Science.gov

Sample records for 90y-sirsphere treatment response

  1. Attraction, Discrepancy and Responses to Psychological Treatment.

    ERIC Educational Resources Information Center

    Patton, Michael J.

    The responses of a laboratory subject (S) to a counselor-accomplice and to the psychological treatment situation are examined by manipulating experimentally interpersonal attraction and communication discrepancy. Four treatment conditions were set up: (1) topic similarity and positive attraction for counselor, (2) topic discrepancy and positive…

  2. 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

  3. 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

  4. Poor response to treatment: beyond medication

    PubMed Central

    Carvajal, César

    2004-01-01

    In psychiatry, one of the main factors contributing to poor response to pharmacological treatment is adherence. Noncompliance with maintenance treatments for chronic illnesses such as schizophrenia and affective disorders can exceed 50%, Poor adherence can be due to drug-related factors (tolerance, complexity of prescription, side effects, or cost), patient-related variables (illness symptoms, comorbidity, insight capacity, belief system, or sociocultural environment), and physician-related factors (communication or psychoeducational style). Psychosocial treatments must be used in conjunction with medication during the maintenance phase to improve adherence to treatment and to achieve - through the management of psychological variables - better social, work, and family functioning. This article reviews the concepts of adherence and noncompliance, and their impact on maintenance treatments, as well as the effect of dealing with psychosocial factors in psychiatric treatment. PMID:22034452

  5. Treatment responses to tooth whitening in twins.

    PubMed

    Corby, Patricia M A; Biesbrock, Aaron; Gerlach, Robert; Corby, Andrea L; Moreira, Alexandre; Schork, Nicholas J; Bretz, Walter A

    2014-02-01

    The aim of this study was to determine heritability estimates of treatment responses to a 10% hydrogen peroxide strip-based whitening system in twins. Eighty-five twin pairs were randomly assigned to 10% hydrogen peroxide whitening strips or placebo strips without peroxide. Both twins (monozygotic or dizygotic) received the same treatment. Maxillary teeth were treated for 30 minutes twice daily for 7 days. Efficacy was measured objectively as L* (light-dark), a* (red-green), and b* (yellow-blue) color change from digital images at baseline (∆) and day 8. Heritability estimates for tooth whitening treatment responses for changes from day 8 to baseline were obtained using variance-component methodologies. Whitening treatment responses were highly heritable (h(2) = 71.0) for ∆b* and ∆a*(p < .0001), but not for ∆L* (h(2) = 27.0), which was essentially modulated by environmental factors. This study has demonstrated that both genetic and environmental factors significantly contributed to seven-day whitening treatment responses achieved with 10% hydrogen peroxide strips.

  6. Pharmacogenetics of treatment response in psoriatic arthritis.

    PubMed

    Jani, Meghna; Barton, Anne; Ho, Pauline

    2015-07-01

    TNF-blocking agents, non-biological disease-modifying anti-rheumatic drugs (nbDMARDs) and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed treatments in psoriatic arthritis. A large proportion of patients do not respond to these medications, although unfortunately clinically useful biomarkers that predict future response are currently lacking. Several candidate gene polymorphisms have been associated with responses to biologic therapies and nbDMARDs; however, replication and validation of these variants in large prospective psoriatic arthritis cohorts are required before translating these to clinical practice. In this review, we discuss the advances made in pharmacogenetics of treatment response in psoriatic arthritis to date, with focus on biologic therapies approved for use, nbDMARDs and NSAIDs, as well as outline emerging methodologies to obtain data that will help inform a future precision medicine approach in this condition.

  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. Biosocial processes predicting multisystemic therapy treatment response.

    PubMed

    Ryan, Stacy R; Brennan, Patricia A; Cunningham, Phillippe B; Foster, Sharon L; Brock, Rebecca L; Whitmore, Elizabeth

    2013-02-01

    This study examined biological (testosterone) and social (deviant peer affiliation) factors early in treatment as predictors of treatment outcome among adolescent boys receiving Multisystemic Therapy (MST) in community settings. Outcome variables included changes in youth aggression and delinquency as reported by the primary caregiver. Testosterone and deviant peer affiliation were assessed at treatment onset; and outcome variables (aggression and delinquency) were assessed at treatment onset, mid-treatment and end-of-treatment. Participants were 112 adolescent boys (M age=15.42, SD=1.31) and their caregivers. Growth curve analyses revealed that the combination of high testosterone and high deviant peer affiliation early in treatment were significantly associated with less of a decline in aggression and delinquency over the course of treatment. Results provide novel evidence for the role of testosterone in the prediction of future externalizing behaviors. Clinical and theoretical implications are discussed. PMID:23247043

  9. Metaflammatory responses during obesity: Pathomechanism and treatment.

    PubMed

    Debnath, Monalisa; Agrawal, Shruti; Agrawal, Aruna; Dubey, G P

    2016-01-01

    Obesity induced inflammation acts as a reflex produced due to altered metabolic homeostasis in accordance to the nutrient overload on the metabolic cells. It involves up-regulation of the genes encoding for cytokines, chemokines and other inflammatory mediators through activated transcription factors - nuclear factor-kB, activator protein-1, nuclear factor of activated T cells and signal transducer and activator of transcription 3. These execute macromolecular innate immune cell sensor - inflammasome to activate caspase-1 pathway resulting in proteolytic maturation. Secretion of pro-inflammatory cytokines including TNF-α, IL-6, CRP, IL-1β, etc. from the M1 macrophages of white adipose tissue is increased, whereas there occurs a steep decline in the production of anti-inflammatory cytokines like IL-10, IL-Ra, adiponectin. Not only the adipose tissue, but also the immune cells, liver, brain, muscles and pancreas suffers from the inflammatory insult during obese condition and are exaggeratedly affected. The inflammatory kinases like JNK and IKK apart from inhibiting insulin action and glucose uptake, down-regulate transcriptional process resulting in increased expression of pro-inflammatory cytokines. Macrophage-like Kupffer cells initiate the inflammatory process in the liver preceding the inflammatory signals produced by the white adipose tissue which may further lead to hepatic-necro-inflammation. The muscle-fibre is affected by the cytokines and therefore results in decreased glycogen synthesis. The triggered hypothalamic-pituitary-adrenal axis further affects the expression of inflammatory cytokines thus altering insulin homeostasis and initiating glucose intolerance. Anti-inflammatory treatment so as to curb the severity of inflammatory responses includes administration of synthetic drugs to target the actual inflammatory molecules and various therapeutic interventions. PMID:26614484

  10. Metaflammatory responses during obesity: Pathomechanism and treatment.

    PubMed

    Debnath, Monalisa; Agrawal, Shruti; Agrawal, Aruna; Dubey, G P

    2016-01-01

    Obesity induced inflammation acts as a reflex produced due to altered metabolic homeostasis in accordance to the nutrient overload on the metabolic cells. It involves up-regulation of the genes encoding for cytokines, chemokines and other inflammatory mediators through activated transcription factors - nuclear factor-kB, activator protein-1, nuclear factor of activated T cells and signal transducer and activator of transcription 3. These execute macromolecular innate immune cell sensor - inflammasome to activate caspase-1 pathway resulting in proteolytic maturation. Secretion of pro-inflammatory cytokines including TNF-α, IL-6, CRP, IL-1β, etc. from the M1 macrophages of white adipose tissue is increased, whereas there occurs a steep decline in the production of anti-inflammatory cytokines like IL-10, IL-Ra, adiponectin. Not only the adipose tissue, but also the immune cells, liver, brain, muscles and pancreas suffers from the inflammatory insult during obese condition and are exaggeratedly affected. The inflammatory kinases like JNK and IKK apart from inhibiting insulin action and glucose uptake, down-regulate transcriptional process resulting in increased expression of pro-inflammatory cytokines. Macrophage-like Kupffer cells initiate the inflammatory process in the liver preceding the inflammatory signals produced by the white adipose tissue which may further lead to hepatic-necro-inflammation. The muscle-fibre is affected by the cytokines and therefore results in decreased glycogen synthesis. The triggered hypothalamic-pituitary-adrenal axis further affects the expression of inflammatory cytokines thus altering insulin homeostasis and initiating glucose intolerance. Anti-inflammatory treatment so as to curb the severity of inflammatory responses includes administration of synthetic drugs to target the actual inflammatory molecules and various therapeutic interventions.

  11. 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…

  12. Vegetation response to western juniper slash treatments.

    PubMed

    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

  13. 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…

  14. 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.

  15. 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...

  16. [Individual response to treatments using Teuscher activator].

    PubMed

    Nielsen, I L; Lagerström, L O

    1991-12-01

    Variations in facial growth and dentoalveolar development were studied in a group of 40 patients treated with the Teuscher appliance, a functional appliance which is a combination of an activator and a high-pull headgear. Patients were selected for this study on the basis of an initial Class II Division 1 malocclusion and on being consecutively treated with this appliance. The results showed that in 80% of the patients the maxilla either remained unchanged in it's relationship to the anterior cranial base (NSL) or became more retrusive during the treatment period. The mandible in 70% of the patients became more prognathic, only in four cases did the mandible become slightly more retrognathic. The analysis further showed that no statistically significant change occurred in the inclination of the mandible during treatment. Correlation analysis of the association between pretreatment mandibular plane angle and the changes during treatment showed no association. The dentoalveolar changes were characterized by retroclination of the maxillary incisors in 90% of the patients which occurred in spite of the torque springs, intended to maintain the inclination of these teeth. In contrast, the mandibular incisors on average showed no statistically significant change during treatment. This may be attributed to the capping of these teeth. Analysis of the association between the pretreatment inclination and the change during treatment of the mandibular incisors showed an inverse relationship. Mandibular incisors, that initially were proclined, tended to become more upright which is in contrast to previous studies indicating that functional appliance treatment generally increases the inclination of these teeth. The results of this study suggest that the correction of the skeletal component of the Class II malocclusion with the Teuscher appliance in most instances takes place by restriction of forward development of the maxilla in combination with downward-forward growth of the

  17. Using biological markers to inform a clinically meaningful treatment response.

    PubMed

    Yehuda, Rachel; Bierer, Linda M; Pratchett, Laura C; Pelcovitz, Michelle

    2010-10-01

    Combat veterans with posttraumatic stress disorder (PTSD) demonstrate less robust improvement following treatments than do civilians with PTSD. This paper discusses a theoretical model for evaluating treatment response based on the extent of change in biological markers of symptom severity or resilience between treatment initiation and termination. Such analysis permits a determination of biological change associated with the liberal criteria commonly used to determine treatment response in combat PTSD, and a comparison of this to the biological change associated with clinical response determined according to the conservative definition more appropriate to civilian PTSD. Interim data supporting the utility of this approach is presented based on preliminary analyses from our work in progress. We propose that future studies consider the unique consequences of combat trauma and develop treatments that incorporate the complex nature of the exposure and response characteristic of a veteran population. PMID:20955338

  18. 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.

  19. Hepatitis B: treatment choice and monitoring for response and resistance.

    PubMed

    Liu, Sze-Hang Kevin; Seto, Wai-Kay; Lai, Ching-Lung; Yuen, Man-Fung

    2016-06-01

    Despite effective preventive primary prevention with vaccination, many people remain infected with hepatitis B virus (HBV) and suffer from its complications. Effective treatments such as interferon-based regimens and oral nucleoside/nucleotides have been developed over the last 30 years, but they are not perfect. Each of the treatments has its own merits, but none can eradicate HBV from the host. As a result, regular monitoring of the response during treatment and after treatment is required. The choice and monitoring of selected treatments, new potential therapeutic agents, and treatment options for drug resistance are discussed in this review. PMID:26799653

  20. Prognosis of Treatment Response (Pathological Complete Response) in Breast Cancer

    PubMed Central

    Nikas, Jason B.; Low, Walter C.; Burgio, Paul A.

    2012-01-01

    Pertaining to the female population in the USA, breast cancer is the leading cancer in terms of annual incidence rate and, in terms of mortality, the second most lethal cancer. There are currently no biomarkers available that can predict which breast cancer patients will respond to chemotherapy with both sensitivity and specificity > 80%, as mandated by the latest FDA requirements. In this study, we have developed a prognostic biomarker model (complex mathematical function) that—based on global gene expression analysis of tumor tissue collected during biopsy and prior to the commencement of chemotherapy—can identify with a high accuracy those patients with breast cancer (clinical stages I–III) who will respond to the paclitaxel-fluorouracil-doxorubicin-cyclophosphamide chemotherapy and will experience pathological complete response (Responders), as well as those breast cancer patients (clinical stages I–III) who will not do so (Non-Responders). Most importantly, both the application and the accuracy of our breast cancer prognostic biomarker model are independent of the status of the hormone receptors ER, PR, and HER2, as well as of the ethnicity and age of the subjects. We developed our prognostic biomarker model with 50 subjects [10 responders (R) and 40 non-responders (NR)], and we validated it with 43 unknown (new and different) subjects [10 responders (R) and 33 non-responders (NR)]. All 93 subjects were recruited at five different clinical centers around the world. The overall sensitivity and specificity of our prognostic biomarker model were 90.0% and 91.8%, respectively. The nine most significant genes identified, which comprise the input variables to the mathematical function, are involved in regulation of transcription; cell proliferation, invasion, and migration; oncogenesis; suppression of immune response; and drug resistance and cancer recurrence. PMID:22619502

  1. 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.

  2. Toward Optimal Outcome Following Pivotal Response Treatment: A Case Series

    PubMed Central

    Ventola, Pamela E.; Oosting, Devon R.; Keifer, Cara M.; Friedman, Hannah E.

    2015-01-01

    There is a growing literature on children with autism spectrum disorder (ASD) who respond favorably to behavioral treatment, which is often termed “optimal outcome.” Rates and definitions of optimal outcome vary widely. The current case series describes an empirically validated behavioral treatment approach called Pivotal Response Treatment (PRT). We present two preschool-aged children who received an intensive course of PRT and seem to be on a trajectory toward potential optimal outcome. Understanding response to treatment and predictors of response is crucial, not necessarily to predict who may succeed, but to individualize medicine and match children with customized treatment programs that will be best tailored to their unique and varied needs. PMID:25745373

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

    PubMed Central

    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. PMID:26306256

  4. Psoriatic arthritis treatment: biological response modifiers.

    PubMed

    Mease, P J; Antoni, C E

    2005-03-01

    In recent years there has been a surge of interest in the treatment of chronic inflammatory disorders as a result of the development and application of targeted biological therapies. The elucidation of the overlapping cellular and cytokine immunopathology of such diverse conditions as rheumatoid arthritis (RA), Crohn's disease, and psoriasis points to specific targets for bioengineered proteins or small molecules. Similar to clinical trials in RA, trials in psoriatic arthritis (PsA) have shown excellent clinical results with the tumour necrosis factor (TNF) blockers, etanercept, infliximab, and adalimumab in a variety of domains including the joints, quality of life, function, and slowing of disease progress as evidenced radiologically. In addition, these agents have shown benefit in domains more unique to PsA, such as the skin lesions of psoriasis, enthesitis, and dactylitis, pointing out the similar pathogenesis of the disease in the skin, the tendons, and the synovial membrane. This therapy has been generally safe and well tolerated in clinical trials of PsA. Other logical candidates for targeted therapy in development include other anti-TNF agents, costimulatory blockade agents that affect T cell function, blockers of other cytokines such as interleukin (IL)-1, 6, 12, 15, or 18, and B cell modulatory medicines. Also, it will be useful to learn more about the effects of combining traditional disease modifying drugs and the newer biologicals.

  5. 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…

  6. 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…

  7. Evaluation of Histologic Cutpoints for Treatment Response in Eosinophilic Esophagitis

    PubMed Central

    Wolf, W. Asher; Cotton, Cary C.; Green, Daniel J.; Hughes, Julia T.; Woosley, John T.; Shaheen, Nicholas J.; Dellon, Evan S.

    2016-01-01

    Aim No consensus exists on the definition of successful treatment in eosinophilic esophagitis (EoE). The aim of this study was to identify the optimal histologic cutpoint to define successful treatment of EoE by assessing rates of symptomatic and endoscopic improvement. Materials and Methods We performed a retrospective cohort study utilizing the University of North Carolina EoE Clinicopathologic Database between 2006 and 2013. Rates of symptomatic and endoscopic improvement were determined, as were post-treatment eosinophil counts. The area under the receiver operator characteristic curve (AUC) was calculated for symptomatic and endoscopic response at several possible eosinophil count cutpoints (eos/hpf). Predictors of response were also assessed. Results Of 224 treatments in 199 patients, 76% were associated with symptomatic improvement, 68% with endoscopic improvement, and 60% with both. Of treatments that resulted in a post-treatment count of <15 eos/hpf, 90% were associated with an endoscopic response, 88% with a symptomatic response, and 81% with both symptomatic and endoscopic responses. Using a <15 eos/hpf threshold, the area under the curves (AUCs) were 0.70, 0.78, and 0.75 for symptomatic, endoscopic, and symptomatic/endoscopic responses, respectively. Lower histologic cut-points did not result in a substantial gain in response, but decreased the AUC. Conclusion In this large cohort of EoE patients, rates of symptomatic and endoscopic improvement were generally associated with histologic improvement. A histologic cutoff for treatment response of <15 eos/hpf may balance clinical outcomes and test performance. PMID:27110513

  8. Factors affecting response to biologic treatment in psoriasis.

    PubMed

    Karczewski, Jacek; Poniedziałek, Barbara; Rzymski, Piotr; Adamski, Zygmunt

    2014-01-01

    Psoriasis is a chronic, immune-mediated inflammatory skin disease, affecting approximately 2-4% of the population in western countries. Patients with a more severe form of the disease are typically considered for systemic therapy, including biologics. In spite of the overall superiority of biologic agents, the treatment response may differ substantially among individual patients. As with other medical conditions, a range of factors contribute to response heterogeneity observed in psoriasis. Proper identification of these factors can significantly improve the therapeutic decisions. This review focuses on potential genetic and nongenetic factors that may affect the treatment response and outcomes in patients with psoriasis.

  9. Circulating tumour cells-monitoring treatment response in prostate cancer.

    PubMed

    Miyamoto, David T; Sequist, Lecia V; Lee, Richard J

    2014-07-01

    The availability of new therapeutic options for the treatment of metastatic castration-resistant prostate cancer (mCRPC) has heightened the importance of monitoring and assessing treatment response. Accordingly, there is an unmet clinical need for reliable biomarkers that can be used to guide therapy. Circulating tumour cells (CTCs) are rare cells that are shed from primary and metastatic tumour deposits into the peripheral circulation, and represent a means of performing noninvasive tumour sampling. Indeed, enumeration of CTCs before and after therapy has shown that CTC burden correlates with prognosis in patients with mCRPC. Moreover, studies have demonstrated the potential of molecular analysis of CTCs in monitoring and predicting response to therapy in patients. This Review describes the challenges associated with monitoring treatment response in mCRPC, and the advancements in CTC-analysis technologies applied to such assessments and, ultimately, guiding prostate cancer treatment.

  10. 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.

  11. Defining treatment response in trichotillomania: a signal detection analysis.

    PubMed

    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

    2015-12-01

    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.

  12. Mechanisms underlying the antidepressant response and treatment resistance

    PubMed Central

    Levinstein, Marjorie R.; Samuels, Benjamin A.

    2014-01-01

    Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance. PMID:25018708

  13. 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.

  14. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment.

    PubMed

    Coussens, Anna K; Wilkinson, Robert J; Hanifa, Yasmeen; Nikolayevskyy, Vladyslav; Elkington, Paul T; Islam, Kamrul; Timms, Peter M; Venton, Timothy R; Bothamley, Graham H; Packe, Geoffrey E; Darmalingam, Mathina; Davidson, Robert N; Milburn, Heather J; Baker, Lucy V; Barker, Richard D; Mein, Charles A; Bhaw-Rosun, Leena; Nuamah, Rosamond; Young, Douglas B; Drobniewski, Francis A; Griffiths, Christopher J; Martineau, Adrian R

    2012-09-18

    Calcidiol, the major circulating metabolite of vitamin D, supports induction of pleiotropic antimicrobial responses in vitro. Vitamin D supplementation elevates circulating calcidiol concentrations, and thus has a potential role in the prevention and treatment of infection. The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported. To characterize these effects, we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were randomized to receive adjunctive high-dose vitamin D or placebo in a clinical trial, and who fulfilled criteria for per-protocol analysis. Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia, monocytosis, hypercytokinaemia, and hyperchemokinaemia. Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses, but attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4, CC chemokine ligand 5, and IFN-α. We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment. Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality.

  15. Predicting and Monitoring Cancer Treatment Response with DW-MRI

    PubMed Central

    Thoeny, Harriet C.; Ross, Brian D.

    2010-01-01

    An imaging biomarker that would provide for an early quantitative metric of clinical treatment response in cancer patients would provide for a paradigm shift in cancer care. Currently, non-image based clinical outcome metrics include morphology, clinical and laboratory parameters however, these are obtained relatively late following treatment. Diffusion-weighted MRI (DW-MRI) holds promise for use as a cancer treatment response biomarker as it is sensitive to macromolecular and microstructural changes which can occur at the cellular level earlier than anatomical changes during therapy. Studies have shown that successful treatment of a many tumor types can be detected using DW-MRI as an early increase in the apparent diffusion coefficient (ADC) values. Additionally, low pre-treatment ADC values of various tumors are often predictive of better outcome. These capabilities, once validated, could provide for an important opportunity to individualize therapy thereby minimizing unnecessary systemic toxicity associated with ineffective therapies with the additional advantage of improving overall patient health care and associated costs. In this report, we provide a brief technical overview of DW-MRI acquisition protocols, quantitative image analysis approaches and review studies which have implemented DW-MRI for the purpose of early prediction of cancer treatment response. PMID:20575076

  16. Treatment of acute schizophrenia with paliperidone ER: predictors for treatment response and benzodiazepine use.

    PubMed

    Heres, Stephan; Don, Liana; Herceg, Miroslav; Bidzan, Leszek; Blanc, Michel; Siracusano, Alberto; Maciulis, Valentinas; Lahaye, Marjolein; Schreiner, Andreas

    2014-01-01

    The Paliperidone ER Treatment in Acute Intervention (PERTAIN) study was designed to explore treatment response, tolerability, and safety of flexible doses of paliperidone ER in patients with schizophrenia admitted for an acute exacerbation. This paper addresses a secondary analysis of PERTAIN data designed to explore predictors for treatment response, flexible dosing, and concomitant benzodiazepine use. This prospective, multicenter, phase 3b, open-label, single-arm, 6-week study used flexible doses of paliperidone ER (3 to 12mg once daily) to treat patients hospitalized for an acute exacerbation of schizophrenia, reflecting more closely daily clinical practice. Predictive models were evaluated for paliperidone ER flexible dosing, treatment response, and concomitant treatment with benzodiazepines as distinct independent variables. For the analysis of explanatory variables, a stepwise logistic regression was used, taking into account patient age, gender, body mass index, diagnosis and duration of schizophrenia, number of prior hospitalizations, psychotic symptoms (PANSS), disease severity (CGI-S), and patient functioning (PSP) at baseline. Early response (defined as response within 2weeks of treatment initiation) was also used as a predictor. Clinical response (defined as ≥30% decrease in PANSS total score and ≥1 point decrease in CGI-S from baseline to endpoint) was predicted by early clinical response (p<0.001) and there was a trend for the diagnosis of paranoid schizophrenia vs. other types of schizophrenia to predict clinical response (p=0.0525). High response (defined as ≥50% decrease in PANSS total score and ≥2 points decrease in CGI-S from baseline to endpoint) was predicted by early high response, higher baseline CGI-S, or female gender. More severely ill patients with a higher baseline CGI-S were twice likely to be treated concomitantly with a benzodiazepine. PMID:24096139

  17. 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.

  18. 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.

  19. Rethinking responsibility in offenders with acquired paedophilia: punishment or treatment?

    PubMed

    Gilbert, Frédéric; Focquaert, Farah

    2015-01-01

    This article reviews the current neurobiological literature on the aetiology of developmental and acquired paedophilia and examines what the consequences could be in terms of responsibility and treatment for the latter. Addressing the question of responsibility and punishment of offenders with acquired paedophilia from a neurobiological perspective is controversial. Consequently it is essential to avoid hasty conclusions based strictly on neurobiological abnormality justifications. This study establishes a distinction between developmental and acquired paedophilia. The article investigates whether offenders who fulfil the diagnosis of acquired paedophilia should be held fully responsible, particularly in cases where the offender's conduct appears to result from volitionally controlled behaviour that is seemingly incompatible with a neurological cause. Moreover, the article explores how responsibility can be compromised when offenders with acquired paedophilia have (partially) preserved moral knowledge despite their sexual disorder. The article then examines the option of offering mandatory treatment as an alternative to imprisonment for offenders with acquired paedophilia. Furthermore, the article addresses the ethical issues related to offering any form of quasi-coercive treatment as a condition of release. This study concludes that decisions to fully or partially excuse an individual who fulfil the diagnosis of acquired paedophilia should take all relevant information into account, both neurobiological and other environmental evidence, and should proceed on a careful case by case analysis before sentencing or offering treatment.

  20. Genetics of the bone response to bisphosphonate treatments

    PubMed Central

    Massart, Francesco; Brandi, Maria Luisa

    2009-01-01

    Bone mineral density (BMD) is the best established marker for bone health. Over the last years a large number of studies have pointed to the variability in many target genes and their relation with bone mass and with other determinants of fracture risk such as ultrasound bone properties, skeletal geometry and bone turnover markers. The importance of genetic factors in the bone quality is substantial, but no consensus exists yet on the genes that are involved. Furthermore, there are many differences of clinical outcomes during bone-active treatments in the population-based studies. Heterogeneity in drug response may reflect varying responsiveness to boneactive treatments due to allele variation in the polymorphic target genes. In this regard, polymorphisms of vitamin D receptor and estrogen receptor loci appear genetic determinants of their corresponding hormonal treatment response such as vitamin D and estrogens. The present review focuses on the genetic determinants involved in the clinical response to bisphosphonate treatments for bone disorders. Knowledge of the molecular and functional consequences of the target genes is crucial to fully appreciate their significance and understand their potential clinical implications. PMID:22461098

  1. 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…

  2. 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…

  3. 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…

  4. Pre-Treatment Amygdala Volume Predicts Electroconvulsive Therapy Response

    PubMed Central

    ten Doesschate, Freek; van Eijndhoven, Philip; Tendolkar, Indira; van Wingen, Guido A.; van Waarde, Jeroen A.

    2014-01-01

    Background: Electroconvulsive therapy (ECT) is an effective treatment for patients with severe depression. Knowledge on factors predicting therapeutic response may help to identify patients who will benefit most from the intervention. Based on the neuroplasticity hypothesis, volumes of the amygdala and hippocampus are possible candidates for predicting treatment outcome. Therefore, this prospective cohort study examines the predictive value of amygdala and hippocampal volumes for the effectiveness of ECT. Methods: Prior to ECT, 53 severely unipolar depressed patients [mean age 57 ± 14 years; 40% (n = 21) male] received structural magnetic resonance imaging (MRI) at 1.5 T. Normalized amygdala and hippocampal volumes were calculated based on automatic segmentation by FreeSurfer (FS). Regression analyses were used to test if the normalized volumes could predict the response to a course of ECT based on the Montgomery–Åsberg Depression Rating Scale (MADRS) scores. Results: A larger amygdala volume independently and significantly predicted a lower post-ECT MADRS score (β = −0.347, P = 0.013). The left amygdala volume had greater predictive value for treatment outcome relative to the right amygdala volume. Hippocampal volume had no independent predictive value. Conclusion: A larger pre-treatment amygdala volume predicted more effective ECT, independent of other known predictors. Almost all patients continued their medication during the study, which might have influenced the course of treatment in ways that were not taken into account. PMID:25505429

  5. Pharmacogenetics of antipsychotic treatment response and side effects

    PubMed Central

    Mackenzie, B; Souza, RP; Likhodi, O; Tiwari, AK; Zai, CC; Sturgess, J

    2011-01-01

    Antipsychotic drugs are particularly interesting in pharmacogenetic studies as they are associated with a large interindividual variability in terms of response and side effects and, therefore, frequently need to be discontinued, requiring switches to other antipsychotics. Any information that allows the prediction of outcome to a given antipsychotic in a particular patient will, therefore, be of great help for the clinician to minimize time and find the right drug for the right patient, thus optimizing response and minimizing side effects. This will also have a substantial impact on compliance and doctor–patient relationships. Moreover, antipsychotic drug treatments are often required for life-long treatment and are also frequently prescribed to the more ‘vulnerable’ populations: children, adolescents and the elderly. This article focuses on some important studies performed with candidate gene variants associated with antipsychotic response. In addition, important findings in pharmacogenetic studies of antipsychotic-induced side effects will be briefly summarized, such as antipsychotic treatment induced tardive dyskinesia and weight gain. PMID:22287936

  6. 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.

  7. Atomoxetine pharmacogenetics: associations with pharmacokinetics, treatment response and tolerability.

    PubMed

    Brown, Jacob T; Bishop, Jeffrey R

    2015-01-01

    Atomoxetine is indicated for the treatment of attention deficit hyperactivity disorder and is predominantly metabolized by the CYP2D6 enzyme. Differences in pharmacokinetic parameters as well as clinical treatment outcomes across CYP2D6 genotype groups have resulted in dosing recommendations within the product label, but clinical studies supporting the use of genotype guided dosing are currently lacking. Furthermore, pharmacokinetic and clinical studies have primarily focused on extensive as compared with poor metabolizers, with little information known about other metabolizer categories as well as genes involved in the pharmacodynamics of atomoxetine. This review describes the pharmacogenetic associations with atomoxetine pharmacokinetics, treatment response and tolerability with considerations for the clinical utility of this information.

  8. 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. PMID:25499183

  9. Large granular lymphocyte leukemia: natural history and response to treatment.

    PubMed

    Fortune, Anne F; Kelly, Kevin; Sargent, Jeremy; O'Brien, David; Quinn, Fiona; Chadwick, Nick; Flynn, Catherine; Conneally, Eibhlin; Browne, Paul; Crotty, Gerard M; Thornton, Patrick; Vandenberghe, Elisabeth

    2010-05-01

    Large granular lymphocyte leukemia (T-LGL) is an indolent T lymphoproliferative disorder that was difficult to diagnose with certainty until clonality testing of the T cell receptor gene became routinely available. We studied the natural history and response to treatment in 25 consecutive patients with T-LGL diagnosed between 2004 and 2008 in which the diagnosis was confirmed by molecular analysis, to define an effective treatment algorithm. The median age at diagnosis was 61 years (range 27-78), with a male to female ratio of 1:1.8 and presenting features of fatigue (n = 13), recurrent infections (n = 9), and/or abnormal blood counts (n = 5). Thirteen patients with symptomatic disease were treated as follows: pentostatin (nine patients), cyclosporine (six patients), methotrexate (three patients), and alemtuzumab in two patients in whom pentostatin was ineffective. Pentostatin was the single most effective therapy, with a response rate of 75% and minimal toxicity. The overall survival (OS) and progression-free survival (PFS) 37 months from diagnosis were 80% and 52%, respectively. Treatment of T-LGL should be reserved for patients with symptomatic disease, but in this series, pentostatin treatment was less toxic and more effective than cyclosporine or methotrexate. PMID:20367569

  10. MRI Predictors of Treatment Response in Late-Life Depression

    PubMed Central

    Aizenstein, Howard J.; Khalef, Alexander; Walker, Sarah E.; Andreescu, Carmen

    2014-01-01

    In older adults, depression not only results in more years lived with disability than any other disease, but it also carries additional risk for suicide, medical comorbidities, and family care-giving burden. Because it can take many months to identify an effective treatment regimen, it is of upmost importance to shorten the window of time and identify early on what medication(s) and dosages will work effectively for individuals suffering from depression. Late-life depression (LLD) has been associated with greater burden of age-related changes, including atrophy, white matter ischemic changes, and alterations in functional connectivity (FC). Depression in midlife has been shown to alter affective reactivity and regulation, and functional magnetic resonance imaging (fMRI) studies in LLD have replicated the same abnormalities. Effective treatment can normalize these alterations. This article provides a review of the current literature using structural and functional neuroimaging to identify magnetic resonance imaging (MRI) predictors of treatment response in LLD. The majority of the literature on structural MRI has focused on the vascular depression hypothesis, and studies support the view that loss of brain volume and white matter integrity is associated with poorer treatment outcomes. Studies using fMRI have reported that lower task-based activity in the prefrontal cortex (PFC) and limbic regions is associated with poorer outcome. These imaging markers may be integrated into clinical decision-making to better treatment outcomes in the future. PMID:24381231

  11. Validating indicators of treatment response: application to trichotillomania.

    PubMed

    Nelson, Samuel O; Rogers, Kate; Rusch, Natalie; McDonough, Lauren; Malloy, Elizabeth J; Falkenstein, Martha J; Banis, Maria; Haaga, David A F

    2014-09-01

    Different studies of the treatment of trichotillomania (TTM) have used varying standards to determine the proportion of patients who obtain clinically meaningful benefits, but there is little information on the similarity of results yielded by these methods or on their comparative validity. Data from a stepped-care (Step 1: Web-based self-help; Step 2: Individual behavior therapy; N = 60) treatment study of TTM were used to evaluate 7 potential standards: complete abstinence, ≥ 25% symptom reduction, recovery of normal functioning, and clinical significance (recovery + statistically reliable change), each of the last 3 being measured by self-report (Massachusetts General Hospital Hairpulling Scale; MGH-HPS) or interview (Psychiatric Institute Trichotillomania Scale). Depending on the metric, response rates ranged from 25 to 68%. All standards were significantly associated with one another, though less strongly for the 25% symptom reduction metrics. Concurrent (with deciding to enter Step 2 treatment) and predictive (with 3-month follow-up treatment satisfaction, TTM-related impairment, quality of life, and diagnosis) validity results were variable but generally strongest for clinical significance as measured via self-report. Routine reporting of the proportion of patients who make clinically significant improvement on the MGH-HPS, supplemented by data on complete abstinence, would bolster the interpretability of TTM treatment outcome findings. PMID:24708079

  12. Enteric Microbiome Metabolites Correlate with Response to Simvastatin Treatment

    PubMed Central

    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

  13. Clinical Evaluation of Tuberculosis Viability Microscopy for Assessing Treatment Response

    PubMed Central

    Datta, Sumona; Sherman, Jonathan M.; Bravard, Marjory A.; Valencia, Teresa; Gilman, Robert H.; Evans, Carlton A.

    2015-01-01

    Background. It is difficult to determine whether early tuberculosis treatment is effective in reducing the infectiousness of patients' sputum, because culture takes weeks and conventional acid-fast sputum microscopy and molecular tests cannot differentiate live from dead tuberculosis. Methods. To assess treatment response, sputum samples (n = 124) from unselected patients (n = 35) with sputum microscopy–positive tuberculosis were tested pretreatment and after 3, 6, and 9 days of empiric first-line therapy. Tuberculosis quantitative viability microscopy with fluorescein diacetate, quantitative culture, and acid-fast auramine microscopy were all performed in triplicate. Results. Tuberculosis quantitative viability microscopy predicted quantitative culture results such that 76% of results agreed within ±1 logarithm (rS = 0.85; P < .0001). In 31 patients with non-multidrug-resistant (MDR) tuberculosis, viability and quantitative culture results approximately halved (both 0.27 log reduction, P < .001) daily. For patients with non-MDR tuberculosis and available data, by treatment day 9 there was a >10-fold reduction in viability in 100% (24/24) of cases and quantitative culture in 95% (19/20) of cases. Four other patients subsequently found to have MDR tuberculosis had no significant changes in viability (P = .4) or quantitative culture (P = .6) results during early treatment. The change in viability and quantitative culture results during early treatment differed significantly between patients with non-MDR tuberculosis and those with MDR tuberculosis (both P < .001). Acid-fast microscopy results changed little during early treatment, and this change was similar for non-MDR tuberculosis vs MDR tuberculosis (P = .6). Conclusions. Tuberculosis quantitative viability microscopy is a simple test that within 1 hour predicted quantitative culture results that became available weeks later, rapidly indicating whether patients were responding to tuberculosis therapy

  14. Novel Approaches to Thyroid Cancer Treatment and Response Assessment.

    PubMed

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

    2016-03-01

    The incidence of thyroid cancer has been increasing. After total thyroidectomy of well-differentiated thyroid tumors with intermediate- or high-risk features on pathology, radioiodine remains one of the mainstays of therapy for both thyroid remnant ablation as well as for treatment of metastatic disease. SPECT/CT, a relatively new modality, has been 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 treatment failure, FDG-PET/CT may provide prognostic information based on extent and intensity of metabolically active metastatic sites as well as serve as an important imaging test for response assessment in patients treated with chemotherapy, targeted therapies, or radiotherapy, thereby affecting patient management in multiple ways. The role of newer redifferentiation drugs has been evaluated with the use of I-124 PET/CT. PMID:26897715

  15. 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

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

    PubMed

    Hu, Xiaoqing; Yang, Jingli; Li, Chenghao

    2015-12-02

    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.

  17. 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

  18. [Treatment response of depressive patients with comorbid problem drink].

    PubMed

    Ishikawa, Hiromi; Hashimoto, Eri; Tayama, Masaya; Saito, Toshikazu

    2013-10-01

    In this study, we investigated the impact of Problem Drink on depression. Forty participants with depression were divided into 2 groups: non-Problem Drinker (NPD) group (n = 22) and Problem Drinker (PD) group (n = 18) according to Alcohol Use Disorder Identification Test (AUDIT) score (NPD < 12, PD > or = 12). Depression was assessed by the Mini-International Neuropsychiatric Interview. The effect of medication on depressive symptoms was monitored over 12 weeks using the Hamilton Rating Scale for Depression (HAM-D). Significant improvement in HAM-D score was observed at 2 weeks in NPD patients but not until 4 weeks in PD patients. Total HAM-D scores were lower in NPD than in PD patients at the end of the treatment period. Therapeutic doses (dose of antidepressant used was equivalent to greater than 75 mg of imipramine) of antidepressants resulted in significant improvement in HAM-D scores at 2 weeks in NPD patients, but not until 8 weeks in PD patients and brought lower HAM-D scores in NPD than in PD patients at the end of the treatment period. The AUDIT score and total alcohol consumption during the study period were negatively correlated to the improvement in HAM-D score. In NPD patients, the level of education of patients in remission was higher than those by patients not in remission. In contrast, level of education of patients in remission were similar to those in PD patients not in remission. The above results suggest that co-occurrence of alcohol use disorders with depression is associated with a lower response to antidepressants which may reflect not only the result of biological alterations in the brain by chronic ethanol ingestion but also an inhibitory effect of ethanol on antidepressant action in the brain. Drinking-related cognitive dysfunction may also relate to the decreased response to treatment in the depressed patients with comorbid Problem Drinker. PMID:24427900

  19. Voice acoustic measures of depression severity and treatment response collected via interactive voice response (IVR) technology

    PubMed Central

    Mundt, James C.; Snyder, Peter J.; Cannizzaro, Michael S.; Chappie, Kara; Geralts, Dayna S.

    2011-01-01

    Efforts to develop more effective depression treatments are limited by assessment methods that rely on patient-reported or clinician judgments of symptom severity. Depression also affects speech. Research suggests several objective voice acoustic measures affected by depression can be obtained reliably over the telephone. Thirty-five physician-referred patients beginning treatment for depression were assessed weekly, using standard depression severity measures, during a six-week observational study. Speech samples were also obtained over the telephone each week using an IVR system to automate data collection. Several voice acoustic measures correlated significantly with depression severity. Patients responding to treatment had significantly greater pitch variability, paused less while speaking, and spoke faster than at baseline. Patients not responding to treatment did not show similar changes. Telephone standardization for obtaining voice data was identified as a critical factor influencing the reliability and quality of speech data. This study replicates and extends previous research with a larger sample of patients assessing clinical change associated with treatment. The feasibility of obtaining voice acoustic measures reflecting depression severity and response to treatment using computer-automated telephone data collection techniques is also established. Insight and guidance for future research needs are also identified. PMID:21253440

  20. Early treatment response predicted subsequent clinical response in patients with schizophrenia taking paliperidone extended-release.

    PubMed

    Yeh, En-Chi; Huang, Ming-Chyi; Tsai, Chang-Jer; Chen, Chun-Tse; Chen, Kuan-Yu; Chiu, Chih-Chiang

    2015-11-30

    This 6-week open-labeled study investigated whether early treatment response in patients receiving paliperidone extended-release (paliperidone ER) can facilitate prediction of responses at Week 6. Patients with schizophrenia or schizoaffective disorder were administered 9mg/day of paliperidone ER during the first 2 weeks, after which the dose was adjusted clinically. They were assessed on Days 0, 4, 7, 14, 28, and 42 by the Positive and Negative Syndrome Scale (PANSS). The serum concentrations of 9-hydroxyrisperidone were examined on Days 14 and 42. Among the 41 patients enrolled, 26 were classified as responders (≧50% improvement on total PANSS scores at Week 6). In the receiver-operator curves (ROC) analyses, the changes in total PANSS scores at Week 2 appeared to show more accurate predictability compared to Day 4 and Day 7. At Week 6, no significant correlation was observed between blood 9-hydroxyrisperidone concentration and the total score or changes of PANSS scores. The results suggest that early treatment response to paliperidone ER, particularly at Week 2, can serve as a suitable outcome predictor at Week 6. Using 9mg/day paliperidone ER as an initial dose for schizophrenia treatment exhibited relatively favorable tolerability and feasibility.

  1. 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

  2. [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.

  3. Salivary Biomarkers of Periodontal Disease in Response to Treatment

    PubMed Central

    Sexton, William Michael; Lin, Yushun; Kryscio, Richard J.; Dawson, Dolphus R.; Ebersole, Jeffrey L.; Miller, Craig S.

