Exploring the associations between drug side-effects and therapeutic indications.

PubMed

Wang, Fei; Zhang, Ping; Cao, Nan; Hu, Jianying; Sorrentino, Robert

2014-10-01

Drug therapeutic indications and side-effects are both measurable patient phenotype changes in response to the treatment. Inferring potential drug therapeutic indications and identifying clinically interesting drug side-effects are both important and challenging tasks. Previous studies have utilized either chemical structures or protein targets to predict indications and side-effects. In this study, we compared drug therapeutic indication prediction using various information including chemical structures, protein targets and side-effects. We also compared drug side-effect prediction with various information sources including chemical structures, protein targets and therapeutic indication. Prediction performance based on 10-fold cross-validation demonstrates that drug side-effects and therapeutic indications are the most predictive information source for each other. In addition, we extracted 6706 statistically significant indication-side-effect associations from all known drug-disease and drug-side-effect relationships. We further developed a novel user interface that allows the user to interactively explore these associations in the form of a dynamic bipartitie graph. Many relationship pairs provide explicit repositioning hypotheses (e.g., drugs causing postural hypotension are potential candidates for hypertension) and clear adverse-reaction watch lists (e.g., drugs for heart failure possibly cause impotence). All data sets and highly correlated disease-side-effect relationships are available at http://astro.temple.edu/∼tua87106/druganalysis.html. Copyright © 2014 Elsevier Inc. All rights reserved.

Prediction of polypharmacological profiles of drugs by the integration of chemical, side effect, and therapeutic space.

PubMed

Cheng, Feixiong; Li, Weihua; Wu, Zengrui; Wang, Xichuan; Zhang, Chen; Li, Jie; Liu, Guixia; Tang, Yun

2013-04-22

Prediction of polypharmacological profiles of drugs enables us to investigate drug side effects and further find their new indications, i.e. drug repositioning, which could reduce the costs while increase the productivity of drug discovery. Here we describe a new computational framework to predict polypharmacological profiles of drugs by the integration of chemical, side effect, and therapeutic space. On the basis of our previous developed drug side effects database, named MetaADEDB, a drug side effect similarity inference (DSESI) method was developed for drug-target interaction (DTI) prediction on a known DTI network connecting 621 approved drugs and 893 target proteins. The area under the receiver operating characteristic curve was 0.882 ± 0.011 averaged from 100 simulated tests of 10-fold cross-validation for the DSESI method, which is comparative with drug structural similarity inference and drug therapeutic similarity inference methods. Seven new predicted candidate target proteins for seven approved drugs were confirmed by published experiments, with the successful hit rate more than 15.9%. Moreover, network visualization of drug-target interactions and off-target side effect associations provide new mechanism-of-action of three approved antipsychotic drugs in a case study. The results indicated that the proposed methods could be helpful for prediction of polypharmacological profiles of drugs.

[Cardiovascular side effects of non-steroidal anti-inflammatory drugs in the light of recent recommendations. Diclofenac is not more dangerous].

PubMed

Horváth, Viktor József; Tabák, Gy Ádám; Szabó, Gergely; Putz, Zsuzsanna; Koós, Csaba Géza; Lakatos, Péter

2015-03-29

Among their beneficial effects, non-steroidal anti-inflammatory drugs may also exert several side effects which depend on the dosage and the type of these medications. The most frequent gastrointestinal side effects usually develop shortly after the beginning of their administration, but others such as cardiovascular interactions (which are present much less frequently than gastrointestinal side effects) can also occur after the beginning of drug administration without a latency period. For a long-term treatment, non-steroidal anti-inflammatory drugs are most frequently used in the elderly population where patients typically have high cardiovascular risk and take other medicines, e.g. low dose acetylsalicylic acid that can interact with non-steroidal anti-inflammatory drugs; in this aspect diclofenac may cause less side effects. In this review, the authors briefly review cardiovascular side effects of non-steroidal anti-inflammatory drugs, the processes which potentially influence them, therapeutic consequences and their interaction with acetylsalicylic acid.

Integrative relational machine-learning for understanding drug side-effect profiles

PubMed Central

2013-01-01

Background Drug side effects represent a common reason for stopping drug development during clinical trials. Improving our ability to understand drug side effects is necessary to reduce attrition rates during drug development as well as the risk of discovering novel side effects in available drugs. Today, most investigations deal with isolated side effects and overlook possible redundancy and their frequent co-occurrence. Results In this work, drug annotations are collected from SIDER and DrugBank databases. Terms describing individual side effects reported in SIDER are clustered with a semantic similarity measure into term clusters (TCs). Maximal frequent itemsets are extracted from the resulting drug x TC binary table, leading to the identification of what we call side-effect profiles (SEPs). A SEP is defined as the longest combination of TCs which are shared by a significant number of drugs. Frequent SEPs are explored on the basis of integrated drug and target descriptors using two machine learning methods: decision-trees and inductive-logic programming. Although both methods yield explicit models, inductive-logic programming method performs relational learning and is able to exploit not only drug properties but also background knowledge. Learning efficiency is evaluated by cross-validation and direct testing with new molecules. Comparison of the two machine-learning methods shows that the inductive-logic-programming method displays a greater sensitivity than decision trees and successfully exploit background knowledge such as functional annotations and pathways of drug targets, thereby producing rich and expressive rules. All models and theories are available on a dedicated web site. Conclusions Side effect profiles covering significant number of drugs have been extracted from a drug ×side-effect association table. Integration of background knowledge concerning both chemical and biological spaces has been combined with a relational learning method for discovering rules which explicitly characterize drug-SEP associations. These rules are successfully used for predicting SEPs associated with new drugs. PMID:23802887

Integrative relational machine-learning for understanding drug side-effect profiles.

PubMed

Bresso, Emmanuel; Grisoni, Renaud; Marchetti, Gino; Karaboga, Arnaud Sinan; Souchet, Michel; Devignes, Marie-Dominique; Smaïl-Tabbone, Malika

2013-06-26

Drug side effects represent a common reason for stopping drug development during clinical trials. Improving our ability to understand drug side effects is necessary to reduce attrition rates during drug development as well as the risk of discovering novel side effects in available drugs. Today, most investigations deal with isolated side effects and overlook possible redundancy and their frequent co-occurrence. In this work, drug annotations are collected from SIDER and DrugBank databases. Terms describing individual side effects reported in SIDER are clustered with a semantic similarity measure into term clusters (TCs). Maximal frequent itemsets are extracted from the resulting drug x TC binary table, leading to the identification of what we call side-effect profiles (SEPs). A SEP is defined as the longest combination of TCs which are shared by a significant number of drugs. Frequent SEPs are explored on the basis of integrated drug and target descriptors using two machine learning methods: decision-trees and inductive-logic programming. Although both methods yield explicit models, inductive-logic programming method performs relational learning and is able to exploit not only drug properties but also background knowledge. Learning efficiency is evaluated by cross-validation and direct testing with new molecules. Comparison of the two machine-learning methods shows that the inductive-logic-programming method displays a greater sensitivity than decision trees and successfully exploit background knowledge such as functional annotations and pathways of drug targets, thereby producing rich and expressive rules. All models and theories are available on a dedicated web site. Side effect profiles covering significant number of drugs have been extracted from a drug ×side-effect association table. Integration of background knowledge concerning both chemical and biological spaces has been combined with a relational learning method for discovering rules which explicitly characterize drug-SEP associations. These rules are successfully used for predicting SEPs associated with new drugs.

The study of CD side to side error in line/space pattern caused by post-exposure bake effect

NASA Astrophysics Data System (ADS)

Huang, Jin; Guo, Eric; Ge, Haiming; Lu, Max; Wu, Yijun; Tian, Mingjing; Yan, Shichuan; Wang, Ran

2016-10-01

In semiconductor manufacturing, as the design rule has decreased, the ITRS roadmap requires crucial tighter critical dimension (CD) control. CD uniformity is one of the necessary parameters to assure good performance and reliable functionality of any integrated circuit (IC) [1] [2], and towards the advanced technology nodes, it is a challenge to control CD uniformity well. The study of corresponding CD Uniformity by tuning Post-Exposure bake (PEB) and develop process has some significant progress[3], but CD side to side error happening to some line/space pattern are still found in practical application, and the error has approached to over the uniformity tolerance. After details analysis, even though use several developer types, the CD side to side error has not been found significant relationship to the developing. In addition, it is impossible to correct the CD side to side error by electron beam correction as such error does not appear in all Line/Space pattern masks. In this paper the root cause of CD side to side error is analyzed and the PEB module process are optimized as a main factor for improvement of CD side to side error.

Development of Antidepressants as Novel Agents to Treat Small Cell Lung Cancer

DTIC Science & Technology

2015-10-01

in patients based on the recommendation of a psychiatrist that Desipramine would have fewer side - effects than Imipramine and on very early... side effects and no obvious efficacy, even though very few patients were treated), we re-examined the effects of Desipramine in vivo. This took a...imipramine (10mg/kg), Tretament with daily IP inejctions for 30 days at 10mg/kg did not lead to any obvious side effects in mice but did not have a

The association of HIV/AIDS treatment side effects with health status, work productivity, and resource use.

PubMed

daCosta DiBonaventura, Marco; Gupta, Shaloo; Cho, Michelle; Mrus, Joseph

2012-01-01

Due to stable incidence and improved survival rates, there are an increasing number of patients living with HIV/AIDS in the USA. Although highly effective, current antiretroviral therapies are associated with a variety of side effects. The role side effects play on health outcomes has not been fully examined. The current study assessed the association of medication side effects with (1) self-assessed health status; (2) work productivity and activity impairment; and (3) healthcare resource utilization. Data were from a cross-sectional patient-reported survey fielded in the USA using a dual methodology of Internet and paper questionnaires. A total of 953 patients living with HIV/AIDS who were currently taking a medication for their condition were included in the analyses. The most frequent side effects reported by patients were fatigue (70.72%), diarrhea (62.96%), insomnia (58.97%), dizziness (52.78%), neuropathy (52.68%), joint pain (52.36%), nausea (51.63%), and abdominal pain (50.37%). The presence of each side effect was associated with reduced self-assessed health status, increased productivity loss, increased activity impairment, and increased healthcare resource use. Controlling for CD4 cell counts in regression modeling did little to diminish the impact of side effects. Although not all side effects were associated with all outcomes, every side effect was associated with worse health status, some measure of increased work productivity loss, and/or some measure of increased healthcare resource use. Patients are living longer with HIV and, therefore, spending a greater length of time on treatment. The results of the current study suggest that many of these patients are experiencing a wide array of side effects from these therapies. These side effects have demonstrated a profound association with self-assessed health, work productivity, and healthcare resource use. Improved management of these side effects or development of treatments with a better side effect profile may have a substantial humanistic and economic benefit.

Performance of back-primed and factory-finished hardboard lap siding in southern Florida

Treesearch

Charles. Carll; Mark. Knaebe; Vyto. Malinauskas; Peter. Sotos; Anton. TenWolde

2000-01-01

Because of performance problems with hardboard siding in southern Florida, the U.S. Department of Housing and Urban Development (HUD) proposed a local standard requiring prefinishing of siding and priming of all siding surfaces, including the back. However, the effectiveness of these practices was questioned. To determine if back-priming or factory finishing improves...

[Psychoanalysis and Side Effect].

PubMed

Shirahase, Joichiro

2015-01-01

A study of psychoanalysis from the perspective of side effects reveals that its history was a succession of measures to deal with its own side effects. This, however, does not merely suggest that, as a treatment method, psychoanalysis is incomplete and weak: rather, its history is a record of the growth and development of psychoanalysis that discovered therapeutic significance from phenomena that were initially regarded as side effects, made use of these discoveries, and elaborated them as a treatment method. The approach of research seen during the course of these developments is linked to the basic therapeutic approach of psychoanalysis. A therapist therefore does not draw conclusions about a patient's words and behaviors from a single aspect, but continues to make efforts to actively discover a variety of meanings and values from them, and to make the patient's life richer and more productive. This therapeutic approach is undoubtedly one of the unique aspects of psychoanalysis. I discuss the issue of psychoanalysis and side effects with the aim of clarifying this unique characteristic of psychoanalysis. The phenomenon called resistance inevitably emerges during the process of psychoanalytic treatment. Resistance can not only obstruct the progress of therapy; it also carries the risk of causing a variety of disadvantages to the patient. It can therefore be seen as an adverse effect. However, if we re-examine this phenomenon from the perspective of transference, we find that resistance is in fact a crucial tool in psychoanalysis, and included in its main effect, rather than a side effect. From the perspective of minimizing the character of resistance as a side effect and maximizing its character as a main effect, I have reviewed logical organization, dynamic evaluation, the structuring of treatment, the therapist's attitudes, and the training of therapists. I conclude by stating that psychoanalysis has aspects that do not match the perspective known as a side effect.

