years). Fifty-six patients (74%) responded to antibiotics and 20 of the patients required surgical intervention. Patients treated with antibiotics were hospitalized for an average of 6.32±2.8 days versus 12.75±5.6 days for those who required surgery (p=0.021). Patients who were surgically treated had a mean size of TOA of 67.9±11.2 mm versus 53.6±9.4 mm for those treated with antibiotics alone (p=0.036). There were no significant differences between groups in laboratory parameters, except for initial white blood cell (WBC) counts. The complications of surgery included in descending order of frequency blood transfusions, surgical wound infections, bowel injury, and bladder injury. Conclusion An increased size of pelvic mass, higher initial WBC counts, advanced age, and smoking were all associated with failed response to conservative treatment. It is important to identify the risk factors to distinguish patients who

  14. Lymphocytosis after treatment with dasatinib in chronic myeloid leukemia: Effects on response and toxicity

    PubMed Central

    Cortes, Jorge E.; Hochhaus, Andreas; Saglio, Giuseppe; le Coutre, Philipp; Porkka, Kimmo; Mustjoki, Satu; Mohamed, Hesham; Shah, Neil P.

    2016-01-01

    BACKGROUND The proliferation of clonal cytotoxic T‐cells or natural killer cells has been observed after dasatinib treatment in small studies of patients with chronic myeloid leukemia (CML). METHODS The incidence of lymphocytosis and its association with response, survival, and side effects were assessed in patients from 3 large clinical trials. Overall, 1402 dasatinib‐treated patients with newly diagnosed CML in chronic phase (CML‐CP), CML‐CP refractory/intolerant to imatinib, or with CML in accelerated or myeloid‐blast phase were analyzed. RESULTS Lymphocytosis developed in 32% to 35% of patients and persisted for >12 months. This was not observed in the patients who received treatment with imatinib. Dasatinib‐treated patients in all stages of CML who developed lymphocytosis were more likely to achieve a complete cytogenetic response, and patients who had CML‐CP with lymphocytosis were more likely to achieve major and deep molecular responses. Progression‐free and overall survival rates were significantly longer in patients with CML‐CP who were refractory to or intolerant of imatinib and had lymphocytosis. Pleural effusions developed more commonly in patients with lymphocytosis. CONCLUSIONS Overall, lymphocytosis occurred and persisted in many dasatinib‐treated patients in all phases of CML. Its presence was associated with higher response rates, significantly longer response durations, and increased overall survival, suggesting an immunomodulatory effect. Prospective studies are warranted to characterize the functional activity of these cells and to assess whether an immunologic effect against CML is detectable. Cancer 2016;122:1398–1407. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. PMID:26998677

  15. Microbial control of soil organic matter mineralization responses to labile carbon in subarctic climate change treatments.

    PubMed

    Rousk, Kathrin; Michelsen, Anders; Rousk, Johannes

    2016-12-01

    Half the global soil carbon (C) is held in high-latitude systems. Climate change will expose these to warming and a shift towards plant communities with more labile C input. Labile C can also increase the rate of loss of native soil organic matter (SOM); a phenomenon termed 'priming'. We investigated how warming (+1.1 °C over ambient using open top chambers) and litter addition (90 g m(-2)  yr(-1) ) treatments in the subarctic influenced the susceptibility of SOM mineralization to priming, and its microbial underpinnings. Labile C appeared to inhibit the mineralization of C from SOM by up to 60% within hours. In contrast, the mineralization of N from SOM was stimulated by up to 300%. These responses occurred rapidly and were unrelated to microbial successional dynamics, suggesting catabolic responses. Considered separately, the labile C inhibited C mineralization is compatible with previously reported findings termed 'preferential substrate utilization' or 'negative apparent priming', while the stimulated N mineralization responses echo recent reports of 'real priming' of SOM mineralization. However, C and N mineralization responses derived from the same SOM source must be interpreted together: This suggested that the microbial SOM-use decreased in magnitude and shifted to components richer in N. This finding highlights that only considering SOM in terms of C may be simplistic, and will not capture all changes in SOM decomposition. The selective mining for N increased in climate change treatments with higher fungal dominance. In conclusion, labile C appeared to trigger catabolic responses of the resident microbial community that shifted the SOM mining to N-rich components; an effect that increased with higher fungal dominance. Extrapolating from these findings, the predicted shrub expansion in the subarctic could result in an altered microbial use of SOM, selectively mining it for N-rich components, and leading to a reduced total SOM-use.

  16. The effect of doxycycline treatment on the postvaccinal immune response in pigs

    SciTech Connect

    Pomorska-Mól, Małgorzata Kwit, Krzysztof; Markowska-Daniel, Iwona; Pejsak, Zygmunt

    2014-07-01

    The effect of a seven-day antibiotic therapy with doxycycline was investigated on the postvaccinal humoral and cellular immune response in pigs. The selected parameters of non-specific immunity were also studied. Fifty pigs were used (control not vaccinated (C, n = 10), control vaccinated (CV, n = 20), and experimental — received doxycycline (DOXY, n = 20)). For vaccination live-attenuated vaccine against pseudorabies (PR) was used. From day − 1 to day 5 pigs from DOXY group received doxycycline orally with drinking water, at the recommended dose. Pigs from DOXY and CV groups were vaccinated at 8 and 10 weeks of age. The results of the present study showed that cell-mediated postvaccinal immune response can be modulated by oral treatment with doxycycline. Significantly lower values of stimulation index were observed after PRV restimulation in doxycycline-treated pigs. Moreover, in the DOXY group a significant decrease in IFN-γ production after PRV restimulation was noted. The significantly lower number of CD4+CD8 + cells was also observed in doxy-treated, vaccinated pigs, 2 weeks after final vaccination. Simultaneously, specific humoral response was not disturbed. This study demonstrated the importance of defining the immune modulatory activity of doxycycline because it may alter the immune responses to vaccines. The exact mechanism of T-cell response suppression by doxycycline remains to be elucidated, however the influence of doxycycline on the secretion of various cytokines, including IFN-γ, may be considered as a possible cause. The present observations should prompt further studies on the practical significance of such phenomena in terms of clinical implications. - Highlights: • We examine the postvaccinal immune response in pigs treated with doxycycline. • Doxycycline negatively influenced the specific proliferation after recall stimulation. • Doxycycline negatively influenced secretion of IFN-γ after recall stimulation. • The lower number of

  17. Polymorphisms in tumor necrosis factor and lymphotoxin A in tuberculosis without and with response to treatment.

    PubMed

    García-Elorriaga, Guadalupe; Carrillo-Montes, Guadalupe; Mendoza-Aguilar, Melby; González-Bonilla, César

    2010-08-01

    This study compared the frequency of the genetic polymorphisms of tumor necrosis factor (TNF) in pulmonary tuberculosis without and with response to treatment. We carried out an observational, prospective, comparative study. Three groups were studied: healthy subjects, responders, and non-responders to directly observed treatment short-course. We took a peripheral blood sample for identification of polymorphic genotypes TNF -308G/A and lymphotoxin A (LTA) +252G/A by polymerase chain reaction, and their later digestion with the Nco1 restriction enzyme. We studied a total of 138 subjects: 42 (non-responders) and 48 in each of the remaining groups. Healthy subjects had significantly high frequency of the LTA +252A allele compared to groups of patients and could be related with protection from the disease. Patients had higher frequency of the non-polymorphic allele LTA +252G than healthy subjects. With regard to LTA +252G/A genotype, we did find a significant difference with a greater frequency in the group of patients. The LTA +252G/A genotype was associated with impaired response to treatment.

  18. Quality of life of methylphenidate treatment-responsive adolescents with attention-deficit/hyperactivity disorder.

    PubMed

    Yang, Pin-Chen; Lung, For-Wey; Chiou, Shyh-Shin; Yen, Cheng-Fang; Fuh, Jong-Ling

    2012-05-01

    Quality of life (QOL) in methylphenidate treatment-responsive adolescents with attention deficit/hyperactivity disorder (ADHD) was assessed. Patients were 12- to 18-year-old adolescents with ADHD (total n = 45) who had been on methylphenidate treatment for at least 3 months and were clinically judged to be improved. The self-completed Taiwanese Quality of Life Questionnaire for Adolescents (TQOLQA) was used, and the resulting measures were compared between adolescents with ADHD and: (1) community adolescents (n = 2316); (2) treatment-responsive adolescents with a chronic medical condition (i.e., adolescents with leukemia in its first and complete continuous remission for at least 3 years after chemotherapy) (n = 39). Patients' cognitive profile and their daily executive functioning were also obtained for analysis. The QOL of the treated adolescents with ADHD was reported to be worse than that of both the community healthy adolescents and the adolescent leukemia survivors in the self-reported TQOLQA domain of "psychological well-being". Treated adolescents with ADHD still had impaired executive skills in natural, everyday environments, and the scores for daily executive abilities could predict the QOL measures. Factors besides pharmacotherapy should be explored to further improve the QOL of medication-treated adolescents with ADHD.

  19. Carbon-11-methionine and PET in evaluation of treatment response of breast cancer.

    PubMed Central

    Huovinen, R.; Leskinen-Kallio, S.; Någren, K.; Lehikoinen, P.; Ruotsalainen, U.; Teräs, M.

    1993-01-01

    Uptake of L-methyl-11C-methionine (11C-methionine) in breast cancer metastases was studied with positron emission tomography (PET). Eight patients with soft tissue metastases were studied twice: before the onset of chemotherapy (4), hormonal therapy (3) or radiotherapy (1) and 3-14 weeks later. The radioactivity concentration of the low molecular weight fraction of venous plasma samples separated by fast gel filtration was used as input function. The input corrected uptake rate of 11C-methionine (Ki) in breast cancer metastases before the treatment ranged between 0.035 and 0.186 1 min-1 and the standardised uptake value (SUV) between 2.0 and 11.4. The uptake of 11C-methionine into the metastases decreased when clinical objective stability or regression of the metastases was later obtained and increased in cases where progressive disease was seen during treatment. We conclude that metabolic changes in the amino acid metabolism detected by PET precede the clinical response, and may be of clinical value in predicting the treatment response. Images Figure 1 PMID:8471437

  20. The interplay between genotype, metabolic state and cofactor treatment governs phenylalanine hydroxylase function and drug response.

    PubMed

    Staudigl, Michael; Gersting, Søren W; Danecka, Marta K; Messing, Dunja D; Woidy, Mathias; Pinkas, Daniel; Kemter, Kristina F; Blau, Nenad; Muntau, Ania C

    2011-07-01

    The discovery of a pharmacological treatment for phenylketonuria (PKU) raised new questions about function and dysfunction of phenylalanine hydroxylase (PAH), the enzyme deficient in this disease. To investigate the interdependence of the genotype, the metabolic state (phenylalanine substrate) and treatment (BH(4) cofactor) in the context of enzyme function in vitro and in vivo, we (i) used a fluorescence-based method for fast enzyme kinetic analyses at an expanded range of phenylalanine and BH(4) concentrations, (ii) depicted PAH function as activity landscapes, (iii) retraced the analyses in eukaryotic cells, and (iv) translated this into the human system by analyzing the outcome of oral BH(4) loading tests. PAH activity landscapes uncovered the optimal working range of recombinant wild-type PAH and provided new insights into PAH kinetics. They demonstrated how mutations might alter enzyme function in the space of varying substrate and cofactor concentrations. Experiments in eukaryotic cells revealed that the availability of the active PAH enzyme depends on the phenylalanine-to-BH(4) ratio. Finally, evaluation of data from BH(4) loading tests indicated that the patient's genotype influences the impact of the metabolic state on drug response. The results allowed for visualization and a better understanding of PAH function in the physiological and pathological state as well as in the therapeutic context of cofactor treatment. Moreover, our data underscore the need for more personalized procedures to safely identify and treat patients with BH(4)-responsive PAH deficiency.

  1. Digital holographic microscopy for imaging growth and treatment response in 3D tumor models

    NASA Astrophysics Data System (ADS)

    Li, Yuyu; Petrovic, Ljubica; Celli, Jonathan P.; Yelleswarapu, Chandra S.

    2014-03-01

    While three-dimensional tumor models have emerged as valuable tools in cancer research, the ability to longitudinally visualize the 3D tumor architecture restored by these systems is limited with microscopy techniques that provide only qualitative insight into sample depth, or which require terminal fixation for depth-resolved 3D imaging. Here we report the use of digital holographic microscopy (DHM) as a viable microscopy approach for quantitative, non-destructive longitudinal imaging of in vitro 3D tumor models. Following established methods we prepared 3D cultures of pancreatic cancer cells in overlay geometry on extracellular matrix beds and obtained digital holograms at multiple timepoints throughout the duration of growth. The holograms were digitally processed and the unwrapped phase images were obtained to quantify nodule thickness over time under normal growth, and in cultures subject to chemotherapy treatment. In this manner total nodule volumes are rapidly estimated and demonstrated here to show contrasting time dependent changes during growth and in response to treatment. This work suggests the utility of DHM to quantify changes in 3D structure over time and suggests the further development of this approach for time-lapse monitoring of 3D morphological changes during growth and in response to treatment that would otherwise be impractical to visualize.

  2. The relationship of structural brain imaging parameters to antipsychotic treatment response: a review.

    PubMed Central

    Friedman, L; Lys, C; Schulz, S C

    1992-01-01

    Over the last decade, a number of studies have attempted to relate brain morphology to treatment response to neuroleptics. This approach has scientific potential to define subtypes of schizophrenia as well as potential clinical utility. In the present report, a review of 33 studies, including a meta-analysis, is provided. Although the overall test of the effect was not significant, the analysis revealed marked heterogeneity in the results of the various studies. The following factors were significant predictors of effect size: age, illness duration and age of onset of the patient cohort, the percentage of patients with marked structural abnormality included in the study overall, the duration of treatment and the degree of symptom improvement in the study overall. The following factors were unrelated to study effect size: date of study, gender, and the presence of a washout period. In future studies, attention to the parameters utilized in the meta-analysis should help to clarify the strength and generality of the relationship between brain morphology and treatment response. PMID:1353369

  3. Pathological gambling and age: differences in personality, psychopathology, and response to treatment variables.

    PubMed

    González-Ibáñez, A; Mora, M; Gutiérrez-Maldonado, J; Ariza, A; Lourido-Ferreira, M R

    2005-02-01

    The aim of this study was to ascertain the possible differences in personality, psychopathology, and response to treatment in pathological gambling according to age. The sample, comprising 67 participants, was divided into three groups: 32.6% with ages ranging between 17 and 26 years, 31.3% between 27 and 43 years, and 35.8% over 44 years of age. The participants were administered the following tests, Minnesota Multiphasic Personality Inventory [MMPI; Hathaway, S.R. & McKinley, J.C. (1943, 1961). Cuestionario de personalidad MMPI. Madrid Seccion de Estudios de TEA ed. 1970, 1975], sensation-seeking questionnaire [SSS; Zuckerman, M. (1979). Sensation seeking; beyond the optimal level of arousal. Hillsdale, NJ: Lawrence Erlbaum Associates], and the Symptom Check List Revised [SCL-90-R; Derogatis, L.R. (1977). Symptom check list-90 revised. Administration scoring and procedures manual. Baltimore]. All underwent a group treatment programme that was carried out in the Pathological Gambling Unit at Ciutat Sanitaria i Universitaria de Bellvitge (CSUB), Teaching hospital, Barcelona, Spain. The findings show differences depending on age in the participants' personality and in psychopathology and in their response to treatment.

  4. Anatomical differences in response to treatment of port-wine stains by the pulsed dye laser

    NASA Astrophysics Data System (ADS)

    Renfro, Lisa; Geronemus, Roy G.

    1992-06-01

    Two-hundred and fifty-seven patients (136 adults and 121 children) with port-wine stains of the head and neck were treated with the flashlamp-pumped pulsed dye laser. The head and neck was subdivided into 8 anatomical regions (forehead/temple, periorbital, medial cheek, nose, upper cutaneous lip, lateral cheek, chin and neck) which were independently evaluated for response. Response to treatment was found to be associated with the anatomical location of the lesion; in both adults and children the mid-facial region (medial cheek, nose and upper cutaneous lip) responded less favorably to treatment than the other regions of the head and neck (periorbital, forehead/temple, lateral cheek, neck and chin). In adults and children, mean percent lesional lightening of the mid-facial regions was 70.7% compared to 82.3% of the other regions of the head and neck with an estimated difference of 11.6% (95% confidence interval: 8.7% - 14.6%). The mean number of treatments for adults was 3.7, while this number in children was 3.9. All side effects were transient, and included cutaneous depressions, hypopigmentation and hyperpigmentation.

  5. FacPad: Bayesian sparse factor modeling for the inference of pathways responsive to drug treatment

    PubMed Central

    Ma, Haisu; Zhao, Hongyu

    2012-01-01

    Motivation: It is well recognized that the effects of drugs are far beyond targeting individual proteins, but rather influencing the complex interactions among many relevant biological pathways. Genome-wide expression profiling before and after drug treatment has become a powerful approach for capturing a global snapshot of cellular response to drugs, as well as to understand drugs’ mechanism of action. Therefore, it is of great interest to analyze this type of transcriptomic profiling data for the identification of pathways responsive to different drugs. However, few computational tools exist for this task. Results: We have developed FacPad, a Bayesian sparse factor model, for the inference of pathways responsive to drug treatments. This model represents biological pathways as latent factors and aims to describe the variation among drug-induced gene expression alternations in terms of a much smaller number of latent factors. We applied this model to the Connectivity Map data set (build 02) and demonstrated that FacPad is able to identify many drug–pathway associations, some of which have been validated in the literature. Although this method was originally designed for the analysis of drug-induced transcriptional alternation data, it can be naturally applied to many other settings beyond polypharmacology. Availability and implementation: The R package ‘FacPad’ is publically available at: http://cran.open-source-solution.org/web/packages/FacPad/ Contact: hongyu.zhao@yale.edu Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:22923307

  6. Neural response to eye contact and paroxetine treatment in generalized social anxiety disorder.

    PubMed

    Schneier, Franklin R; Pomplun, Marc; Sy, Melissa; Hirsch, Joy

    2011-12-30

    Generalized social anxiety disorder (GSAD) is characterized by excessive fears of scrutiny and negative evaluation, but neural circuitry related to scrutiny in GSAD has been little studied. In this study, 16 unmedicated adults with GSAD and 16 matched healthy comparison (HC) participants underwent functional magnetic resonance imaging to assess neural response to viewed images of faces simulating movement into eye contact versus away from eye contact. GSAD patients were then treated for 8 weeks with paroxetine, and 15 patients were re-imaged. At baseline, GSAD patients had elevated neural response to eye contact in parahippocampal cortex, inferior parietal lobule, supramarginal gyrus, posterior cingulate and middle occipital cortex. During paroxetine treatment, symptomatic improvement was associated with decreased neural response to eye contact in regions including inferior and middle frontal gyri, anterior cingulate, posterior cingulate, precuneus and inferior parietal lobule. Both the magnitude of GSAD symptom reduction with paroxetine treatment and the baseline comparison of GSAD vs. HCs were associated with neural processing of eye contact in distributed networks that included regions involved in self-referential processing. These findings demonstrate that eye contact in GSAD engages neurocircuitry consistent with the heightened self-conscious emotional states known to characterize GSAD patients during scrutiny.

  7. Imaging Caspase-3 Activation as a Marker of Apoptosis-Targeted Treatment Response in Cancer

    PubMed Central

    Chen, Delphine L.; Engle, Jacquelyn T.; Griffin, Elizabeth A.; Miller, J. Philip; Chu, Wenhua; Zhou, Dong; Mach, Robert H.

    2016-01-01

    Purpose We tested whether positron emission tomography (PET) with the caspase-3 targeted isatin analog [18F]WC-4-116 could image caspase-3 activation in response to an apoptosis-inducing anticancer therapy. Procedures [18F]WC-4-116 uptake was determined in etoposide-treated EL4 cells. Biodistribution studies with [18F]WC-4-116 and [18F]ICMT-18, a non-caspase-3-targeted tracer, as well as [18F]WC-4-116 microPET imaging assessed responses in Colo205 tumor bearing mice treated with death receptor 5 (DR5) targeted agonist antibodies. Immunohistochemical staining and enzyme assays confirmed caspase-3 activation. Two-way analysis of variance or Student’s t-test assessed for treatment-related changes in tracer uptake. Results [18F]WC-4-116 increased 8 ± 2-fold in etoposide-treated cells. The [18F]WC-4-116 %ID/g also increased significantly in tumors with high caspase-3 enzyme activity (p < 0.05). [18F]ICMT-18 tumor uptake did not differ in tumors with high or low caspase-3 enzyme activity. Conclusions [18F]WC-4-116 uptake in vivo reflects increased caspase-3 activation and may be useful for detecting caspase-3 mediated apoptosis treatment responses in cancer. PMID:25344147

  8. Optimization of Electrochemical Treatment Process Conditions for Distillery Effluent Using Response Surface Methodology.

    PubMed

    Arulmathi, P; Elangovan, G; Begum, A Farjana

    2015-01-01

    Distillery industry is recognized as one of the most polluting industries in India with a large amount of annual effluent production. In this present study, the optimization of electrochemical treatment process variables was reported to treat the color and COD of distillery spent wash using Ti/Pt as an anode in a batch mode. Process variables such as pH, current density, electrolysis time, and electrolyte dose were selected as operation variables and chemical oxygen demand (COD) and color removal efficiency were considered as response variable for optimization using response surface methodology. Indirect electrochemical-oxidation process variables were optimized using Box-Behnken response surface design (BBD). The results showed that electrochemical treatment process effectively removed the COD (89.5%) and color (95.1%) of the distillery industry spent wash under the optimum conditions: pH of 4.12, current density of 25.02 mA/cm(2), electrolysis time of 103.27 min, and electrolyte (NaCl) concentration of 1.67 g/L, respectively.

  9. Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression.

    PubMed

    Haile, C N; Murrough, J W; Iosifescu, D V; Chang, L C; Al Jurdi, R K; Foulkes, A; Iqbal, S; Mahoney, J J; De La Garza, R; Charney, D S; Newton, T F; Mathew, S J

    2014-02-01

    Ketamine produces rapid antidepressant effects in treatment-resistant depression (TRD), but the magnitude of response varies considerably between individual patients. Brain-derived neurotrophic factor (BDNF) has been investigated as a biomarker of treatment response in depression and has been implicated in the mechanism of action of ketamine. We evaluated plasma BDNF and associations with symptoms in 22 patients with TRD enrolled in a randomized controlled trial of ketamine compared to an anaesthetic control (midazolam). Ketamine significantly increased plasma BDNF levels in responders compared to non-responders 240 min post-infusion, and Montgomery-Åsberg Depression Rating Scale (MADRS) scores were negatively correlated with BDNF (r=-0.701, p = 0.008). Plasma BDNF levels at 240 min post-infusion were highly negatively associated with MADRS scores at 240 min (r = -0.897, p=.002), 24 h (r = -0.791, p = 0.038), 48 h (r = -0.944, p = 0.001) and 72 h (r = -0.977, p = 0.010). No associations with BDNF were found for patients receiving midazolam. These data support plasma BDNF as a peripheral biomarker relevant to ketamine antidepressant response.

  10. Predicting therapeutic response to secondary treatment with bupropion: dichotic listening tests of functional brain asymmetry.

    PubMed

    Bruder, Gerard E; Stewart, Jonathan W; Schaller, Jennifer D; McGrath, Patrick J

    2007-10-31

    Studies using neuroimaging, electrophysiologic and cognitive measures have raised hopes for developing predictors of therapeutic response to antidepressants. Pretreatment measures of functional brain asymmetry have been found to be related to response to the selective serotonin reuptake inhibitor fluoxetine. This report examines the extent to which dichotic listening tests also predict clinical response to an antidepressant with a different mechanism of action, i.e., bupropion. Dichotic listening data were obtained for 17 unmedicated depressed patients who were subsequently treated with bupropion. Right-handed outpatients were tested on dichotic fused-words and complex-tones tests. Seven patients who responded to bupropion and 10 nonresponders did not differ in gender, age or education. Bupropion responders had significantly larger left-hemisphere advantage for perceiving words when compared to nonresponders, but there was no difference in their right-hemisphere advantage for tones. All patients having a left-hemisphere advantage above the normal mean responded to bupropion, whereas only 9% of patients below the normal mean responded to treatment. These findings should encourage further study of the clinical value of dichotic listening and other measures of functional brain asymmetry for identifying depressed patients who most benefit from treatment with different classes of antidepressants.

  11. Proteome changes in banana fruit peel tissue in response to ethylene and high-temperature treatments

    PubMed Central

    Du, Lina; Song, Jun; Forney, Charles; Palmer, Leslie Campbell; Fillmore, Sherry; Zhang, ZhaoQi

    2016-01-01

    Banana (Musa AAA group) is one of the most consumed fruits in the world due to its flavor and nutritional value. As a typical climacteric fruit, banana responds to ethylene treatment, which induces rapid changes of color, flavor (aroma and taste), sweetness and nutritional composition. It has also been reported that ripening bananas at temperatures above 24 °C inhibits chlorophyll breakdown and color formation but increases the rate of senescence. To gain fundamental knowledge about the effects of high temperature and ethylene on banana ripening, a quantitative proteomic study employing multiplex peptide stable isotope dimethyl labeling was conducted. In this study, green (immature) untreated banana fruit were subjected to treatment with 10 μL L−1 of ethylene for 24 h. After ethylene treatment, treated and untreated fruit were stored at 20 or 30 °C for 24 h. Fruit peel tissues were then sampled after 0 and 1 day of storage, and peel color and chlorophyll fluorescence were evaluated. Quantitative proteomic analysis was conducted on the fruit peels after 1 day of storage. In total, 413 common proteins were identified and quantified from two biological replicates. Among these proteins, 91 changed significantly in response to ethylene and high-temperature treatments. Cluster analysis on these 91 proteins identified 7 groups of changed proteins. Ethylene treatment and storage at 20 °C induced 40 proteins that are correlated with pathogen resistance, cell wall metabolism, ethylene biosynthesis, allergens and ribosomal proteins, and it repressed 36 proteins that are associated with fatty acid and lipid metabolism, redox–oxidative responses, and protein biosynthesis and modification. Ethylene treatment and storage at 30 °C induced 32 proteins, which were mainly similar to those in group 1 but also included 8 proteins in group 3 (identified as chitinase, cinnamyl alcohol dehydrogenase 1, cysteine synthase, villin-2, leucine-transfer RNA ligase, CP47

  12. Lower Viral Response to Pegylated Interferon Alpha 2a Treatment of Chronic Hepatitis B in Roma People in Eastern Slovakia

    PubMed Central

    Drazilova, Sylvia; Janicko, Martin; Kristian, Pavol; Schreter, Ivan; Kucinsky, Branislav; Kozlej, Marek; Hockickova, Ivana; Jarcuska, Peter

    2016-01-01

    Aim. To evaluate the compliance and virological response to pegylated interferon alpha 2a treatment of chronic hepatitis B in Roma population compared to majority Caucasian population in Slovakia. Methods. Retrospective evaluation of a cohort of all Roma patients treated with pegylated interferon alpha 2a from 2007 to 2013 in 3 centers for treatment of chronic viral hepatitis B. The Study included 43 Roma patients with chronic viral hepatitis B and randomly selected control group. Treatment duration was 48 weeks. Viral response was evaluated after 24 weeks, at the end of treatment, and 24 weeks after the end of treatment. Results. Complete treatment course was finished by 79.1% of Roma patients compared to all patients from the control group (p = 0.0009). There was a tendency toward lower viral response rate in Roma at all time points; however significant difference was only at end of treatment viral response (51.2% Roma versus 81.4% majority, p = 0.003). We also did not find significant difference at the rate of HBsAg loss. Conclusion. Roma patients with chronic hepatitis B have significantly worse compliance to treatment with pegylated interferon and they have significantly lower rate of end of treatment viral response. PMID:26858755

  13. Bone Scan Index: A Quantitative Treatment Response Biomarker for Castration-Resistant Metastatic Prostate Cancer

    PubMed Central

    Dennis, Elizabeth R.; Jia, Xiaoyu; Mezheritskiy, Irina S.; Stephenson, Ryan D.; Schoder, Heiko; Fox, Josef J.; Heller, Glenn; Scher, Howard I.; Larson, Steven M.; Morris, Michael J.