    2011-01-01

    Background Salivary biomarkers of periodontitis were assessed longitudinally to determine response to therapy. Methods A 6-month case-controlled study of adults with chronic periodontitis was performed, with 33 participants receiving oral hygiene instructions (OHI) alone and 35 with scaling and root planing (SRP) combined with OHI. Saliva samples collected at week 0, 16 and 28 were analyzed for interleukin-1β (IL-1β), IL-8, macrophage inflammatory protein (MIP)-1α, matrix metalloproteinase-8 (MMP-8), osteoprotegerin (OPG) and tumor necrosis factor-α (TNF)-α. Clinical measures of periodontal disease were recorded at each visit. Results All parameters of periodontal health improved significantly in both groups by week 16 (p<0.0001) with the SRP group demonstrating greater benefit at week 16 and 28. Baseline OPG and TNF-α levels changed significantly at both follow-up visits (p<0.03), regardless of treatment group. IL-1β and MMP-8 levels decreased significantly from baseline (p≤0.04) in the SRP group only. OPG, MMP-8 and MIP-1α were significantly reduced in responders compared with non-responders (p=0.04, 0.01, 0.05 respectively). In receiver operating characteristic analyses, MMP-8 produced the highest area under the curve (≥ 0.7; p=0.01). Conclusion Salivary levels of IL-1β, MMP-8, OPG and MIP-1α reflected disease severity and response to therapy suggesting their potential utility for monitoring periodontal disease status. PMID:21480939

  4. Biological response of cancer cells to radiation treatment

    PubMed Central

    Baskar, Rajamanickam; Dai, Jiawen; Wenlong, Nei; Yeo, Richard; Yeoh, Kheng-Wei

    2014-01-01

    Cancer is a class of diseases characterized by uncontrolled cell growth and has the ability to spread or metastasize throughout the body. In recent years, remarkable progress has been made toward the understanding of proposed hallmarks of cancer development, care, and treatment modalities. Radiation therapy or radiotherapy is an important and integral component of cancer management, mostly conferring a survival benefit. Radiation therapy destroys cancer by depositing high-energy radiation on the cancer tissues. Over the years, radiation therapy has been driven by constant technological advances and approximately 50% of all patients with localized malignant tumors are treated with radiation at some point in the course of their disease. In radiation oncology, research and development in the last three decades has led to considerable improvement in our understanding of the differential responses of normal and cancer cells. The biological effectiveness of radiation depends on the linear energy transfer (LET), total dose, number of fractions and radiosensitivity of the targeted cells or tissues. Radiation can either directly or indirectly (by producing free radicals) damages the genome of the cell. This has been challenged in recent years by a newly identified phenomenon known as radiation induced bystander effect (RIBE). In RIBE, the non-irradiated cells adjacent to or located far from the irradiated cells/tissues demonstrate similar responses to that of the directly irradiated cells. Understanding the cancer cell responses during the fractions or after the course of irradiation will lead to improvements in therapeutic efficacy and potentially, benefitting a significant proportion of cancer patients. In this review, the clinical implications of radiation induced direct and bystander effects on the cancer cell are discussed. PMID:25988165

  5. Treatment heterogeneity in asthma: genetics of response to leukotriene modifiers.

    PubMed

    Lima, John J

    2007-01-01

    Despite advances in treatment, asthma continues to be a significant health and economic burden. Although asthma cannot be cured, several drugs, including beta2 agonists, corticosteroids, and leukotriene (LT) modifiers, are well tolerated and effective in minimizing symptoms, improving lung function, and preventing exacerbations. However, inter-patient variability in response to asthma drugs limits their effectiveness. It has been estimated that 60-80% of this inter-patient variability may be attributable to genetic variation. LT modifiers, in particular, have been associated with heterogeneity in response. These drugs exert their action by inhibiting the activity of cysteinyl leukotrienes (CysLTs), which are potent bronchoconstrictors and pro-inflammatory agents. Two classes of LT modifiers are 5-lipoxygenase (ALOX5) inhibitors (zileuton) and leukotriene receptor antagonists (LTRAs) [montelukast, pranlukast, and zarfirlukast]. LT modifiers can be used as alternatives to low-dose inhaled corticosteroids (ICS) in mild persistent asthma, as add-on therapy to low- to medium-dose ICS in moderate persistent asthma, and as add-on to high-dose ICS and a long-acting ss2 agonist in severe persistent asthma. At least six genes encode key proteins in the LT pathway: arachidonate 5-lipoxygenase (ALOX5), ALOX5 activating protein (ALOX5AP [FLAP]), leukotriene A4 hydrolase (LTA4H), LTC4 synthase (LTC4S), the ATP-binding cassette family member ABCC1 (multidrug resistance protein 1 [MRP1]), and cysteinyl leukotriene receptor 1 (CYSLTR1). Studies have reported that genetic variation in ALOX5, LTA4H, LTC4S, and ABCC1 influences response to LT modifiers. Plasma concentrations of LTRAs vary considerably among patients. Physio-chemical characteristics make it likely that membrane efflux and uptake transporters mediate the absorption of LTRAs into the systemic circulation following oral administration. Genes that encode efflux and uptake transport proteins harbor many variants that could

  6. Localized Aggressive Periodontitis Treatment Response in Primary and Permanent Dentitions

    PubMed Central

    MERCHANT, SHERIN. N.; VOVK, ANDREA.; KALASH, DANNY.; HOVENCAMP, NICOLE; AUKHIL, IKRAMUDDIN.; HARRISON, PETER; ZAPERT, EDWARD; BIDWELL, JOHN; VARNADO, PHYLLIS; SHADDOX, LUCIANA. M.

    2014-01-01

    Background The comparative treatment response of children and young adults with localized aggressive periodontitis (LAP) affecting primary and permanent dentition is unknown. The objective of this study was to evaluate the influence of non-surgical periodontal therapy with adjunctive systemic antibiotics on the clinical outcome of children/young adults with primary versus permanent dentition affected by LAP. Methods A cohort of 97 African-American participants between the ages of 5–21 (30M; 66F; 22 primary and 75 permanent dentition affected), diagnosed with LAP were included. Patients presented with no significant medical history. All patients underwent periodontal therapy, which consisted of full mouth mechanical debridement at baseline, 3, 6, and 12 month appointments. Additionally, all patients were prescribed a one-week regimen of systemic antibiotics at the initial appointment. Clinical parameters were analyzed, including probing depth (PD), clinical attachment levels (CAL), bleeding on probing (BOP) and percentage of visible plaque. Results Overall, periodontal therapy was found to be effective in improving the clinical outcomes of both primary and permanent dentitions. Although baseline CAL were similar between the groups, the reductions in mean CAL at 3, 6 and 12 months as well as reduction in % Plaque at 3 months were significantly greater in primary dentition as compared to permanent dentition. Conclusions Non-surgical therapy with systemic antibiotics is effective for LAP in both primary and permanent dentitions. A greater reduction in CAL in LAP of primary dentition may suggest that younger children may carry a greater propensity for positive treatment outcomes and healing potential as compared to children/young adults with permanent dentition. PMID:25186780

  7. 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

  8. 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

  9. The Need for Treatment Responsive Translational Biomarkers in Alcoholism Research.

    PubMed

    Heilig, Markus; Sommer, Wolfgang H; Spanagel, Rainer

    2016-01-01

    Over the past two decades, major advances have been made in the basic neuroscience of alcohol addiction. However, few of these have been translated into clinically useful treatments, which remain limited. In the past decade, psychiatric drug development in general has been stalled, with many preclinically validated mechanisms failing in clinical development. Despite the existence of appealing preclinical models in the area of addictive disorders, drug development for these conditions has been impacted by the exodus of major pharma from psychiatric neuroscience. Here, we discuss translational biomarker strategies that may help turn this tide. Following an approach patterned on an endophenotype approach to complex behavioral traits, we hypothesize that relatively simple biological measures should be sought that can be obtained both in experimental animals and in humans, and that may be responsive to alcoholism medications. These biomarkers have to be tailored to the specific mechanism targeted by candidate medications and may in fact also help identify biologically more homogeneous subpopulations of patients. We introduce as examples alcohol-induced dopamine (DA) release, measures of central glutamate levels, and network connectivity, and discuss our experience to date with these biomarker strategies. PMID:27240677

  10. 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. PMID:26931196

  11. 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

  12. Initial response as a predictor of 12-week buprenorphine-naloxone treatment response in a prescription opioid dependent population

    PubMed Central

    McDermott, Katherine A.; Griffin, Margaret L.; Connery, Hilary S.; Hilario, E. Yvette; Fiellin, David A.; Fitzmaurice, Garrett M.; Weiss, Roger D.

    2015-01-01

    Objective Initial medication response has been shown to predict treatment outcome across a variety of substance use disorders, but no studies have examined the predictive power of initial response to buprenorphine-naloxone in the treatment of prescription opioid dependence. We therefore conducted a secondary analysis of data from the Prescription Opioid Addiction Treatment Study to determine whether initial response to buprenorphine-naloxone predicted 12-week treatment outcome in a prescription opioid-dependent population. Method Using data from a multi-site, randomized controlled trial of buprenorphine-naloxone plus counseling for DSM-IV prescription opioid dependence (June 2006–July 2009), we conducted a secondary analysis to investigate the relationship between initial medication response and 12-week treatment outcome to establish how soon the efficacy of buprenorphine-naloxone could be predicted. Outcomes were determined from the Substance Use Report, a self-report measure of substance use, and confirmatory urinalysis. Predictive values were calculated to determine the importance of abstinence vs. use at various time points within the first month of treatment (week 1, weeks 1–2, 1–3, or 1–4) in predicting successful vs. unsuccessful treatment outcome (based on abstinence or near-abstinence from opioids) in the last 4 weeks of buprenorphine-naloxone treatment (weeks 9–12). Results Outcome was best predicted by medication response after two weeks of treatment. Two weeks of initial abstinence was moderately predictive of treatment success (positive predictive value = 71%), while opioid use in both of the first two weeks was strongly predictive of unsuccessful treatment outcome (negative predictive value (NPV) = 84%), especially when successful outcome was defined as total abstinence from opioids in weeks 9–12 (NPV = 94%). Conclusion Evaluating prescription opioid-dependent patients after two weeks of buprenorphine-naloxone treatment may help determine

  13. Effects of response satiation procedures in the treatment of aerophagia.

    PubMed

    Holburn, C S; Dougher, M J

    1986-07-01

    A contingent response that previously increased self-injurious air-swallowing (aerophagia) by a profoundly mentally retarded woman (Holburn & Dougher, 1985) was shown to decrease her air-swallowing when the response was presented in accord with the response deprivation/satiation hypothesis, which suggests that any free-operant response can serve as a reinforcer or a punisher depending upon specific contigency arrangements. The results offer an explanation for the earlier increase in air-swallowing. PMID:3740118

  14. Controlled trial of azathioprine in treatment of steroid-responsive nephrotic syndrome of childhood.

    PubMed Central

    Barratt, T M; Cameron, J S; Chantler, C; Counahan, R; Ogg, C S; Soothill, J F

    1977-01-01

    A controlled trial of azathioprine treatment of steroid-responsive frequent-relapsing nephrotic syndrome of childhood failed to show a therapeutic effect on the stability of remission after withdrawal of corticosteroid treatment. PMID:879831

  15. Treatment of landfill leachate by irrigation of willow coppice--plant response and treatment efficiency.

    PubMed

    Aronsson, Pär; Dahlin, Torleif; Dimitriou, Ioannis

    2010-03-01

    Landfill leachates usually need to be treated before discharged, and using soil-plant systems for this has gained substantial interest in Sweden and in the UK. A three-year field study was conducted in central Sweden to quantify plant response, treatment efficiency and impact on groundwater quality of landfill leachate irrigation of short-rotation willow coppice (Salix). Two willow varieties were tested and four irrigation regimes in sixteen 400-m2 plots. The willow plants did not react negatively, despite very high annual loads of nitrogen (Treatment efficiency varied considerably for different elements, but was adequate when moderate loads were applied.

  16. 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…

  17. 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…

  18. Temporary treatment during primary HIV infection does not affect virologic response to subsequent long-term treatment.

    PubMed

    Grijsen, Marlous L; Wit, Ferdinand W N M; Jurriaans, Suzanne; Kroon, Frank P; Schippers, Emile F; Koopmans, Peter; Gras, Luuk; Lange, Joep M A; Prins, Jan M

    2014-01-01

    Temporary cART during primary HIV-infection (PHI) did not select for drug resistance mutations after treatment interruption and did not affect the subsequent virological response to long-term cART. Our data demonstrate that fear of drug resistance development is not a valid argument to refrain from temporary early treatment during PHI.

  19. 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...

  20. 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.

  1. 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…

  2. Greater hippocampal volume is associated with PTSD treatment response.

    PubMed

    Rubin, Mikael; Shvil, Erel; Papini, Santiago; Chhetry, Binod T; Helpman, Liat; Markowitz, John C; Mann, J John; Neria, Yuval

    2016-06-30

    Previous research associates smaller hippocampal volume with posttraumatic stress disorder (PTSD). It is unclear, however, whether treatment affects hippocampal volume or vice versa. Seventy-six subjects, 40 PTSD patients and 36 matched trauma-exposed healthy resilient controls, underwent clinical assessments and magnetic resonance imaging (MRI) at baseline, and 10 weeks later, during which PTSD patients completed ten weeks of Prolonged Exposure (PE) treatment. The resilient controls and treatment responders (n=23) had greater baseline hippocampal volume than treatment non-responders (n=17) (p=0.012 and p=0.050, respectively), perhaps due to more robust fear-extinction capacity in both the initial phase after exposure to trauma and during treatment. PMID:27179314

  3. Responses of some Nigerian vegetables of plant growth regulator treatments.

    PubMed

    Kadiri, M; Mukhtar, F; Agboola, D A

    1997-03-01

    The effects of single and combined growth regulator treatments of indole-3-acetic acid (IAA), gibberellic acid (GA3) and coconut milk on plant height, yield, chlorophyll and vitamin contents of Abelmoschus esculetus L and Solanum gilo L were investigated. The single growth regulator treatments consisted of 50mg/L, 100 mg/L of IAA and GA3 and 10%, 15% of coconut milk. In case of combined growth regulator treatments, the treatments were 100mg/L IAA + 100mg/L GA3, 100mg/L IAA + 15% coconut milk and 100mg/L GA3 + 15% coconut milk. Control vegetable plants were sprayed with water. Single treatments of 100mg/L IAA,100mg/L GA3. 10% and 15% coconut milk resulted in significantly increased plant height, chlorophyll contents and yield of A. esculentus, H. sabdariffa and S. gilo while only combined treatments of 100mg/L IAA + 10% coconut milk and 100mg/L GA3 + 15% coconut milk had such an effect on A. esculentus and S. gilo but not on H. sabdariffa. Moreover, singletreatments of 100mg/L GA3 and 15% coconut milk caused significantly higher vitamins A, B6 and C contents of treated plants whereas the combined treatments produced such an effect on only vitamin C contents of treated plants. Growth regulator treatments of 100mg/L GA3 and 15% coconut milk were consistently the best out of the entire growth regulator treatments tried with the treated plants having the greatest plant height, yield, chlorophyll and vitamin C contents. PMID:9404511

  4. 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…

  5. 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,…

  6. 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…

  7. 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

  8. 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…

  9. Predictors of Treatment Response for Suicidal Youth Referred for Emergency Psychiatric Hospitalization

    ERIC Educational Resources Information Center

    Huey, Jr., Stanley J.; Henggeler, Scott W.; Rowland, Melisa D.; Halliday-Boykins, Colleen A.; Cunningham, Phillippe B.; Pickrel, Susan G.

    2005-01-01

    This study evaluated factors that predicted poor treatment response for 70 suicidal youth (ages 10 to 17 years; 67% African American) who received either multisystemic therapy (MST) or inpatient psychiatric hospitalization. Following treatment, suicidal youth were classified as either treatment responders or nonresponders based on caregiver or…

  10. 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…

  11. Current Approaches, Challenges and Future Directions for Monitoring Treatment Response in Prostate Cancer

    PubMed Central

    Wallace, T.J.; Torre, T.; Grob, M.; Yu, J.; Avital, I.; Brücher, BLDM; Stojadinovic, A.; Man, Y.G.

    2014-01-01

    Prostate cancer is the most commonly diagnosed non-cutaneous neoplasm in men in the United States and the second leading cause of cancer mortality. One in 7 men will be diagnosed with prostate cancer during their lifetime. As a result, monitoring treatment response is of vital importance. The cornerstone of current approaches in monitoring treatment response remains the prostate-specific antigen (PSA). However, with the limitations of PSA come challenges in our ability to monitor treatment success. Defining PSA response is different depending on the individual treatment rendered potentially making it difficult for those not trained in urologic oncology to understand. Furthermore, standard treatment response criteria do not apply to prostate cancer further complicating the issue of treatment response. Historically, prostate cancer has been difficult to image and no single modality has been consistently relied upon to measure treatment response. However, with newer imaging modalities and advances in our understanding and utilization of specific biomarkers, the future for monitoring treatment response in prostate cancer looks bright. PMID:24396494

  12. Clinical and biochemical responses to the treatment of milk fever.

    PubMed

    Mullen, P A

    1975-08-01

    One hundred and eighty-six cases of milk fever in 80 herds spread over five counties were used to compare treatment with 8g calcium plus 500 mg magnesium in aspartate with the conventional 12-36g calcium as borogluconate. The data obtained from both the herds and their individual cases show that the treatments gave broadly similar results, and a single intravenous treatment cured 74-7 per cent of cases. It appeared that milk fever was not likely to recur with each succeeding parturition. No breed susceptibility was recognised. No correlation was found between the severity of the clinical signs and the inorganic phosphate concentrations. An incidence of milk fever of 8-79 per cent was recorded.

  13. 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

  14. Behavioral activation: a strategy to enhance treatment response.

    PubMed

    Sudak, Donna M; Majeed, Muhammad H; Youngman, Branden

    2014-07-01

    Behavioral activation is an empirically validated treatment for depression pioneered in 1973 by Ferster, based on B.F. Skinner's behavioral principles. After publication of Beck's work on cognitive therapy, the boundaries of behavioral and cognitive therapies were blurred and the two now overlap substantially. Behavioral activation is also used as a stand-alone treatment and can also be effective in conjunction with antidepressant medication. Case conceptualization in behavioral activation entails an assessment of the behaviors that the patient has stopped that produce pleasure or are of importance, as well as behaviors essential to self-care. Activity monitoring, which provides treatment targets and leads to the case conceptualization in behavioral activation, consists of using charts, forms, or other prompts to track the relationship between activities and other variables (e.g., mood, enjoyment). That technique is also used to target rumination, procrastination, and avoidance and may also be helpful for patients with psychosis. PMID:25036582

  15. Spinal cord response to laser treatment of injured peripheral nerve

    SciTech Connect

    Rochkind, S.; Vogler, I.; Barr-Nea, L. )

    1990-01-01

    The authors describe the changes occurring in the spinal cord of rats subjected to crush injury of the sciatic nerve followed by low-power laser irradiation of the injured nerve. Such laser treatment of the crushed peripheral nerve has been found to mitigate the degenerative changes in the corresponding neurons of the spinal cord and induce proliferation of neuroglia both in astrocytes and oligodendrocytes. This suggests a higher metabolism in neurons and a better ability for myelin production under the influence of laser treatment.

  16. 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…

  17. Amygdala response to explicit sad face stimuli at baseline predicts antidepressant treatment response to scopolamine in major depressive disorder.

    PubMed

    Szczepanik, Joanna; Nugent, Allison C; Drevets, Wayne C; Khanna, Ashish; Zarate, Carlos A; Furey, Maura L

    2016-08-30

    The muscarinic antagonist scopolamine produces rapid antidepressant effects in individuals with major depressive disorder (MDD). In healthy subjects, manipulation of acetyl-cholinergic transmission modulates attention in a stimulus-dependent manner. This study tested the hypothesis that baseline amygdalar activity in response to emotional stimuli correlates with antidepressant treatment response to scopolamine and could thus potentially predict treatment outcome. MDD patients and healthy controls performed an attention shifting task involving emotional faces while undergoing functional magnetic resonance imaging (fMRI). We found that blood oxygenation level dependent (BOLD) signal in the amygdala acquired while MDD patients processed sad face stimuli correlated positively with antidepressant response to scopolamine. Amygdalar response to sad faces in MDD patients who did not respond to scopolamine did not differ from that of healthy controls. This suggests that the pre-treatment task elicited amygdalar activity that may constitute a biomarker of antidepressant treatment response to scopolamine. Furthermore, in MDD patients who responded to scopolamine, we observed a post-scopolamine stimulus processing shift towards a pattern demonstrated by healthy controls, indicating a change in stimulus-dependent neural response potentially driven by attenuated cholinergic activity in the amygdala. PMID:27366831

  18. 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)

  19. 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…

  20. DYNAMIC PREDICTION OF TREATMENT RESPONSE IN LATE-LIFE DEPRESSION

    PubMed Central

    Joel, Ian; Begley, Amy E.; Mulsant, Benoit H.; Lenze, Eric J.; Mazumdar, Sati; Dew, Mary Amanda; Blumberger, Daniel; Butters, Meryl; Reynolds, Charles F.

    2013-01-01

    Objective 1) identify actionable predictors of remission to antidepressant pharmacotherapy in depressed older adults and 2) use signal detection theory to develop decision trees to guide clinical decision making Method We treated 277 participants with current major depression using open-label venlafaxine XR (up to 300 mg/day) for 12 weeks, in an NIMH-sponsored randomized, placebo-controlled augmentation trial of adjunctive aripiprazole. Multiple logistic regression and signal detection approaches identified predictors of remission in both completer and intent-to-treat samples. Results Higher baseline depressive symptom severity (OR, 0.86, 95% CI, 0.80-0.93; p <0.001), smaller symptom improvement during the first two weeks of treatment (OR, 0.96, 95% CI, 0.94-0.97; p <0.001), male sex (OR, 0.41 95% CI, 0.18-0.93, p=0.03), duration of current episode ≥ 2 years (OR, 0.26 95% CI, 0.12-0.57, p<0.001) and adequate past depression treatment (ATHF >=3) (OR, 0.34 95% CI, 0.16-0.74, p=0.006) predicted lower probability of remission in the completer sample. Subjects with Montgomery Asberg (MADRS) decreasing by >27% in the first two weeks and with baseline MADRS scores of <27 (percentile rank = 51) had the best chance of remission (89%). Subjects with small symptom decrease in the first 2 weeks with adequate prior treatment and younger than 75 yrs old had the lowest chance of remission (16%). Conclusion Our results suggest the clinical utility of measuring pre-treatment illness severity and change during the first two weeks of treatment in predicting remission of late-life major depression. PMID:23567441

  1. Resting state functional connectivity and treatment response in late-life depression

    PubMed Central

    Andreescu, Carmen; Tudorascu, Dana L.; Butters, Meryl A.; Tamburo, Erica; Patel, Meenal; Price, Julie; Karp, Jordan F.; Reynolds, Charles F.; Aizenstein, Howard

    2013-01-01

    Indices of functional connectivity in the default mode network (DMN) are promising neural markers of treatment response in late-life depression. We examined the differences in DMN functional connectivity between treatment-responsive and treatment-resistant depressed older adults. Forty-seven depressed older adults underwent MRI scanning pre- and post- pharmacotherapy. Forty-six never depressed older adults underwent MR scanning as comparison subjects. Treatment response was defined as achieving a Hamilton Depression Rating Scale of 10 or less post-treatment. We analyzed resting state functional connectivity using the posterior cingulate cortex as the seed region-of-interest. The resulting correlation maps were employed to investigate between-group differences. Additionally we examined the association between white matter hyperintensity burden and functional connectivity results. Comparison of pre- and post-treatment scans of depressed participants revealed greater post-treatment functional connectivity in the frontal precentral gyrus. Relative to treatment-responsive participants, treatment-resistant participants had increased functional connectivity in the left striatum. When adjusting for white matter hyperintensity burden, the observed differences lost significance for the PCC-prefrontal functional connectivity, but not for the PCC-striatum functional connectivity. The post-treatment “frontalization” of the DMN connectivity suggests a normalizing effect of antidepressant treatment. Moreover, our study confirms the central role of white matter lesions in disrupting brain functional connectivity. PMID:24144505

  2. Resting state functional connectivity and treatment response in late-life depression.

    PubMed

    Andreescu, Carmen; Tudorascu, Dana L; Butters, Meryl A; Tamburo, Erica; Patel, Meenal; Price, Julie; Karp, Jordan F; Reynolds, Charles F; Aizenstein, Howard

    2013-12-30

    Indices of functional connectivity in the default mode network (DMN) are promising neural markers of treatment response in late-life depression. We examined the differences in DMN functional connectivity between treatment-responsive and treatment-resistant depressed older adults. Forty-seven depressed older adults underwent MRI scanning pre- and post-pharmacotherapy. Forty-six never depressed older adults underwent MR scanning as comparison subjects. Treatment response was defined as achieving a Hamilton Depression Rating Scale of 10 or less post-treatment. We analyzed resting state functional connectivity using the posterior cingulate cortex as the seed region-of-interest. The resulting correlation maps were employed to investigate between-group differences. Additionally we examined the association between white matter hyperintensity burden and functional connectivity results. Comparison of pre- and post-treatment scans of depressed participants revealed greater post-treatment functional connectivity in the frontal precentral gyrus. Relative to treatment-responsive participants, treatment-resistant participants had increased functional connectivity in the left striatum. When adjusting for white matter hyperintensity burden, the observed differences lost significance for the PCC-prefrontal functional connectivity, but not for the PCC-striatum functional connectivity. The post-treatment "frontalization" of the DMN connectivity suggests a normalizing effect of antidepressant treatment. Moreover, our study confirms the central role of white matter lesions in disrupting brain functional connectivity. PMID:24144505

  3. Pretreatment anterior cingulate activity predicts antidepressant treatment response in major depressive episodes.

    PubMed

    Rentzsch, Johannes; Adli, Mazda; Wiethoff, Katja; Gómez-Carrillo de Castro, Ana; Gallinat, Jürgen

    2014-04-01

    Major depressive disorder leads to substantial individual and socioeconomic costs. Despite the ongoing efforts to improve the treatment for this condition, a trial-and-error approach until an individually effective treatment is established still dominates clinical practice. Searching for clinically useful treatment response predictors is one of the most promising strategies to change this quandary therapeutic situation. This study evaluated the predictive value of a biological and a clinical predictor, as well as a combination of both. Pretreatment EEGs of 31 patients with a major depressive episode were analyzed with neuroelectric brain imaging technique to assess cerebral oscillations related to treatment response. Early improvement of symptoms served as a clinical predictor. Treatment response was assessed after 4 weeks of antidepressant treatment. Responders showed more slow-frequency power in the right anterior cingulate cortex compared to non-responders. Slow-frequency power in this region was found to predict response with good sensitivity (82 %) and specificity (100 %), while early improvement showed lower accuracy (73 % sensitivity and 65 % specificity). Combining both parameters did not further improve predictive accuracy. Pretreatment activity within the anterior cingulate cortex is related to antidepressive treatment response. Our results support the search for biological treatment response predictors using electric brain activity. This technique is advantageous due to its low individual and socioeconomic burden. The benefits of combining both, a clinically and a biologically based predictor, should be further evaluated using larger sample sizes.

  4. Suicidal Behavior in Mood Disorders: Response to Pharmacological Treatment.

    PubMed

    Tondo, Leonardo; Baldessarini, Ross J

    2016-09-01

    Suicidal behavior is strongly associated with depression, especially if accompanied by behavioral activation, dysphoria, or agitation. It may respond to some treatments, but the design of scientifically sound, ethical trials to test for therapeutic effects on suicidal behavior is highly challenging. In bipolar disorder, and possibly also unipolar major depression, an underprescribed medical intervention with substantial evidence of preventive effects on suicidal behavior is long-term treatment with lithium. It is unclear whether this effect is specifically antisuicidal or reflects beneficial effects of lithium on depression, mood instability, and perhaps aggression and impulsivity. Antisuicidal effects of anticonvulsant mood stabilizers (carbamazepine, lamotrigine, valproate) appear to be less than with lithium. Further evaluation is needed for potential antisuicidal effects of atypical antipsychotics with growing evidence of efficacy in depression, particularly acute bipolar depression, while generally lacking risk of inducing agitation, mania, or mood instability. Short-term and long-term value and safety of antidepressants are relatively secure for unipolar depression but uncertain and poorly tested for bipolar depression; their effects on suicidal risk in unipolar depression may be age-dependent. Sedative anxiolytics are virtually unstudied as regards suicidal risks. Adequate management of suicidal risks in mood disorder patients requires comprehensive, clinically skillful monitoring and timely interventions. PMID:27542851

  5. 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

  6. 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 PMID:27031606

  7. High occupational level is associated with poor response to treatment of depression.

    PubMed

    Mandelli, Laura; Serretti, Alessandro; Souery, Daniel; Mendlewicz, Julien; Kasper, Siegfried; Montgomery, Stuart; Zohar, Joseph

    2016-08-01

    Depression may be complicated by work-related stress and, in turn, depression is a leading cause of disability in workplaces. Though available effective treatments, only one third of patients reach full remission after a first treatment trial and nearly half of the patients are non-responders. Occupational level has been found to be a reliable predictor of health outcome in the general population. In the present study we tested the potential association of occupational level of those in work with response to treatment of depression in a large multinational sample. Major depressive disorder patients (n=654) stratified in three occupational levels (high, middle, low) were considered for the present study. Response to last treatment for current episode and treatment resistant depression, defined as non-response to 2 or more previous adequate treatment trials, were considered the outcome variables. Depressed patients from the high occupational level had a higher level of educational achievement. They showed a significantly poorer response to the last treatment with lower remission rates and more treatment resistance than the other occupational level groups. They were treated less with Serotonin Reuptake Inhibitors (SRIs). Potential confounding factors did not influence the main effect. The present findings indicate that those working at a high occupational level may be a risk factor for poor response to medication for depression and this has potential implications for clinicians and their patients, for future research, for employers and for public policy. PMID:27211903

  8. 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…

  9. 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

  10. A thermo-responsive protein treatment for dry eyes.

    PubMed

    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

    2015-02-10

    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.

  11. 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.

  12. 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.

  13. Platelet response during the second cycle of decitabine treatment predicts response and survival for myelodysplastic syndrome patients.

    PubMed

    Jung, Hyun Ae; Maeng, Chi Hoon; Kim, Moonjin; Kim, Sungmin; Jung, Chul Won; Jang, Jun Ho

    2015-06-30

    Despite the efficacy of decitabine to myelodysplastic syndrome (MDS), there is a wide range of responses, and no definite predictive marker has been identified. This study aimed to describe the efficacy of decitabine and to identify potential predictors of response and survival in patients with MDS. We retrospectively analyzed clinical data of MDS patients at Samsung Medical Center between August 2008 and August 2011. The response assessment was conducted using the International Working Group (IWG) response criteria for MDS. We analyzed 101 MDS patients (total 613 cycles) who received decitabine for a median of four cycles. The overall response was 52.5% (n = 53/101). The median time to any response was two cycles with the median overall survival of 16.7 months. Patients who showed hematologic improvement had significantly longer survival than those who did not (9.8 vs. 22.9 months, p = 0.004). The difference in OS was evident in the Intermediate-2/High risk group (p = 0.002) but not in the Intermediate-1 risk group (p = 0.145). Multivariate analysis confirmed that platelet response (no platelet transfusions for at least 3 days) during the second cycle of treatment was an independent predictor for response, OS and Leukemia free survival. Based on the results of this study, for patients with hematological improvement, recovery of platelet count by the second cycle of therapy can be used as an early predictive marker of improved survival and an increased response rate.

  14. Personality and treatment response in agoraphobia with panic attacks.

    PubMed

    Clair, A L; Oei, T P; Evans, L

    1992-01-01

    The present study investigated the association of specific personality characteristics with agoraphobia, and whether they predicted long-term outcome following a group cognitive behavior therapy program. Thirty-three patients with agoraphobia with panic attacks, 18 with social phobia, and 26 "normals" were used in the study. Personality factors were measured with the Maudsley Personality Inventory (MPI), the Hostility and Direction of Hostility Questionnaire (HDHQ), and the Fundamental Interpersonal Relations Orientation-Behavior Scale (FIRO-B). The results showed that (1) agoraphobics are more extroverted and more likely to include others in their activities than are social phobics; however, they are less extroverted, more neurotic, more hostile and intropunitive, and less likely to include others in their activities than are normals; (2) social phobics are similarly less extroverted, more neurotic, and more hostile and intropunitive than normals, but, in addition, are less likely to exert control over others, more likely to want to be controlled, and less expressive of affection than normals; and (3) personality characteristics did not predict treatment outcome.

  15. 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.

  16. 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.

  17. 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. PMID:20079979

  18. 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:…

  19. 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…

  20. Neural correlates of inhibition and contextual cue processing related to treatment response in PTSD.

    PubMed

    van Rooij, Sanne J H; Geuze, Elbert; Kennis, Mitzy; Rademaker, Arthur R; Vink, Matthijs

    2015-02-01

    Thirty to fifty percent of posttraumatic stress disorder (PTSD) patients do not respond to treatment. Understanding the neural mechanisms underlying treatment response could contribute to improve response rates. PTSD is often associated with decreased inhibition of fear responses in a safe environment. Importantly, the mechanism of effective treatment (psychotherapy) relies on inhibition and so-called contextual cue processing. Therefore, we investigate inhibition and contextual cue processing in the context of treatment. Forty-one male war veterans with PTSD and 22 healthy male war veterans (combat controls) were scanned twice with a 6- to 8-month interval, in which PTSD patients received treatment (psychotherapy). We distinguished treatment responders from nonresponders on the base of percentage symptom decrease. Inhibition and contextual cue processing were assessed with the stop-signal anticipation task. Behavioral and functional MRI measures were compared between PTSD patients and combat controls, and between responders and nonresponders using repeated measures analyses. PTSD patients showed behavioral and neural deficits in inhibition and contextual cue processing at both time points compared with combat controls. These deficits were unaffected by treatment; therefore, they likely represent vulnerability factors or scar aspects of PTSD. Second, responders showed increased pretreatment activation of the left inferior parietal lobe (IPL) during contextual cue processing compared with nonresponders. Moreover, left IPL activation predicted percentage symptom improvement. The IPL has an important role in contextual cue processing, and may therefore facilitate the effect of psychotherapy. Hence, increased left IPL activation may represent a potential predictive biomarker for PTSD treatment response.

  1. 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…

  2. 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.

  3. 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.

  4. 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…

  5. 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…

  6. 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…

  7. Assessment of treatment response in chronic constipation clinical trials

    PubMed Central

    Ervin, Claire M; Fehnel, Sheri E; Baird, Mollie J; Carson, Robyn T; Johnston, Jeffrey M; Shiff, Steven J; Kurtz, Caroline B; Mangel, Allen W

    2014-01-01

    Background While chronic constipation (CC) clinical trials have focused primarily on bowel symptoms (symptoms directly related to bowel movements), abdominal symptoms are also prevalent among patients. The United States Food and Drug Administration’s (FDA’s) guidance on the use of patient-reported outcome measures to support product approvals or labeling claims recommends that endpoints be developed with direct patient input and include all symptoms important to patients. Aim To identify a comprehensive set of CC symptoms that are important to patients for measurement in clinical trials. Methods Following a targeted literature review to identify CC symptoms previously reported by patients, 28 patient interviews were conducted consistent with the FDA’s guidance on patient-reported outcomes. Subsequent to open-ended questions eliciting descriptions of all symptoms, rating and ranking methods were used to identify those of greatest importance to patients. Results All 67 studies reviewed included bowel symptoms; more than half also addressed at least one abdominal symptom. Interview participants reported 62 potentially distinct concepts: 12 bowel symptoms; 21 abdominal symptoms; and 29 additional symptoms/impacts. Patients’ descriptions revealed that many symptom terms were highly related and/or could be considered secondary to CC. The rating and ranking task results suggest that both bowel (for example, stool frequency and consistency) and abdominal symptoms (for example, bloating, abdominal pain) comprise patients’ most important symptoms. Further, improvements in both bowel and abdominal symptoms would constitute an improvement in patients’ CC overall. Conclusion Abdominal symptoms in CC patients are equal in relevance to bowel symptoms and should also be addressed in clinical trials to fully evaluate treatment benefit. PMID:24940076

  8. Aldosterone response to metoclopramide in patients with prolactinoma: effect of short-term bromocriptine treatment.

    PubMed

    Zacharieva, S; Stoeva, I; Andreeva, M; Kalinov, K; Matrozov, P; Andonova, K

    1996-11-01

    The acute effect of 10 mg metoclopramide i.v. on prolactin and aldosterone levels was studied in 8 women with prolactinoma and 8 normal women. The prolactin response to metoclopramide was blunted in hyperprolactinemic patients in comparison with controls. Metoclopramide induced similar aldosterone increases in patients and controls, but hyperprolactinemic women showed a more sustained aldosterone response. Bromocriptine treatment (10 mg daily p.o. for 5 days) in patients with prolactinoma completely suppressed the prolactin response to metoclopramide and the aldosterone response curve was very similar to that of controls. The results did not exclude some degree of suppression of aldosterone in response to bromocriptine.

  9. 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…

  10. 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…

  11. 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.

  12. Auditory brainstem responses in patients under treatment of hemodialysis.

    PubMed

    Aspris, Andreas K; Thodi, Chryssoula D; Balatsouras, Dimitrios G; Thodis, Elias D; Vargemezis, Vassilis; Danielides, Vassilis

    2008-01-01

    This study evaluated the effects of end stage chronic renal failure (CRF) on auditory function and changes in auditory function following a single session of hemodialysis. The experimental group included 31 patients with end-stage renal failure on chronic hemodialysis. The control group consisted of 31 healthy volunteers. The patients were examined prior to and following a session of hemodialysis. Measurements included pure tone audiometry, tympanometry and acoustic reflex measurements, auditory brainstem responses (ABR), and blood now chemistry parameters. Controls underwent the same test battery, with the exception of biochemical and hematological assessment. Prior to hemodialysis sessions, all ABR latencies except interpeak latency I-III were significantly prolonged in the experimental group. A comparison between controls and the experimental group following hemodialysis indicated that wave V absolute latency and interpeak latencies III-V and I-V were significantly prolonged in the slow repetition rate paradigm. In the fast repetition rate, absolute latencies of waves I and V and III-V interpeak latencies were prolonged in the experimental group. Comparison of ABR recordings prior to and following hemodialysis showed overall significant difference between the measures. Post hoc analysis showed a significant improvement in wave I and V latencies in the slow repetition rate and wave V latency in the fast repetition rate. This study showed that neural conduction along the auditory pathway is delayed in patients with end stage CRF as compared to healthy subjects. Dialysis sessions improve overall neural auditory function. However, patients with end stage CRF show delayed conduction even after a session of hemodialysis. PMID:18569911

  13. Early Response to Antipsychotic Drug Therapy as a Clinical Marker of Subsequent Response in the Treatment of Schizophrenia

    PubMed Central

    Kinon, Bruce J; Chen, Lei; Ascher-Svanum, Haya; Stauffer, Virginia L; Kollack-Walker, Sara; Zhou, Wei; Kapur, Shitij; Kane, John M

    2010-01-01

    Our objective was to prospectively assess whether early (ie, 2 weeks) response to an antipsychotic predicts later (12-week) response and whether ‘switching' early non-responders to another antipsychotic is a better strategy than ‘staying'. This randomized, double-blind, flexible-dosed, 12-week study enrolled 628 patients diagnosed with schizophrenia or schizoaffective disorder. All initiated treatment with risperidone. Early response was defined as ⩾20% improvement on the Positive and Negative Syndrome Scale (PANSS) total score following 2 weeks of treatment. Early responders (ERs) continued on risperidone, whereas early non-responders (ENRs) were randomized (1 : 1) to continue on risperidone 2–6 mg/day or switch to olanzapine 10–20 mg/day for 10 additional weeks. Compared with ENRs, risperidone ERs showed significantly greater reduction in PANSS total score (end point; p<001). Early response/non-response was highly predictive of subsequent clinical outcomes. Switching risperidone ENRs to olanzapine at week 2 resulted in a small but significantly greater reduction in PANSS total score (end point; p=0.020) and in depressive symptoms (end point; p=0.004); the reduction in PANSS was greater among those who were still moderately ill at 2 weeks. Switching risperidone ENRs to olanzapine also resulted in significantly greater increases in triglycerides, a significantly greater decrease in prolactin, and significantly less treatment-emergent dyskinesia. This is the first study to prospectively show that early response/non-response to an antipsychotic (risperidone) is a reliable clinical marker of subsequent clinical outcomes and that a ‘switching' strategy based on this information may lead to greater clinical improvement than staying on a drug for a longer period in some patients. PMID:19890258

  14. The impact of transient combination antiretroviral treatment in early HIV infection on viral suppression and immunologic response in later treatment

    PubMed Central

    Pantazis, Nikos; Touloumi, Giota; Meyer, Laurence; Olson, Ashley; Costagliola, Dominique; Kelleher, Anthony D.; Lutsar, Irja; Chaix, Marie-Laure; Fisher, Martin; Moreno, Santiago; Porter, Kholoud

    2016-01-01

    Objective: Effects of transient combination antiretroviral treatment (cART) initiated during early HIV infection (EHI) remain unclear. We investigate whether this intervention affects viral suppression and CD4+ cell count increase following its reinitiation in chronic infection (CHI). Design: Longitudinal observational study. Methods: We identified adult patients from Concerted Action of Seroconversion to AIDS and Death in Europe who seroconverted after 1/1/2000, had a 12 months or less HIV test interval and initiated cART from naive. We classified individuals as ‘pretreated in EHI’ if treated within 6 months of seroconversion, interrupted for at least 12 weeks, and reinitiated during CHI. Statistical analysis was performed using survival analysis methods and mixed models. Results: Pretreated and initiated in CHI groups comprised 202 and 4263 individuals, with median follow-up after CHI treatment 4.5 and 3 years, respectively. Both groups had similar virologic response and relapse rates (P = 0.585 and P = 0.206) but pretreated individuals restarted treatment with higher baseline CD4+ cell count (∼80 cells/μl; P < 0.001) and retained significantly higher CD4+ cell count for more than 3 years after treatment (re)initiation. Assuming common baseline CD4+ cell count, differences in CD4+ cell count slopes were nonsignificant. Immunovirologic response to CHI treatment was not associated with timing or duration of the transient treatment. Conclusion: Although treatment interruptions are not recommended, stopping cART initiated in EHI does not seem to reduce the chance of a successful outcome of treatment in CHI. PMID:26636925

  15. Fast response hydrogen sensors based on anodic aluminum oxide with pore-widening treatment

    NASA Astrophysics Data System (ADS)

    Wu, Shuanghong; Zhou, Han; Hao, Mengmeng; Wei, Xiongbang; Li, Shibin; Yu, He; Wang, Xiangru; Chen, Zhi

    2016-09-01

    Fast response hydrogen sensors operating at room temperature based on nanoporous palladium (Pd) films supported by treated anodic aluminum oxide (AAO) template have been demonstrated. It was found that the nanoporous Pd film had a quicker and reversible response by a 30-min pore-widening treatment of the AAO template, due to its faster absorption and desorption of hydrogen. We obtained a sensor response time as short as 14 s at 1.4% hydrogen concentration with the 30-min pore-widening treatment of AAO template. The sensor exhibited very good performance at hydrogen concentrations from 0.1% to 2%.

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

    PubMed Central

    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, we seek to identify the variables that were associated with response across both treatments as well as variables that predicted superior response in one treatment over the other. The sample consisted of 180 depressed outpatients: 60 of whom were randomly assigned to cognitive therapy; 120 were assigned to antidepressant medications. Treatment was provided for 16 weeks. Chronic depression, older age, and lower intelligence each predicted relatively poor response across both treatments. Three prescriptive variables were identified: marriage, unemployment, and having experienced a greater number of recent life events predicted superior response to cognitive therapy compared to antidepressant medications. Thus, six markers of treatment outcome were identified, each of which might be expected to carry considerable clinical utility. The three prognostic variables identify subgroups that might benefit from alternative treatment strategies; the three prescriptive variables identify groups who appear to respond particularly well to cognitive therapy. PMID:19634969

  17. The efficacy of a response cost-based treatment package for managing aggressive behavior in preschoolers.

    PubMed

    Reynolds, L K; Kelley, M L

    1997-04-01

    The present study examined the effectiveness of a response cost treatment package for improving the classroom behavior of four aggressive preschoolers. Using a multiple baseline design, teachers implemented the response cost system during the treatment phases of the study. The system required teachers to remove smiley faces contingent on aggressive behavior. Each face loss was accompanied by a reprimand. If the child retained at least one smiley face at the end of the observation period, he was allowed to choose from a list of rewards. Rewards were easily administered at school. The results indicated that the response cost treatment package substantially decreased aggressive behavior and was a highly acceptable classroom treatment to teachers and parents. PMID:9086867

  18. The efficacy of a response cost-based treatment package for managing aggressive behavior in preschoolers.

    PubMed

    Reynolds, L K; Kelley, M L

    1997-04-01

    The present study examined the effectiveness of a response cost treatment package for improving the classroom behavior of four aggressive preschoolers. Using a multiple baseline design, teachers implemented the response cost system during the treatment phases of the study. The system required teachers to remove smiley faces contingent on aggressive behavior. Each face loss was accompanied by a reprimand. If the child retained at least one smiley face at the end of the observation period, he was allowed to choose from a list of rewards. Rewards were easily administered at school. The results indicated that the response cost treatment package substantially decreased aggressive behavior and was a highly acceptable classroom treatment to teachers and parents.

  19. 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

  20. Therapygenetics: Using genetic markers to predict response to psychological treatment for mood and anxiety disorders

    PubMed Central

    2013-01-01

    Considerable variation is evident in response to psychological therapies for mood and anxiety disorders. Genetic factors alongside environmental variables and gene-environment interactions are implicated in the etiology of these disorders and it is plausible that these same factors may also be important in predicting individual differences in response to psychological treatment. In this article, we review the evidence that genetic variation influences psychological treatment outcomes with a primary focus on mood and anxiety disorders. Unlike most past work, which has considered prediction of response to pharmacotherapy, this article reviews recent work in the field of therapygenetics, namely the role of genes in predicting psychological treatment response. As this is a field in its infancy, methodological recommendations are made and opportunities for future research are identified. PMID:23388219

  1. 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.

  2. 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. PMID:27085227

  3. Monitoring the Response to Tyrosine Kinase Inhibitor (TKI) Treatment in Chronic Myeloid Leukemia (CML)

    PubMed Central

    Haznedaroglu, Ibrahim C.