Relating drug–protein interaction network with drug side effects

PubMed Central

Mizutani, Sayaka; Pauwels, Edouard; Stoven, Véronique; Goto, Susumu; Yamanishi, Yoshihiro

2012-01-01

Motivation: Identifying the emergence and underlying mechanisms of drug side effects is a challenging task in the drug development process. This underscores the importance of system–wide approaches for linking different scales of drug actions; namely drug-protein interactions (molecular scale) and side effects (phenotypic scale) toward side effect prediction for uncharacterized drugs. Results: We performed a large-scale analysis to extract correlated sets of targeted proteins and side effects, based on the co-occurrence of drugs in protein-binding profiles and side effect profiles, using sparse canonical correlation analysis. The analysis of 658 drugs with the two profiles for 1368 proteins and 1339 side effects led to the extraction of 80 correlated sets. Enrichment analyses using KEGG and Gene Ontology showed that most of the correlated sets were significantly enriched with proteins that are involved in the same biological pathways, even if their molecular functions are different. This allowed for a biologically relevant interpretation regarding the relationship between drug–targeted proteins and side effects. The extracted side effects can be regarded as possible phenotypic outcomes by drugs targeting the proteins that appear in the same correlated set. The proposed method is expected to be useful for predicting potential side effects of new drug candidate compounds based on their protein-binding profiles. Supplementary information: Datasets and all results are available at http://web.kuicr.kyoto-u.ac.jp/supp/smizutan/target-effect/. Availability: Software is available at the above supplementary website. Contact: yamanishi@bioreg.kyushu-u.ac.jp, or goto@kuicr.kyoto-u.ac.jp PMID:22962476

Novel Molecular Strategies and Targets for Opioid Drug Discovery for the Treatment of Chronic Pain

PubMed Central

Olson, Keith M.; Lei, Wei; Keresztes, Attila; LaVigne, Justin; Streicher, John M.

2017-01-01

Opioid drugs like morphine and fentanyl are the gold standard for treating moderate to severe acute and chronic pain. However, opioid drug use can be limited by serious side effects, including constipation, tolerance, respiratory suppression, and addiction. For more than 100 years, we have tried to develop opioids that decrease or eliminate these liabilities, with little success. Recent advances in understanding opioid receptor signal transduction have suggested new possibilities to activate the opioid receptors to cause analgesia, while reducing or eliminating unwanted side effects. These new approaches include designing functionally selective ligands, which activate desired signaling cascades while avoiding signaling cascades that are thought to provoke side effects. It may also be possible to directly modulate downstream signaling through the use of selective activators and inhibitors. Separate from downstream signal transduction, it has also been found that when the opioid system is stimulated, various negative feedback systems are upregulated to compensate, which can drive side effects. This has led to the development of multi-functional molecules that simultaneously activate the opioid receptor while blocking various negative feedback receptor systems including cholecystokinin and neurokinin-1. Other novel approaches include targeting heterodimers of the opioid and other receptor systems which may drive side effects, and making endogenous opioid peptides druggable, which may also reduce opioid mediated side effects. Taken together, these advances in our molecular understanding provide a path forward to break the barrier in producing an opioid with reduced or eliminated side effects, especially addiction, which may provide relief for millions of patients. PMID:28356897

What side effects are problematic for patients prescribed antipsychotic medication? The Maudsley Side Effects (MSE) measure for antipsychotic medication.

PubMed

Wykes, T; Evans, J; Paton, C; Barnes, T R E; Taylor, D; Bentall, R; Dalton, B; Ruffell, T; Rose, D; Vitoratou, S

2017-10-01

Capturing service users' perspectives can highlight additional and different concerns to those of clinicians, but there are no up to date, self-report psychometrically sound measures of side effects of antipsychotic medications. Aim To develop a psychometrically sound measure to identify antipsychotic side effects important to service users, the Maudsley Side Effects (MSE) measure. An initial item bank was subjected to a Delphi exercise (n = 9) with psychiatrists and pharmacists, followed by service user focus groups and expert panels (n = 15) to determine item relevance and language. Feasibility and comprehensive psychometric properties were established in two samples (N43 and N50). We investigated whether we could predict the three most important side effects for individuals from their frequency, severity and life impact. MSE is a 53-item measure with good reliability and validity. Poorer mental and physical health, but not psychotic symptoms, was related to side-effect burden. Seventy-nine percent of items were chosen as one of the three most important effects. Severity, impact and distress only predicted 'putting on weight' which was more distressing, more severe and had more life impact in those for whom it was most important. MSE is a self-report questionnaire that identifies reliably the side-effect burden as experienced by patients. Identifying key side effects important to patients can act as a starting point for joint decision making on the type and the dose of medication.

Flow processes in overexpanded chemical rocket nozzles. Part 2: Side loads due to asymmetric separation

NASA Technical Reports Server (NTRS)

Schmucker, R. H.

1984-01-01

Methods for measuring the lateral forces, occurring as a result of asymmetric nozzle flow separation, are discussed. The effect of some parameters on the side load is explained. A new method was developed for calculation of the side load. The values calculated are compared with side load data of the J-2 engine. Results are used for predicting side loads of the space shuttle main engine.

Discovery of Boolean metabolic networks: integer linear programming based approach.

PubMed

Qiu, Yushan; Jiang, Hao; Ching, Wai-Ki; Cheng, Xiaoqing

2018-04-11

Traditional drug discovery methods focused on the efficacy of drugs rather than their toxicity. However, toxicity and/or lack of efficacy are produced when unintended targets are affected in metabolic networks. Thus, identification of biological targets which can be manipulated to produce the desired effect with minimum side-effects has become an important and challenging topic. Efficient computational methods are required to identify the drug targets while incurring minimal side-effects. In this paper, we propose a graph-based computational damage model that summarizes the impact of enzymes on compounds in metabolic networks. An efficient method based on Integer Linear Programming formalism is then developed to identify the optimal enzyme-combination so as to minimize the side-effects. The identified target enzymes for known successful drugs are then verified by comparing the results with those in the existing literature. Side-effects reduction plays a crucial role in the study of drug development. A graph-based computational damage model is proposed and the theoretical analysis states the captured problem is NP-completeness. The proposed approaches can therefore contribute to the discovery of drug targets. Our developed software is available at " http://hkumath.hku.hk/~wkc/APBC2018-metabolic-network.zip ".

"Side effects" of ECT are mainly depressive phenomena and are independent of age.

PubMed

Brodaty, H; Berle, D; Hickie, I; Mason, C

2001-10-01

The aetiology of reported side effects of electroconvulsive therapy (ECT) is unclear. We examined the interaction of depression and age on adverse neuropsychological and putative side effects of ECT. Inpatients (N=81; median age 70 years) with major depression were assessed prospectively pre-ECT, immediately post-ECT and 1-3 years later. Patients were administered the Hamilton Rating Scale for Depression (HRSD), the Global Assessment of Functioning scale (GAF) and neuropsychological tests from the Wechsler Memory Scale. Side effects and total burden scores were rated pre- and post-treatment. HRSD and GAF scores improved with treatment after ECT, but the prevalence and total burden of side effects were unchanged. Side effect burden was related to depression level before and after ECT. Improvement in depression correlated with reduction in side effect burden. There was a significant decline in side effect burden after controlling for change in depression. Patients' scores on neuropsychological measures did not appear to change after ECT or between pre-ECT and follow-up. Re-analysis, allowing for age, chronicity of depression, medication use and development of dementia, did not alter the findings. lack of a control group, lack of information on ECT technique, incomplete data sets and limited neuropsychological testing. ECT, an effective treatment for depression, does not cause significant side effects or neuropsychological impairment, which are more likely to be depressive phenomena. ECT appears to be safe for old (> or =65 years) and very old (> or =75 years) patients, who do not appear to be more susceptible to adverse effects.

Sediment sorting at a side channel bifurcation

NASA Astrophysics Data System (ADS)

van Denderen, Pepijn; Schielen, Ralph; Hulscher, Suzanne

2017-04-01

Side channels have been constructed to reduce the flood risk and to increase the ecological value of the river. In various Dutch side channels large aggradation in these channels occurred after construction. Measurements show that the grain size of the deposited sediment in the side channel is smaller than the grain size found on the bed of the main channel. This suggest that sorting occurs at the bifurcation of the side channel. The objective is to reproduce with a 2D morphological model the fining of the bed in the side channel and to study the effect of the sediment sorting on morphodynamic development of the side channel. We use a 2D Delft3D model with two sediment fractions. The first fraction corresponds with the grain size that can be found on the bed of the main channel and the second fraction corresponds with the grain size found in the side channel. With the numerical model we compute several side channel configurations in which we vary the length and the width of the side channel, and the curvature of the upstream channel. From these computations we can derive the equilibrium state and the time scale of the morphodynamic development of the side channel. Preliminary results show that even when a simple sediment transport relation is used, like Engelund & Hansen, more fine sediment enters the side channel than coarse sediment. This is as expected, and is probably related to the bed slope effects which are a function of the Shields parameter. It is expected that by adding a sill at the entrance of the side channel the slope effect increases. This might reduce the amount of coarse sediment which enters the side channel even more. It is unclear whether the model used is able to reproduce the effect of such a sill correctly as modelling a sill and reproducing the correct hydrodynamic and morphodynamic behaviour is not straightforward in a 2D model. Acknowledgements: This research is funded by STW, part of the Dutch Organization for Scientific Research under grant number P12-P14 (RiverCare Perspective Programme) project number 13516.

Dissatisfaction with opioid maintenance treatment partly explains reported side effects of medications.

PubMed

Muller, Ashley Elizabeth; Bjørnestad, Ronny; Clausen, Thomas

2018-03-29

Drop-out is a core problem in opioid maintenance treatment (OMT), but patients' reactions to and acceptance of the various OMT medications are insufficiently investigated. In Norway, there has been vocal patient resistance to the newest medication, buprenorphine-naloxone (BNX), and complaints have focused on the side effect profile. There has been no comparison of patient satisfaction and side effects of the three most common OMT medications. To compare patient satisfaction with OMT and side effects of BNX, buprenorphine monopreparate (BUP), and methadone (MET) as reported by patients. Data were drawn from a national peer-to-peer survey developed by a patient advocacy group. The survey engaged more than 1000 OMT patients, corresponding to one seventh of OMT patients in Norway. The associations between side effects, treatment satisfaction, and patient characteristics were tested in multinomial logistic regressions. High patient satisfaction with OMT overall was reported despite lower satisfaction with medication itself and widely prevalent side effects. Among each medication group, dissatisfaction with medications or OMT in general along with poor health status increased the relative risk ratio of reporting the heaviest side effect burden. MET users reported the highest side effect burden and BNX users the lightest, but BNX users were more dissatisfied with their medication. Side effects are a concern for nearly all OMT patients, and they do not appear to accumulate with age or length of treatment. BNX users' dissatisfaction with their medication is of particular concern, and expectations and preferences of medication may be influencing their dissatisfaction. Copyright © 2018. Published by Elsevier B.V.

Fractional ablative laser skin resurfacing: a review.

PubMed

Tajirian, Ani L; Tarijian, Ani L; Goldberg, David J

2011-12-01

Ablative laser technology has been in use for many years now. The large side effect profile however has limited its use. Fractional ablative technology is a newer development which combines a lesser side effect profile along with similar efficacy. In this paper we review fractional ablative laser skin resurfacing.

Ocular side effects of biological agents in oncology: what should the clinician be aware of?

PubMed Central

Hager, Tobias; Seitz, B

2014-01-01

During the last 20 years, biologicals have become increasingly relevant in oncologic therapy. Depending on the medication used, there are different profiles of ocular side effects. Although these can be present in up to 70% of patients, they are generally underreported in the literature. Therefore, the pathophysiological details of their development are often poorly understood. Herein we attempt to identify groups of biologicals to which a specific side effect profile can be assigned. We also tried to capture all relevant side effects and therefore conducted several database investigation including Medline, Cochrane library, and the drugs section of the US Food and Drug Administration (FDA), using the following search strings: “name of biological agent (both generic and commercial names)” AND “eye” OR “ocular”. If we found a side effect that has been associated with a drug, we researched Medline using the following search string: “name of biological agent” (both generic and commercial names) AND “term for the specific side effect”. Due to the wealth of material we report only the drugs that are approved by the FDA. PMID:24391443

Development of a New Self-Reporting Instrument Measuring Benefits and Side Effects of Corticosteroids in Duchenne Muscular Dystrophy: Report from a Pilot Study.