    2012-01-01

    Purpose There is currently no imaging biomarker for metastatic prostate cancer. The bone scan index (BSI) is a promising candidate, being a reproducible, quantitative expression of tumor burden seen on bone scintigraphy. Prior studies have shown the prognostic value of a baseline BSI. This study tested whether treatment-related changes in BSI are prognostic for survival and compared BSI to prostate-specific antigen (PSA) as an outcome measure. Patients and Methods We retrospectively examined serial bone scans from patients with castration-resistant metastatic prostate cancer (CRMPC) enrolled in four clinical trials. We calculated BSI at baseline and at 3 and 6 months on treatment and performed univariate and bivariate analyses of PSA, BSI, and survival. Results Eighty-eight patients were scanned, 81 of whom have died. In the univariate analysis, the log percent change in BSI from baseline to 3 and 6 months on treatment prognosticated for survival (hazard ratio [HR], 2.44; P = .0089 and HR, 2.54; P < .001, respectively). A doubling in BSI resulted in a 1.9-fold increase in risk of death. Log percent change in PSA at 6 months on treatment was also associated with survival (HR, 1.298; P = .013). In the bivariate analysis, change in BSI while adjusting for PSA was prognostic at 3 and 6 months on treatment (HR, 2.368; P = .012 and HR, 2.226; P = .002, respectively), but while adjusting for BSI, PSA was not prognostic. Conclusion These data furnish early evidence that on-treatment changes in BSI are a response indicator and support further exploration of bone scintigraphy as an imaging biomarker in CRMPC. PMID:22231045

  14. Chronic intermittent nicotine treatment dose-dependently alters serotonergic neurons response to citalopram in the rat.

    PubMed

    Touiki, Khalid; Rat, Pascal; Arib, Ouafa; Molimard, Robert; Chait, Abderrahman; de Beaurepaire, Renaud

    2008-05-01

    Acetylcholine nicotinic systems and serotonergic systems are known to interact. In rodents, acute and chronic nicotine treatments have consequences on several aspects of the activity of dorsal raphe serotonin (DRN 5-HT) neurons. One hypothesis is that states of functioning of DRN 5-HT neurons (firing rate and sensitivity) vary as a function of nicotine dose and mode of administration during chronic nicotine treatment. In the present study, the firing rate and sensitivity of DRN 5-HT neurons were investigated using single (0.5 and 1 mg/kg) or multiple (3 injections of 0.7 mg/kg) daily injections of nicotine over 10 days. The sensitivity of neurons was tested by the cumulative dose of the selective serotonin reuptake inhibitor citalopram necessary to inhibit their firing. The activity of neurons was tested during treatment, and then 24 and 48 h after nicotine withdrawal. The results show that, on day 10, DRN 5-HT neurons were desensitized (reduced response to citalopram) after chronic single daily injection treatments with the high dose of nicotine (1 mg/kg), while their sensitivity remained unaltered after single daily injections with the low dose (0.5 mg/kg), and after the multiple daily injection paradigm. None of the treatments altered the firing rate of DRN 5-HT neurons. The dose-dependent and time-dependent alterations of serotonergic neurons sensitivity after chronic nicotine treatments are likely the consequences of long-term adaptations of nicotinic receptors. The desensitization of DRN 5-HT neurons after chronic single daily injections of 1 mg/kg of nicotine suggests an antidepressant-like effect of chronic nicotine.

  15. Monitoring interferon β treatment response with magnetic resonance spectroscopy in relapsing remitting multiple sclerosis.

    PubMed

    Yetkin, Mehmet Fatih; Mirza, Meral; Dönmez, Halil

    2016-09-01

    The aim of this study is to compare the white matter of multiple sclerosis (MS) patients with healthy controls and to monitor the response to the treatment with magnetic resonance spectroscopy (MRS).Fifteen healthy controls and 36 recently diagnosed MS patients never treated with interferon β were included in this study. In the patient group, MRS was performed before treatment, at 6th and 12th month after the initiation of treatment and once in control group. Patient group was divided into 3 interferon groups randomly. Physical examination findings were recorded as Expanded Disability Status Scale scores before treatment, at 6th and 12th month of interferon treatment.At the end of 1 year follow up, 26 of 36 patients completed the study. In patients' white matter lesions, N-acetylaspartate/creatine (NAA/Cr) ratios were lower than control group's white matters. NAA/Cr ratios were higher in control group's white matter than patient's normal appearing white matter but this difference was not statistically significant. There was no difference in choline/creatine (Cho/Cr) ratios between 2 groups. In follow-up period, NAA/Cr and Cho/Cr ratios obtained from patients' white matter lesions and normal appearing white matter did not change statistically.This study showed that in MS patients' white matters, especially in white matter lesions, neuron viability is reduced compared with healthy controls' normal white matter; and in the patients treated with interferon β NAA/Cr ratios remained stable. These stable levels of metabolite ratios in the patients who received interferon β therapy can be explained with either the shortness of the follow-up period post-treatment or may reflect a positive effect of the beta interferon therapy on the progress of MS.

  16. Monitoring interferon β treatment response with magnetic resonance spectroscopy in relapsing remitting multiple sclerosis

    PubMed Central

    Yetkin, Mehmet Fatih; Mirza, Meral; Dönmez, Halil

    2016-01-01

    Abstract The aim of this study is to compare the white matter of multiple sclerosis (MS) patients with healthy controls and to monitor the response to the treatment with magnetic resonance spectroscopy (MRS). Fifteen healthy controls and 36 recently diagnosed MS patients never treated with interferon β were included in this study. In the patient group, MRS was performed before treatment, at 6th and 12th month after the initiation of treatment and once in control group. Patient group was divided into 3 interferon groups randomly. Physical examination findings were recorded as Expanded Disability Status Scale scores before treatment, at 6th and 12th month of interferon treatment. At the end of 1 year follow up, 26 of 36 patients completed the study. In patients’ white matter lesions, N-acetylaspartate/creatine (NAA/Cr) ratios were lower than control group's white matters. NAA/Cr ratios were higher in control group's white matter than patient's normal appearing white matter but this difference was not statistically significant. There was no difference in choline/creatine (Cho/Cr) ratios between 2 groups. In follow-up period, NAA/Cr and Cho/Cr ratios obtained from patients’ white matter lesions and normal appearing white matter did not change statistically. This study showed that in MS patients’ white matters, especially in white matter lesions, neuron viability is reduced compared with healthy controls’ normal white matter; and in the patients treated with interferon β NAA/Cr ratios remained stable. These stable levels of metabolite ratios in the patients who received interferon β therapy can be explained with either the shortness of the follow-up period post-treatment or may reflect a positive effect of the beta interferon therapy on the progress of MS. PMID:27603381

  17. Circulating tumor cell status monitors the treatment responses in breast cancer patients: a meta-analysis.

    PubMed

    Yan, Wen-Ting; Cui, Xiang; Chen, Qing; Li, Ya-Fei; Cui, You-Hong; Wang, Yan; Jiang, Jun

    2017-03-24

    Whether circulating tumor cells (CTCs) can be used as an indicator of treatment response in breast cancer (BC) needs to be clarified. We addressed this issue by a meta-analysis. PubMed, EMBase and Cochrane library databases were searched in June 2016. Effect measures were estimated as pooled risk ratio (RR), odds ratio (OR) or mean difference by fixed- or random-effect models, according to heterogeneity of included studies. In total, 50 studies with 6712 patients were recruited. Overall analysis showed that there was a significant reduction of CTC-positive rate (RR = 0.68, 95% CI: 0.61-0.76, P < 0.00001) after treatment. Subgroup analyses revealed that neoadjuvant treatment, adjuvant treatment, metastatic treatment or combination therapy could reduce the CTC-positive rate, but surgery could not; moreover, the reduction was only found in HER2+ or HER2- patients but not in the triple-negative ones. Reduction of CTC-positive rate was associated with lower probability of disease progression (OR = 0.54, 95% CI: 0.33-0.89, P = 0.01) and longer overall survival period (mean difference = 11.61 months, 95% CI: 8.63-14.59, P < 0.00001) as well as longer progression-free survival period (mean difference = 5.07 months, 95% CI: 2.70-7.44, P < 0.0001). These results demonstrate that CTC status can serve as an indicator to monitor the effectiveness of treatments and guide subsequent therapies in BC.

  18. Circulating tumor cell status monitors the treatment responses in breast cancer patients: a meta-analysis

    PubMed Central

    Yan, Wen-Ting; Cui, Xiang; Chen, Qing; Li, Ya-Fei; Cui, You-Hong; Wang, Yan; Jiang, Jun

    2017-01-01

    Whether circulating tumor cells (CTCs) can be used as an indicator of treatment response in breast cancer (BC) needs to be clarified. We addressed this issue by a meta-analysis. PubMed, EMBase and Cochrane library databases were searched in June 2016. Effect measures were estimated as pooled risk ratio (RR), odds ratio (OR) or mean difference by fixed- or random-effect models, according to heterogeneity of included studies. In total, 50 studies with 6712 patients were recruited. Overall analysis showed that there was a significant reduction of CTC-positive rate (RR = 0.68, 95% CI: 0.61–0.76, P < 0.00001) after treatment. Subgroup analyses revealed that neoadjuvant treatment, adjuvant treatment, metastatic treatment or combination therapy could reduce the CTC-positive rate, but surgery could not; moreover, the reduction was only found in HER2+ or HER2- patients but not in the triple-negative ones. Reduction of CTC-positive rate was associated with lower probability of disease progression (OR = 0.54, 95% CI: 0.33–0.89, P = 0.01) and longer overall survival period (mean difference = 11.61 months, 95% CI: 8.63–14.59, P < 0.00001) as well as longer progression-free survival period (mean difference = 5.07 months, 95% CI: 2.70–7.44, P < 0.0001). These results demonstrate that CTC status can serve as an indicator to monitor the effectiveness of treatments and guide subsequent therapies in BC. PMID:28337998

  19. [Epstein-Barr virus presence in Colombian Hodgkin lymphoma cases and its relation to treatment response].

    PubMed

    Quijano, Sandra; Saavedra, Carlos; Fiorentino, Susana; Orozco, Oscar; Bravo, María Mercedes

    2004-06-01

    The role of Epstein-Barr virus as etiologic agent in Hodgkin lymphoma (HL) development has been supported by the detection of viral DNA in the Reed-Sternberg cell in a subset of HL, and the high levels of latent membrane protein 1 expression in these tumors. To gain further evidence of this relationship, lymph nodes from 67 patients with HL were analyzed for the presence of Epstein-Barr virus using EBERs in situ hybridization and LMP-1 immunohistochemistry. Virus presence was related to histological subtype, patients' treatment response and tumor infiltrating lymphocytes phenotype. EBERs transcripts were found in 67% of the cases and LMP-1 in the Reed-Sternberg tumor cells at a 56.7% rate. The prevalence, as determined by histological subtype, was 69.81% for nodular sclerosing, 85.71% for mixed cellularity and 40% for lymphocyte-rich. Epstein-Barr virus presence was more frequent in children (84.2%) in comparison with adults (60.4%). Positive patients presented higher failure-free survival rates than Epstein-Barr virus negative patients. CD4 positive infiltrating T cells were present in a higher proportion in relation to CD8 positive T infiltrating cells, the mean percentages for both subsets were higher in Epstein-Barr virus positive cases. A high percentage of Epstein-Barr virus was present in HL with a probable association with treatment response. This suggests an application of Epstein-Barr virus detection to use as a prognosis marker in treatment response for HL cases.

  20. Quantifying the Stress Responses of Brassica Rapa Genotypes, With Experimental Drought in Two Nitrogen Treatments

    NASA Astrophysics Data System (ADS)

    Hickerson, J. L.; Pleban, J. R.; Mackay, D. S.; Aston, T.; Ewers, B. E.; Weinig, C.

    2014-12-01

    In a greenhouse study designed to quantify and compare stress responses of four genotypes of Brassica rapa, broccolette (bro), cabbage (cab), turnip (tur), and oil, leaf water potential and net CO2 assimilations were measured. Individuals from each genotype, grown either with high or low nitrogen, were exposed to experimental drought of the same duration. One hypothesis was that the genotypes would differ significantly in their responses to periodic drought. The other hypothesis was that the nitrogen treatment versus no nitrogen treatment would play a significant role in the stress responses during drought. It would be expected that the nitrogen treated would have greater dry leaf mass. A LI-6400 XT portable photosynthesis system was used to obtain A/Ci curves (net CO2 assimilation rate versus substomatal CO2) for each treatment group. Predawn and midday water potentials were obtained throughout the hydrated and drought periods using a Model 670 pressure chamber. The dry leaf mass was significantly greater among the high nitrogen group versus the low nitrogen group for each genotype. Nitrogen and genotype were both determinants in variation of water potentials and net CO2 assimilation. Bro and cab genotypes with high nitrogen showed the highest net CO2 assimilation rates during hydration, but the assimilation rates dropped to the lowest during droughts. The water potentials for bro and cab were lower than values for tur and oil. Nitrogen treated genotypes had lower water potentials, but higher net CO2 assimilation rates. Bayesian ecophysiological modeling with the TREES model showed significant differences in trait expression, quantified in terms of differences in model parameter posteriors, among the four genotypes.

  1. Catatonia in DSM 5: controversies regarding its psychopathology, clinical presentation and treatment response.

    PubMed

    Ungvari, Gabor S

    2014-12-01

    Over the past two decades, there has been an upsurge of interest in catatonia, which is reflected in the attention it received in DSM 5, where it appears as a separate subsection of the Schizophrenia Spectrum and Other Psychotic Disorders (APA, 2013). This commentary argues that due to the lack of solid scientific evidence, the extended coverage of catatonia in DSM 5 was a premature, and consequently, a necessarily ambiguous decision. The psychopathological foundations of the modern catatonia concept are lacking therefore its boundaries are fuzzy. There are only a few, methodologically sound clinical, treatment response and small-scale neurobiological studies. The widely recommended use of benzodiazepines for the treatment of catatonia is based on case reports and open-label studies instead of placebo-controlled, randomized trials. In conclusion, the catatonic concept espoused by DSM 5 is necessarily vague reflecting the current state of knowledge.

  2. Emerging aspects of molecular biomarkers for diagnosis, prognosis and treatment response in rheumatoid arthritis.

    PubMed

    Márquez, Ana; Martín, Javier; Carmona, F David

    2016-06-01

    Important advances have occurred during the last decade in the understanding of the pathogenesis of rheumatoid arthritis (RA). However, we are still far from having a clear picture of the molecular network that predisposes an individual to develop the disease, to worsen the symptoms after that, or to successfully respond to a specific treatment. In this sense, different -omics fields (including transcriptomics, proteomics, metabolomics, genomics and epigenomics) have recently produced promising insights that could definitively help us to sharpen such picture if integrated trough a systems biology approach. In this review we will summarise and discuss the recent progress achieved in those fields and its possible impact on the discovery of suitable biomarkers for RA diagnosis, prognosis and treatment response.

  3. Treatment of tattoos by Q-switched ruby laser. A dose-response study

    SciTech Connect

    Taylor, C.R.; Gange, R.W.; Dover, J.S.; Flotte, T.J.; Gonzalez, E.; Michaud, N.; Anderson, R.R. )

    1990-07-01

    Tattoo treatment with Q-switched ruby laser pulses (694 nm, 40 to 80 nanoseconds) was studied by clinical assessment and light and electron microscopy. Fifty-seven blue-black tattoos or portions thereof (35 amateur and 22 professional) were irradiated with 1.5 to 8.0 J/cm2 at a mean interval of 3 weeks. Substantial lightening or total clearing occurred in 18 (78%) of 23 amateur tattoos and 3 (23%) of 13 professional tattoos in which the protocol was completed. Response was related to exposure dose. Scarring occurred in one case, and persistent confettilike hypopigmentation was frequent. Optimal fluence was 4 to 8 J/cm2. Clinicohistologic correlation was poor. Q-switched ruby laser pulses can provide an effective treatment for tattoos.

  4. Integrated Biomarker Responses of Effluents from Municipal Sewage Treatment Works in Goldfish

    NASA Astrophysics Data System (ADS)

    Lu, G. H.; Xia, J.; Zhang, H. Z.; Wang, C.

    2010-11-01

    The organic toxicants were extracted from the effluents from municipal sewage treatment works (STWs) in Nanjing (Chengbei, Suojincun and Jiangxinzhou STWs) by using solid phase extraction. AChE, GST, EROD, GPx and Na+/K+-ATPase activities in goldfish (Carassius auratus) were determmed after exposure of the extracted components. The extracts of water samples from the three STWs induced AChE, GST, EROD and Na+/K+-ATPase activities. The responses of enzymatic activities were mostly significant for those exposures of intermediate polar components, weakly polar components and/or nonpolar hexane extracts. Integrated biomarker response (IBR) index were calculated and used to evaluate an integrated impact of organic toxicants from different sampling sites. The order of negative biological effects of the three STWs was Jiangxinzhou>Chengbei>Suojincun.

  5. Influence of copper treatment on the immune response in an air-breathing teleost, Saccobranchus fossilis

    SciTech Connect

    Khangarot, B.S.; Ray, P.K.; Singh, K.P.

    1988-08-01

    The introduction of small amounts of copper ions from natural and anthropogenic sources into the aquatic environment causes multiple changes in freshwater organisms, even at non-lethal levels. Exposure of mammalian test animals to heavy metals, even at moderate levels of contract, may alter the immunological responses. Therefore, there is an increasing interest in the use of the immune systems as a target organ for detecting toxicity of environmental pollutants. The fish immune system is well defined and has many sensitive parameters whose alteration, as a result of pollutant exposure, are easily determined. The effect of copper on the fish immune system is of particular interest since it is known that chronic treatment of copper decreases resistance of the blue gourami (Trichogaster trichopterus) to virus and bacterial (Roales and Perlmutter 1977). The purpose of this study was to determine if sublethal doses of copper would alter the immune response of the air-breathing fish, Saccobranchus fossilis.

  6. Three-month treatment response and exacerbation in chronic obstructive pulmonary disease.

    PubMed

    Lee, Jung Su; Rhee, Chin Kook; Yoo, Kwang Ha; Lee, Ji-Hyun; Yoon, Ho Il; Kim, Tae-Hyung; Kim, Woo Jin; Lee, JinHwa; Lim, Seong Yong; Park, Tai Sun; Lee, Jae Seung; Lee, Sei Won; Lee, Sang-Do; Oh, Yeon-Mok

    2015-01-01

    The aim of this study was to investigate relationships between acute exacerbation and Forced Expiratory Volume 1 second (FEV1) improvement after treatment with combined long-acting beta-agonist (LABA) and inhaled corticosteroid (ICS) in patients with chronic obstructive pulmonary disease (COPD). A total of 137 COPD patients were classified as responders or nonresponders according to FEV1 improvement after 3 months of LABA/ICS treatment in fourteen referral hospitals in Korea. Exacerbation occurrence in these two subgroups was compared over a period of 1 yr. Eighty of the 137 COPD patients (58.4%) were classified as responders and 57 (41.6%) as nonresponders. Acute exacerbations occurred in 25 patients (31.3%) in the responder group and in 26 patients (45.6%) in the nonresponder group (P=0.086). FEV1 improvement after LABA/ICS treatment was a significant prognostic factor for fewer acute exacerbations in a multivariate Cox proportional hazard model adjusted for age, sex, FEV1, smoking history, 6 min walk distance, body mass index, exacerbation history in the previous year, and dyspnea scale.Three-month treatment response to LABA/ICS might be a prognostic factor for the occurrence of acute exacerbation in COPD patients.

  7. Structural Imaging in Late Life Depression: Association with Mood and Cognitive Responses to Antidepressant Treatment

    PubMed Central

    Marano, Christopher M.; Workman, Clifford I.; Lyman, Christopher H.; Munro, Cynthia A.; Kraut, Michael A.; Smith, Gwenn S.

    2014-01-01

    Objectives Recent positron emission tomography studies of cerebral glucose metabolism have identified the functional neural circuitry associated with mood and cognitive responses to antidepressant treatment in late life depression (LLD). The structural alterations in these networks are not well understood. The present study used magnetic resonance (MR) imaging and voxel-based morphometry (VBM) to evaluate the association between grey matter volumes and changes in mood symptoms and cognitive function with treatment with the antidepressant citalopram. Design Open label trial with baseline brain MR scan. Mood and cognitive assessments performed at baseline and during citalopram treatment. Setting Outpatient clinics of an academic medical center. Participants 17 previously unmedicated patients age 55 or older with a major depressive episode and 17 non-depressed comparison subjects. Intervention 12 week trial of flexibly dosed citalopram. Measurements Grey matter volumes, Hamilton Depression Rating Scale, California Verbal Learning Test, Delis–Kaplan Executive Function System™. Results In LLD, higher grey matter volumes in the cingulate gyrus, superior and middle frontal gyri, middle temporal gyrus and precuneus was associated with greater mood improvement. Higher grey matter volumes in primarily frontal areas were associated with greater improvement in verbal memory and verbal fluency performance. Conclusions Associations with antidepressant induced improvements in mood and cognition were observed in several brain regions previously correlated with normalization of glucose metabolism after citalopram treatment in LLD. Future studies will investigate molecular mechanisms underlying these associations (e.g. beta-amyloid, inflammation, glutamate). PMID:24238925

  8. Updated Site Response Analyses for the Waste Treatment Plant, DOE Hanford, Site, Washington.

    SciTech Connect

    Youngs, Robert R.

    2007-06-29

    This document describes the calculations performed to develop updated relative amplification functions for the Waste Treatment and Immobilization Plant (WTP) facility at the DOE Hanford Site, Washington State. The original 2,000-year return period design spectra for the WTP were based on the results of a probabilistic seismic hazard analysis (PSHA) performed for the DOE Hanford Site by Geomatrix (1996). Geomatrix (1996) performed the PSHA using empirical soil-site ground motion models based primarily on recordings from California. As part of that study, site response analyses were performed to evaluate ground motions at the Hanford sites and California deep soil sites. As described in Appendix A of Geomatrix (1996), characteristic site profiles and dynamic soil properties representative of conditions at various Hanford sites and California deep soil strong motion recording stations were defined. Relative site responses of the Hanford profiles and California profiles were then compared. Based on the results of those site response analyses, it was concluded that ground motions at the Hanford sites underlain by deep soil deposits are similar in character to those on California deep soil sites and it was judged appropriate to use empirical deep soil site attenuation relationships based primarily on California ground motion data to develop design spectra for the Hanford sites. In a subsequent analysis, Geomatrix (2003) updated the site response analyses of Geomatrix (1996, Appendix A) to incorporate randomization of the California and Hanford profiles. The results of that analysis also led to the conclusion that the response of the Hanford profiles was similar to the response of deep soil sites in California.

  9. Updated Site Response Analyses for the Waste Treatment Plant, DOE Hanford Site, Washington

    SciTech Connect

    Youngs RR

    2007-06-01

    This document describes the calculations performed to develop updated relative amplification functions for the Waste Treatment and Immobilization Plant (WTP) facility at the DOE Hanford Site, Washington State. The original 2,000-year return period design spectra for the WTP were based on the results of a probabilistic seismic hazard analysis (PSHA) performed for the DOE Hanford Site by Geomatrix (1996). Geomatrix (1996) performed the PSHA using empirical soil-site ground motion models based primarily on recordings from California. As part of that study, site response analyses were performed to evaluate ground motions at the Hanford sites and California deep soil sites. As described in Appendix A of Geomatrix (1996), characteristic site profiles and dynamic soil properties representative of conditions at various Hanford sites and California deep soil strong motion recording stations were defined. Relative site responses of the Hanford profiles and California profiles were then compared. Based on the results of those site response analyses, it was concluded that ground motions at the Hanford sites underlain by deep soil deposits are similar in character to those on California deep soil sites and it was judged appropriate to use empirical deep soil site attenuation relationships based primarily on California ground motion data to develop design spectra for the Hanford sites. In a subsequent analysis, Geomatrix (2003) updated the site response analyses of Geomatrix (1996, Appendix A) to incorporate randomization of the California and Hanford profiles. The results of that analysis also led to the conclusion that the response of the Hanford profiles was similar to the response of deep soil sites in California.

  10. RHD zygosity predicts degree of platelet response to anti-D immune globulin treatment in children with immune thrombocytopenia.

    PubMed

    Despotovic, Jenny M; McGann, Patrick T; Smeltzer, Matthew; Aygun, Banu; Ware, Russell E

    2013-09-01

    Anti-D immunoglobulin is a common front-line treatment for childhood immune thrombocytopenia (ITP) that typically results in a rapid and significant increase in platelet count. Unpredictable treatment responses and interpatient variability limit more widespread use. We hypothesized that anti-D response variability is influenced by RHD gene zygosity and erythrocyte D antigen expression. We compared RHD zygosity and quantitative D antigen expression to anti-D treatment results. Hemizygous RHD subjects demonstrated significantly higher platelet increases and peak platelet counts than homozygous RHD subjects. Future studies should investigate the mechanisms by which RHD zygosity and D antigen expression affect platelet responses to anti-D immunoglobulin.

  11. MicroRNAs for the Prediction of Early Response to Sorafenib Treatment in Human Hepatocellular Carcinoma

    PubMed Central

    Nishida, Naoshi; Arizumi, Tadaaki; Hagiwara, Satoru; Ida, Hiroshi; Sakurai, Toshiharu; Kudo, Masatoshi

    2017-01-01

    Background Several studies suggest the role of circulating microRNAs (miRNAs) as biomarkers of hepatocellular carcinoma (HCC). However, the serum miRNA profile associated with the response to sorafenib remains to be elucidated. The aim of this study was to clarify the specific miRNAs in serum that could predict the early response of HCC to sorafenib treatment. Summary Analyzing the sera from 16 HCC patients, we selected five miRNAs that showed differences in serum levels between patients with and without tumor responses among 179 known secretory miRNAs by using locked nucleic acid probe-based quantitative PCR. Through further analysis using a validation cohort that included 53 HCC patients who underwent sorafenib treatment and 8 healthy control subjects, we found that miR-181a-5p and miR-339-5p showed significant differences in serum levels among patients with partial response (PR), stable disease (SD), and progressive disease (PD), where PR patients showed the highest and PD the lowest levels. We also analyzed the factors associated with disease control (DC; PR or SD) 3 months after the initiation of sorafenib treatment; patients with DC showed a significantly higher level of serum miR-181a-5p than non-DC patients or healthy control subjects (p = 0.0349 and 0.0180 for DC vs. non-DC and control vs. non-DC by Tukey-Kramer test, respectively). We further conducted multivariate analysis among HCC patients with Barcelona Clinic Liver Cancer stage C using extrahepatic metastasis, serum decarboxyprothrombin, and miR-181a-5p levels as covariables; serum miR-181a-5p was the only independent factor for achieving DC (p = 0.0092, odds ratio 0.139, and 95% confidence interval 0.011-0.658). In addition, miR-181a-5p level was also the only independent factor affecting overall survival (p = 0.0194, hazard ratio 0.267, and 95% confidence interval 0.070-0.818). Key Messages A high serum level of miR-181a-5p before treatment is associated with DC after the initiation of sorafenib.

  12. Identification of Genes and Genetic Variants Associated with Poor Treatment Response in Patients with Prostate Cancer

    DTIC Science & Technology

    2013-10-01

    to die from their prostate cancer. We will further stratify and study these cases by their response to castration (chemical or physical ) treatment...months = 2 o 6-9 months = 3 o 9-12 months= 4 o >12 months= 5 Time of initiation of androgen deprivation therapy (castration) after definitive... therapy : o 0-6 months=1 o 6-12 month=2 o 12-24 months =3 o 24 months = 4 PSA after 7 months of castration: o <. 02= 1 o 0.02-4=2 o 4-10=3

  13. Chronic treatment with indacaterol and airway response to salbutamol in stable COPD.

    PubMed

    Cazzola, Mario; Rogliani, Paola; Ruggeri, Paolo; Segreti, Andrea; Proietto, Alfio; Picciolo, Stefano; Matera, Maria Gabriella

    2013-06-01

    Tolerance to both the bronchoprotective effect, and, to a lesser extent, the bronchodilator activity, occurs with all inhaled β2-agonists. Assumed the importance of this topic and the lack of a clinical evaluation specifically designed to assess the impact of chronic administration of indacaterol on the response to salbutamol, we sought to compare the effect of 4-week treatment with indacaterol 150 μg once-daily versus formoterol 12 μg twice-daily on the dose-response curve to inhaled salbutamol (total cumulative dose of 800 μg) in a non-double-blinded, crossover, randomised, and controlled pilot trial that enrolled 20 outpatients with moderate to severe COPD. At the end of 4-week treatments, there was not a statistically significant difference between the two trough FEV1 (p = 0.16), and both indacaterol and formoterol were able to produce a significant (p < 0.001) increase in FEV1 mean differences (L) = indacaterol 0.15 (95% confidence interval (CI) 0.12-0.18); formoterol 0.10, (95% CI 0.08-0.12) 2 h after their inhalation. Salbutamol elicited an evident dose-dependent increase in FEV1 and this occurred also after regular treatment with indacaterol and formoterol with a further mean maximum increase of 0.10L (95% CI 0.05-0.14) and 0.05L (95% CI 0.02-0.08), respectively. The differences between indacaterol and formoterol in FEV1 increases after salbutamol were never statistically significant. The results of this study support the use of salbutamol as rescue medication for rapid relief of bronchospasm in patients suffering from COPD, even when they are under regular treatment with indacaterol.