    2014-01-01

    The aim of oral tyrosine kinase inhibitor (TKI) treatment in chronic myeloid leukemia (CML) is to get ideal hematological, cytogenetic, molecular responses at the critical time points. The depth of the response obtained with TKI and the time to achieve this response are both important in predicting the prognosis in patients with CML. The high efficacy of the TKI treatment of CML has prompted the need for accurate methods to monitor response at levels below the landmark of CCyR. Quantification of BCR-ABL transcripts has proven to be the most sensitive method available and has shown prognostic impact with regard to progression-free survival. European LeukemiaNet (ELN) molecular program harmonized the reporting of results according to the IS (International harmonization of Scale) in Europe. The aim of this review is to outline monitoring the response to optimal TKI treatment based on the ELN CML 2013 recommendations from the clinical point of view as a physician. Careful cytogenetic and molecular monitoring could help to select the most convenient TKI drug and to optimize TKI treatment. Excessive monitoring may have an economic cost, but failure to optimize TKI treatment may result in CML disease acceleration and death. PMID:24455118

  4. PCLO rs2522833 modulates HPA system response to antidepressant treatment in major depressive disorder.

    PubMed

    Schuhmacher, Anna; Mössner, Rainald; Höfels, Susanne; Pfeiffer, Ute; Guttenthaler, Vera; Wagner, Michael; Schwab, Sibylle G; Maier, Wolfgang; Zobel, Astrid

    2011-03-01

    Variant rs2522833 of the Piccolo-encoding gene PCLO has recently been found to be associated with major depressive disorder (MDD). PCLO encodes a presynaptic cytomatrix protein which influences monoamine neurotransmitter release. Piccolo could therefore play an important role in treatment response to antidepressant therapy and the improvement of alterations in HPA system reactivity. We investigated the influence of the coding variant rs2522833 in the PCLO gene on treatment response in 205 in-patients with unipolar depression. Treatment response was measured (1) at the level of psychopathology using the Hamilton Depression Rating Scale (HAMD) and (2) with the combined dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, which is a refined tool for showing dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system, a neurobiological finding in depression. While we did not find an association between variation in PCLO and HAMD scores, HPA dysregulation was less pronounced in carriers of the AA genotype than in carriers of one or two C alleles. HPA activity of individuals with the AA genotype only marginally changed during 4-wk antidepressant treatment, whereas C allele carriers showed a higher hormonal secretion at admission than carriers of the AA genotype but lower responsivity to the Dex/CRH challenge after 4 wk. Our results point to a moderating role of PCLO SNP rs2522833 on HPA regulation during antidepressant treatment, which may represent a neurobiological feature of stability of clinical response.

  5. 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.

  6. Shrub resprouting response after fuel reduction treatments: comparison of prescribed burning, clearing and mastication.

    PubMed

    Fernández, Cristina; Vega, José A; Fonturbel, Teresa

    2013-03-15

    Fuel reduction treatments are commonly used to reduce the risk of severe wildfire. However, more information about the effects on plant resprouting is needed to help land managers select the most appropriate treatment. To address this question, we evaluated the resprouting ability of five shrub species after the application of different types of fuel reduction methods (prescribed burning, clearing and mastication) in two contrasting shrubland areas in northern Spain. The shrub species were Erica australis, Pterospartum tridentatum and Halimium lasianthum spp. alyssoides, Ulex gallii and Erica cinerea. For most of the species under study (E. australis, P. tridentatum, H. lasianthum spp. alyssoides and U. gallii), neither plant mortality nor the number nor length of sprouted shoots per plant differed between treatments, although in E. cinerea the number of shoots was more negatively affected by prescribed burning than by clearing or mastication. The pre-treatment plant size did not affect plant mortality or plant resprouting response, suggesting that this parameter alone is not a good indicator of plant resprouting after fuel reduction treatments. Stem minimum diameter after treatments, a proxy of treatment severity, was not related to plant mortality, number or length of resprouted shoots. The duration of temperatures higher than 300 °C during burning in plant crown had a negative effect on the length of resprouted shoots, only in E. cinerea. The results show that fuel reduction treatments did not prevent shrub response in any case. Some reflections on the applicability of treatments are discussed.

  7. Inflammation and clinical response to treatment in depression: A meta-analysis.

    PubMed

    Strawbridge, R; Arnone, D; Danese, A; Papadopoulos, A; Herane Vives, A; Cleare, A J

    2015-10-01

    The depressive state has been characterised as one of elevated inflammation, which holds promise for better understanding treatment-resistance in affective disorders as well as for future developments in treatment stratification. Aiming to investigate alterations in the inflammatory profiles of individuals with depression as putative biomarkers for clinical response, we conducted meta-analyses examining data from 35 studies that investigated inflammation before and after treatment in depressed patients together with a measure of clinical response. There were sufficient data to analyse IL-6, TNFα and CRP. Levels of IL-6 decreased with antidepressant treatment regardless of outcome, whereas persistently elevated TNFα was associated with prospectively determined treatment resistance. Treatment non-responders tended to have higher baseline inflammation, using a composite measure of inflammatory markers. Our findings suggest that elevated levels of inflammation are contributory to treatment resistance. Combining inflammatory biomarkers might prove a useful tool to improve diagnosis and detection of treatment refractoriness, and targeting persistent inflammation in treatment-resistant depression may offer a potential target for the development of novel intervention strategies. PMID:26169573

  8. 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.

  9. 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

  10. Within patient microevolution of Mycobacterium tuberculosis correlates with heterogeneous responses to treatment

    PubMed Central

    Liu, Qingyun; Via, Laura E.; Luo, Tao; Liang, Lili; Liu, Xin; Wu, Sufang; Shen, Qingyu; Wei, Wang; Ruan, Xianglin; Yuan, Xing; Zhang, Guolong; Barry, Clifton E.; Gao, Qian

    2015-01-01

    Genetic heterogeneity of Mycobacterium tuberculosis (MTB) within a patient has caused great concern as it might complicate antibiotic treatment and cause treatment failure. But the extent of genetic heterogeneity has not been described in detail nor has its association with heterogeneous treatment response. During treatment of a subject with MDR-TB, serial computed tomography (CT) scans showed this subject had six anatomically discrete lesions and they responded to treatment with disparate kinetics, suggesting heterogeneous MTB population may exist. To investigate this heterogeneity, we applied deep whole genome sequencing of serial sputum isolates and discovered that the MTB population within this patient contained three dominant sub-clones differing by 10 ~ 14 single nucleotide polymorphisms (SNPs). Differential mutation patterns in known resistance alleles indicated these sub-clones had different drug-resistance patterns, which may explain the heterogeneous treatment responses between lesions. Our results showed clear evidence of branched microevolution of MTB in vivo, which led to a diverse bacterial community. These findings indicated that complex sub-populations of MTB might coexist within patient and contribute to lesions’ disparate responses to antibiotic treatment. PMID:26620446

  11. Assessing Tumor Response to Treatment in Patients with Lung Cancer Using Dynamic Contrast-Enhanced CT

    PubMed Central

    Strauch, Louise S.; Eriksen, Rie Ø.; Sandgaard, Michael; Kristensen, Thomas S.; Nielsen, Michael B.; Lauridsen, Carsten A.

    2016-01-01

    The aim of this study was to provide an overview of the literature available on dynamic contrast-enhanced computed tomography (DCE-CT) as a tool to evaluate treatment response in patients with lung cancer. This systematic review was compiled according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only original research articles concerning treatment response in patients with lung cancer assessed with DCE-CT were included. To assess the validity of each study we implemented Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). The initial search yielded 651 publications, and 16 articles were included in this study. The articles were divided into groups of treatment. In studies where patients were treated with systemic chemotherapy with or without anti-angiogenic drugs, four out of the seven studies found a significant decrease in permeability after treatment. Four out of five studies that measured blood flow post anti-angiogenic treatments found that blood flow was significantly decreased. DCE-CT may be a useful tool in assessing treatment response in patients with lung cancer. It seems that particularly permeability and blood flow are important perfusion values for predicting treatment outcome. However, the heterogeneity in scan protocols, scan parameters, and time between scans makes it difficult to compare the included studies. PMID:27455330

  12. 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

  13. 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

  14. Whole-genome expression analysis reveals genes associated with treatment response to escitalopram in major depression.

    PubMed

    Pettai, Kristi; Milani, Lili; Tammiste, Anu; Võsa, Urmo; Kolde, Raivo; Eller, Triin; Nutt, David; Metspalu, Andres; Maron, Eduard

    2016-09-01

    The reasons for variability in treatment response in major depressive disorder (MDD) are not fully understood, but there is accumulating evidence suggesting that therapeutic outcomes of antidepressants can be influenced by genetic factors. In the present study we applied the microarray Illumina platform for whole genome expression profiling in depressive patients treated with escitalopram medication in order to identify genes underlying response to antidepressant treatment. The initial study sample consisted of 135 outpatients with major depressive disorder (mean age 31.1±11.6 years, 68% females) treated with escitalopram 10-20mg/day for 12 weeks, from which 87 patients (55 females) were included in gene expression analyzing. The gene expression profiles were measured on peripheral blood cells at baseline, at week 4 and at the end of treatment (week 12) using BeadChips Illumina. The fold change was used to demonstrate rate of changes in average gene expressions between studied groups. Statistical analyses were performed using the false discovery rate (FDR). The most interesting gene, which showed the predictive effect on treatment outcome by delineating low dose responders and treatment-resistant patients at the beginning of medication, was NLGN2, belonging to a family of neuronal cell surface proteins and involving in synapse formation. In addition, the several gene clusters, related to immune response, signal transduction and neurotrophin pathway, have distinguished responders from non-responders at the week 4 of treatment. After 4 weeks of escitalopram treatment (10mg/day), the YWHAZ gene has showed the highest transcriptional change in responders as compared with non-responders. Finally, at the end of the treatment we noticed that at least three genes (NR2C2, ZNF641, FKBP1A) have been strongly associated with resistance to escitalopram. Thus the results of this study support that exploration of peripheral gene expression is a useful tool in the further

  15. Whole-genome expression analysis reveals genes associated with treatment response to escitalopram in major depression.

    PubMed

    Pettai, Kristi; Milani, Lili; Tammiste, Anu; Võsa, Urmo; Kolde, Raivo; Eller, Triin; Nutt, David; Metspalu, Andres; Maron, Eduard

    2016-09-01

    The reasons for variability in treatment response in major depressive disorder (MDD) are not fully understood, but there is accumulating evidence suggesting that therapeutic outcomes of antidepressants can be influenced by genetic factors. In the present study we applied the microarray Illumina platform for whole genome expression profiling in depressive patients treated with escitalopram medication in order to identify genes underlying response to antidepressant treatment. The initial study sample consisted of 135 outpatients with major depressive disorder (mean age 31.1±11.6 years, 68% females) treated with escitalopram 10-20mg/day for 12 weeks, from which 87 patients (55 females) were included in gene expression analyzing. The gene expression profiles were measured on peripheral blood cells at baseline, at week 4 and at the end of treatment (week 12) using BeadChips Illumina. The fold change was used to demonstrate rate of changes in average gene expressions between studied groups. Statistical analyses were performed using the false discovery rate (FDR). The most interesting gene, which showed the predictive effect on treatment outcome by delineating low dose responders and treatment-resistant patients at the beginning of medication, was NLGN2, belonging to a family of neuronal cell surface proteins and involving in synapse formation. In addition, the several gene clusters, related to immune response, signal transduction and neurotrophin pathway, have distinguished responders from non-responders at the week 4 of treatment. After 4 weeks of escitalopram treatment (10mg/day), the YWHAZ gene has showed the highest transcriptional change in responders as compared with non-responders. Finally, at the end of the treatment we noticed that at least three genes (NR2C2, ZNF641, FKBP1A) have been strongly associated with resistance to escitalopram. Thus the results of this study support that exploration of peripheral gene expression is a useful tool in the further

  16. 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.

  17. Dissecting the Heterogeneity of Treatment Response in First-Episode Schizophrenia.

    PubMed

    Malhotra, Anil K

    2015-11-01

    The Mental Health Centers for Intervention Development and Applied Research (CIDAR) program prioritized research to provide an evidence base for biomarker development. At the Zucker Hillside Hospital (ZHH), our CIDAR grant supported research on a comprehensive investigation of treatment response and outcome in first episode schizophrenia. Results provide evidence that baseline neuroimaging, neurocognitive, and genetic measures are significantly associated with clinical response to treatment, and that our currently available interventions can effectively treat aspects of psychotic illness, as well as potentially reduce comorbidity associated with illness. Future research may include combining modalities to more robustly predict response and identify treatment targets, as well as to further develop more effective intervention strategies for these devastating and disabling disorders. PMID:26333841

  18. 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

  19. Gender Differences in Obstructive Sleep Apnea and Treatment Response to Continuous Positive Airway Pressure

    PubMed Central

    Ye, Lichuan; Pien, Grace W.; Ratcliffe, Sarah J.; Weaver, Terri E.

    2009-01-01

    Objectives: Whether gender differences exist in clinical manifestations of obstructive sleep apnea (OSA) and whether women's responses to continuous positive airway pressure (CPAP) are similar to those of men are critical areas of exploration in sleep disordered breathing. This exploratory analysis addressed these questions by examining gender differences over a wide range of clinical outcomes at baseline and in response to CPAP in participants with severe OSA. Methods: Data from 152 men and 24 women who participated in a multicenter CPAP effectiveness study were analyzed. Gender differences in functional status (functional outcomes of sleep questionnaire, sickness impact profile), daytime sleepiness (epworth sleepiness scale, multiple sleep latency test), mood disturbance (profile of mood states), apnea symptoms (multivariable apnea prediction index), and neurobehavioral performance (psychomotor vigilance task) were examined. Treatment response was examined by the change in each outcome from baseline to 3 months after treatment. Results: Despite similar age, body mass index, and apnea-hypopnea index, women reported significantly lower functional status, more subjective daytime sleepiness, higher frequency of apnea symptoms, more mood disturbance, and poorer neurobehavioral performance compared to men at baseline. CPAP treatment significantly improved functional status and relieved symptoms for both genders. The magnitude of improvement in each clinical outcome did not vary by gender. Conclusions: Women with OSA showed greater impairment in daytime functioning and symptoms than men. Both genders benefit from CPAP treatment. Adequately powered studies considering possible referral and response bias are necessary to examine gender differences in OSA clinical manifestations and response to CPAP treatment. Citation: Ye L; Pien GW; Ratcliffe SJ; Weaver TE. Gender Differences in Obstructive Sleep Apnea and Treatment Response to Continuous Positive Airway Pressure. J Clin

  20. Neural Correlates of Treatment in Adolescents with Bipolar Depression During Response Inhibition

    PubMed Central

    Segreti, Anna Maria; Ladouceur, Cecile D; Almeida, Jorge RC; Birmaher, Boris; Axelson, David A; Phillips, Mary L; Pan, Lisa

    2013-01-01

    Abstract Objective Abnormal prefrontal and subcortical activity during cognitive control tasks is identified in non-depressed adolescents with bipolar disorder (BD); however, little is known about the neural correlates of bipolar adolescents in a depressed state (BDd). We aimed to investigate baseline versus after-treatment patterns of neural activity underlying motor response and response inhibition in adolescents with BDd. Methods In this functional magnetic resonance imaging (fMRI) study, 10 adolescents with BDd relative to 10 age- and sex-matched healthy controls (HC) completed a well-validated go/no go block-design cognitive control task at baseline and after 6 weeks of naturalistic treatment. We used whole-brain analysis and controlled our results for multiple comparisons. Results There was significant improvement in depression scores (mean change: 57%±28). There was no behavioral difference in BDd baseline versus HC and after treatment. BDd adolescents relative to HC had higher baseline cortical, but not subcortical, neural activity (e.g., bilateral ventrolateral prefrontal during both the go [motor control] and the no go [response inhibition] conditions, and left superior temporal during the no go condition). However, after-treatment activity relative to baseline neural activity during response inhibition was significantly increased in subcortical (e.g., right hippocampus and left thalamus), but not cortical, regions. In addition, at baseline, lower left thalamus activity was correlated with higher depression scores. Conclusions Adolescents with BDd had baseline prefrontal and temporal hyperactivity underlying motor control and response inhibition that did not change after treatment in contrast to relatively decreased baseline subcortical activity underlying response inhibition associated with the depressive state that was increased after the treatment. PMID:23607410

  1. Effect of Parental Age on Treatment Response in Adolescents with Schizophrenia

    PubMed Central

    Opler, Mark; Malaspina, Dolores; Gopal, Srihari; Nuamah, Isaac; Savitz, Adam J; Singh, Jaskaran; Hough, David

    2013-01-01

    Background Advanced paternal age (APA) is associated with increased risk for schizophrenia, but its effect on treatment response has not been longitudinally studied. Methods Association of parental ages at the time of the child's birth with age of onset, initial symptom severity and treatment response (to placebo and three different weight-based doses of paliperidone ER) in adolescents with schizophrenia was assessed in a post-hoc analysis using data from a 6-week double-blind study, the primary results of which are published (NCT 00518323). Results The mean (SD) paternal age was 29.2 (6.2) years, range (16-50) and maternal age was 26.8 (5.7) years, range (17-42) at childbirth for the 201 adolescents (ages 12-17 years) included in the analysis. While parental ages were uncorrelated with age of onset or initial symptom severity, both maternal and paternal age showed significant effects on treatment response (p < 0.03) of all paliperidone ER arms versus placebo. Paternal age was significantly correlated to improvement in positive symptoms and maternal age significantly related to negative symptoms, although only paternal age remained significantly associated with the treatment response in analyses that included both parents’ ages. Conclusions APA was associated with greater treatment response to both paliperidone ER and placebo, but not to age of onset or initial symptom severity in adolescents with schizophrenia. The results support the contention that APA-related schizophrenia has distinct underpinnings from other cases. Further studies are required to explore the role of genetic and environmental factors, and their interactions, in treatment response in this complex disorder. PMID:24144440

  2. Pharmacogenetics and pharmacogenomics for rheumatoid arthritis responsiveness to methotrexate treatment: the 2013 update.

    PubMed

    Zhu, Hong; Deng, Fei-Yan; Mo, Xing-Bo; Qiu, Ying-Hua; Lei, Shu-Feng

    2014-03-01

    Rheumatoid arthritis (RA) is a complex, systemic autoimmune disease characterized by chronic inflammation of multiple peripheral joints, which leads to serious destruction of cartilage and bone, progressive deformity and severe disability. Methotrexate (MTX) is one of the first-line drugs commonly used in RA therapy owing to its excellent long-term efficacy and cheapness. However, the efficacy and toxicity of MTX treatment have significant interpatient variability. Genetic factors contribute to this variability. In this review, we have summarized and updated the progress of RA response to MTX treatment since 2009 by focusing on the fields of pharmacogenetics and pharmacogenomics. Identification of genetic factors involved in MTX treatment response will increase the understanding of RA pathology and the development of new personalized treatments.

  3. Evaluation of treatment response in depression studies using a Bayesian parametric cure rate model.

    PubMed

    Santen, Gijs; Danhof, Meindert; Della Pasqua, Oscar

    2008-10-01

    Efficacy trials with antidepressant drugs often fail to show significant treatment effect even though efficacious treatments are investigated. This failure can, amongst other factors, be attributed to the lack of sensitivity of the statistical method as well as of the endpoints to pharmacological activity. For regulatory purposes the most widely used efficacy endpoint is still the mean change in HAM-D score at the end of the study, despite evidence from literature showing that the HAM-D scale might not be a sensitive tool to assess drug effect and that changes from baseline at the end of treatment may not reflect the extent of response. In the current study, we evaluate the prospect of applying a Bayesian parametric cure rate model (CRM) to analyse antidepressant effect in efficacy trials with paroxetine. The model is based on a survival approach, which allows for a fraction of surviving patients indefinitely after completion of treatment. Data was extracted from GlaxoSmithKline's clinical databases. Response was defined as a 50% change from baseline HAM-D at any assessment time after start of therapy. Survival times were described by a log-normal distribution and drug effect was parameterised as a covariate on the fraction of non-responders. The model was able to fit the data from different studies accurately and results show that response to treatment does not lag for two weeks, as is mythically believed. In conclusion, we demonstrate how parameterisation of a survival model can be used to characterise treatment response in depression trials. The method contrasts with the long-established snapshot on changes from baseline, as it incorporates the time course of response throughout treatment.

  4. 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

  5. Scaling up HIV treatment and prevention through national responses and innovative leadership.

    PubMed

    Kanki, Phyllis; Kakkattil, Pradeep; Simao, Mariangela

    2012-08-01

    Over the past decade, there has been an unprecedented global response to the AIDS epidemic. This infusion of new funding has led to a rapid scale-up of HIV treatment and prevention and consequently has saved millions of lives and transformed communities around the world. However, as clearly demonstrated by a review of national responses, successes have been due in large part to strong and innovative leadership from governments, the private sector, and nongovernmental organizations. Examples from Brazil, Botswana, Nigeria, Uganda, and India illustrate the vital role played by bold and collaborative leadership in the global and local scale-up of HIV prevention and treatment.

  6. Pharmacogenetics and individual responses to treatment of hyperglycemia in type 2 diabetes.

    PubMed

    Engelbrechtsen, Line; Andersson, Ehm; Roepstorff, Soeren; Hansen, Torben; Vestergaard, Henrik

    2015-10-01

    The aim of this study was to summarize current knowledge and provide perspectives on the relationships between human genetic variants, type 2 diabetes, antidiabetic treatment, and disease progression. Type 2 diabetes is a complex disease with clear-cut diagnostic criteria and treatment guidelines. Yet, the interindividual response to therapy and slope of disease progression varies markedly among patients with type 2 diabetes. Gene-gene, gene-environment, and gene-treatment interactions may explain some of the variation in disease progression. Several genetic variants have been suggested to be associated with response to antidiabetic drugs. Some are present in drug receptors or drug metabolizers (OCT genes, KCNJ11, ABCC8, and CYP2C9). Numerous type 2 diabetes risk variants have been identified, but genetic risk score models applying these variants have failed to identify 'disease progressors' among patients with diabetes. Although genetic risk scores are based on a few known loci and only explain a fraction of the heritability of type 2 diabetes, it seems that the genes responsible for the development of diabetes may not be the same driving disease progression after the diagnosis has been made. Pharmacogenetic interactions explain some of the interindividual variation in responses to antidiabetic treatment and may provide the foundation for future genotype-based treatment standards. PMID:26181639

  7. 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

  8. Mass spectrometry-based quantification of the cellular response to methyl methanesulfonate treatment in human cells.

    PubMed

    Aslanian, Aaron; Yates, John R; Hunter, Tony

    2014-03-01

    Faithful transmission of genetic material is essential for cell viability and organism health. The occurrence of DNA damage, due to either spontaneous events or environmental agents, threatens the integrity of the genome. The consequences of these insults, if allowed to perpetuate and accumulate over time, are mutations that can lead to the development of diseases such as cancer. Alkylation is a relevant DNA lesion produced endogenously as well as by exogenous agents including certain chemotherapeutics. We sought to better understand the cellular response to this form of DNA damage using mass spectrometry-based proteomics. For this purpose, we performed sub-cellular fractionation to monitor the effect of methyl methanesulfonate (MMS) treatment on protein localization to chromatin. The levels of over 500 proteins were increased in the chromatin-enriched nuclear lysate including histone chaperones. Levels of ubiquitin and subunits of the proteasome were also increased within this fraction, suggesting that ubiquitin-mediated degradation by the proteasome has an important role in the chromatin response to MMS treatment. Finally, the levels of some proteins were decreased within the chromatin-enriched lysate including components of the nuclear pore complex. Our spatial proteomics data demonstrate that many proteins that influence chromatin organization are regulated in response to MMS treatment, presumably to open the DNA to allow access by other DNA damage response proteins. To gain further insight into the cellular response to MMS-induced DNA damage, we also performed phosphorylation enrichment on total cell lysates to identify proteins regulated via post-translational modification. Phosphoproteomic analysis demonstrated that many nuclear phosphorylation events were decreased in response to MMS treatment. This reflected changes in protein kinase and/or phosphatase activity in response to DNA damage rather than changes in total protein abundance. Using these two mass

  9. The treatment of “anxiety-depression” via positive reinforcement and response cost1

    PubMed Central

    Reisinger, James John

    1972-01-01

    A target behavior program, structured within a token economy project, was implemented to modify the behavior of an institutionalized patient who exhibited excessive rates of crying and no smiling responses. To affect both responses concurrently, token costs were made contingent upon crying and token payments and/or social reinforcements were provided for smiling. The results indicated both the feasibility of eliminating “anxiety-depression” within an institutional environment and the efficacy of the treatment procedures 14 months after discharge. PMID:16795330

  10. The treatment of "anxiety-depression" via positive reinforcement and response cost.

    PubMed

    Reisinger, J J

    1972-01-01

    A target behavior program, structured within a token economy project, was implemented to modify the behavior of an institutionalized patient who exhibited excessive rates of crying and no smiling responses. To affect both responses concurrently, token costs were made contingent upon crying and token payments and/or social reinforcements were provided for smiling. The results indicated both the feasibility of eliminating "anxiety-depression" within an institutional environment and the efficacy of the treatment procedures 14 months after discharge.

  11. Working memory fMRI activation in cocaine dependent subjects: association with treatment response

    PubMed Central

    Moeller, F. Gerard; Steinberg, Joel L.; Schmitz, Joy M.; Ma, Liangsuo; Liu, Shijing; Kjome, Kimberly L.; Rathnayaka, Nuvan; Kramer, Larry A.; Narayana, Ponnada A.

    2010-01-01

    fMRI studies of early abstinence cocaine users offer information about the state of the brain when most cocaine users seek treatment. This study examined the relationship between pretreatment brain function and subsequent treatment response in 19 treatment-seeking early abstinence cocaine dependent (CD) subjects. These subjects and 14 non-drug using control subjects underwent fMRI while performing a working memory task with three levels of difficulty. CD subjects were then randomized to treatment studies. Results showed CD subjects had significantly lower (random effects, corrected for multiple comparisons) brain activation in caudate, putamen, cingulate gyrus, middle and superior frontal gyri, inferior frontal gyrus pars triangularis and pars opercularis, precentral gyrus, and thalamus compared to non-drug using controls. Within CD subjects, thalamic activation significantly correlated with treatment response. This study shows CD subjects in early abstinence have alteration of brain function in frontal, striatal, and thalamic brain regions known to be part of a circuit associated with motor control, reward, and cognition. Subjects with pretreatment thalamic deactivation showed the poorest treatment response, possibly related to thalamic involvement in mesocortical and mesolimbic dopamine projections. PMID:20153142

  12. 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

  13. PET/CT Imaging for Monitoring Recurrence and Evaluating Response to Treatment in Breast Cancer.

    PubMed

    Lei, Lei; Wang, Xiaojia; Chen, Zhanhong

    2016-01-01

    Monitoring recurrence and evaluating response to therapy are important aspects of clinical decision making in the treatment of breast cancer. In this literature review, the authors highlight several of the key areas where integrated fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) measurements are anticipated to have a significant impact on monitoring recurrence and evaluating response to therapy. These areas include comparing FDG PET/CT with conventional imaging for detecting breast cancer metastases; evaluating the role of FDG PET/CT in the presence of elevated tumor markers during follow-up period after the primary surgery; using FDG PET/CT to assess response to neoadjuvant chemotherapy (NAC), targeted and endocrine therapies; using FDG PET/CT to predict response to NAC according to different molecular phenotypes of breast cancer; and applying PET/CT and some new breast-related PET tracers to evaluate response to anticancer treatment. The authors consider the relative advantages afforded by PET/CT and summarize current evidence as to the likely value of PET/CT in recurrence detection and anticancer treatment response prediction. PMID:27627573

  14. Clinical Predictors of Response to Clozapine in Patients with Treatment Resistant Schizophrenia

    PubMed Central

    A.P., Rajkumar; C., Chitra; S., Bhuvaneshwari; B., Poonkuzhali; A., Kuruvilla; K.S., Jacob

    2011-01-01

    Objectives Despite clozapine’s superior clinical efficacy in Treatment Resistant Schizophrenia (TRS), its adverse effects, need for periodic leukocyte monitoring, cost and variable clinical outcomes make the therapeutic decision making process difficult and mandate a clinical need to predict its treatment response. Hence, we investigated various clinical variables associated with treatment responses and adverse events of clozapine in TRS. Experimental Design We assessed socio-demographic and clinical profiles, premorbid adjustment, traumatic life events, cognition, disability, psychopathology and serum clozapine levels of 101 patients with TRS on stable dose of clozapine using the following instruments: Brief Psychiatric Rating Scale, Abnormal Involuntary Movements Scale, Addenbrooke’s Cognitive Examination—Revised, WHO Disability Assessment Scale-II, Childhood and Recent Traumatic Events Scale, and Premorbid Assessment Scale. We defined clozapine response a priori, adopted a case-control design framework and employed appropriate multivariate analyses. Principal Observations Past history of catatonia (p = 0.005), smoking more than one pack/day (p = 0.008), hyper-somnolence (p = 0.03) and cognitive dysfunction (p = 0.007) were associated with non-response to clozapine. Outcome definitions of non-response to clozapine influenced its association with clinical predictors. Conclusions Clinical variables are useful to predict response to clozapine. Smoking can be a potentially modifiable risk factor. Future longitudinal studies, investigating clinical and pharmacogenetic variables together, are desired.

  15. 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

  16. Hemisphere Asymmetry of Response to Pharmacologic Treatment in an Alzheimer's Disease Mouse Model.

    PubMed

    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.

  17. Hemisphere Asymmetry of Response to Pharmacologic Treatment in an Alzheimer's Disease Mouse Model.

    PubMed

    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

  18. The Usefulness of Serum CXCR3 Ligands for Evaluating the Early Treatment Response in Tuberculosis

    PubMed Central

    Chung, Wou Young; Yoon, Dukyong; Lee, Keu Sung; Jung, Yun Jung; Kim, Young Sun; Sheen, Seung Soo; Park, Kwang Joo

    2016-01-01

    Abstract Cell-mediated immunity plays an important role in the pathobiology of tuberculosis (TB). The ligands for CXC chemokine receptor 3 (CXCR3) activate the T-helper type 1 lymphocyte pathway. The CXCR3 ligands are reportedly useful clinical markers for the diagnosis and follow-up of TB. The objective of this study was to assess the utility of CXCR3 ligands for evaluating early treatment responses in TB. We recruited 88 patients who underwent antituberculous chemotherapy. The serum levels of interferon (IFN)-γ and the CXCR3 ligands CXCL9 (monokine induced by IFN-γ [MIG]), CXCL10 (IFN-γ-inducible 10-kDa protein [IP-10]), and CXCL11 (IFN-inducible T-cell α chemoattractant [I-TAC]) were measured before and 2 months after the start of treatment. Treatment responses were divided into “fast” and “slow” based on the clinical, radiological, and bacteriological improvement at 2 months. A change in level of 20% or more at 2 months was defined as “significant.” In patients with treatment success, 58 patients exhibited a fast response and 20 patients exhibited a slow response. Treatment failure occurred in 5 patients, and the diagnoses were changed to non-TB diseases in 5 patients. The levels of all CXCR3 ligands significantly decreased in the fast-response group (P < 0.01) but did not decrease in the other groups. IFN-γ levels showed no significant changes. The ability of significant decreases in marker levels to predict a fast response was evaluated. CXCL9 showed a sensitivity of 83%, and CXCL10 showed a specificity of 100%. Use of various combinations of CXCR3 ligands resulted in improvements in sensitivity (88%–93%), while specificity (92%–96%) was similar to that using single CXCR3 ligands. The decreases in CXCR3 ligand levels were less marked in the 2-month Mycobacterium tuberculosis culture-positive group than in the culture-negative group. There were significant differences in treatment outcomes in terms of 2-month culture positivity (P

  19. A Meta-Analysis of Executive Dysfunction and Antidepressant Treatment Response in Late-Life Depression

    PubMed Central

    Pimontel, Monique A.; Rindskopf, David; Rutherford, Bret R.; Brown, Patrick J.; Roose, Steven P.; Sneed, Joel R.

    2015-01-01

    Objective Depressed older adults with executive dysfunction (ED) may respond poorly to antidepressant treatment. ED is a multifaceted construct and different studies have measured different aspects of ED, making it unclear which aspects predict poor response. Meta-analytic methods were used to determine whether ED predicts poor antidepressant treatment response in late-life depression and to determine which domains of executive functioning are responsible for this relationship. Methods A Medline search was conducted to identify regimented treatment trials contrasting executive functioning between elderly responders and nonresponders; only regimented treatment trials for depressed outpatients aged 50 and older were included. Following the most recent PRISMA guidelines, 25 measures of executive functioning were extracted from eight studies. Six domains were identified: cognitive flexibility, planning and organization, response inhibition, selective attention, verbal fluency, and the Dementia Rating Scale Initiation/Perseveration composite score (DRS I/P). Hedge’s g was calculated for each measure of executive functioning. A three-level Bayesian hierarchical linear model (HLM) was used to estimate effect sizes for each domain of executive functioning. Results The effect of planning and organization was significantly different from zero (Bayesian HLM estimate of domain effect size: 0.91; 95% CI: 0.32–1.58), whereas cognitive flexibility, response inhibition, selective attention, verbal fluency, and the DRS I/P composite score were not. Conclusion The domain of planning and organization is meaningfully associated with poor antidepressant treatment response in late-life depression. These findings suggest that therapies that focus on planning and organization may provide effective augmentation strategies for antidepressant nonresponders with late-life depression. PMID:26282222

  20. A response adaptive randomization platform trial for efficient evaluation of Ebola virus treatments: A model for pandemic response.

    PubMed

    Berry, Scott M; Petzold, Elizabeth A; Dull, Peter; Thielman, Nathan M; Cunningham, Coleen K; Corey, G Ralph; McClain, Micah T; Hoover, David L; Russell, James; Griffiss, J McLeod; Woods, Christopher W

    2016-02-01

    The outbreak of Ebola virus disease in West Africa is the largest ever recorded. Numerous treatment alternatives for Ebola have been considered, including widely available repurposed drugs, but initiation of enrollment into clinical trials has been limited. The proposed trial is an adaptive platform design. Multiple agents and combinations will be investigated simultaneously. Additionally, new agents may enter the trial as they become available, and failing agents may be removed. In order to accommodate the many possible agents and combinations, a critical feature of this design is the use of response adaptive randomization to assign treatment regimens. As the trial progresses, the randomization ratio evolves to favor the arms that are performing better, making the design also suitable for all-cause pandemic preparedness planning. The study was approved by US and Sierra Leone ethics committees, and reviewed by the US Food and Drug Administration. Additionally, data management, drug supply lines, and local sites were prepared. However, in response to the declining epidemic seen in February 2015, the trial was not initiated. Sierra Leone remains ready to rapidly activate the protocol as an emergency response trial in the event of a resurgence of Ebola. (ClinicalTrials.gov Identifier: NCT02380625.) In summary, we have designed a single controlled trial capable of efficiently identifying highly effective or failing regimens among a rapidly evolving list of proposed therapeutic alternatives for Ebola virus disease and to treat the patients within the trial effectively based on accruing data. Provision of these regimens, if found safe and effective, would have a major impact on future epidemics by providing effective treatment options. PMID:26768569

  1. A response adaptive randomization platform trial for efficient evaluation of Ebola virus treatments: A model for pandemic response.

    PubMed

    Berry, Scott M; Petzold, Elizabeth A; Dull, Peter; Thielman, Nathan M; Cunningham, Coleen K; Corey, G Ralph; McClain, Micah T; Hoover, David L; Russell, James; Griffiss, J McLeod; Woods, Christopher W

    2016-02-01

    The outbreak of Ebola virus disease in West Africa is the largest ever recorded. Numerous treatment alternatives for Ebola have been considered, including widely available repurposed drugs, but initiation of enrollment into clinical trials has been limited. The proposed trial is an adaptive platform design. Multiple agents and combinations will be investigated simultaneously. Additionally, new agents may enter the trial as they become available, and failing agents may be removed. In order to accommodate the many possible agents and combinations, a critical feature of this design is the use of response adaptive randomization to assign treatment regimens. As the trial progresses, the randomization ratio evolves to favor the arms that are performing better, making the design also suitable for all-cause pandemic preparedness planning. The study was approved by US and Sierra Leone ethics committees, and reviewed by the US Food and Drug Administration. Additionally, data management, drug supply lines, and local sites were prepared. However, in response to the declining epidemic seen in February 2015, the trial was not initiated. Sierra Leone remains ready to rapidly activate the protocol as an emergency response trial in the event of a resurgence of Ebola. (ClinicalTrials.gov Identifier: NCT02380625.) In summary, we have designed a single controlled trial capable of efficiently identifying highly effective or failing regimens among a rapidly evolving list of proposed therapeutic alternatives for Ebola virus disease and to treat the patients within the trial effectively based on accruing data. Provision of these regimens, if found safe and effective, would have a major impact on future epidemics by providing effective treatment options.

  2. 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…

  3. 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…

  4. Evaluation of genotypic variation of broccoli (brassica oleracea var. italic) in response to selenium treatment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Broccoli (Brassica oleracea var. italic) fortified with selenium (Se) has been promoted as a functional food. Here we evaluated 38 broccoli accessions for their capacity to accumulate Se and for their responses to selenate treatment in terms of nutritional qualities and sulfur gene expression. We fo...

  5. 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…

  6. 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.)…

  7. 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,…

  8. The Effects of Response Effort on Safe Performance by Therapists at an Autism Treatment Facility

    ERIC Educational Resources Information Center

    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…

  9. 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…

  10. 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…

  11. 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…

  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. Basal ganglia volume in unmedicated patients with schizophrenia is associated with treatment response to antipsychotic medication.

    PubMed

    Hutcheson, Nathan L; Clark, David G; Bolding, Mark S; White, David M; Lahti, Adrienne C

    2014-01-30

    We investigated the relationship between basal ganglia volume and treatment response to the atypical antipsychotic medication risperidone in unmedicated patients with schizophrenia. Basal ganglia volumes included the bilateral caudate, putamen, and pallidum and were measured using the Freesurfer automated segmentation pipeline in 23 subjects. Also, baseline symptom severity, duration of illness, age, gender, time off medication, and exposure to previous antipsychotic were measured. Treatment response was significantly correlated with all three regions of the bilateral basal ganglia (caudate, putamen, and pallidum), baseline symptom severity, duration of illness, and age but not gender, time off antipsychotic medication, or exposure to previous antipsychotic medication. The caudate volume was the basal ganglia region that demonstrated the strongest correlation with treatment response and was significantly negatively correlated with patient age. Caudate volume was not significantly correlated with any other measure. We demonstrated a novel finding that the caudate volume explains a significant amount of the variance in treatment response over the course of 6 weeks of risperidone pharmacotherapy even when controlling for baseline symptom severity and duration of illness.

  14. 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.…

  15. Response to patient-initiated plant extract treatment for atopic dermatitis.

    PubMed

    Strickland, Nicole; Patel, Gopal; Agim, Nnenna G

    2013-01-01

    Ethnomedical practices are increasing in all parts of the world, including many urban centers. We describe a unique case of a 7-year-old girl with atopic dermatitis who was responsive to parent-initiated treatment with the extract of a plant from the Chenopodium genus. A brief discussion raises awareness of such practices to the practicing dermatologist. PMID:23458206

  16. The Efficacy of a Response Cost-Based Treatment Package for Managing Aggressive Behavior in Preschoolers.

    ERIC Educational Resources Information Center

    Reynolds, Larissa Kern; Kelley, Mary Lou

    1997-01-01

    Examined the effectiveness of a response cost treatment package for improving the classroom behavior of four aggressive preschoolers. Teachers removed smiley faces and reprimanded children contingent on aggressive behavior. Results indicate that this method substantially decreased aggressive behavior and was a highly acceptable classroom treatment…

  17. Whole-genome association analysis of treatment response in obsessive-compulsive disorder.

    PubMed

    Qin, H; Samuels, J F; Wang, Y; Zhu, Y; Grados, M A; Riddle, M A; Greenberg, B D; Knowles, J A; Fyer, A J; McCracken, J T; Murphy, D L; Rasmussen, S A; Cullen, B A; Piacentini, J; Geller, D; Stewart, S E; Pauls, D; Bienvenu, O J; Goes, F S; Maher, B; Pulver, A E; Valle, D; Lange, C; Mattheisen, M; McLaughlin, N C; Liang, K-Y; Nurmi, E L; Askland, K D; Nestadt, G; Shugart, Y Y

    2016-02-01

    Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n=514) or 'non-response' (n=290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 × 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P<10(-5)) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877 and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave P-values of 2.86 × 10(-6) and 8.41 × 10(-6), respectively. The other 35 variations with signals of potential significance (P<10(-4)) involve multiple genes expressed in the brain, including GRIN2B, PCDH10 and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (false discovery rate (FDR)=0.0097) and the serotonergic system (FDR=0.0213). Although the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed. PMID:25824302

  18. Immune response against large tumors eradicated by treatment with cyclophosphamide and IL-12.

    PubMed

    Tsung, K; Meko, J B; Tsung, Y L; Peplinski, G R; Norton, J A

    1998-02-01

    Previous studies have demonstrated eradication of small (4-8 mm) established murine MCA207 sarcomas by treatment with systemic IL-12. Analysis of the mechanism has revealed a cellular and molecular immune response at the tumor typical of a Th1 cell-mediated, macrophage-effected, delayed-type hypersensitivity (DTH) response. In the current study we investigate the immune response against long term established, large MCA207 tumors induced by combined treatment with IL-12 and cyclophosphamide (Cy), an agent known to potentiate the DTH response. Our results demonstrate that s.c. large MCA207 tumors (15-20 mm) that are refractory to treatment by either IL-12 or Cy alone can be completely eradicated by the combination of Cy and IL-12. IL-12 is apparently the only cytokine capable of mediating tumor eradication, and the effect is dependent on IFN-gamma. The contribution of Cy is probably due to immunopotentiation of DTH rather than to direct cytotoxicity to the tumor. The regression of these large tumors takes >4 wk and, in many cases, is self-sustained, in that little or no additional IL-12 is needed beyond the initial week of administration. Analysis of the cellular and molecular events at the tumor site suggests that the mechanism is a Th1-mediated antitumor immune response.

  19. Identifying and Investigating Unexpected Response to Treatment: A Diabetes Case Study.

    PubMed

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

    2016-09-01

    The availability of electronic health records creates fertile ground for developing computational models of various medical conditions. We present a new approach for detecting and analyzing patients with unexpected responses to treatment, building on machine learning and statistical methodology. Given a specific patient, we compute a statistical score for the deviation of the patient's response from responses observed in other patients having similar characteristics and medication regimens. These scores are used to define cohorts of patients showing deviant responses. Statistical tests are then applied to identify clinical features that correlate with these cohorts. We implement this methodology in a tool that is designed to assist researchers in the pharmaceutical field to uncover new features associated with reduced response to a treatment. It can also aid physicians by flagging patients who are not responding to treatment as expected and hence deserve more attention. The tool provides comprehensive visualizations of the analysis results and the supporting data, both at the cohort level and at the level of individual patients. We demonstrate the utility of our methodology and tool in a population of type II diabetic patients, treated with antidiabetic drugs, and monitored by the HbA1C test. PMID:27541627

  20. 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. PMID:6116742

  1. 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.

  2. AMERICAN CUTANEOUS LEISHMANIASIS WITH UNUSUAL CLINICAL PRESENTATION AND RESPONSE TO TREATMENT

    PubMed Central

    FERNANDES, Andrea Claudia Bekner Silva; PEDROSO, Raíssa Bocchi; VENAZZI, Eneide Aparecida Sabaini; ZANZARINI, Paulo Donizeti; ARISTIDES, Sandra Mara Alessi; LONARDONI, Maria Valdrinez Campana; SILVEIRA, Thaís Gomes Verzignassi

    2016-01-01

    The clinical manifestations and prognosis of cutaneous leishmaniasis (CL) can be influenced by the immune response of the patient and the species of the parasite. A case of atypical clinical presentation of CL, with development of non-characteristic lesions, poor response to therapy, and a long time to resolution is reported. Confirmatory laboratory tests included parasite detection, indirect immunofluorescence, Montenegro skin test, polymerase chain reaction, and parasite identification by multilocus enzyme electrophoresis. The parasite was identified as Leishmaniabraziliensis. The lesion was unresponsive to three complete courses of N-methylglucamine antimoniate intramuscular, and to treatment with pentamidine. The patient did not tolerate amphotericin B. The lesion finally receded after treatment with intravenous N-methylglucamine antimoniate. It is essential to ensure the accuracy of diagnosis and the appropriate treatment, which can include the use a second choice drug or a different route of administration. PMID:27007563

  3. Treatment-induced cell cycle kinetics dictate tumor response to chemotherapy

    PubMed Central

    Hallett, Robin M.; Huang, Cheng; Motazedian, Ali; Auf der Mauer, Stefanie; Pond, Gregory R.; Hassell, John A.; Nordon, Robert E.; Draper, Jonathan S.