PubMed

Hendriksen, Ruben G F; Lionarons, Judith M; Hendriksen, Jos G M; Vles, Johan S H; McAdam, Laura C; Biggar, W Douglas

There is no cure for Duchenne Muscular Dystrophy (DMD); treatment is symptomatic and corticosteroids slow the progression. Side effects of corticosteroids - especially the physical effects - have been described, however patients' and caregivers perception on chronic corticosteroid treatment and their side effects is less well known, in particular with regards to cognition, behaviour, and emotional functioning. The primary aim of this pilot study was to (i) construct a self-report questionnaire to assess the perceived benefits and side effects of corticosteroids for patients with DMD and their parents. Furthermore we aimed to (ii) investigate the psychometric qualities of this questionnaire, (iii) whether there was a difference between parents' and patient's perceptions, and finally (iv) to what extent reported side effects may alter over time. A 23-item questionnaire (SIDECORT: side effect of corticosteroids) was constructed to assess the perception of these benefits and side effects in a systematic manner. In total, 86 patients (aged 5 - 28 years) and 125 of their parents completed the questionnaire. Internal consistency was good. Using factor analyses on the side effect items as reported by parents, two underlying factors were found, with the first factor describing cognitive, behavioural and emotional functioning, and the second factor describing physical functioning. The potential benefits of corticosteroids were highly rated among both parents and patients, although parents rated the importance of the benefits higher than their sons (p = 0.002). Similarly, parents rated the severity of the side effects generally higher than their sons (p = 0.011), especially with regards to the physical side effects (p = 0.014). Based on the parent's perception, the neurodevelopmental side effects generally appeared to decline the longer corticosteroids were used. To our knowledge, this is the first explicit study on perceived cognitive-, behavioural-, and emotional side effects and the allocation of benefits to corticosteroids in DMD. On the basis of our research we suggest a short form questionnaire, which proves to be reliable and valid for research- and clinical practice. This questionnaire could provide useful insights for the care of boys and men with DMD.

Leukopenia and neutropenia induced by quetiapine.

PubMed

Cowan, Colin; Oakley, Clare

2007-01-30

Leukopenia and neutropenia are recognised as side effects of antipsychotic medication, notably clozapine. A case is presented in which a female Caucasian patient who had previously developed these side effects with clozapine also developed them with quetiapine in conjunction with semisodium valproate. There was no such reaction to zuclopenthixol, sulpiride, olanzapine and aripiprazole. It is concluded that caution should be exercised when treating with quetiapine especially where there has been neutropenia with a previous antipsychotic agent.

Anxiety Sensitivity and Nicotine Replacement Therapy Side Effects: Examining the Role of Emotion Dysregulation Among Treatment-Seeking Smokers.

PubMed

Zvolensky, Michael J; Paulus, Daniel J; Garey, Lorra; Raines, Amanda M; Businelle, Michael; Shankman, Stewart A; Manning, Kara; Goodwin, Renee D; Schmidt, Norman B

2017-11-01

Nicotine replacement therapy (NRT) significantly increases the likelihood of quit success at least over the short term, yet some smokers prematurely discontinue use. NRT side effects are often cited as the primary reason for medication discontinuation. The current study examined a theoretical pathway by which two smoking-related emotional vulnerabilities (anxiety sensitivity and emotion dysregulation) were related to the number of NRT (nicotine patch) side effects reported 1 week following a scheduled quit attempt. It was hypothesized that anxiety sensitivity would have an indirect effect on NRT side effects through emotion dysregulation. A total of 179 treatment-seeking, adult daily smokers with elevated anxiety sensitivity (47.5% male; M age = 39.73 years, SD = 13.87) were enrolled in a smoking cessation trial. Covariate-adjusted analyses provided support for the hypothesized pathway, such that emotion dysregulation explained the association between anxiety sensitivity and NRT side effects (b = 0.02, SE = 0.01, 95% CI [0.002, 0.03]; completely standardized estimate = .15). The findings underscore the importance of developing cessation treatments that incorporate techniques to enhance emotion regulation, particularly among smokers higher in anxiety sensitivity, to decrease the risk of NRT side effects.

Two-sided friction stir riveting by extrusion: A process for joining dissimilar materials

DOE PAGES

Evans, William T.; Cox, Chase D.; Strauss, Alvin M.; ...

2016-06-25

Two-sided friction stir riveting (FSR) by extrusion is an innovative process developed to rapidly, efficiently, and securely join dissimilar materials. This process extends a previously developed one sided friction stir extrusion process to create a strong and robust joint by producing a continuous, rivet-like structure through a preformed hole in one of the materials with a simultaneous, two-sided friction stir spot weld. The two-sided FSR by extrusion process securely joins the dissimilar materials together and effectively locks them in place without the use of any separate materials or fasteners. Lastly, in this paper we demonstrate the process by joining aluminummore » to steel and illustrate its potential application to automotive and aerospace manufacturing processes.« less

[Prevention of side effects and complications after operation for partial ileal bypass].

PubMed

Mirchuk, K K; Sedletskiĭ, Iu I

2014-01-01

Side effects and complications of the application of partial ileal bypass used for dislipidemia were analyzed in 162 patients with atherosclerosis. It was shown, that the partial ileal bypass operation could lead to the development of series of undesirable side effects such as diarrhea, hypovitaminosis B12, off-state intestine enteritis. The application of modification of partial ileal bypass such as formation of ileo-ileoanastomosis 5-6 cm long near ileocecal valve with the maintenance of its functions disposed the diarrhea and minimized the risk of the development of hypovitaminosis B12 after operation. It is possible to prevent the development of enteritis of off-state loop of the small intestine by using microanastomosis between off-state and functioning iliac intestine. The partial ileal bypass operation didn't influence on body weight, wouldn't increase the risk of stone formation in the gallbladder and kidneys. The risk of the development of hypovitaminosis B12 is minimal after operation.

General equilibrium effects of a supply side GHG mitigation option under the Clean Development Mechanism.

PubMed

Timilsina, Govinda R; Shrestha, Ram M

2006-09-01

The Clean Development Mechanism (CDM) under the Kyoto Protocol to the United Nations Framework Convention on Climate Change is considered a key instrument to encourage developing countries' participation in the mitigation of global climate change. Reduction of greenhouse gas (GHG) emissions through the energy supply and demand side activities are the main options to be implemented under the CDM. This paper analyses the general equilibrium effects of a supply side GHG mitigation option-the substitution of thermal power with hydropower--in Thailand under the CDM. A static multi-sector general equilibrium model has been developed for the purpose of this study. The key finding of the study is that the substitution of electricity generation from thermal power plants with that from hydropower plants would increase economic welfare in Thailand. The supply side option would, however, adversely affect the gross domestic product (GDP) and the trade balance. The percentage changes in economic welfare, GDP and trade balance increase with the level of substitution and the price of certified emission reduction (CER) units.

A survey of the awareness, knowledge and behavior of hair dye use in a korean population with gray hair.

PubMed

Kim, Jung Eun; Jung, Hee Dam; Kang, Hoon

2012-08-01

Gray hair naturally develops in the process of human aging. Many people with gray hair periodically dye their hair. Hair dyeing products are widely used and they can cause adverse effects. Therefore, the user's knowledge and recognition about hair dyeing and related side effects are important. The goal of this study was to lay the foundation for understanding, preventing and treating side effects caused by hair coloring products. We conducted a questionnaire survey for adult males and females aged over 20 who had gray hair. A total of 500 subjects were included in this study and statistical analysis was performed. Large numbers of the people who had experience with hair dye (233 out of 319 people, 73.0%) did not know about the exact brand name of the hair dye product that they were using. Of 319 hair dye users, 23.8% (76 out of 319) people stated that they experienced side effects. Despite the occurrence of side effects from hair dyeing products, it seems they did not realize the seriousness of the side effects or the need for treatment. It is advisable to introduce a system that enables users to become aware of the ingredients and side effects of hair coloring products and give opportunities for users to become aware of the side effects of hair coloring through education, publicity and publication of an informational booklet.

Women with breast cancer report substantially more disease- and treatment-related side or late effects than registered by clinical oncologists: a cross-sectional study of a standard follow-up program in an oncological department.

PubMed

Ellegaard, Mai-Britt Bjørklund; Grau, Cai; Zachariae, Robert; Jensen, Anders Bonde

2017-08-01

Follow-up after breast cancer treatment is standard due to the risk of development of new primary cancers and recurrent disease. The aim of the present study was to evaluate a standard follow-up program in an oncological department by assessing: (1) Symptoms or signs of new primary cancer or recurrent disease, (2) Disease- and treatment-related physical and psychosocial side or late effects, and (3) relevant actions by oncology staff. In a cross-sectional study, 194 women who came for follow-up visit after treatment for primary surgery were included. The clinical oncologists registered symptoms and signs of recurrent disease or new primary cancer. Side or late effects were both assessed by patient and the clinical oncologists. Loco-regional or distant signs of recurrent disease were suspected in eight (5%) patients. Further examinations revealed no disease recurrence. Most patients (93%) reported some degree of side or late effects. Statistically significant more side or late effects were reported by the women (average: 6.9) than registered by the clinical oncologists (average: 2.4), p < 0.001. The three most often patient-reported side or late effects were hot flushes (35%), fatigue (32%), and sleep disturbance (31%). None of the scheduled or additional visits resulted in detection of recurrent disease. Furthermore, the majority of patients reported side or late effects. Statistically significant more women reported side or late effects than registered by the clinical oncologists. This suggests the need for rethinking of the follow-up programs with more emphasis upon side or late effects of the treatment.

The dark side of browning.

PubMed

Tamucci, Kirstin A; Namwanje, Maria; Fan, Lihong; Qiang, Li

2018-02-01

The induction of brown-like adipocyte development in white adipose tissue (WAT) confers numerous metabolic benefits by decreasing adiposity and increasing energy expenditure. Therefore, WAT browning has gained considerable attention for its potential to reverse obesity and its associated co-morbidities. However, this perspective has been tainted by recent studies identifying the detrimental effects of inducing WAT browning. This review aims to highlight the adverse outcomes of both overactive and underactive browning activity, the harmful side effects of browning agents, as well as the molecular brake-switch system that has been proposed to regulate this process. Developing novel strategies that both sustain the metabolic improvements of WAT browning and attenuate the related adverse side effects is therefore essential for unlocking the therapeutic potential of browning agents in the treatment of metabolic diseases.

Managing the oral side-effects of medications used to treat multiple sclerosis.

PubMed

Cockburn, N; Pateman, K; Taing, M W; Pradhan, A; Ford, P J

2017-09-01

Many medications used to manage multiple sclerosis (MS) affect oral health. This review aimed to identify the oral side-effects of the current drugs recommended in Australia to treat MS and make dental practitioners aware of the range of symptoms. The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat MS. For each medication, the generic name, class, route of administration, dosage and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (MIMs) database. Meyler's Side-effect of Drugs Encyclopaedia was used to identify any additional oral adverse reactions to medications used to treat MS. Fourteen drugs were identified for the treatment of MS progression and 13 drugs for the treatment of MS symptoms. For these medications, 18 oral side-effects were documented: xerostomia was the most common, followed by dysgeusia, dysphagia, mouth ulceration and sinusitis. Anticholinergic drugs caused xerostomia while immunosuppressants resulted in more infection-related side-effects. Dental practitioners should be aware of the range of symptoms likely to be reported by this population. Clinicians are encouraged to continue providing dental care for their patients who develop MS and refer complex cases to specialists. © 2017 Australian Dental Association.

Systematic review of genuine versus spurious side-effects of beta-blockers in heart failure using placebo control: Recommendations for patient information☆☆☆

PubMed Central

Barron, Anthony J.; Zaman, Nabeela; Cole, Graham D.; Wensel, Roland; Okonko, Darlington O.; Francis, Darrel P.