  14. Adiponectin treatment attenuates inflammatory response during early sepsis in obese mice

    PubMed Central

    Wang, XianFeng; Buechler, Nancy L; Yoza, Barbara K; McCall, Charles E; Vachharajani, Vidula

    2016-01-01

    Background Morbid obesity increases the cost of care in critically ill patients. Sepsis is the leading cause of death in noncoronary intensive care units. Circulating cell–endothelial cell interactions in microcirculation are the rate-determining factors in any inflammation; obesity increases these interactions further. Adiponectin deficiency is implicated in increased cardiovascular risk in obese patients. We have shown that adiponectin deficiency increases microvascular dysfunction in early sepsis. In the present study, we investigated the effect of adiponectin replacement on nutritionally obese mice with early sepsis. Methods We used cecal ligation and puncture model of sepsis in mice with diet-induced obesity (DIO) vs control diet (CTRL), with or without adiponectin treatment. We studied leukocyte/platelet adhesion in the cerebral microcirculation in early sepsis. We also studied the effect of adiponectin on free fatty acid (FFA)-fed and lipopolysaccharide-stimulated bone marrow-derived macrophages (BMDM) for mechanistic studies. Results Leukocyte and platelet adhesion increased in the cerebral microcirculation of DIO and CTRL mice with early sepsis vs. sham; moreover cell adhesion in DIO-sepsis group was significantly higher than in the CTRL-sepsis group. Adiponectin replacement decreased leukocyte/platelet adhesion in CTRL and DIO mice. In FFA-fed BMDM, adiponectin treatment decreased tumor necrosis factor-alpha mRNA expression and increased sirtuin-1 (SIRT1) mRNA expression. Furthermore, using BMDM from SIRT1 knockout mice, we showed that the adiponectin treatment decreased inflammatory response in FFA-fed BMDM via SIRT1-dependent and -independent pathways. Conclusion Adiponectin replacement attenuates microvascular inflammation in DIO-sepsis mice. Mechanistically, adiponectin treatment in FFA-fed mouse macrophages attenuates inflammatory response via SIRT1-dependent and -independent pathways. PMID:27785087

  15. Masked polycythaemia vera: presenting features, response to treatment and clinical outcomes.

    PubMed

    Alvarez-Larrán, Alberto; Angona, Anna; Ancochea, Agueda; García-Pallarols, Francesc; Fernández, Concepción; Longarón, Raquel; Bellosillo, Beatriz; Besses, Carlos

    2016-01-01

    Masked polycythaemia vera (PV) has been proposed as a new entity with poorer outcome than overt PV. In this study, the initial clinical and laboratory characteristics, response to treatment and outcome of masked and overt PV were compared using red cell mass and haemoglobin or haematocrit levels for the distinction between both entities. Sixty-eight of 151 PV patients (45%) were classified as masked PV according to World Health Organisation diagnostic criteria, whereas 16 (11%) were classified as masked PV using the British Committee for Standards in Haematology (BCSH). In comparison with overt PV, a higher platelet count and a lower JAK2V617F allele burden at diagnosis were observed in masked PV. Patients with masked PV needed lower phlebotomies and responded faster to hydroxcarbamide than those with overt PV. Complete haematological response was more frequently achieved in masked than in overt PV (79% vs. 58%, P = 0.001). There were no significant differences in the duration of haematological response, the rate of resistance or intolerance to hydroxycarbamide and the probability of molecular response according to type of PV (masked vs. overt). Overall survival, rate of thrombosis and major bleeding, and probability of transformation was superimposable among patients with masked and overt PV.

  16. Effect of ketoprofen treatment on the uterine inflammatory response after AI of jennies with frozen semen.

    PubMed

    Vilés, K; Rabanal, R; Rodríguez-Prado, M; Miró, J

    2013-04-15

    Artificial insemination (AI) involving the placing of frozen-thawed semen directly into the jenny uterine body is associated with very low pregnancy rates. This might be because of an exacerbation of the acute response of the endometrium to sperm, as seen in mares with persistent induced mating endometritis. Pregnancy rates can be increased in such mares, however, by including anti-inflammatory treatments in the insemination protocol (Bucca S, Carli A, Buckley T, Dolci G, Fogarty U. The use of dexamethasone administered to mares at breeding time in the modulation of persistent mating induced endometritis. Theriogenology 2008;70:1093-100; Rojer H, Aurich C. Treatment of persistent mating-induced endometritis in mares with the non-steroid anti-inflammatory drug vedaprofen. Reprod Domest Anim 2010;45:e458-60). To investigate the endometritis caused by the use of frozen-thawed semen in jennies, and to assess the response to ketoprofen treatment, endometrial cytological samples and biopsies from six healthy jennies were examined in a crossover design experiment. Samples were taken from jennies in estrus (E; control) and at 6 hours after AI with or without ketoprofen (+K and -K, respectively). Ketoprofen was administered iv 24 hours before and for 4 days after insemination (total = 2.2 mg/kg/24 hours for 5 days). All animals showed a severe inflammatory response to semen deposition. Polymorphonuclear neutrophil numbers in the cytological smears and biopsies differed significantly between the +K and E animals. No significant differences were recorded, however, between the +K and -K treatments. Eosinophils were observed in all sample types from all groups; these cells appear to be a feature of the normal jenny endometrium. Slight fibrosis was observed in some biopsies, but no significant relationship with inflammation was found. Intense cyclooxygenase-2 (COX-2) immunohistochemical labeling was detected in the -K biopsies. Less intense labeling was seen in those of the +K

  17. Polymorphism of the dopamine transporter type 1 gene modifies the treatment response in Parkinson's disease.

    PubMed

    Moreau, Caroline; Meguig, Sayah; Corvol, Jean-Christophe; Labreuche, Julien; Vasseur, Francis; Duhamel, Alain; Delval, Arnaud; Bardyn, Thomas; Devedjian, Jean-Christophe; Rouaix, Nathalie; Petyt, Gregory; Brefel-Courbon, Christine; Ory-Magne, Fabienne; Guehl, Dominique; Eusebio, Alexandre; Fraix, Valérie; Saulnier, Pierre-Jean; Lagha-Boukbiza, Ouhaid; Durif, Frank; Faighel, Mirela; Giordana, Caroline; Drapier, Sophie; Maltête, David; Tranchant, Christine; Houeto, Jean-Luc; Debû, Bettina; Azulay, Jean-Philippe; Tison, François; Destée, Alain; Vidailhet, Marie; Rascol, Olivier; Dujardin, Kathy; Defebvre, Luc; Bordet, Régis; Sablonnière, Bernard; Devos, David

    2015-05-01

    After more than 50 years of treating Parkinson's disease with l-DOPA, there are still no guidelines on setting the optimal dose for a given patient. The dopamine transporter type 1, now known as solute carrier family 6 (neurotransmitter transporter), member 3 (SLC6A3) is the most powerful determinant of dopamine neurotransmission and might therefore influence the treatment response. We recently demonstrated that methylphenidate (a dopamine transporter inhibitor) is effective in patients with Parkinson's disease with motor and gait disorders. The objective of the present study was to determine whether genetic variants of the dopamine transporter type 1-encoding gene (SLC6A3) are associated with differences in the response to treatment of motor symptoms and gait disorders with l-DOPA and methylphenidate (with respect to the demographic, the disease and the treatment parameters and the other genes involved in the dopaminergic neurotransmission). This analysis was part of a multicentre, parallel-group, double-blind, placebo-controlled, randomized clinical trial of methylphenidate in Parkinson's disease (Protocol ID:2008-005801-20; ClinicalTrials.gov:NCT00914095). We scored the motor Unified Parkinson's Disease Rating Scale and the Stand-Walk-Sit Test before and after a standardized acute l-DOPA challenge before randomization and then after 3 months of methylphenidate treatment. Patients were screened for variants of genes involved in dopamine metabolism: rs28363170 and rs3836790 polymorphisms in the SLC6A3 gene, rs921451 and rs3837091 in the DDC gene (encoding the aromatic L-amino acid decarboxylase involved in the synthesis of dopamine from l-DOPA), rs1799836 in the MAOB gene (coding for monoamine oxidase B) and rs4680 in the COMT gene (coding for catechol-O-methyltransferase). Investigators and patients were blinded to the genotyping data throughout the study. Eighty-one subjects were genotyped and 61 were analysed for their acute motor response to l-DOPA. The SLC6A3

  18. Can we predict the response in the treatment of epilepsy with vagus nerve stimulation?

    PubMed

    Arcos, A; Romero, L; Gelabert, M; Prieto, A; Pardo, J; Osorio, X Rodriguez; Arráez, M A

    2014-10-01

    Despite the introduction of new antiepileptic drugs and advances in the surgical treatment of epilepsy, an important group of patients still remains uncontrolled by any of these methods. The relatively recent introduction of vagus nerve stimulation is yet another possible treatment for refractory epilepsy. This safe, simple, and adjustable technique reduces the number of seizures and multiple publications support its increasing efficacy and effectiveness, with few adverse effects. The goal of our study is to determine the efficacy of this procedure and the factors predicting a response, particularly in the presence of a temporal lobe discharge on the video electroencephalogram (video-EEG) and magnetic resonance imaging (MRI) lesions. We undertook a retrospective study of all the patients with refractory epilepsy who underwent implantation of a vagus nerve stimulator between 2003 and 2009, and with a minimum follow-up of 6 months. The statistical analysis was done with SPSS for Windows. The stimulator was implanted in 40 patients, of whom 38 had a minimum follow-up of 6 months. In one patient, the device had to be removed due to infection, so the series comprised 37 patients. These were divided into different groups, according to the epidemiologic, clinical, radiologic, and electroencephalographic data. In addition, an analysis of the response was performed. The efficacy of the procedure was established according to the reduction in the mean seizure frequency. The baseline value of these seizures was 80.97 ± 143.59, falling to 37 ± 82.51 at the last revision. The response rate (reduction in seizures ≥ 50 %) at 6 months was 51.4 %, with 62.2 % of the patients showing this reduction at the last evaluation. Significant differences in the response were seen for the variables: baseline frequency of seizures, temporal lobe discharge on VideoEEG and MRI lesions. The mean time to response was 10 months in patients with lower rate of seizures versus 25 months of those

  19. Neurochemical correlates of rapid treatment response to electroconvulsive therapy in patients with major depression

    PubMed Central

    Njau, Stephanie; Joshi, Shantanu H.; Espinoza, Randall; Leaver, Amber M.; Vasavada, Megha; Marquina, Antonio; Woods, Roger P.; Narr, Katherine L.

    2017-01-01

    Background Electroconvulsive therapy (ECT) is a highly effective brain stimulation treatment for severe depression. Identifying neurochemical changes linked with ECT may point to biomarkers and predictors of successful treatment response. Methods We used proton magnetic resonance spectroscopy (1H-MRS) to measure longitudinal changes in glutamate/glutamine (Glx), creatine (Cre), choline (Cho) and N-acetylaspartate (NAA) in the dorsal (dACC) and subgenual anterior cingulate cortex (sgACC) and bilateral hippocampus in patients receiving ECT scanned at baseline, after the second ECT session and after the ECT treatment series. Patients were compared with demographically similar controls at baseline. Controls were assessed twice to establish normative values and variance. Results We included 50 patients (mean age 43.78 ± 14 yr) and 33 controls (mean age 39.33 ± 12 yr) in our study. Patients underwent a mean of 9 ± 4.1 sessions of ECT. At baseline, patients showed reduced Glx in the sgACC, reduced NAA in the left hippocampus and increased Glx in the left hippocampus relative to controls. ECT was associated with significant increases in Cre in the dACC and sgACC and decreases in NAA in the dACC and right hippocampus. Lower NAA levels in the dACC at baseline predicted reductions in depressive symptoms. Both ECT and symptom improvement were associated with decreased Glx in the left hippocampus and increased Glx in the sgACC. Limitations Attrition and clinical heterogeneity may have masked more subtle findings. Conclusion ECT elicits robust effects on brain chemistry, impacting Cre, NAA and Glx, which suggests restorative and neurotrophic processes. Differential effects of Glx in the sgACC and hippocampus, which approach control values with treatment, may reflect previously implicated underactive cortical and overactive subcortical limbic circuitry in patients with major depression. NAA levels at baseline are predictive of therapeutic outcome and could inform future

  20. Differential responsiveness to a parenting intervention for mothers in substance abuse treatment.

    PubMed

    Paris, Ruth; Herriott, Anna; Holt, Melissa; Gould, Karen

    2015-12-01

    This study examines the relationship between levels of psychological distress in substance-dependent mothers and their differential response to a dyadic parent-child intervention. A sample of 66 mothers who were receiving treatment for substance abuse, as well as a simultaneous parenting intervention, were interviewed pre and post-treatment on measures of psychological distress, adult and child trauma history, parental reflective functioning, and child social-emotional development. Additionally, clinicians provided assessments of the parent-child relationships. As anticipated, trauma histories for mothers and children, children's social emotional development, and parental reflective functioning were associated with aspects of maternal psychological distress. Kruskal-Wallis and subsequent Wilcoxson signed rank tests revealed that women with highest levels of baseline psychological distress showed significant improvements in psychological functioning post-treatment while women with moderately elevated levels of psychological distress did not. Women who were most distressed at baseline showed increased levels of parental reflective functioning post-treatment while women with moderate and lower levels of baseline psychological distress showed improvements on clinician-rated assessments of parent-child relationships. Chi Square analyses showed that parents who endorsed the highest levels of distress at baseline reported that their children's risk status regarding social-emotional development decreased post-treatment. Despite similarities in substance dependence, mothers in this sample had different needs and outcomes in the context of this parenting intervention due to variation in mental health. Given this variation, parenting interventions for substance-dependent mothers need to account for the individual differences in levels of psychological distress.

  1. Hormonal and lactational responses to growth hormone-releasing hormone treatment in lactating Japanese Black cows.

    PubMed

    Shingu, H; Hodate, K; Kushibiki, S; Ueda, Y; Touno, E; Shinoda, M; Ohashi, S

    2004-06-01

    Ten multiparous lactating Japanese Black cows (beef breed) were used to evaluate the effects of bovine growth hormone-releasing hormone (GHRH) analog on milk yield and profiles of plasma hormones and metabolites. The cows received 2 consecutive 21-d treatments (a daily s.c. injection of 3-mg GHRH analog or saline) in a 2 (group) x 2 (period) Latin square crossover design. The 5 cows in group A received GHRH analog during period 1 (from d 22 to 42 postpartum) and saline during period 2 (from d 57 to 77 postpartum), and those in group B received saline and GHRH analog during periods 1 and 2, respectively. Mean milk yield decreased in saline treated compared with that during the 1-wk period before treatment 7.4 and 19.1% during periods 1 (group B) and 2 (group A), respectively. Treatment with GHRH analog increased milk yield 17.4% (period 1, group A) and 6.3% (period 2, group B). Treatment with GHRH analog induced higher basal plasma concentrations of growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin, and glucose compared with saline-treated cows. In glucose challenge, the GHRH analog-treated beef cows had greater insulin secretion than the saline-treated beef cows. In insulin challenge, however, there were no significant differences in the areas surrounded by hypothetical lines of basal glucose concentrations and glucose response curves between GHRH analog- and saline-treated cows. These results demonstrate that GHRH analog treatment facilitates endogenous GH secretion in lactating Japanese Black cows, leading to increases in milk yield and plasma concentrations of IGF-1, insulin, and glucose.

  2. Interaction between nanoparticles generated by zinc chloride treatment and oxidative responses in rat liver

    PubMed Central

    Azzouz, Inès; Trabelsi, Hamdi; Hanini, Amel; Ferchichi, Soumaya; Tebourbi, Olfa; Sakly, Mohsen; Abdelmelek, Hafedh

    2014-01-01

    The aim of the present study was to investigate the interaction of zinc chloride (3 mg/kg, intraperitoneally [ip]) in rat liver in terms of the biosynthesis of nanoparticles. Zinc treatment increased zinc content in rat liver. Analysis of fluorescence revealed the presence of red fluorescence in the liver following zinc treatment. Interestingly, the co-exposure to zinc (3 mg/kg, ip) and selenium (0.20 mg/L, per os [by mouth]) led to a higher intensity of red fluorescence compared to zinc-treated rats. In addition, X-ray diffraction measurements carried out on liver fractions of zinc-treated rats point to the biosynthesis of zinc sulfide and/or selenide nanocomplexes at nearly 51.60 nm in size. Moreover, co-exposure led to nanocomplexes of about 72.60 nm in size. The interaction of zinc with other mineral elements (S, Se) generates several nanocomplexes, such as ZnS and/or ZnSe. The nanocomplex ZnX could interact directly with enzyme activity or indirectly by the disruption of mineral elements’ bioavailability in cells. Subacute zinc or selenium treatment decreased malondialdehyde levels, indicating a drop in lipid peroxidation. In addition, antioxidant enzyme assays showed that treatment with zinc or co-treatment with zinc and selenium increased the activities of glutathione peroxidase, catalase, and superoxide dismutase. Consequently, zinc complexation with sulfur and/or selenium at nanoscale level could enhance antioxidative responses, which is correlated to the ratio of number of ZnX nanoparticles (X=sulfur or X=selenium) to malondialdehyde level in rat liver. PMID:24403828

  3. Early responses of human cancer cells upon photodynamic treatment monitored by laser phase microscopy

    NASA Astrophysics Data System (ADS)

    Roelofs, Theo A.; Graschew, Georgi; Perevedentseva, Elena V.; Rakowsky, Stefan; Dressler, Cathrin; Beuthan, Juergen; Schlag, Peter M.

    2001-04-01

    Photodynamic treatment of cancer cells is known to eventually cause cell death in most cases. The precise pathways and the time course seem to vary among different cell types and modes of photodynamic treatment. In this contribution, the focus was put on the responses of human colon carcinoma cells HCT-116 within the first 15 minutes after laser irradiation in the presence of Photofrin« II (PII). To monitor the cell response in this early time period laser phase microscopic imaging was used, a method sensitive to changes in overall cell shape and intracellular structures, mediated by changes in the local refractive index. Laser irradiation of cells loaded with PII induced a significant reduction of the phase shifts, which probably reflects the induced damage to the different cellular membrane structures. The data suggest that even within the first 30 s after the onset of laser illumination, a significant reduction of the phase shifts can be detected. These results underline that laser phase microscopy is a suitable diagnostic tool for cellular research, also in the early time domain.

  4. Genetically Determined Response to Artemisinin Treatment in Western Kenyan Plasmodium falciparum Parasites

    PubMed Central

    Chebon, Lorna J.; Ngalah, Bidii S.; Ingasia, Luicer A.; Juma, Dennis W.; Muiruri, Peninah; Cheruiyot, Jelagat; Opot, Benjamin; Mbuba, Emmanuel; Imbuga, Mabel; Akala, Hoseah M.; Bulimo, Wallace; Andagalu, Ben; Kamau, Edwin

    2016-01-01

    Genetically determined artemisinin resistance in Plasmodium falciparum has been described in Southeast Asia. The relevance of recently described Kelch 13-propeller mutations for artemisinin resistance in Sub-Saharan Africa parasites is still unknown. Southeast Asia parasites have low genetic diversity compared to Sub-Saharan Africa, where parasites are highly genetically diverse. This study attempted to elucidate whether genetics provides a basis for discovering molecular markers in response to artemisinin drug treatment in P. falciparum in Kenya. The genetic diversity of parasites collected pre- and post- introduction of artemisinin combination therapy (ACT) in western Kenya was determined. A panel of 12 microsatellites and 91 single nucleotide polymorphisms (SNPs) distributed across the P. falciparum genome were genotyped. Parasite clearance rates were obtained for the post-ACT parasites. The 12 microsatellites were highly polymorphic with post-ACT parasites being significantly more diverse compared to pre-ACT (p < 0.0001). The median clearance half-life was 2.55 hours for the post-ACT parasites. Based on SNP analysis, 15 of 90 post-ACT parasites were single-clone infections. Analysis revealed 3 SNPs that might have some causal association with parasite clearance rates. Further, genetic analysis using Bayesian tree revealed parasites with similar clearance phenotypes were more closely genetically related. With further studies, SNPs described here and genetically determined response to artemisinin treatment might be useful in tracking artemisinin resistance in Kenya. PMID:27611315

  5. Treatment with Pyranopyran-1, 8-Dione Attenuates Airway Responses in Cockroach Allergen Sensitized Asthma in Mice

    PubMed Central

    Jung, Kyung-Hwa; Song, Joohyun; Kim, You Ah; Cho, Hi Jae; Min, Byung-Il; Bae, Hyunsu

    2014-01-01

    Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. Viticis Fructus (VF) has long been used in China and Korea as a traditional herbal remedy for treating various inflammatory diseases. Previously, we have isolated a novel phytochemical, pyranopyran-1, 8-dione (PPY), from VF. This study was conducted to evaluate the ability of PPY to prevent airway inflammation and to attenuate airway responses in a cockroach allergen-induced asthma model in mice. The mice sensitized to and challenged with cockroach allergen were treated with oral administration of PPY. The infiltration of total cells, eosinophils and lymphocytes into the BAL fluid was significantly inhibited in cockroach allergen-induced asthma mice treated with PPY (1, 2, or 10 mg/kg). Th2 cytokines and chemokine, such as IL-4, IL-5, IL-13 and eotaxin in BAL fluid were also reduced to normal levels following treatment with PPY. In addition, the levels of IgE were also markedly suppressed after PPY treatment. Histopathological examination demonstrated that PPY substantially inhibited eosinophil infiltration into the airway, goblet cell hyperplasia and smooth muscle hypertrophy. Taken together, these results demonstrate that PPY possesses a potent efficacy on controlling allergic asthma response such as airway inflammation and remodeling. PMID:24489937

  6. Hoarding in Youth with Autism Spectrum Disorders and Anxiety: Incidence, Clinical Correlates, and Behavioral Treatment Response.

    PubMed

    Storch, Eric A; Nadeau, Joshua M; Johnco, Carly; Timpano, Kiara; McBride, Nicole; Jane Mutch, P; Lewin, Adam B; Murphy, Tanya K

    2016-05-01

    This study examined the nature and correlates of hoarding among youth with autism spectrum disorders (ASD). Forty children with ASD and a comorbid anxiety disorder were administered a battery of clinician-administered measures assessing presence of psychiatric disorders and anxiety severity. Parents completed questionnaires related to child hoarding behaviors, social responsiveness, internalizing and externalizing behaviors, and functional impairment. We examined the impact of hoarding behaviors on treatment response in a subsample of twenty-six youth who completed a course of personalized cognitive-behavioral therapy targeting anxiety symptoms. Hoarding symptoms were common and occurred in a clinically significant manner in approximately 25 % of cases. Overall hoarding severity was associated with increased internalizing and anxiety/depressive symptoms, externalizing behavior, and attention problems. Discarding items was associated with internalizing and anxious/depressive symptoms, but acquisition was not. Hoarding decreased following cognitive-behavioral therapy but did not differ between treatment responders and non-responders. These data are among the first to examine hoarding among youth with ASD; implications of study findings and future directions are highlighted.

  7. Pediatric Neurocysticercosis: Usefulness of Antibody Response in Cysticidal Treatment Follow-Up

    PubMed Central

    Atluri, Venkata Subba Rao; Gogulamudi, Venkateswara Reddy; Singhi, Pratibha; Khandelwal, Niranjan; Parasa, Lakshmana Swamy; Malla, Nancy

    2014-01-01

    Serum and urine samples were collected from 33 NCC patients before the albendazole treatment, 3–6 and 12 months PT. At 3 months PT, 24 (72.7%) patients had no detectable CT/MRI lesions and 9 (27.2%) patients had persistent lesions. Antibody response to crude soluble extract (CSE), excretory secretory (ES), and lower molecular mass (LMM) (10–30 KDa) antigenic fraction of T. solium cysticerci was detected in serum and urine samples by ELISA. Before the treatment, out of 33 NCC children, 14 (42.4%), 22 (66.6%), and 11 (33.3%) serum samples were found positive with the use of CSE, ES, and LMM antigen, respectively. At 3–6 months PT, positivity rate was 5 (15.1%), 2 (6%), and 4 (12.1%) and at 12 months PT, positivity rate was 5 (15.1%), 0, and 3 (9%) with the use of CSE, ES, and LMM antigen, respectively. There was no significant difference in the positivity with the use of three antigens in pretreatment and PT urine samples. The study suggests that the use of ES antigen to detect antibody in serum samples may serve better purpose to evaluate the therapeutic response in patients with NCC. PMID:25215297

  8. A Reactive 1O2 - Responsive Combined Treatment System of Photodynamic and Chemotherapy for Cancer

    NASA Astrophysics Data System (ADS)

    Wang, Xiaojun; Meng, Guoqing; Zhang, Song; Liu, Xinli

    2016-07-01

    The development of reactive oxygen species (ROS)-responsive drug delivery and drug release has gradually attracted much attention in recent years as a promising therapeutic strategy. Singlet oxygen (1O2) as the major ROS species is widely used in photodynamic therapy (PDT) of cancer. In the present study, we introduce a combined treatment using ROS-sensitive thioketal (TK) linkage as a linker between upconversion nanoparticles (UNs)-based PDT and doxorubicin (DOX)-based chemotherapy. UNs can not only play a role in PDT, but can also be used as a nanocarrier for drug delivery of DOX. Moreover, the products of 1O2 during PDT are able to cleave TK linker inducing the release of DOX which can further achieve the goal of chemotherapy. By using this 1O2-responsive nanocarrier delivery system, DOX can easily reach the tumor site and be accumulated in the nuclei to effectively kill the cancer cells, and therefore decreasing the side effects of chemotherapy on the body. Thus, PDT also has the function of controlling drug release in this combination treatment strategy. Compared with monotherapy, the combination of PDT with chemotherapy also possesses excellent drug loading capability and anticancer efficiency.

  9. Process optimization via response surface methodology in the treatment of metal working industry wastewater with electrocoagulation.

    PubMed

    Guvenc, Senem Yazici; Okut, Yusuf; Ozak, Mert; Haktanir, Birsu; Bilgili, Mehmet Sinan

    2017-02-01

    In this study, process parameters in chemical oxygen demand (COD) and turbidity removal from metal working industry (MWI) wastewater were optimized by electrocoagulation (EC) using aluminum, iron and steel electrodes. The effects of process variables on COD and turbidity were investigated by developing a mathematical model using central composite design method, which is one of the response surface methodologies. Variance analysis was conducted to identify the interaction between process variables and model responses and the optimum conditions for the COD and turbidity removal. Second-order regression models were developed via the Statgraphics Centurion XVI.I software program to predict COD and turbidity removal efficiencies. Under the optimum conditions, removal efficiencies obtained from aluminum electrodes were found to be 76.72% for COD and 99.97% for turbidity, while the removal efficiencies obtained from iron electrodes were found to be 76.55% for COD and 99.9% for turbidity and the removal efficiencies obtained from steel electrodes were found to be 65.75% for COD and 99.25% for turbidity. Operational costs at optimum conditions were found to be 4.83, 1.91 and 2.91 €/m(3) for aluminum, iron and steel electrodes, respectively. Iron electrode was found to be more suitable for MWI wastewater treatment in terms of operational cost and treatment efficiency.

  10. Host response to various treatments to reduce Salmonella infections in swine.

    PubMed Central

    Letellier, A; Messier, S; Lessard, L; Chénier, S; Quessy, S

    2001-01-01

    Host response was evaluated following the administration of various treatments, such as probiotics, prebiotics, and vaccination, to reduce Salmonella in swine. Response to the treatments were studied by the evaluation of phagocytosis rates by flow cytometry, by studying the activation of whole-blood phagocytes by bioluminescence, the production of IgA against S. Typhimurium, and by histopathology. Significant differences were observed in the activation of whole-blood phagocytes in all groups of treated pigs (P = 0.0001). In SC54 vaccinated pigs, a significant reduction of Salmonella in the ileum was observed (P < 0.05) and the production of IgA against S. Typhimurium was higher in this group in comparison to uninfected control pigs (P = 0.0007). Furthermore, significant histopathological (P < 0.05) changes were observed in SC54 vaccinated pigs. Villus height and mucus and goblet cells density in the small intestine were reduced in vaccinated pigs in comparison to infected control pigs. Taken together, these findings suggest that SC54 vaccine can stimulate local immunity and reduce the presence of Salmonella in the ileum in swine. Use of SC54 vaccine should thus be considered in further field experiments. PMID:11480522

  11. Genetically Determined Response to Artemisinin Treatment in Western Kenyan Plasmodium falciparum Parasites.

    PubMed

    Chebon, Lorna J; Ngalah, Bidii S; Ingasia, Luicer A; Juma, Dennis W; Muiruri, Peninah; Cheruiyot, Jelagat; Opot, Benjamin; Mbuba, Emmanuel; Imbuga, Mabel; Akala, Hoseah M; Bulimo, Wallace; Andagalu, Ben; Kamau, Edwin

    2016-01-01

    Genetically determined artemisinin resistance in Plasmodium falciparum has been described in Southeast Asia. The relevance of recently described Kelch 13-propeller mutations for artemisinin resistance in Sub-Saharan Africa parasites is still unknown. Southeast Asia parasites have low genetic diversity compared to Sub-Saharan Africa, where parasites are highly genetically diverse. This study attempted to elucidate whether genetics provides a basis for discovering molecular markers in response to artemisinin drug treatment in P. falciparum in Kenya. The genetic diversity of parasites collected pre- and post- introduction of artemisinin combination therapy (ACT) in western Kenya was determined. A panel of 12 microsatellites and 91 single nucleotide polymorphisms (SNPs) distributed across the P. falciparum genome were genotyped. Parasite clearance rates were obtained for the post-ACT parasites. The 12 microsatellites were highly polymorphic with post-ACT parasites being significantly more diverse compared to pre-ACT (p < 0.0001). The median clearance half-life was 2.55 hours for the post-ACT parasites. Based on SNP analysis, 15 of 90 post-ACT parasites were single-clone infections. Analysis revealed 3 SNPs that might have some causal association with parasite clearance rates. Further, genetic analysis using Bayesian tree revealed parasites with similar clearance phenotypes were more closely genetically related. With further studies, SNPs described here and genetically determined response to artemisinin treatment might be useful in tracking artemisinin resistance in Kenya.