    2015-01-01

    Chemotherapy fails to provide durable cure for the majority of cancer patients. To identify mechanisms associated with chemotherapy resistance, we identified genes differentially expressed before and after chemotherapeutic treatment of breast cancer patients. Treatment response resulted in either increased or decreased cell cycle gene expression. Tumors in which cell cycle gene expression was increased by chemotherapy were likely to be chemotherapy sensitive, whereas tumors in which cell cycle gene transcripts were decreased by chemotherapy were resistant to these agents. A gene expression signature that predicted these changes proved to be a robust and novel index that predicted the response of patients with breast, ovarian, and colon tumors to chemotherapy. Investigations in tumor cell lines supported these findings, and linked treatment induced cell cycle changes with p53 signaling and G1/G0 arrest. Hence, chemotherapy resistance, which can be predicted based on dynamics in cell cycle gene expression, is associated with TP53 integrity. PMID:25749523

  4. Clinical manifestations and treatment response of steroid in pediatric Hashimoto encephalopathy.

    PubMed

    Yu, Hee Joon; Lee, Jeehun; Seo, Dae Won; Lee, Munhyang

    2014-07-01

    Hashimoto encephalopathy is a steroid-responsive encephalopathy associated with elevated titers of antithyroid antibodies. Clinical symptoms are characterized by behavioral and cognitive changes, speech disturbance, seizures, myoclonus, psychosis, hallucination, involuntary movements, cerebellar signs, and coma. The standard treatment is the use of corticosteroids along with the treatment of any concurrent dysthyroidism. Other options are immunoglobulins and plasmapheresis. We described symptoms and outcomes on 3 teenage girls with Hashimoto encephalopathy. Presenting symptoms were seizure or altered mental status. One patient took levothyroxine due to hypothyroidism before presentation of Hashimoto encephalopathy. After confirmation of elevated antithyroid antibodies, all patients were treated with steroids. One patient needed plasmapheresis because of the lack of response to steroids and immunoglobulins. Hashimoto encephalopathy should be considered in any patient presenting with acute or subacute unexplained encephalopathy and seizures. Even though the use of steroids is the first line of treatment, plasmapheresis can rescue steroid-resistant patients.

  5. Response of Holstein cows with milk fever to first treatment using two calcium regimens: a retrospective clinical study.

    PubMed

    Sasaki, Kouya; Sasaki, Kazuya; Sato, Yukiko; Devkota, Bhuminand; Furuhama, Kazuhisa; Yamagishi, Norio

    2013-01-01

    The responses of 64 Holstein cows with milk fever to first treatment with 500 ml of either of 2 intravenous calcium (Ca) solutions, one containing Ca alone (group A, n = 32) or 1 containing Ca, phosphate and magnesium (group B, n = 32), were evaluated by selected clinical signs and serum biochemical data. Based on the cow's ability to stand, treatment response was categorized into "immediate response" (stood after single treatment), "delayed response" (stood after repeated treatments) and "non-response" (slaughtered despite repeated treatments). No significant differences among the response categories were found between the two groups, suggesting that the solution containing Ca borogluconate alone was sufficient for the first treatment of milk fever.

  6. Expression Profiling of Rectal Tumors Defines Response to Neoadjuvant Treatment Related Genes

    PubMed Central

    Conde-Muiño, Raquel; Comino, Ana; Bueno, Pablo; Ferrón, J. Antonio; Cuadros, Marta

    2014-01-01

    To date, no effective method exists that predicts the response to preoperative chemoradiation (CRT) in locally advanced rectal cancer (LARC). Nevertheless, identification of patients who have a higher likelihood of responding to preoperative CRT could be crucial in decreasing treatment morbidity and avoiding expensive and time-consuming treatments. The aim of this study was to identify signatures or molecular markers related to response to pre-operative CRT in LARC. We analyzed the gene expression profiles of 26 pre-treatment biopsies of LARC (10 responders and 16 non-responders) without metastasis using Human WG CodeLink microarray platform. Two hundred and fifty seven genes were differentially over-expressed in the responder patient subgroup. Ingenuity Pathway Analysis revealed a significant ratio of differentially expressed genes related to cancer, cellular growth and proliferation pathways, and c-Myc network. We demonstrated that high Gng4, c-Myc, Pola1, and Rrm1 mRNA expression levels was a significant prognostic factor for response to treatment in LARC patients (p<0.05). Using this gene set, we were able to establish a new model for predicting the response to CRT in rectal cancer with a sensitivity of 60% and 100% specificity. Our results reflect the value of gene expression profiling to gain insight about the molecular pathways involved in the response to treatment of LARC patients. These findings could be clinically relevant and support the use of mRNA levels when aiming to identify patients who respond to CRT therapy. PMID:25380052

  7. 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. PMID:26169574

  8. Hyperbaric Oxygen Treatment Induces a Two-Phase Antinociceptive Response of Unusually Long Duration in Mice

    PubMed Central

    Chung, Eunhee; Zelinski, Lisa M.; Ohgami, Yusuke; Shirachi, Donald Y.; Quock, Raymond M.

    2009-01-01

    Hyperbaric oxygen (HBO2) therapy is approved by the FDA for limited clinical indications but is reported to produce pain relief in several chronic pain conditions. However, there have been no studies to explain this apparent analgesic effect of HBO2. Research conducted in our laboratory demonstrates that four daily 60-min HBO2 treatments at 3.5 ATA induced an unparalleled antinociceptive response that consists of 1) an early phase that lasted at least six hours after the HBO2 treatment before dissipating; and 2) a late phase that emerged about 18 hours after the early phase and lasted for up to three weeks. The early phase was sensitive to antagonism by acutely intracerebroventricular (i.c.v.)-administered opioid antagonist naltrexone and the nitric oxide synthase (NOS)-inhibitor L-NAME. The late phase was inhibited by treatment with i.c.v. naltrexone or L-NAME during the four HBO2 treatments but was not antagonized by either naltrexone or L-NAME following acute pretreatment two weeks after HBO2 treatment. These experimental results implicate a novel mechanism that is activated by HBO2, resulting in an antinociceptive response of unusually long duration that is of potential interest in the clinical management of pain. Perspective Hyperbaric oxygen treatment of mice can induce a two-phase antinociceptive response of unusually long duration. Nitric oxide and opioid receptors appear to initiate or mediate both phases of the antinociceptive response. Further elucidation of the underlying mechanism may potentially identify molecular targets that cause long-lasting activation of endogenous analgesic systems. PMID:20418186

  9. Chelation efficacy and erythroid response during deferasirox treatment in patients with myeloproliferative neoplasms in fibrotic phase.

    PubMed

    Latagliata, Roberto; Montagna, Chiara; Porrini, Raffaele; Di Veroli, Ambra; Leonetti, Sabrina Crescenzi; Niscola, Pasquale; Ciccone, Fabrizio; Spadea, Antonio; Breccia, Massimo; Maurillo, Luca; Rago, Angela; Spirito, Francesca; Cedrone, Michele; De Muro, Marianna; Montanaro, Marco; Andriani, Alessandro; Bagnato, Antonino; Montefusco, Enrico; Alimena, Giuliana

    2016-06-01

    At present, very few data are available on deferasirox (DFX) in the treatment of patients with Philadelphia-negative myeloproliferative neoplasms in fibrotic phase (FP-MPN) and transfusion dependence. To address this issue, a retrospective analysis of 28 patients (22 male and 6 female) with FP-MPN and iron overload secondary to transfusion dependence was performed, based on patients enrolled in the database of our regional cooperative group who received treatment with DFX. DFX was started after a median interval from diagnosis of 12.8 months (IR 7.1-43.1) with median ferritin values of 1415 ng/mL (IR 1168-1768). Extra-hematological toxicity was reported in 16 of 28 patients (57.1%), but only two patients discontinued treatment due to toxicity. Among 26 patients evaluable for response (≥6 months of treatment), after a median treatment period of 15.4 months (IR 8.1-22.3), 11 patients (42.3%) achieved a stable and consistent reduction in ferritin levels <1000 ng/mL. As for hematological improvement, 6 of 26 patients (23%) showed a persistent (>3 months) rise of Hb levels >1.5 g/dL, with disappearance of transfusion dependence in four cases. Treatment with DFX is feasible and effective in FP-MPN with iron overload. Moreover, in this setting, an erythroid response can occur in a significant proportion of patients.

  10. Future clinical uses of neurophysiological biomarkers to predict and monitor treatment response for schizophrenia.

    PubMed

    Light, Gregory A; Swerdlow, Neal R

    2015-05-01

    Advances in psychiatric neuroscience have transformed our understanding of impaired and spared brain functions in psychotic illnesses. Despite substantial progress, few (if any) laboratory tests have graduated to clinics to inform diagnoses, guide treatments, and monitor treatment response. Providers must rely on careful behavioral observation and interview techniques to make inferences about patients' inner experiences and then secondary deductions about impacted neural systems. Development of more effective treatments has also been hindered by a lack of translational quantitative biomarkers that can span the brain-behavior treatment knowledge gap. Here, we describe an example of a simple, low-cost, and translatable electroencephalography (EEG) measure that offers promise for improving our understanding and treatment of psychotic illnesses: mismatch negativity (MMN). MMN is sensitive to and/or predicts response to some pharmacologic and nonpharmacologic interventions and accounts for substantial portions of variance in clinical, cognitive, and psychosocial functioning in schizophrenia (SZ). This measure has recently been validated for use in large-scale multisite clinical studies of SZ. Finally, MMN greatly improves our ability to forecast which individuals at high clinical risk actually develop a psychotic illness. These attributes suggest that MMN can contribute to personalized biomarker-guided treatment strategies aimed at ameliorating or even preventing the onset of psychosis. PMID:25752648

  11. Chelation efficacy and erythroid response during deferasirox treatment in patients with myeloproliferative neoplasms in fibrotic phase.

    PubMed

    Latagliata, Roberto; Montagna, Chiara; Porrini, Raffaele; Di Veroli, Ambra; Leonetti, Sabrina Crescenzi; Niscola, Pasquale; Ciccone, Fabrizio; Spadea, Antonio; Breccia, Massimo; Maurillo, Luca; Rago, Angela; Spirito, Francesca; Cedrone, Michele; De Muro, Marianna; Montanaro, Marco; Andriani, Alessandro; Bagnato, Antonino; Montefusco, Enrico; Alimena, Giuliana

    2016-06-01

    At present, very few data are available on deferasirox (DFX) in the treatment of patients with Philadelphia-negative myeloproliferative neoplasms in fibrotic phase (FP-MPN) and transfusion dependence. To address this issue, a retrospective analysis of 28 patients (22 male and 6 female) with FP-MPN and iron overload secondary to transfusion dependence was performed, based on patients enrolled in the database of our regional cooperative group who received treatment with DFX. DFX was started after a median interval from diagnosis of 12.8 months (IR 7.1-43.1) with median ferritin values of 1415 ng/mL (IR 1168-1768). Extra-hematological toxicity was reported in 16 of 28 patients (57.1%), but only two patients discontinued treatment due to toxicity. Among 26 patients evaluable for response (≥6 months of treatment), after a median treatment period of 15.4 months (IR 8.1-22.3), 11 patients (42.3%) achieved a stable and consistent reduction in ferritin levels <1000 ng/mL. As for hematological improvement, 6 of 26 patients (23%) showed a persistent (>3 months) rise of Hb levels >1.5 g/dL, with disappearance of transfusion dependence in four cases. Treatment with DFX is feasible and effective in FP-MPN with iron overload. Moreover, in this setting, an erythroid response can occur in a significant proportion of patients. PMID:26277477

  12. 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.

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

    PubMed

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

    2015-06-01

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

  14. Differential treatment response trajectories in individuals with subclinical and clinical PTSD.

    PubMed

    Korte, Kristina J; Allan, Nicholas P; Gros, Daniel F; Acierno, Ron

    2016-03-01

    Subclinical presentations of posttraumatic stress disorder (PTSD), wherein patients are one or two symptom criteria short of the full disorder, are prevalent and associated with levels of distress and impaired functioning approximating that of full PTSD. Nonetheless, research examining treatment efficacy for this group is in the nascent stage. The purpose of the present study was to examine whether the subclinical PTSD group would: (1) show a greater reduction in PTSD symptoms at pre and post treatment in response to an exposure based treatment and (2) show a greater rate of change over the course of treatment, when compared to the full criteria PTSD group. We also examined whether differences would emerge when examining PTSD symptom clusters. Consistent with predictions, the subclinical PTSD group demonstrated a greater reduction in PTSD symptoms at post-treatment (29%) than those with a PTSD diagnosis (14%). Further, the groups had different treatment trajectories, with the subclinical PTSD group showing a marginally greater rate of change during the course of treatment. Findings also varied by symptom cluster with the subclinical group showing a greater rate of change in the intrusions, hypervigilance, and avoidance symptom clusters. There was not a significant between group difference in the numbing symptom cluster. This study provides preliminary evidence that treating PTSD symptoms at the subclinical level may result in a larger, and more rapid symptom reduction, and thus has implications supporting treatment earlier in the developmental trajectory of the disorder.

  15. Melatonin treatment prevents modulation of cell-mediated immune response induced by propoxur in rats.

    PubMed

    Suke, Sanvidhan G; Pathak, Rahul; Ahmed, Rafat S; Tripathi, A K; Banerjee, B D

    2008-08-01

    The effect of melatonin, a major secretory product of the pineal gland, in attenuation of propoxur (2-isopropoxy phenyl N-methyl carbamate)-induced modulation of cell-mediated immune (CMI) response was studied in rats. Male Wistar albino rats were exposed to propoxur (a widely used pesticide) orally (10 mg/kg) and/or melatonin (10 mg/kg) orally for 4 weeks. CMI was measured by delayed-type hypersensitivity (DTH), leucocyte and macrophage migration inhibition (LMI and MMI) responses and estimation of cytokines TNF-alpha and IFN-gamma levels. Rats exposed to propoxur for 4 weeks showed significant decrease in DTH, LMI and MMI responses. Propoxur also suppressed TNF-alpha and IFN-gamma production significantly. Administration of melatonin alone caused a significant increase in DTH response. Although there were no changes in the LMI and MMI response, the cytokine levels were significantly increased, as compared to control. Co-administration of melatonin along with propoxur significantly nullified the effect of the pesticide on the CMI response, except DTH and reversed levels of cytokines to near control/normal values. Thus, melatonin treatment considerably attenuated immunomodulation caused by sub-chronic treatment of propoxur in experimental animals.

  16. Grief responses and coping strategies among infertile women after failed in vitro fertilization treatment.

    PubMed

    Lee, Shu-Hsin; Wang, Shu-Chuan; Kuo, Ching-Pyng; Kuo, Pi-Chao; Lee, Maw-Sheng; Lee, Meng-Chih

    2010-09-01

    Reproductive technology has increased the childbearing potential for many infertile women, but in vitro fertilization (IVF) failures are common, which often trigger grief responses and coping strategies to manage the stressful life event. The present cross-sectional study investigated 66 women who had experienced at least one failure with IVF treatment. The data were gathered by a self-administered structured questionnaire, and included the participant's personal profile, grief responses and the Jalowiec's coping scale. The most common grief response among the respondents was bargaining, followed by acceptance, depression, anger, denial, and isolation. The order of coping strategies used, from highest-to-lowest, were confrontative, optimistic, self-reliant, fatalistic, supportive, evasive, palliative, and emotive. Use and self-perceived effectiveness among all coping strategies had a high correlation, except emotion. Bargaining, the most common grief response, was associated with a variety of coping strategies. All coping strategies were correlated with grief responses. The results of identifying the grief responses and associated coping strategies of women who have undergone failed IVF treatment may assist nurses and other health care professionals in their efforts to provide appropriate information, care and psychological support.

  17. 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

  18. Does prior sepsis alter subsequent circadian and sickness behaviour response to lipopolysaccharide treatment in mice?

    PubMed

    Anderson, Sean T; O'Callaghan, Emma K; Commins, Sean; Coogan, Andrew N

    2015-08-01

    Previous data has shown that prior history of immune challenge may affect central and behavioural responses to subsequent immune challenge, either leading to exaggerated responses via priming mechanisms or lessened responses via endotoxin tolerance. In this set of experiments we have examined how previously lipopolysaccharide (LPS)-induced sepsis shapes the response to subsequent treatment with lower dose LPS. After treatment with LPS (5 mg/kg) or saline mice were allowed to recover for 3-4 months before being challenged with a lower dose of LPS (100 μg/kg) for assessment of sickness behaviours. Performance on the open field test and the tail suspension test was assessed, and no evidence was found that prior sepsis altered sickness or depressive-like behaviour following LPS treatment. We then examined the responsiveness of the circadian system of mice to LPS. We found that in control animals, LPS induced a significant phase delay of the behavioural rhythm and that this was not the case in post-septic animals (4-6 weeks after sepsis), indicating that prior sepsis alters the responsivity of the circadian system to subsequent immune challenge. We further assessed the induction of the immediate early genes c-Fos and EGR1 in the hippocampus and the suprachiasmatic nucleus (SCN; the master circadian pacemaker) by LPS in control or post-septic animals, and found that post-septic animals show elevated expression in the hippocampus but not the SCN. These data suggest that previous sepsis has some effect on behavioural and molecular responses to subsequent immune challenge in mice.

  19. 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.

  20. Clinical characteristics and treatment response to SSRI in a female pedophile.

    PubMed

    Chow, Eva W C; Choy, Alberto L

    2002-04-01

    Although much investigation has been done with male sex offenders, there have been few studies on female sex offenders. Female sex offenders have been reported as having a high incidence of psychiatric disorders, but female paraphilics were rarely described. The literature on the treatment of female sex offenders is also limited and treatment with a selective serotonin reuptake inhibitor (SSRI) has not been reported. This paper presents the case of a woman with DSM-IV pedophilia. Her clinical characteristics, her offense history, and her positive response to treatment with sertraline (a SSRI) are described. This case adds to the limited literature on female pedophiles and suggests that SSRIs may be an effective treatment for paraphilic disorders in female sex offenders.

  1. 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

  2. Young Stand Thinning and Diversity Study: Response of Songbird Community One Decade Post-Treatment

    USGS Publications Warehouse

    Hagar, Joan; Friesen, Cheryl

    2009-01-01

    The response of songbird assemblages to commercial thinning is likely to change as vegetation develops over time after thinning. The influence of thinning intensity and pattern on the timing of transitions in bird community composition following thinning is of interest to managers when a goal is to maintain diversity and accelerate the development of late-seral forest structure. We investigated changes in the composition of songbird assemblages and density of individual species from 2 years before to 12 years after experimental thinning of 40-year-old stands dominated by Douglas-fir (Pseudotsuga menziesii) in the Oregon Cascades. Species richness, and density for five species and the neotropical migrant group were greater in thinned than in unthinned control stands over all post-treatment years of the study. Similarly, three species maintained a negative response to thinning over the post-treatment period. The initial positive influence of thinning was no longer in evidence a decade after harvest for five species. Of seven species with an initial negative response to thinning, three indicated recovery towards pre-treatment densities by the end of the most recent post-treatment survey. Our study is one of the first to document long-term effects of commercial thinning on forest songbird assemblages in the Pacific Northwest.

  3. Pre-treatment prediction of response to peginterferon plus ribavirin in chronic hepatitis C genotype 3

    PubMed Central

    Marciano, Sebastián; Borzi, Silvia M; Dirchwolf, Melisa; Ridruejo, Ezequiel; Mendizabal, Manuel; Bessone, Fernando; Sirotinsky, María E; Giunta, Diego H; Trinks, Julieta; Olivera, Pablo A; Galdame, Omar A; Silva, Marcelo O; Fainboim, Hugo A; Gadano, Adrián C

    2015-01-01

    AIM: To evaluate pre-treatment factors associated with sustained virological response (SVR) in patients with hepatitis C virus (HCV) genotype 3 treated with peginterferon and ribavirin (RBV). METHODS: We retrospectively analyzed treatment naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV. Exclusion criteria included presence of other liver disease, alcohol consumption and African American or Asian ethnicity. The variables collected and compared between patients who achieved an SVR and patients who did not were as follows: gender, age, fibrosis stage, diabetes, body mass index, steatosis, INFL3 polymorphism, pre-treatment HCV-RNA, type of peginterferon, RBV dose and adherence. RESULTS: A total of 107 patients treated between June, 2004 and March, 2013 were included. Mean treatment duration was 25.1 (± 1.8) wk. Overall, 58% (62/107) of the patients achieved an SVR and 42% (45/107) did not. In the multivariate logistic regression analysis, pre-treatment HCV-RNA ≥ 600000 UI/mL (OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis (OR = 0.278, 95%CI: 0.113-0.684, P = 0.005) were significantly associated with low SVR rates. In patients with pre-treatment HCV-RNA ≥ 600000 UI/mL and advanced fibrosis, the probability of achieving an SVR was 29% (95%CI: 13.1-45.2). In patients with pre-treatment HCV-RNA < 600000 UI/mL and mild to moderate fibrosis, the probability of achieving an SVR was 81% (95%CI: 68.8-93.4). CONCLUSION: In patients with HCV genotype 3 infections the presence of advance fibrosis and high pre-treatment viral load might be associated with poor response to peginterferon plus RBV. These patients could benefit the most from new direct antiviral agents-based regimes. PMID:25866607

  4. Pathologic response to neoadjuvant treatment in locally advanced rectal cancer and impact on outcome

    PubMed Central

    Davis, Sidney; Mohebbi, Mohammadreza; Sugamaran, Bhuvana; Porter, Ian W.; Bell, Stephen; Warrier, Satish K.; Wale, Roger

    2016-01-01

    Background Downstaging and pathologic complete response (pCR) after chemoradiotherapy (CRT) may improve progression-free survival and overall survival (OS) after curative therapy of locally advanced adenocarcinoma of rectum. The purpose of this study is to evaluate the pathologic response subsequent to neoadjuvant chemoradiation in locally advanced rectal adenocarcinoma and any impact of response on oncological outcome [disease-free survival (DFS), OS]. Methods A total of 127 patients with histologically-proven rectal adenocarcinoma, locally advanced, were treated with preoperative radiotherapy and concurrent 5-fluorouracil (5 FU), and followed by curative surgery. Pathologic response to neoadjuvant treatment was evaluated by comparing pathologic TN (tumour and nodal) staging (yp) with pre-treatment clinical staging. DFS and OS were compared in patients with: pCR, partial pathologic response and no response to neoadjuvant therapy. Results 14.96% (19 patients) had a pCR, 58.27% [74] showed downstaging and 26.77% [34] had no change in staging. At follow-up (range, 4–9 years, median 6 years 2 months or 74 months), 17.32% [22] showed recurrence: 15.74% [20] distant metastasis, 1.57% [2] pelvic failure. 10.5% [2] of the patients with pCR showed distant metastasis, none showed local recurrence. In the downstaged group, nine developed distant failure and two had local recurrence (14.86%). Distant failure was seen in 26.47% [9] of those with no response to neoadjuvant treatment. DFS and OS rates for all groups were 82.67% and 88.97% respectively. Patients with pCR showed 89.47% DFS and 94.7% OS. In partial responders, DFS was 85.1% and OS was 90.5%. In non-responders, DFS and OS were 73.5% and 82.3% respectively. Patients with pCR had a significantly greater probability of DFS and OS than non-responders. Rectal cancer-related death was 11.02% [14]: one patient (5.26%) with pCR, 9.47% [7] in the downstaged group and 17.64% [6] of non-responders. Conclusions The majority

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

    PubMed Central

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

    2015-01-01

    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. PMID:26720509

  6. Semiparametric Estimation of Treatment Effect with Time-Lagged Response in the Presence of Informative Censoring

    PubMed Central

    Lu, Xiaomin; Tsiatis, Anastasios A.

    2011-01-01

    In many randomized clinical trials, the primary response variable, for example, the survival time, is not observed directly after the patients enroll in the study but rather observed after some period of time (lag time). It is often the case that such a response variable is missing for some patients due to censoring that occurs when the study ends before the patient’s response is observed or when the patients drop out of the study. It is often assumed that censoring occurs at random which is referred to as noninformative censoring; however, in many cases such an assumption may not be reasonable. If the missing data are not analyzed properly, the estimator or test for the treatment effect may be biased. In this paper, we use semiparametric theory to derive a class of consistent and asymptotically normal estimators for the treatment effect parameter which are applicable when the response variable is right censored. The baseline auxiliary covariates and post-treatment auxiliary covariates, which may be time-dependent, are also considered in our semiparametric model. These auxiliary covariates are used to derive estimators that both account for informative censoring and are more efficient then the estimators which do not consider the auxiliary covariates. PMID:21706378

  7. Semiparametric estimation of treatment effect with time-lagged response in the presence of informative censoring.

    PubMed

    Lu, Xiaomin; Tsiatis, Anastasios A

    2011-10-01

    In many randomized clinical trials, the primary response variable, for example, the survival time, is not observed directly after the patients enroll in the study but rather observed after some period of time (lag time). It is often the case that such a response variable is missing for some patients due to censoring that occurs when the study ends before the patient's response is observed or when the patients drop out of the study. It is often assumed that censoring occurs at random which is referred to as noninformative censoring; however, in many cases such an assumption may not be reasonable. If the missing data are not analyzed properly, the estimator or test for the treatment effect may be biased. In this paper, we use semiparametric theory to derive a class of consistent and asymptotically normal estimators for the treatment effect parameter which are applicable when the response variable is right censored. The baseline auxiliary covariates and post-treatment auxiliary covariates, which may be time-dependent, are also considered in our semiparametric model. These auxiliary covariates are used to derive estimators that both account for informative censoring and are more efficient then the estimators which do not consider the auxiliary covariates. PMID:21706378

  8. 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.

  9. Novel enzymatic assay predicts minoxidil response in the treatment of androgenetic alopecia.

    PubMed

    Goren, Andy; Castano, Juan Antonio; McCoy, John; Bermudez, Fernando; Lotti, Torello

    2014-01-01

    Topical minoxidil is the most common drug used for the treatment of androgenetic alopecia (AGA) in men and women. Although topical minoxidil exhibits a good safety profile, the efficacy in the overall population remains relatively low at 30-40%. To observe significant improvement in hair growth, minoxidil is typically used daily for a period of at least 3-4 months. Due to the significant time commitment and low response rate, a biomarker for predicting patient response prior to therapy would be advantageous. Minoxidil is converted in the scalp to its active form, minoxidil sulfate, by the sulfotransferase enzyme SULT1A1. We hypothesized that SULT1A1 enzyme activity in the hair follicle correlates with minoxidil response for the treatment of AGA. Our preliminary retrospective study of a SULT1A1 activity assay demonstrates 95% sensitivity and 73% specificity in predicting minoxidil treatment response for AGA. A larger prospective study is now under way to further validate this novel assay. PMID:24283387

  10. Novel enzymatic assay predicts minoxidil response in the treatment of androgenetic alopecia.

    PubMed

    Goren, Andy; Castano, Juan Antonio; McCoy, John; Bermudez, Fernando; Lotti, Torello

    2014-01-01

    Topical minoxidil is the most common drug used for the treatment of androgenetic alopecia (AGA) in men and women. Although topical minoxidil exhibits a good safety profile, the efficacy in the overall population remains relatively low at 30-40%. To observe significant improvement in hair growth, minoxidil is typically used daily for a period of at least 3-4 months. Due to the significant time commitment and low response rate, a biomarker for predicting patient response prior to therapy would be advantageous. Minoxidil is converted in the scalp to its active form, minoxidil sulfate, by the sulfotransferase enzyme SULT1A1. We hypothesized that SULT1A1 enzyme activity in the hair follicle correlates with minoxidil response for the treatment of AGA. Our preliminary retrospective study of a SULT1A1 activity assay demonstrates 95% sensitivity and 73% specificity in predicting minoxidil treatment response for AGA. A larger prospective study is now under way to further validate this novel assay.

  11. Biologic Response of Degenerative Living Human Nucleus Pulposus Cells to Treatment with Cytokines

    PubMed Central

    Kim, Sang Hyun; Kim, Keung Nyun; Park, Jeong Yoon; Cho, Ki Hong; Chin, Dong Kyu; Kim, Keun Su; Cho, Yong Eun

    2015-01-01

    Purpose To investigate the molecular responses of various genes and proteins related to disc degeneration upon treatment with cytokines that affect disc-cell proliferation and phenotype in living human intervertebral discs (IVDs). Responsiveness to these cytokines according to the degree of disc degeneration was also evaluated. Materials and Methods The disc specimens were classified into two groups: group 1 (6 patients) showed mild degeneration of IVDs and group 2 (6 patients) exhibited severe degeneration of IVDs. Gene expression was analyzed after treatment with four cytokines: recombinant human bone morphogenic protein (rhBMP-2), transforming growth factor-β (TGF-β), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). Molecular responses were assessed after exposure of cells from the IVD specimens to these cytokines via real-time polymerase chain reaction and immunofluorescence staining. Results mRNA gene expression was significantly greater for aggrecan, type I collagen, type II collagen, alkaline phosphatase, osteocalcin, and Sox9 in group 1 than mRNA gene expression in group 2, when the samples were not treated with cytokines. Analysis of mRNA levels for these molecules after morphogen treatment revealed significant increases in both groups, which were much higher in group 1 than in group 2. The average number of IVD cells that were immunofluorescence stained positive for alkaline phosphatase increased after treatment with rhBMP-2 and TGF-β in group 1. Conclusion The biologic responsiveness to treatment of rhBMP-2, TGF-β, TNF-α, and IL-1β in the degenerative living human IVD can be different according to the degree of degeneration of the IVD. PMID:25510775

  12. 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

  13. Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study

    PubMed Central

    Isenberg, David; Appel, Gerald B.; Contreras, Gabriel; Dooley, Mary A.; Ginzler, Ellen M.; Jayne, David; Sánchez-Guerrero, Jorge; Wofsy, David; Yu, Xueqing

    2010-01-01

    Objective. To compare the efficacy and safety of mycophenolate mofetil (MMF) and intravenous cyclophosphamide (IVC) as induction treatment for lupus nephritis (LN), by race, ethnicity and geographical region. Methods. A total of 370 patients with active Class III–V LN received MMF (target dose 3.0 g/day) or IVC (0.5–1.0 g/m2/month), plus tapered prednisone, for 24 weeks. Renal function, global disease activity, immunological complement (C3 and C4) and anti-dsDNA levels are the outcomes that were assessed in this study. Results. MMF was not superior to IVC as induction treatment (primary objective). There were important pre-specified interactions between treatment and race (P = 0.047) and treatment and region (P = 0.069) (primary endpoint). MMF and IVC response rates were similar for Asians (53.2 vs 63.9%; P = 0.24) and Whites (56.0 vs 54.2%; P = 0.83), but differed in the combined Other and Black group (60.4 vs 38.5%; P = 0.03). Fewer patients in the Black (40 vs 53.9%; P = 0.39) and Hispanic (38.8 vs 60.9%; P = 0.011) groups responded to IVC. Latin American patients had lower response to IVC (32 vs 60.7%; P = 0.003). Baseline disease characteristics were not predictive of response. The incidence of adverse events (AEs) was similar across groups. Serious AEs were slightly more prevalent among Asians. Conclusions. MMF and IVC have similar efficacy overall to short-term induction therapy for LN. However, race, ethnicity and geographical region may affect treatment response; more Black and Hispanic patients responded to MMF than IVC. As these factors are inter-related, it is difficult to draw firm conclusions about their importance. Trial registration. National Institutes of Health, www.clinicaltrials.gov, registration number NCT00377637. PMID:19933596

  14. Effects of Duloxetine Treatment on Brain Response to Painful Stimulation in Major Depressive Disorder

    PubMed Central

    López-Solà, Marina; Pujol, Jesus; Hernández-Ribas, Rosa; Harrison, Ben J; Contreras-Rodríguez, Oren; Soriano-Mas, Carles; Deus, Joan; Ortiz, Héctor; Menchón, José M; Vallejo, Julio; Cardoner, Narcís

    2010-01-01

    Major depressive disorder (MDD) is characterized by a constellation of affective, cognitive, and somatic symptoms associated with functional abnormalities in relevant brain systems. Painful stimuli are primarily stressful and can trigger consistent responses in brain regions highly overlapping with the regions altered in MDD patients. Duloxetine has proven to be effective in treating both core emotional symptoms and somatic complaints in depression. This study aimed to assess the effects of duloxetine treatment on brain response to painful stimulation in MDD patients. A total of 13 patients and a reference group of 20 healthy subjects were assessed on three occasions (baseline, treatment week 1, and week 8) with functional magnetic resonance imaging (fMRI) during local application of painful heat stimulation. Treatment with duloxetine was associated with a significant reduction in brain responses to painful stimulation in MDD patients in regions generally showing abnormally enhanced activation at baseline. Clinical improvement was associated with pain-related activation reductions in the pregenual anterior cingulate cortex, right prefrontal cortex, and pons. Pontine changes were specifically related to clinical remission. Increased baseline activations in the right prefrontal cortex and reduced deactivations in the subgenual anterior cingulate cortex predicted treatment responders at week 8. This is the first fMRI study addressed to assess the effect of duloxetine in MDD. As a novel approach, the application of painful stimulation as a basic neural stressor proved to be effective in mapping brain response changes associated with antidepressant treatment and brain correlates of symptom improvement in regions of special relevance to MDD pathophysiology. PMID:20668437

  15. 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

  16. Monitoring response to treatment in melanoma patients: potential of a serum glycomic marker.

    PubMed

    Selvan, Senthamil R; Dillman, Robert O; Fowler, Abner W; Carbonell, Denysha J; Ravindranath, Mepur H

    2008-03-15

    A mechanistic marker correlating with tumor progression and clinical response is useful for assessing therapeutic response and determining the course of therapy. Since serum-total-ganglioside (sTG) and antiganglioside-IgM antibody levels reflected tumor progression, the feasibility of utilizing sTG for assessing the response to immunotherapy of metastatic-melanoma was tested. Patients (n = 34) were immunized with dendritic cells cocultured with irradiated, IFN gamma-treated autologous tumor cells admixed with GM-CSF. Levels of sTG and antiganglioside-IgM antibody titers were measured in sera of vaccine recipients at 0, 4 and 24 weeks of treatment. Based on sTG-level, whether lower (L) or higher (H) than the mean + 1 SD of normal and healthy volunteers on weeks 0, 4 and 24, patients were categorized into cohorts-I (LLL, n = 16), II (HHL/HLL, n = 4), III (LLH/LHH/LHL, n = 7) and IV (HHH/HLH, n = 7). The cohorts were regrouped as sTG- downregulators (sTG-DR; n = 20) and upregulators (sTG-UR; n = 14). These two cohorts differed significantly in their overall (p < 0.012) and progression-free (p = 0.0001) survival post-treatment. 43% sTG-UR died within 39 months, with a median survival of 39 months, whereas 61% of the sTG-DR survived for 48 months. Both endogenous and vaccine-induced antiganglioside-IgM antibodies appeared to regulate sTG levels. Nonresponders had increased sTG with no or low IgM antibody response. The sTG level is regulated within 24 weeks post-treatment and therefore, may serve as an ideal biomarker for assessing therapeutic responses in patients. Clinical correlations of sTG indicate that sTG-downregulating therapy may be an effective treatment strategy for melanoma. PMID:17960619

  17. Photosensitizer dosimetry controlled PDT treatment planning reduces inter-individual variability in response to PDT

    NASA Astrophysics Data System (ADS)

    Zhou, Xiaodong; Pogue, Brian W.; Chen, Bin; Demidenko, Eugene; Joshi, Rohan; Hoopes, Jack; Hasan, Tayyaba

    2006-02-01

    Effective Photodynamic therapy (PDT) treatment depends on the amount of active photosensitizer and the delivered light in the targeting tissue. For the same PDT treatment protocol, variation in photosensitizer uptake between animals induces variation in the treatment response between animals. This variation can be compensated via control of delivered light dose through photodynamic dose escalation based on online dosimetry of photosensitizer in the animal. The subcutaneous MAT-LyLu Dunning prostate tumor model was used in this study. Photosensitizer BPD-MA uptake was quantified by multiple fluorescence micro-probe measurements at 3 hours after verteporfin administration. PDT irradiation was carried out after photosensitizer uptake measurement with a total light dose of 75 J/cm2 and a light dose rate of 50 mW/cm2. Therapeutic response of PDT treatments was evaluated by the tumor regrowth assay. Verteporfin uptake varied considerably among tumors (inter-tumor variation 56% standard deviation) and within a tumor (largest intra-tumor variation 64%). An inverse correlation was found between mean photosensitizer intensity and PDT treatment effectiveness (R2 = 37.3%, p < 0.005). In order to compensate individual PDT treatments, photodynamic doses were calculated on an individual animal basis, by matching the light delivered to provide an equal photosensitizer dose multiplied by light dose. This was completed for the lower-quartile, mean and upper-quartile of the photosensitizer distribution. The coefficient of variance in the surviving fraction decreased from 24.9% in non-compensated PDT (NC-PDT) treatments to 16.0%, 14.0% and 15.9% in groups compensated to the lower-quartile (CL-PDT), the median (CM-PDT) and the upper-quartile (CU-PDT), respectively. In terms of treatment efficacy, the CL-PDT group was significantly less effective compared with NC-PDT, CM-PDT and CU-PDT treatments (p < 0.005). No significant difference in effectiveness was observed between NC-PDT, CM

  18. Individual characteristics and response to Contingency Management treatment for cocaine addiction.

    PubMed

    García-Fernández, Gloria; Secades-Villa, Roberto; García-Rodríguez, Olaya; Alvarez-López, Heli; Sánchez-Hervás, Emilio; Fernández-Hermida, José Ramón; Fernández-Artamendi, Sergio

    2011-02-01

    Voucher-based contingency management (CM) research has demonstrated efficacy for treating cocaine addiction, but few studies have examined associations between individual baseline characteristics and response to CM treatments. The aim of this study, involving 50 cocaine outpatients receiving CM for cocaine addiction, was to assess the impact of baseline characteristics on abstinence outcomes after six months of treatment. Patients who were abstinent after six months of treatment accounted for 58% of the sample. Patients with higher scores on the Alcohol area of the EuropASI and patients that were non-abstinent during the first month of treatment were less likely to achieve abstinence. These outcome predictors have implications both for treatment research and for clinical practice. Patients who do not respond early to treatment may need a more intensive intervention, and concomitant problematic alcohol use should be detected and treated. The remaining baseline variables examined were not statistically significant predictors of abstinence. This finding is important for the generalizability of CM across the range of individual characteristics of treatment-seeking cocaine abusers.

  19. Interaction between two HTR2A polymorphisms and gender is associated with treatment response in MDD.

    PubMed

    Viikki, Merja; Huuhka, Kaija; Leinonen, Esa; Illi, Ari; Setälä-Soikkeli, Eija; Huuhka, Martti; Mononen, Nina; Lehtimäki, Terho; Kampman, Olli

    2011-08-21

    The 5HT2A receptor gene (HTR2A) polymorphisms rs7997012 and rs6311 have in some earlier studies been associated with serotonin selective reuptake inhibitor (SSRI) treatment response in major depressive disorder (MDD), but the findings are inconsistent. The aim of the present study was to test for an association between two HTR2A polymorphisms (rs7997012 and rs6311), their interaction and the Montgomery and Åsberg Depression Rating Scale (MADRS) score change after ECT or SSRI treatment. The total number of patients was 218. All were treated in outpatient care. Of these, 119 subjects had treatment-resistant MDD and were treated with ECT and 99 were depressive patients treated with SSRI. Treatment response was assessed by MADRS. Patients scoring <8 on post-treatment MADRS were considered remitters. Neither rs7997012 nor rs6311 HTR2A polymorphism was significantly associated with MADRS score change alone, but the interaction between them and gender explained 14% of the variance in MADRS score change. The finding suggests an association between MADRS score change and interaction of HTR2A polymorphisms, rs7997012 and rs6311 and gender.

  20. The effect of Mendelian disease on human health. II: Response to treatment.

    PubMed

    Hayes, A; Costa, T; Scriver, C R; Childs, B

    1985-06-01

    We describe an attempt to measure efficacy of treatment in the Mendelian diseases of man. We used the McKusick Catalogs to identify 351 single gene diseases. We scored the impact of each disease in seven phenotypic categories: lifespan, reproductive capability, somatic growth, intellectual development, learning ability, capacity to work, and cosmetic effect. We then scored the success of treatment in ameliorating each of these component manifestations separately and together. The response to treatment was slight in the whole sample (n = 351): lifespan was increased in 15%, reproductive capability in 11%, and social adaptation in 6%. We observed that the mutant gene product was known in only 15% of the conditions comprising our sample. Since the mutant polypeptide is known in most inborn errors of metabolism, the diseases of this type (n = 65) in our sample of Mendelian traits were studied separately. In each of the seven categories of phenotypic impact, only a few of the hereditary metabolic diseases responded in any degree to specific treatment: the treatment gave complete relief in 12%, there was a partial response in 40%, and none in the remaining 48%. These findings have implications for prognosis, genetic counseling, and medical care of patients with Mendelian disease.

  1. Whole genome association analysis of treatment response in obsessive-compulsive disorder

    PubMed Central

    Qin, H; Samuels, JF; Wang, Y; Zhu, Y; Grados, MA; Riddle, MA; Greenberg, BD; Knowles, JA; Fyer, AJ; McCracken, JT; Murphy, DL; Rasmussen, SA; Cullen, BA; Piacentini, J; Geller, D; Stewart, SE; Pauls, D; Bienvenu, OJ; Goes, FS; Maher, B; Pulver, AE; Valle, D; Lange, C; Mattheisen, M; McLaughlin, NC; Liang, K-Y; Nurmi, EL; Askland, KD; Nestadt, G; Shugart, YY

    2015-01-01

    Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as “response” (n = 514) or “non-response” (n = 290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top SNP was rs17162912 (P = 1.76×10−8) which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P <10−5) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877, and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave p-values of 2.86×10−6 and 8.41×10−6, respectively. The other 35 variations with signals of potential significance (P <10−4) involve multiple genes expressed in the brain, including GRIN2B, PCDH10, and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (FDR = 0.0097) and the serotonergic system (FDR = 0.0213). While the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed. PMID:25824302

  2. 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.

  3. Systems analysis of transcriptome data provides new hypotheses about Arabidopsis root response to nitrate treatments.

    PubMed

    Canales, Javier; Moyano, Tomás C; Villarroel, Eva; Gutiérrez, Rodrigo A

    2014-01-01

    Nitrogen (N) is an essential macronutrient for plant growth and development. Plants adapt to changes in N availability partly by changes in global gene expression. We integrated publicly available root microarray data under contrasting nitrate conditions to identify new genes and functions important for adaptive nitrate responses in Arabidopsis thaliana roots. Overall, more than 2000 genes exhibited changes in expression in response to nitrate treatments in Arabidopsis thaliana root organs. Global regulation of gene expression by nitrate depends largely on the experimental context. However, despite significant differences from experiment to experiment in the identity of regulated genes, there is a robust nitrate response of specific biological functions. Integrative gene network analysis uncovered relationships between nitrate-responsive genes and 11 highly co-expressed gene clusters (modules). Four of these gene network modules have robust nitrate responsive functions such as transport, signaling, and metabolism. Network analysis hypothesized G2-like transcription factors are key regulatory factors controlling transport and signaling functions. Our meta-analysis highlights the role of biological processes not studied before in the context of the nitrate response such as root hair development and provides testable hypothesis to advance our understanding of nitrate responses in plants.

  4. 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

  5. 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

    2016-01-01

    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

  6. 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.

  7. Influence of Religiosity on 12-Step Participation and Treatment Response Among Substance-Dependent Adolescents*

    PubMed Central

    Kelly, John F.; Pagano, Maria E.; Stout, Robert L.; Johnson, Shannon M.