2013-01-01

Background Patients trying life-preserving agents such as beta-blockers may be discouraged by listings of harmful effects provided in good faith by doctors, drug information sheets, and media. We systematically review the world experience of side-effect information in blinded, placebo-controlled beta-blockade in heart failure. We present information for a physician advising a patient experiencing an unwanted symptom and suspecting the drug. Methods We searched Medline for double-blinded randomized trials of beta-blocker versus placebo in heart failure reporting side-effects. We calculated, per 100 patients reporting the symptom on beta-blockade, how many would have experienced it on placebo: the “proportion of symptoms non-pharmacological”. Results 28 of the 33 classically-described side-effects are not significantly more common on beta-blockers than placebo. Of the 100 patients developing dizziness on beta-blockers, 81 (95% CI 73–89) would have developed it on placebo. For diarrhoea this proportion is 82/100 (70–95), and hyperglycaemia 83/100 (68–98). For only two side-effects is this under half (i.e. predominantly due to beta-blocker): bradycardia (33/100, CI 21–44) and intermittent claudication (41/100, 2–81). At least 6 so-called side-effects are less common on beta-blocker than placebo, including depression (reduced by 35%, p < 0.01) and insomnia (by 27%, p = 0.01). Conclusions Clinicians might reconsider whether it is scientifically and ethically correct to warn a patient that a drug might cause them a certain side-effect, when randomized controlled trials show no significant increase, or indeed a significant reduction. A better informed consultation could, in patients taking beta-blockers, alleviate suffering. In patients who might otherwise not take the drug, it might prevent deaths. PMID:23796325

Factors associated with current and severe physical side-effects after prostate cancer treatment: What men report.

PubMed

Steentjes, L; Siesling, S; Drummond, F J; van Manen, J G; Sharp, L; Gavin, A

2018-01-01

We identified patient and disease characteristics associated with (1) "current" physical side-effects of any severity; and (2) "severe" physical side-effects "ever" experienced by 3,348 (54%) prostate cancer (PCa) survivors in Ireland diagnosed 2-18 years previously. Postal questionnaires collected symptoms at diagnosis, post-biopsy complications, comorbidities, primary treatments and physical side-effects post-treatment (urinary incontinence, erectile dysfunction, libido loss, bowel problems, breast changes, hot flushes, and fatigue, "ever" and "current" at time of questionnaire completion). Men were grouped by "early" (localised) and "late" (locally advanced/advanced) disease at diagnosis. Multivariable logistic regression analysis identified patient and disease-related factors associated with post-treatment side-effects. Complications post-biopsy were associated with higher risk of "current" libido loss and impotence. Radical prostatectomy was associated with higher risk of "current" and "severe" incontinence, libido loss and impotence in both early and late disease. In early disease, brachytherapy was associated with lower risk of "current" fatigue and "severe" impotence. Comorbidities were associated with higher risk of "current" experience of four side-effects (incontinence, libido loss, bowel problems, fatigue). Men on active surveillance/watchful-waiting reported lower risk of sexual dysfunction. These findings could inform development of tailored information on side-effects, which, in turn, could inform treatment decision-making and post-treatment monitoring. © 2016 John Wiley & Sons Ltd.

Developmental neurotoxicity of succeeding generations of insecticides

PubMed Central

Abreu-Villaça, Yael; Levin, Edward D.

2016-01-01

Insecticides are by design toxic. They must be toxic to effectively kill target species of insects. Unfortunately, they also have off-target toxic effects that can harm other species, including humans. Developmental neurotoxicity is one of the most prominent off-target toxic risks of insecticides. Over the past seven decades several classes of insecticides have been developed, each with their own mechanisms of effect and toxic side effects. This review covers the developmental neurotoxicity of the succeeding generations of insecticides including organochlorines, organophosphates, pyrethroids, carbamates and neonicotinoids. The goal of new insecticide development is to more effectively kill target species with fewer toxic side effects on non-target species. From the experience with the developmental neurotoxicity caused by the generations of insecticides developed in the past advice is offered how to proceed with future insecticide development to decrease neurotoxic risk. PMID:27908457

The treatment of Parkinson's disease with deep brain stimulation: current issues.

PubMed

Moldovan, Alexia-Sabine; Groiss, Stefan Jun; Elben, Saskia; Südmeyer, Martin; Schnitzler, Alfons; Wojtecki, Lars

2015-07-01

Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients' mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.

Positive Side Effects of a Job-Related Training Program for Older Adults in South Korea

ERIC Educational Resources Information Center

Lee, Minhong; Choi, Jae-Sung

2012-01-01

The objective of the current study was to evaluate empirically positive side effects of a job-related training program on older adults' self-esteem, depression, and social networks. A total of 70 older adults participated in the study after completing the Older Paraprofessional Training Program developed and provided by the Continuing Education…

Monitoring Metabolic Side Effects of Atypical Antipsychotics in People with an Intellectual Disability

ERIC Educational Resources Information Center

Teeluckdharry, Sadira; Sharma, Sujit; O'Rourke, Elizabeth; Tharian, Priyanka; Gondalekar, Anjali; Nainar, Feroz; Roy, Meera

2013-01-01

This audit was undertaken prospectively to examine the compliance of a group of psychiatrists against guidelines they developed for monitoring the onset of metabolic syndrome, a potential side effect of antipsychotic medication, especially second generation or atypical ones. Phase 1 of the audit was to set standards by a questionnaire survey of…

Low Voltage Activated Calcium Channels - Their Role in HER2 Driven Breast Cancer and Potential as a New Therapeutic Target

DTIC Science & Technology

2016-10-01

combined with chemotherapy , but chemotherapy causes undesirable side effects due to off-target effects on normal tissue, which diminishes quality of life...highest response rates when combined with chemotherapy , but chemotherapy causes undesirable side effects due to off-target effects on normal...patients. Therefore, the overall goal of this proposal is to develop a tumor-specific, safe and effective therapy for breast cancer. We concentrate on

A Diffusion Model for Two-sided Service Systems

NASA Astrophysics Data System (ADS)

Homma, Koichi; Yano, Koujin; Funabashi, Motohisa

A diffusion model is proposed for two-sided service systems. ‘Two-sided’ refers to the existence of an economic network effect between two different and interrelated groups, e.g., card holders and merchants in an electronic money service. The service benefit for a member of one side depends on the number and quality of the members on the other side. A mathematical model by J. H. Rohlfs explains the network (or bandwagon) effect of communications services. In Rohlfs' model, only the users' group exists and the model is one-sided. This paper extends Rohlfs' model to a two-sided model. We propose, first, a micro model that explains individual behavior in regard to service subscription of both sides and a computational method that drives the proposed model. Second, we develop macro models with two diffusion-rate variables by simplifying the micro model. As a case study, we apply the models to an electronic money service and discuss the simulation results and actual statistics.

The Other Side of the Story: Israeli and Palestinian Teachers Write a History Textbook Together

ERIC Educational Resources Information Center

Steinberg, Shoshana; Bar-On, Dan

2009-01-01

In this essay, Shoshana Steinberg and Dan Bar-On present the work of a team of Israeli and Palestinian teachers who developed a history textbook that includes both groups' narratives of the same events side by side. These teachers then tested the effects of its use in both Israeli and Palestinian classrooms; for the first time, students on each…

Quantitative prediction of drug side effects based on drug-related features.

PubMed

Niu, Yanqing; Zhang, Wen

2017-09-01

Unexpected side effects of drugs are great concern in the drug development, and the identification of side effects is an important task. Recently, machine learning methods are proposed to predict the presence or absence of interested side effects for drugs, but it is difficult to make the accurate prediction for all of them. In this paper, we transform side effect profiles of drugs as their quantitative scores, by summing up their side effects with weights. The quantitative scores may measure the dangers of drugs, and thus help to compare the risk of different drugs. Here, we attempt to predict quantitative scores of drugs, namely the quantitative prediction. Specifically, we explore a variety of drug-related features and evaluate their discriminative powers for the quantitative prediction. Then, we consider several feature combination strategies (direct combination, average scoring ensemble combination) to integrate three informative features: chemical substructures, targets, and treatment indications. Finally, the average scoring ensemble model which produces the better performances is used as the final quantitative prediction model. Since weights for side effects are empirical values, we randomly generate different weights in the simulation experiments. The experimental results show that the quantitative method is robust to different weights, and produces satisfying results. Although other state-of-the-art methods cannot make the quantitative prediction directly, the prediction results can be transformed as the quantitative scores. By indirect comparison, the proposed method produces much better results than benchmark methods in the quantitative prediction. In conclusion, the proposed method is promising for the quantitative prediction of side effects, which may work cooperatively with existing state-of-the-art methods to reveal dangers of drugs.

Radiogenic Side Effects After Hypofractionated Stereotactic Photon Radiotherapy of Choroidal Melanoma in 212 Patients Treated Between 1997 and 2007

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

Dunavoelgyi, Roman; Dieckmann, Karin; Gleiss, Andreas

2012-05-01

Purpose: To evaluate side effects of hypofractionated stereotactic photon radiotherapy for patients with choroidal melanoma. Patients and Methods: Two hundred and twelve patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at the Medical University of Vienna between 1997 and 2007 with a Linac with 6-MV photon beams in five fractions with 10, 12, or 14 Gy per fraction. Examinations for radiogenic side effects were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and then once a year thereafter until 10 years after radiotherapy.more » Adverse side effects were assessed using slit-lamp examination, funduscopy, gonioscopy, tonometry, and, if necessary, fundus photography and fluorescein angiography. Evaluations of incidence of side effects are based on an actuarial analysis. Results: One hundred and eighty-nine (89.2%) and 168 (79.2%) of the tumors were within 3 mm of the macula and the optic disc, respectively. The five most common radiotherapy side effects were retinopathy and optic neuropathy (114 cases and 107 cases, respectively), cataract development (87 cases), neovascular glaucoma (46 cases), and corneal epithelium defects (41 cases). In total, 33.6%, 38.5%, 51.2%, 75.5%, and 77.6% of the patients were free of any radiation retinopathy, optic neuropathy, cataract, neovascular glaucoma, or corneal epithelium defects 5 years after radiotherapy, respectively. Conclusion: In centrally located choroidal melanoma hypofractionated stereotactic photon radiotherapy shows a low to moderate rate of adverse long-term side effects comparable with those after proton beam radiotherapy. Future fractionation schemes should seek to further reduce adverse side effects rate while maintaining excellent local tumor control.« less

The treatment of Parkinson's disease with deep brain stimulation: current issues

PubMed Central

Moldovan, Alexia-Sabine; Groiss, Stefan Jun; Elben, Saskia; Südmeyer, Martin; Schnitzler, Alfons; Wojtecki, Lars

2015-01-01

Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients’ mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation. PMID:26330809

Do the frequencies of adverse events increase, decrease, or stay the same with long-term use of statins?

PubMed

Huddy, Karlyn; Dhesi, Pavittarpaul; Thompson, Paul D

2013-02-01

Statins are widely used for their cholesterol-lowering properties and proven reduction of cardiovascular disease risk. Many patients take statins as long-term treatment for a variety of conditions without a clear-cut understanding of how treatment duration affects the frequency of adverse effects. We aimed to evaluate whether the frequencies of documented adverse events increase, decrease, or remain unchanged with long-term statin use. We reviewed the established literature to define the currently known adverse effects of statin therapy, including myopathy, central nervous system effects, and the appearance of diabetes, and the frequency of these events with long-term medication use. The frequency of adverse effects associated with long-term statin therapy appears to be low. Many patients who develop side effects from statin therapy do so relatively soon after initiation of therapy, so the frequency of side effects from statin therapy when expressed as a percentage of current users decreases over time. Nevertheless, patients may develop side effects such as muscle pain and weakness years after starting statin therapy; however, the absolute number of patients affected by statin myopathy increases with treatment duration. Also, clinical trials of statin therapy rarely exceed 5 years, so it is impossible to determine with certainty the frequency of long-term side effects with these drugs.

Analgesic Prodrugs for Combating their Side-Effects: Rational Approach.