  12. Technical Basis for Radiological Emergency Plan Annex for WTD Emergency Response Plan: West Point Treatment Plant

    SciTech Connect

    Hickey, Eva E.; Strom, Daniel J.

    2005-08-01

    Staff of the King County Wastewater Treatment Division (WTD) have concern about the aftermath of a radiological dispersion event (RDE) leading to the introduction of significant quantities of radioactive material into the combined sanitary and storm sewer system in King County, Washington. Radioactive material could come from the use of a radiological dispersion device (RDD). RDDs include "dirty bombs" that are not nuclear detonations but are explosives designed to spread radioactive material (National Council on Radiation Protection and Measurements (NCRP) 2001). Radioactive material also could come from deliberate introduction or dispersion of radioactive material into the environment, including waterways and water supply systems. This document, Volume 3 of PNNL-15163 is the technical basis for the Annex to the West Point Treatment Plant (WPTP) Emergency Response Plan related to responding to a radiological emergency at the WPTP. The plan primarily considers response to radioactive material that has been introduced in the other combined sanitary and storm sewer system from a radiological dispersion device, but is applicable to any accidental or deliberate introduction of materials into the system.

  13. A Systematic Review of the Effect of Expectancy on Treatment Responses to Acupuncture

    PubMed Central

    Colagiuri, Ben; Smith, Caroline A.

    2012-01-01

    Randomised controlled trials (RCTs) of acupuncture often find equivalent responses to real and placebo acupuncture despite both appearing superior to no treatment. This raises questions regarding the mechanisms of acupuncture, especially the contribution of patient expectancies. We systematically reviewed previous research assessing the relationship between expectancy and treatment responses following acupuncture, whether real or placebo. To be included, studies needed to assess and/or manipulate expectancies about acupuncture and relate these to at least one health-relevant outcome. Nine such independent studies were identified through systematic searches of Medline, PsycInfo, PubMed, and Cochrane Clinical Trials Register. The methodology and reporting of these studies were quite heterogeneous, meaning that meta-analysis was not possible. A descriptive review revealed that five studies found statistically significant effects of expectancy on a least one outcome, with three also finding evidence suggestive of an interaction between expectancy and type of acupuncture (real or placebo). While there were some trends in significant effects in terms of study characteristics, their generality is limited by the heterogeneity of study designs. The differences in design across studies highlight some important methodological considerations for future research in this area, particularly regarding whether to assess or manipulate expectancies and how best to assess expectancies. PMID:22203882

  14. A Reactive 1O2 - Responsive Combined Treatment System of Photodynamic and Chemotherapy for Cancer

    PubMed Central

    Wang, Xiaojun; Meng, Guoqing; Zhang, Song; Liu, Xinli

    2016-01-01

    The development of reactive oxygen species (ROS)-responsive drug delivery and drug release has gradually attracted much attention in recent years as a promising therapeutic strategy. Singlet oxygen (1O2) as the major ROS species is widely used in photodynamic therapy (PDT) of cancer. In the present study, we introduce a combined treatment using ROS-sensitive thioketal (TK) linkage as a linker between upconversion nanoparticles (UNs)-based PDT and doxorubicin (DOX)-based chemotherapy. UNs can not only play a role in PDT, but can also be used as a nanocarrier for drug delivery of DOX. Moreover, the products of 1O2 during PDT are able to cleave TK linker inducing the release of DOX which can further achieve the goal of chemotherapy. By using this 1O2-responsive nanocarrier delivery system, DOX can easily reach the tumor site and be accumulated in the nuclei to effectively kill the cancer cells, and therefore decreasing the side effects of chemotherapy on the body. Thus, PDT also has the function of controlling drug release in this combination treatment strategy. Compared with monotherapy, the combination of PDT with chemotherapy also possesses excellent drug loading capability and anticancer efficiency. PMID:27443831

  15. Modifying dielectrophoretic response of nonviable yeast cells by ionic surfactant treatment.

    PubMed

    Tang, Shi-Yang; Zhang, Wei; Baratchi, Sara; Nasabi, Mahyar; Kalantar-Zadeh, Kourosh; Khoshmanesh, Khashayar

    2013-07-02

    Nonviable cells are essential biosystems, due to the functionalities they offer and their effects on viable cells. Therefore, the separation and immobilization of nonviable cells separately or in the vicinity of viable cells is of great importance for many fundamentals investigations in cell biology. However, most nonviable cells become less polarizable than the surrounding medium at conductivities above 0.01 S/m. This means that in such a medium, dielectrophoresis, despite its great versatilities for manipulation of cells, cannot be employed for immobilizing nonviable cells. Here, we present a novel approach to change the dielectrophoretic (DEP) response of nonviable yeast cells by treating them with low concentrations of ionic surfactants such as sodium dodecyl sulfate. After this treatment, they exhibit a strong positive DEP response, even at high medium conductivities. The capability of this treatment is demonstrated in two proof-of-concept experiments. First, we show the sorting and immobilization of viable and nonviable yeast cells, along consecutive microelectrode arrays. Second, we demonstrate the immobilization of viable and nonviable cells in the vicinity of each other along the same microelectrode array. The proposed technique allows DEP platforms to be utilized for the immobilization and subsequent postanalysis of both viable and nonviable cells with and without the presence of each other.

  16. Microbial response to single-cell protein production and brewery wastewater treatment

    PubMed Central

    Lee, Jackson Z; Logan, Andrew; Terry, Seth; Spear, John R

    2015-01-01

    As global fisheries decline, microbial single-cell protein (SCP) produced from brewery process water has been highlighted as a potential source of protein for sustainable animal feed. However, biotechnological investigation of SCP is difficult because of the natural variation and complexity of microbial ecology in wastewater bioreactors. In this study, we investigate microbial response across a full-scale brewery wastewater treatment plant and a parallel pilot bioreactor modified to produce an SCP product. A pyrosequencing survey of the brewery treatment plant showed that each unit process selected for a unique microbial community. Notably, flow equalization basins were dominated by Prevotella, methanogenesis effluent had the highest levels of diversity, and clarifier wet-well samples were sources of sequences for the candidate bacterial phyla of TM7 and BD1-5. Next, the microbial response of a pilot bioreactor producing SCP was tracked over 1 year, showing that two different production trials produced two different communities originating from the same starting influent. However, SCP production resulted generally in enrichment of several clades of rhizospheric diazotrophs of Alphaproteobacteria and Betaproteobacteria in the bioreactor and even more so in the final product. These diazotrophs are potentially useful as the basis of a SCP product for commercial feed production. PMID:24837420

  17. The effect of doxycycline treatment on the postvaccinal immune response in pigs.

    PubMed

    Pomorska-Mól, Małgorzata; Kwit, Krzysztof; Markowska-Daniel, Iwona; Pejsak, Zygmunt

    2014-07-01

    The effect of a seven-day antibiotic therapy with doxycycline was investigated on the postvaccinal humoral and cellular immune response in pigs. The selected parameters of non-specific immunity were also studied. Fifty pigs were used (control not vaccinated (C, n=10), control vaccinated (CV, n=20), and experimental - received doxycycline (DOXY, n=20)). For vaccination live-attenuated vaccine against pseudorabies (PR) was used. From day -1 to day 5 pigs from DOXY group received doxycycline orally with drinking water, at the recommended dose. Pigs from DOXY and CV groups were vaccinated at 8 and 10 weeks of age. The results of the present study showed that cell-mediated postvaccinal immune response can be modulated by oral treatment with doxycycline. Significantly lower values of stimulation index were observed after PRV restimulation in doxycycline-treated pigs. Moreover, in the DOXY group a significant decrease in IFN-γ production after PRV restimulation was noted. The significantly lower number of CD4+CD8+ cells was also observed in doxy-treated, vaccinated pigs, 2 weeks after final vaccination. Simultaneously, specific humoral response was not disturbed. This study demonstrated the importance of defining the immune modulatory activity of doxycycline because it may alter the immune responses to vaccines. The exact mechanism of T-cell response suppression by doxycycline remains to be elucidated, however the influence of doxycycline on the secretion of various cytokines, including IFN-γ, may be considered as a possible cause. The present observations should prompt further studies on the practical significance of such phenomena in terms of clinical implications.

  18. Nonverbal communication sets the conditions for the relationship between parental bonding and the short-term treatment response in depression.

    PubMed

    Geerts, Erwin; van Os, Titus; Gerlsma, Coby

    2009-01-30

    The role of parental bonding and nonverbal communication in the short-term treatment response was investigated in 104 depressed outpatients. At baseline patients completed the Parental Bonding Instrument. We registered the nonverbal involvement behaviour of patients and interviewers from video recordings of baseline clinical interviews and calculated the convergence between patient-interviewer behaviour over the interview. The course of depression was assessed with the Beck Depression Inventory. As hypothesized, low maternal care and high paternal overprotection predicted a poor response to an 8-week treatment. Maternal care was positively correlated with nonverbal convergence. Moreover, convergence moderated the relationship between maternal care and the response to treatment: Lack of convergence between patients and interviewers turned out to annul the positive effects of maternal care on the treatment response. The findings link theories on early parenting to interpersonal theories of depression.

  19. A methodology for assessing treatment response in Hashimoto's encephalopathy: a case study demonstrating repeated computerized neuropsychological testing.

    PubMed

    Brooks, Brian L; Barlow, Karen M

    2011-06-01

    Hashimoto's encephalopathy, a steroid-responsive encephalopathy, presents with cognitive deterioration, psychiatric symptoms, and seizures and is often associated with elevation of anti-thyroid peroxidase antibodies or thyroid dysfunction. Because of the absence of a gold-standard diagnostic test and serological marker of disease, improvement in cognitive impairment is an important sign when assessing response to corticosteroid treatment. The purpose of this case study is to present a methodology for tracking neurocognitive functioning using computerized testing (CNS Vital Signs) in a 14-year-old girl with Hashimoto's encephalopathy. Computerized neuropsychological testing was done prior to commencing corticosteroid treatment, as well as at 7 follow-up assessments over 1 year. Improvement in cognitive, psychological, and behavioral functioning heralded a response to treatment, which was sustained during tapering of medication. Computerized neuropsychological testing seems to be a viable tool for tracking cognitive functioning (when rapid assessments are desired) and assessing response to corticosteroid treatment in Hashimoto's encephalopathy.

  20. Risk profiles for poor treatment response to internet-delivered CBT in people with social anxiety disorder.

    PubMed

    Tillfors, Maria; Furmark, Tomas; Carlbring, Per; Andersson, Gerhard

    2015-06-01

    In social anxiety disorder (SAD) co-morbid depressive symptoms as well as avoidance behaviors have been shown to predict insufficient treatment response. It is likely that subgroups of individuals with different profiles of risk factors for poor treatment response exist. This study aimed to identify subgroups of social avoidance and depressive symptoms in a clinical sample (N = 167) with SAD before and after guided internet-delivered CBT, and to compare these groups on diagnostic status and social anxiety. We further examined individual movement between subgroups over time. Using cluster analysis we identified four subgroups, including a high-problem cluster at both time-points. Individuals in this cluster showed less remission after treatment, exhibited higher levels of social anxiety at both assessments, and typically remained in the high-problem cluster after treatment. Thus, in individuals with SAD, high levels of social avoidance and depressive symptoms constitute a risk profile for poor treatment response.

  1. Predictors of Treatment Response to Fluoxetine in PTSD Following a Recent History of War Zone Stress Exposure

    DTIC Science & Technology

    2010-07-01

    1-0283 TITLE: Predictors of Treatment Response to Fluoxetine in PTSD Following a Recent History of War Zone Stress Exposure...SUBTITLE Predictors of Treatment Response to 5a. CONTRACT NUMBER W81XWH-07-1-0283 Fluoxetine in PTSD Following a Recent History of...controlled trial of fluoxetine as an early intervention for recently redeployed soldiers, as well as to develop methodologies for understanding the

  2. Methylphenidate for the treatment of apathy in Alzheimer disease: prediction of response using dextroamphetamine challenge.

    PubMed

    Herrmann, Nathan; Rothenburg, Lana S; Black, Sandra E; Ryan, Michelle; Liu, Barbara A; Busto, Usoa E; Lanctôt, Krista L

    2008-06-01

    Apathy is a common behavioral symptom of Alzheimer's disease (AD), being present in up to 70% of patients. Apathy in AD and non-AD populations has been associated with dysfunction in the dopaminergic brain reward system, suggesting that pharmacotherapeutic targeting of this system may be an effective treatment for apathy in AD. We therefore performed a randomized, double-blind, placebo-controlled crossover trial of methylphenidate in a sample of 13 apathetic AD patients (6 men, 7 women; age mean 77.9 years [SD, 7.8 years]; Mini Mental Status Examination score, 19.9 [SD, 4.7]). Patients were treated with methylphenidate (10 mg PO twice a day) or an identical placebo in two 2-week phases separated by a 1-week placebo washout. All patients participated in a dextroamphetamine challenge test (one 10-mg oral dose) before treatment with methylphenidate to gauge the functional integrity of the dopamine brain reward system. Overall, patients demonstrated greater improvement with methylphenidate compared with placebo according to Apathy Evaluation Scale total change scores (end of treatment - baseline: Wilcoxon Z = -2.00; P = 0.047). However, a significantly greater proportion of patients experienced at least 1 adverse event with methylphenidate compared with placebo (3 vs 1; chi = 4.33, P = 0.038). Two patients experienced serious adverse events with methylphenidate, consisting of delusions, agitation, anger, irritability, and insomnia, which resolved upon discontinuation of the medication. Response to methylphenidate was associated with increases in inattention on a continuous performance task after dextroamphetamine challenge. Psychostimulants may be effective in treating features of apathy in AD, and dopaminergic changes may predict response.

  3. Comprehensive Analysis of miRNome Alterations in Response to Sorafenib Treatment in Colorectal Cancer Cells

    PubMed Central

    Pehserl, Anna-Maria; Ress, Anna Lena; Stanzer, Stefanie; Resel, Margit; Karbiener, Michael; Stadelmeyer, Elke; Stiegelbauer, Verena; Gerger, Armin; Mayr, Christian; Scheideler, Marcel; Hutterer, Georg C.; Bauernhofer, Thomas; Kiesslich, Tobias; Pichler, Martin

    2016-01-01

    MicroRNAs (miRNAs) are master regulators of drug resistance and have been previously proposed as potential biomarkers for the prediction of therapeutic response in colorectal cancer (CRC). Sorafenib, a multi-kinase inhibitor which has been approved for the treatment of liver, renal and thyroid cancer, is currently being studied as a monotherapy in selected molecular subtypes or in combination with other drugs in metastatic CRC. In this study, we explored sorafenib-induced cellular effects in Kirsten rat sarcoma viral oncogene homolog olog (KRAS) wild-type and KRAS-mutated CRC cell lines (Caco-2 and HRT-18), and finally profiled expression changes of specific miRNAs within the miRNome (>1000 human miRNAs) after exposure to sorafenib. Overall, sorafenib induced a time- and dose-dependent growth-inhibitory effect through S-phase cell cycle arrest in KRAS wild-type and KRAS-mutated CRC cells. In HRT-18 cells, two human miRNAs (hsa-miR-597 and hsa-miR-720) and two small RNAs (SNORD 13 and hsa-miR-3182) were identified as specifically sorafenib-induced. In Caco-2 cells, nine human miRNAs (hsa-miR-3142, hsa-miR-20a, hsa-miR-4301, hsa-miR-1290, hsa-miR-4286, hsa-miR-3182, hsa-miR-3142, hsa-miR-1246 and hsa-miR-720) were identified to be differentially regulated post sorafenib treatment. In conclusion, we confirmed sorafenib as a potential anti-neoplastic treatment strategy for CRC cells by demonstrating a growth-inhibitory and cell cycle–arresting effect of this drug. Changes in the miRNome indicate that some specific miRNAs might be relevant as indicators for sorafenib response, drug resistance and potential targets for combinatorial miRNA-based drug strategies. PMID:27916938

  4. Bacterial response to a shock load of nanosilver in an activated sludge treatment system.

    PubMed

    Liang, Zhihua; Das, Atreyee; Hu, Zhiqiang

    2010-10-01

    The growing release of nanosilver into sewage systems has increased the concerns on the potential adverse impacts of silver nanoparticles (AgNPs) in wastewater treatment plants. The inhibitory effects of nanosilver on wastewater treatment and the response of activated sludge bacteria to the shock loading of AgNPs were evaluated in a Modified Ludzack-Ettinger (MLE) activated sludge treatment system. Before shock-loading experiments, batch extant respirometric assays determined that at 1mg/L of total Ag, nitrification inhibitions by AgNPs (average size=1-29 nm) and Ag(+) ions were 41.4% and 13.5%, respectively, indicating that nanosilver was more toxic to nitrifying bacteria in activated sludge than silver ions. After a 12-h period of nanosilver shock loading to reach a final peak silver concentration of 0.75 mg/L in the MLE system, the total silver concentration in the mixed liquor decreased exponentially. A continuous flow-through model predicted that the silver in the activated sludge system would be washed out 25 days after the shock loading. Meanwhile, a prolonged period of nitrification inhibition (>1 month, the highest degree of inhibition=46.5%) and increase of ammonia/nitrite concentration in wastewater effluent were observed. However, nanosilver exposure did not affect the growth of heterotrophs responsible for organic matter removal. Microbial community structure analysis indicated that the ammonium-oxidizing bacteria and nitrite-oxidizing bacteria, Nitrospira, had experienced population decrease while Nitrobacter was washed out after the shock loading.

  5. Comprehensive Analysis of miRNome Alterations in Response to Sorafenib Treatment in Colorectal Cancer Cells.

    PubMed

    Pehserl, Anna-Maria; Ress, Anna Lena; Stanzer, Stefanie; Resel, Margit; Karbiener, Michael; Stadelmeyer, Elke; Stiegelbauer, Verena; Gerger, Armin; Mayr, Christian; Scheideler, Marcel; Hutterer, Georg C; Bauernhofer, Thomas; Kiesslich, Tobias; Pichler, Martin

    2016-12-01

    MicroRNAs (miRNAs) are master regulators of drug resistance and have been previously proposed as potential biomarkers for the prediction of therapeutic response in colorectal cancer (CRC). Sorafenib, a multi-kinase inhibitor which has been approved for the treatment of liver, renal and thyroid cancer, is currently being studied as a monotherapy in selected molecular subtypes or in combination with other drugs in metastatic CRC. In this study, we explored sorafenib-induced cellular effects in Kirsten rat sarcoma viral oncogene homolog olog (KRAS) wild-type and KRAS-mutated CRC cell lines (Caco-2 and HRT-18), and finally profiled expression changes of specific miRNAs within the miRNome (>1000 human miRNAs) after exposure to sorafenib. Overall, sorafenib induced a time- and dose-dependent growth-inhibitory effect through S-phase cell cycle arrest in KRAS wild-type and KRAS-mutated CRC cells. In HRT-18 cells, two human miRNAs (hsa-miR-597 and hsa-miR-720) and two small RNAs (SNORD 13 and hsa-miR-3182) were identified as specifically sorafenib-induced. In Caco-2 cells, nine human miRNAs (hsa-miR-3142, hsa-miR-20a, hsa-miR-4301, hsa-miR-1290, hsa-miR-4286, hsa-miR-3182, hsa-miR-3142, hsa-miR-1246 and hsa-miR-720) were identified to be differentially regulated post sorafenib treatment. In conclusion, we confirmed sorafenib as a potential anti-neoplastic treatment strategy for CRC cells by demonstrating a growth-inhibitory and cell cycle-arresting effect of this drug. Changes in the miRNome indicate that some specific miRNAs might be relevant as indicators for sorafenib response, drug resistance and potential targets for combinatorial miRNA-based drug strategies.

  6. Upregulation of Na+ transporter abundances in response to chronic thiazide or loop diuretic treatment in rats.

    PubMed

    Na, Ki Young; Oh, Yoon Kyu; Han, Jin Suk; Joo, Kwon Wook; Lee, Jung Sang; Earm, Jae-Ho; Knepper, Mark A; Kim, Gheun-Ho

    2003-01-01

    Furosemide and hydrochlorothiazide (HCTZ) exert their diuretic actions by binding to apical Na(+) transporters, viz., the Na(+)-K(+)-2Cl(-) cotransporter in the thick ascending limb and the Na(+)-Cl(-) cotransporter in the distal convoluted tubule, respectively. We carried out semiquantitative immunoblotting and immunohistochemistry of rat kidneys to investigate whether chronic administration of furosemide or HCTZ is associated with compensatory changes in the abundance of Na(+) transporters downstream from the primary site of action. Osmotic minipumps were implanted into Sprague-Dawley rats to deliver furosemide (12 mg/day) or HCTZ (3.75 mg/day) for 7 days. To prevent volume depletion, all animals were offered tap water and a solution containing 0.8% NaCl and 0.1% KCl as drinking fluid. The diuretic/natriuretic response was quantified in response to both agents by using quantitative urine collections. Semiquantitative immunoblotting revealed that the abundances of thick ascending limb Na(+)-K(+)-2Cl(-) cotransporter and all three subunits of the epithelial Na(+) channel (ENaC) were increased by furosemide infusion. HCTZ infusion increased the abundances of thiazide-sensitive Na(+)-Cl(-) cotransporter and beta-ENaC in the cortex and beta- and gamma-ENaC in the outer medulla. Consistent with these results, beta-ENaC immunohistochemistry showed a remarkable increase in immunoreactivity in the principal cells of collecting ducts with either diuretic treatment. These increases in the abundance of Na(+) transporters in response to chronic diuretic treatment may account for the generation of diuretic tolerance associated with long-term diuretic use.

  7. Some aspects of salinity responses in peppermint (Mentha × piperita L.) to NaCl treatment.

    PubMed

    Li, Zhe; Yang, Hetong; Wu, Xiaoqing; Guo, Kai; Li, Jishun

    2015-05-01

    Salinity is a major stress that adversely affects plant growth and crop production. Understanding the cellular responses and molecular mechanisms by which plants perceive and adopt salinity stress is of fundamental importance. In this work, some of the cellular signaling events including cell death, reactive oxygen species (ROS) generation, and the behaviors of organelles were analyzed in a salt-tolerant species (Keyuan-1) of peppermint (Mentha × piperita L.) under NaCl treatment. Our results showed that 200 mM NaCl treatment elicited a distinct progress of cell death with chromatin condensation and caspase-3-like activation and a dramatic burst of ROS which was required for the execution of cell death. The major ROS accumulation occurred in the mitochondria and chloroplasts, which were the sources of ROS production under NaCl stress. Moreover, mitochondrial activity and photosynthetic capacity also exhibited the obvious decrease in the ROS-dependent manner under 200 mM NaCl stress. Furthermore, the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), and dehydroascorbate reductase (DHAR) as well as the contents of ascorbate and glutathione changed in the concentration-dependent manner under NaCl stress. Altogether, our data showed the execution of programmed cell death (PCD), the ROS dynamics, and the behaviors of organelles especially mitochondria and chloroplasts in the cellular responses of peppermint to NaCl stress which can be used for the tolerance screening, and contributed to the understanding of the cellular responses and molecular mechanisms of peppermint to salinity stress, providing the theoretic basis for the further development and utilization of peppermint in saline areas.

  8. Cognitive style, alprazolam plasma levels, and treatment response in panic disorder.

    PubMed

    Uhlenhuth, E H; Starcevic, Vladan; Qualls, Clifford; Antal, Edward J; Matuzas, William; Javaid, Javaid I; Barnhill, Jamie

    2008-01-01

    This study investigated an anxiety-prone cognitive style (measured by the Anxious Thoughts and Tendencies Questionnaire, AT&T) as a predictor of the acute response to increasing alprazolam plasma levels in panic disorder. Panic disorder patients (n=26) were treated with escalating doses of alprazolam for 4 weeks, then a fixed dose of 1 mg four times a day for 4 weeks. At 0, 1, 2, 3, 4, 6, and 8 weeks, trough alprazolam plasma levels; clinical, self-report, and performance measures; and vital signs were assessed. Panic attack data were from daily diaries. The repeated response measures were analyzed in relation to alprazolam plasma levels using SAS GENMOD, with patients classified as high or low on the baseline AT&T. Panic attacks, anticipatory anxiety, fear, avoidance, overall agoraphobia, the Hamilton Anxiety Rating Scale, and clinicians' global ratings improved with increasing alprazolam plasma levels. Hopkins Symptom Checklist-90 Anger-Hostility; Profile of Mood States Vigor, Confusion, and Friendliness; and speed and accuracy of performance worsened. Patients with high AT&T scores were worse throughout the study on situational panics, fear, avoidance, overall agoraphobia, the Hamilton Anxiety Rating Scale, the Hamilton Rating Scale for Depression, and Clinical Global Improvement; most Hopkins Symptom Checklist-90 clusters; Profile of Mood States Anxiety, Depression, and Confusion; and Continuous Performance Task omissions. We conclude that in panic disorder: (1) alprazolam has a broad spectrum of clinical activity related to plasma levels in individual patients; (2) sedation, disinhibition, and performance deficits may persist for at least a month after dose escalation ends; (3) marked anxiety-prone cognitions predict more symptoms throughout treatment, but do not modify the response to alprazolam and therefore should not influence the choice of alprazolam as treatment.

  9. Influence of Study Design on Treatment Response in Anxiety Disorder Clinical Trials

    PubMed Central

    Rutherford, Bret R; Bailey, Veronika S.; Schneier, Franklin R.; Pott, Emily; Brown, Patrick J.; Roose, Steven P.

    2016-01-01

    Objective The influence of study design variables and publication year on response to medication and placebo was investigated in clinical trials for social anxiety disorder (SAD), generalized anxiety disorder (GAD), and panic disorder (PD). Method Hierarchical linear modeling determined whether publication year, treatment assignment (medication vs. placebo), study type (placebo-controlled or active comparator), study duration, and the number of study visits affected the mean change associated with medication and placebo. Results In the 66 trials examined, the change associated with both medication and placebo increased over time (t = 4.23, df = 39, P < .001), but average drug–placebo differences decreased over time (t = −2.04, df = 46, P = .047). More severe baseline illness was associated with greater drug–placebo differences for serotonin norepinephrine reuptake inhibitors (SNRIs, t = 3.46, df = 106, P = .001) and selective serotonin reuptake inhibitors (SSRI, t = 10.37, df = 106, P < .001). Improvement with medication was significantly greater in active-comparator studies compared to placebo-controlled trials (t = 3.41, df = 39, P = .002). A greater number of study visits was associated with greater symptom improvement in PD trials relative to SAD (t = 2.83, df = 39, P = .008) and GAD (t = 2.16, df = 39, P= .037). Conclusions Placebo response is substantial in SAD, GAD, and PD trials, and its rise over time has been associated with diminished drug–placebo differences. Study design features that influence treatment response in anxiety disorder trials include patient expectancy, frequency of follow-up visits, and baseline illness severity. PMID:26437267

  10. Transient In Vivo Resistance Mechanisms of Burkholderia pseudomallei to Ceftazidime and Molecular Markers for Monitoring Treatment Response

    PubMed Central

    Cummings, Jason E.; Slayden, Richard A.