    2011-01-01

    Objective: Religious practices among adults are associated with more 12-step participation which, in turn, is linked to better treatment outcomes. Despite recommendations for adolescents to participate in mutual-help groups, little is known about how religious practices influence youth 12-step engagement and outcomes. This study examined the relationships among lifetime religiosity, during-treatment 12-step participation, and outcomes among adolescents, and tested whether any observed beneficial relation between higher religiosity and outcome could be explained by increased 12-step participation. Method: Adolescents (n = 195; 52% female, ages 14–18) court-referred to a 2-month residential treatment were assessed at intake and discharge. Lifetime religiosity was assessed with the Religious Background and Behaviors Questionnaire; 12-step assessments measured meeting attendance, step work (General Alcoholics Anonymous Tools of Recovery), and Alcoholics Anonymous (AA)/Narcotics Anonymous (NA)-related helping. Substance-related outcomes and psychosocial outcomes were assessed with toxicology screens, the Adolescent–Obsessive Compulsive Drinking Scale, the Children's Global Assessment Scale, and the Narcissistic Personality Inventory. Results: Greater lifetime formal religious practices at intake were associated with increased step work and AA/NA-related helping during treatment, which in turn were linked to improved substance outcomes, global functioning, and reduced narcissistic entitlement. Increased step work mediated the effect of religious practices on increased abstinence, whereas AA/NA-related helping mediated the effect of religiosity on reduced craving and entitlement. Conclusions: Findings extend the evidence for the protective effects of lifetime religious behaviors to an improved treatment response among adolescents and provide preliminary support for the 12-step proposition that helping others in recovery may lead to better outcomes. Youth with low or

  8. Volume analysis of treatment response of head and neck lesions using 3D level set segmentation

    NASA Astrophysics Data System (ADS)

    Hadjiiski, Lubomir; Street, Ethan; Sahiner, Berkman; Gujar, Sachin; Ibrahim, Mohannad; Chan, Heang-Ping; Mukherji, Suresh K.

    2008-03-01

    A computerized system for segmenting lesions in head and neck CT scans was developed to assist radiologists in estimation of the response to treatment of malignant lesions. The system performs 3D segmentations based on a level set model and uses as input an approximate bounding box for the lesion of interest. In this preliminary study, CT scans from a pre-treatment exam and a post one-cycle chemotherapy exam of 13 patients containing head and neck neoplasms were used. A radiologist marked 35 temporal pairs of lesions. 13 pairs were primary site cancers and 22 pairs were metastatic lymph nodes. For all lesions, a radiologist outlined a contour on the best slice on both the pre- and post treatment scans. For the 13 primary lesion pairs, full 3D contours were also extracted by a radiologist. The average pre- and post-treatment areas on the best slices for all lesions were 4.5 and 2.1 cm2, respectively. For the 13 primary site pairs the average pre- and post-treatment primary lesions volumes were 15.4 and 6.7 cm 3 respectively. The correlation between the automatic and manual estimates for the pre-to-post-treatment change in area for all 35 pairs was r=0.97, while the correlation for the percent change in area was r=0.80. The correlation for the change in volume for the 13 primary site pairs was r=0.89, while the correlation for the percent change in volume was r=0.79. The average signed percent error between the automatic and manual areas for all 70 lesions was 11.0+/-20.6%. The average signed percent error between the automatic and manual volumes for all 26 primary lesions was 37.8+/-42.1%. The preliminary results indicate that the automated segmentation system can reliably estimate tumor size change in response to treatment relative to radiologist's hand segmentation.

  9. Dose-response effects of atropine and HI-6 treatment of organophosphorus poisoning in guinea pigs

    SciTech Connect

    Koplovitz, I.; Menton, R.; Matthews, C.; Shutz, M.; Nalls, C.

    1995-12-31

    H1-6 (1-2-hydrnxyiminomethyl-1 pyridino-3-(4-carbameyl- 1--pyddino)-2- oxaprnpane dichioride) has been evaluated as an oxime alternative to pralidoxime, and toxogonin in the treatment of organophosphorus (OP) poisoning. The dose response effects of atropine (ATR) and HI-6 were investigated to more fully explore the interaction of these compounds in the treatment of OP poisoning. ATR, HI-6 and various combinations of the two drugs were evaluated against lethal poisoning by soman (GD) and tabun (GA) in guinea pigs. The effect of adjunctive diazepam treatment on the efficacy of atropine and HI-6 against soman was also investigated. Animals of either sex were challenged s.c. with OP and treated i.m. 1 min later with ATR and/or HI-6. When used, diazepam was injected immediately after ATR+HI6. LD50s of each treatment were calculated from probit models based on 24-hour survival against 5 levels of nerve agent and 6 animals per challenge level. A protective index (PI) was calculated by dividing the nerve agent LD50 in the presence of treatment by the LD50 in the absence of treatment. Treatment with HI-6 alone had little effect on the toxicity of either OP. Treatment with ATR alone was more effective than HI-6 alone and was significantly more effective against soman than against tabun. When used in combination atropine and HI-6 had a strong synergistic effect against both agents. The dose of atropine used with HI-6 was critical in determining the efficacy of HI-6 against either agent. The slopes of the dose-lethality curves were minimally affected by the dose of ATR or HI-6. Adjunctive treatment with diazepam enhanced the efficacy of HI-6 and atropine against soman.

  10. Rapidly eroding piñon-juniper woodlands in New Mexico: response to slash treatment.

    PubMed

    Hastings, Brian K; Smith, Freeman M; Jacobs, Brian F

    2003-01-01

    The piñon (Pinus edulis Engelm.)-juniper [Juniperus monosperma (Engelm.) Sarg.] woodlands of Bandelier National Monument are experiencing accelerated erosion. Earlier studies suggest that causes of these rapidly eroding woodlands are related to an unprecedented rapid transition of ponderosa pine (Pinus ponderosa C. Lawson) savanna to piñon-juniper woodlands as a result of cumulative historical effects of overgrazing, fire suppression, and severe drought. To study the effectiveness of slash treatment in reducing accelerated erosion, we used sediment check dams to quantify sediment yield from twelve paired microwatersheds (300-1100 m2) within an existing paired water-shed study. Six of the twelve microwatersheds were located in a 41-ha (treatment) watershed with scattered slash treatment, whereas six microwatersheds were located in an adjacent 35-ha untreated (control) watershed. The primary purpose of our research was to quantify the rates of sediment yield between the treated and control microwatersheds. Sediment yield was measured from 15 individual storms during the months of June-September (2000 and 2001). In response to slash treatment, mean seasonal sediment yield for 2000 equaled 2.99 Mg/ha in the control vs. 0.03 Mg/ha in the treatment and 2.07 Mg/ha in the control vs. 0.07 Mg/ha in the treatment in 2001. The practice of slash treatment demonstrates efficacy in reducing erosion in degraded piñon-juniper woodlands by encouraging herbaceous recovery. Our data show that slash treatment increases total ground cover (slash and herbaceous growth) beyond a potential erosion threshold. Restored piñon-juniper woodlands, as the result of slash treatment, provide a forest structure similar to pre-grazing and pre-fire suppression conditions and decrease catastrophic fire hazard. PMID:12931884

  11. Rapidly eroding piñon-juniper woodlands in New Mexico: response to slash treatment.

    PubMed

    Hastings, Brian K; Smith, Freeman M; Jacobs, Brian F

    2003-01-01

    The piñon (Pinus edulis Engelm.)-juniper [Juniperus monosperma (Engelm.) Sarg.] woodlands of Bandelier National Monument are experiencing accelerated erosion. Earlier studies suggest that causes of these rapidly eroding woodlands are related to an unprecedented rapid transition of ponderosa pine (Pinus ponderosa C. Lawson) savanna to piñon-juniper woodlands as a result of cumulative historical effects of overgrazing, fire suppression, and severe drought. To study the effectiveness of slash treatment in reducing accelerated erosion, we used sediment check dams to quantify sediment yield from twelve paired microwatersheds (300-1100 m2) within an existing paired water-shed study. Six of the twelve microwatersheds were located in a 41-ha (treatment) watershed with scattered slash treatment, whereas six microwatersheds were located in an adjacent 35-ha untreated (control) watershed. The primary purpose of our research was to quantify the rates of sediment yield between the treated and control microwatersheds. Sediment yield was measured from 15 individual storms during the months of June-September (2000 and 2001). In response to slash treatment, mean seasonal sediment yield for 2000 equaled 2.99 Mg/ha in the control vs. 0.03 Mg/ha in the treatment and 2.07 Mg/ha in the control vs. 0.07 Mg/ha in the treatment in 2001. The practice of slash treatment demonstrates efficacy in reducing erosion in degraded piñon-juniper woodlands by encouraging herbaceous recovery. Our data show that slash treatment increases total ground cover (slash and herbaceous growth) beyond a potential erosion threshold. Restored piñon-juniper woodlands, as the result of slash treatment, provide a forest structure similar to pre-grazing and pre-fire suppression conditions and decrease catastrophic fire hazard.

  12. 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

  13. Postharvest response of avocado fruits of different maturity to delayed ethylene treatments.

    PubMed

    Adato, I; Gazit, S

    1974-06-01

    The effect of 10, 100, 1000, 10,000 ppm of ethylene, applied for 3, 6, 12, and 24 hours, on the ripening rate of "Hass" avocado (Persea americana Mill.) fruits at three stages of maturity was investigated. Ethylene treatments were started either immediately after picking or 2 days later. A sharp peak of ethylene production was found to precede full softening by about 2 days and the occurrence of this peak was used to determine ripening rate. Hastening of fruit ripening was much more marked following ethylene treatment which began 2 days after harvesting than immediately after. The difference in response diminished gradually as the fruit became more mature.These results can be explained by the assumption that the factors which prevent avocado ripening on the tree, continue to exert their influence for a limited period after harvest and inhibit the ripening response in the freshly picked fruit. This inhibition decreases with advancing fruit maturity.

  14. 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

  15. Inhaled corticosteroid treatment modulates ZNF432 gene variant's effect on bronchodilator response in asthmatics

    PubMed Central

    Wu, Ann C.; Himes, Blanca E.; Lasky-Su, Jessica; Litonjua, Augusto; Peters, Stephen P.; Lima, John; Kubo, Michiaki; Tamari, Mayumi; Nakamura, Yusuke; Qiu, Weiliang; Weiss, Scott T.; Tantisira, Kelan

    2013-01-01

    Background Single nucleotide polymorphisms (SNPs) influence a patient's response to inhaled corticosteroids and β2-agonists, and the effect of treatment with inhaled corticosteroids is synergistic with the effect of β2-agonists. We hypothesized that use of inhaled corticosteroids could influence the effect of SNPs associated with bronchodilator response. Objective To assess whether, among asthma subjects, the association of SNPs with bronchodilator response is different between those treated with inhaled corticosteroids vs. those on placebo. Methods A genome-wide association analysis was conducted using 581 white subjects from the Childhood Asthma Management Program (CAMP). Using data for 449,540 SNPs, we conducted a gene by environment analysis in PLINK with inhaled corticosteroid treatment as the environmental exposure and bronchodilator response as the outcome measure. We attempted to replicate the top 12 SNPs in the Leukotriene Modifier Or Corticosteroid or Corticosteroid-Salmeterol (LOCCS) Trial. Results The combined P-value for the CAMP and LOCCS populations was 4.81E-08 for rs3752120, which is located in the zinc finger protein gene ZNF432, and has unknown function. Conclusions Inhaled corticosteroids appear to modulate the association of bronchodilator response with variant(s) in the ZNF432 gene among adults and children with asthma. Clinical Implications Clinicians who treat asthma patients with inhaled corticosteroids should be aware that the patient's genetic makeup likely influences response as measured in lung function. Capsule Summary Our study suggests that inhaled corticosteroids could influence the effect of multiple SNPs associated with bronchodilator response across the genome. PMID:24280104

  16. In vivo immune responses to Candida albicans modified by treatment with recombinant murine gamma interferon.

    PubMed

    Garner, R E; Kuruganti, U; Czarniecki, C W; Chiu, H H; Domer, J E

    1989-06-01

    The immunologic effects of in vivo administration of recombinant murine gamma interferon (rMuIFN-gamma) were determined in a murine model of candidiasis. Naive mice were given graded doses of rMuIFN-gamma and then challenged intravenously with Candida albicans. Increased morbidity and mortality were noted in four different strains of mice, viz., BALB/c, A/J, Swiss Webster, and CBA/J, providing the mice had not been immunized with C. albicans before challenge. Quantitative culture of selected organs of Swiss Webster and CBA/J mice surviving treatment with rMuIFN-gamma revealed elevated numbers of C. albicans cells, particularly in the kidneys, but also in the liver, lungs, and spleen. The lungs, livers, and spleen of female CBA/J mice were more protected from increased multiplication of the fungus than were those of males of the same species or female Swiss Webster mice. On the basis of these initial findings, the effect of treatment with 5,000 U of rMuIFN-gamma on immune responses in a gastrointestinal model of candidiasis was determined. CBA/J mice that had been colonized with C. albicans as infants were boosted with a cutaneous inoculation of the fungus when 6 to 10 weeks old; development of delayed hypersensitivity (DH), antibodies, and protective responses was assayed at intervals thereafter. Daily treatment with rMuIFN-gamma (beginning 1 day before cutaneous inoculation) suppressed weak immune responses but had little effect on responses which were strong. For example, DH and anti-C. albicans antibody production were suppressed in animals colonized with C. albicans but not boosted by cutaneous inoculation, and DH was suppressed in uncolonized animals that had been inoculated once cutaneously with the fungus as well. There was no rMuIFN-gamma-induced suppressive effect of DH in mice which had been stimulated maximally with C. albicans, i.e., colonized animals that had been boosted cutaneously with the organisms. Collectively, these data indicate that naive mice

  17. In vivo immune responses to Candida albicans modified by treatment with recombinant murine gamma interferon.

    PubMed Central

    Garner, R. E.; Kuruganti, U.; Czarniecki, C. W.; Chiu, H. H.; Domer, J. E.

    1989-01-01

    The immunologic effects of in vivo administration of recombinant murine gamma interferon (rMuIFN-gamma) were determined in a murine model of candidiasis. Naive mice were given graded doses of rMuIFN-gamma and then challenged intravenously with Candida albicans. Increased morbidity and mortality were noted in four different strains of mice, viz., BALB/c, A/J, Swiss Webster, and CBA/J, providing the mice had not been immunized with C. albicans before challenge. Quantitative culture of selected organs of Swiss Webster and CBA/J mice surviving treatment with rMuIFN-gamma revealed elevated numbers of C. albicans cells, particularly in the kidneys, but also in the liver, lungs, and spleen. The lungs, livers, and spleen of female CBA/J mice were more protected from increased multiplication of the fungus than were those of males of the same species or female Swiss Webster mice. On the basis of these initial findings, the effect of treatment with 5,000 U of rMuIFN-gamma on immune responses in a gastrointestinal model of candidiasis was determined. CBA/J mice that had been colonized with C. albicans as infants were boosted with a cutaneous inoculation of the fungus when 6 to 10 weeks old; development of delayed hypersensitivity (DH), antibodies, and protective responses was assayed at intervals thereafter. Daily treatment with rMuIFN-gamma (beginning 1 day before cutaneous inoculation) suppressed weak immune responses but had little effect on responses which were strong. For example, DH and anti-C. albicans antibody production were suppressed in animals colonized with C. albicans but not boosted by cutaneous inoculation, and DH was suppressed in uncolonized animals that had been inoculated once cutaneously with the fungus as well. There was no rMuIFN-gamma-induced suppressive effect of DH in mice which had been stimulated maximally with C. albicans, i.e., colonized animals that had been boosted cutaneously with the organisms. Collectively, these data indicate that naive mice

  18. 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

  19. Variable Response to Propranolol Treatment of Kaposiform Hemangioendothelioma, Tufted Angioma, and Kasabach-Merritt Phenomenon

    PubMed Central

    Chiu, Yvonne E.; Drolet, Beth A.; Blei, Francine; Carcao, Manuel; Fangusaro, Jason; Kelly, Michael E.; Krol, Alfons; Lofgren, Sabra; Mancini, Anthony J.; Metry, Denise W.; Recht, Michael; Silverman, Robert A.; Tom, Wynnis L.; Pope, Elena

    2012-01-01

    Propranolol is a non-selective beta-adrenergic antagonist successfully used in a case of kaposiform hemangioendothelioma associated with Kasabach-Merritt phenomenon. We report eleven patients treated with propranolol for kaposiform hemangioendothelioma and the related variant tufted angioma, six of whom also had Kasabach-Merritt phenomenon. The varied responses to treatment, with only 36% responding in our series, demonstrate the need for further study of this medication before routine use for these indications. PMID:22648868

  20. 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

  1. 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

  2. Improvement of Electrochemical Response of Cocaine Sensors Based on DNA Aptamer by Heat Treatment.

    PubMed

    Arimoto, Satoshi; Shimono, Ken; Yasukawa, Tomoyuki; Mizutani, Fumio; Yoshioka, Toshihiko

    2016-01-01

    We report on a biosensor for cocaine based on the conformation change of DNA aptamer by capturing the cocaine molecules. The oxidation current of ferrocene conjugated on the terminal end of aptamer immobilized on an Au electrode increased with increasing cocaine concentration. The sensor response has been improved by a simple heat treatment after immobilization, since the aggregates of DNA aptamer generated during the immobilization step could be dissociated and rearranged on the electrode. PMID:27063722

  3. Prediction of treatment response and metastatic disease in soft tissue sarcoma

    NASA Astrophysics Data System (ADS)

    Farhidzadeh, Hamidreza; Zhou, Mu; Goldgof, Dmitry B.; Hall, Lawrence O.; Raghavan, Meera.; Gatenby, Robert A.

    2014-03-01

    Soft tissue sarcomas (STS) are a heterogenous group of malignant tumors comprised of more than 50 histologic subtypes. Based on spatial variations of the tumor, predictions of the development of necrosis in response to therapy as well as eventual progression to metastatic disease are made. Optimization of treatment, as well as management of therapy-related side effects, may be improved using progression information earlier in the course of therapy. Multimodality pre- and post-gadolinium enhanced magnetic resonance images (MRI) were taken before and after treatment for 30 patients. Regional variations in the tumor bed were measured quantitatively. The voxel values from the tumor region were used as features and a fuzzy clustering algorithm was used to segment the tumor into three spatial regions. The regions were given labels of high, intermediate and low based on the average signal intensity of pixels from the post-contrast T1 modality. These spatially distinct regions were viewed as essential meta-features to predict the response of the tumor to therapy based on necrosis (dead tissue in tumor bed) and metastatic disease (spread of tumor to sites other than primary). The best feature was the difference in the number of pixels in the highest intensity regions of tumors before and after treatment. This enabled prediction of patients with metastatic disease and lack of positive treatment response (i.e. less necrosis). The best accuracy, 73.33%, was achieved by a Support Vector Machine in a leave-one-out cross validation on 30 cases predicting necrosis < 90% post treatment and metastasis.

  4. Genetic polymorphisms in the PACAP and PAC1 receptor genes and treatment response to venlafaxine XR in generalized anxiety disorder.

    PubMed

    Cooper, Alissa J; Narasimhan, Sneha; Rickels, Karl; Lohoff, Falk W

    2013-12-30

    The pituitary adenylate cyclase-activating peptide (PACAP) and its receptor (PAC1) are involved in stress response and anxiety. Genotypes for PACAP/PAC1 were examined for effects on treatment response to venlafaxine XR in generalized anxiety disorder. The Asp54Gly (rs2856966) variant in the PACAP gene was associated with better treatment outcome.

  5. Clinicopathological correlation and treatment response of primary focal segmental glomerulosclerosis in adults and adolescents

    PubMed Central

    Dhanapriya, J.; Dineshkumar, T.; Gopalakrishnan, N.; Sakthirajan, R.; Balasubramaniyan, T.

    2016-01-01

    The incidence of focal segmental glomerulosclerosis (FSGS) is approximately 10% in children <6 years, 20% in adolescents, and 20-25% in adults. A retrospective observational study was done to document clinicopathological correlation, treatment response, and risk factors in the progression of chronic kidney disease (CKD) of primary FSGS in adults and adolescents. A total of 170 patients were studied with a mean follow-up of 4.32 ± 1.2 years. FSGS not otherwise specified was the most common subtype (56%) followed by tip variant (24%). About 32% had complete remission (CR) at a mean time of 6.4 months, 23% had partial remission (PR) at a mean time of 5.7 months, and 45% had no response to steroids. Persistent nephrotic proteinuria at 3rd and 6th month and presence of interstitial fibrosis and tubular atrophy >30% in renal biopsy are the independent predictors of poor response to treatment. Presence of anemia, interstitial fibrosis, and tubular atrophy of >30% in renal biopsy and the absence of remission after treatment were the independent predictors of CKD progression. Overall renal survival was 78% at 3 years and 54% at 5 years. Renal survival difference with or without nephrotic proteinuria at onset was 39% and 69% at 5 years. Renal survival was higher in patients with normal renal function (66%) compared with those who had renal failure (42%) at 5 years. Renal survival at 5 years for CR was 69%, PR was 49%, and no remission was 42%.

  6. 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

  7. 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. PMID:26631269

  8. Adolescent nicotine treatment changes the response of acetylcholine systems to subsequent nicotine administration in adulthood.

    PubMed

    Slotkin, Theodore A; Bodwell, Bethany E; Ryde, Ian T; Seidler, Frederic J

    2008-05-15

    Nicotine alters the developmental trajectory of acetylcholine (ACh) systems in the immature brain, with vulnerability extending from fetal stages through adolescence. We administered nicotine to adolescent rats (postnatal days PN30-47) and then examined the subsequent response to nicotine given in adulthood (PN90-107), simulating plasma levels in smokers, and performing evaluations during nicotine treatment (PN105) and withdrawal (PN110, PN120 and PN130), as well as assessing persistent changes at 6 months of age (PN180). We measured nicotinic acetylcholine receptor (nAChR) binding, choline acetyltransferase (ChAT) activity, a marker for ACh terminals, and hemicholinium-3 (HC3) binding to the choline transporter, an index of ACh presynaptic activity. By itself, adolescent nicotine exposure evoked sex-selective deficits in cerebrocortical HC3 binding while elevating ChAT in young adulthood in striatum and midbrain. Nicotine given in adulthood produced profound nAChR upregulation lasting 2 weeks after discontinuing treatment, and decrements in cerebrocortical and striatal HC3 binding emerged during withdrawal, indicative of reduced ACh synaptic activity. For all three parameters, adolescent nicotine altered the responses to nicotine given in adulthood, producing both sensitization and desensitization that depended on sex and brain region, effects that parallel the disparate behavioral outcomes reported for these treatments. The interaction seen here for the impact of adolescent nicotine exposure on adult nicotine responses was substantially greater than that found previously for the effects of prenatal nicotine exposure on adult responses. Our findings thus reinforce the importance of adolescence as a critical period in which the future responsiveness to nicotine is programmed.

  9. Adolescent nicotine treatment changes the response of acetylcholine systems to subsequent nicotine administration in adulthood.

    PubMed

    Slotkin, Theodore A; Bodwell, Bethany E; Ryde, Ian T; Seidler, Frederic J

    2008-05-15

    Nicotine alters the developmental trajectory of acetylcholine (ACh) systems in the immature brain, with vulnerability extending from fetal stages through adolescence. We administered nicotine to adolescent rats (postnatal days PN30-47) and then examined the subsequent response to nicotine given in adulthood (PN90-107), simulating plasma levels in smokers, and performing evaluations during nicotine treatment (PN105) and withdrawal (PN110, PN120 and PN130), as well as assessing persistent changes at 6 months of age (PN180). We measured nicotinic acetylcholine receptor (nAChR) binding, choline acetyltransferase (ChAT) activity, a marker for ACh terminals, and hemicholinium-3 (HC3) binding to the choline transporter, an index of ACh presynaptic activity. By itself, adolescent nicotine exposure evoked sex-selective deficits in cerebrocortical HC3 binding while elevating ChAT in young adulthood in striatum and midbrain. Nicotine given in adulthood produced profound nAChR upregulation lasting 2 weeks after discontinuing treatment, and decrements in cerebrocortical and striatal HC3 binding emerged during withdrawal, indicative of reduced ACh synaptic activity. For all three parameters, adolescent nicotine altered the responses to nicotine given in adulthood, producing both sensitization and desensitization that depended on sex and brain region, effects that parallel the disparate behavioral outcomes reported for these treatments. The interaction seen here for the impact of adolescent nicotine exposure on adult nicotine responses was substantially greater than that found previously for the effects of prenatal nicotine exposure on adult responses. Our findings thus reinforce the importance of adolescence as a critical period in which the future responsiveness to nicotine is programmed. PMID:18395624

  10. 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

  11. Laboratory recommendations for scoring deep molecular responses following treatment for chronic myeloid leukemia.

    PubMed

    Cross, N C P; White, H E; Colomer, D; Ehrencrona, H; Foroni, L; Gottardi, E; Lange, T; Lion, T; Machova Polakova, K; Dulucq, S; Martinelli, G; Oppliger Leibundgut, E; Pallisgaard, N; Barbany, G; Sacha, T; Talmaci, R; Izzo, B; Saglio, G; Pane, F; Müller, M C; Hochhaus, A

    2015-05-01

    Treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors has advanced to a stage where many patients achieve very low or undetectable levels of disease. Remarkably, some of these patients remain in sustained remission when treatment is withdrawn, suggesting that they may be at least operationally cured of their disease. Accurate definition of deep molecular responses (MRs) is therefore increasingly important for optimal patient management and comparison of independent data sets. We previously published proposals for broad standardized definitions of MR at different levels of sensitivity. Here we present detailed laboratory recommendations, developed as part of the European Treatment and Outcome Study for CML (EUTOS), to enable testing laboratories to score MR in a reproducible manner for CML patients expressing the most common BCR-ABL1 variants. PMID:25652737

  12. 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. PMID:27630277

  13. Serum prolactin and response to treatment among cocaine-dependent individuals.

    PubMed

    Patkar, Ashwin A; Hill, Kevin P; Sterling, Robert C; Gottheil, Edward; Berrettini, Wade H; Weinstein, Stephen P

    2002-01-01

    Considerable evidence indicates that dopaminergic mechanisms may modulate the central effects of cocaine. We investigated whether basal serum prolactin, a measure of central dopamine activity, differed between cocaine-dependent subjects and controls, and whether prolactin levels among cocaine patients were related to their response to treatment. Eighty-six African-American cocaine-dependent outpatients and 35 African-American controls were studied. Prolactin concentrations in fasting blood samples were assayed by radioimmunoassay. The outcome measures were: number of negative urine drug screens, retention in treatment, counselor ratings of improvement and discharge status. Chi-square tests and independent t-tests were used for data analyses. The basal prolactin(ng/ml) among cocaine patients (9.12 +/- 4.12) was significantly higher compared to controls (7.14 +/- 3.36) (t = 2.52, p < 0.02). Furthermore, the higher prolactin subjects (median prolactin = 7.71) had significantly fewer negative urine screens (p < 0.05) and received less favorable ratings of improvement by counselors (p < 0.01) compared to the lower prolactin group. However, the two groups did not differ significantly in treatment retention (p = 0.13) or discharge status (p = 0.08). The higher basal prolactin among cocaine patients relative to controls may reflect changes in DA activity among cocaine patients. Moreover, higher prolactin seems to be related negatively with certain measures of response to treatment among cocaine patients.

  14. Evolution of testosterone treatment over 25 years: symptom responses, endocrine profiles and cardiovascular changes

    PubMed Central

    Carruthers, Malcolm; Cathcart, Paul; Feneley, Mark R.

    2015-01-01

    Abstract Introduction: Testosterone treatment has evolved rapidly over the past 25 years as new, more effective and convenient methods have become available. This study reports experience with seven different methods, introduced on the market in the UK. Aim: To establish the symptom response when testosterone treatment was initiated on the basis of clinical features and symptoms of androgen deficiency, and the resulting endocrine, biochemical and physiological responses. Methods: Of 2693 patients attending the 3 Men’s Health Centers – The UK Androgen Study (UKAS), 2247 were treated. Treatments included pellet implants, oral testosterone undecanoate (Testocaps), mesterolone (Proviron), testosterone gel (Testogel), testosterone scrotal cream (Andromen) and scrotal gel (Tostran). Results: There was no correlation between initial testosterone level, initial symptom score or the success of treatment as defined by adequate resolution of symptoms. Despite the diverse endocrine patterns produced, the testosterone preparations appear equally safe over prolonged periods, with either no change or improvement of cardiovascular risk factors, especially in lowering cholesterol and diastolic blood pressure. Conclusions: It is suggested that because of excessive reliance on laboratory measures of androgens and undue safety concerns, many men who could benefit from symptom relief, improvement in related clinical conditions and given preventive medical benefits remain untreated. PMID:26218766

  15. Evaluation of the response to treatment and clinical evolution in patients with burning mouth syndrome

    PubMed Central

    Rodríguez-de Rivera-Campillo, Eugenia

    2013-01-01

    Objective: the aim of this study is to investigate the clinical evolution, the spontaneous remission of the symptomatology and the response to different treatments in a group of burning mouth syndrome patients. Study Design: the sample was formed by a group of patients that were visited in the Unit of Oral Medicine of the Dentistry Clinic of the University of Barcelona, from the year 2000 to 2011. After revising the clinical records of all the patients that had been under control for a period of time of 18 months or longer, they were contacted by telephone. In the telephone interview, they were questioned about the symptomatology evolution and the response to the treatments received, noting down the data in a questionnaire previously performed. Results: the average duration of the symptoms was 6.5 years (+/-2.5 years). The most frequent treatments were: chlorhexidine mouthrinses, oral benzodiazepines, topical clonazepam, antiinflamatory drugs, antidepressants, antifungicals, vitamins, psycotherapy, salivary substitutes and topical corticoids. The specialists that were consulted with a higher frequency were: dermatologists (30%), othorrynolaringologists (10%) and psychiatrists (3%). In 41 patients the oral symptoms did not improve, 35 reported partial improvements, 12 patients worsened, and only in 3 patients the symptoms remitted. Conclusions: In three of the 91 patients studied the symptoms remitted spontaneously within the five years of treatment. Only 42% of the study population had improved the symptomatology significantly, and this improvement would reach 60% if clonazepam were associated to psychotherapy. Key words:Burning mouth syndrome, stomatodynia, oral pain, clonazepam. PMID:23229252

  16. 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

  17. Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease.

    PubMed

    Patterson, C E; Todd, S A; Passmore, A P

    2011-12-01

    Factors that influence response to drug treatment are of increasing importance. We report an analysis of genetic factors affecting response to cholinesterase inhibitor therapy in 165 subjects with Alzheimer's disease (AD). The presence of apolipoprotein E ε4 (APOE ε4) allele was associated with early and late cognitive response to cholinesterase inhibitor treatment in mild AD (Mini-Mental State Examination (MMSE) ≥21) (P<0.01). In moderate-to-severe AD (MMSE ≤15), presence of the BCHE-K variant was associated with late response to cholinesterase inhibitor treatment (P=0.02). Testing for APOE and BCHE genotypes may be useful in therapeutic decision making.

  18. The tridimensional personality questionnaire as a predictor of response to nefazodone treatment of depression.

    PubMed

    Nelson, E C; Cloninger, C R

    1995-10-01

    Personality traits have emerged as the strongest identified predictors of response to antidepressant treatment of major depressive disorder (Peselow et al., 1992; Joyce et al., 1994). 18 subjects in the midst of a major depressive episode were treated with nefazodone in an open trial. All subjects completed Cloninger's tridimensional personality questionnaire (TPQ) before beginning treatment. A multiple regression analysis was performed in an attempt to replicate Joyce et al.'s (1994) finding that temperament type, as assessed by the TPQ, is a strong predictor of antidepressant response. A model involving TPQ reward dependence and harm avoidance scores, and their interaction, was found to significantly predict the response to nefazodone (r2 = 0.47, P < 0.027). When response was defined as a 50% decrease in HAM-D score at last visit, high reward dependence score alone significantly separated responders from nonresponders (Fisher's exact P = 0.050, df = 1). These results raise the intriguing possibility that TPQ scores may have direct clinical applications. PMID:8557887

  19. Melatonin treatment in old mice enables a more youthful response to LPS in the brain.

    PubMed Central

    Perreau, V.M.; Bondy, S.C.; Cotman, C.W.; Sharman, K.G.; Sharman, E.H.

    2007-01-01

    Melatonin modulates the expression of a number of genes related to inflammation and immunity. Declining levels of melatonin with age may thus relate to some of the changes in immune function that occur with age. mRNA expression levels in murine CNS were measured using oligonucleotide microarrays in order to determine whether a dietary melatonin supplement may modify age-related changes in the response to an inflammatory challenge. CB6F1 male mice were fed 40ppm melatonin for 9 weeks prior to sacrifice at 26.5 months of age, and compared with age-matched untreated controls and 4.5-month-old controls. A subset of both young and old animals was injected i.p. with lipopolysaccharide (LPS). After 3 hours, total RNA was extracted from whole brain (excluding brain stem and cerebellum), and individual samples were hybridized to Affymetrix Mouse 430-2.0 arrays. Data were analyzed in Dchip and GeneSpring. Melatonin treatment markedly altered the response in gene expression of older animals subjected to an LPS challenge. These changes in general, caused the response to more closely resemble that of young animals subjected to the same LPS challenge. Thus melatonin treatment effects a major shift in the response of the CNS to an inflammatory challenge, causing a transition to a more youthful mRNA expression profile. PMID:17070935

  20. Slower Fibrosis Progression Among Liver Transplant Recipients With Sustained Virological Response After Hepatitis C Treatment

    PubMed Central

    Habib, Shahid; Meister, Edward; Habib, Sana; Murakami, Traci; Walker, Courtney; Rana, Abbas; Shaikh, Obaid S.

    2015-01-01

    Background The natural course of hepatic fibrosis in HCV allograft recipients with sustained virological response (SVR) after anti-HCV therapy remains debatable. The aim of this study was to examine the progression of fibrosis in a cohort of patients who achieved SVR compared with those without treatment. Methods The 167 patients who met the inclusion and exclusion criteria were chosen from a transplant database. All patients were required to have histological evidence of recurrent HCV infection post-liver transplantation and a follow-up biopsy. The 140 of these patients had received anti-viral therapy. Twenty-seven patients were identified as controls and were matched with the treatment group in all respects. The patients were categorized into four groups based on treatment response: 1) no treatment (control) (n = 27); 2) non-responders (n = 81); 3) relapsers (n = 32); and 4) SVR (n = 27). The endpoint was the stage of fibrosis on the follow-up liver biopsy. Results The treated and untreated groups were similar in clinical characteristics at the time of transplantation and prior to the initiation of treatment. The 72% of the cohort showed a fibrosis progression of ≥ 1 stage; this change did not significantly differ between the patient groups. Nonetheless, the fibrosis progression rate was the highest in the untreated group and lowest in the patients who achieved SVR. A coefficient of determination was used. Improvements in fibrosis scores were found with greater treatment duration. These improvements were most evident with the achievement of SVR. Conclusions In conclusion, SVR after anti-viral therapy for recurrent hepatitis C infection post-transplantation was associated with slower fibrosis progression and significantly improved graft survival.

  1. 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. PMID:25486545

  2. 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.

  3. Exposure and Response Prevention Process Predicts Treatment Outcome in Youth with OCD

    PubMed Central

    Kircanski, Katharina; Peris, Tara S.

    2014-01-01

    Recent research on the treatment of adults with anxiety disorders suggests that aspects of the in-session exposure therapy process are relevant to clinical outcomes. However, few comprehensive studies have been conducted with children and adolescents. In the present study, 35 youth diagnosed with primary obsessive-compulsive disorder (OCD; M age=12.9 years, 49% male, 63% Caucasian) completed 12 sessions of exposure and response prevention (ERP) in one of two treatment conditions as part of a pilot randomized controlled testing of a family focused intervention for OCD. Key exposure process variables, including youth self-reported distress during ERP and the quantity and quality of ERP completed, were computed. These variables were examined as predictors of treatment outcomes assessed at mid-treatment, post-treatment, and three-month follow-up, partialing treatment condition. In general, greater variability of distress during ERP and completing a greater proportion of combined exposures (i.e., exposures targeting more than one OC symptom at once) were predictive of better outcomes. Conversely, greater distress at the end of treatment was generally predictive of poorer outcomes. Finally, several variables, including within- and between-session decreases in distress during ERP, were not consistently predictive of outcomes. Findings signal potentially important facets of exposure for youth with OCD and have implications for treatment. A number of results also parallel recent findings in the adult literature, suggesting that there may be some continuity in exposure processes from child to adult development. Future work should examine additional measures of exposure process, such as psychophysiological arousal during exposure, in youth. PMID:25052626

  4. 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.

  5. 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

  6. 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

  7. Ictal adipokines are associated with pain severity and treatment response in episodic migraine

    PubMed Central

    Chai, Nu Cindy; Gelaye, Bizu; Tietjen, Gretchen E.; Dash, Paul D.; Gower, Barbara A.; White, Linda W.; Ward, Thomas N.; Scher, Ann I.

    2015-01-01

    Objective: To evaluate ictal adipokine levels in episodic migraineurs and their association with pain severity and treatment response. Methods: This was a double-blind, placebo-controlled trial evaluating peripheral blood specimens from episodic migraineurs at acute pain onset and 30 to 120 minutes after treatment with sumatriptan/naproxen sodium vs placebo. Total adiponectin (T-ADP), ADP multimers (high molecular weight [HMW], middle molecular weight, and low molecular weight [LMW]), leptin, and resistin levels were evaluated by immunoassays. Results: Thirty-four participants (17 responders, 17 nonresponders) were included. In all participants, pretreatment pain severity increased with every quartile increase in both the HMW:T-ADP ratio (coefficient of variation [CV] 0.51; 95% confidence interval [CI]: 0.08, 0.93; p = 0.019) and resistin levels (CV 0.58; 95% CI: 0.21, 0.96; p = 0.002), but was not associated with quartile changes in leptin levels. In responders, T-ADP (CV −0.98; 95% CI: −1.88, −0.08; p = 0.031) and resistin (CV −0.95; 95% CI: −1.83, −0.07; p = 0.034) levels decreased 120 minutes after treatment as compared with pretreatment. In addition, in responders, the HMW:T-ADP ratio (CV −0.04; 95% CI: −0.07, −0.01; p = 0.041) decreased and the LMW:T-ADP ratio (CV 0.04; 95% CI: 0.01, 0.07; p = 0.043) increased at 120 minutes after treatment. In nonresponders, the LMW:T-ADP ratio (CV −0.04; 95% CI: −0.07, −0.01; p = 0.018) decreased 120 minutes after treatment. Leptin was not associated with treatment response. Conclusions: Both pretreatment migraine pain severity and treatment response are associated with changes in adipokine levels. Adipokines represent potential novel migraine biomarkers and drug targets. PMID:25746563

  8. Post-treatment vascular leakage and inflammatory responses around brain cysts in porcine neurocysticercosis.

    PubMed

    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

    2015-03-01

    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

  9. 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.

  10. The effects of chronic ethanol treatment on endothelium-dependent responses in rat thoracic aorta.

    PubMed

    Williams, S P; Adams, R D; Mustafa, S J

    1990-01-01

    The purpose of this study was to investigate the effects of chronic ethanol consumption on blood pressure and vascular responses, specifically, the possible alterations in endothelium-dependent relaxation which are associated with ethanol-induced hypertension in the rat model. Male rats received ethanol in drinking water for 13 weeks. Systolic pressure was recorded weekly. Following treatment, segments of thoracic aorta with and without intact endothelium were used to generate relaxation-response curves to the endothelium-dependent agents, acetylcholine, ATP and bradykinin, as well as the endothelium-independent agents, adenosine and sodium nitroprusside. Mean systolic pressures at the end of the treatment period were: 127.8 +/- 1.2 and 151.1 +/- 1.3 mmHg for controls and ethanol-treated rats, respectively. Ethanol treatment did not affect the relaxation produced by either acetylcholine, ATP or sodium nitroprusside in aorta with or without endothelium. In contrast, ring segments with intact endothelium from ethanol-treated rats exhibited augmented relaxation in response to both adenosine and bradykinin compared to controls. Removal of the endothelium abolished the relaxation produced by bradykinin in both groups. Although removal of the endothelium had no effect on the relaxation produced by adenosine in the control group, it attenuated the adenosine-induced relaxation in the ethanol-treated group back to control levels. These data suggest that chronic ingestion of ethanol causes elevated blood pressure and augments the endothelium-dependent relaxation to bradykinin. These findings also suggest that chronic ethanol treatment can cause the appearance of an endothelium-dependent component in the relaxation produced by adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Association of HLA-DRB1 Haplotypes With Rheumatoid Arthritis Severity, Mortality, and Treatment Response

    PubMed Central

    Viatte, Sebastien; Plant, Darren; Han, Buhm; Fu, Bo; Yarwood, Annie; Thomson, Wendy; Symmons, Deborah P. M.; Worthington, Jane; Young, Adam; Hyrich, Kimme L.; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Raychaudhuri, Soumya; Barton, Anne

    2016-01-01

    IMPORTANCE Advances have been made in identifying genetic susceptibility loci for autoimmune diseases, but evidence is needed regarding their association with prognosis and treatment response. OBJECTIVE To assess whether specific HLA-DRB1 haplotypes associated with rheumatoid arthritis (RA) susceptibility are also associated with radiological severity, mortality, and response to tumor necrosis factor (TNF) inhibitor drugs. DESIGN, SETTING, AND PARTICIPANTS The Norfolk Arthritis Register (NOAR; 1691 patients and 2811 radiographs; recruitment: 1989–2008; 2008 as final follow-up) was used as a discovery cohort and the Early Rheumatoid Arthritis Study (421 patients and 3758 radiographs; recruitment: 1986–1999; 2005 as final follow-up) as an independent replication cohort for studies of radiographic outcome. Mortality studies were performed in the NOAR cohort (2432 patients; recruitment: 1990–2007; 2011 as final follow-up) and studies of treatment response in the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort (1846 patients enrolled at initiation of TNF inhibitor; recruitment: 2006–2010; 2011 as final follow-up). Longitudinal statistical modeling was performed to integrate multiple radiograph records per patient over time. All patients were from the United Kingdom and had self-reported white ancestry. EXPOSURES Sixteen HLA-DRB1 haplotypes defined by amino acids at positions 11, 71, and 74. MAIN OUTCOMES AND MEASURES Radiological outcome using the Larsen score (range: 0 [none] to 200 [severe joint damage]) and erosions of the hands and feet on radiographs, all-cause mortality, and treatment response measured by change in Disease Activity Score based on 28 joint counts and European League Against Rheumatism (EULAR) response. RESULTS Patients with RA and valine at position 11 of HLA-DRB1 had the strongest association with radiological damage (OR, 1.75 [95% CI, 1.51–2.05], P = 4.6E-13). By year 5, the percentages of patients with

  12. 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.

  13. 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

  14. Hyperprolactinemia in men: clinical and biochemical features and response to treatment.

    PubMed

    De Rosa, Michele; Zarrilli, Stefano; Di Sarno, Antonella; Milano, Nicola; Gaccione, Maria; Boggia, Bartolomeo; Lombardi, Gaetano; Colao, Annamaria

    2003-01-01

    Hyperprolactinemia induces hypogonadism by inhibiting gonadotropin-releasing hormone pulsatile secretion and, consequently, follicle-stimulating hormone, luteinizing hormone, and testosterone pulsatility. This leads to spermatogenic arrest, impaired motility, and sperm quality and results in morphologic alterations of the testes similar to those observed in prepubertal testes. Men with hyperprolactinemia present more frequently with a macroadenoma than a microadenoma. Symptoms directly related to hypogonadism are prevalent. In men hypogonadism leads to impaired libido, erectile dysfunction, diminished ejaculate volume, and oligospermia. It is present in 16% of patients with erectile dysfunction and in approx 11% of men with oligospermia. Treatment with bromocriptine or cabergoline (CAB) is effective in men with prolactinomas, with a response that is in general comparable to treatment in women. Seminal fluid abnormalities rapidly improve with CAB treatment, while other dopaminergic compounds require longer periods of treatment. Moreover, to improve gonadal function in men, the integrity of the hypothalamic-pituitary-gonadal axis is necessary. New promising data indicate that a substantial proportion of patients with either micro- or macroprolactinoma do not present hyperprolactinemia after long-term withdrawal from CAB. Whether this corresponds to a definitive cure is still unknown, but treatment withdrawal should be attempted in patients achieving normalization of prolactin levels and disappearance of tumor mass to investigate this issue.