PubMed

Ruchita; Sucheta; Nanda, Sanju; Pathak, Dharampal

2017-01-01

Analgesics are the drugs which bring insensibility to pain without loosing consciousness. Treatment strategy is generally based on the type of pain. Most of the analgesics are associated with serious side effects, such as NSAIDS can cause severe GI disturbance and opioids can cause addiction. There are various ways to reduce their side effects The analgesic prodrug approach is one of the several strategies used to attain the required pharmacological response with a considerable decrease in side effects. The aim of this paper is to introduce in depth the rational behind the use of the analgesic prodrug approach from past to present. Data is collected from online as well as from extensive literature survey which have appeared on this subject during the last decades. This review will map the origins and development of the most important of the analgesic prodrugs to date. This review indicates that, designing analgesic prodrugs represent successful strategy to gain the required pharmacological activity with a considerable decrease in side effects. However thorough knowledge of diverse biological phenomena is needed which enables scientists to invent and design superior, nontoxic and better-targeted prodrugs. The newly synthesized chemical entity or prodrugs may or may not have intrinsic pharmacological activity and also synthesizing novel molecules consume a lot of time and money than developing prodrugs of existing clinically used analgesic drugs which is surely an attractive and promising area of research now a days. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Institute for High Heat Flux Removal (IHHFR). Phases I, II, and III

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

Boyd, Ronald D.

2014-08-31

The IHHFR focused on interdisciplinary applications as it relates to high heat flux engineering issues and problems which arise due to engineering systems being miniaturized, optimized, or requiring increased high heat flux performance. The work in the IHHFR focused on water as a coolant and includes: (1) the development, design, and construction of the high heat flux flow loop and facility; (2) test section development, design, and fabrication; and, (3) single-side heat flux experiments to produce 2-D boiling curves and 3-D conjugate heat transfer measurements for single-side heated test sections. This work provides data for comparisons with previously developed andmore » new single-side heated correlations and approaches that address the single-side heated effect on heat transfer. In addition, this work includes the addition of single-side heated circular TS and a monoblock test section with a helical wire insert. Finally, the present work includes: (1) data base expansion for the monoblock with a helical wire insert (only for the latter geometry), (2) prediction and verification using finite element, (3) monoblock model and methodology development analyses, and (4) an alternate model development for a hypervapotron and related conjugate heat transfer controlling parameters.« less

Effects on craniofacial growth and development of unilateral botulinum neurotoxin injection into the masseter muscle.

PubMed

Tsai, Chi-Yang; Chiu, Wan Chi; Liao, Yi-Hsuan; Tsai, Chih-Mong

2009-02-01

The effects of botulinum neurotoxin type A (BoNT/A) on masseter muscles, when injected for cosmetic purposes (volumetric reduction) or treatment of excessive muscle activity (bruxism), have been investigated. However, the full anatomic effects of treatment are not known, particularly with respect to the mandible and relevant anthropometric measurements. The intent of this study was to use unilaterial BoNT/A injections to induce localized masseter atrophy and paresis and then to measure the effects of muscle influence on craniofacial growth and development. Growing male Wistar rats, 30 days old, were studied. The experimental group consisted of 8 rats. One side of the masseter muscle was injected with BoNT/A and the other side of the masseter muscle was injected with saline. The side with BoNT/A belonged to 1 group and the side with saline was the sham group. Three rats without injections was the control. After 45 days, the masseter muscles were dissected and weighed. Dry skulls were prepared, and anthropometric measurements determined. One-way ANOVA showed that the animals maintained their weight in both groups; however, the muscles injected with BoNT/A were smaller than the sham or control muscles. Anthropometric measurements of the bony structures attached to the masseter muscle showed a significant treatment effect. After localized masseter muscle atrophy induced by BoNT/A injection, alterations of craniofacial bone growth and development were seen. The results agree with the functional matrix theory that soft tissues regulate bone growth.

Propellers in yaw

NASA Technical Reports Server (NTRS)

Ribner, Herbert S

1945-01-01

It was realized as early as 1909 that a propeller in yaw develops a side force like that of a fin. In 1917, R. G. Harris expressed this force in terms of the torque coefficient for the unyawed propeller. Of several attempts to express the side force directly in terms of the shape of the blades, however, none has been completely satisfactory. An analysis that incorporates induction effects not adequately covered in previous work and that gives good agreement with experiment over a wide range of operating conditions is presented. The present analysis shows that the fin analogy may be extended to the form of the side-force expression and that the effective fin area may be taken as the projected side area of the propeller.

Adjuvant endocrine therapy after breast cancer: a qualitative study of factors associated with adherence

PubMed Central

Boulton, Mary; Fenlon, Debbie; Hulbert-Williams, Nick J; Walter, Fiona M; Donnelly, Peter; Lavery, Bernadette A; Morgan, Adrienne; Morris, Carolyn; Watson, Eila K

2018-01-01

Introduction Despite evidence of the efficacy of adjuvant endocrine therapy (AET) in reducing the risk of recurrence and mortality after treatment for primary breast cancer, adherence to AET is suboptimal. This study aimed to explore factors that influence adherence and nonadherence to AET following breast cancer to inform the development of supportive interventions. Methods Interviews were conducted with 32 women who had been prescribed AET, 2–4 years following their diagnosis of breast cancer. Both adherers (n=19) and nonadherers (n=13) were recruited. The analysis was conducted using the Framework approach. Results Factors associated with adherence were as follows: managing side effects including information and advice on side effects and taking control of side effects, supportive relationships, and personal influences. Factors associated with nonadherence were as follows: burden of side effects, feeling unsupported, concerns about long-term AET use, regaining normality, including valuing the quality of life over length of life, and risk perception. Conclusion Provision of timely information to prepare women for the potential side effects of AET and education on medication management strategies are needed, including provision of timely and accurate information on the efficacy of AET in reducing breast cancer recurrence and on potential side effects and ways to manage these should they arise. Trust in the doctor–patient relationship and clear patient pathways for bothersome side effects and concerns with AET are important. Training and education on AET for GPs should be considered alongside novel care pathways such as primary care nurse cancer care review and community pharmacist follow-up. PMID:29497284

Dobutamine stress MRI. Part I. Safety and feasibility of dobutamine cardiovascular magnetic resonance in patients suspected of myocardial ischemia.

PubMed

Kuijpers, Dirkjan; Janssen, Caroline H C; van Dijkman, Paul R M; Oudkerk, Matthijs

2004-10-01

The aim of the study was to evaluate safety and feasibility of dobutamine cardiovascular magnetic resonance (CMR) in patients with proven or suspected coronary artery disease. Dobutamine CMR was evaluated retrospectively in 400 consecutive patients with suspicion of myocardial ischemia. Dobutamine was infused using an incremental protocol up to 40 microg/kg body weight per minute. All anti-anginal medication was stopped 4 days before the CMR study and infusion time of dobutamine was 6 min per stage. Hemodynamic data, CMR findings and side effects were reported. Patients with contraindications to CMR (metallic implants and claustrophobia) were excluded from analysis. Dobutamine CMR was successfully performed in 355 (89%) patients. Forty-five (11%) patients could not be investigated adequately because of non-cardiac side effects in 29 (7%) and cardiac side effects in 16 (4%) patients. Hypotension (1.5%) and arrhythmias (1%) were the most frequent cardiac side effects. One patient developed a severe complication (ventricular fibrillation) at the end of the study. There were no myocardial infarctions or fatal complications of the stress test. The most frequent non-cardiac side effects were nausea, vomiting and claustrophobia. Age >70 years, prior myocardial infarction and rest wall motion abnormalities showed no significant differences with side effects (P>0.05). Dobutamine CMR is safe and feasible in patients with suspicion of myocardial ischemia. Copyright 2004 Springer-Verlag

Pattern of Self Prescribed Analgesic Use in a Rural Area of Delhi: Exploring the Potential Role of Internet.

PubMed

Kochhar, Anjali; Gupta, Tanya

2017-07-01

Analgesics are the most common self prescribed drugs. Although considered to be relatively safe, side effects are often seen when these drugs are used for prolonged period, in high doses or used where contraindicated. Majority of the consumers are not aware of the side effects. These days ample amount of information is available on web, it is important to explore its role in educating the population regarding the safe use of self prescribed analgesics. To explore pattern of analgesic use, to identify population at risk of developing side effects related to analgesic use, awareness of side effects and potential role of internet to bring awareness about safe use of self prescribed analgesic drugs in a rural area of Delhi. A cross-sectional survey based study was done on 500 adults in the age group of 18-65 years of Madanpur Khadar area of South Delhi, India. Data collection was done by conducting visits to pharmacy shops from the people who were buying drugs without prescription and taking face to face interviews using a semi-structured questionnaire. Statistical analysis was performed using descriptive tests with Microsoft office excel 2007. Results of our study showed that among all the self prescribed analgesics paracetamol (57%) was used most frequently followed by aspirin and other NSAIDs. It was found that 9.6% of the consumers were having associated co-morbid illness, 11.4% were simultaneously taking other drugs and 15.2% were alcoholics. Majority (65.4%) of the buyers were not aware about any kind of side effects of the analgesics. Internet friendly consumers were found to be 44%. Ability to use internet and education level were found to be directly related (r=0.802). The pattern of analgesic consumption in the rural population of Delhi shows that a large number of consumers may be at risk of developing side effects of self prescribed analgesics. The awareness about the side effects is limited. A significant number of consumers are internet friendly. Hence, we recommend use of website/mobile apps as potential source of information in educating the population regarding the use of self prescribed analgesics.

Opioid Receptors: Toward Separation of Analgesic from Undesirable Effects

PubMed Central

Law, P.Y.; Reggio, Patricia H.; Loh, H.H.

2013-01-01

The use of opioid analgesics for pain has always been hampered by their many side effects; in particular, the addictive liability associated with chronic use. Recently, attempts to develop analgesic agents with reduced side effects have targeted either the putative opioid receptor splice variants or the receptor heterooligomers. This review discusses the potential for receptor splice variant- and the hetero-oligomer-based discovery of new opioid analgesics. We also examine an alternative approach of using receptor mutants for pain management. Finally, we discuss the role of the biased agonism observed and the recently reported opioid receptor crystal structures in guiding the future development of opioid analgesics PMID:23598157

Current perspectives in NSAID-induced gastropathy.

PubMed

Sinha, Mau; Gautam, Lovely; Shukla, Prakash Kumar; Kaur, Punit; Sharma, Sujata; Singh, Tej P

2013-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, anti-inflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection.

Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) as a Target for Concurrent Management of Diabetes and Obesity-Related Cancer.

PubMed

Wang, Qingqing; Imam, Mustapha Umar; Yida, Zhang; Wang, Fudi

2017-01-01

Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear receptor superfamily of ligand-inducible transcription factors that regulate adipogenesis, lipid metabolism, cell proliferation, inflammation and insulin sensitization. Abnormalities in PPARγ signaling have been associated with obesity, diabetes and cancer. The use of agonists to manage these diseases has been limited by their side effects. Accordingly, dual or pan agonists targeting the PPARα or PPARα and PPARδ, respectively, in addition to the PPARγ have been developed to overcome these side effects. This review details the shared PPARγ-dependent mechanisms between obesity-related cancers and diabetes and their potential therapeutic values. We performed a systematic literature search through pubmed, Scopus and google scholar for articles on PPARγ-dependent signaling in diabetes or cancer. There is growing co-occurrence of obesity-related cancers and diabetes, necessitating the use of effective therapies with the least amount of side effects for concurrent management of these diseases, by targeting potentially shared PPARγ-dependent mechanisms including abnormalities of the wnt/β-catenin, lysosomal acid lipase, inflammatory and cell cycle pathways, and the plasminogen activator system. Taking advantage of the multiple docking sites of the PPARγ and the pleiotropic nature of its signaling, structure-activity relationship and molecular docking studies have provided insights into designer PPARγ agonists or dual PPARα/γ agonists that modulate PPARγ signaling and negate side effects of full PPARγ agonists. Effective therapies, possibly devoid of side effects, for concurrent management of obesity-related cancers and diabetes can be developed through diligent structure-activity and molecular docking studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

PubMed Central

Diebold, Becky A.; Smith, Susan M.E.; Li, Yang

2015-01-01

Abstract Significance: NOX2 is important for host defense, and yet is implicated in a large number of diseases in which inflammation plays a role in pathogenesis. These include acute and chronic lung inflammatory diseases, stroke, traumatic brain injury, and neurodegenerative diseases, including Alzheimer's and Parkinson's Diseases. Recent Advances: Recent drug development programs have targeted several NOX isoforms that are implicated in a variety of diseases. The focus has been primarily on NOX4 and NOX1 rather than on NOX2, due, in part, to concerns about possible immunosuppressive side effects. Nevertheless, NOX2 clearly contributes to the pathogenesis of many inflammatory diseases, and its inhibition is predicted to provide a novel therapeutic approach. Critical Issues: Possible side effects that might arise from targeting NOX2 are discussed, including the possibility that such inhibition will contribute to increased infections and/or autoimmune disorders. The state of the field with regard to existing NOX2 inhibitors and targeted development of novel inhibitors is also summarized. Future Directions: NOX2 inhibitors show particular promise for the treatment of inflammatory diseases, both acute and chronic. Theoretical side effects include pro-inflammatory and autoimmune complications and should be considered in any therapeutic program, but in our opinion, available data do not indicate that they are sufficiently likely to eliminate NOX2 as a drug target, particularly when weighed against the seriousness of many NOX2-related indications. Model studies demonstrating efficacy with minimal side effects are needed to encourage future development of NOX2 inhibitors as therapeutic agents. Antioxid. Redox Signal. 23, 375–405. PMID:24512192

Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations.