    2017-01-01

    Much is known about the mode of action of drugs and resistance mechanisms under laboratory growth conditions, but research on the bacterial transcriptional response to drug pressure in vivo or efficacious mode of action and transient resistance mechanisms of clinically employed drugs is limited. Accordingly, to assess active alternative metabolism and transient resistance mechanisms, and identify molecular markers of treatment response, the in vivo transcriptional response of Burkholderia pseudomallei 1026b to treatment with ceftazidime in infected lungs was compared to the in vitro bacterial response in the presence of drug. There were 1,688 transcriptionally active bacterial genes identified that were unique to in vivo treated conditions. Of the in vivo transcriptionally active bacterial genes, 591 (9.4% coding capacity) genes were differentially expressed by ceftazidime treatment. In contrast, only 186 genes (2.7% coding capacity) were differentially responsive to ceftazidime treatment under in vitro culturing conditions. Within the genes identified were alternative PBP proteins that may compensate for target inactivation and transient resistance mechanisms, such as β-lactamses that may influence the potency of ceftazidime. This disparate observation is consistent with the thought that the host environment significantly alters the bacterial metabolic response to drug exposure compared to the response observed under in vitro growth. Notably, this study revealed 184 bacterial genes and ORFs that were unique to in vivo ceftazidime treatment and thus provide candidate molecular markers for treatment response. This is the first report of the unique transcriptional response of B. pseudomallei from host tissues in an animal model of infection and elucidates the in vivo metabolic vulnerabilities, which is important in terms of defining the efficacious mode of action and transient resistance mechanisms of a frontline meliodosis chemotherapeutic, and biomarkers for

  11. Substance use and response to psychiatric treatment in methadone-treated outpatients with comorbid psychiatric disorder

    PubMed Central

    Kidorf, Michael; King, Van L.; Peirce, Jessica; Gandotra, Neeraj; Ghazarian, Sharon; Brooner, Robert K.

    2014-01-01

    The psychiatric care of opioid users receiving agonist therapies is often complicated by high rates of illicit drug use (Brooner et al., 2013). The present study evaluates if illicit drug use (i.e., opioids, cocaine, sedatives) detected at the start of psychiatric care affects treatment response. Methadone maintenance patients (n = 125) with at least one current psychiatric disorder completed a 3-month randomized clinical trial evaluating the efficacy of financial incentives on attendance to on-site integrated substance abuse and psychiatric services (Kidorf et al., 2013). The present study re-analyzes the data set by grouping participants into one of two conditions based on the 4-week baseline observation: 1) no illicit drug use (Baseline Negative; n = 50), or 2) any illicit drug use (Baseline Positive; n = 75). All participants received a similar schedule of psychiatric services, and had good access to prescribed psychiatric medications. The Global Severity Index (GSI) of the Hopkins Symptom Checklist-Revised was administered monthly to evaluate changes in psychiatric distress. Results showed that while both conditions evidenced similar utilization of on-site psychiatric services, Baseline Negative participants remained in treatment somewhat longer (80.7 vs. 74.8 days, p = .04) and demonstrated greater reductions in GSI scores than Baseline Positive participants at Month 3 (p = .004). These results have implications for interpreting previous studies that have shown inconsistent efficacy of pharmacotherapy and other psychiatric treatments, and for providing clinical care for patients with co-occurring substance use and psychiatric disorders. PMID:25468006

  12. NANOG Expression as a Responsive Biomarker during Treatment with Hedgehog Signal Inhibitor in Acute Myeloid Leukemia

    PubMed Central

    Kakiuchi, Seiji; Minami, Yosuke; Miyata, Yoshiharu; Mizutani, Yu; Goto, Hideaki; Kawamoto, Shinichiro; Yakushijin, Kimikazu; Kurata, Keiji; Matsuoka, Hiroshi; Minami, Hironobu

    2017-01-01

    Aberrant activation of the Hedgehog (Hh) signaling pathway is involved in the maintenance of leukemic stem cell (LSCs) populations. PF-0444913 (PF-913) is a novel inhibitor that selectively targets Smoothened (SMO), which regulates the Hh pathway. Treatment with PF-913 has shown promising results in an early phase study of acute myeloid leukemia (AML). However, a detailed mode of action for PF-913 and relevant biomarkers remain to be elucidated. In this study, we examined bone marrow samples derived from AML patients under PF-913 monotherapy. Gene set enrichment analysis (GSEA) revealed that PF-913 treatment affected the self-renewal signature and cell-cycle regulation associated with LSC-like properties. We then focused on the expression of a pluripotency factor, NANOG, because previous reports showed that a downstream effector in the Hh pathway, GLI, directly binds to the NANOG promoter and that the GLI-NANOG axis promotes stemness and growth in several cancers. In this study, we found that a change in NANOG transcripts was closely associated with GLI-target genes and NANOG transcripts can be a responsive biomarker during PF-913 therapy. Additionally, the treatment of AML with PF-913 holds promise, possibly through inducing quiescent leukemia stem cells toward cell cycling. PMID:28245563

  13. The Heart of Change: Acceptance and Intimacy Mediate Treatment Response in a Brief Couples Intervention

    PubMed Central

    Hawrilenko, Matt; Gray, Tatiana D.; Cordova, James V.

    2015-01-01

    This study examined mediators of a brief couples intervention. Intimate safety, acceptance, and activation were examined in two roles: their contribution to marital satisfaction gains in the first two weeks after treatment (contemporaneous effects), and how early changes in the mediators influenced longer-term changes in marital satisfaction over two years of follow-up (lagged effects). Married couples (N = 215) were randomized to intervention or wait-list control and followed for two years. Latent change score models were used to examine contemporaneous and time-lagged mediation. A booster intervention in the second year was used for a replication study. Changes in intimate safety and acceptance were uniquely associated with contemporaneous treatment effects on relationship satisfaction in year one, but only acceptance was uniquely associated with contemporaneous effects in year two. With respect to lagged effects, early changes in acceptance partially mediated later changes in marital satisfaction in year one, whereas the same effect for intimate safety was marginally significant. These lagged paths were moderate in size and indirect effects were small. No lagged effects were significant in year two. Changes in activation were not significant as either a contemporaneous or lagged predictor of changes in relationship satisfaction. This study found moderate support for acceptance and more limited support for intimate safety as mediators of short and long-term treatment response, suggesting that these processes play an important role in sustaining marital health. PMID:26524618

  14. Effect of chronic antidepressant treatment on responses to apomorphine in selectively bred rat strains.

    PubMed

    Pucilowski, O; Overstreet, D H

    1993-01-01

    The purpose of this study was to verify the dopamine-sensitizing behavioral effect of chronic antidepressant treatment in two selectively bred rat strains: the hypercholinergic Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL). Two antidepressants, desipramine HCl (DMI) and sertraline HCl, were injected IP in separate groups of FSL and FRL rats in a dose of 16.5 mumol/kg twice daily for 16 days. Twenty-four hours after withdrawal, locomotor and hypothermic responses to 0.2 mg/kg of apomorphine, SC, were examined. Attenuation of the effect of apomorphine was observed in the open field: FRLs withdrawn from sertraline were significantly less mobile than control FRLs, and the same trend was found in FSL rats. Chronic DMI resulted in similar changes in the locomotor activity. Sertraline treatment decreased apomorphine-induced hypothermia by almost half in FSLs, whereas slight hyperthermia was induced in FRL rats instead. The present results suggest that in these selectively bred strains, a serotonergic antidepressant such as sertraline may have sensitized dopaminergic autoreceptors and/or desensitized postsynaptic receptors. Apomorphine-induced hypothermia could be mediated by serotonergic neuron function that may have been altered by chronic sertraline but not DMI treatment.

  15. Amino Acid PET – An Imaging Option to Identify Treatment Response, Posttherapeutic Effects, and Tumor Recurrence?

    PubMed Central

    Galldiks, Norbert; Langen, Karl-Josef

    2016-01-01

    Routine diagnostics and treatment monitoring in patients with primary and secondary brain tumors is usually based on contrast-enhanced standard MRI. However, the capacity of standard MRI to differentiate neoplastic tissue from non-specific posttreatment effects may be limited particularly after therapeutic interventions such as radio- and/or chemotherapy or newer treatment options, e.g., immune therapy. Metabolic imaging using PET may provide relevant additional information on tumor metabolism, which allows a more accurate diagnosis especially in clinically equivocal situations, particularly when radiolabeled amino acids are used. Amino acid PET allows a sensitive monitoring of a response to various treatment options, the early detection of tumor recurrence, and an improved differentiation of tumor recurrence from posttherapeutic effects. In the past, this method had only limited availability due to the use of PET tracers with a short half-life, e.g., C-11. In recent years, however, novel amino acid PET tracers labeled with positron emitters with a longer half-life (F-18) have been developed and clinically validated, which allow a more efficient and cost-effective application. These developments and the well-documented diagnostic performance of PET using radiolabeled amino acids suggest that its application continues to spread and that this technique may be available as a routine diagnostic tool for several indications in the field of neuro-oncology. PMID:27516754

  16. Energy loss of ions in a magnetized plasma: conformity between linear response and binary collision treatments.

    PubMed

    Nersisyan, H B; Zwicknagel, G; Toepffer, C

    2003-02-01

    The energy loss of a heavy ion moving in a magnetized electron plasma is considered within the linear response (LR) and binary collision (BC) treatments with the purpose to look for a connection between these two models. These two complementary approaches yield close results if no magnetic field is present, but there develop discrepancies with growing magnetic field at ion velocities that are lower than, or comparable with, the thermal velocity of the electrons. We show that this is a peculiarity of the Coulomb interaction which requires cutoff procedures to account for its singularity at the origin and its infinite range. The cutoff procedures in the LR and BC treatments are different as the order of integrations in velocity and in ordinary (Fourier) spaces is reversed in both treatments. While BC involves a velocity average of Coulomb logarithms, there appear in LR Coulomb logarithms of velocity averaged cutoffs. The discrepancies between LR and BC vanish, except for small contributions of collective modes, for smoothened potentials that require no cutoffs. This is shown explicitly with the help of an improved BC in which the velocity transfer is treated up to second order in the interaction in Fourier space.

  17. Difference in physiological responses to sound stimulation in subjects with and without fear of dental treatments.

    PubMed

    Kudo, Takumu; Mishima, Riho; Yamamura, Kensuke; Mostafeezur, Rahman; Zakir, Hossain Md; Kurose, Masayuki; Yamada, Yoshiaki

    2008-07-01

    The effects of sound generated by an ultrasonic dental scaler and a dental turbine on heart rate, systolic and diastolic blood pressure, and hemodynamic changes in the frontal cortex were measured and compared with those of pure tone stimulation in 17 young volunteers. Near-infrared spectroscopy and the Finapres technique were used to measure hemodynamic and cardiovascular responses, respectively. The dental sound changed the various physiological parameters. To determine if this change was related to participants' previous experiences with dental treatment, participants were divided into two groups: those who had a previous unpleasant experience with dental treatment and those who had not. Participants with previous unpleasant dental experiences showed a significant decrease in cerebral blood flow. Participants who had not had an unpleasant dental experience did not show significant changes in cerebral blood flow. Thus, although sounds associated with dental treatment may reduce cerebral blood flow, this effect may depend on the dental experiences of the patient. It is recommended that dentists treat patients gently and with empathy to promote a friendly image of dentistry.

  18. H2 antagonists in the treatment of reflux oesophagitis: can physiological studies predict the response?

    PubMed Central

    Robertson, D A; Aldersley, M A; Shepherd, H; Lloyd, R S; Smith, C L

    1987-01-01

    Ambulatory oesophageal pH, oesophageal manometry and fasting serum gastrin concentrations were carried out on 28 patients with reflux oesophagitis, before and during treatment with ranitidine 300 mg bd. Fourteen patients healed endoscopically at six weeks (group A) and 14 had residual oesophagitis (group B). Group A were characterised by a lower serum gastrin concentration before treatment (4.52 pmol/l; 2.4-10: mean and range) than group B (11.1 pmol/l; 3.5-21: p less than 0.05) and showed a marked reduction in acid reflux on treatment to near normal values. Mean per cent time below pH4 fell from 14.9 to 4.2 in group A (p less than 0.05) but was not affected in group B (14.2-15.6, not significant). Abnormal oesophageal motility was found in 13 patients from each group. This did not inhibit the response to ranitidine, and was not improved by healing of oesophagitis. PMID:3666562

  19. Predictors of response to a behavioral treatment in patients with chronic gastric motility disorders

    NASA Technical Reports Server (NTRS)

    Rashed, Hani; Cutts, Teresa; Abell, Thomas; Cowings, Patricia; Toscano, William; El-Gammal, Ahmed; Adl, Dima

    2002-01-01

    Chronic gastric motility disorders have proven intractable to most traditional therapies. Twenty-six patients with chronic nausea and vomiting were treated with a behavioral technique, autonomic training (AT) with directed imagery (verbal instructions), to help facilitate physiological control. After treatment, gastrointestinal symptoms decreased by >30% in 58% of the treated patients. We compared those improved patients to the 43% who did not improve significantly. No significant differences existed in baseline symptoms and autonomic measures between both groups. However, baseline measures of gastric emptying and autonomic function predicted treatment outcome. Patients who improved manifested mild to moderate delay in baseline gastric emptying measures. The percent of liquid gastric emptying at 60 mins and the sympathetic adrenergic measure of percent of change in the foot cutaneous blood flow in response to cold stress test predicted improvement in AT outcome, with clinical diagnostic values of 77% and 71%, respectively. We conclude that AT treatment can be efficacious in some patients with impaired gastric emptying and adrenergic dysfunction. More work is warranted to compare biofeedback therapy with gastric motility patients and controls in population-based studies.

  20. Defining normoxia, physoxia and hypoxia in tumours—implications for treatment response

    PubMed Central

    2014-01-01

    Tumour hypoxia is increasingly recognized as a major deleterious factor in cancer therapies, as it compromises treatment and drives malignant progression. This review seeks to clarify the oxygen levels that are pertinent to this issue. It is argued that normoxia (20% oxygen) is an extremely poor comparator for “physoxia”, i.e. the much lower levels of oxygen universally found in normal tissues, which averages about 5% oxygen, and ranges from about 3% to 7.4%. Importantly, it should be recognized that the median oxygenation in untreated tumours is significantly much lower, falling between approximately 0.3% and 4.2% oxygen, with most tumours exhibiting median oxygen levels <2%. This is partially dependent on the tissue of origin, and it is notable that many prostate and pancreatic tumours are profoundly hypoxic. In addition, therapy can induce even further, often unrecognized, changes in tumour oxygenation that may vary longitudinally, increasing or decreasing during treatment in ways that are not always predictable. Studies that fail to take cognizance of the actual physiological levels of oxygen in tissues (approximately 5%) and tumours (approximately 1%) may fail to identify the real circumstances driving tumour response to treatment and/or malignant progression. This can be of particular importance in genetic studies in vitro when comparison to human tumours is required. PMID:24588669

  1. Detection and characterization of differences in plasma corticoid response to treatments.

    PubMed

    Adkinson, R W; Thatcher, W W; Wilcox, C J; Gwazdauskas, F C; Head, H H

    1976-04-01

    Ten experiments involving 3013 observations and 103 animals were studied to characterize variation associated with bovine plasma corticoid concentrations (ng/ml). Total corticoids, corticosterone, or cortisol were measured by competitve protein binding assay. Animals were noncystic or cystic, and measurements were made to establish basal concentrations or to estimate response to stimulation by adrenocorticotrophic hormone injection. Data were analyzed by least squares with the nested model: treatment regimen, animal in treatment, sample in animal in treatment, and sampling time to the highest order of regression (up to seventh) which was statistically significant (P less than .05). Estimates of error variances ranged from .31 for basal cortisol in cystic animals to 233.27 for total corticoids in noncystic, stimulated animals. Coefficients of variation among experiments ranged from 33 to 87% with mean 61%. In most analyses, estimates of experimental error were large indicating need for careful attention to experimental design to insure efficient least-cost experimentation. Use of the power function for nested analysis of variance to accomplish this is demonstrated.

  2. Hybridization in endophyte symbionts alters host response to moisture and nutrient treatments.

    PubMed

    Hamilton, Cyd E; Dowling, Thomas E; Faeth, Stanley H

    2010-05-01

    When a host organism is infected by a symbiont, the resulting symbiotum has a phenotype distinct from uninfected hosts. Genotypic interactions between the partners may increase phenotypic variation of the host at the population level. Neotyphodium is an asexual, vertically transmitted endophytic symbiont of grasses often existing in hybrid form. Hybridization in Neotyphodium rapidly increases the symbiotum's genomic content and is likely to increase the phenotypic variation of the host. This phenotypic variation is predicted to enhance host performance, especially in stressful environments. We tested this hypothesis by comparing the growth, survival, and resource allocation of hybrid and nonhybrid infected host plants exposed to controlled variation in soil moisture and nutrients. Infection by a hybrid endophyte did not fit our predictions of comparatively higher root and total biomass production under low moisture/low nutrient treatments. Regardless of whether the host was infected by a hybrid or nonhybrid endophyte, both produced significantly higher root/total biomass when both nutrient and moisture were high compared to limited nutrient/moisture treatments. However, infection by hybrid Neotyphodium did result in significantly higher total biomass and host survival compared to nonhybrid infected hosts, regardless of treatment. Endophyte hybridization alters host strategies in response to stress by increasing survival in depauperate habitats and thus, potentially increasing the relative long-term host fitness.

  3. Patient Violence Towards Counselors in Substance Use Disorder Treatment Programs: Prevalence, Predictors, and Responses

    PubMed Central

    Bride, Brian E.; Choi, Y. Joon; Olin, Ilana W.; Roman, Paul M.

    2015-01-01

    Workplace violence disproportionately impacts healthcare and social service providers. Given that substance use and abuse are documented risk factors for the perpetration of violence, SUD treatment personnel are at risk for patient-initiated violence. However, little research has addressed SUD treatment settings. Using data nationally representative of the U. S., the present study explores SUD counselors’ experiences of violent behaviors perpetrated by patients. More than half (53%) of counselors personally experienced violence, 44% witnessed violence, and 61% had knowledge of violence directed at a colleague. Counselors reported that exposure to violence led to an increased concern for personal safety (29%), impacted their treatment of patients (15%), and impaired job performance (12%). In terms of organizational responses to patient violence, 70% of organizations increased training on de-escalation of violent situations and 58% increased security measures. Exposure to verbal assault was associated with age, minority, tenure, recovery status, 12-step philosophy, training in MI/MET, and higher caseloads of patients with co-occurring disorders. Exposure to physical threats was associated with age gender, minority, tenure, recovery status, and higher caseloads of patients with co-occurring disorders. Exposure to physical assault was associated with age, gender, and sample. Implications of these findings for organizations and individuals are discussed. PMID:26025921

  4. Interleukin-28b CC genotype predicts early treatment response and CT/TT genotypes predicts non-response in patients infected with HCV genotype 3.

    PubMed

    Gupta, Abhishak Chander; Trehanpati, Nirupma; Sukriti, Sukriti; Hissar, Syed; Midha, Vandana; Sood, Ajit; Sarin, Shiv K

    2014-04-01

    Response to antiviral therapy for hepatitis C virus (HCV) depends upon the genotype and host immune response. IL28b gene mutations have been shown to modulate host antiviral immune response against genotype 1. However, the predictive value of IL28b polymorphism in genotype 3 HCV patients is largely unknown. The association of IL28b polymorphism with virological response was studied in 356 patients with genotype 3 chronic HCV undergoing treatment with peg-interferon and ribavirin and was compared with matched controls. IL28b genotyping followed by DNA sequencing was performed to identify the CC, CT, or TT genotypes. Two log reduction of HCV RNA at Day 7 (Quick Viral Response, QVR) and HCV RNA negativity at Day 28 (Rapid Viral Response, RVR) were analyzed with CC and non-CC genotypes in addition to other predictors of response. The associations of alleles with the response patterns were predicted. Sustained viral response was seen in 250 (70.2%) patients and the IL28b genotype CC/CT/TT distribution was 61.1%; 30.5%; and 8.4%, respectively. The non-CC genotypes were significantly higher in non-responders when compared to responders (67.6% vs. 38.9%, P < 0.001). Interestingly, the rapid viral response in responders was observed in 72.7% with the CC genotype and in 27.2% with the non-CC genotype (P < 0.001). Multivariate analysis showed CC genotype as an independent factor predicting the sustained viral response in patients infected with HCV genotype 3. In conclusion, the IL28b CT/TT genotype strongly correlates with treatment non-response in patients infected with HCV genotype 3 and CC genotype of IL28b is associated with higher quick viral response.

  5. The systemic immune response to trauma: an overview of pathophysiology and treatment.

    PubMed

    Lord, Janet M; Midwinter, Mark J; Chen, Yen-Fu; Belli, Antonio; Brohi, Karim; Kovacs, Elizabeth J; Koenderman, Leo; Kubes, Paul; Lilford, Richard J

    2014-10-18

    Improvements in the control of haemorrhage after trauma have resulted in the survival of many people who would otherwise have died from the initial loss of blood. However, the danger is not over once bleeding has been arrested and blood pressure restored. Two-thirds of patients who die following major trauma now do so as a result of causes other than exsanguination. Trauma evokes a systemic reaction that includes an acute, non-specific, immune response associated, paradoxically, with reduced resistance to infection. The result is damage to multiple organs caused by the initial cascade of inflammation aggravated by subsequent sepsis to which the body has become susceptible. This Series examines the biological mechanisms and clinical implications of the cascade of events caused by large-scale trauma that leads to multiorgan failure and death, despite the stemming of blood loss. Furthermore, the stark and robust epidemiological finding--namely, that age has a profound influence on the chances of surviving trauma irrespective of the nature and severity of the injury--will be explored. Advances in our understanding of the inflammatory response to trauma, the impact of ageing on this response, and how this information has led to new and emerging treatments aimed at combating immune dysregulation and reduced immunity after injury will also be discussed.

  6. The systemic immune response to trauma: an overview of pathophysiology and treatment

    PubMed Central

    Lord, Janet M; Midwinter, Mark J; Chen, Yen-Fu; Belli, Antonio; Brohi, Karim; Kovacs, Elizabeth J; Koenderman, Leo; Kubes, Paul; Lilford, Richard J

    2016-01-01

    Improvements in the control of haemorrhage after trauma have resulted in survival of many people who would otherwise have died from the initial loss of blood. However, the danger is not over once bleeding has been arrested and blood pressure restored. Two-thirds of patients who die following major trauma now do so as a result of causes other than exsanguination. Trauma evokes a systemic reaction that include an acute, non-specific, immune response associated, paradoxically, with reduced resistance to infection. The result is damage to multiple organs caused by the initial cascade of inflammation aggravated by subsequent sepsis to which the body has become susceptible. This Series examines the biological mechanisms and clinical implications of the cascade of events caused by large-scale trauma that leads to multiorgan failure and death, despite the stemming of blood loss. Furthermore, the stark and robust epidemiological finding – namely, that age has a profound influence on the chances of surviving trauma irrespective of the nature and severity of the injury – will be explored. Advances in our understanding of the inflammatory response to trauma, the impact of ageing on this response, and how this information has led to new and emerging treatments aimed at combating immune dysregulation and reduced immunity after injury will also be discussed. PMID:25390327

  7. Computational drug treatment simulations on projections of dysregulated protein networks derived from the myelodysplastic mutanome match clinical response in patients.

    PubMed

    Drusbosky, Leylah; Medina, Cindy; Martuscello, Regina; Hawkins, Kimberly E; Chang, Myron; Lamba, Jatinder K; Vali, Shireen; Kumar, Ansu; Singh, Neeraj Kumar; Abbasi, Taher; Sekeres, Mikkael A; Mallo, Mar; Sole, Francesc; Bejar, Rafael; Cogle, Christopher R

    2017-01-01

    Although the majority of MDS patients fail to achieve clinical improvement to approved therapies, some patients benefit from treatment. Predicting patient response prior to therapy would improve treatment effectiveness, avoid treatment-related adverse events and reduce healthcare costs. Three separate cohorts of MDS patients were used to simulate drug response to lenalidomide alone, hypomethylating agent (HMA) alone, or HMA plus lenalidomide. Utilizing a computational biology program, genomic abnormalities in each patient were used to create an intracellular pathway map that was then used to screen for drug response. In the lenalidomide treated cohort, computer modeling correctly matched clinical responses in 37/46 patients (80%). In the second cohort, 15 HMA patients were modeled and correctly matched to responses in 12 (80%). In the third cohort, computer modeling correctly matched responses in 10/10 patients (100%). This computational biology network approach identified GGH overexpression as a potential resistance factor to HMA treatment and paradoxical activation of beta-catenin (through Csnk1a1 inhibition) as a resistance factor to lenalidomide treatment. We demonstrate that a computational technology is able to map the complexity of the MDS mutanome to simulate and predict drug response. This tool can improve understanding of MDS biology and mechanisms of drug sensitivity and resistance.

  8. Examining the Relationship Between Parental Anxiety and Treatment Response in Children and Adolescents with Autism Spectrum Disorder and Anxiety.

    PubMed

    Reaven, Judy; Washington, Lindsay; Moody, Eric J; Stern, Jessica A; Hepburn, Susan L; Blakeley-Smith, Audrey

    2015-08-01

    In response to the high co-occurrence of anxiety symptoms in youth with autism spectrum disorder (ASD), several interventions have been developed for this population. In spite of promising findings, some youth with ASD respond only minimally to such interventions. To understand potential factors that may impact treatment response, the current study explores the role of parental anxiety in youth treatment outcome. Thirty-one youth with ASD, ages 7-18, and their parents participated in the study. Parents completed the State/Trait Anxiety Inventory pre- and post-treatment. Contrary to previous research, there was no correlation between parental anxiety and youth anxiety at baseline or post-treatment. However, parental trait anxiety significantly decreased from pre- to post-treatment for parents of treatment responders. The findings are consistent with previous research and suggest a youth-to-parent influence.

  9. Predictors and Moderators of Response to Cognitive Behavioral Therapy and Medication for the Treatment of Binge Eating Disorder

    ERIC Educational Resources Information Center

    Grilo, Carlos M.; Masheb, Robin M.; Crosby, Ross D.

    2012-01-01

    Objective: To examine predictors and moderators of response to cognitive behavioral therapy (CBT) and medication treatments for binge-eating disorder (BED). Method: 108 BED patients in a randomized double-blind placebo-controlled trial testing CBT and fluoxetine treatments were assessed prior, throughout, and posttreatment. Demographic factors,…

  10. Stream periphyton responses to mesocosm treatments of equal specific conductance but different major ion contents measured with in situ fluorometry

    EPA Science Inventory

    A stream mesocosm experiment was designed to compare biotic responses among streams exposed to an equal excess specific conductivity target of 850 µS/cm relative to a control that was set for 200 µS/cm and three treatments comprised of different major ion contents. Each treatment...

  11. Biologically relevant 3D tumor arrays: treatment response and the importance of stromal partners

    NASA Astrophysics Data System (ADS)

    Rizvi, Imran; Celli, Jonathan P.; Xu, Feng; Evans, Conor L.; Abu-Yousif, Adnan O.; Muzikansky, Alona; Elrington, Stefan A.; Pogue, Brian W.; Finkelstein, Dianne M.; Demirci, Utkan; Hasan, Tayyaba

    2011-02-01

    The development and translational potential of therapeutic strategies for cancer is limited, in part, by a lack of biological models that capture important aspects of tumor growth and treatment response. It is also becoming increasingly evident that no single treatment will be curative for this complex disease. Rationally-designed combination regimens that impact multiple targets provide the best hope of significantly improving clinical outcomes for cancer patients. Rapidly identifying treatments that cooperatively enhance treatment efficacy from the vast library of candidate interventions is not feasible, however, with current systems. There is a vital, unmet need to create cell-based research platforms that more accurately mimic the complex biology of human tumors than monolayer cultures, while providing the ability to screen therapeutic combinations more rapidly than animal models. We have developed a highly reproducible in vitro three-dimensional (3D) tumor model for micrometastatic ovarian cancer (OvCa), which in conjunction with quantitative image analysis routines to batch-process large datasets, serves as a high throughput reporter to screen rationally-designed combination regimens. We use this system to assess mechanism-based combination regimens with photodynamic therapy (PDT), which sensitizes OvCa to chemo and biologic agents, and has shown promise in clinic trials. We show that PDT synergistically enhances carboplatin efficacy in a sequence dependent manner. In printed heterocellular cultures we demonstrate that proximity of fibroblasts enhances 3D tumor growth and investigate co-cultures with endothelial cells. The principles described here could inform the design and evaluation of mechanism-based therapeutic options for a broad spectrum of metastatic solid tumors.