  15. 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.

  16. The responsive amygdala: treatment-induced alterations in functional connectivity in pediatric complex regional pain syndrome.

    PubMed

    Simons, L E; Pielech, M; Erpelding, N; Linnman, C; Moulton, E; Sava, S; Lebel, A; Serrano, P; Sethna, N; Berde, C; Becerra, L; Borsook, D

    2014-09-01

    The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear, and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-sex matched control subjects before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared with control subjects, with differences predominantly in the left amygdala in the pretreated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy control subjects from time 1 to time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores; and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity after an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response.

  17. Serum Strongylus vulgaris-specific antibody responses to anthelmintic treatment in naturally infected horses.

    PubMed

    Nielsen, Martin K; Vidyashankar, Anand N; Bellaw, Jennifer; Gravatte, Holli S; Cao, Xin; Rubinson, Emily F; Reinemeyer, Craig R

    2015-02-01

    Strongylus vulgaris is the most pathogenic helminth parasite of horses, causing verminous endarteritis with thromboembolism and infarction. A serum enzyme-linked immunosorbent assay (ELISA) has been validated for detection of antibodies to an antigen produced by migrating larvae of this parasite. The aim was to evaluate ELISA responses to anthelmintic treatment in cohorts of naturally infected horses. Fifteen healthy horses harboring patent S. vulgaris infections were turned out for communal grazing in May 2013 (day 0). On day 55, horses were ranked according to ELISA titers and randomly allocated to the following three groups: no treatment followed by placebo pellets daily; ivermectin on day 60 followed by placebo pellets daily; or ivermectin on day 60 followed by daily pyrantel tartrate. Fecal and serum samples were collected at ∼28-day intervals until study termination on day 231. Increased ELISA values were observed for the first 53 days following ivermectin treatment. Titers were significantly reduced 80 days after ivermectin treatment. Horses receiving daily pyrantel tartrate maintained lower ELISA values from 137 days post ivermectin treatment until trial termination. These results illustrate that a positive ELISA result is indicative of either current or prior exposure to larval S. vulgaris infection within the previous 5 months.

  18. 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. PMID:18330131

  19. Serum Strongylus vulgaris-specific antibody responses to anthelmintic treatment in naturally infected horses.

    PubMed

    Nielsen, Martin K; Vidyashankar, Anand N; Bellaw, Jennifer; Gravatte, Holli S; Cao, Xin; Rubinson, Emily F; Reinemeyer, Craig R

    2015-02-01

    Strongylus vulgaris is the most pathogenic helminth parasite of horses, causing verminous endarteritis with thromboembolism and infarction. A serum enzyme-linked immunosorbent assay (ELISA) has been validated for detection of antibodies to an antigen produced by migrating larvae of this parasite. The aim was to evaluate ELISA responses to anthelmintic treatment in cohorts of naturally infected horses. Fifteen healthy horses harboring patent S. vulgaris infections were turned out for communal grazing in May 2013 (day 0). On day 55, horses were ranked according to ELISA titers and randomly allocated to the following three groups: no treatment followed by placebo pellets daily; ivermectin on day 60 followed by placebo pellets daily; or ivermectin on day 60 followed by daily pyrantel tartrate. Fecal and serum samples were collected at ∼28-day intervals until study termination on day 231. Increased ELISA values were observed for the first 53 days following ivermectin treatment. Titers were significantly reduced 80 days after ivermectin treatment. Horses receiving daily pyrantel tartrate maintained lower ELISA values from 137 days post ivermectin treatment until trial termination. These results illustrate that a positive ELISA result is indicative of either current or prior exposure to larval S. vulgaris infection within the previous 5 months. PMID:25358238

  20. 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

  1. 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

    2016-01-01

    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 (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. PMID:27549343

  2. Magnetic resonance imaging predictors of treatment response in late-life depression.

    PubMed

    Aizenstein, Howard J; Khalaf, Alexander; Walker, Sarah E; Andreescu, Carmen

    2014-03-01

    In older adults, depression not only results in more years lived with disability than any other disease but it also carries additional risks of suicide, medical comorbidities, and family caregiving burden. Because it can take many months to identify an effective treatment regimen, it is of utmost importance to shorten the window of time and identify early on what medications and dosages will work effectively for individuals having depression. Late-life depression (LLD) has been associated with greater burden of age-related changes (eg, atrophy, white matter ischemic changes, and functional connectivity). Depression in midlife has been shown to alter affective reactivity and regulation, and functional magnetic resonance imaging (fMRI) studies in LLD have replicated the same abnormalities. Effective treatment can normalize these alterations. This article provides a review of the current literature using structural and functional neuroimaging to identify MRI predictors of treatment response in LLD. The majority of the literature on structural MRI has focused on the vascular depression hypothesis, and studies support the view that loss of brain volume and white matter integrity was associated with poorer treatment outcomes. Studies using fMRI have reported that lower task-based activity in the prefrontal cortex and limbic regions was associated with poorer outcome. These imaging markers may be integrated into clinical decision making to attain better treatment outcomes in the future. PMID:24381231

  3. Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods.

    PubMed

    Ahmed, Rafay; Oborski, Matthew J; Hwang, Misun; Lieberman, Frank S; Mountz, James M

    2014-01-01

    Malignant gliomas consist of glioblastomas, anaplastic astrocytomas, anaplastic oligodendrogliomas and anaplastic oligoastrocytomas, and some less common tumors such as anaplastic ependymomas and anaplastic gangliogliomas. Malignant gliomas have high morbidity and mortality. Even with optimal treatment, median survival is only 12-15 months for glioblastomas and 2-5 years for anaplastic gliomas. However, recent advances in imaging and quantitative analysis of image data have led to earlier diagnosis of tumors and tumor response to therapy, providing oncologists with a greater time window for therapy management. In addition, improved understanding of tumor biology, genetics, and resistance mechanisms has enhanced surgical techniques, chemotherapy methods, and radiotherapy administration. After proper diagnosis and institution of appropriate therapy, there is now a vital need for quantitative methods that can sensitively detect malignant glioma response to therapy at early follow-up times, when changes in management of nonresponders can have its greatest effect. Currently, response is largely evaluated by measuring magnetic resonance contrast and size change, but this approach does not take into account the key biologic steps that precede tumor size reduction. Molecular imaging is ideally suited to measuring early response by quantifying cellular metabolism, proliferation, and apoptosis, activities altered early in treatment. We expect that successful integration of quantitative imaging biomarker assessment into the early phase of clinical trials could provide a novel approach for testing new therapies, and importantly, for facilitating patient management, sparing patients from weeks or months of toxicity and ineffective treatment. This review will present an overview of epidemiology, molecular pathogenesis and current advances in diagnoses, and management of malignant gliomas.

  4. Delay discounting is associated with treatment response among cocaine-dependent outpatients.

    PubMed

    Washio, Yukiko; Higgins, Stephen T; Heil, Sarah H; McKerchar, Todd L; Badger, Gary J; Skelly, Joan M; Dantona, Robert L

    2011-06-01

    Delay discounting (DD) describes the rate at which reinforcers lose value as the temporal delay to their receipt increases. Steeper discounting has been positively associated with vulnerability to substance use disorders, including cocaine use disorders. In the present study, we examined whether DD of hypothetical monetary reinforcers is associated with the duration of cocaine abstinence achieved among cocaine-dependent outpatients. Participants were 36 adults who were participating in a randomized controlled trial examining the efficacy of voucher-based contingency management (CM) using low-magnitude (N = 18) or high-magnitude (N = 18) voucher monetary values. DD was associated with the number of continuous weeks of cocaine abstinence achieved, even after adjusting for treatment condition during the initial 12-week, t(33) = 2.48, p = .045 and entire recommended 24-week of treatment, t(33) = 2.40, p = .022. Participants who exhibited steeper discounting functions achieved shorter periods of abstinence in the Low-magnitude voucher condition (12-week: t(16) = 2.48, p = .025; 24-week: t(16) = 2.68, p = .017), but not in the High-magnitude voucher condition (12-week: t(16) = 0.51, p = .618; 24-week: t(16) = 1.08, p = .298), although the interaction between DD and treatment condition was not significant (12-week: t(32) = -1.12, p = .271; 24-week: t(32) = -0.37, p = .712). These results provide further evidence on associations between DD and treatment response and extend those observations to a new clinical population (i.e., cocaine-dependent outpatients), while also suggesting that a more intensive intervention like the High-magnitude CM condition may diminish this negative relationship between DD and treatment response.

  5. Nanoparticles responsive to the inflammatory microenvironment for targeted treatment of arterial restenosis.

    PubMed

    Feng, Shibin; Hu, Ying; Peng, Song; Han, Songling; Tao, Hui; Zhang, Qixiong; Xu, Xiaoqiu; Zhang, Jianxiang; Hu, Houyuan

    2016-10-01

    Coronary arterial disease (CAD) remains the leading cause of death globally. Percutaneous coronary interventions are frequently used nonsurgical techniques for treating CAD, which may unfortunately lead to arterial restenosis. Currently, there are no effective drugs that can thoroughly prevent restenosis. We hypothesize inflammation-triggerable nanomedicines may function as effective therapeutics for targeted therapy of restenosis, by preferentially releasing their payload at the diseased site. To demonstrate our hypothesis and develop targeted nanotherapies for restenosis, this study was designed to examine effectiveness of nanomedicines responsive to the inflammatory microenvironment with mild acidity and high reactive oxygen species (ROS). To this end, an acetalated β-cyclodextrin (β-CD) material (Ac-bCD) was synthesized as a pH-responsive carrier material, while a ROS-responsive material (Ox-bCD) was produced by hydrophobic functionalization of β-CD with an oxidation-labile group. Based on these two responsive materials, either pH- or ROS-responsive nanoparticles (NPs) were produced by a nanoprecipitation technique and fully characterized. Using rapamycin (RAP) as a candidate drug, responsive nanotherapies were fabricated. In vitro hydrolysis and release studies confirmed these nanovehicles and nanotherapies exhibited desirable responsive behaviors. Both in vitro cell culture and in vivo evaluations revealed their good safety profile. These responsive NPs could be effectively internalized by rat vascular smooth muscle cells, which in turn notably potentiated anti-proliferation and anti-migration activities of RAP. After intravenous (i.v.) injection, NPs may be accumulated at the injured site in the carotid artery of rats subjected to balloon angioplasty injury. Compared with a non-responsive nanotherapy based on poly(lactide-co-glycolide), treatment with either pH- or ROS-responsive nanotherapy by i.v. injection more effectively attenuated neointimal

  6. Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids

    PubMed Central

    L'Espérance, Sylvain; Bachvarova, Magdalena; Tetu, Bernard; Mes-Masson, Anne-Marie; Bachvarov, Dimcho

    2008-01-01

    Background Chemotherapy (CT) resistance in ovarian cancer (OC) is broad and encompasses diverse unrelated drugs, suggesting more than one mechanism of resistance. To better understand the molecular mechanisms controlling the immediate response of OC cells to CT exposure, we have performed gene expression profiling in spheroid cultures derived from six OC cell lines (OVCAR3, SKOV3, TOV-112, TOV-21, OV-90 and TOV-155), following treatment with 10,0 μM cisplatin, 2,5 μM paclitaxel or 5,0 μM topotecan for 72 hours. Results Exposure of OC spheroids to these CT drugs resulted in differential expression of genes associated with cell growth and proliferation, cellular assembly and organization, cell death, cell cycle control and cell signaling. Genes, functionally involved in DNA repair, DNA replication and cell cycle arrest were mostly overexpressed, while genes implicated in metabolism (especially lipid metabolism), signal transduction, immune and inflammatory response, transport, transcription regulation and protein biosynthesis, were commonly suppressed following all treatments. Cisplatin and topotecan treatments triggered similar alterations in gene and pathway expression patterns, while paclitaxel action was mainly associated with induction of genes and pathways linked to cellular assembly and organization (including numerous tubulin genes), cell death and protein synthesis. The microarray data were further confirmed by pathway and network analyses. Conclusion Most alterations in gene expression were directly related to mechanisms of the cytotoxics actions in OC spheroids. However, the induction of genes linked to mechanisms of DNA replication and repair in cisplatin- and topotecan-treated OC spheroids could be associated with immediate adaptive response to treatment. Similarly, overexpression of different tubulin genes upon exposure to paclitaxel could represent an early compensatory effect to this drug action. Finally, multicellular growth conditions that are

  7. 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

  8. 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

  9. 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

  10. Abnormal plasma monoamine metabolism in schizophrenia and its correlation with clinical responses to risperidone treatment.

    PubMed

    Cai, Hua-Lin; Fang, Ping-Fei; Li, Huan-De; Zhang, Xiang-Hui; Hu, Li; Yang, Wen; Ye, Hai-Sen

    2011-07-30

    Abnormalities in plasma monoamine metabolism reflect partly the illness of schizophrenia and sometimes the symptoms. Such studies have been repeatedly reported but have rarely taken both metabolites and parent amines or inter-amine activity ratios into account. In this study, the monoamines, their metabolites, turnovers and between-metabolite ratios in plasma were measured longitudinally in 32 schizophrenic patients treated with risperidone for 6 weeks, to examine possible biochemical alterations in schizophrenia, and to examine the association between treatment responses and psychopathology assessed according to the Positive and Negative Syndrome Scale (PANSS). The results showed lower level of plasma 3,4-dihydroxyphenylacetic acid (DOPAC) in relapsed versus first-episode schizophrenic patients, higher norepinephrine (NE) turnover rate (TR) in undifferentiated in comparison to paranoid schizophrenic patients and relatively higher metabolic activity of dopamine (DA) to serotonin (5-HT) in first-episode versus relapsed schizophrenic patients. Risperidone treatment induced a decrement of plasma DA levels and increments of plasma DOPAC and DA TR in the total group of schizophrenic patients. The turnover rate of 5-HT was was reduced in undifferentiated and relapsed subgroups of schizophrenic patients. The linkages between 5-HT TR, DA/NE relative activity and clinical symptomatology were also identified. These findings are consistent with an involvement of these systems in the pathogenesis of schizophrenia as well as in the responses to treatment, and the usefulness of certain biochemical indices as markers for subgrouping.

  11. 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.

  12. 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.

  13. Proteome changes in banana fruit peel tissue in response to ethylene and high-temperature treatments.

    PubMed

    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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. Optimization of Electrochemical Treatment Process Conditions for Distillery Effluent Using Response Surface Methodology

    PubMed Central

    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/cm2, electrolysis time of 103.27 min, and electrolyte (NaCl) concentration of 1.67 g/L, respectively. PMID:26491716

  19. 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. PMID:26491716

  20. 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

  1. 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. PMID:27603381

  2. Comparative Analysis of Different Approaches to Measure Treatment Response in Acute Myeloid Leukemia

    PubMed Central

    Inaba, Hiroto; Coustan-Smith, Elaine; Cao, Xueyuan; Pounds, Stanley B.; Shurtleff, Sheila A.; Wang, Kathleen Y.; Raimondi, Susana C.; Onciu, Mihaela; Jacobsen, Jeffrey; Ribeiro, Raul C.; Dahl, Gary V.; Bowman, W. Paul; Taub, Jeffrey W.; Degar, Barbara; Leung, Wing; Downing, James R.; Pui, Ching-Hon; Rubnitz, Jeffrey E.; Campana, Dario

    2012-01-01

    Purpose In acute myeloid leukemia (AML), initial treatment response by morphologic analysis of bone marrow predicts long-term outcome. Response can now be assessed by minimal residual disease (MRD) monitoring with flow cytometry or polymerase chain reaction (PCR). We determined the relation among the results of these approaches and their prognostic value. Patients and Methods In the multicenter AML02 study, follow-up bone marrow samples from 203 children and adolescents with newly diagnosed AML were examined by flow cytometry (n = 1,514), morphology (n = 1,382), and PCR amplification of fusion transcripts (n = 508). Results were correlated with treatment outcome. Results Among 1,215 samples with less than 5% leukemic myeloblasts by morphology, 100 (8.2%) were MRD positive (≥ 0.1%) by flow cytometry, whereas 96 (57.5%) of the 167 samples with ≥ 5% blasts were MRD negative. Virtually all (308 of 311; 99.0%) MRD-negative samples by PCR were also MRD negative by flow cytometry. However, only 19 (9.6%) of the 197 PCR-positive samples were flow cytometry positive, with analyses of AML1-ETO and CBFβ-MYH11 accounting for most discrepancies, whereas eight of 13 MLL-positive samples had detectable MRD by flow cytometry. MRD by flow cytometry after induction 1 or 2 predicted lower event-free survival and higher relapse rate (P < .001) and was an independent prognostic factor in a multivariable analysis; prediction was not improved by morphologic information or molecular findings. Conclusion In childhood AML, morphologic assessment of treatment response has limited value if MRD is measured by flow cytometry. MLL fusion transcripts can provide prognostic information in some patients, whereas monitoring of AML1-ETO and CBFβ-MYH11 transcripts is largely uninformative. PMID:22965955

  3. 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.

  4. Dose-response effects of atropine and HI-6 treatment of organophosphorus poisoning in guinea pigs.

    PubMed

    Koplovitz, I; Menton, R; Matthews, C; Shutz, M; Nalls, C; Kelly, S

    1995-01-01

    HI-6 (1-2-hydroxyiminomethyl-1-pyridino-3-(4-carbamoyl-1-pyridino -2- oxapropane dichloride) has been evaluated as an oxime alternative to pralidoxime, and toxogonin in the treatment of organophosphorus (OP) poisoning. The dose response effects of atropine (ATR) and HI-6 were investigated to more fully explore the interaction of these compounds in the treatment of OP poisoning. ATR, HI-6 and various combinations of the two drugs were evaluated against lethal poisoning by soman (GD) and tabun (GA) in guinea pigs. The effect of adjunctive diazepam treatment on the efficacy of atropine and HI-6 against soman was also investigated. Animals of either sex were challenged s.c. with OP and treated i.m. 1 min later with ATR and/or HI-6. When used, diazepam was injected immediately after ATR+HI6. LD50s of each treatment were calculated from probit models based on 24-hour survival against 5 levels of nerve agent and 6 animals per challenge level. A protective index (PI) was calculated by dividing the nerve agent LD50 in the presence of treatment by the LD50 in the absence of treatment. Treatment with HI6 alone had little effect on the toxicity of either OP. Treatment with ATR alone was more effective than HI-6 alone and was significantly more effective against soman than against tabun. When used in combination atropine and HI-6 had a strong synergistic effect against both agents. The dose of atropine used with HI-6 was critical in determining the efficacy of HI-6 against either agent. The slopes of the dose-lethality curves were minimally affected by the dose of ATR or HI-6. Adjunctive treatment with diazepam enhanced the efficacy of HI-6 and atropine against soman. It is concluded that 1) ATR has a large effect on the efficacy of HI-6 against OP poisoning, 2) the dose of ATR must be carefully selected in studies investigating the efficacy of HI-6 against OP poisoning, 3) the effective dose of ATR in the guinea pig is approximately 16 mg/kg, and 4) diazepam is a useful

  5. A β-Lactamase-Imprinted Responsive Hydrogel for the Treatment of Antibiotic-Resistant Bacteria.

    PubMed

    Li, Wen; Dong, Kai; Ren, Jinsong; Qu, Xiaogang

    2016-07-01

    Antibiotics play important roles in infection treatment and prevention. However, the effectiveness of antibiotics is now threatened by the prevalence of drug-resistant bacteria. Furthermore, antibiotic abuse and residues in the environment cause serious health issues. In this study, a stimuli-responsive imprinted hydrogel was fabricated by using β-lactamase produced by bacteria for deactivating antibiotics as the template molecule. The imprinted hydrogel could initially trap β-lactamase excreted by drug-resistant bacteria, thus making bacteria sensitive to antibiotics. After the bactericidal treatment, the "imprinted sites" on the hydrogel could be reversibly abolished with a temperature stimulus, which resulted in the reactivation of β-lactamase to degrade antibiotic residues. We also present an example of the use of this antibacterial design to treat wound infection. PMID:27159893

  6. 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.

  7. Beyond morality: the need for psychodynamic understanding and treatment of responses to the AIDS crisis.

    PubMed

    Rogers, R R

    1989-09-01

    The purpose of this paper is to identify a broad range of issues that both impact, and are impacted by, psychiatric intervention in AIDS and AIDS-related cases, with a special concern towards emphasizing the need for application of a psychodynamic perspective, in the understanding and treatment of pathological responses to the AIDS crisis. As a cornerstone of the psychiatric model, psychodynamic evaluation and treatment can provide a breadth of focus and depth of understanding crucial to a resolution of some of the deeper psychosocial aspects involved in the reaction to and spread of the AIDS virus. A case example is used to illustrate psychodynamic factors which precluded the patient's ability to choose monogamy, and which contributed to the "transmission" of a cyclic pattern of psychodynamic pathology.

  8. Body mass index influence interferon-beta treatment response in multiple sclerosis.

    PubMed

    Kvistad, Silje Stokke; Myhr, Kjell-Morten; Holmøy, Trygve; Šaltytė Benth, Jūratė; Wergeland, Stig; Beiske, Antonie G; Bjerve, Kristian S; Hovdal, Harald; Lilleås, Finn; Midgard, Rune; Pedersen, Tom; Bakke, Søren J; Michelsen, Annika E; Aukrust, Pål; Ueland, Thor; Sagen, Jørn V; Torkildsen, Øivind

    2015-11-15

    Obesity is a possible risk factor of multiple sclerosis (MS), but the association between obesity and MS disease activity has not been explored. In a cohort of 86 MS patients, 80% of overweight or obese patients (BMI≥25kg/m(2)) had MRI activity compared to 48% of the normal-weight patients (BMI<25kg/m(2)) (p=0.001) during interferon-beta treatment. NEDA-status (no evidence of disease activity) was defined as a composite that consisted of absence of any relapses, sustained disability-progression and MRI-activity. Among normal-weight patients 26% obtained NEDA-status compared to only 13% of patients with BMI >25 (p=0.05). This may indicate that BMI affects interferon-beta treatment response.

  9. 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.

  10. Analysis of physiological responses associated with emotional changes induced by viewing video images of dental treatments.

    PubMed

    Sekiya, Taki; Miwa, Zenzo; Tsuchihashi, Natsumi; Uehara, Naoko; Sugimoto, Kumiko

    2015-01-01

    Since the understanding of emotional changes induced by dental treatments is important for dentists to provide a safe and comfortable dental treatment, we analyzed physiological responses during watching video images of dental treatments to search for the appropriate objective indices reflecting emotional changes. Fifteen healthy young adult subjects voluntarily participated in the present study. Electrocardiogram (ECG), electroencephalogram (EEG) and corrugator muscle electromyogram (EMG) were recorded and changes of them by viewing videos of dental treatments were analyzed. The subjective discomfort level was acquired by Visual Analog Scale method. Analyses of autonomic nervous activities from ECG and four emotional factors (anger/stress, joy/satisfaction, sadness/depression and relaxation) from EEG demonstrated that increases in sympathetic nervous activity reflecting stress increase and decreases in relaxation level were induced by the videos of infiltration anesthesia and cavity excavation, but not intraoral examination. The corrugator muscle activity was increased by all three images regardless of video contents. The subjective discomfort during watching infiltration anesthesia and cavity excavation was higher than intraoral examination, showing that sympathetic activities and relaxation factor of emotion changed in a manner consistent with subjective emotional changes. These results suggest that measurement of autonomic nervous activities estimated from ECG and emotional factors analyzed from EEG is useful for objective evaluation of subjective emotion. PMID:26111531

  11. 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

  12. 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.

  13. Utility of functional imaging in prediction or assessment of treatment response and prognosis following thermotherapy

    PubMed Central

    Dewhirst, Mark W.; Thrall, Donald E.; Palmer, Gregory; Schroeder, Thies; Vujaskovic, Zeljko; Charles, H. Cecil; MacFall, James; Wong, Terence

    2009-01-01

    The purpose of this review is to examine the roles that functional imaging may play in prediction of treatment response and determination of overall prognosis in patients who are enrolled in thermotherapy trials, either in combination with radiotherapy, chemotherapy or both. Most of the historical work that has been done in this field has focused on MRI/MRS methods, so the emphasis will be there, although some discussion of the role that PET might play will also be examined. New optical technologies also hold promise for obtaining low cost, yet valuable physiologic data from optically accessible sites. The review is organized by traditional outcome parameters: local response, local control and progression free or overall survival. Included in the review is a discussion of future directions for this type of translational work. PMID:20170362

  14. 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.

  15. Induction of Response to Psychotropic Medications in Depression and Panic After Concurrent Treatment of Diabetes

    PubMed Central

    Srinivasa, Murthy Vasantmeghna; Pradeep, Bombe Abhijeet; Sadashiv, Lokhande Chetan; Bhagwandas, Shah Nilesh

    2014-01-01

    We present a case of depression with panic disorder, which did not respond to adequate psychiatric interventions over a period of several months. However, it improved completely with the diagnosis and treatment of diabetes mellitus. Hence, we infer that comorbid diabetes mellitus can render depression resistant to psychiatric interventions and must always be ruled out when treating patients who show poor response to adequate interventions for an adequate period of time. The role of antidepressants should also be considered in poor glycemic control. PMID:24860227

  16. Response competition and stimulus preference in the treatment of automatically reinforced behavior: a comparison.

    PubMed

    Groskreutz, Mark P; Groskreutz, Nicole C; Higbee, Thomas S

    2011-01-01

    Clinicians are particularly challenged by the development of interventions for behavior maintained by automatic reinforcement because reinforcers that maintain the responses often cannot be directly observed or manipulated. Researchers have conducted either preference assessments or competing items assessments when developing effective treatments for behavior maintained by automatic reinforcement. However, interventions based on these assessments have not been directly compared. The current study evaluated procedures to make such a comparison. High-competition items resulted in greater reductions in vocal stereotypy than did high-preference items for a preschool boy with autism. PMID:21541129

  17. Neuroanatomical correlates of apathy in late-life depression and antidepressant treatment response

    PubMed Central

    Yuen, Genevieve S.; Gunning, Faith M.; Woods, Eric; Klimstra, Sibel A.; Hoptman, Matthew J.; Alexopoulos, George S.

    2014-01-01

    Background Apathy is a prominent feature of geriatric depression that predicts poor clinical outcomes and hinders depression treatment. Yet little is known about the neurobiology and treatment of apathy in late-life depression. This study examined apathy prevalence in a clinical sample of depressed elderly, response of apathy to selective serotonin reuptake inhibitor (SSRI) treatment, and neuroanatomical correlates that distinguished responders from nonresponders and healthy controls. Methods Participants included 45 non-demented, elderly with major depression and 43 elderly comparison individuals. After a 2-week single-blind placebo period, depressed participants received escitalopram 10mg daily for 12 weeks. The Apathy Evaluation Scale (AES) and 24-item Hamilton Depression Rating Scale (HDRS) were administered at baseline and 12 weeks. MRI scans were acquired at baseline for concurrent structural and diffusion tensor imaging of anterior cingulate grey matter and associated white matter tracts. Results 35.5% of depressed patients suffered from apathy. This declined to 15.6% (p<0.1) following treatment, but 43% of initial sufferers continued to report significant apathy. Improvement of apathy with SSRI was independent of change in depression but correlated with larger left posterior subgenual cingulate volumes and greater fractional anisotropy of left uncinate fasciculi. Limitations modest sample size, no placebo control, post-hoc secondary analysis, use of 1.5T MRI scanner Conclusions While prevalent in geriatric depression, apathy is separable from depression with regards to medication response. Structural abnormalities of the posterior subgenual cingulate and uncinate fasciculus may perpetuate apathetic states by interfering with prefrontal cortical recruitment of limbic activity essential to motivated behavior. PMID:25012429

  18. 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

  19. Macular morphology and response to ranibizumab treatment in patients with wet age-related macular degeneration

    PubMed Central

    Dervenis, Nikolaos; Younis, Saad

    2016-01-01

    Purpose The purpose of this study was to assess whether specific characteristics of spectral domain optical coherence tomography (SD-OCT) affect structural and functional outcomes and number of injections needed in ranibizumab (0.05 mL of 10 mg/mL Lucentis solution)-treated wet age-related macular degeneration (AMD) patients. Patients and methods This retrospective case series included 62 newly diagnosed wet AMD patients treated with three monthly intravitreal ranibizumab injections followed by monthly follow-up and pro re nata retreatment. The presence of dome-shaped pigment epithelial detachment (PED), disruption of the retinal pigment epithelium (RPE), and subretinal and intraretinal fluid was associated with changes in Early Treatment of Diabetic Retinopathy Study visual acuity, central macular thickness (CMT), and number of injections needed during the 6-month follow-up. Results The presence of PED was associated with lower values of CMT at presentation (399 μm [±132 μm] vs 310 μm [±51 μm], P=0.005). The presence of RPE disruption was associated with worse visual acuity in month 6 (0.36 [±0.22] vs 0.61 [0.45], P=0.027) and fewer injections (4.23 [±0.92] vs 3.55 [±0.60], P=0.007). The presence of intraretinal fluid at presentation was associated with worse visual acuity outcomes in month 4 (P=0.045) but not in month 6. Conclusion The dome-shaped PED was associated with lower CMT at presentation, but it did not affect response to treatment. RPE disruption was associated with worse functional outcomes with fewer injections. Intraretinal fluid at presentation may suggest delayed response to treatment. Individualized SD-OCT analysis could lead to individualized approach to wet AMD patients. SD-OCT can offer imaging biomarkers to assess the prognosis of anti-VEGF treatment in AMD patients. PMID:27366051

  20. Treatment of lymphatic malformations of head and neck with OK-432 sclerotherapy induce systemic inflammatory response.

    PubMed

    Närkiö-Mäkelä, Mervi; Mäkelä, Teppo; Saarinen, Pia; Salminen, Päivi; Julkunen, Ilkka; Pitkäranta, Anne

    2011-01-01

    Systemic immune responses after OK-432 (Picibanil) sclerotherapy in patients with head and neck lymphatic malformations (LM) were examined to achieve a better understanding of the mechanism of OK-432 sclerotherapy and to evaluate the long-term treatment outcome. Serum samples from 17 consecutive patients with head and neck LMs were collected during a total of 26 OK-432 treatment episodes. Serum C-reactive protein (CRP), interleukins (IL) 1β, 6, 8, 10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, RANTES, immune protein (IP)-10 and macrophage chemoattractant protein (MCP)-1 as well as blood leukocyte counts were determined. Clinical outcome of the treatment was evaluated at the last visit and from patient files. Elevated serum levels of IP-10 (means at baseline 702 ng/L, after 1 day 1180 ng/L, after 4 weeks 691 ng/L) were seen on day one after OK-432 sclerotherapy (p < 0.05). C-reactive protein and leukocyte counts 1 day after treatment differed statistically significantly (p < 0.05) from the baseline. No significant differences with other cytokines investigated were observed. Patients with macrocystic LM responded better than patients with microcystic LM (p = 0.01). The elevated levels of IP-10, C-reactive protein and leukocyte levels indicate that OK-432 sclerotherapy induces systemic immune responses in patients with LM. The mechanisms of OK-432 sclerotherapy are still not precisely understood, but the IP-10 elevation may reflect local antiangiogenetic properties of immunoactivation induced by OK-432.

  1. Responses of soil buffering capacity to acid treatment in three typical subtropical forests.

    PubMed

    Jiang, Jun; Wang, Ying-Ping; Yu, Mengxiao; Li, Kun; Shao, Yijing; Yan, Junhua

    2016-09-01

    Elevated anthropogenic acid deposition can significantly affect forest ecosystem functioning by changing soil pH, nutrient balance, and chemical leaching and so on. These effects generally differ among different forests, and the dominant mechanisms for those observed responses often vary, depending on climate, soil conditions and vegetation types. Using soil monoliths (0-40cm) from pine forest (pioneer), coniferous and broadleaved mixed forest (transitional) and broadleaved forest (mature) in southern China, we conducted a leaching experiment with acid treatments at different pH levels (control: pH≈4.5; pH=3.5; pH=2.5). We found that pH3.5 treatment significantly reduced dissolved organic carbon (DOC) concentrations in leachate from the pioneer forest soil. pH2.5 treatment significantly increased concentrations of NO3(-), SO4(2-), Ca(2+), Mg(2+), Al(3+), Fe(3+) and DOC in leachate from the pioneer forest soil, and also concentrations of NO3(-), SO4(2-), Mg(2+), Al(3+), Fe(3+) and DOC in leachate from the transitional forest soil. All acid treatments had no significant effects on concentrations of these chemicals in leachate from the mature forest soil. The responses can be explained by the changes in soil pH, acid neutralizing capacity (ANC) and concentrations of Al and Fe. Our results showed that acid buffering capacity of the pioneer or transitional forest soil was lower than that of the mature forest soil. Therefore preserving mature forests in southern China is important for reducing the adverse impacts of high acid deposition on stream water quality at present and into the future. PMID:27185346

  2. 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.

  3. 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.

  4. Response to Fluid Boluses in the Fluid and Catheter Treatment Trial

    PubMed Central

    Aiello, Brianne; Burg, Gregory T.; Rehman, Tayyab; Douglas, Ivor S.; Wheeler, Arthur P.; deBoisblanc, Bennett P.

    2015-01-01

    BACKGROUND: Recent emphasis has been placed on methods to predict fluid responsiveness, but the usefulness of using fluid boluses to increase cardiac index in critically ill patients with ineffective circulation or oliguria remains unclear. METHODS: This retrospective analysis investigated hemodynamic responses of critically ill patients in the ARDS Network Fluid and Catheter Treatment Trial (FACTT) who were given protocol-based fluid boluses. Fluid responsiveness was defined as ≥ 15% increase in cardiac index after a 15 mL/kg fluid bolus. RESULTS: A convenience sample of 127 critically ill patients enrolled in FACTT was analyzed for physiologic responses to 569 protocolized crystalloid or albumin boluses given for shock, low urine output (UOP), or low pulmonary artery occlusion pressure (PAOP). There were significant increases in mean central venous pressure (9.9 ± 4.5 to 11.1 ± 4.8 mm Hg, P < .0001) and mean PAOP (11.6 ± 3.6 to 13.3 ± 4.3 mm Hg, P < .0001) following fluid boluses. However, there were no significant changes in UOP, and there were clinically small changes in heart rate, mean arterial pressure, and cardiac index. Only 23% of fluid boluses led to a ≥ 15% change in cardiac index. There was no significant difference in the frequency of fluid responsiveness between boluses given for shock or oliguria vs boluses given only for low PAOP (24.0% vs 21.8%, P = .59). There were no significant differences in 90-day survival, need for hemodialysis, or return to unassisted breathing between patients defined as fluid responders and fluid nonresponders. CONCLUSIONS: In this cohort of critically ill patients with ARDS who were previously resuscitated, the rate of fluid responsiveness was low, and fluid boluses only led to small hemodynamic changes. PMID:26020673

  5. European Treatment and Outcome Study score does not predict imatinib treatment response and outcome in chronic myeloid leukemia patients

    PubMed Central

    Yamamoto, Eri; Fujisawa, Shin; Hagihara, Maki; Tanaka, Masatsugu; Fujimaki, Katsumichi; Kishimoto, Kumiko; Hashimoto, Chizuko; Itabashi, Megumi; Ishibashi, Daisuke; Nakajima, Yuki; Tachibana, Takayoshi; Kawasaki, Rika; Kuwabara, Hideyuki; Koharazawa, Hideyuki; Yamazaki, Etsuko; Tomita, Naoto; Sakai, Rika; Fujita, Hiroyuki; Kanamori, Heiwa; Ishigatsubo, Yoshiaki

    2014-01-01

    The Sokal and Hasford scores were developed in the chemotherapy and interferon era and are widely used as prognostic indicators in patients with chronic myeloid leukemia (CML). Recently, a new European Treatment and Outcome Study (EUTOS) scoring system was developed. We performed a multicenter retrospective study to validate the effectiveness of each of the three scoring systems. The study cohort included 145 patients diagnosed with CML in chronic phase who were treated with imatinib. In the EUTOS low- and high-risk groups, the cumulative incidence of complete cytogenetic response (CCyR) at 18 months was 86.9% and 87.5% (P = 0.797) and the 5-year overall survival rate was 92.6% and 93.3% (P = 0.871), respectively. The cumulative incidence of CCyR at 12 months, 5-year event-free survival and 5-year progression-free survival were not predicted using the EUTOS scoring system. However, there were significant differences in both the Sokal score and Hasford score risk groups. In our retrospective validation study, the EUTOS score did not predict the prognosis of patients with CML in chronic phase treated with imatinib. PMID:24450386

  6. Predictors of response to treatment in children and adolescents with mood disorders.

    PubMed

    Emslie, Graham J; Mayes, Taryn L; Laptook, Rebecca S; Batt, Melissa

    2003-06-01

    Depression and bipolar disorder are frequently chronic disorders, with onset often beginning in childhood. Mood disorders are becoming more recognized in children and adolescents, and treatment of these disorders has received much attention, particularly in the past 10 years. Recent studies have demonstrated efficacy of antidepressant medications (particularly SSRIs) and specific psychotherapies (primarily CBT). Rates of remission (little or no symptoms) in these studies, however, have remained quite low (35% to 40% in most acute studies). Furthermore, recurrence is common in this population, and affects 40% to 50%. Early onset mood disorders are also associated with increased risk of developing other psychiatric disorders, substance abuse, and suicide, and having poor academic, work, and social functioning. The lifelong implications are serious. Identifying factors that may predict response to treatment, both in general and to specific treatments, may lead to improved outcomes for these patients. Unfortunately, studies have typically been inconsistent. Most studies do not identify demographic variables as predictive of outcome, although older age has been associated with poor prognosis in several studies. Psychosocial factors have yielded some results, particularly with regard to family environments. Generally, intact families with positive interaction styles and less dysfunction have been associated with better outcomes. Psychiatric disorders among parents not only predicts the development of the disorder, but is also associated with poorer prognosis. Finally, several clinical factors have been linked to poorer outcome in children and adolescents with mood disorders. More frequent episodes, increased severity (particularly suicidality and psychosis), and comorbid disorders are likely to lead to fewer recoveries, longer episodes, and increased rate of recurrence. Recent attention has focused on mediators and moderators of outcomes to treatment. In general, the

  7. Differential response profiles in children and adolescents with attention-deficit/hyperactivity disorder: treatment with atomoxetine.

    PubMed

    Wietecha, Linda A; Wang, Shufang; Saylor, Keith E; Day, Kathleen A; Wu, Sheng Hu; Kelsey, Doug

    2015-02-01

    Atomoxetine has been shown to be safe and effective in the treatment of attention-deficit/hyperactivity disorder (ADHD). The purpose of this post hoc analysis was to examine response trajectories of pediatric patients treated with atomoxetine. Data were pooled from 7 atomoxetine double-blind, placebo-controlled clinical trials conducted in pediatric patients between November 1998 and June 2004. Growth mixture modeling was applied to the investigator-rated ADHD rating scale (ADHDRS-Inv) and Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) scores in the randomized acute phase (6-9 weeks) to explore whether there were groups of patients who differed in their response to atomoxetine. Classification and regression tree analyses were performed to identify predictors that can help categorize subjects to different response profiles. Patients (N = 925) were mostly male (73%) and of the combined subtype (74%). Most patients had a response pattern characterized by gradual, modest improvement, while a smaller group experienced early, robust improvement. PMID:25371450

  8. Glutathione S-transferase polymorphisms influence chemotherapy response and treatment outcome in breast cancer.

    PubMed

    Wang, J; Wang, T; Yin, G-Y; Yang, L; Wang, Z-G; Bu, X-B

    2015-01-01

    The aim of this study was to evaluate the role of GSTM1 null/present, GSTT1 null/present, and GSTP1 IIe105Val polymorphisms in the clinical response to chemotherapy and treatment outcome of patients with breast cancer. A total of 262 subjects were randomly selected from among patients with a histologically confirmed breast cancer. The genotypes of GSTM1, GSTT1, and GSTP1 IIe105Val polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Our study found that the null genotype of GSTM1 was associated with a better response to chemo-therapy, and the odds ratio [95% confidence interval (CI)] was 1.78 (1.03-3.08). In the Cox proportional hazard model, the hazard ratio (95%CI) for overall survival (OS) in patients carrying the null genotype of GSTM1 was 0.57 (0.32-0.98) using the non-null genotype as the reference variable. However, we observed no significant association between the GSTT1 and GSTP1 polymorphisms and response to chemotherapy and OS in patients with breast cancer. In conclusion, our study found that the GSTM1 polymorphism plays an important role in influencing the chemotherapy response and OS in patients with breast cancer. PMID:26400343

  9. Impairment of innate immune responses in cirrhotic patients and treatment by branched-chain amino acids.

    PubMed

    Nakamura, Ikuo

    2014-06-21

    It has been reported that host defense responses, such as phagocytic function of neutrophils and natural killer (NK) cell activity of lymphocytes, are impaired in cirrhotic patients. This review will concentrate on the impairment of innate immune responses in decompensated cirrhotic patients and the effect of the treatment by branched-chain amino acids (BCAA) on innate immune responses. We already reported that phagocytic function of neutrophils was significantly improved by 3-mo BCAA supplementation. In addition, the changes of NK activity were also significant at 3 mo of supplementation compared with before supplementation. Also, Fisher's ratios were reported to be significantly increased at 3 mo of BCAA supplementation compared with those before oral supplementation. Therefore, administration of BCAA could reduce the risk of bacterial and viral infection in patients with decompensated cirrhosis by restoring impaired innate immune responses of the host. In addition, it was also revealed that BCAA oral supplementation could reduce the risk of development of hepatocellular carcinoma in cirrhotic patients. The mechanisms of the effects will also be discussed in this review article.

  10. Dual-responsive polymer coated superparamagnetic nanoparticle for targeted drug delivery and hyperthermia treatment.

    PubMed

    Patra, Santanu; Roy, Ekta; Karfa, Paramita; Kumar, Sunil; Madhuri, Rashmi; Sharma, Prashant K

    2015-05-01

    In this work, we have prepared water-soluble superparamgnetic iron oxide nanoparticles (SPIONs) coated with a dual responsive polymer for targeted delivery of anticancer hydrophobic drug (curcumin) and hyperthermia treatment. Herein, superparamagnetic mixed spinel (MnFe2O4) was used as a core material (15-20 nm) and modified with carboxymethyl cellulose (water-soluble component), folic acid (tagging agent), and dual responsive polymer (poly-N isopropylacrylamide-co-poly glutamic acid) by microwave radiation. Lower critical solution temperature (LCST) of the thermoresponsive copolymer was observed to be around 40 °C, which is appropriate for drug delivery. The polymer-SPIONs show high drug loading capacity (89%) with efficient and fast drug release at the desired pH (5.5) and temperature (40 °C) conditions. Along with this, the SPIONs show a very fast increase in temperature (45 °C in 2 min) when interacting with an external magnetic field, which is an effective and appropriate temperature for the localized hyperthermia treatment of cancer cells. The cytocompatibility of the curcumin loaded SPIONs was studied by the methyl thiazol tetrazolium bromide (MTT) assay, and cells were imaged by fluorescence microscopy. To explore the targeting behavior of curcumin loaded SPIONs, a simple magnetic capturing system (simulating a blood vessel) was constructed and it was found that ∼99% of the nanoparticle accumulated around the magnet in 2 min by traveling a distance of 30 cm. Along with this, to explore an entirely different aspect of the responsive polymer, its antibacterial activity toward an E. coli strain was also studied. It was found that responsive polymer is not harmful for normal or cancer cells but shows a good antibacterial property. PMID:25893447

  11. Interreader and Inter-test Agreement in Assessing Treatment Response Following Transarterial Embolization for Hepatocellular Carcinoma

    PubMed Central

    Donati, Olivio F.; Do, Richard Kinh Gian; Hötker, Andreas M.; Katz, Seth S.; Zheng, Junting; Moskowitz, Chaya S.; Beattie, Christopher; Brown, Karen T.