PubMed

Perez-Lopez, Áron R; Szalay, Kristóf Z; Türei, Dénes; Módos, Dezső; Lenti, Katalin; Korcsmáros, Tamás; Csermely, Peter

2015-05-11

Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates.

Local and Systemic Therapies for Breast Cancer Patients: Reducing Short-term Symptoms with the Methods of Integrative Medicine

PubMed Central

Hack, C. C.; Voiß, P.; Lange, S.; Paul, A. E.; Conrad, S.; Dobos, G. J.; Beckmann, M. W.; Kümmel, S.

2015-01-01

With improved prognosis due to advances in the diagnosis and therapy of breast cancer, physicians and therapists now focus on aspects such as quality of life and the management of side effects from breast cancer treatment. Therapy- and disease-related side effects often reduce the patientʼs quality of life and can place a further burden on patients, with non-compliance or discontinuation of therapy a potential consequence. Study data have shown that therapy- and disease-related side effects can be reduced using the methods of integrative medicine. Reported benefits include improving patientsʼ wellbeing and quality of life, reducing stress, and improving patientsʼ mood, sleeping patterns and capacity to cope with disease. Examining the impact of integrative medicine on the side effects of cancer treatment would be beyond the scope of this review. This article therefore looks at short-term side effects of cancer treatment which are usually temporary and occur during or after local and systemic therapy. The focus is on mind-body medicine, acupuncture and classic naturopathic treatments developed by Sebastian Kneipp as complementary therapies. The latter includes hydrotherapy, phytotherapy, nutritional therapy, exercise therapy and a balanced lifestyle. PMID:26257404

Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations

NASA Astrophysics Data System (ADS)

Perez-Lopez, Áron R.; Szalay, Kristóf Z.; Türei, Dénes; Módos, Dezső; Lenti, Katalin; Korcsmáros, Tamás; Csermely, Peter

2015-05-01

Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates.

Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations

PubMed Central

Perez-Lopez, Áron R.; Szalay, Kristóf Z.; Türei, Dénes; Módos, Dezső; Lenti, Katalin; Korcsmáros, Tamás; Csermely, Peter

2015-01-01

Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates. PMID:25960144

Suspected side effects of doxycycline use in dogs - a retrospective study of 386 cases.

PubMed

Schulz, B S; Hupfauer, S; Ammer, H; Sauter-Louis, C; Hartmann, K

2011-08-27

This study investigated doxycycline-related side effects in a large population of dogs. Data from 386 dogs that had received doxycycline for the treatment of various infectious diseases were analysed retrospectively. Potential side effects that developed during treatment were documented, and correlations with signalment, dose, duration of treatment, frequency of application, doxycycline preparation and use of additional drugs were investigated. Vomiting was reported in 18.3 per cent of dogs, 7.0 per cent developed diarrhoea and 2.5 per cent developed anorexia. While being treated with doxycycline, 39.4 per cent of dogs showed an increase in alanine aminotransferase (ALT) activity and 36.4 per cent showed an increase in alkaline phosphatase (ALP) activity. There was a dose-related risk of an increase in ALP activity (P=0.011, odds ratio [OR]=1.27, 95 per cent confidence interval [CI] 1.06 to 1.53), and older dogs treated with doxycycline were more likely to develop an increase in ALT activity (P=0.038, OR=1.23, 95 per cent CI 1.01 to 1.50) and vomiting (P=0.017, OR=1.11, 95 per cent CI 1.02 to 1.21).

Sunny Side Up in Mathematics.

ERIC Educational Resources Information Center

LaHart, David, Ed.

Energy is a problem affecting all individuals. To help today's students understand the problem and become realistic decision-makers, materials have been developed by the Sunny Side Up (in Mathematics) program to introduce energy concepts into the mathematics curriculum. Objectives of the program are to: (1) provide highly effective practice in…

Research on key factors and their interaction effects of electromagnetic force of high-speed solenoid valve.

PubMed

Liu, Peng; Fan, Liyun; Hayat, Qaisar; Xu, De; Ma, Xiuzhen; Song, Enzhe

2014-01-01

Analysis consisting of numerical simulations along with lab experiments of interaction effects between key parameters on the electromagnetic force based on response surface methodology (RSM) has been also proposed to optimize the design of high-speed solenoid valve (HSV) and improve its performance. Numerical simulation model of HSV has been developed in Ansoft Maxwell environment and its accuracy has been validated through lab experiments. Effect of change of core structure, coil structure, armature structure, working air gap, and drive current on the electromagnetic force of HSV has been analyzed through simulation model and influence rules of various parameters on the electromagnetic force have been established. The response surface model of the electromagnetic force has been utilized to analyze the interaction effect between major parameters. It has been concluded that six interaction factors including working air gap with armature radius, drive current with armature thickness, coil turns with side pole radius, armature thickness with its radius, armature thickness with side pole radius, and armature radius with side pole radius have significant influence on the electromagnetic force. Optimal match values between coil turns and side pole radius; armature thickness and side pole radius; and armature radius and side pole radius have also been determined.

Research on Key Factors and Their Interaction Effects of Electromagnetic Force of High-Speed Solenoid Valve

PubMed Central

Fan, Liyun; Xu, De; Ma, Xiuzhen; Song, Enzhe

2014-01-01

Analysis consisting of numerical simulations along with lab experiments of interaction effects between key parameters on the electromagnetic force based on response surface methodology (RSM) has been also proposed to optimize the design of high-speed solenoid valve (HSV) and improve its performance. Numerical simulation model of HSV has been developed in Ansoft Maxwell environment and its accuracy has been validated through lab experiments. Effect of change of core structure, coil structure, armature structure, working air gap, and drive current on the electromagnetic force of HSV has been analyzed through simulation model and influence rules of various parameters on the electromagnetic force have been established. The response surface model of the electromagnetic force has been utilized to analyze the interaction effect between major parameters. It has been concluded that six interaction factors including working air gap with armature radius, drive current with armature thickness, coil turns with side pole radius, armature thickness with its radius, armature thickness with side pole radius, and armature radius with side pole radius have significant influence on the electromagnetic force. Optimal match values between coil turns and side pole radius; armature thickness and side pole radius; and armature radius and side pole radius have also been determined. PMID:25243217

Classics in Chemical Neuroscience: Aripiprazole.

PubMed

Casey, Austen B; Canal, Clinton E

2017-06-21

Aripiprazole was the first antipsychotic developed to possess agonist properties at dopamine D 2 autoreceptors, a groundbreaking strategy that presented a new vista for schizophrenia drug discovery. The dopamine D 2 receptor is the crucial target of all extant antipsychotics, and all developed prior to aripiprazole were D 2 receptor antagonists. Extensive blockade of these receptors, however, typically produces extrapyramidal (movement) side effects, which plagued first-generation antipsychotics, such as haloperidol. Second-generation antipsychotics, such as clozapine, with unique polypharmacology and D 2 receptor binding kinetics, have significantly lower risk of movement side effects but can cause myriad additional ones, such as severe weight gain and metabolic dysfunction. Aripiprazole's polypharmacology, characterized by its unique agonist activity at dopamine D 2 and D 3 and serotonin 5-HT 1A receptors, as well as antagonist activity at serotonin 5-HT 2A receptors, translates to successful reduction of positive, negative, and cognitive symptoms of schizophrenia, while also mitigating risk of weight gain and movement side effects. New observations, however, link aripiprazole to compulsive behaviors in a small group of patients, an unusual side effect for antipsychotics. In this review, we discuss the chemical synthesis, pharmacology, pharmacogenomics, drug metabolism, and adverse events of aripiprazole, and we present a current understanding of aripiprazole's neurotherapeutic mechanisms, as well as the history and importance of aripiprazole to neuroscience.

The safety of tocolytics used for the inhibition of preterm labour.

PubMed

Lamont, Callum D; Jørgensen, Jan Stener; Lamont, Ronald F

2016-09-01

Preterm birth is the major cause of neonatal mortality and morbidity worldwide and a huge cost burden on healthcare. Between 22 and 26 completed weeks of gestation, for every day that delivery is delayed, survival increases by 3%. Following a systematic review of the literature, we have provided an overview of the use of tocolytics for the prevention of preterm birth and have examined the fetal and maternal adverse effects of the various tocolytic agents currently in use. No tocolytic currently in use was developed specifically to treat preterm labour so most have multi-organ side effects. β2-agonists are relatively safe for the fetus but have rare and potentially serious maternal adverse effects. In contrast, prostaglandin synthetase inhibitors have potentially serious side effects for the fetus and neonate but have mild maternal gastrointestinal side effects. In Europe, the choice of first line therapy is either atosiban or nifedipine. The evidence base for atosiban is much more robust than for nifedipine. While their efficacy is similar, atosiban has placebo level side effects and is safer than nifedipine but is much more expensive.

Cardiac ion channels

PubMed Central

Priest, Birgit T; McDermott, Jeff S

2015-01-01

Ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Consequently, ion channels are key targets for therapeutics aimed at cardiac pathophysiologies such as atrial fibrillation or angina. At the same time, off-target interactions of drugs with cardiac ion channels can be the cause of unwanted side effects. This manuscript aims to review the physiology and pharmacology of key cardiac ion channels. The intent is to highlight recent developments for therapeutic development, as well as elucidate potential mechanisms for drug-induced cardiac side effects, rather than present an in-depth review of each channel subtype. PMID:26556552

Transient three-dimensional startup side load analysis of a regeneratively cooled nozzle

NASA Astrophysics Data System (ADS)

Wang, Ten-See

2009-07-01

The objective of this effort is to develop a computational methodology to capture the side load physics and to anchor the computed aerodynamic side loads with the available data by simulating the startup transient of a regeneratively cooled, high-aspect-ratio nozzle, hot-fired at sea level. The computational methodology is based on an unstructured-grid, pressure-based, reacting flow computational fluid dynamics and heat transfer formulation, and a transient inlet history based on an engine system simulation. Emphases were put on the effects of regenerative cooling on shock formation inside the nozzle, and ramp rate on side load reduction. The results show that three types of asymmetric shock physics incur strong side loads: the generation of combustion wave, shock transitions, and shock pulsations across the nozzle lip, albeit the combustion wave can be avoided with sparklers during hot-firing. Results from both regenerative cooled and adiabatic wall boundary conditions capture the early shock transitions with corresponding side loads matching the measured secondary side load. It is theorized that the first transition from free-shock separation to restricted-shock separation is caused by the Coanda effect. After which the regeneratively cooled wall enhances the Coanda effect such that the supersonic jet stays attached, while the hot adiabatic wall fights off the Coanda effect, and the supersonic jet becomes detached most of the time. As a result, the computed peak side load and dominant frequency due to shock pulsation across the nozzle lip associated with the regeneratively cooled wall boundary condition match those of the test, while those associated with the adiabatic wall boundary condition are much too low. Moreover, shorter ramp time results show that higher ramp rate has the potential in reducing the nozzle side loads.

Current Perspectives in NSAID-Induced Gastropathy

PubMed Central

Sinha, Mau; Gautam, Lovely; Shukla, Prakash Kumar; Kaur, Punit; Sharma, Sujata; Singh, Tej P.

2013-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, anti-inflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection. PMID:23576851

Emerging therapeutic options in GERD.

PubMed

Woodland, Philip; Amarasinghe, Gehanjali; Sifrim, Daniel

2013-06-01

Gastroesophageal reflux disease (GERD) is a prevalent problem resulting in a high level of healthcare consultation and expenditure in the Western World. Although standard medical therapy (in the form of proton pump inhibitor drugs) is effective in the majority of cases, there remains a significant proportion who are refractory to treatment. In addition, surgical therapy (in the form of laparoscopic fundoplication) is not always effective, and in some can be associated with significant side-effects, particularly gas-bloat, flatulence and dysphagia. As such there remains an unmet need in GERD to develop new therapies for refractory cases, and to develop alternatives to fundoplication with fewer side-effects. This article discusses the current state of pharmacological and non-pharmacological emerging therapies for GERD. Copyright © 2013 Elsevier Ltd. All rights reserved.