  12. Interrelated role of cigarette smoking, oxidative stress, and immune response in COPD and corresponding treatments.

    PubMed

    Zuo, Li; He, Feng; Sergakis, Georgianna G; Koozehchian, Majid S; Stimpfl, Julia N; Rong, Yi; Diaz, Philip T; Best, Thomas M

    2014-08-01

    Cigarette smoking (CS) can impact the immune system and induce pulmonary disorders such as chronic obstructive pulmonary disease (COPD), which is currently the fourth leading cause of chronic morbidity and mortality worldwide. Accordingly, the most significant risk factor associated with COPD is exposure to cigarette smoke. The purpose of the present study is to provide an updated overview of the literature regarding the effect of CS on the immune system and lungs, the mechanism of CS-induced COPD and oxidative stress, as well as the available and potential treatment options for CS-induced COPD. An extensive literature search was conducted on the PubMed/Medline databases to review current COPD treatment research, available in the English language, dating from 1976 to 2014. Studies have investigated the mechanism by which CS elicits detrimental effects on the immune system and pulmonary function through the use of human and animal subjects. A strong relationship among continued tobacco use, oxidative stress, and exacerbation of COPD symptoms is frequently observed in COPD subjects. In addition, therapeutic approaches emphasizing smoking cessation have been developed, incorporating counseling and nicotine replacement therapy. However, the inability to reverse COPD progression establishes the need for improved preventative and therapeutic strategies, such as a combination of intensive smoking cessation treatment and pharmaceutical therapy, focusing on immune homeostasis and redox balance. CS initiates a complex interplay between oxidative stress and the immune response in COPD. Therefore, multiple approaches such as smoking cessation, counseling, and pharmaceutical therapies targeting inflammation and oxidative stress are recommended for COPD treatment.

  13. Biomarkers of alopecia areata disease activity and response to corticosteroid treatment.

    PubMed

    Fuentes-Duculan, Judilyn; Gulati, Nicholas; Bonifacio, Kathleen M; Kunjravia, Norma; Zheng, Xiuzhong; Suárez-Fariñas, Mayte; Shemer, Avner; Guttman-Yassky, Emma; Krueger, James G

    2016-04-01

    Alopecia areata (AA) is a common inflammatory disease targeting the anagen-stage hair follicle. Different cytokines have been implicated in the disease profile, but their pathogenic role is not yet fully determined. We studied biopsies of pretreatment lesional and non-lesional (NL) scalp and post-treatment (intra-lesional steroid injection) lesional scalp of 6 patchy patients with AA using immunohistochemistry and gene expression analysis. Immunohistochemistry showed increases in CD3(+) , CD8(+) T cells, CD11c(+) dendritic cells and CD1a(+) Langerhans cells within and around hair follicles of pretreatment lesional scalp, which decreased upon treatment. qRT-PCR showed in pretreatment lesional scalp (compared to NL) significant increases (P < 0.05) in expression of inflammatory markers (IL-2, IL-2RA, JAK3, IL-15), Th1 (CXCL10 and CXCL9), Th2 (IL-13, CCL17 and CCL18), IL-12/IL-23p40 and IL-32. Among these, we observed significant downregulation with treatment in IL-12/IL-23p40, CCL18 and IL-32. We also observed significant downregulation of several hair keratins in lesional scalp, with significant upregulation of KRT35, KRT75 and KRT86 in post-treatment lesional scalp. This study shows concurrent activation of Th1 and Th2 immune axes as well as IL-23 and IL-32 cytokine pathways in lesional AA scalp and defined a series of response biomarkers to corticosteroid injection. Clinical trials with selective antagonists coupled with cytokine-pathway biomarkers will be necessary to further dissect pathogenic immunity.

  14. Internight sleep variability: its clinical significance and responsiveness to treatment in primary and comorbid insomnia.

    PubMed

    Sánchez-Ortuño, María M; Edinger, Jack D

    2012-10-01

    Although sleep diary and actigraphy data are usually collected daily for 1 or 2 weeks, traditional analytical approaches aggregate these data into mean values. Internight variability of sleep often accompanies insomnia. However, few studies have explored the relevance of this 'construct' in the context of diagnosis, clinical impact, treatment effects and/or whether having 'variable sleep' carries any prognostic significance. We explored these questions by conducting secondary analyses of data from a randomized clinical trial. The sample included primary (PI: n = 40) and comorbid insomnia (CMI: n = 41) sufferers receiving four biweekly sessions of cognitive-behavioural therapy (CBT) or sleep hygiene education. Using the within-subject standard deviations of diary- and actigraphy-derived measures collected for 2-week periods [sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST) and sleep efficiency (SE)], we found that CMI sufferers displayed more variable self-reported SOLs and SEs than PI sufferers. However, higher variability in diary and actigraphy-derived measures was related to poorer sleep quality only within the PI group, as measured by the Pittsburgh Sleep Quality Index (PSQI). Within both groups, the variability of diary-derived measures was reduced after CBT, but the variability of actigraphy-derived measures remained unchanged. Interestingly, the variability of actigraphy measures at baseline was correlated with PSQI scores at 6-month follow-up. Higher SOL variability was associated with worse treatment outcomes within the PI group, whereas higher WASO variability was correlated with better treatment outcomes within the CMI group. Sleep variability differences across insomnia diagnoses, along with their distinctive correlates, suggest that mechanisms underlying the sleep disruption/complaint and treatment response in both patient groups are distinct. Further studies are warranted to support variability as a useful metric in

  15. Age-Stratified Treatment Response Rates in Hospitalized Patients with Clostridium difficile Infection Treated with Metronidazole.

    PubMed

    Pham, Vy P; Luce, Andrea M; Ruppelt, Sara C; Wei, Wenjing; Aitken, Samuel L; Musick, William L; Roux, Ryan K; Garey, Kevin W

    2015-10-01

    Consensus on the optimal treatment of Clostridium difficile infection (CDI) is rapidly changing. Treatment with metronidazole has been associated with increased clinical failure rates; however, the reasons for this are unclear. The purpose of this study was to assess age-related treatment response rates in hospitalized patients with CDI treated with metronidazole. This was a retrospective, multicenter cohort study of hospitalized patients with CDI. Patients were assessed for refractory CDI, defined as persistent diarrhea after 7 days of metronidazole therapy, and stratified by age and clinical characteristics. A total of 242 individuals, aged 60 ± 18 years (Charlson comorbidity index, 3.8 ± 2.4; Horn's index, 1.7 ± 1.0) were included. One hundred twenty-eight patients (53%) had severe CDI. Seventy patients (29%) had refractory CDI, a percentage that increased from 22% to 28% and to 37% for patients aged less than 50 years, for patients from 50 to 70 years, and for patients aged >70 years, respectively (P = 0.05). In multivariate analysis, Horn's index (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.50 to 2.77; P < 0.001), severe CDI (OR, 2.25; 95% CI, 1.15 to 4.41; P = 0.018), and continued use of antibiotics (OR, 2.65; 95% CI, 1.30 to 5.39; P = 0.0072) were identified as significant predictors of refractory CDI. Age was not identified as an independent risk factor for refractory CDI. Therefore, hospitalized elderly patients with CDI treated with metronidazole had increased refractory CDI rates likely due to increased underlying severity of illness, severity of CDI, and concomitant antibiotic use. These results may help identify patients that may benefit from alternative C. difficile treatments other than metronidazole.

  16. Low Doses of Traditional Nanophytomedicines for Clinical Treatment: Manufacturing Processes and Nonlinear Response Patterns.

    PubMed

    Bell, Iris R; Sarter, Barbara; Standish, Leanna J; Banerji, Prasanta; Banerji, Pratip

    2015-06-01

    The purpose of the present paper is to (a) summarize evidence for the nanoparticle nature and biological effects of traditional homeopathically-prepared medicines at low and ultralow doses; (b) provide details of historically-based homeopathic green manufacturing materials and methods, relating them to top-down mechanical attrition and plant-based biosynthetic processes in modern nanotechnology; (c) outline the potential roles of nonlinear dose-responses and dynamical interactions with complex adaptive systems in generating endogenous amplification processes during low dose treatment. Possible mechanisms of low dose effects, for which there is evidence involving nanoparticles and/or homeopathically-manufactured medicines, include hormesis, time-dependent sensitization, and stochastic resonance. All of the proposed mechanisms depend upon endogenous nonlinear amplification processes in the recipient organism in interaction with the salient, albeit weak signal properties of the medicine. Conventional ligand-receptor mechanisms relevant to higher doses are less likely involved. Effects, especially for homeopathically-prepared nanophytomedicines, include bidirectional host state-dependent changes in function. Homeopathic clinicians report successful treatment of serious infections and cancers. Preclinical biological evidence is consistent with such claims. Controlled biological data on homeopathically-prepared medicines indicate modulation of gene expression and biological signaling pathways regulating cell cycles, immune reactions, and central nervous system function from studies on cells, animals, and human subjects. As a 200-year old system of traditional medicine used by millions of people worldwide, homeopathy offers a pulsed low dose treatment strategy and strong safety record to facilitate progress in translational nanomedicine with plants and other natural products. In turn, modern nanotechnology methods can improve homeopathic manufacturing procedures

  17. Examining the Relationship between Parental Anxiety and Treatment Response in Children and Adolescents with Autism Spectrum Disorder and Anxiety

    ERIC Educational Resources Information Center

    Reaven, Judy; Washington, Lindsay; Moody, Eric J.; Stern, Jessica A.; Hepburn, Susan L.; Blakeley-Smith, Audrey

    2015-01-01

    In response to the high co-occurrence of anxiety symptoms in youth with autism spectrum disorder (ASD), several interventions have been developed for this population. In spite of promising findings, some youth with ASD respond only minimally to such interventions. To understand potential factors that may impact treatment response, the current…

  18. Long-term treatment with responsive brain stimulation in adults with refractory partial seizures

    PubMed Central

    Bergey, Gregory K.; Mizrahi, Eli M.; Goldman, Alica; King-Stephens, David; Nair, Dileep; Srinivasan, Shraddha; Jobst, Barbara; Gross, Robert E.; Shields, Donald C.; Barkley, Gregory; Salanova, Vicenta; Olejniczak, Piotr; Cole, Andrew; Cash, Sydney S.; Noe, Katherine; Wharen, Robert; Worrell, Gregory; Murro, Anthony M.; Edwards, Jonathan; Duchowny, Michael; Spencer, David; Smith, Michael; Geller, Eric; Gwinn, Ryder; Skidmore, Christopher; Eisenschenk, Stephan; Berg, Michel; Heck, Christianne; Van Ness, Paul; Fountain, Nathan; Rutecki, Paul; Massey, Andrew; O'Donovan, Cormac; Labar, Douglas; Duckrow, Robert B.; Hirsch, Lawrence J.; Courtney, Tracy; Sun, Felice T.; Seale, Cairn G.

    2015-01-01

    Objective: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. Methods: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. Results: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). Conclusions: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. Classification of evidence: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years. PMID:25616485

  19. Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

    PubMed Central

    Markworth, James F.; Vella, Luke; Lingard, Benjamin S.; Tull, Dedreia L.; Rupasinghe, Thusitha W.; Sinclair, Andrew J.; Maddipati, Krishna Rao

    2013-01-01

    Classical proinflammatory eicosanoids, and more recently discovered lipid mediators with anti-inflammatory and proresolving bioactivity, exert a complex role in the initiation, control, and resolution of inflammation. Using a targeted lipidomics approach, we investigated circulating lipid mediator responses to resistance exercise and treatment with the NSAID ibuprofen. Human subjects undertook a single bout of unaccustomed resistance exercise (80% of one repetition maximum) following oral ingestion of ibuprofen (400 mg) or placebo control. Venous blood was collected during early recovery (0–3 h and 24 h postexercise), and serum lipid mediator composition was analyzed by LC-MS-based targeted lipidomics. Postexercise recovery was characterized by elevated levels of cyclooxygenase (COX)-1 and 2-derived prostanoids (TXB2, PGE2, PGD2, PGF2α, and PGI2), lipooxygenase (5-LOX, 12-LOX, and 15-LOX)-derived hydroxyeicosatetraenoic acids (HETEs), and leukotrienes (e.g., LTB4), and epoxygenase (CYP)-derived epoxy/dihydroxy eicosatrienoic acids (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of bioactive lipid mediators with anti-inflammatory and proresolving properties, including arachidonic acid-derived lipoxins (LXA4 and LXB4), and the EPA (E-series) and DHA (D-series)-derived resolvins (RvD1 and RvE1), and protectins (PD1 isomer 10S, 17S-diHDoHE). Ibuprofen treatment blocked exercise-induced increases in COX-1 and COX-2-derived prostanoids but also resulted in off-target reductions in leukotriene biosynthesis, and a diminished proresolving lipid mediator response. CYP pathway product metabolism was also altered by ibuprofen treatment, as indicated by elevated postexercise serum 5,6-DiHETrE and 8,9-DiHETrE only in those receiving ibuprofen. These findings characterize the blood inflammatory lipid mediator response to unaccustomed resistance exercise in humans and show that acute proinflammatory signals are mechanistically linked to the induction of a

  20. Patient-derived glioblastoma cells show significant heterogeneity in treatment responses to the inhibitor-of-apoptosis-protein antagonist birinapant

    PubMed Central

    Zakaria, Z; Tivnan, A; Flanagan, L; Murray, D W; Salvucci, M; Stringer, B W; Day, B W; Boyd, A W; Kögel, D; Rehm, M; O'Brien, D F; Byrne, A T; Prehn, J H M

    2016-01-01

    Background: Resistance to temozolomide (TMZ) greatly limits chemotherapeutic effectiveness in glioblastoma (GBM). Here we analysed the ability of the Inhibitor-of-apoptosis-protein (IAP) antagonist birinapant to enhance treatment responses to TMZ in both commercially available and patient-derived GBM cells. Methods: Responses to TMZ and birinapant were analysed in a panel of commercial and patient-derived GBM cell lines using colorimetric viability assays, flow cytometry, morphological analysis and protein expression profiling of pro- and antiapoptotic proteins. Responses in vivo were analysed in an orthotopic xenograft GBM model. Results: Single-agent treatment experiments categorised GBM cells into TMZ-sensitive cells, birinapant-sensitive cells, and cells that were insensitive to either treatment. Combination treatment allowed sensitisation to therapy in only a subset of resistant GBM cells. Cell death analysis identified three principal response patterns: Type A cells that readily activated caspase-8 and cell death in response to TMZ while addition of birinapant further sensitised the cells to TMZ-induced cell death; Type B cells that readily activated caspase-8 and cell death in response to birinapant but did not show further sensitisation with TMZ; and Type C cells that showed no significant cell death or moderately enhanced cell death in the combined treatment paradigm. Furthermore, in vivo, a Type C patient-derived cell line that was TMZ-insensitive in vitro and showed a strong sensitivity to TMZ and TMZ plus birinapant treatments. Conclusions: Our results demonstrate remarkable differences in responses of patient-derived GBM cells to birinapant single and combination treatments, and suggest that therapeutic responses in vivo may be greatly affected by the tumour microenvironment. PMID:26657652

  1. Neural correlates of emotional processing in depression: changes with cognitive behavioral therapy and predictors of treatment response.

    PubMed

    Ritchey, Maureen; Dolcos, Florin; Eddington, Kari M; Strauman, Timothy J; Cabeza, Roberto

    2011-05-01

    Major depressive disorder (MDD) is characterized by the presence of disturbances in emotional processing. However, the neural correlates of these alterations, and how they may be affected by therapeutic interventions, remain unclear. The present study addressed these issues in a preliminary investigation using functional magnetic resonance imaging (fMRI) to examine neural responses to positive, negative, and neutral pictures in unmedicated MDD patients (N = 22) versus controls (N = 14). After this initial scan, MDD patients were treated with cognitive behavioral therapy (CBT) and scanned again after treatment. Within regions that showed pre-treatment differences between patients and controls, we tested the association between pre-treatment activity and subsequent treatment response as well as activity changes from pre- to post-treatment. This study yielded three main findings. First, prior to treatment and relative to controls, patients exhibited overall reduced activity in the ventromedial prefrontal cortex (PFC), diminished discrimination between emotional and neutral items in the amygdala, caudate, and hippocampus, and enhanced responses to negative versus positive stimuli in the left anterior temporal lobe (ATL) and right dorsolateral PFC. Second, CBT-related symptom improvement in MDD patients was predicted by increased activity at baseline in ventromedial PFC as well as the valence effects in the ATL and dorsolateral PFC. Third, from pre- to post-treatment, MDD patients exhibited overall increases in ventromedial PFC activation, enhanced arousal responses in the amygdala, caudate, and hippocampus, and a reversal of valence effects in the ATL. The study was limited by the relatively small sample that was able to complete both scan sessions, as well as an inability to determine the influence of comorbid disorders within the current sample. Nevertheless, components of the neural networks corresponding to emotion processing disturbances in MDD appear to resolve

  2. Interaction between anthelmintic treatment and vaccine responses in ponies naturally infected with cyathostomins.

    PubMed

    Nielsen, M K; Rubinson, E F; Chambers, T M; Horohov, D W; Wagner, B; Betancourt, A; Reedy, S E; Jacobsen, S

    2015-04-15

    Anthelmintics and vaccines are commonly given concurrently in routine equine management, but it is unknown to what extent an interaction between the two exists. Cyathostomins can modulate the local immune response by stimulating a type 2 helper T cell (Th2) response. In addition, anti-inflammatory effects of ivermectin have been found in rodent models. It is unknown whether these anti-inflammatory effects affect the acute phase response elicited by commonly used vaccines. This study evaluated how the acute phase inflammatory response, leukocyte expression of pro-inflammatory cytokines, and vaccine-specific titers induced by simultaneous injection of three vaccines (West Nile Virus, Equine Herpes Rhinopneumonitis, and Keyhole Limpet Hemocyanin) were modulated by concurrent administration of ivermectin or pyrantel pamoate in ponies naturally infected with cyathostomins. Mixed-breed yearling ponies were blocked by gender and fecal strongyle egg count, then randomly assigned to three treatment groups: ivermectin (n=8), pyrantel pamoate (n=8), and control (n=7). All ponies received vaccinations intramuscularly on days 0 and 29, and anthelmintics were administered on the same days. Whole blood, serum and plasma samples were collected one, three and 14 days after each vaccination. Samples were analyzed for concentrations of acute phase reactants (haptoglobin, serum amyloid A, fibrinogen and iron), mRNA expression levels of cytokines (interleukin (IL)-1β, IL-4, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ) in leukocytes, and vaccine-specific antibody titers. A marked acute-phase response was noted following both vaccinations. In contrast, the pattern of change in cytokine expression was less pronounced and more variable. Statistical differences were observed between groups for haptoglobin, fibrinogen, IL-1β, IL-4, and IL-10, but differences were generally small and none of the vaccine titers were different between the groups. Taken together, the study

  3. Response of garlic (Allium sativum L.) bolting and bulbing to temperature and photoperiod treatments

    PubMed Central

    Wu, Cuinan; Wang, Mengyi; Cheng, Zhihui; Meng, Huanwen

    2016-01-01

    ABSTRACT This research was conducted to evaluate the effect of temperature and photoperiod treatments on the bolting and bulb formation of three local garlic cultivars (cvs) in two consecutive years. Naturally vernalized plants of cvs G107, G025 and G064 were transplanted into growth chambers and subjected to various combinations of temperature [T15/10, 15°C/10°C; T20/15, 20°C/15°C and T25/18, 25°C/18°C (day/night)] and photoperiod (L8, 8 h and L14,14 h) treatments. Plant growth, endogenous phytohormone and methyl jasmonate (MeJA) levels, along with the bolting and yield of garlic were evaluated. The experimental results from two consecutive years indicated that higher temperature (20°C or 25°C) and longer photoperiod (14 h) treatments significantly enhanced the garlic bolting, bulbing and cloving with a shorter growth period and a higher bulb weight. Moreover, the endogenous phytohormone and MeJA levels in the test plants were significantly increased by the higher temperature (25°C for the phytohormone level; 20°C for the MeJA level) and longer photoperiod [14 h, except for abscisic acid (ABA), which had the highest level at 8 h] conditions and were decreased by the lowest test temperature (15°C) and shorter photoperiod (8 h, except for ABA) conditions. This response coincided with that of the bulbing index, bolting rate, growth period and bulb weight. In addition, plants treated under the conditions of 20°C/15°C–14 h and 25°C/18°C–14 h produced the highest phytohormone levels (except for ABA) for cvs G025 and G064, respectively, and showed the best bolting and bulbing behavior. It is reasonable to assume that endogenous phytohormone (especially gibberellic acid) and MeJA levels are highly related to garlic bolting and bulbing, which might lead to the different responses of the three studied cultivars to the combination of temperature and photoperiod treatments. Furthermore, cvs G107 and G025 bolt well and have better bulb

  4. Personalized Circulating Tumor DNA Biomarkers Dynamically Predict Treatment Response and Survival In Gynecologic Cancers

    PubMed Central

    Anand, Sanya; Sebra, Robert; Catalina Camacho, Sandra; Garnar-Wortzel, Leopold; Nair, Navya; Moshier, Erin; Wooten, Melissa; Uzilov, Andrew; Chen, Rong; Prasad-Hayes, Monica; Zakashansky, Konstantin; Beddoe, Ann Marie; Schadt, Eric; Dottino, Peter; Martignetti, John A.

    2015-01-01

    Background High-grade serous ovarian and endometrial cancers are the most lethal female reproductive tract malignancies worldwide. In part, failure to treat these two aggressive cancers successfully centers on the fact that while the majority of patients are diagnosed based on current surveillance strategies as having a complete clinical response to their primary therapy, nearly half will develop disease recurrence within 18 months and the majority will die from disease recurrence within 5 years. Moreover, no currently used biomarkers or imaging studies can predict outcome following initial treatment. Circulating tumor DNA (ctDNA) represents a theoretically powerful biomarker for detecting otherwise occult disease. We therefore explored the use of personalized ctDNA markers as both a surveillance and prognostic biomarker in gynecologic cancers and compared this to current FDA-approved surveillance tools. Methods and Findings Tumor and serum samples were collected at time of surgery and then throughout treatment course for 44 patients with gynecologic cancers, representing 22 ovarian cancer cases, 17 uterine cancer cases, one peritoneal, three fallopian tube, and one patient with synchronous fallopian tube and uterine cancer. Patient/tumor-specific mutations were identified using whole-exome and targeted gene sequencing and ctDNA levels quantified using droplet digital PCR. CtDNA was detected in 93.8% of patients for whom probes were designed and levels were highly correlated with CA-125 serum and computed tomography (CT) scanning results. In six patients, ctDNA detected the presence of cancer even when CT scanning was negative and, on average, had a predictive lead time of seven months over CT imaging. Most notably, undetectable levels of ctDNA at six months following initial treatment was associated with markedly improved progression free and overall survival. Conclusions Detection of residual disease in gynecologic, and indeed all cancers, represents a diagnostic

  5. Improving Question-Asking Initiations in Young Children with Autism Using Pivotal Response Treatment

    PubMed Central

    Koegel, Robert; Bradshaw, Jessica; Ashbaugh, Kristen; Koegel, Lynn Kern

    2013-01-01

    Social initiations make up a core deficit for children with autism spectrum disorder. In particular, initiated questions during social interactions are often minimal or absent in this population. In the context of a multiple baseline design, the efficacy of using the motivational procedures of Pivotal Response Treatment to increase social question asking for three young children with autism was assessed. Results indicated that participants initiated a greater number of targeted questions following intervention. Additionally, all children exhibited increases in initiation of untargeted questions during social interaction in novel settings. Furthermore, post intervention data revealed collateral gains in communication and adaptive behavior. Theoretical implications of incorporating motivational strategies into intervention to improve social initiations in young children with ASD are discussed. PMID:24014174

  6. Tracing Plant Defense Responses in Roots upon MAMP/DAMP Treatment.

    PubMed

    Hiruma, Kei; Saijo, Yusuke

    2016-01-01

    This chapter describes how to apply microbe-associated molecular pattern (MAMP) or damage-associated molecular pattern (DAMP) solutions to Arabidopsis roots to trace defense responses in the root. Plants sense the presence of microbes via the perception of MAMPs or DAMPs by surface-localized pattern recognition receptors. The mechanisms governing plant root immunity are poorly characterized compared with those underlying plant immunity in the leaf, despite the fact that plant roots constantly interact with countless microbes living in soils that carry potential MAMPs and could stimulate the production of plant-derived DAMPs during colonization. To understand how a plant root immune system detects and reacts to the potential sources of a stimulus, we describe a simple method to monitor activation of root immunity upon MAMP/DAMP treatment by measuring relative expression of defense-related genes by RT-qPCR.

  7. Shared Responsibility: Massachusetts Legislators, Physicians, and An Act Relative to Substance Use Treatment, Education, and Prevention.

    PubMed

    Rudder, Meghan; Tsao, Lulu; Jack, Helen E

    2016-09-01

    Recent passage of the Massachusetts law, An Act Relative to Substance Use, Treatment, Education, and Prevention, represents an admirable public health approach to substance use disorder (SUD), a stigmatized chronic disease that affects some of society's most vulnerable people. With its seven-day supply limit on first-time opioid prescriptions, this legislation takes an unusual approach to state government involvement in health care. By intervening in individual physicians' practices, state legislators have entered a space traditionally reserved for clinical teams. The seven-day supply limit and the process through which it was developed highlight competing priorities and dialogue between physicians and legislators, limits of physician self-regulation, and standards of evidence in policy making and health care. Addressing these issues requires both physicians and legislators to recognize and fulfill new responsibilities in order to better assist the populations they serve.

  8. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) after treatment for Hodgkin's lymphoma.

    PubMed

    Mashima, Kyoko; Suzuki, Shigeaki; Mori, Takehiko; Shimizu, Toshihiko; Yamada, Satoshi; Hirose, Shigemichi; Okamoto, Shinichiro; Suzuki, Norihiro

    2015-12-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare central nervous system (CNS) disorder with distinct radiological features. However, CLIPPERS may mimic CNS lymphoma, and several cases in which CLIPPERS occurred premonitory to CNS lymphoma have been reported. We report a 31-year-old man presenting with progressive gait ataxia and the characteristic MRI features of CLIPPERS. He was diagnosed with stage II Hodgkin's lymphoma at the age of 15, and we considered the possibility of newly emerged CNS lymphoma occurring in the immunosuppressive condition after the treatment of Hodgkin's lymphoma. Histological findings showed no evidence of CNS lymphoma and the neurological symptoms were resolved by steroids. Although CLIPPERS developed in the reverse order in this case, CLIPPERS should be considered in different diagnosis for CNS lymphoma.

  9. How Attendance and Quality of Participation Affect Treatment Response to Parent Management Training

    PubMed Central

    Nix, Robert L.; Bierman, Karen L.; McMahon, Robert J.

    2012-01-01

    This study examined whether attendance and quality of participation in parent management training predicted treatment response. Data were from 445 parents (55% minority, 62% single; almost all of low socioeconomic status) who had 1st-grade children with severe conduct problems. Quality of participation in weekly parent groups was based on group leader ratings. Parent outcomes were based on interviewer ratings, behavioral observations, parent reports, and teacher ratings. Results of hierarchical linear models suggested that few family characteristics predicted attendance in this efficacy trial and that attendance was not related to changes in parenting over the year. However, several family characteristics predicted quality of participation in parent management training, and this in turn predicted changes in parental perceptions, warmth, physical punishment, and school involvement. From a clinical perspective, these findings suggest that it is not enough to get parents to attend sessions; it is also necessary to facilitate their active engagement in the therapeutic process. PMID:19485585

  10. How attendance and quality of participation affect treatment response to parent management training.

    PubMed

    Nix, Robert L; Bierman, Karen L; McMahon, Robert J

    2009-06-01

    This study examined whether attendance and quality of participation in parent management training predicted treatment response. Data were from 445 parents (55% minority, 62% single; almost all of low socioeconomic status) who had 1st-grade children with severe conduct problems. Quality of participation in weekly parent groups was based on group leader ratings. Parent outcomes were based on interviewer ratings, behavioral observations, parent reports, and teacher ratings. Results of hierarchical linear models suggested that few family characteristics predicted attendance in this efficacy trial and that attendance was not related to changes in parenting over the year. However, several family characteristics predicted quality of participation in parent management training, and this in turn predicted changes in parental perceptions, warmth, physical punishment, and school involvement. From a clinical perspective, these findings suggest that it is not enough to get parents to attend sessions; it is also necessary to facilitate their active engagement in the therapeutic process.

  11. Opportunities for Energy Efficiency and Open Automated Demand Response in Wastewater Treatment Facilities in California -- Phase I Report

    SciTech Connect

    Lekov, Alex; Thompson, Lisa; McKane, Aimee; Song, Katherine; Piette, Mary Ann

    2009-04-01

    This report summarizes the Lawrence Berkeley National Laboratory?s research to date in characterizing energy efficiency and automated demand response opportunities for wastewater treatment facilities in California. The report describes the characteristics of wastewater treatment facilities, the nature of the wastewater stream, energy use and demand, as well as details of the wastewater treatment process. It also discusses control systems and energy efficiency and automated demand response opportunities. In addition, several energy efficiency and load management case studies are provided for wastewater treatment facilities.This study shows that wastewater treatment facilities can be excellent candidates for open automated demand response and that facilities which have implemented energy efficiency measures and have centralized control systems are well-suited to shift or shed electrical loads in response to financial incentives, utility bill savings, and/or opportunities to enhance reliability of service. Control technologies installed for energy efficiency and load management purposes can often be adapted for automated demand response at little additional cost. These improved controls may prepare facilities to be more receptive to open automated demand response due to both increased confidence in the opportunities for controlling energy cost/use and access to the real-time data.