    2016-01-01

    Purpose To evaluate interreader and inter-test agreement in applying size- and necrosis-based response assessment criteria after transarterial embolization (TAE) for hepatocellular carcinoma (HCC), applying two different methods of European Association for the Study of the Liver (EASL) criteria. Methods and Materials Seventy-four patients (median age, 67 years) from a prospectively accrued study population were included in this retrospective study. Four radiologists independently evaluated CT data at 2–3 (1st FU) and 10–12 (2nd FU) weeks after TAE and assessed treatment response using size-based (WHO, RECIST) and necrosis-based criteria (mRECIST, EASL) criteria. Enhancing tissue was bidimensionally measured (EASLmeas) and also visually estimated (EASLest). Interreader and inter-test agreement were assessed using intraclass correlation coefficient (ICC) and κ statistics. Results Interreader agreement for all response assessment methods ranged from moderate to substantial (κ=0.578–0.700) at 1st follow-up and was substantial (κ=0.716–0.780) at 2nd follow-up. Inter-test agreement was substantial between WHO and RECIST (κ=0.610–0.799, 1st FU; κ=0.655–0.782, 2nd FU) and excellent between EASLmeas and EASLest (κ=0.899–0.918, 1st FU; κ=0.843–0.877, 2nd FU). Conclusion Size- and necrosis-based criteria both show moderate to excellent interreader agreement in evaluating treatment response after TAE for HCC. Inter-test agreement regarding EASLmeas and EASLest was excellent, suggesting that either may be used. PMID:25850892

  12. Liver Stiffness Decreases Rapidly in Response to Successful Hepatitis C Treatment and Then Plateaus

    PubMed Central

    Bichoupan, Kian; Sefcik, Roberta; Doobay, Kamini; Chang, Sanders; DelBello, David; Harty, Alyson; Dieterich, Douglas T.; Perumalswami, Ponni V.; Branch, Andrea D.

    2016-01-01

    Background and Aim To investigate the impact of a sustained virological response (SVR) to hepatitis C virus (HCV) treatment on liver stiffness (LS). Methods LS, measured by transient elastography (FibroScan), demographic and laboratory data of patients treated with interferon (IFN)-containing or IFN-free regimens who had an SVR24 (undetectable HCV viral load 24 weeks after the end of treatment) were analyzed using two-tailed paired t-tests, Mann-Whitney Wilcoxon Signed-rank tests and linear regression. Two time intervals were investigated: pre-treatment to SVR24 and SVR24 to the end of follow-up. LS scores ≥ 12.5 kPa indicated LS-defined cirrhosis. A p-value below 0.05 was considered statistically significant. Results The median age of the patients (n = 100) was 60 years [IQR (interquartile range) 54–64); 72% were male; 60% were Caucasian; and 42% had cirrhosis pre-treatment according to the FibroScan measurement. The median LS score dropped from 10.40 kPa (IQR: 7.25–18.60) pre-treatment to 7.60 kPa (IQR: 5.60–12.38) at SVR24, p <0.01. Among the 42 patients with LS-defined cirrhosis pre-treatment, 25 (60%) of patients still had LS scores ≥ 12.5 kPa at SVR24, indicating the persistence of cirrhosis. The median change in LS was similar in patients receiving IFN-containing and IFN-free regimens: -1.95 kPa (IQR: -5.75 –-0.38) versus -2.40 kPa (IQR: -7.70 –-0.23), p = 0.74. Among 56 patients with a post-SVR24 LS measurement, the LS score changed by an additional -0.90 kPa (IQR: -2.98–0.5) during a median follow-up time of 1.17 (IQR: 0.88–1.63) years, which was not a statistically significant decrease (p = 0.99). Conclusions LS decreased from pre-treatment to SVR24, but did not decrease significantly during additional follow-up. Earlier treatment may be needed to reduce the burden of liver disease. PMID:27442255

  13. Non-responsiveness to intravitreal aflibercept treatment in neovascular age-related macular degeneration: implications of serous pigment epithelial detachment

    PubMed Central

    Nagai, Norihiro; Suzuki, Misa; Uchida, Atsuro; Kurihara, Toshihide; Kamoshita, Mamoru; Minami, Sakiko; Shinoda, Hajime; Tsubota, Kazuo; Ozawa, Yoko

    2016-01-01

    The prognosis of neovascular age-related macular degeneration (AMD) has been improved by anti-vascular endothelial growth factor treatments, including intravitreal aflibercept (IVA) treatment. However, many patients remain incurable. In this study, we retrospectively evaluated non-responsiveness to IVA monotherapy at 12 months in 133 eyes of 133 AMD patients. Sixty-two patients were initially treatment-naive, and 71 had received other treatments before IVA (the treatment-switched group). Mean best-corrected visual acuity (BCVA) was improved in the treatment-naive group but not in the treatment-switched group, although mean central retinal thickness (CRT) decreased in both groups. The respective percentages of non-responders as determined by worsened BCVA in the treatment-naive and treatment-switched groups were 8.1% and 15.5%, and via fundus findings, they were 12.9% and 8.5%. Multivariate analyses adjusted for age, gender, CRT, and greatest linear dimension showed that serous pigment epithelial detachment (PED) at baseline was associated with non-responsiveness in both groups as determined by BCVA and by fundus findings, and fibrovascular PED measurements indicated no response as determined by fundus findings in the treatment-switched group. The results reported herein may assist the formulation of appropriate treatment protocols for AMD patients. PMID:27403807

  14. A systematic review and evaluation of response redirection as a treatment for challenging behavior in individuals with developmental disabilities.

    PubMed

    Lydon, Sinéad; Healy, Olive; O'Reilly, Mark; McCoy, Anna

    2013-10-01

    Response redirection is widely used in clinical practice as a treatment for repetitive behavior or stereotypy in persons with developmental disabilities. However, to date the procedure has received comparatively little empirical evaluation. The current review sought to examine the literature describing the efficacy of response redirection alone, response interruption and redirection (RIRD), and multi-element treatment packages incorporating response redirection, as interventions for challenging behavior in individuals with developmental disabilities. Additionally, the status of response redirection, and RIRD, as evidence-based practice was evaluated in accordance with Reichow's (2011) recently developed criteria. Results indicated that interventions involving response redirection or RIRD typically led to large decreases in challenging behavior but did not result in behavioral suppression. On the basis of the current literature and in accordance with Reichow's criteria, interventions incorporating response redirection do not yet constitute evidence-based practice. The implications of these findings, for both research and practice, are discussed.

  15. 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.

  16. 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. PMID:26455262

  17. Rapid-response process reduces mortality, facilitates speedy treatment for patients with sepsis.

    PubMed

    2013-08-01

    To reduce mortality and improve the care of patients with sepsis, Wake Forest Baptist Medical Center in Winston-Salem, NC, created a new rapid-response protocol aimed at facilitating earlier diagnosis and treatment. In this approach, clinicians who suspect a patient may have sepsis can call a Code Sepsis, which will fast-track the series of tests and evaluations that are needed to confirm the diagnosis and get appropriate patients on IV antibiotics quickly. Administrators say the approach fits in with the culture of the ED, and it has quickly slashed time-to-treatment in this environment. In just one year, the hospital has been able to reduce its risk-adjusted mortality index from 1.8 to less than 1.25. In the ED, where a modified version of the approach has been in place since April 1 of this year, the percentage of patients with sepsis receiving antibiotics within one hour of diagnosis has increased from 25% to 85%. Key to the success of the approach are specially trained rapid-response nurses who are called in on a case whenever a diagnosis of sepsis is suspected and a series of policy changes designed to facilitate needed diagnostic tests to confirm a diagnosis. A mandated online education module helped to bring all clinicians and staff up to speed on the new process quickly. PMID:23923521

  18. Microbial response to single-cell protein production and brewery wastewater treatment.

    PubMed

    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

  19. 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.

  20. Elevated Vibration Perception Thresholds in CIDP Patients Indicate More Severe Neuropathy and Lower Treatment Response Rates

    PubMed Central

    Abraham, Alon; Albulaihe, Hana; Alabdali, Majed; Qrimli, Mohammad; Breiner, Ari; Barnett, Carolina; Katzberg, Hans D.; Lovblom, Leif E.; Perkins, Bruce A.; Bril, Vera

    2015-01-01

    Introduction Vibration perception threshold (VPT) examination using a neurothesiometer provides objective, sensitive and specific information, and has been utilized mainly in patients with diabetic polyneropathy. Objectives Explore the utility of VPT examination in CIDP patients. Methods CIDP subjects attending the Neuromuscular clinic between 01/2013 and 12/2014 were evaluated. Demographic data, clinical history, physical examination, VPT values, and electrophysiologic data from their charts were extracted. Results 70 charts were reviewed. 55 CIDP patients had elevated VPT, associated with higher frequency of abnormal sensory testing for various modalities (92.7% vs. 46.7%, p<0.0001), lower sensory and motor amplitudes and reduced conduction velocities on nerve conduction studies, and lower treatment response rates (54% vs. 93%, p = 0.01). Conclusion VPT examination is a simple tool, which is a reliable and sensitive measure not only for diabetic neuropathy, but also for CIDP. Moreover, in CIDP, elevated VPT values are also associated with lower treatment response rates. PMID:26545096

  1. Hepatocellular Carcinoma and Diffusion-Weighted MRI: Detection and Evaluation of Treatment Response

    PubMed Central

    Gluskin, Jill S; Chegai, Fabrizio; Monti, Serena; Squillaci, Ettore; Mannelli, Lorenzo

    2016-01-01

    Differentiating between cancerous tissue and healthy liver parenchyma could represent a challenge with the only conventional Magnetic Resonance (MR) imaging. Diffusion weighted imaging (DWI) exploits different tissue characteristics to conventional Magnetic Resonance Imaging (MRI) sequences that enhance hepatocellular carcinoma (HCC) detection, characterization, and post-treatment evaluation. Detection of HCC is improved by DWI, infact this technology increases conspicuity of lesions that might otherwise not be identified due to obscuration by adjacent vessels or due to low contrast between the lesion and background liver. It is important to remember that DWI combined with contrast-enhanced MRI has higher sensitivity than DWI alone, and that some patients are not eligible for use of contrast on CT and MRI; in these patients DWI has a prominent role. MRI has advanced beyond structural anatomic imaging to now showing pathophysiologic processes. DWI is a promising way to characterize lesions utilizing the inherent contrast within the liver and has the benefit of not requiring contrast injection. DWI improves detection and characterization of HCC. Proposed clinical uses for DWI include: assessing prognosis, predicting response, monitoring response to therapy, and distinguishing tumor recurrence from treatment effect. Ideally, DWI will help risk stratify patients and will participate in prognostic modeling. PMID:27471573

  2. 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

  3. 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

  4. Low-resolution electromagnetic tomography and treatment response in obsessive-compulsive disorder.

    PubMed

    Fontenelle, Leonardo F; Mendlowicz, Mauro V; Ribeiro, Pedro; Piedade, Roberto A; Versiani, Marcio

    2006-02-01

    We investigated whether findings from pretreatment low-resolution electromagnetic tomography (LORETA) predicted response to drug treatment in patients with obsessive-compulsive disorder (OCD). The 3D intra-cerebral distribution of neuronal electrical activity from the scalp-recorded potential distribution of 17 drug-free patients with OCD was assessed with LORETA. They were treated with antidepressants in the maximum tolerated doses for at least 12 wk. Individuals were considered to be treatment responders if they displayed a reduction of at least 35% on the initial YBOCS scores and had a final CGI score of 1 or 2. The SPM-99 t test for independent samples was employed to compare, voxel-by-voxel, the brain electrical activities of responders (n = 10) and non-responders (n = 7). Responders exhibited significantly lower activities in beta band in the rostral anterior cingulate [Brodmann's area (BA) 24 and 32] (p = 0.002) and the medial frontal gyrus (BA 10) (p = 0.002), suggesting that a distinctive pattern of activity within the medial surface of the frontal lobe predicts therapeutic response in OCD.

  5. 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.

  6. 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

  7. Biosorption and biodegradation of pyrene by Brevibacillus brevis and cellular responses to pyrene treatment.

    PubMed

    Liao, Liping; Chen, Shuona; Peng, Hui; Yin, Hua; Ye, Jinshao; Liu, Zehua; Dang, Zhi; Liu, Zhichen

    2015-05-01

    Biodegradation has been proposed as an effective approach to remove pyrene, however, the information regarding cellular responses to pyrene treatment is limited thus far. In this study, the biodegradation and biosorption of pyrene by Brevibacillus brevis, along with cellular responses caused by pollutant were investigated by means of flow cytometry assay and scanning electron microscopy. The experimental results showed that pyrene was initially adsorbed by B. brevis and subsequently transported and intracellularly degraded. During this process, pyrene removal was primarily dependent on biodegradation. Cell invagination and cell surface corrugation occurred due to pyrene exposure. Nevertheless, cell regrowth after 96h treatment was observed, and the proportion of necrotic cell was only 2.8% after pyrene exposure for 120h, confirming that B. brevis could utilize pyrene as a sole carbon source for growth. The removal and biodegradation amount of pyrene (1mg/L) at 168h were 0.75 and 0.69mg/L, respectively, and the biosorption amount by inactivated cells was 0.41mg/L at this time.

  8. Antibody response in children infected with Giardia intestinalis before and after treatment with Secnidazole.

    PubMed

    Jiménez, Juan C; Pinon, Anthony; Dive, Daniel; Capron, Monique; Dei-Cas, Eduardo; Convit, Jacinto

    2009-01-01

    We examined 364 school children for intestinal parasites in a sub-urban zone of Caracas, Venezuela. Giardia intestinalis was the most prevalent parasite in stool samples from 34 children. Levels of IgA and IgG antibodies to G. intestinalis were assessed by enzyme-linked immunosorbent assay and Western blot before and after treatment with secnidazole. All patients were cured with a reduction of IgA antibody levels in 26 of 34 children and a reduction in IgG-specific antibody levels in 18 of 34 children. Serum of infected patients reacted with proteins of 14 kD to 137 kD. Some patients did not show a change in IgA serum reactivity for parasite proteins by Western blot after treatment. Seventeen children showed reduction of the reactivity or disappearance of protein reactivity (mainly the 14-kD, 122-kD, and 137-kD proteins). Antibody response was not related to clinical status, but quantitative and qualitative serum antibody response against G. intestinalis infection could be used to assess levels of new protein markers that decrease or disappear with successful chemotherapy. PMID:19141831

  9. 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

  10. Hepatocellular Carcinoma and Diffusion-Weighted MRI: Detection and Evaluation of Treatment Response.

    PubMed

    Gluskin, Jill S; Chegai, Fabrizio; Monti, Serena; Squillaci, Ettore; Mannelli, Lorenzo

    2016-01-01

    Differentiating between cancerous tissue and healthy liver parenchyma could represent a challenge with the only conventional Magnetic Resonance (MR) imaging. Diffusion weighted imaging (DWI) exploits different tissue characteristics to conventional Magnetic Resonance Imaging (MRI) sequences that enhance hepatocellular carcinoma (HCC) detection, characterization, and post-treatment evaluation. Detection of HCC is improved by DWI, infact this technology increases conspicuity of lesions that might otherwise not be identified due to obscuration by adjacent vessels or due to low contrast between the lesion and background liver. It is important to remember that DWI combined with contrast-enhanced MRI has higher sensitivity than DWI alone, and that some patients are not eligible for use of contrast on CT and MRI; in these patients DWI has a prominent role. MRI has advanced beyond structural anatomic imaging to now showing pathophysiologic processes. DWI is a promising way to characterize lesions utilizing the inherent contrast within the liver and has the benefit of not requiring contrast injection. DWI improves detection and characterization of HCC. Proposed clinical uses for DWI include: assessing prognosis, predicting response, monitoring response to therapy, and distinguishing tumor recurrence from treatment effect. Ideally, DWI will help risk stratify patients and will participate in prognostic modeling. PMID:27471573

  11. Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer

    PubMed Central

    Du, Meijun; Dittmar, Rachel L.; Lee, Adam; Nandy, Debashis; Yuan, Tiezheng; Guo, Yongchen; Wang, Yuan; Tschannen, Michael R.; Worthey, Elizabeth; Jacob, Howard; See, William; Kilari, Deepak; Wang, Xuexia; Hovey, Raymond L.; Huang, Chiang-Ching; Wang, Liang

    2015-01-01

    Liquid biopsies, examinations of tumor components in body fluids, have shown promise for predicting clinical outcomes. To evaluate tumor-associated genomic and genetic variations in plasma cell-free DNA (cfDNA) and their associations with treatment response and overall survival, we applied whole genome and targeted sequencing to examine the plasma cfDNAs derived from 20 patients with advanced prostate cancer. Sequencing-based genomic abnormality analysis revealed locus-specific gains or losses that were common in prostate cancer, such as 8q gains, AR amplifications, PTEN losses and TMPRSS2-ERG fusions. To estimate tumor burden in cfDNA, we developed a Plasma Genomic Abnormality (PGA) score by summing the most significant copy number variations. Cox regression analysis showed that PGA scores were significantly associated with overall survival (p < 0.04). After androgen deprivation therapy or chemotherapy, targeted sequencing showed significant mutational profile changes in genes involved in androgen biosynthesis, AR activation, DNA repair, and chemotherapy resistance. These changes may reflect the dynamic evolution of heterozygous tumor populations in response to these treatments. These results strongly support the feasibility of using non-invasive liquid biopsies as potential tools to study biological mechanisms underlying therapy-specific resistance and to predict disease progression in advanced prostate cancer. PMID:25915538

  12. 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. PMID:27611315

  13. Survey and online discussion groups to develop a patient-rated outcome measure on acceptability of treatment response in vitiligo

    PubMed Central

    2014-01-01

    Background Vitiligo is a chronic depigmenting skin disorder which affects around 0.5-1% of the world’s population. The outcome measures used most commonly in trials to judge treatment success focus on repigmentation. Patient-reported outcome measures of treatment success are rarely used, although recommendations have been made for their inclusion in vitiligo trials. This study aimed to evaluate the face validity of a new patient-reported outcome measure of treatment response, for use in future trials and clinical practice. Method An online survey to gather initial views on what constitutes treatment success for people with vitiligo or their parents/carers, followed by online discussion groups with patients to reach consensus on what constitutes treatment success for individuals with vitiligo, and how this can be assessed in the context of trials. Participants were recruited from an existing database of vitiligo patients and through posts on the social network sites Facebook and Twitter. Results A total of 202 survey responses were received, of which 37 were excluded and 165 analysed. Three main themes emerged as important in assessing treatment response: a) the match between vitiligo and normal skin (how well it blends in); b) how noticeable the vitiligo is and c) a reduction in the size of the white patches. The majority of respondents said they would consider 80% or more repigmentation to be a worthwhile treatment response after 9 months of treatment. Three online discussion groups involving 12 participants led to consensus that treatment success is best measured by asking patients how noticeable their vitiligo is after treatment. This was judged to be best answered using a 5-point Likert scale, on which a score of 4 or 5 represents treatment success. Conclusions This study represents the first step in developing a patient reported measure of treatment success in vitiligo trials. Further work is now needed to assess its construct validity and responsiveness to

  14. Integrative Analysis of Response to Tamoxifen Treatment in ER-Positive Breast Cancer Using GWAS Information and Transcription Profiling

    PubMed Central

    Hicks, Chindo; Kumar, Ranjit; Pannuti, Antonio; Miele, Lucio

    2012-01-01

    Variable response and resistance to tamoxifen treatment in breast cancer patients remains a major clinical problem. To determine whether genes and biological pathways containing SNPs associated with risk for breast cancer are dysregulated in response to tamoxifen treatment, we performed analysis combining information from 43 genome-wide association studies with gene expression data from 298 ER+ breast cancer patients treated with tamoxifen and 125 ER+ controls. We identified 95 genes which distinguished tamoxifen treated patients from controls. Additionally, we identified 54 genes which stratified tamoxifen treated patients into two distinct groups. We identified biological pathways containing SNPs associated with risk for breast cancer, which were dysregulated in response to tamoxifen treatment. Key pathways identified included the apoptosis, P53, NFkB, DNA repair and cell cycle pathways. Combining GWAS with transcription profiling provides a unified approach for associating GWAS findings with response to drug treatment and identification of potential drug targets. PMID:22399860

  15. 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.

  16. Treatment Response Assessment of Head and Neck Cancers on CT Using Computerized Volume Analysis

    PubMed Central

    Hadjiiski, L.; Mukherji, S.K.; Gujar, S.K.; Sahiner, B.; Ibrahim, M.; Street, E.; Moyer, J.; Worden, F.P.; Chan, H.-P.

    2013-01-01

    Background and Purpose Head and neck cancer can cause substantial morbidity and mortality Our aim was to evaluate the potential usefulness of a computerized system for segmenting lesions in head and neck CT scans and for estimation of volume change of head and neck malignant tumors in response to treatment. Materials and Methods CT scans from a pretreatment examination and a post 1-cycle chemotherapy examination of 34 patients with 34 head and neck primary-site cancers were collected. The computerized system was developed in our laboratory. It performs 3D segmentation on the basis of a level-set model and uses as input an approximate bounding box for the lesion of interest. The 34 tumors included tongue, tonsil, vallecula, supraglottic, epiglottic, and hard palate carcinomas. As a reference standard, 1 radiologist outlined full 3D contours for each of the 34 primary tumors for both the pre- and posttreatment scans and a second radiologist verified the contours. Results The correlation between the automatic and manual estimates for both the pre- to post-treatment volume change and the percentage volume change for the 34 primary-site tumors was 0.95, with an average error of −2.4 ± 8.5% by automatic segmentation. There was no substantial difference and specific trend in the automatic segmentation accuracy for the different types of primary head and neck tumors, indicating that the computerized segmentation performs relatively robustly for this application. Conclusions The tumor size change in response to treatment can be accurately estimated by the computerized segmentation system relative to radiologists' manual estimations for different types of head and neck tumors. PMID:20595363

  17. 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.

  18. Cortical and subcortical responses to high and low effective placebo treatments.

    PubMed

    Geuter, Stephan; Eippert, Falk; Hindi Attar, Catherine; Büchel, Christian

    2013-02-15

    The effectiveness of placebo treatments depends on the recipient's expectations, which are at least in part shaped by previous experiences. Thus, positive past experience together with an accordant verbal instruction should enhance outcome expectations and subsequently lead to higher placebo efficacy. This should be reflected in subjective valuation reports and in activation of placebo-related brain structures. We tested this hypothesis in a functional magnetic resonance imaging study, where subjects experienced different levels of pain relief and conforming information about price levels for two placebo treatments during a manipulation phase, thereby establishing a weak and a strong placebo. As expected, both placebos led to a significant pain relief and the strong placebo induced better analgesic efficacy. Individual placebo value estimates reflected treatment efficacy, i.e. subjects were willing to pay more money for the strong placebo even though pain stimulation was completed at this time. On the neural level, placebo effects were associated with activation of the rostral anterior cingulate cortex, the anterior insula, and the ventral striatum and deactivations in the thalamus and secondary somatosensory cortex. However, only placebo-related responses in rostral anterior cingulate cortex were consistent across both the anticipation of painful stimuli and their actual administration. Most importantly, rostral anterior cingulate cortex responses were higher for the strong placebo, thus mirroring the behavioral effects. These results directly link placebo analgesia to anticipatory activity in the ventral striatum, a region involved in reward processing, and highlight the role of the rostral anterior cingulate cortex, as its activity consistently scaled with increasing analgesic efficacy.

  19. Cortical and subcortical responses to high and low effective placebo treatments

    PubMed Central

    Geuter, Stephan; Eippert, Falk; Attar, Catherine Hindi; Büchel, Christian

    2013-01-01

    The effectiveness of placebo treatments depends on the recipient’s expectations, which are at least in part shaped by previous experiences. Thus, positive past experience together with an accordant verbal instruction should enhance outcome expectations and subsequently lead to higher placebo efficacy. This should be reflected in subjective valuation reports and in activation of placebo-related brain structures. We tested this hypothesis in a functional magnetic resonance imaging study, where subjects experienced different levels of pain relief and conforming information about price levels for two placebo treatments during a manipulation phase, thereby establishing a weak and a strong placebo. As expected, both placebos led to a significant pain relief and the strong placebo induced better analgesic efficacy. Individual placebo value estimates reflected treatment efficacy, i.e. subjects were willing to pay more money for the strong placebo even though pain stimulation was completed at this time. On the neural level, placebo effects were associated with activation of the rostral anterior cingulate cortex, the anterior insula, and the ventral striatum and deactivations in the thalamus and secondary somatosensory cortex. However, only placebo-related responses in rostral anterior cingulate cortex were consistent across both the anticipation of painful stimuli and their actual administration. Most importantly, rostral anterior cingulate cortex responses were higher for the strong placebo, thus mirroring the behavioral effects. These results directly link placebo analgesia to anticipatory activity in the ventral striatum, a region involved in reward processing, and highlight the role of the rostral anterior cingulate cortex, as its activity consistently scaled with increasing analgesic efficacy. PMID:23201367

  20. 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.

  1. Growth response to antiretroviral treatment in HIV-infected children: A cohort study from Lilongwe, Malawi

    PubMed Central

    Weigel, Ralf; Phiri, Sam; Chiputula, Fred; Gumulira, Joe; Brinkhof, Martin; Gsponer, Thomas; Tweya, Hannock; Egger, Matthias; Keiser, Olivia

    2013-01-01

    Summary Objective Malnutrition is common in HIV-infected children in Africa and an indication for antiretroviral treatment (ART). We examined anthropometric status and response to ART in children treated at a large public-sector clinic in Malawi. Methods All children aged <15 years who started ART between January 2001 and December 2006 were included and followed until March 2008. Weight and height were measured at regular intervals from 1 year before to 2 years after the start of ART. Sex- and age-standardized z-scores were calculated for weight-for-age (WAZ) and height-for-age (HAZ). Predictors of growth were identified in multivariable mixed-effect models. Results A total of 497 children started ART and were followed for 972 person-years. Median age (inter-quartile range; IQR) was 8 years (4 to 11 years). Most children were underweight (52% of children), stunted (69%), in advanced clinical stages (94% in WHO stages 3 or 4) and had severe immunodeficiency (77%). After starting ART median (IQR) WAZ and HAZ increased from −2.1 (−2.7 to −1.3) and −2.6 (−3.6 to −1.8) to −1.4 (−2.1 to −0.8) and −1.8 (−2.4 to −1.1) at 24 months, respectively (p<0.001). In multivariable models, baseline WAZ and HAZ scores were the most important determinants of growth trajectories on ART. Conclusions Despite a sustained growth response to ART among children remaining on therapy, normal values were not reached. Interventions leading to earlier HIV diagnosis and initiation of treatment could improve growth response. PMID:20561308

  2. [Responsible gambling: is it an alternative for prevention and treatment of pathological gambling?].

    PubMed

    Echeburua, Enrique; de Corral, Paz

    2008-01-01

    This paper deals with the new development of controlled gambling embedded in a harm-reduction context as a viable solution both for primary prevention at school and for treatment of some kinds of problematic gamblers. Pathological gambling significantly improves with psychological therapies, such as stimulus control and in vivo exposure with response prevention or cognitive interventions. In some cases psychopharmacological therapy may complement the benefits of treatment for pathological gambling when patients have comorbid depression or high impulsivity. However, in this mental disorder the goal of treatment (total abstinence or controlled gambling) is currently a controversial issue. Controlled gambling may be a therapeutic option for young gamblers or patients without severe dependence. Furthermore, controlled gambling may be a relevant issue for health education in schools, with a view to teaching teenagers how to cope with actual and virtual exposure to gambling. Likewise, the gambling industry and governments are involved in harm minimization initiatives. Thus, it is necessary to coordinate a program of research that includes the industry, science, and public representatives, based on cooperative research that will permit the introduction of controlled gambling within a global strategic framework. We discuss the relevance of this review for clinical practice and for future research, as well as the unsolved problems in this field.

  3. 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.

  4. Amino Acid PET - An Imaging Option to Identify Treatment Response, Posttherapeutic Effects, and Tumor Recurrence?

    PubMed

    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

  5. 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

  6. Patient Violence Towards Counselors in Substance Use Disorder Treatment Programs: Prevalence, Predictors, and Responses.

    PubMed

    Bride, Brian E; Choi, Y Joon; Olin, Ilana W; Roman, Paul M

    2015-10-01

    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

  7. Substance use and response to psychiatric treatment in methadone-treated outpatients with comorbid psychiatric disorder.

    PubMed

    Kidorf, Michael; King, Van L; Peirce, Jessica; Gandotra, Neeraj; Ghazarian, Sharon; Brooner, Robert K

    2015-04-01

    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.

  8. [Neurolymphomatosis: diagnosis of extension and assessment of response to treatment with PET-CT].

    PubMed

    Durán, C; Infante, J R; Serrano, J; Rayo, J I; García, L; Domínguez, M L; Sánchez, R

    2009-01-01

    Neurolymphomatosis is a rare neurological manifestation of non-Hodgkin's lymphoma (NHL) and it may be its first and sole manifestation. Diagnosis is often difficult and nerve biopsy is generally required. However, this it is not always possible to perform or is not conclusive. We present the case of a 66-year-old woman diagnosed with giant B-cell NHL. After 6 cycles of chemotherapy, imaging and molecular biology techniques showed complete remission. At four months after treatment, the patient complained of low back pain of radicular distribution. CT and MRI imaging showed signs of lymphoproliferative activity of L5 and also lesions to thoracic nerve roots. A PET-CT was requested in order to complete the diagnosis and plan the treatment. Imaging confirmed the presence of tumor recurrence with neurolymphomatosis and also indicated lesions on the chest and abdominal level. Thus, it was decided to start a new line of chemotherapy, without performing the histological study through biopsy. This case illustrates the important role played by PET-CT imaging in neurolymphomatosis diagnosis. This technique can help the patient avoid more aggressive procedures, such as a biopsy, and can also be useful in the follow-up and assessment of the treatment response to NHL-diagnosed patients.

  9. 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.

  10. 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

  11. Genetics as a molecular window into recovery, its treatment, and stress responses after stroke.

    PubMed

    Juth, Vanessa; Holman, E Alison; Chan, Michelle K; Cramer, Steven C

    2016-06-01

    Stroke remains a major source of adult disability in the USA and worldwide. Most patients show some recovery during the weeks to months following a stroke, but this is generally incomplete. An emerging branch of therapeutics targets the processes underlying this behavioral recovery from stroke toward 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. Pharmacogenomic factors might also provide insights into inter-subject differences in treatment side effects for pharmacological prescriptions, and behavioral interventions, and others. These efforts must be conducted with the strictest ethical standards given the highly sensitive nature of genetic 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.

  12. Sensory Over-Responsivity in a Sample of Children Seeking Treatment for Anxiety

    PubMed Central

    Conelea, Christine A.; Carter, Alice C.; Freeman, Jennifer B.

    2014-01-01

    Objective Sensory over-responsivity (SOR) refers to an exaggerated, intense, or prolonged behavioral response to ordinary sensory stimuli. The relationship of SOR to psychiatric disorders remains poorly understood. The current study examined the SOR construct within typically developing children with clinically significant anxiety, including the prevalence and course of SOR symptoms and relationship between SOR symptoms, demographic factors, and psychopathology. Method Children presenting at an anxiety specialty clinic (n = 88) completed a psychiatric diagnostic assessment, which included parent-report measures of SOR, anxiety, obsessive-compulsive disorder (OCD), and global behavior and child-report measures of anxiety, depression, and OCD. Results SOR symptoms were very common: 93.2% were bothered by at least one tactile or auditory sensation, and the mean number of bothersome sensations was 9.2 (SD = 7.4). SOR symptoms were reported to be “moderately bothersome” on average and to onset at an early age. Sensory Over-Responsivity Inventory (SensOR) scores did not differ by psychiatric disorder diagnosis, but SensOR scores significantly correlated with measures of obsessive compulsive disorder (OCD) and depression. Higher SensOR scores were associated with greater global impairment. Conclusion A high rate of SOR symptom occurrence was observed in this sample of children seeking anxiety treatment, suggesting that SOR may not be entirely independent of anxiety and may be closely associated with OCD. Future research on the validity and nosology of SOR using psychiatric samples is warranted. PMID:25186122

  13. 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.

  14. 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

  15. Effects of corticosterone treatment on responses to fasting in Japanese quail.

    PubMed

    Wall, Julian P; Cockrem, John F

    2009-10-01

    Plasma concentrations of corticosterone, a glucocorticoid hormone, have been reported to increase during fasting in some species of birds. Although Japanese quail are widely used in laboratory studies, corticosterone responses to fasting have not been described for this species. We therefore investigated the effects of 24h of fasting on plasma corticosterone concentrations in quail. Previous work has shown that the corticosterone response to handling in quail may be affected by treatment with corticosterone, so we also measured corticosterone responses to 24h of fasting in quail treated with corticosterone in their drinking water, and determined the effects of corticosterone on food intake immediately after a fast. Plasma corticosterone concentrations were unaffected by 24h of fasting in controls and in three out of four groups of birds with varying corticosterone intakes. Fasting in birds can be divided into three phases, and our results suggest that quail remained in phase I during the 24h fast. Food intake in the 3h immediately after fasting was higher in four groups of birds with varying corticosterone intakes than in the control group, and was greatest in quail with the highest corticosterone intake. The current results suggest that corticosterone can stimulate food intake in quail following a period of food deprivation. PMID:19539044

  16. Baseline Factors Predicting Placebo Response to Treatment in Children and Adolescents With Autism Spectrum Disorders

    PubMed Central

    King, Bryan H.; Dukes, Kimberly; Donnelly, Craig L.; Sikich, Linmarie; McCracken, James T.; Scahill, Lawrence; Hollander, Eric; Bregman, Joel D.; Anagnostou, Evdokia; Robinson, Fay; Sullivan, Lisa; Hirtz, Deborah

    2016-01-01

    IMPORTANCE The finding of factors that differentially predict the likelihood of response to placebo over that of an active drug could have a significant impact on study design in this population. OBJECTIVE To identify possible nonspecific, baseline predictors of response to intervention in a large randomized clinical trial of children and adolescents with autism spectrum disorders. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of citalopram hydrobromide for children and adolescents with autism spectrum disorders and prominent repetitive behavior. Baseline data at study entry were examined with respect to final outcome to determine if response predictors could be identified. A total of 149 children and adolescents 5 to 17 years of age (mean [SD] age, 9.4 [3.1] years) from 6 academic centers were randomly assigned to citalopram (n = 73) or placebo (n = 76). Participants had autistic disorder, Asperger syndrome, or pervasive developmental disorder, not otherwise specified; had illness severity ratings that were moderate or more than moderate on the Clinical Global Impression–Severity scale; and scored moderate or more than moderate on compulsive behaviors measured with the modified Children’s Yale-Brown Obsessive-Compulsive Scale. INTERVENTIONS Twelve weeks of treatment with citalopram (10 mg/5 mL) or placebo. The mean (SD) maximum dose of citalopram was 16.5 (6.5) mg by mouth daily (maximum dose, 20 mg/d). MAIN OUTCOMES AND MEASURES A positive response was defined as having a score of at least much improved on the Clinical Global Impression–Improvement scale at week 12. Baseline measures included demographic (sex, age, weight, and pubertal status), clinical, and family measures. Clinical variables included baseline illness severity ratings (the Aberrant Behavior Checklist, the Child and Adolescent Symptom Inventory, the Vineland Adaptive Behavior Scales, the Repetitive Behavior Scale–Revised, and the Children’s Yale-Brown Obsessive

  17. 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.

  18. 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. PMID:25778837

  19. 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.

  20. fMRI response to negative words and SSRI treatment outcome in major depressive disorder: a preliminary study.

    PubMed

    Miller, Jeffrey Morris; Schneck, Noam; Siegle, Greg J; Chen, Yakuan; Ogden, R Todd; Kikuchi, Toshiaki; Oquendo, Maria A; Mann, J John; Parsey, Ramin V

    2013-12-30

    Clinically useful predictors of treatment outcome in major depressive disorder (MDD) remain elusive. We examined associations between functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) signal during active negative word processing and subsequent selective serotonin reuptake inhibitor (SSRI) treatment outcome in MDD. Unmedicated MDD subjects (n=17) performed an emotional word processing fMRI task, and then received eight weeks of standardized antidepressant treatment with escitalopram. Lower pre-treatment BOLD responses to negative words in midbrain, dorsolateral prefrontal cortex, paracingulate, anterior cingulate, thalamus and caudate nuclei correlated significantly with greater improvement following escitalopram treatment. Activation of these regions in response to negative words correlated significantly with reaction time for rating word relevance. Maximally predictive clusters of voxels identified using a cross-validation approach predicted 48% of the variance in response to treatment. This study provides preliminary evidence that SSRIs may be most beneficial in patients who are less able to engage cognitive control networks while processing negative stimuli. Differences between these findings and previous fMRI studies of SSRI treatment outcome may relate to differences in task design. Regional BOLD responses to negative words predictive of SSRI outcome in this study were both overlapping and distinct from those predictive of outcome with cognitive behavioral therapy (CBT) in previous studies using the same task. Future studies may examine prediction of differential outcome across treatments in the context of a randomized controlled trial.

  1. Epidemiological and Clinical Baseline Characteristics as Predictive Biomarkers of Response to Anti-VEGF Treatment in Patients with Neovascular AMD.

    PubMed

    Tsilimbaris, Miltiadis K; López-Gálvez, Maria I; Gallego-Pinazo, Roberto; Margaron, Philippe; Lambrou, George N

    2016-01-01

    Purpose. To review the current literature investigating patient response to antivascular endothelial growth factor-A (VEGF) therapy in the treatment of neovascular age-related macular degeneration (nAMD) and to identify baseline characteristics that might predict response. Method. A literature search of the PubMed database was performed, using the keywords: AMD, anti-VEGF, biomarker, optical coherence tomography, treatment outcome, and predictor. The search was limited to articles published from 2006 to date. Exclusion criteria included phase 1 trials, case reports, studies focusing on indications other than nAMD, and oncology. Results. A total of 1467 articles were identified, of which 845 were excluded. Of the 622 remaining references, 47 met all the search criteria and were included in this review. Conclusion. Several baseline characteristics correlated with anti-VEGF treatment response, including best-corrected visual acuity, age, lesion size, and retinal thickness. The majority of factors were associated with disease duration, suggesting that longer disease duration before treatment results in worse treatment outcomes. This highlights the need for early treatment for patients with nAMD to gain optimal treatment outcomes. Many of the identified baseline characteristics are interconnected and cannot be evaluated in isolation; therefore multivariate analyses will be required to determine any specific relationship with treatment response. PMID:27073691

  2. Epidemiological and Clinical Baseline Characteristics as Predictive Biomarkers of Response to Anti-VEGF Treatment in Patients with Neovascular AMD

    PubMed Central

    López-Gálvez, Maria I.; Margaron, Philippe; Lambrou, George N.

    2016-01-01

    Purpose. To review the current literature investigating patient response to antivascular endothelial growth factor-A (VEGF) therapy in the treatment of neovascular age-related macular degeneration (nAMD) and to identify baseline characteristics that might predict response. Method. A literature search of the PubMed database was performed, using the keywords: AMD, anti-VEGF, biomarker, optical coherence tomography, treatment outcome, and predictor. The search was limited to articles published from 2006 to date. Exclusion criteria included phase 1 trials, case reports, studies focusing on indications other than nAMD, and oncology. Results. A total of 1467 articles were identified, of which 845 were excluded. Of the 622 remaining references, 47 met all the search criteria and were included in this review. Conclusion. Several baseline characteristics correlated with anti-VEGF treatment response, including best-corrected visual acuity, age, lesion size, and retinal thickness. The majority of factors were associated with disease duration, suggesting that longer disease duration before treatment results in worse treatment outcomes. This highlights the need for early treatment for patients with nAMD to gain optimal treatment outcomes. Many of the identified baseline characteristics are interconnected and cannot be evaluated in isolation; therefore multivariate analyses will be required to determine any specific relationship with treatment response. PMID:27073691

  3. 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,…

  4. 77 FR 31858 - Draft Guidance for Industry on Pathologic Complete Response in Neoadjuvant Treatment of High-Risk...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-30

    ... in Neoadjuvant Treatment of High-Risk Early-Stage Breast Cancer: Use as an Endpoint To Support... entitled ``Pathologic Complete Response in Neoadjuvant Treatment of High-Risk Early-Stage Breast Cancer... applicants in designing trials to support marketing approval of drugs to treat breast cancer in...

  5. fMRI response to negative words and SSRI treatment outcome in major depressive disorder: a preliminary study

    PubMed Central

    Miller, Jeffrey Morris; Schneck, Noam; Siegle, Greg J.; Chen, Yakuan; Ogden, R. Todd; Kikuchi, Toshiaki; Oquendo, Maria A.; Mann, J. John; Parsey, Ramin V.

    2013-01-01

    Clinically useful predictors of treatment outcome in major depressive disorder (MDD) remain elusive. We examined associations between functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) signal during active negative word processing and subsequent selective serotonin reuptake inhibitor (SSRI) treatment outcome in MDD. Unmedicated MDD subjects (n=17) performed an emotional word processing fMRI task, and then received eight weeks of standardized antidepressant treatment with escitalopram. Lower pre-treatment BOLD responses to negative words in midbrain, dorsolateral prefrontal cortex, paracingulate, anterior cingulate, thalamus and caudate nuclei correlated significantly with greater improvement following escitalopram treatment. Activation of these regions in response to negative words correlated significantly with reaction time for rating word relevance. Maximally predictive clusters of voxels identified using a cross-validation approach predicted 48% of the variance in response to treatment. This study provides preliminary evidence that SSRIs may be most beneficial in patients who are less able to engage cognitive control networks while processing negative stimuli. Differences between these findings and previous fMRI studies of SSRI treatment outcome may relate to differences in task design. Regional BOLD responses to negative words predictive of SSRI outcome in this study were both overlapping and distinct from those predictive of outcome with cognitive behavioral therapy (CBT) in previous studies using the same task. Future studies may examine prediction of differential outcome across treatments in the context of a randomized controlled trial. PMID:24446548

  6. Predictors of lack of serological response to syphilis treatment in HIV-infected subjects

    PubMed Central

    Spagnuolo, Vincenzo; Poli, Andrea; Galli, Laura; Cernuschi, Massimo; Nozza, Silvia; Maillard, Myriam; Gianotti, Nicola; Hasson, Hamid; Bossolasco, Simona; Lazzarin, Adriano; Castagna, Antonella

    2014-01-01

    Introduction The aim of this study was to determine factors associated with lack of serological response (LSR) to treatment of syphilis among HIV-infected subjects. Materials and Methods Retrospective, longitudinal study on HIV-infected subjects diagnosed and treated for syphilis and with an assessable serological response between 1 January 2004 and 15 September 2013. LSR was defined as a <4-fold decline of rapid plasma reagin (RPR) titer or a failed reversion to nonreactive (if RPR ≤1:4 at diagnosis) after one year since treatment. Diagnoses of syphilis were staged in early syphilis (primary, secondary and early latent) or late syphilis (tertiary and late latent) according to clinical examination and patient's history. Syphilis was classified in new infections [NI: positive RPR and TPHA (Treponema pallidum Haemagglutination assay) titers in subjects without previous history of syphilis] or re-infections [ReI: a ≥4-fold increase of RPR titer in subjects previously successfully treated for syphilis]. Syphilis treatment was prescribed according to CDC guidelines. The crude incidence rates (IRs) of LSR were calculated per 1000-person months of follow-up (PMFU) as the total number of LSR episodes divided by the cumulative time contributed by all subjects (interval time since each syphilis diagnosis and the date of ascertainment of response). Results are described as median (IQR) or frequency (%). Results 565 diagnoses of syphilis with an assessable serological response in 421 patients; 458 (81%) were early syphilis, 189 (33%) were NI, 376 (67%) were ReI. At first, diagnosis of syphilis median age was 41 (36–47) years, 419 (99.5%) males, 391 (93%) MSM, HIV-infected since 7.7 (3.5–12.9) years, 75 (18%) HCV or HBV co-infected, 56 (13%) with a previous AIDS diagnosis, 82 (19%) antiretroviral treatment naïve, 102 (24%) with HIV-RNA ≥50 cp/mL, CD4+=576 (437–749) cells/mm3, nadir CD4+=308 (194–406) cells/mm3. LSRs were observed in 70/565 (12.4%) treated

  7. 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. PMID:26661294

  8. Exercise physiological responses to drug treatments in chronic thromboembolic pulmonary hypertension.

    PubMed

    Charalampopoulos, Athanasios; Gibbs, J Simon R; Davies, Rachel J; Gin-Sing, Wendy; Murphy, Kevin; Sheares, Karen K; Pepke-Zaba, Joanna; Jenkins, David P; Howard, Luke S

    2016-09-01

    We tested the hypothesis that patients with chronic thromboembolic pulmonary hypertension (CTEPH) that was deemed to be inoperable were more likely to respond to drugs for treating pulmonary arterial hypertension (PAH) by using cardiopulmonary exercise (CPX) testing than those with CTEPH that was deemed to be operable. We analyzed CPX testing data of all patients with CTEPH who were treated with PAH drugs and had undergone CPX testing before and after treatment at a single pulmonary hypertension center between February 2009 and March 2013. Suitability for pulmonary endarterectomy (PEA) was decided by experts in PEA who were associated with a treatment center. The group with inoperable CTEPH included 16 patients, the operable group included 26 patients. There were no differences in demographics and baseline hemodynamic data between the groups. Unlike patients in the operable group, after drug treatment patients with inoperable CTEPH had a significantly higher peak V̇o2 (P < 0.001), work load (P = 0.002), and oxygen pulse (P < 0.001). In terms of gas exchange, there was an overall net trend toward improved V̇e/V̇co2 in the group with inoperable CTEPH, with an increased PaCO2 (P = 0.01), suggesting reduced hyperventilation. No changes were observed in patients with operable CTEPH. In conclusion, treatment with PAH drug therapy reveals important pathophysiological differences between inoperable and operable CTEPH, with significant pulmonary vascular and cardiac responses in inoperable disease. Drug effects on exercise function observed in inoperable CTEPH cannot be translated to all forms of CTEPH.