No blank slates: Pre-existing schemas about pharmaceuticals predict memory for side effects.

PubMed

Heller, Monika K; Chapman, Sarah C E; Horne, Rob

2017-04-01

Attribution of symptoms as medication side effects is informed by pre-existing beliefs about medicines and perceptions of personal sensitivity to their effects (pharmaceutical schemas). We tested whether (1) pharmaceutical schemas were associated with memory (recall/recognition) for side effect information (2) memory explained the attribution of a common unrelated symptom as a side effect. In this analogue study participants saw the patient leaflet of a fictitious asthma drug listing eight side effects. We measured recall and recognition memory for side effects and used a vignette to test whether participants attributed an unlisted common symptom (headache) as a side effect. Participants who perceived pharmaceuticals as more harmful in general recalled fewer side effects correctly (r Correct Recall  = -.273), were less able to differentiate between listed and unlisted side effects (r Recognition Sensitivity  = -.256) and were more likely to attribute the unlisted headache symptom as a side effect (r side effect attribution  = .381, ps < .01). The effect of harm beliefs on side effect attribution was partially mediated by correct recall of side effects. Pharmaceutical schemas are associated with memory for side effect information. Memory may explain part of the association between pharmaceutical schemas and the attribution of unrelated symptoms as side effects.

Ginger augmented chemotherapy: A novel multitarget nontoxic approach for cancer management.

PubMed

Saxena, Roopali; Rida, Padmashree C G; Kucuk, Omer; Aneja, Ritu

2016-06-01

Cancer, referred to as the 'disease of civilization', continues to haunt humanity due to its dreadful manifestations and limited success of therapeutic interventions such as chemotherapy in curing the disease. Although effective, chemotherapy has repeatedly demonstrated inadequacy in disease management due to its debilitating side effects arising from its deleterious nonspecific effects on normal healthy cells. In addition, development of chemoresistance due to mono-targeting often results in cessation of chemotherapy. This urgently demands development and implementation of multitargeted alternative therapies with mild or no side effects. One extremely promising strategy that yet remains untapped in the clinic is augmenting chemotherapy with dietary phytochemicals or extracts. Ginger, depository of numerous bioactive molecules, not only targets cancer cells but can also mitigate chemotherapy-associated side effects. Consequently, combination therapy involving ginger extract and chemotherapeutic agents may offer the advantage of being efficacious with reduced toxicity. Here we discuss the remarkable and often overlooked potential of ginger extract to manage cancer, the possibility of developing ginger-based combinational therapies, and the major roadblocks along with strategies to overcome them in clinical translation of such inventions. We are optimistic that clinical implementation of such combination regimens would be a much sought after modality in cancer management. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Herbal products and serious side effects: a case of ginseng-induced manic episode.

PubMed

Vázquez, I; Agüera-Ortiz, L F

2002-01-01

Ginseng root extract is a widely used herbal product not devoid of side effects. This report describes the development of manic symptoms after ginseng consumption in a patient with affective disorder. Other potentially harmful side effects of ginseng are also reviewed. A single case report. A 56-year-old woman with previous affective disorder presented a manic episode during ginseng intake. Symptoms disappeared rapidly with low doses of neuroleptics and benzodiazepines after ginseng suppression. Ginseng may produce manic symptoms. A special risk situation seems to be affective patients under antidepressant medication. The case emphasizes the lack of harmlessness of herbal products. Patients should be routinely asked about the use of herbal products and diet supplements.

Advances in Pharmacotherapeutics of Space Motion Sickness

NASA Technical Reports Server (NTRS)

Putcha, Lakshmi

2006-01-01

Space Motion Sickness (SMS) is common occurrence in the U.S. manned space flight program and nearly 2/3 of Shuttle crewmembers experience SMS. Several drugs have been prescribed for therapeutic management of SMS. Typically, orally-administered SMS medications (scopolamine, promethazine) have poor bioavailability and often have detrimental neurocognitive side effects at recommended doses. Intramuscularly administered promethazine (PMZ) is perceived to have optimal efficacy with minimal side effects in space. However, intramuscular injections are painful and the sedating neurocognitive side effects of promethazine, significant in controlled ground testing, may be masked in orbit because injections are usually given prior to crew sleep. Currently, EVAs cannot be performed by symptomatic crew or prior to flight day three due to the lack of a consistently efficacious drug, concern about neurocognitive side effects, and because an in-suit vomiting episode is potentially fatal. NASA has long sought a fast acting, consistently effective anti-motion sickness medication which has only minor neurocognitive side effects. Development of intranasal formulations of scopolamine and promethazine, the two commonly used SMS drugs at NASA for both space and reduced gravity environment medical operations, appears to be a logical alternative to current treatment modalities for SMS. The advantages are expected to be fast absorption, reliable and high bioavailability, and probably reduced neurocognitive side effects owing to dose reduction. Results from clinical trials with intranasal scopolamine gel formulation and pre-clinical testing of a prototype microcapsule intranasal gel dosage form of PMZ (INPMZ) will be discussed. These formulations are expected to offer a dependable and effective noninvasive treatment option for SMS.

Small-molecule inhibitors of the receptor tyrosine kinases: promising tools for targeted cancer therapies.

PubMed

Hojjat-Farsangi, Mohammad

2014-08-08

Chemotherapeutic and cytotoxic drugs are widely used in the treatment of cancer. In spite of the improvements in the life quality of patients, their effectiveness is compromised by several disadvantages. This represents a demand for developing new effective strategies with focusing on tumor cells and minimum side effects. Targeted cancer therapies and personalized medicine have been defined as a new type of emerging treatments. Small molecule inhibitors (SMIs) are among the most effective drugs for targeted cancer therapy. The growing number of approved SMIs of receptor tyrosine kinases (RTKs) i.e., tyrosine kinase inhibitors (TKIs) in the clinical oncology imply the increasing attention and application of these therapeutic tools. Most of the current approved RTK-TKIs in preclinical and clinical settings are multi-targeted inhibitors with several side effects. Only a few specific/selective RTK-TKIs have been developed for the treatment of cancer patients. Specific/selective RTK-TKIs have shown less deleterious effects compared to multi-targeted inhibitors. This review intends to highlight the importance of specific/selective TKIs for future development with less side effects and more manageable agents. This article provides an overview of: (1) the characteristics and function of RTKs and TKIs; (2) the recent advances in the improvement of specific/selective RTK-TKIs in preclinical or clinical settings; and (3) emerging RTKs for targeted cancer therapies by TKIs.

A Partnership Training Program: Studying Targeted Drug Delivery Using Nanoparticles In Breast Cancer Diagnosis and Therapy

DTIC Science & Technology

2015-12-01

have been approved by FDA or are under development. Their use aims to minimize drug degradation, prevent undesirable side effects , and increase drug...efficacy, while simultaneously reducing side effects , owing to properties such as more targeted localization in tumors and active cellular uptake...with Dr. Vreeland suggested that the lipid was below the transition temperature of the lipid, which likely contributed to the poor size distribution

Are Senna based laxatives safe when used as long term treatment for constipation in children?

PubMed

Vilanova-Sanchez, Alejandra; Gasior, Alessandra C; Toocheck, Nicole; Weaver, Laura; Wood, Richard J; Reck, Carlos A; Wagner, Andrea; Hoover, Erin; Gagnon, Renae; Jaggers, Jordon; Maloof, Tassiana; Nash, Onnalisa; Williams, Charae; Levitt, Marc A

2018-04-01

Senna is a stimulant laxative commonly used by pediatricians, pediatric gastroenterologists, and pediatric surgeons. Many clinicians avoid Senna for reasons such as tolerance or side effects but this has little scientific justification. We recently found several patients we were caring for developed perineal blistering during the course of Senna treatment. Because of this we chose to review the literature to identify side effects in children taking this medication as well as to analyze our Center's experience with Senna's secondary effects. We performed a literature review (MEDLINE, PUBMED) using the keywords of Senna, sen, sennosides and children, and pediatric and functional (idiopathic) constipation. We looked for articles with information regarding perineal blisters related to Senna as well as other secondary effects of Senna laxatives in children when used on a long-term basis. We also reviewed the charts of our patients who had previously taken Senna or are currently taking Senna, looking for adverse reactions. Eight articles in the literature reported perineal blisters after administration of Senna laxatives in 28 patients. Of those occurrences, 18 patients (64%) had accidental administration of Senna and 10 (36%) had Senna prescribed as a long term treatment. All of the blistering episodes were related to high dose, night-time accidents, or intense diarrhea with a long period of stool to skin contact. At our institution, from 2014 to 2017, we prescribed Senna and have recorded data to 640 patients. During the study period, 17 patients (2.2%) developed blisters during their treatment. Patients who developed blisters had higher doses 60mg/day; 60 [12-100] vs. 17.5 [1.7-150] (p<0.001). All of the blistering episodes were related to night-time accidents, with a long period of stool to skin contact. 83 (13%) patients presented minor side effects such as abdominal cramping, vomiting or diarrhea which resolved once the type of laxatives were changed or enemas were started. The doses of Senna was not significantly different in these patients 15mg/day [4.4-150] vs. 17.5mg/day [1.5-150]. There were no other long-term side effects from Senna found in the pediatric literature for long-term treatment besides abdominal cramping or diarrhea during the first weeks of administration. We found no evidence of tolerance to Senna in our review. There is a paucity of information in the literature regarding side effects of sennosides as a long-term therapy, and to our knowledge, this is the first review of Senna side effects in children. Senna induced dermatitis is rare, but may occur when patients need a higher dose. All of the cases described had a long period of exposure of the skin to stool. Besides the perineal rash with blisters, we could find no other described major side effect with Senna administration in the pediatric population or evidence of the frequently mentioned concern of the development of tolerance to Senna. Pediatric caregivers should advise families of the rare side effect of skin blistering and educate them to change the diaper frequently in children who are not toilet- trained to reduce stool to skin exposure. We can conclude from this review that Senna is a safe treatment option for constipation in children. IV. Copyright © 2018 Elsevier Inc. All rights reserved.

TARGETING POLYMER THERAPEUTICS TO BONE

PubMed Central

Low, Stewart; Kopeček, Jindřich

2012-01-01

An aging population in the developing world has led to an increase in musculoskeletal diseases such as osteoporosis and bone metastases. Left untreated many bone diseases cause debilitating pain and in the case of cancer, death. Many potential drugs are effective in treating diseases but result in side effects preventing their efficacy in the clinic. Bone, however, provides an unique environment of inorganic solids, which can be exploited in order to effectively target drugs to diseased tissue. By integration of bone targeting moieties to drug-carrying water-soluble polymers, the payload to diseased area can be increased while side effects decreased. The realization of clinically relevant bone targeted polymer therapeutics depends on (1) understanding bone targeting moiety interactions, (2) development of controlled drug delivery systems, as well as (3) understanding drug interactions. The latter makes it possible to develop bone targeted synergistic drug delivery systems. PMID:22316530

[Methylphenidate of retard forms in children and adolescents with ADHD - an overview].

PubMed

Pelz, R; Banaschewski, T; Becker, K

2008-01-01

As yet, stimulants remain the preferred means of treating attention-deficit/hyperactivity disorder (ADHD) pharmacologically. They are indicated when measures based on behavioural therapy or psychoeducation alone are not sufficient. How-ever, the period of effectiveness of immediate release stimulants is often not satisfactory. A variety of retarded forms of methylphenidate have now been developed and approved for the German market. This paper presents an overview of clinical studies on effectiveness, period of effectiveness and the profile of side effects of different forms stimulants available in Germany. In clinical practice, the new retard products represent effective alternatives. There is an advantage in administering this drug in a once-daily single dose. At the same time, the side effects that are caused by an extended period of effectiveness have to be studied in detail. A more precise adaptation to the daily obligations and needs of children and adolescents is needed. Possibly, a combination with unretareded MPH might lead to a better effect/side-effect profile.