  12. Modulations of the Chicken Cecal Microbiome and Metagenome in Response to Anticoccidial and Growth Promoter Treatment

    PubMed Central

    Danzeisen, Jessica L.; Kim, Hyeun Bum; Isaacson, Richard E.; Tu, Zheng Jin; Johnson, Timothy J.

    2011-01-01

    With increasing pressures to reduce or eliminate the use of antimicrobials for growth promotion purposes in production animals, there is a growing need to better understand the effects elicited by these agents in order to identify alternative approaches that might be used to maintain animal health. Antibiotic usage at subtherapeutic levels is postulated to confer a number of modulations in the microbes within the gut that ultimately result in growth promotion and reduced occurrence of disease. This study examined the effects of the coccidiostat monensin and the growth promoters virginiamycin and tylosin on the broiler chicken cecal microbiome and metagenome. Using a longitudinal design, cecal contents of commercial chickens were extracted and examined using 16S rRNA and total DNA shotgun metagenomic pyrosequencing. A number of genus-level enrichments and depletions were observed in response to monensin alone, or monensin in combination with virginiamycin or tylosin. Of note, monensin effects included depletions of Roseburia, Lactobacillus and Enterococcus, and enrichments in Coprococcus and Anaerofilum. The most notable effect observed in the monensin/virginiamycin and monensin/tylosin treatments, but not in the monensin-alone treatments, was enrichments in Escherichia coli. Analysis of the metagenomic dataset identified enrichments in transport system genes, type I fimbrial genes, and type IV conjugative secretion system genes. No significant differences were observed with regard to antimicrobial resistance gene counts. Overall, this study provides a more comprehensive glimpse of the chicken cecum microbial community, the modulations of this community in response to growth promoters, and targets for future efforts to mimic these effects using alternative approaches. PMID:22114729

  13. Cereblon and IRF4 Variants Affect Risk and Response to Treatment in Multiple Myeloma.

    PubMed

    Butrym, Aleksandra; Łacina, Piotr; Rybka, Justyna; Chaszczewska-Markowska, Monika; Mazur, Grzegorz; Bogunia-Kubik, Katarzyna

    2017-01-12

    Multiple myeloma (MM) is a plasma-cell malignancy derived from an early precursor of the B-cell lineage characterised by bone-marrow infiltration, lytic bone lesions, and the presence of a monoclonal protein in serum and/or urine. Interferon regulatory factor 4 (IRF4) is a critical transcriptional regulator in B-cell development and function that is required during immune response for lymphocyte activation and the generation of immunoglobulin-secreting plasma cells. Immunomodulatory drugs, derivatives of thalidomide, are commonly used in therapy against MM. They are known to target a protein called cereblon (CRBN); however, the exact mechanism remains unknown. The present study aimed to assess the association of two (rs12203592 and rs872071) polymorphisms within the IRF4 gene and two (rs711613 and rs1045433) in the CRBN gene with MM susceptibility, progression, and response to treatment. For this purpose, 144 MM patients and 126 healthy individuals were genotyped for the IRF4 and CRBN alleles. The presence of the IRF4 (rs872071) G allele was more frequently detected in patients than healthy individuals (OR 1.78; P = 0.034), and this relationship was especially pronounced in women (OR 2.83; P = 0.012). The CRBN (rs711613) A allele-carriers were better responders to the treatment (P = 0.012), in particular to thalidomide including therapy (P = 0.023). These results underline the prognostic significance of the IRF4 and CRBN polymorphisms in patients with MM.

  14. Modulations of the chicken cecal microbiome and metagenome in response to anticoccidial and growth promoter treatment.

    PubMed

    Danzeisen, Jessica L; Kim, Hyeun Bum; Isaacson, Richard E; Tu, Zheng Jin; Johnson, Timothy J

    2011-01-01

    With increasing pressures to reduce or eliminate the use of antimicrobials for growth promotion purposes in production animals, there is a growing need to better understand the effects elicited by these agents in order to identify alternative approaches that might be used to maintain animal health. Antibiotic usage at subtherapeutic levels is postulated to confer a number of modulations in the microbes within the gut that ultimately result in growth promotion and reduced occurrence of disease. This study examined the effects of the coccidiostat monensin and the growth promoters virginiamycin and tylosin on the broiler chicken cecal microbiome and metagenome. Using a longitudinal design, cecal contents of commercial chickens were extracted and examined using 16S rRNA and total DNA shotgun metagenomic pyrosequencing. A number of genus-level enrichments and depletions were observed in response to monensin alone, or monensin in combination with virginiamycin or tylosin. Of note, monensin effects included depletions of Roseburia, Lactobacillus and Enterococcus, and enrichments in Coprococcus and Anaerofilum. The most notable effect observed in the monensin/virginiamycin and monensin/tylosin treatments, but not in the monensin-alone treatments, was enrichments in Escherichia coli. Analysis of the metagenomic dataset identified enrichments in transport system genes, type I fimbrial genes, and type IV conjugative secretion system genes. No significant differences were observed with regard to antimicrobial resistance gene counts. Overall, this study provides a more comprehensive glimpse of the chicken cecum microbial community, the modulations of this community in response to growth promoters, and targets for future efforts to mimic these effects using alternative approaches.

  15. The effect of dexmedetomidine post-treatment on the inflammatory response of astrocyte induced by lipopolysaccharide.

    PubMed

    Xie, Cuiying; Wang, Zhenhong; Tang, Jiajia; Shi, Zhiqian; He, Zhenzhou

    2015-01-01

    To explore the effect of dexmedetomidine (DEX) post-treatment on the inflammatory response of astrocyte induced by lipopolysaccharide (LPS). The astrocytes of neonatal mice were primarily cultured in vitro. After purification and identification, the cells were divided into five groups: group C: control group; group L: astrocytes were treated with 1 μg/ml LPS for 24 h; group D1, D2, and D3: astrocytes were pretreated with 1 μg/ml for 24 h LPS, and then cultured with low (0.1 μM), medium (1 μM), high (10 μM) concentration of DEX for 30 min, respectively. The cell survival rate was detected by cell counting kit. The expressions of inducible nitric oxide synthase (iNOS) mRNA, tumor necrosis gactor-α (TNF-α) mRNA, and interleukin-1β (IL-1β) mRNA were measured by RT-PCR in cell lysis solution of every group. The concentration of nitric oxide (NO) was detected by Griess method. The concentrations of IL-1β and TNF-α were measured, respectively, by enzyme-linked immuno sorbent assay. Compared with the group C, the expressions of iNOS mRNA, TNF-α mRNA, and IL-1βm RNA were significantly up-regulated, the release of NO, TNF-α, and IL-1β was significantly increased in group L (P < 0.05). Compared with group L, mRNA levels of inflammation-related factors and release of inflammatory factors were significantly down-regulated in group D2 and D3 (P < 0.05). There was no statistical difference between group D1 and group L. Pre-treatment with medium and high concentration of DEX can inhibit the LPS-induced inflammatory response of astrocyte.

  16. Longitudinal Study of Cone Photoreceptors during Retinal Degeneration and in Response to Ciliary Neurotrophic Factor Treatment

    PubMed Central

    Talcott, Katherine E.; Ratnam, Kavitha; Sundquist, Sanna M.; Lucero, Anna S.; Lujan, Brandon J.; Tao, Weng; Porco, Travis C.; Roorda, Austin

    2011-01-01

    Purpose. To study cone photoreceptor structure and function in patients with inherited retinal degenerations treated with sustained-release ciliary neurotrophic factor (CNTF). Methods. Two patients with retinitis pigmentosa and one with Usher syndrome type 2 who participated in a phase 2 clinical trial received CNTF delivered by an encapsulated cell technology implant in one eye and sham surgery in the contralateral eye. Patients were followed longitudinally over 30 to 35 months. Adaptive optics scanning laser ophthalmoscopy (AOSLO) provided high-resolution images at baseline and at 3, 6, 12, 18, and 24 months. AOSLO measures of cone spacing and density and optical coherence tomography measures of retinal thickness were correlated with visual function, including visual acuity (VA), visual field sensitivity, and full-field electroretinography (ERG). Results. No significant changes in VA, visual field sensitivity, or ERG responses were observed in either eye of the three patients over 24 months. Outer retinal layers were significantly thicker in CNTF-treated eyes than in sham-treated eyes (P < 0.005). Cone spacing increased by 2.9% more per year in sham-treated eyes than in CNTF-treated eyes (P < 0.001, linear mixed model), and cone density decreased by 9.1%, or 223 cones/degree2 more per year in sham-treated than in CNTF-treated eyes (P = 0.002, linear mixed model). Conclusions. AOSLO images provided a sensitive measure of disease progression and treatment response in patients with inherited retinal degenerations. Larger studies of cone structure using high-resolution imaging techniques are urgently needed to evaluate the effect of CNTF treatment in patients with inherited retinal degenerations. (ClinicalTrials.gov number, NCT00447980.) PMID:21087953

  17. Repeated dexamphetamine treatment alters the dopaminergic system and increases the phMRI response to methylphenidate

    PubMed Central

    Schrantee, Anouk; Tremoleda, Jordi L.; Wylezinska-Arridge, Marzena; Bouet, Valentine; Hesseling, Peter; Meerhoff, Gideon F.; de Bruin, Kora M.; Koeleman, Jan; Freret, Thomas; Boulouard, Michel; Desfosses, Emilie; Galineau, Laurent; Gozzi, Alessandro; Dauphin, François; Gsell, Willy; Booij, Jan; Lucassen, Paul J.; Reneman, Liesbeth

    2017-01-01

    Dexamphetamine (AMPH) is a psychostimulant drug that is used both recreationally and as medication for attention deficit hyperactivity disorder. Preclinical studies have demonstrated that repeated exposure to AMPH can induce damage to nerve terminals of dopamine (DA) neurons. We here assessed the underlying neurobiological changes in the DA system following repeated AMPH exposure and pre-treated rats with AMPH or saline (4 times 5 mg/kg s.c., 2 hours apart), followed by a 1-week washout period. We then used pharmacological MRI (phMRI) with a methylphenidate (MPH) challenge, as a sensitive and non-invasive in-vivo measure of DAergic function. We subsequently validated the DA-ergic changes post-mortem, using a.o. high-performance liquid chromatography (HPLC) and autoradiography. In the AMPH pre-treated group, we observed a significantly larger BOLD response to the MPH challenge, particularly in DA-ergic brain areas and their downstream projections. Subsequent autoradiography studies showed that AMPH pre-treatment significantly reduced DA transporter (DAT) density in the caudate-putamen (CPu) and nucleus accumbens, whereas HPLC analysis revealed increases in the DA metabolite homovanillic acid in the CPu. Our results suggest that AMPH pre-treatment alters DAergic responsivity, a change that can be detected with phMRI in rats. These phMRI changes likely reflect increased DA release together with reduced DAT binding. The ability to assess subtle synaptic changes using phMRI is promising for both preclinical studies of drug discovery, and for clinical studies where phMRI can be a useful tool to non-invasively investigate DA abnormalities, e.g. in neuropsychiatric disorders. PMID:28241065

  18. The MTHFR C677T Variant is Associated with Responsiveness to Disulfiram Treatment for Cocaine Dependency

    PubMed Central

    Spellicy, Catherine J.; Kosten, Thomas R.; Hamon, Sara C.; Harding, Mark J.; Nielsen, David A.

    2013-01-01

    Objective: Disulfiram is a one of the few pharmacotherapies for cocaine addiction that shows promise. Since disulfiram and cocaine both affect levels of global methylation we hypothesized the MTHFR gene, whose product is involved in supplying methyl groups for DNA and protein methylation, may be associated with responsiveness to disulfiram in cocaine-dependent individuals. Methods: Sixty-seven cocaine-dependent patients were stabilized on methadone for 2 weeks and then randomized into disulfiram (250 mg/day, N = 32) and placebo groups (N = 35) for 10 weeks. Patients were genotyped for the MTHFR (rs1801133, also known as C677T) polymorphism and the data was evaluated for association with cocaine-free urines in the disulfiram or placebo groups. Data from patients that completed all 10 weeks of the study (N = 56) were analyzed using repeated measures analysis of variance (ANOVA), corrected for population structure. Results: The CT or TT MTHFR genotype group (N = 32) dropped from 73 to 52% cocaine-positive urines on disulfiram (p = 0.0001), while the placebo group showed no treatment effect. The CC MTHFR genotype group (N = 24) showed a smaller, but still significant, reduction in cocaine-positive urines on disulfiram compared to placebo; 81–69% (p = 0.007). Conclusion: This study indicates that a patient’s MTHFR genotype may be used to identify individuals who might show improved response to disulfiram treatment for cocaine dependence. Clinical Trial: Pharmacogenetics of Disulfiram for Cocaine, clinicaltrials.gov/ct2/show/NCT00149630, NIDA-18197-2, NCT00149630. PMID:23335901

  19. Tumour-infiltrating regulatory T cell density before neoadjuvant chemoradiotherapy for rectal cancer does not predict treatment response.

    PubMed

    McCoy, Melanie J; Hemmings, Chris; Anyaegbu, Chidozie C; Austin, Stephanie J; Lee-Pullen, Tracey F; Miller, Timothy J; Bulsara, Max K; Zeps, Nikolajs; Nowak, Anna K; Lake, Richard A; Platell, Cameron F

    2017-02-03

    Neoadjuvant (preoperative) chemoradiotherapy (CRT) decreases the risk of rectal cancer recurrence and reduces tumour volume prior to surgery. However, response to CRT varies considerably between individuals and factors associated with response are poorly understood. Foxp3+ regulatory T cells (Tregs) inhibit anti-tumour immunity and may limit any response to chemotherapy and radiotherapy. We have previously reported that a low density of Tregs in the tumour stroma following neoadjuvant CRT for rectal cancer is associated with improved tumour regression. Here we have examined the association between Treg density in pre-treatment diagnostic biopsy specimens and treatment response, in this same patient cohort. We aimed to determine whether pre-treatment tumour-infiltrating Treg density predicts subsequent response to neoadjuvant CRT. Foxp3+, CD8+ and CD3+ cell densities in biopsy samples from 106 patients were assessed by standard immunohistochemistry (IHC) and evaluated for their association with tumour regression grade and survival. We found no association between the density of any T cell subset pre-treatment and clinical outcome, indicating that tumour-infiltrating Treg density does not predict response to neoadjuvant CRT in rectal cancer. Taken together with the findings of the previous study, these data suggest that in the context of neoadjuvant CRT for rectal cancer, the impact of chemotherapy and/or radiotherapy on anti-tumour immunity may be more important than the state of the pre-existing local immune response.

  20. Transcriptional Response of Silkworm (Bombyx mori) Eggs to O2 or HCl Treatment

    PubMed Central

    Gong, Jing; Tian, Sha; Zhou, Xia; Yang, Huan; Zhu, Yong; Hou, Yong

    2016-01-01

    Diapause is a common biological phenomenon that occurs in many organisms, including fish, insects, and nematodes. In the silkworm (Bombyx mori), diapause generally occurs in the egg stage. Treatment with O2, HCl, or other compounds can prevent egg diapause. Here, we characterized the transcriptomic responses of newly laid eggs treated with O2 or HCl. Digital gene expression analysis showed that 610 genes in O2-treated eggs and 656 in HCl-treated eggs were differentially expressed. Of these, 343 genes were differentially expressed in both treatments. In addition to trehalases, sorbic acid dehydrogenases, and some enzymes involved in the carbohydrate metabolism, we also identified heat shock proteins, cytochrome P450, and GADD45, which are related to stress tolerance. Gene ontology enrichment analysis showed differentially expressed genes in O2-treated eggs were involved in oxidoreductase activity as well as in binding, catalytic, and metabolic processes. The Kyoto Encyclopedia of Genes and Genomes analysis showed that the pathways for ribosome biogenesis, spliceosome, and circadian rhythm were significantly enriched in HCl-treated eggs. The reliability of the data was confirmed by qRT-PCR analysis. Our results improved the understanding of the mechanism of diapause blocking in silkworm eggs treated with O2 or HCl and identified novel molecular targets for future studies. PMID:27941611

  1. Reproductive and metabolic responses of desert adapted common spiny male mice (Acomys cahirinus) to vasopressin treatment.

    PubMed

    Bukovetzky, Elena; Fares, Fuad; Schwimmer, Hagit; Haim, Abraham

    2012-08-01

    Sufficient amounts of water and food are important cues for reproduction in an unpredictable environment. We previously demonstrated that increased osmolarity levels, or exogenous vasopressin (VP) treatment halt reproduction of desert adapted golden spiny mice Acomys russatus. In this research we studied gonad regulation by VP and food restriction (FR) in desert adapted common spiny mouse (A. cahirinus) males, kept under two different photoperiod regimes-short (SD-8L:16D) and long (LD-16L:8D) days. Mice were treated with VP, FR, and VP+FR for three weeks. Response was assessed from changes in relative testis mass, serum testosterone levels and mRNA receptor gene expression of VP, aldosterone and leptin in treated groups, compared with their controls. SD-acclimation increased testosterone levels, VP treatment decreased expression of aldosterone mRNA receptor in the testes of SD-acclimated males. FR under SD-conditions resulted in testosterone decrease and elevation of VP- receptor gene expression in testes. Aldosterone receptor mRNA expression was also detected in WAT. These results support the idea that water and food availability in the habitat may be used as signals for activating the reproductive system through direct effects of VP, aldosterone and leptin on the testes or through WAT by indirect effects.

  2. Biomarkers for diagnosis, monitoring of progression, and treatment responses in ankylosing spondylitis and axial spondyloarthritis.

    PubMed

    Reveille, John D

    2015-06-01

    With the growing awareness of the impact of chronic back pain and axial spondyloarthritis and recent breakthroughs in genetics and the development of novel treatments which may impact best on early disease, the need for markers that can facilitate early diagnosis and profiling those individuals at the highest risk for a bad outcome has never been greater. The genetic basis of ankylosing spondylitis has been considerably advanced, and HLA-B27 testing has a role in the diagnosis. Knowledge is still incomplete of the rest of the genetic contribution to disease susceptibility, and it is likely premature to use extensive genetic testing (other than HLA-B27) for diagnosis. Serum and plasma biomarkers have been examined extensively in assessing disease activity, treatment response, and as predictors or radiographic severity. For assessing disease activity, other than C-reactive protein and erythrocyte sedimentation rate, the most work has been in examining cytokines (particularly interleukin 17 and 23), matrix metalloproteinase (MMP) markers (particularly MMP3). For assessing those at the highest risk for radiographic progression, biomarkers of bony metabolism, cartilage and connective tissue degradation products, and adipokines have been most extensively assessed. The problem is that no individual biomarkers has been reproducibly shown to assess disease activity or predict outcome, and this area still remains an unmet need, of relevance to industry stakeholders, to regulatory bodies, to the healthcare system, to academic investigators, and finally to patients and providers.

  3. Responses of herbivore and predatory mites to tomato plants exposed to jasmonic acid seed treatment.

    PubMed

    Smart, Lesley E; Martin, Janet L; Limpalaër, Marlène; Bruce, Toby J A; Pickett, John A

    2013-10-01

    Jasmonic acid (JA) signalling can influence plant defense and the production of plant volatiles that mediate interactions with insects. Here, we tested whether a JA seed treatment could alter direct and indirect defenses. First, oviposition levels of herbivorous mites, Tetranychus urticae, on JA seed-treated and control tomato plants were compared. They were not significantly different on tomato cv. 'Moneymaker', however, there was a significant reduction in oviposition on treated plants in additional experiments with cv. 'Carousel'. Second, responses of predatory mites, Phytoseiulus persimilis, were assessed in a Y-tube olfactometer. Volatiles from JA seed-treated tomato cv. 'Moneymaker' plants were significantly more attractive than volatiles from control plants. Volatiles collected from plants were analysed by GC/MS, and samples from JA seed-treated plants contained more methyl salicylate and (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene (TMTT) than samples from control plants. Our results indicate that JA seed treatment can make tomato plants more attractive to predatory mites, but that direct effects on herbivorous mites are variable and cultivar dependent.

  4. Pediatric Pemphigus Vulgaris: Durable Treatment Responses Achieved with Prednisone and Mycophenolate Mofetil (MMF)

    PubMed Central

    Baratta, Andrea; Camarillo, Diana; Papa, Christine; Treat, James R.; Payne, Aimee S.; Rozenber, Suzanne S.; Yan, Albert C.

    2013-01-01

    Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease of the skin and mucous membranes. Most cases occur in adults; cases in children are rare. This report describes the clinical presentations and treatment responses of three children with PV, as confirmed according to histology and indirect immunofluorescence studies. In all three cases, oral prednisone used in conjunction with mycophenolate mofetil (MMF) resulted in complete clinical remission, during which all pharmacotherapy was successfully discontinued. Resolution of the skin and mucosal blistering tended to occur quickly with prednisone, and after initiation of treatment with MMF, discontinuation of all pharmacotherapy was achieved within a range of 10 to 30 months in the three patients. One patient experienced a recurrence of genital lesions 19 months after discontinuation of therapy, but the condition remitted within 2 weeks with topical corticosteroid therapy. At the time of this report, the duration of complete remission ranged from 6 to 19 months. In summary, combination therapy with prednisone and MMF for pediatric PV appears to be a safe and effective approach that is associated with durable remission. PMID:22747679

  5. Serological Response to Treatment of Syphilis with Doxycycline Compared with Penicillin in HIV-infected Individuals.

    PubMed

    Salado-Rasmussen, Kirsten; Hoffmann, Steen; Cowan, Susan; Jensen, Jørgen Skov; Benfield, Thomas; Gerstoft, Jan; Katzenstein, Terese Lea

    2016-08-23

    Serological response to treatment of syphilis with orally administered doxycycline or intramuscularly administered penicillin was assessed in patients with concurrent HIV. All HIV-infected individuals diagnosed with syphilis attending 3 hospitals in Copenhagen, Denmark were included. Odds ratios (ORs) with 95% confidence intervals (CI) associated with serological outcome were modelled using propensity-score-adjusted logistic regression analysis. In total, 202 cases were treated with doxycycline or intramuscular penicillin. At 12 months, serological failure was observed in 12 cases (15%) treated with doxycycline and in 8 cases (17%) treated with penicillin (OR 0.78 (95% CI 0.16-3.88), p = 0.76). The serological cure rate at 12 months was highest in patients with primary syphilis (100%), followed by patients with secondary (89%), early latent (71%) and late latent (67%) syphilis (p = 0.006). In conclusion, this study provides evidence for the use of doxycycline as a treatment option when treating a HIV-infected population for syphilis.

  6. Pediatric pemphigus vulgaris: durable treatment responses achieved with prednisone and mycophenolate mofetil (MMF).

    PubMed

    Baratta, Andrea; Camarillo, Diana; Papa, Christine; Treat, James R; Payne, Aimee S; Rozenber, Suzanne S; Yan, Albert C

    2013-01-01

    Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease of the skin and mucous membranes. Most cases occur in adults; cases in children are rare. This report describes the clinical presentations and treatment responses of three children with PV, as confirmed according to histology and indirect immunofluorescence studies. In all three cases, oral prednisone used in conjunction with mycophenolate mofetil (MMF) resulted in complete clinical remission, during which all pharmacotherapy was successfully discontinued. Resolution of the skin and mucosal blistering tended to occur quickly with prednisone, and after initiation of treatment with MMF, discontinuation of all pharmacotherapy was achieved within a range of 10 to 30 months in the three patients. One patient experienced a recurrence of genital lesions 19 months after discontinuation of therapy, but the condition remitted within 2 weeks with topical corticosteroid therapy. At the time of this report, the duration of complete remission ranged from 6 to 19 months. In summary, combination therapy with prednisone and MMF for pediatric PV appears to be a safe and effective approach that is associated with durable remission.

  7. Multi-modality imaging to assess metabolic response to dichloroacetate treatment in tumor models

    PubMed Central

    Neveu, Marie-Aline; Preter, Géraldine De; Joudiou, Nicolas; Bol, Anne; Brender, Jeffery R.; Saito, Keita; Kishimoto, Shun; Grégoire, Vincent; Jordan, Bénédicte F.; Krishna, Murali C.; Feron, Olivier; Gallez, Bernard

    2016-01-01

    Reverting glycolytic metabolism is an attractive strategy for cancer therapy as upregulated glycolysis is a hallmark in various cancers. Dichloroacetate (DCA), long used to treat lactic acidosis in various pathologies, has emerged as a promising anti-cancer drug. By inhibiting the pyruvate dehydrogenase kinase, DCA reactivates the mitochondrial function and decreases the glycolytic flux in tumor cells resulting in cell cycle arrest and apoptosis. We recently documented that DCA was able to induce a metabolic switch preferentially in glycolytic cancer cells, leading to a more oxidative phenotype and decreasing proliferation, while oxidative cells remained less sensitive to DCA treatment. To evaluate the relevance of this observation in vivo, the aim of the present study was to characterize the effect of DCA in glycolytic MDA-MB-231 tumors and in oxidative SiHa tumors using advanced pharmacodynamic metabolic biomarkers. Oxygen consumption, studied by 17O magnetic resonance spectroscopy, glucose uptake, evaluated by 18F-FDG PET and pyruvate transformation into lactate, measured using hyperpolarized 13C-magnetic resonance spectroscopy, were monitored before and 24 hours after DCA treatment in tumor bearing mice. In both tumor models, no clear metabolic shift was observed. Surprisingly, all these imaging parameters concur to the conclusion that both glycolytic tumors and oxidative tumors presented a similar response to DCA. These results highlight a major discordance in metabolic cancer cell bioenergetics between in vitro and in vivo setups, indicating critical role of the local microenvironment in tumor metabolic behaviors. PMID:28082726

  8. Neuroimaging biomarkers to predict treatment response in schizophrenia: the end of 30 years of solitude?

    PubMed

    Dazzan, Paola

    2014-12-01

    Studies that have used structural magnetic resonance imaging (MRI) suggest that individuals with psychoses have brain alterations, particularly in frontal and temporal cortices, and in the white matter tracts that connect them. Furthermore, these studies suggest that brain alterations may be particularly prominent, already at illness onset, in those individuals more likely to have poorer outcomes (eg, higher number of hospital admissions, and poorer symptom remission, level of functioning, and response to the first treatment with antipsychotic drugs). The fact that, even when present, these brain alterations are subtle and distributed in nature, has limited, until now, the utility of MRI in the clinical management of these disorders. More recently, MRI approaches, such as machine learning, have suggested that these neuroanatomical biomarkers can be used for direct clinical benefits. For example, using support vector machine, MRI data obtained at illness onset have been used to predict, with significant accuracy, whether a specific individual is likely to experience a remission of symptoms later on in the course of the illness. Taken together, this evidence suggests that validated, strong neuroanatomical markers could be used not only to inform tailored intervention strategies in a single individual, but also to allow patient stratification in clinical trials for new treatments.

  9. Predictors of the Treatment Response of Spontaneous Intracranial Hypotension to an Epidural Blood Patch.

    PubMed

    Karm, Myong-Hwan; Choi, Jae-Hyung; Kim, Doohwan; Park, Jun Young; Yun, Hye Joo; Suh, Jeong Hun

    2016-05-01

    Spontaneous intracranial hypotension (SIH) is characterized by postural headache because of low cerebrospinal fluid (CSF) pressure. Brain magnetic resonance imaging (MRI) and radioisotope (RI) cisternography can be used to identify the site of a CSF leakage. Although autologous epidural blood patch (EBP) is a very effective treatment modality, some patients require a repeat autologous EBP. We investigated whether autologous EBP responses correlate with surrogate markers of quantitative findings.All cases of autologous EBP for SIH from January 2006 to December 2014 were enrolled. The demographic variables, number of EBPs, pain scores, RI cisternography (early visualization of bladder activity), and MRI findings (subdural fluid collections, pachymeningeal enhancement, engorgement of venous structures, pituitary hyperemia, and sagging of the brain) were reviewed.Patients with early bladder activity on RI cisternography had a tendency to need a higher number of autologous EBPs. Only sagging of the brain and no other variables showed a statistically significant negative correlation with the number of autologous EBPs.The response to autologous EBP may be related to the radiologic findings of early bladder activity on RI cisternography and sagging of the brain on MRI.