  9. 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.

  10. Inherited behaviors, BDNF expression and response to treatment in a novel multifactorial rat model for depression.

    PubMed

    Gersner, Roman; Gal, Ram; Levit, Ofir; Moshe, Hagar; Zangen, Abraham

    2014-06-01

    Major depressive disorder (MDD) is a common and devastating mental illness behaviorally characterized by various symptoms, including reduced motivation, anhedonia and psychomotor retardation. Although the etiology of MDD is still obscure, a genetic predisposition appears to play an important role. Here we used, for the first time, a multifactorial selective breeding procedure to generate a distinct 'depressed' rat line (DRL); our selection was based upon mobility in the forced swim test, sucrose preference and home-cage locomotion, three widely used tests associated with core characteristics of MDD. Other behavioral effects of the selection process, as well as changes in brain-derived neurotrophic factor (BDNF) and the response to three antidepressant treatments, were also examined. We show that decreased mobility in the forced swim test and decreased sucrose preference (two directly selected traits), as well as decreased exploration in the open field test (an indirectly selected trait), are hereditary components in DRL rats. In addition, lower BDNF levels are observed in the dorsal hippocampus of DRL rats, complying with the neurotrophic hypothesis of depression. Finally, electroconvulsive shocks (ECS) but not pharmacological treatment normalizes both the depressive-like behavioral impairments and the BDNF-related molecular alterations in DRL rats, highlighting the need for robust treatment when the disease is inherited and not necessarily triggered by salient chronic stress. We therefore provide a novel multifactorial genetic rat model for depression-related behaviors. The model can be used to further study the etiology of the disease and suggest molecular correlates and possible treatments for the disease. PMID:24513109

  11. Exercise physiological responses to drug treatments in chronic thromboembolic pulmonary hypertension.

    PubMed

    Charalampopoulos, Athanasios; Gibbs, J Simon R; Davies, Rachel J; Gin-Sing, Wendy; Murphy, Kevin; Sheares, Karen K; Pepke-Zaba, Joanna; Jenkins, David P; Howard, Luke S

    2016-09-01

    We tested the hypothesis that patients with chronic thromboembolic pulmonary hypertension (CTEPH) that was deemed to be inoperable were more likely to respond to drugs for treating pulmonary arterial hypertension (PAH) by using cardiopulmonary exercise (CPX) testing than those with CTEPH that was deemed to be operable. We analyzed CPX testing data of all patients with CTEPH who were treated with PAH drugs and had undergone CPX testing before and after treatment at a single pulmonary hypertension center between February 2009 and March 2013. Suitability for pulmonary endarterectomy (PEA) was decided by experts in PEA who were associated with a treatment center. The group with inoperable CTEPH included 16 patients, the operable group included 26 patients. There were no differences in demographics and baseline hemodynamic data between the groups. Unlike patients in the operable group, after drug treatment patients with inoperable CTEPH had a significantly higher peak V̇o2 (P < 0.001), work load (P = 0.002), and oxygen pulse (P < 0.001). In terms of gas exchange, there was an overall net trend toward improved V̇e/V̇co2 in the group with inoperable CTEPH, with an increased PaCO2 (P = 0.01), suggesting reduced hyperventilation. No changes were observed in patients with operable CTEPH. In conclusion, treatment with PAH drug therapy reveals important pathophysiological differences between inoperable and operable CTEPH, with significant pulmonary vascular and cardiac responses in inoperable disease. Drug effects on exercise function observed in inoperable CTEPH cannot be translated to all forms of CTEPH. PMID:27418685

  12. 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

  13. Effects of MK-801 and amphetamine treatments on allergic lung inflammatory response in mice.

    PubMed

    Hamasato, Eduardo Kenji; Ligeiro de Oliveira, Ana Paula; Lino-dos-Santos-Franco, Adriana; Ribeiro, Alison; Ferraz de Paula, Viviane; Peron, Jean Pierre Schatzmann; Damazo, Amílcar Sabino; Tavares-de-Lima, Wothan; Palermo-Neto, João

    2013-08-01

    Glutamate acts as a neurotransmitter within the Central Nervous System (CNS) and modifies immune cell activity. In lymphocytes, NMDA glutamate receptors regulate intracellular calcium, the production of reactive oxygen species and cytokine synthesis. MK-801, a NMDA receptor open-channel blocker, inhibits calcium entry into mast cells, thereby preventing mast cell degranulation. Several lines of evidence have shown the involvement of NMDA glutamate receptors in amphetamine (AMPH)-induced effects. AMPH treatment has been reported to modify allergic lung inflammation. This study evaluated the effects of MK-801 (0.25mg/kg) and AMPH (2.0mg/kg), given alone or in combination, on allergic lung inflammation in mice and the possible involvement of NMDA receptors in this process. In OVA-sensitized and challenged mice, AMPH and MK-801 given alone decreased cellular migration into the lung, reduced IL-13 and IL10 levels in BAL supernatant, reduced ICAM-1 and L-selectin expression in granulocytes in the BAL and decreased mast cell degranulation. AMPH treatment also decreased IL-5 levels. When both drugs were administered, treatment with MK-801 reversed the decrease in the number of eosinophils and neutrophils induced by AMPH in the BAL of OVA-sensitized and challenged mice as well as the effects on the expression of L-selectin and ICAM-1 in granulocytes, the IL-10, IL-5 and IL-13 levels in BAL supernatants and increased mast cell degranulation. At the same time, treatment with MK-801, AMPH or with MK-801+AMPH increased corticosterone serum levels in allergic mice. These results are discussed in light of possible indirect effects of AMPH and MK-801 via endocrine outflow from the CNS (i.e., HPA-axis activity) to the periphery and/or as a consequence of the direct action of these drugs on immune cell activity, with emphasis given to mast cell participation in the allergic lung response of mice.

  14. Age-Stratified Treatment Response Rates in Hospitalized Patients with Clostridium difficile Infection Treated with Metronidazole

    PubMed Central

    Pham, Vy P.; Luce, Andrea M.; Ruppelt, Sara C.; Wei, Wenjing; Aitken, Samuel L.; Musick, William L.; Roux, Ryan K.

    2015-01-01

    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. PMID:26195522

  15. 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.

  16. Pre-treatment neutrophil to lymphocyte ratio as a predictive marker for pathological response to preoperative chemoradiotherapy in pancreatic cancer

    PubMed Central

    HASEGAWA, SHINICHIRO; EGUCHI, HIDETOSHI; TOMOKUNI, AKIRA; TOMIMARU, YOSHITO; ASAOKA, TADAFUMI; WADA, HIROSHI; HAMA, NAOKI; KAWAMOTO, KOICHI; KOBAYASHI, SHOGO; MARUBASHI, SHIGERU; KONNNO, MASAMITSU; ISHII, HIDESHI; MORI, MASAKI; DOKI, YUICHIRO; NAGANO, HIROAKI

    2016-01-01

    An elevated neutrophil to lymphocyte ratio (NLR) has been reported to be associated with the pathological response to neoadjuvant therapies in numerous types of cancer. The aim of the current study was to clarify the association between pre-treatment NLR and the pathological response to preoperative chemoradiotherapy in pancreatic cancer patients. This retrospective analysis included data from 56 consecutive patients whose tumors were completely surgically resected. All patients received preoperative therapy, consisting of gemcitabine-based chemotherapy (alone or in combination with S-1) combined with 40 or 50.4 Gy irradiation, prior to surgery. Predictive factors, including NLR, platelet to lymphocyte ratio (PLR), modified Glasgow prognostic score and prognostic nutrition index, were measured prior to treatment. A comparison was made between those who responded well pathologically (good response group, Evans classification IIb/III) and those with a poor response (Evans I/IIa). NLR was determined to be significantly higher in the poor response group. Multivariate analysis identified an elevated NLR as an independent risk factor for the poor pathological response [odds ratio (OR), 5.35; P=0.0257]. The pre-treatment NLR (≥2.2/<2.2) was found to be a statistically significant predictive indicator of pathological response (P=0.00699). The results demonstrate that pre-treatment NLR may be a useful predictive marker for the pathological response to preoperative therapy in pancreatic cancer patients. PMID:26893780

  17. Aminolevulinic Acid-Photodynamic Therapy of Basal Cell Carcinoma and Factors Affecting the Response to Treatment: A Clinical Trial

    PubMed Central

    Tehranchinia, Zohreh; Rahimi, Hoda; Ahadi, Mahsa Seyed; Ahadi, Maral Seyed

    2013-01-01

    Background: Basal cell carcinoma (BCC) is the most common type of skin cancer in humans. Photodynamic therapy (PDT) is a non-invasive therapeutic modality that may be considered as a valuable treatment option for BCC. This study was designed with the aim of evaluating the efficacy of PDT in treatment of BCC and factors that may affect the response rate. Materials and Methods: This clinical trial was conducted on 12 patients (28 BCC lesions) who were treated with aminulevulinic acid (ALA)-PDT, monthly, up to 6 sessions and the clinical response, cosmetic results, and possible side effects were evaluated. Results: The study was performed on 28 BCC lesions from 12 patients. Complete response was achieved in 9 (32.1%) lesions. Complete response rate was higher in younger patients (P < 0.01) and those with smaller lesions (P < 0.001). Superficial type also had significant higher response rate (P < 0.05). Patients with history of radiotherapy for the treatment of tinea capitis in childhood showed less response (P < 0.05). Cosmetic results were excellent or good in 77.5% cases. After 6 months of follow-up, none of the resolved lesions recurred. Conclusion: PDT would be a good therapeutic option in treatment of BCC with acceptable efficacy and low side effects. Younger patients, superficial BCCs, and smaller lesions show better response to ALA-PDT. History of radiotherapy may be associated with a lower response rate. PMID:23919025

  18. 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…

  19. Intrahepatic Transcriptional Signature Associated with Response to Interferon-α Treatment in the Woodchuck Model of Chronic Hepatitis B.

    PubMed

    Fletcher, Simon P; Chin, Daniel J; Gruenbaum, Lore; Bitter, Hans; Rasmussen, Erik; Ravindran, Palanikumar; Swinney, David C; Birzele, Fabian; Schmucki, Roland; Lorenz, Stefan H; Kopetzki, Erhard; Carter, Jade; Triyatni, Miriam; Thampi, Linta M; Yang, Junming; AlDeghaither, Dalal; Murreddu, Marta G; Murredu, Marta G; Cote, Paul; Menne, Stephan

    2015-09-01

    Recombinant interferon-alpha (IFN-α) is an approved therapy for chronic hepatitis B (CHB), but the molecular basis of treatment response remains to be determined. The woodchuck model of chronic hepatitis B virus (HBV) infection displays many characteristics of human disease and has been extensively used to evaluate antiviral therapeutics. In this study, woodchucks with chronic woodchuck hepatitis virus (WHV) infection were treated with recombinant woodchuck IFN-α (wIFN-α) or placebo (n = 12/group) for 15 weeks. Treatment with wIFN-α strongly reduced viral markers in the serum and liver in a subset of animals, with viral rebound typically being observed following cessation of treatment. To define the intrahepatic cellular and molecular characteristics of the antiviral response to wIFN-α, we characterized the transcriptional profiles of liver biopsies taken from animals (n = 8-12/group) at various times during the study. Unexpectedly, this revealed that the antiviral response to treatment did not correlate with intrahepatic induction of the majority of IFN-stimulated genes (ISGs) by wIFN-α. Instead, treatment response was associated with the induction of an NK/T cell signature in the liver, as well as an intrahepatic IFN-γ transcriptional response and elevation of liver injury biomarkers. Collectively, these data suggest that NK/T cell cytolytic and non-cytolytic mechanisms mediate the antiviral response to wIFN-α treatment. In summary, by studying recombinant IFN-α in a fully immunocompetent animal model of CHB, we determined that the immunomodulatory effects, but not the direct antiviral activity, of this pleiotropic cytokine are most closely correlated with treatment response. This has important implications for the rational design of new therapeutics for the treatment of CHB. PMID:26352406

  20. Suboptimal Response to or Failure of Imatinib Treatment for Chronic Myeloid Leukemia: What Is the Optimal Strategy?

    PubMed Central

    Jabbour, Elias; Cortes, Jorge E.; Kantarjian, Hagop M.

    2009-01-01

    Treatment responses to imatinib vary among patients with chronic myeloid leukemia (CML), and definitions of treatment failure and suboptimal response have been published. This article discusses monitoring and treatment of patients with CML after failure of or suboptimal response to imatinib therapy. We reviewed articles listed on PubMed from January 1, 2002, to July 31, 2008, and abstracts from the 2007 Annual Meeting of the American Society of Hematology. Search terms used were chronic myeloid/myelogenous leukemia, imatinib, and BCR-ABL. To enable early recognition of suboptimal responses, patients should be frequently monitored according to published guidelines, including cytogenetic analysis every 6 months until a complete response is achieved and molecular monitoring every 3 months from the start of therapy or monthly if an increasing BCR-ABL1 transcript level is detected. Mutational analysis of BCR-ABL1 may assist with treatment selection. A recent survey suggests that a notable proportion of physicians do not follow treatment guidelines and that broader communication is required. Recent recommendations state that, in patients whose response to imatinib at 400 mg/d is suboptimal, the dose should be increased, whereas alternative therapies, such as dasatinib, nilotinib, and allogeneic stem cell transplant (in eligible patients), and imatinib dose escalation should be considered after imatinib failure. However, clinical data are lacking to confirm this sequence of treatments, and introducing alternative therapies at an earlier stage of treatment, for example, after a suboptimal response, may produce better long-term outcomes in a higher proportion of patients. Patient and disease characteristics should be carefully considered to optimize treatment strategy for CML. PMID:19181650

  1. 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

  2. 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

  3. Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment.

    PubMed

    Markworth, James F; Vella, Luke; Lingard, Benjamin S; Tull, Dedreia L; Rupasinghe, Thusitha W; Sinclair, Andrew J; Maddipati, Krishna Rao; Cameron-Smith, David

    2013-12-01

    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 biological

  4. Neural correlates of emotional processing in depression: Changes with cognitive behavioral therapy and predictors of treatment response

    PubMed Central

    Ritchey, Maureen; Dolcos, Florin; Eddington, Kari M.; Strauman, Timothy J.; Cabeza, Roberto

    2010-01-01

    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

  5. Response of garlic (Allium sativum L.) bolting and bulbing to temperature and photoperiod treatments.

    PubMed

    Wu, Cuinan; Wang, Mengyi; Cheng, Zhihui; Meng, Huanwen

    2016-01-01

    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 formation under 20

  6. 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

  7. 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

  8. 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

  9. Cluster analysis of cognitive deficits may mark heterogeneity in schizophrenia in terms of outcome and response to treatment

    PubMed Central

    Gilbert, Elsa; Mérette, Chantal; Jomphe, Valérie; Émond, Claudia; Rouleau, Nancie; Bouchard, Roch-Hugo; Roy, Marc-André; Paccalet, Thomas

    2016-01-01

    Cognitive impairments are central to schizophrenia, but their clinical utility for tagging heterogeneity in lifetime outcome and response to treatment is not conclusive. By exploiting four cognitive domains consistently showing large deficits in studies, we tested whether cluster analysis would define separate subsets of patients and then whether the disease heterogeneity marked by these clusters would be related to lifetime outcome and response to treatment. A total of 112 schizophrenia patients completed a neuropsychological evaluation. The PANSS, GAF-S and GAF-F were rated at the onset and endpoint of the illness trajectory. A blind judgment of the lifetime response to treatment was made. The first cluster presented near-normal cognitive performance. Two other clusters of severely impaired patients were identified: one generally impaired in the four cognitive domains and another selectively impaired in visual episodic memory and processing speed, each relating to a different lifetime evolution of disease and treatment response. Although the two impaired clusters were clinically indistinguishable in symptom severity and functioning at disease onset, patients with selective cognitive impairments demonstrated better improvement at outcome, whereas the generally impaired patients were more likely to be treatment refractory. The findings have implications for the management of patients and for clinical trials since particular combinations of cognitive deficits in patients would influence their treatment response. PMID:24173295

  10. Biologically relevant 3D tumor arrays: imaging-based methods for quantification of reproducible growth and analysis of treatment response

    NASA Astrophysics Data System (ADS)

    Celli, Jonathan P.; Rizvi, Imran; Blanden, Adam R.; Abu-Yousif, Adnan O.; Spring, Bryan Q.; Hasan, Tayyaba

    2011-02-01

    Three-dimensional in vitro tumor models have emerged as powerful research tools in cancer biology, though the vast potential of these systems as high-throughput, biologically relevant reporters of treatment response has yet to be adequately explored. Here, building on previous studies, we demonstrate the utility of using 3D models for ovarian and pancreatic cancers in conjunction with quantitative image processing to reveal aspects of growth behavior and treatment response that would not be evident without either modeling or quantitative analysis component. In this report we specifically focus on recent improvements in the imaging component of this integrative research platform and emphasize analysis to establish reproducible growth properties in 3D tumor arrays, a key consideration in establishing the utility of this platform as a reliable reporter of therapeutic response. Building on previous studies using automated segmentation of low magnification image fields containing large numbers of nodules to study size dependent treatment effects, we introduce an improvement to this method using multiresolution decomposition to remove gradient background from transmitted light images for more reliable feature identification. This approach facilitates the development of a new treatment response metric, disruption fraction (Dfrac), which quantifies dose dependent distribution shifts from nodular fragmentation induced by cytotoxic therapies. Using this approach we show that PDT treatment is associated with significant dose-dependent increases in Dfrac, while this is not observed with carboplatin treatment. The ability to quantify this response to therapy could play a key role in design of combination regimens involving these two modalities.

  11. 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.

  12. HEPATOCELLULAR CARCINOMA IN A NON-CIRRHOTIC PATIENT WITH SUSTAINED VIROLOGICAL RESPONSE AFTER HEPATITIS C TREATMENT

    PubMed Central

    de MATTOS, Angelo Alves; MARCON, Patrícia dos Santos; de ARAÚJO, Fernanda Schild Branco; CORAL, Gabriela Perdomo; TOVO, Cristiane Valle

    2015-01-01

    Chronic infection by hepatitis C virus (HCV) is one of the main risk factors for the development of liver cirrhosis and hepatocellular carcinoma. However, the emergence of hepatocellular carcinoma (HCC) in non-cirrhotic HCV patients, especially after sustained virological response (SVR) is an unusual event. Recently, it has been suggested that HCV genotype 3 may have a particular oncogenic mechanism, but the factors involved in these cases as well as the profile of these patients are still not fully understood. Thus, we present the case of a non-cirrhotic fifty-year-old male with HCV infection, genotype 3a, who developed HCC two years after treatment with pegylated-interferon and ribavirin, with SVR, in Brazil. PMID:27049708

  13. A Novel Treatment-Responsive Encephalitis with Frequent Opsoclonus and Teratoma

    PubMed Central

    Armangue, Thaís; Titulaer, Maarten J.; Sabater, Lidia; Pardo-Moreno, Javier; Gresa-Arribas, Nuria; Barbero-Bordallo, Natalia; Kelley, Gordon R.; Kyung-Ha, Noh; Takeda, Akitoshi; Nagao, Takahiro; Takahashi, Yukitoshi; Lizcano, Angélica; Carr, Aisling S.; Graus, Francesc; Dalmau, Josep

    2016-01-01

    Among 249 patients with teratoma-associated encephalitis, 211 had N-methyl-D-aspartate receptor antibodies and 38 were negative for these antibodies. Whereas antibody-positive patients rarely developed prominent brainstem–cerebellar symptoms, 22 (58%) antibody-negative patients developed a brainstem–cerebellar syndrome, which in 45% occurred with opsoclonus. The median age of these patients was 28.5 years (range = 12–41), 91% were women, and 74% had full recovery after therapy and tumor resection. These findings uncover a novel phenotype of paraneoplastic opsoclonus that until recently was likely considered idiopathic or postinfectious. The triad of young age (teenager to young adult), systemic teratoma, and high response to treatment characterize this novel brain-stem–cerebellar syndrome. PMID:23613036

  14. Shared Responsibility: Massachusetts Legislators, Physicians, and An Act Relative to Substance Use Treatment, Education, and Prevention.

    PubMed

    Rudder, Meghan; Tsao, Lulu; Jack, Helen E

    2016-01-01

    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. PMID:27669141

  15. 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.

  16. Pivotal response treatment prompts a functional rewiring of the brain among individuals with autism spectrum disorder.

    PubMed

    Venkataraman, Archana; Yang, Daniel Y-J; Dvornek, Nicha; Staib, Lawrence H; Duncan, James S; Pelphrey, Kevin A; Ventola, Pamela

    2016-09-28

    Behavioral interventions for autism have gained prominence in recent years; however, the neural-systems-level targets of these interventions remain poorly understood. We use a novel Bayesian framework to extract network-based differences before and after a 16-week pivotal response treatment (PRT) regimen. Our results suggest that the functional changes induced by PRT localize to the posterior cingulate and are marked by a shift in connectivity from the orbitofrontal cortex to the occipital-temporal cortex. Our results illuminate a potential PRT-induced learning mechanism, whereby the neural circuits involved during social perception shift from sensory and attentional systems to higher-level object and face processing areas. PMID:27532879

  17. HEPATOCELLULAR CARCINOMA IN A NON-CIRRHOTIC PATIENT WITH SUSTAINED VIROLOGICAL RESPONSE AFTER HEPATITIS C TREATMENT.

    PubMed

    Mattos, Angelo Alves de; Marcon, Patrícia dos Santos; Araújo, Fernanda Schild Branco de; Coral, Gabriela Perdomo; Tovo, Cristiane Valle

    2015-12-01

    Chronic infection by hepatitis C virus (HCV) is one of the main risk factors for the development of liver cirrhosis and hepatocellular carcinoma. However, the emergence of hepatocellular carcinoma (HCC) in non-cirrhotic HCV patients, especially after sustained virological response (SVR) is an unusual event. Recently, it has been suggested that HCV genotype 3 may have a particular oncogenic mechanism, but the factors involved in these cases as well as the profile of these patients are still not fully understood. Thus, we present the case of a non-cirrhotic fifty-year-old male with HCV infection, genotype 3a, who developed HCC two years after treatment with pegylated-interferon and ribavirin, with SVR, in Brazil. PMID:27049708

  18. 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.

  19. Differential prefrontal gray matter correlates of treatment response to fluoxetine or cognitive-behavioral therapy in obsessive-compulsive disorder.

    PubMed

    Hoexter, Marcelo Q; Dougherty, Darin D; Shavitt, Roseli G; D'Alcante, Carina C; Duran, Fabio L S; Lopes, Antonio C; Diniz, Juliana B; Batistuzzo, Marcelo C; Evans, Karleyton C; Bressan, Rodrigo A; Busatto, Geraldo F; Miguel, Euripedes C

    2013-07-01

    Nearly one-third of patients with obsessive-compulsive disorder (OCD) fail to respond to adequate therapeutic approaches such as serotonin reuptake inhibitors and/or cognitive-behavioral therapy (CBT). This study investigated structural magnetic resonance imaging (MRI) correlates as potential pre-treatment brain markers to predict treatment response in treatment-naïve OCD patients randomized between trials of fluoxetine or CBT. Treatment-naïve OCD patients underwent structural MRI scans before randomization to a 12-week clinical trial of either fluoxetine or group-based CBT. Voxel-based morphometry was used to identify correlations between pretreatment regional gray matter volume and changes in symptom severity on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Brain regional correlations of treatment response differed between treatment groups. Notably, symptom improvement in the fluoxetine treatment group (n=14) was significantly correlated with smaller pretreatment gray matter volume within the right middle lateral orbitofrontal cortex (OFC), whereas symptom improvement in the CBT treatment group (n=15) was significantly correlated with larger pretreatment gray matter volume within the right medial prefrontal cortex (mPFC). No significant a priori regional correlations of treatment response were identified as common between the two treatment groups when considering the entire sample (n=29). These findings suggest that pretreatment gray matter volumes of distinct brain regions within the lateral OFC and mPFC were differentially correlated to treatment response to fluoxetine versus CBT in OCD patients. This study further implicates the mPFC in the fear/anxiety extinction process and stresses the importance of lateral portions of the OFC in mediating fluoxetine's effectiveness in OCD. Clinical registration information: http://clinicaltrials.gov-NCT00680602.

  20. Circulating tumor cells are correlated with disease progression and treatment response in an orthotopic hepatocellular carcinoma model.

    PubMed

    Yan, Jun; Fan, Zhichao; Wu, Xiufeng; Xu, Min; Jiang, Jiahao; Tan, Changjun; Wu, Weizhong; Wei, Xunbin; Zhou, Jian

    2015-11-01

    Hepatocellular carcinoma (HCC) is a highly malignant tumor characterized by rapid progression, poor prognosis, and frequent hematogenous metastasis. A minimally invasive diagnostic biomarker that can predict disease progression and treatment response would be of extraordinary benefit. Therefore, we have investigated whether the number of circulating tumor cells (CTCs) is correlated with disease progression and treatment response in HCC. Here we report that the number of CTCs, monitored by in vivo flow cytometry (IVFC), is strongly correlated with disease progression and treatment response in a highly metastatic orthotopic nude mouse model of green fluorescent protein (GFP)-labeled HCC. Sorafenib treatment reduces the number of CTCs significantly. The decreased number of CTCs is consistent with low lung metastasis. This study has demonstrated a considerable clinical value of CTCs as a biomarker in predicting disease progression and monitoring therapeutic efficacy in patients with HCC.

  1. Doppler laser imaging predicts response to topical minoxidil in the treatment of female pattern hair loss.

    PubMed

    McCoy, J; Kovacevic, M; Situm, M; Stanimirovic, A; Bolanca, Z; Goren, A

    2016-01-01

    Topical minoxidil is the only drug approved by the US FDA for the treatment of female pattern hair loss. Unfortunately, following 16 weeks of daily application, less than 40% of patients regrow hair. Several studies have demonstrated that sulfotransferase enzyme activity in plucked hair follicles predicts topical minoxidil response in female pattern hair loss patients. However, due to patients’ discomfort with the procedure, and the time required to perform the enzymatic assay it would be ideal to develop a rapid, non-invasive test for sulfotransferase enzyme activity. Minoxidil is a pro-drug converted to its active form, minoxidil sulfate, by sulfotransferase enzymes in the outer root sheath of hair. Minoxidil sulfate is the active form required for both the promotion of hair regrowth and the vasodilatory effects of minoxidil. We thus hypothesized that laser Doppler velocimetry measurement of scalp blood perfusion subsequent to the application of topical minoxidil would correlate with sulfotransferase enzyme activity in plucked hair follicles. In this study, plucked hair follicles from female pattern hair loss patients were analyzed for sulfotransferase enzyme activity. Additionally, laser Doppler velocimetry was used to measure the change in scalp perfusion at 15, 30, 45, and 60 minutes, after the application of minoxidil. In agreement with our hypothesis, we discovered a correlation (r=1.0) between the change in scalp perfusion within 60 minutes after topical minoxidil application and sulfotransferase enzyme activity in plucked hairs. To our knowledge, this is the first study demonstrating the feasibility of using laser Doppler imaging as a rapid, non-invasive diagnostic test to predict topical minoxidil response in the treatment of female pattern hair loss. PMID:27049083

  2. Doppler laser imaging predicts response to topical minoxidil in the treatment of female pattern hair loss.

    PubMed

    McCoy, J; Kovacevic, M; Situm, M; Stanimirovic, A; Bolanca, Z; Goren, A

    2016-01-01

    Topical minoxidil is the only drug approved by the US FDA for the treatment of female pattern hair loss. Unfortunately, following 16 weeks of daily application, less than 40% of patients regrow hair. Several studies have demonstrated that sulfotransferase enzyme activity in plucked hair follicles predicts topical minoxidil response in female pattern hair loss patients. However, due to patients’ discomfort with the procedure, and the time required to perform the enzymatic assay it would be ideal to develop a rapid, non-invasive test for sulfotransferase enzyme activity. Minoxidil is a pro-drug converted to its active form, minoxidil sulfate, by sulfotransferase enzymes in the outer root sheath of hair. Minoxidil sulfate is the active form required for both the promotion of hair regrowth and the vasodilatory effects of minoxidil. We thus hypothesized that laser Doppler velocimetry measurement of scalp blood perfusion subsequent to the application of topical minoxidil would correlate with sulfotransferase enzyme activity in plucked hair follicles. In this study, plucked hair follicles from female pattern hair loss patients were analyzed for sulfotransferase enzyme activity. Additionally, laser Doppler velocimetry was used to measure the change in scalp perfusion at 15, 30, 45, and 60 minutes, after the application of minoxidil. In agreement with our hypothesis, we discovered a correlation (r=1.0) between the change in scalp perfusion within 60 minutes after topical minoxidil application and sulfotransferase enzyme activity in plucked hairs. To our knowledge, this is the first study demonstrating the feasibility of using laser Doppler imaging as a rapid, non-invasive diagnostic test to predict topical minoxidil response in the treatment of female pattern hair loss.

  3. 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.

  4. 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. PMID:25733954

  5. Treatment of porcine cysticercosis with oxfendazole: a dose-response trial.

    PubMed

    Gonzalez, A E; Falcon, N; Gavidia, C; Garcia, H H; Tsang, V C; Bernal, T; Romero, M; Gilman, R H

    1997-10-18

    Taenia solium cysticercosis is an important public health problem in developing countries. Oxfendazole has been shown to be highly effective against porcine cysticercosis, when given as a single dose at 30 mg/kg bodyweight. This dose, however, was estimated from experience with albendazole. A controlled dose-response trial was therefore undertaken to determine the efficacy and safety of three concentrations of oxfendazole. Twenty-four naturally parasitised pigs were divided into four groups and treated with oxfendazole at 10 mg/kg, 20 mg/kg or 30 mg/kg, or left untreated. Eight to 10 weeks later the pigs were killed and the viability of the parasites assessed by evagination. No side-effects of oxfendazole treatment were observed. In the control group more than 90 per cent of the cysts were viable. Viable cysts were found in the muscle and brain of the pigs treated with 10 or 20 mg/kg oxfendazole. At 30 mg/kg there were no viable cysts in any of the tissues examined, indicating that this concentration of oxfendazole provided an effective treatment against porcine cysticercosis.

  6. 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.

  7. Proximal anterior cruciate ligament tears: the healing response technique versus conservative treatment.

    PubMed

    Wasmaier, Johann; Kubik-Huch, Rahel; Pfirrmann, Christian; Grehn, Holger; Bieg, Christian; Eid, Karim

    2013-08-01

    The healing response technique (HRT) is a nonreconstructive method to promote healing in proximal anterior cruciate ligament (ACL) tears. The study reviews clinical and radiological long-term results. Thirty patients (average age 31 years) were treated according to the protocol described by Steadman et al. For comparison, an age- and gender-matched control group of conservatively treated patients (CST; n = 127) was selected. At follow-up (mean: 4 years), all patients were evaluated using Kneelax-3-arthrometer, magnetic resonance imaging (MRI), and by clinical examination. Two HRT patients were lost to follow-up and 10 (36%) patients needed definitive ACL reconstruction. The rate of secondary ACL reconstruction in the initial CST group was 56% (71 of 127). Nineteen of the conservatively treated patients were selected according to above-mentioned criteria. The average Lysholm score in the HRT group was 91 (CST group = 90), and the Orthopaedische Arbeitsgemeinschaft Knie score was 93 (CST group = 92). Tegner score decreased from 6.8 before injury to 5.7 at the time of follow-up (CST group: 6.0 to 5.1). Kneelax-3-arthrometer showed a significant higher anterior knee laxity compared with the noninjured side in both groups. MRI showed improvement of the ACL in both groups. HRT in adult patients is associated with a high revision rate of 36% secondary ACL reconstruction, comparable with primary conservative treatment (p = 0.056). For the remaining patients (64%), HRT did not result in better outcomes than conservative treatment.

  8. Neuroimaging biomarkers to predict treatment response in schizophrenia: the end of 30 years of solitude?

    PubMed Central

    Dazzan, Paola

    2014-01-01

    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. PMID:25733954

  9. Cellular pharmacokinetics of daunorubicin: relationships with the response to treatment in patients with acute myeloid leukemia.

    PubMed

    Kokenberg, E; Sonneveld, P; Sizoo, W; Hagenbeek, A; Löwenberg, B

    1988-05-01

    In an attempt to identify pharmacokinetic factors that determine the response of acute myeloid leukemia (AML) patients to induction chemotherapy, we determined the concentrations of daunorubicin (DNR) and the main metabolite daunorubicinol (DOL) in vivo and particularly evaluated the concentrations in blood and bone marrow nucleated cells. Cell measurements were obtained in 37 evaluable patients during their first remission induction treatment with DNR and cytarabine (ara-C) and directly compared with the plasma distribution kinetics of DNR. We show that (1) plasma DNR concentrations do not correlate with DNR concentrations in bone marrow nucleated cells; but (2) plasma area under the curve (AUC) values of DNR correlate inversely (P less than .01) with AUC values of DNR in WBCs; (3) concentrations of DNR in WBCs correlate positively (P less than .01) with DNR concentrations in bone marrow nucleated cells; and (4) the concentrations of DNR in WBCs show a negative correlation (P less than .01) with the numbers of peripheral blast cells at diagnosis. We then tested whether the pharmacokinetic parameters had predictive value for the clinical outcome of therapy, but none of the plasma levels or WBC and bone marrow concentrations of DNR predicted treatment outcome. The inverse correlation between the concentrations of DNR in WBC and the numbers of peripheral blast cells suggests that the effective DNR concentrations achieved intracellularly are mainly a function of the tumor load so that lesser amounts of DNR accumulate intracellularly when the AML cell numbers in blood are higher.

  10. 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.

  11. A two-clones tumor model: Spontaneous growth and response to treatment.

    PubMed

    Stura, Ilaria; Venturino, Ezio; Guiot, Caterina

    2016-01-01

    The paper aims at providing a general theoretical frame bridging the macroscopic growth law with the complex heterogeneous structure of real tumors. We apply the "Phenomenological Universality" approach to model the growth of cancer cells accounting for "populations", which are defined not as biologically pre-defined cellular ensemble but as groups of cells behaving homogeneously with respect to their position (e.g. primary or metastatic tumor), growth characteristics, response to treatment, etc. Populations may mutually interact, limit each other their growth or even mutate into another population. To keep the description as simple and manageable as possible only two populations are considered, but the extension to a multiplicity of cell populations is straightforward. Our findings indicate that the eradication of the metastatic population is much more critical in the presence of mutations, either spontaneous or therapy-induced. Furthermore, a treatment that eradicates only the primary tumor, having a low kill rate on the metastases, is ultimately not successful but promotes a "growth spurt" in the latter. PMID:26524141

  12. Understanding physiological responses to pre-treatment inhibitors in ethanologenic fermentations.

    PubMed

    Taylor, Mark P; Mulako, Inonge; Tuffin, Marla; Cowan, Don

    2012-09-01

    Alcohol-based liquid fuels feature significantly in the political and social agendas of many countries, seeking energy sustainability. It is certain that ethanol will be the entry point for many sustainable processes. Conventional ethanol production using maize- and sugarcane-based carbohydrates with Saccharomyces cerevisiae is well established, while lignocellulose-based processes are receiving growing interest despite posing greater technical and scientific challenges. A significant challenge that arises from the chemical hydrolysis of lignocellulose is the generation of toxic compounds in parallel with the release of sugars. These compounds, collectively termed pre-treatment inhibitors, impair metabolic functionality and growth. Their removal, pre-fermentation or their abatement, via milder hydrolysis, are currently uneconomic options. It is widely acknowledged that a more cost effective strategy is to develop resistant process strains. Here we describe and classify common inhibitors and describe in detail the reported physiological responses that occur in second-generation strains, which include engineered yeast and mesophilic and thermophilic prokaryotes. It is suggested that a thorough understanding of tolerance to common pre-treatment inhibitors should be a major focus in ongoing strain engineering. This review is a useful resource for future metabolic engineering strategies. PMID:22331581

  13. Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and chronic opiate treatments.

    PubMed

    Elhabazi, K; Trigo, J M; Mollereau, C; Moulédous, L; Zajac, J-M; Bihel, F; Schmitt, M; Bourguignon, J J; Meziane, H; Petit-demoulière, B; Bockel, F; Maldonado, R; Simonin, F

    2012-01-01

    BACKGROUND AND PURPOSE Opiates remain the most effective compounds for alleviating severe pain across a wide range of conditions. However, their use is associated with significant side effects. Neuropeptide FF (NPFF) receptors have been implicated in several opiate-induced neuroadaptive changes including the development of tolerance. In this study, we investigated the consequences of NPFF receptor blockade on acute and chronic stimulation of opioid receptors in mice by using RF9, a potent and selective antagonist of NPFF receptors that can be administered systemically. EXPERIMENTAL APPROACH The effects of RF9 were investigated on opioid pharmacological responses including locomotor activity, antinociception, opioid-induced hyperalgesia, rewarding properties and physical dependence. KEY RESULTS RF9 had no effect on morphine-induced horizontal hyperlocomotion and slightly attenuated the decrease induced in vertical activity. Furthermore, RF9 dose-dependently blocked the long-lasting hyperalgesia produced by either acute fentanyl or chronic morphine administration. RF9 also potentiated opiate early analgesic effects and prevented the development of morphine tolerance. Finally, RF9 increased morphine-induced conditioned place preference without producing any rewarding effect by itself and decreased naltrexone-precipitated withdrawal syndrome following chronic morphine treatment. CONCLUSION AND IMPLICATIONS The NPFF system is involved in the development of two major undesirable effects: tolerance and dependence, which are clinically associated with prolonged exposure to opiates. Our findings suggest that NPFF receptors are interesting therapeutic targets to improve the analgesic efficacy of opiates by limiting the development of tolerance, and for the treatment of opioid dependence.

  14. Predictors and moderators of response to enhanced cognitive behaviour therapy and interpersonal psychotherapy for the treatment of eating disorders.

    PubMed

    Cooper, Zafra; Allen, Elizabeth; Bailey-Straebler, Suzanne; Basden, Shawnee; Murphy, Rebecca; O'Connor, Marianne E; Fairburn, Christopher G

    2016-09-01

    Consistent predictors, and more especially moderators, of response to psychological treatments for eating disorders have not been identified. The present exploratory study examined predictors and moderators of outcome in adult patients who took part in a randomised clinical trial comparing two leading treatments for these disorders, enhanced cognitive behavioural therapy (CBT-E) and interpersonal psychotherapy (IPT). Four potentially important findings emerged. Firstly, patients with a longer duration of disorder were less likely to benefit from either treatment. Second, across the two treatments the presence, at baseline, of higher levels of over-evaluation of the importance of shape predicted a less good treatment outcome. Third DSM-IV diagnosis did not predict treatment outcome. Fourth, with the exception of patients with baseline low self-esteem who achieved a better outcome with CBT-E, it was generally not possible to identify a subgroup of patients who would differentially benefit from one or other treatment. PMID:27423373

  15. Dose-response characteristics of nebulized albuterol in the treatment of acutely ill, hospitalized asthmatics.

    PubMed

    Ciccolella, D E; Brennan, K; Kelsen, S G; Criner, G J

    1999-09-01

    We investigated the bronchodilator dose-response to nebulized albuterol and the dose of albuterol which produces maximal bronchodilation in the acutely ill, hospitalized asthmatic. Consecutively admitted patients from the emergency room in status asthmaticus who fulfilled the inclusion criteria (age <41 years old and <12 pack-years of smoking) were studied. Albuterol was administered by nebulizer (Puritan-Bennett Raindrop) in repeated 2.5-mg treatments up to a total dose of 10 mg and the bronchodilator response was measured by a computerized spirometer. Twenty-two patients were studied. Baseline spirometry showed a (mean +/- SE) forced expiratory volume in 1 sec (FEV1) of 1.26 +/- 0.14 L (42 +/- 4.0% predicted), which increased significantly (p < 0.05) during albuterol titration to a maximum FEV1 of 1.70 +/- 0.19 L (57 +/- 5% of predicted). After cumulative doses of 2.5, 5.0, 7.5, and 10.0 mg of nebulized albuterol, 27%, 45%, 72%, and 77% of patients, respectively, attained maximum bronchodilation. The remaining 23% of patients did not respond to doses up to 10 mg of albuterol. The maximum FEV1 response to albuterol did not correlate with the initial severity of airflow obstruction (r = 0.36, p > 0.05). Pulse rate and arterial oxygen saturation were not significantly affected by nebulized albuterol up to a total dose of 10 mg. No arrhythmias were noted. In summary, most hospitalized asthmatics (72%) required a cumulative dose of 7.5 mg of nebulized albuterol to achieve maximum bronchodilation and a large fraction (50%) required higher albuterol doses than the standard 2.5 mg. The bronchodilatory response to nebulized albuterol varied widely among patients in status asthmaticus and could not be predicted from the initial severity of airflow obstruction. Because side effects were minimal, it would be reasonable to use 7.5 mg of nebulized albuterol as initial therapy. Alternatively, dose-response titration with albuterol would be advantageous.

  16. 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

  17. 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

  18. Effective treatment protocol for poor ovarian response: A systematic review and meta-analysis.

    PubMed

    Jeve, Yadava Bapurao; Bhandari, Harish Malappa

    2016-01-01

    Poor ovarian response represents an increasingly common problem. This systematic review was aimed to identify the most effective treatment protocol for poor response. We searched MEDLINE, EMBASE, and The Cochrane Library from 1980 to October 2015. Study quality assessment and meta-analyses were performed according to the Cochrane recommendations. We found 61 trials including 4997 cycles employing 10 management strategies. Most common strategy was the use of gonadotropin-releasing hormone antagonist (GnRHant), and was compared with GnRH agonist protocol (17 trials; n = 1696) for pituitary down-regulation which showed no significant difference in the outcome. Luteinizing hormone supplementation (eight trials, n = 847) showed no difference in the outcome. Growth hormone supplementation (seven trials; n = 251) showed significant improvement in clinical pregnancy rate (CPR) and live birth rate (LBR) with an odds ratio (OR) of 2.13 (95% CI 1.06-4.28) and 2.96 (95% CI 1.17-7.52). Testosterone supplementation (three trials; n = 225) significantly improved CPR (OR 2.4; 95% CI 1.16-5.04) and LBR (OR 2.18; 95% CI 1.01-4.68). Aromatase inhibitors (four trials; n = 223) and dehydroepiandrosterone supplementation (two trials; n = 57) had no effect on outcome. PMID:27382230

  19. 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.

  20. Effective treatment protocol for poor ovarian response: A systematic review and meta-analysis.

    PubMed

    Jeve, Yadava Bapurao; Bhandari, Harish Malappa

    2016-01-01

    Poor ovarian response represents an increasingly common problem. This systematic review was aimed to identify the most effective treatment protocol for poor response. We searched MEDLINE, EMBASE, and The Cochrane Library fro