  10. Predictors of the Treatment Response of Spontaneous Intracranial Hypotension to an Epidural Blood Patch

    PubMed Central

    Karm, Myong-Hwan; Choi, Jae-Hyung; Kim, Doohwan; Park, Jun Young; Yun, Hye Joo; Suh, Jeong Hun

    2016-01-01

    Abstract Spontaneous intracranial hypotension (SIH) is characterized by postural headache because of low cerebrospinal fluid (CSF) pressure. Brain magnetic resonance imaging (MRI) and radioisotope (RI) cisternography can be used to identify the site of a CSF leakage. Although autologous epidural blood patch (EBP) is a very effective treatment modality, some patients require a repeat autologous EBP. We investigated whether autologous EBP responses correlate with surrogate markers of quantitative findings. All cases of autologous EBP for SIH from January 2006 to December 2014 were enrolled. The demographic variables, number of EBPs, pain scores, RI cisternography (early visualization of bladder activity), and MRI findings (subdural fluid collections, pachymeningeal enhancement, engorgement of venous structures, pituitary hyperemia, and sagging of the brain) were reviewed. Patients with early bladder activity on RI cisternography had a tendency to need a higher number of autologous EBPs. Only sagging of the brain and no other variables showed a statistically significant negative correlation with the number of autologous EBPs. The response to autologous EBP may be related to the radiologic findings of early bladder activity on RI cisternography and sagging of the brain on MRI. PMID:27149484

  11. Long-term effects of maternal separation on chronic stress response suppressed by amitriptyline treatment.

    PubMed

    Cotella, E M; Mestres Lascano, I; Franchioni, L; Levin, G M; Suárez, M M

    2013-07-01

    Abstract The early-life environment has many long-term effects on mammals. Maternal interaction and early stressful events may affect regulation of the HPA axis during adulthood, leading to differential glucocorticoid secretion in response to stressful situations. These adverse experiences during postnatal development may even sensitize specific neurocircuits to subsequent stressors. Later in life, the overreaction of the HPA axis to stress can constitute a risk factor for metabolic and mental diseases. As tricyclic antidepressants are known to correct glucocorticoid hypersecretion during depression, we treated maternally separated animals with amitriptyline, at a lower dose than habitually used in depression models, to prevent the response to chronic stress during adulthood. Male Wistar rats were separated from the mother for 4.5 h every day for the first 3 weeks of life. From postnatal day 50, animals were subjected to chronic variable stress during 24 d (five types of stressors at different times of day). During the stress, protocol rats were orally administered amitriptyline (5 mg/kg) daily. We observed that maternal separation caused a reduction in plasma ACTH levels (p < 0.05), but evoked hypersecretion of corticosterone (p < 0.05) when it was combined with stress in adulthood. This rise was completely prevented by antidepressant treatment with amitriptyline.

  12. The Role of MR Enterography in Assessing Crohn's Disease Activity and Treatment Response

    PubMed Central

    Moy, Matthew P.; Sauk, Jenny; Gee, Michael S.

    2016-01-01

    MR enterography (MRE) has become the primary imaging modality in the assessment of Crohn's disease (CD) in both children and adults at many institutions in the United States and worldwide, primarily due to its noninvasiveness, superior soft tissue contrast, and lack of ionizing radiation. MRE technique includes distention of the small bowel with oral contrast media with the acquisition of T2-weighted, balanced steady-state free precession, and multiphase T1-weighted fat suppressed gadolinium contrast-enhanced sequences. With the introduction of molecule-targeted biologic agents into the clinical setting for CD and their potential to reverse the inflammatory process, MRE is increasingly utilized to evaluate disease activity and response to therapy as an imaging complement to clinical indices or optical endoscopy. New and emerging MRE techniques, such as diffusion-weighted imaging (DWI), magnetization transfer, ultrasmall superparamagnetic iron oxide- (USPIO-) enhanced MRI, and PET-MR, offer the potential for an expanded role of MRI in detecting occult disease activity, evaluating early treatment response/resistance, and differentiating inflammatory from fibrotic strictures. Familiarity with MR enterography is essential for radiologists and gastroenterologists as the technique evolves and is further incorporated into the clinical management of CD. PMID:26819611

  13. KLHL40-related nemaline myopathy with a sustained, positive response to treatment with acetylcholinesterase inhibitors.

    PubMed

    Natera-de Benito, D; Nascimento, A; Abicht, A; Ortez, C; Jou, C; Müller, J S; Evangelista, T; Töpf, A; Thompson, R; Jimenez-Mallebrera, C; Colomer, J; Lochmüller, H

    2016-03-01

    Congenital myopathies are a group of inherited muscle disorders characterized by hypotonia, weakness and a non-dystrophic muscle biopsy with the presence of one or more characteristic histological features. Neuromuscular transmission defects have recently been reported in several patients with congenital myopathies (CM). Mutations in KLHL40 are among the most common causes of severe forms of nemaline myopathy. Clinical features of affected individuals include fetal akinesia or hypokinesia, respiratory failure, and swallowing difficulties at birth. Muscle weakness is usually severe and nearly half of the individuals have no spontaneous antigravity movement. The average age of death has been reported to be 5 months in a recent case series. Herein we present a case of a patient with a nemaline myopathy due to KLHL40 mutations (c.604delG, p.Ala202Argfs*56 and c.1513G>C, p.Ala505Pro) with an impressive and prolonged beneficial response to treatment with high-dose pyridostigmine. Myasthenic features or response to ACEI have not previously been reported as a characteristic of nemaline myopathy or KLHL40-related myopathy.

  14. An Exploration of Responses to Drug Conditioned Stimuli during Treatment for Substance Dependence

    PubMed Central

    Goddard, Benjamin; Son Hing, Leanne S.; Leri, Francesco

    2013-01-01

    Although it is well established that drug conditioned stimuli produce a variety of conditioned responses, it is not known whether such stimuli can also reinforce an arbitrary operant response and thus serve as conditioned reinforcers. Volunteers (n = 39) recruited from a residential treatment center for substance dependence were tested on a task in which presses on computer keys activated images of drugs/drug paraphernalia on a progressive ratio schedule of reinforcement. They also completed a personalized craving questionnaire and a personalized Implicit Association Test. A significant bias in responding was found for images of preferred drugs/route of drug administration. Craving, however, was low and the images generated negative evaluative reactions. Two additional studies were performed to ascertain the generalizability of the effects to a different population of drug-using individuals (i.e., students who drink) and to incentive stimuli of a different nature (i.e., sexual). The additional studies partially replicated and extended the central findings of the main study. Therefore, although these data should be considered preliminary in light of small group sizes, it is concluded that cue specificity and availability of the unconditioned stimuli (drugs and sex) plays a role in modulating responding maintained by conditioned reinforcers. PMID:24826360

  15. A proteomic kinetic analysis of IGROV1 ovarian carcinoma cell line response to cisplatin treatment.

    PubMed

    Le Moguen, Karen; Lincet, Hubert; Marcelo, Paulo; Lemoisson, Edwige; Heutte, Natacha; Duval, Marilyne; Poulain, Laurent; Vinh, Joëlle; Gauduchon, Pascal; Baudin, Bruno

    2007-11-01

    Ovarian cancer is one of the leading causes of mortality by gynecological cancer. Despite good response to surgery and initial chemotherapy, essentially based on cisplatin (cis-diamino-dichloro-platinum(II) (CDDP)) compounds, frequent recurrences with chemoresistance acquisition are responsible for poor prognosis. Several mechanisms have been described as implicated in CDDP resistance, however they are not sufficient to exhaustively account for this resistance emergence. We applied a proteomic approach based on 2-DE coupled with MS (MALDI-TOF/TOF) to identify proteins associated with chemoresistance induced by CDDP. A kinetic analysis of IGROV1 cell behavior following treatment with CDDP and subsequent statistical analysis revealed time and/or concentration-dependent modifications in protein expression. We evidenced events such as decreased amino-acid and nucleotide synthesis potentially associated with cell cycle blockade, and variations that may be related to resistance acquisition, such as possible enhanced glycolysis and increased proliferating potential. Moreover, overexpressions of aldehyde dehydrogenase 1 and both cytokeratins 8 and 18 were consistent with our previous findings, demonstrating that expression of these proteins was increased in cisplatin-resistant IGROV1-R10 as compared to IGROV1 parental cells. Identification of such proteins could allow improved understanding of the mechanisms leading to cell death or survival and, thus, to the acquisition of chemoresistance.

  16. pH-Responsive Isoniazid-Loaded Nanoparticles Markedly Improve Tuberculosis Treatment in Mice.

    PubMed

    Hwang, Angela A; Lee, Bai-Yu; Clemens, Daniel L; Dillon, Barbara Jane; Zink, Jeffrey I; Horwitz, Marcus A

    2015-10-01

    Tuberculosis is a major global health problem for which improved therapeutics are needed to shorten the course of treatment and combat emergence of drug resistance. Mycobacterium tuberculosis, the etiologic agent of tuberculosis, is an intracellular pathogen of mononuclear phagocytes. As such, it is an ideal pathogen for nanotherapeutics because macrophages avidly ingest nanoparticles even without specific targeting molecules. Hence, a nanoparticle drug delivery system has the potential to target and deliver high concentrations of drug directly into M. tuberculosis-infected cells-greatly enhancing efficacy while avoiding off-target toxicities. Stimulus-responsive mesoporous silica nanoparticles of two different sizes, 100 and 50 nm, are developed as carriers for the major anti-tuberculosis drug isoniazid in a prodrug configuration. The drug is captured by the aldehyde-functionalized nanoparticle via hydrazone bond formation and coated with poly(ethylene imine)-poly(ethylene glycol) (PEI-PEG). The drug is released from the nanoparticles in response to acidic pH at levels that naturally occur within acidified endolysosomes. It is demonstrated that isoniazid-loaded PEI-PEG-coated nanoparticles are avidly ingested by M. tuberculosis-infected human macrophages and kill the intracellular bacteria in a dose-dependent manner. It is further demonstrated in a mouse model of pulmonary tuberculosis that the nanoparticles are well tolerated and much more efficacious than an equivalent amount of free drug.

  17. Genetics as a Molecular Window into Recovery, its Treatment, and Stress Responses After Stroke

    PubMed Central

    Juth, Vanessa; Holman, E. Alison; Chan, Michelle K.; Cramer, Steven C.

    2016-01-01

    Stroke remains a major source of adult disability in the U.S. and worldwide. Most patients show some recovery during the weeks-months following a stroke, but this is generally incomplete. An emerging branch of therapeutics targets the processes underlying this behavioral recovery from stroke towards the goal of reducing long-term disability. A key factor hampering these efforts is the very large degree of variability between stroke survivors. Available data suggest that genetic differences could explain an important fraction of the differences between subjects. The current review considers this from several angles, including genetic differences in relation to drugs that promote recovery. Genetic factors related to physiological and psychological stress responses may also be critically important to understanding recovery after stroke and its treatment. The studies reviewed provide insights into recovery and suggest directions for further research to improve clinical decision-making in this setting. Genetic differences between patients might be used to help clinical trials select specific patient subgroups, on a biological basis, in order to sharpen the precision with which new treatments are evaluated in this context. Pharmacogenomic factors might also provide insights into inter-subject differences in treatment side effects, for pharmacological prescriptions, behavioral interventions, and others. These efforts must be conducted with the strictest ethical standards given the highly sensitive nature of these data. Understanding the effect of selected genetic measures could improve a clinician’s ability to predict the risk and efficacy of a restorative therapy and to make maximally informed decisions, and in so doing facilitate individual patient care. PMID:27045100

  18. Colon Cancer Cells Gene Expression Signature As Response to 5- Fluorouracil, Oxaliplatin, and Folinic Acid Treatment

    PubMed Central

    Negrei, Carolina; Hudita, Ariana; Ginghina, Octav; Galateanu, Bianca; Voicu, Sorina Nicoleta; Stan, Miriana; Costache, Marieta; Fenga, Concettina; Drakoulis, Nikolaos; Tsatsakis, Aristidis M.

    2016-01-01

    5-FU cytotoxicity mechanism has been assigned both to the miss-incorporation of fluoronucleotides into RNA and DNA and to the inhibition of thymidylate synthase. 5-FU is one of the most widely used chemotherapeutic drugs, although it has severe side effects that may vary between patients. Pharmacogenetic studies related to 5-FU have been traditionally focused on the rate-limiting catabolic enzyme, dihydropyrimidine dehydrogenase that breaks 80–85% of 5-FU into its inactive metabolite. Choosing the right dosing scheme and chemotherapy strategy for each individual patient remains challenging for personalized chemotherapy management. In the general effort toward reduction of colorectal cancer mortality, in vitro screening studies play a very important role. To accelerate translation research, increasing interest has been focused on using in vivo-like models such as three-dimensional spheroids. The development of higher throughput assays to quantify phenotypic changes in spheroids is an active research area. Consequently, in this study we used the microarray technology to reveal the HT-29 colorectal adenocarcinoma cells gene expression signature as response to 5-FU/OXP/FA treatment in a state of the art 3D culture system. We report here an increased reactive oxygen species production under treatment, correlated with a decrease in cell viability and proliferation potential. With respect to the HT-29 cells gene expression under the treatment with 5-FU/OXP/FA, we found 15.247 genes that were significantly differentially expressed (p < 0.05) with a fold change higher that two-fold. Among these, 7136 genes were upregulated and 8111 genes were downregulated under experimental conditions as compared to untreated cells. The most relevant and statistic significant (p < 0.01) pathways in the experiment are associated with the genes that displayed significant differential expression and are related to intracellular signaling, oxidative stress, apoptosis, and cancer. PMID

  19. Global measures: utility in defining and measuring treatment response in dementia.

    PubMed

    Reisberg, Barry

    2007-06-01

    Global measures used in treatment trials in dementia encompass two distinct categories: (1) clinician's interview-based global severity scales, and (2) clinician's interview-based global change scales. The global severity scales that have been used include: the Clinical Dementia Rating (CDR) and the related CDR-sum of boxes (CDR-SB), the Global Deterioration Scale (GDS), and the Functional Assessment Staging (FAST) procedure. The global severity scales are clearly useful in subject categorization in treatment trials, in part because they are relatively free of many of the sociocultural biases inherent in mental status and psychometric descriptors. Global severity scales can also be used to demonstrate therapeutic efficacy in terms of the general progression of the dementia process. These measures have also proven to be useful in sensitively assessing pharmacotherapeutic effects in Alzheimer's disease (AD) treatment trials. For example, in pivotal trials: (1) in Mild to Moderate AD, the GDS has shown significant change in response to medication, whereas the results on the Mini-mental State Examination (MMSE) were not significant, and (2) in Moderate to Severe AD, the FAST has shown significant pharmacotherapeutic efficacy, whereas the results using the MMSE were not significant. The global change scales employed in dementia trials differ widely in assessment methodology. Clinical Global Impressions of Change (CGIC) scales do not have defined methodologies, whereas Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) scales are much more elaborate. The CIBIC-Plus procedures require an independent clinician assessment and can provide independent, comprehensive evidence of therapeutic efficacy. The CIBIC-Plus procedure may also be useful in sensitively assessing efficacy in future prevention trials, for example in subjects with Subjective Cognitive Impairment. For Mild Cognitive Impairment (MCI), global severity scales already appear to be

  20. Impact of Comorbid Anxiety and Depressive Disorders on Treatment Response to Cognitive Behavior Therapy for Insomnia

    PubMed Central

    Bélanger, Lynda; Harvey, Allison G.; Fortier-Brochu, Émilie; Beaulieu-Bonneau, Simon; Eidelman, Polina; Talbot, Lisa; Ivers, Hans; Hein, Kerrie; Lamy, Manon; Soehner, Adriane M.; Mérette, Chantal; Morin, Charles M.

    2016-01-01

    Objective To evaluate the impact of comorbid anxiety or depressive disorders on treatment response to cognitive behavior therapy (CBT) for insomnia, behavior therapy (BT), or cognitive therapy (CT). Method Participants were 188 adults (117 women; M age = 47.4 years) with chronic insomnia, including 45 also presenting a comorbid anxiety or mild to moderate depressive disorder. They were randomized to BT (n = 63), CT (n = 65), or CBT (n = 60). Outcome measures were the proportion of treatment responders (decrease of ≥ 8 points on the Insomnia Severity Index; ISI) and remissions (ISI score < 8) and depression and anxiety symptoms. Results Proportion of treatment responders and remitters in the CBT condition was not significantly different between the subgroups with and without comorbidity. However, the proportion of responders was lower in the comorbidity subgroup compared to those without comorbidity in both the BT (34.4% vs 81.6%; p=0.007) and CT (23.6% vs 57.6%; p=0.02) alone conditions, although remission rates and pre-post ISI change scores were not. Pre to post change scores on the depression (−10.6 vs −3.9; p<0.001) and anxiety measures (−9.2 vs −2.5; p=.01) were significantly greater in the comorbidity subgroup relative to the subgroup without comorbidity but only for those treated with the full CBT; no difference was found for those treated with either BT or CT alone. Conclusions The presence of a comorbid anxiety or mild to moderate depressive disorder did not reduce the efficacy of CBT for insomnia, but it did for its single BT and CT components when used alone. PMID:26963600

  1. Low-Dose Involved-Field Radiation in the Treatment of Non-Hodgkin Lymphoma: Predictors of Response and Treatment Failure

    SciTech Connect

    Russo, Andrea L.; Chen, Yu-Hui; Martin, Neil E.; Vinjamoori, Anant; Luthy, Sarah K.; Freedman, Arnold; Michaelson, Evan M.; Silver, Barbara; Mauch, Peter M.; Ng, Andrea K.

    2013-05-01

    Purpose: To investigate clinical and pathologic factors significant in predicting local response and time to further treatment after low-dose involved-field radiation therapy (LD-IFRT) for non-Hodgkin lymphoma (NHL). Methods and Materials: Records of NHL patients treated at a single institution between April 2004 and September 2011 were retrospectively reviewed. Low-dose involved-field radiation therapy was given as 4 Gy in 2 fractions over 2 consecutive days. Treatment response and disease control were determined by radiographic studies and/or physical examination. A generalized estimating equation model was used to assess the effect of tumor and patient characteristics on disease response. A Cox proportional hazards regression model was used to assess time to further treatment. Results: We treated a total of 187 sites in 127 patients with LD-IFRT. Histologies included 66% follicular, 9% chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma, 10% marginal zone, 6% mantle cell lymphoma (MCL), and 8% other. Median follow-up time was 23.4 months (range, 0.03-92.2 months). The complete response, partial response, and overall response rates were 57%, 25%, and 82%, respectively. A CLL histology was associated with a lower response rate (odds ratio 0.2, 95% confidence interval 0.1-0.5, P=.02). Tumor size, site, age at diagnosis, and prior systemic therapy were not associated with response. The median time to first recurrence was 13.6 months. Those with CLL and age ≤50 years at diagnosis had a shorter time to further treatment for local failures (hazard ratio [HR] 3.63, P=.01 and HR 5.50, P=.02, respectively). Those with CLL and MCL had a shorter time to further treatment for distant failures (HR 11.1 and 16.3, respectively, P<.0001). Conclusions: High local response rates were achieved with LD-IFRT across most histologies. Chronic lymphocytic leukemia and MCL histologies and age ≤50 years at diagnosis had a shorter time to further treatment after LD-IFRT.

  2. Sub-chronic exposure to fluoride impacts the response to a subsequent nephrotoxic treatment with gentamicin.

    PubMed

    Cárdenas-González, Mariana; Jacobo Estrada, Tania; Rodríguez-Muñoz, Rafael; Barrera-Chimal, Jonatan; Bobadilla, Norma A; Barbier, Olivier C; Del Razo, Luz M

    2016-02-01

    Fluoride is an important groundwater contaminant, and more than 200 million people are exposed to high fluoride levels in drinking water, the major source of fluoride exposure. Exposure above 2 ppm of fluoride is associated with renal impairment in humans. In rats, moderate levels of fluoride induce kidney injury at early stages in which the glomerular filtration rate (GFR) is not altered. In the present study, we investigated if sub-nephrotoxic stimulus induced by fluoride might impact the response to a subsequent nephrotoxic treatment with gentamicin. Male Wistar rats (~21 days) were exposed to 0, 15 or 50 ppm of fluoride through drinking water during 40 days. Afer that, rats were co-exposed to gentamicin (40 mg kg(-1) day(-1), 7 days). Gentamicin induced a marked decrease in the GFR and an increase in urinary levels as well as the protein and mRNA expression of biomarkers of early kidney injury, such as Kim-1. Interestingly, gentamicin nephrotoxicity was less pronounced in groups previously exposed to fluoride than in the group only treated with gentamicin. Fluoride induced Hsp72, a cytoprotective molecule, which might have improved the response against gentamicin. Moreover, fluoride decreased the expression of megalin, a molecule necessary for internalization of gentamicin into the proximal tubule, potentially reducing gentamicin accumulation. The present results suggest that fluoride reduced gentamicin-induced nephrotoxicity by inducing a compensatory response carried out by Hsp72 and by decreasing gentamicin accumulation. These findings should not be interpreted to suggest that fluoride is a protective agent as megalin deficiency could lead to serious adverse effects on the kidney physiology.

  3. Peak Plasma Concentration of Azithromycin and Treatment Responses in Mycobacterium avium Complex Lung Disease.

    PubMed

    Jeong, Byeong-Ho; Jeon, Kyeongman; Park, Hye Yun; Moon, Seong Mi; Kim, Su-Young; Lee, Soo-Youn; Shin, Sung Jae; Daley, Charles L; Koh, Won-Jung

    2016-10-01

    Macrolides, such as azithromycin (AZM) and clarithromycin, are the cornerstones of treatment for Mycobacterium avium complex lung disease (MAC-LD). Current guidelines recommend daily therapy with AZM for cavitary MAC-LD and intermittent therapy for noncavitary MAC-LD, but the effectiveness of these regimens has not been thoroughly investigated. This study evaluated associations between microbiological response and estimated peak plasma concentrations (Cmax) of AZM. The AZM Cmax was measured in patients receiving daily therapy (250 mg of AZM daily, n = 77) or intermittent therapy (500 mg of AZM three times weekly, n = 89) for MAC-LD and daily therapy for Mycobacterium abscessus complex LD (MABC-LD) (250 mg of AZM daily, n = 55). The AZM Cmax was lower with the daily regimen for MAC-LD (median, 0.24 μg/ml) than with the intermittent regimen for MAC-LD (median, 0.65 μg/ml; P < 0.001) or daily therapy for MABC-LD (median, 0.53 μg/ml; P < 0.001). After adjusting for confounding factors, AZM Cmax was independently associated with favorable microbiological responses in MAC-LD patients receiving a daily regimen (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 1.01 to 2.48; P = 0.044) but not an intermittent regimen (aOR, 0.85; 95% CI, 0.58 to 1.23, P = 0.379). With the daily AZM-based multidrug regimen for MAC-LD, a low AZM Cmax was common, whereas a higher AZM Cmax was associated with favorable microbiologic responses. The results also suggested that the addition of rifampin may lower AZM Cmax When a daily AZM-based multidrug regimen is used for treating severe MAC-LD, such as cavitary disease, the currently recommended AZM dose might be suboptimal. (This study has been registered at ClinicalTrials.gov under identifier NCT00970801.).

  4. Post-treatment of molasses wastewater by electrocoagulation and process optimization through response surface analysis.

    PubMed

    Tsioptsias, C; Petridis, D; Athanasakis, N; Lemonidis, I; Deligiannis, A; Samaras, P

    2015-12-01

    Molasses wastewater is a high strength effluent of food industry such as distilleries, sugar and yeast production plants etc. It is characterized by a dark brown color and exhibits a high content in substances of recalcitrant nature such as melanoidins. In this study, electrocoagulation (EC) was studied as a post treatment step for biologically treated molasses wastewater with high nitrogen content obtained from a baker's yeast industry. Iron and copper electrodes were used in various forms; the influence and interaction of current density, molasses wastewater dilution, and reaction time, on COD, color, ammonium and nitrate removal rates and operating cost were studied and optimized through Box Behnken's response surface analysis. Reaction time varied from 0.5 to 4 h, current density varied from 5 to 40 mA/cm(2) and dilution from 0 to 90% (v/v expressed as water concentration). pH, conductivity and temperature measurements were also carried out during each experiment. From preliminary experiments, it was concluded that the application of aeration and sample dilution, considerably influenced the kinetics of the process. The obtained results showed that COD removal varied between 10 and 54%, corresponding to an operation cost ranging from 0.2 to 33 euro/kg COD removed. Significant removal rates were obtained for nitrogen as nitrate and ammonium (i.e. 70% ammonium removal). A linear relation of COD and ammonium to the design parameters was observed, while operation cost and nitrate removal responded in a curvilinear function. A low ratio of electrode surface to treated volume was used, associated to a low investment cost; in addition, iron wastes could be utilized as low cost electrodes i.e. iron fillings from lathes, aiming to a low operation cost due to electrodes replacement. In general, electrocoagulation proved to be an effective and low cost process for biologically treated molasses-wastewater treatment for additional removal of COD and nitrogen content and

  5. Response to treatment following recently acquired hepatitis C virus infection in a multicentre collaborative cohort.

    PubMed

    Doyle, J S; Deterding, K; Grebely, J; Wedemeyer, H; Sacks-Davis, R; Spelman, T; Matthews, G; Rice, T M; Morris, M D; McGovern, B H; Kim, A Y; Bruneau, J; Lloyd, A R; Page, K; Manns, M P; Hellard, M E; Dore, G J

    2015-12-01

    Pegylated interferon therapy is highly effective in recently acquired HCV. The optimal timing of treatment, regimen and influence of host factors remains unclear. We aimed to measure sustained virological response (SVR) during recent HCV infection and identify predictors of response. Data were from five prospective cohorts of high-risk individuals in Australia, Canada, Germany and the United States. Individuals with acute or early chronic HCV who commenced pegylated interferon therapy were included. The main outcome was SVR, and predictors were assessed using logistic regression. Among 516 with documented recent HCV infection, 237 were treated (pegylated interferon n = 161; pegylated interferon/ribavirin n = 76) (30% female, median age 35 years, 56% ever injected drugs, median duration of infection 6.2 months). Sixteen per cent (n = 38) were HIV/HCV co-infected. SVR among those with HCV mono-infection was 64% by intention to treat; SVR was 68% among HCV/HIV co-infection. Independent predictors of SVR in HCV mono-infection were duration of HCV infection (the odds of SVR declined by 8% per month of infection, aOR 0.92, 95% CI 0.85-0.99, P = 0.033), IFNL4 genotype (adjusted OR 2.27, 95% CI 1.13-4.56, P = 0.021), baseline HCV RNA <400 000 IU/mL (aOR 2.06, 95% CI 1.03-4.12, P = 0.041) and age ≥40 years (vs <30: aOR 2.92, 95% CI 1.31-6.49, P = 0.009), with no difference by drug regimen, HCV genotype, symptomatic infection or gender. The effect of infection duration on odds of SVR was greater among genotype-1 infection. Interferon-based HCV treatment is highly effective in recent HCV infection. Duration of infection, IFNL4 genotype and baseline HCV RNA levels can predict virological response and may inform clinical decision-making.

  6. Toward Measuring Schistosoma Response to Praziquantel Treatment with Appropriate Descriptors of Egg Excretion

    PubMed Central

    Olliaro, Piero L.; Vaillant, Michel; Diawara, Aïssatou; Coulibaly, Jean T.; Garba, Amadou; Keiser, Jennifer; King, Charles H.; Knopp, Stefanie; Landouré, Aly; N’Goran, Eliézer K.; Raso, Giovanna; Scherrer, Alexandra U.; Sousa-Figueiredo, José Carlos; Stete, Katarina; Zhou, Xiao-Nong; Utzinger, Jürg

    2015-01-01

    Background The control of schistosomiasis emphasizes preventive chemotherapy with praziquantel, which aims at decreasing infection intensity and thus morbidity in individuals, as well as transmission in communities. Standardizing methods to assess treatment efficacy is important to compare trial outcomes across settings, and to monitor program effectiveness consistently. We compared customary methods and looked at possible complementary approaches in order to derive suggestions for standardizing outcome measures. Methodology/Principal Findings We analyzed data from 24 studies conducted at African, Asian, and Latin American sites, enrolling overall 4,740 individuals infected with Schistosoma mansoni, S. haematobium, or S. japonicum, and treated with praziquantel at doses of 40–80 mg/kg. We found that group-based arithmetic and geometric means can be used interchangeably to express egg reduction rates (ERR) only if treatment efficacy is high (>95%). For lower levels of efficacy, ERR estimates are higher with geometric than arithmetic means. Using the distribution of individual responses in egg excretion, 6.3%, 1.7% and 4.3% of the subjects treated for S. haematobium, S. japonicum and S. mansoni infection, respectively, had no reduction in their egg counts (ERR = 0). The 5th, 10th, and 25th centiles of the subjects treated for S. haematobium had individual ERRs of 0%, 49.3%, and 96.5%; the corresponding values for S. japonicum were 75%, 99%, and 99%; and for S. mansoni 18.2%, 65.3%, and 99.8%. Using a single rather than quadruplicate Kato-Katz thick smear excluded 19% of S. mansoni-infected individuals. Whilst the effect on estimating ERR was negligi