Analysis of differential secondary effects of novel rexinoids: select rexinoid X receptor ligands demonstrate differentiated side effect profiles

PubMed Central

Marshall, Pamela A; Jurutka, Peter W; Wagner, Carl E; van der Vaart, Arjan; Kaneko, Ichiro; Chavez, Pedro I; Ma, Ning; Bhogal, Jaskaran S; Shahani, Pritika; Swierski, Johnathon C; MacNeill, Mairi

2015-01-01

In order to determine the feasibility of utilizing novel rexinoids for chemotherapeutics and as potential treatments for neurological conditions, we undertook an assessment of the side effect profile of select rexinoid X receptor (RXR) analogs that we reported previously. We assessed pharmacokinetic profiles, lipid and thyroid-stimulating hormone (TSH) levels in rats, and cell culture activity of rexinoids in sterol regulatory element-binding protein (SREBP) induction and thyroid hormone inhibition assays. We also performed RNA sequencing of the brain tissues of rats that had been dosed with the compounds. We show here for the first time that potent rexinoid activity can be uncoupled from drastic lipid changes and thyroid axis variations, and we propose that rexinoids can be developed with improved side effect profiles than the parent compound, bexarotene (1). PMID:26038698

Effects of first premolar extraction on maxillary and mandibular third molar angulation after orthodontic therapy

PubMed Central

Gohilot, Avinash; Pradhan, Tejashri; Keluskar, Kanhoba Mahabaleshwar

2012-01-01

Background/Aims To compare the change in the angulation of developing mandibular third molar in both first premolar extraction and non-extraction cases and to determine whether premolar extraction results in a more mesial movement of the mandibular buccal segment and causes favorable rotational changes in the mandibular third molar tilt, which can enhance later eruption of the third molars. Materials and methods Pretreatment (T1) and post treatment (T2) panoramic radiographs were taken of 25 subjects (age 14–19 years) who had been treated by the extraction of all the first premolars and 25 subjects who had been treated with non-extraction. The horizontal reference plane was used to measure and compare the changes in the angles of the developing mandibular third molars. Results The mean uprighting of the maxillary third molars seen in the extraction group was 4 ± 9° on the left side and −17 ± 13° on the right side following treatment (T2 _ T1). For the non-extraction group the mean difference was −16 ± 12° on the left side and 2 ± 13° on the right side. There was a statistically significant difference between the groups (P _ 0.021 on the right side and P _ 0.041 on the left side). Mandibular 3rd molars in extraction group showed no statistical significant change in the angulation. Conclusion Premolar extractions had a positive influence on the developing maxillary third molar angulations both on right and left. Mandibular 3rd molar have shown change in the angulation but not statistically significant. Non-extraction therapy did not have any adverse effect. PMID:25737843

Effects of first premolar extraction on maxillary and mandibular third molar angulation after orthodontic therapy.

PubMed

Gohilot, Avinash; Pradhan, Tejashri; Keluskar, Kanhoba Mahabaleshwar

2012-01-01

To compare the change in the angulation of developing mandibular third molar in both first premolar extraction and non-extraction cases and to determine whether premolar extraction results in a more mesial movement of the mandibular buccal segment and causes favorable rotational changes in the mandibular third molar tilt, which can enhance later eruption of the third molars. Pretreatment (T1) and post treatment (T2) panoramic radiographs were taken of 25 subjects (age 14-19 years) who had been treated by the extraction of all the first premolars and 25 subjects who had been treated with non-extraction. The horizontal reference plane was used to measure and compare the changes in the angles of the developing mandibular third molars. The mean uprighting of the maxillary third molars seen in the extraction group was 4 ± 9° on the left side and -17 ± 13° on the right side following treatment (T2 _ T1). For the non-extraction group the mean difference was -16 ± 12° on the left side and 2 ± 13° on the right side. There was a statistically significant difference between the groups (P _ 0.021 on the right side and P _ 0.041 on the left side). Mandibular 3rd molars in extraction group showed no statistical significant change in the angulation. Premolar extractions had a positive influence on the developing maxillary third molar angulations both on right and left. Mandibular 3rd molar have shown change in the angulation but not statistically significant. Non-extraction therapy did not have any adverse effect.

Sexual side effects of serotonergic antidepressants: mediated by inhibition of serotonin on central dopamine release?

PubMed

Bijlsma, Elisabeth Y; Chan, Johnny S W; Olivier, Berend; Veening, Jan G; Millan, Mark J; Waldinger, Marcel D; Oosting, Ronald S

2014-06-01

Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducibility of our standardized test procedure that assesses the acute, subchronic and chronic effects of psychoactive compounds in a 30 minute mating test. In addition, we present an overview of the effects of several different (putative) antidepressants on male rat sexual behavior, as tested in our standardized test procedure. By comparing the effects of these mechanistically distinct antidepressants (paroxetine, venlafaxine, bupropion, buspirone, DOV 216,303 and S32006), this review discusses the putative mechanism underlying sexual side effects of antidepressants and their normalization. This review shows that sexual behavior is mainly inhibited by antidepressants that increase serotonin neurotransmission via blockade of serotonin transporters, while those that mainly increase the levels of dopamine and noradrenaline are devoid of sexual side effects. Those sexual disturbances cannot be normalized by simultaneously increasing noradrenaline neurotransmission, but are normalized by increasing both noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that the sexual side effects of selective serotonin reuptake inhibitors may be mediated by their inhibitory effects on dopamine signaling in sex brain circuits. Clinical development of novel antidepressants should therefore focus on compounds that simultaneously increase both serotonin and dopamine signaling. © 2013 Elsevier Inc. All rights reserved.

A unified frame of predicting side effects of drugs by using linear neighborhood similarity.

PubMed

Zhang, Wen; Yue, Xiang; Liu, Feng; Chen, Yanlin; Tu, Shikui; Zhang, Xining

2017-12-14

Drug side effects are one of main concerns in the drug discovery, which gains wide attentions. Investigating drug side effects is of great importance, and the computational prediction can help to guide wet experiments. As far as we known, a great number of computational methods have been proposed for the side effect predictions. The assumption that similar drugs may induce same side effects is usually employed for modeling, and how to calculate the drug-drug similarity is critical in the side effect predictions. In this paper, we present a novel measure of drug-drug similarity named "linear neighborhood similarity", which is calculated in a drug feature space by exploring linear neighborhood relationship. Then, we transfer the similarity from the feature space into the side effect space, and predict drug side effects by propagating known side effect information through a similarity-based graph. Under a unified frame based on the linear neighborhood similarity, we propose method "LNSM" and its extension "LNSM-SMI" to predict side effects of new drugs, and propose the method "LNSM-MSE" to predict unobserved side effect of approved drugs. We evaluate the performances of LNSM and LNSM-SMI in predicting side effects of new drugs, and evaluate the performances of LNSM-MSE in predicting missing side effects of approved drugs. The results demonstrate that the linear neighborhood similarity can improve the performances of side effect prediction, and the linear neighborhood similarity-based methods can outperform existing side effect prediction methods. More importantly, the proposed methods can predict side effects of new drugs as well as unobserved side effects of approved drugs under a unified frame.

What matters when judging intentionality-moral content or normative status? Testing the rational scientist model of the side-effect.

PubMed

Papadopoulos, C; Hayes, B K

2018-06-01

Previous work has demonstrated a "side-effect effect," such that intentionality is more likely to be attributed to agents who bring about negatively valenced as opposed to positively valenced side effects. The rational-scientist model explains this by suggesting that norm-violating side effects are more informative for inferring intentionality than norm-conforming side effects. In the present study we reexamined this account, addressing limitations of previous empirical tests (e.g., Uttich & Lombrozo, Cognition 116: 87-100, 2010). Side-effect valence and norm status were manipulated factorially, enabling an examination of the impact of norm status on intentionality judgments in both positively and negatively valenced side effects. Additionally, the impact of side-effect norm status on the perceived valences of side effects and agents was examined. Effects of norm status were found for both positive and negative side effects. Violation of an ostensibly neutral norm led to negative perceptions of the side effect. However, a norm status effect on intentionality judgments persisted when these effects were controlled. These results support the view that the side-effect effect is the result of the rational use of social-cognitive evidence.

Reentry vehicle aerodynamics and control at very high angle of attack

NASA Astrophysics Data System (ADS)

Merret, Jason Michael

In recent flight tests the X-38 reentry test vehicle spins during the deployment of the drogue parachute. An experimental aerodynamic study has been conducted at the University of Illinois using a scale model of the X-38 to explore the cause of this problem. A six-component sting balance was used to measure the forces and moments on the 4.7% wind tunnel model at angles of attack from -7° to 95°. In addition, surface pressure taps and flow visualization techniques were utilized to determine the forebody pressures and surface flowfield on the model. The effect of Reynolds number and boundary-layer state were also examined. The investigation suggests that the spinning under the drogue parachute was caused by asymmetric vortex formation. At angles of attack between 75° and 90° vortex asymmetry developed in all of the cases without separation geometrically fixed. This flow asymmetry produced large side forces and yawing moments. The Reynolds number effect and the effect of the boundary-layer state were noticeable, but did not greatly change the side force and yawing moment characteristics of the model. The micro-geometry of the model had a large effect on the side force generated by the vortex positioning. The effects of forced oscillations were also examined and it was determined that the side forces were still present during the oscillations. Control of the vortices and side forces was obtained by applying strakes to the side of the forebody of the model.

Neurotoxicity of cancer chemotherapy☆

PubMed Central

Yang, Miyoung; Moon, Changjong

2013-01-01

There is accumulating clinical evidence that chemotherapeutic agents induce neurological side effects, including memory deficits and mood disorders, in cancer patients who have undergone chemotherapeutic treatments. This review focuses on chemotherapy-induced neurodegeneration and hippocampal dysfunctions and related mechanisms as measured by in vivo and in vitro approaches. These investigations are helpful in determining how best to further explore the causal mechanisms of chemotherapy-induced neurological side effects and in providing direction for the future development of novel optimized chemotherapeutic agents. PMID:25206457

Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study

PubMed Central

Haas, Marion; Viney, Rosalie; Pearson, Sallie-Anne; Haywood, Philip; Brown, Chris; Ward, Robyn

2017-01-01

Aim Chemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia. Methods We conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics. Results Side effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects. Conclusion This research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers. PMID:29016607

Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study.

PubMed

Pearce, Alison; Haas, Marion; Viney, Rosalie; Pearson, Sallie-Anne; Haywood, Philip; Brown, Chris; Ward, Robyn

2017-01-01

Chemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia. We conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics. Side effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects. This research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers.

[A patient with acute Philadelphia-chromosome-positive mixed phenotype leukemia developing ecthyma gangrenosum while undergoing combined imatinib mesylate chemotherapy].

PubMed

Suzuki, Kei; Sekine, Takao

2014-05-01

A 67-year-old woman with acute Philadelphia-chromosome-positive mixed phenotype leukemia developed bilateral periorbital ecthyma gangrenousum (EG) subsequent to periorbital edema while undergoing combined imatinib mesylate (imatinib) chemotherapy. Although initial periorbital edema was considered an imatinib side effect, the lesion deteriorated rapidly with high fever in the neutropenic phase, and the woman died of septic shock. Cultures from blood and exudative fluid grew Pseudomonas aeruginosa, after which EG was diagnosed. EG is a well-recognized emergent cutaneous infection most commonly associated with Pseudomonas aeruginosa bactremia. Because some patients present with EG a few days prior to developing life-threatening septicemia, it is important that EG be diagnosed correctly. Imatinib side effects such as edema are usually tolerable, and imatinib is widely used to treat Philadelphia-chromosome-positive leukemia, particularly in those with acute lymphoblastic leukemia, and neutropenic patients undergoing imatinib therapy are expected to increase in number. Delay in initiating appropriate therapy is correlated with poor outcome, so drug side effects and EG must be carefully differentiated when skin edema with surrounding erythema is noted in neutropenic patients undergoing imatinib therapy.

Development and evaluation of an audiovisual information resource to promote self-management of chemotherapy side-effects.

PubMed

Carey, Mariko; Jefford, Michael; Schofield, Penelope; Kelly, Siobhan; Krishnasamy, Meinir; Aranda, Sanchia

2006-04-01

Based on a theoretical framework, we developed an audiovisual resource to promote self-management of eight common chemotherapy side-effects. A patient needs analysis identified content domains, best evidence for preparing patients for threatening medical procedures and a systematic review of effective self-care strategies informed script content. Patients and health professionals were invited to complete a written evaluation of the video. A 25-min video was produced. Fifty health professionals and 37 patients completed the evaluation. All considered the video informative and easy to understand. The majority believed the video would reduce anxiety and help patients prepare for chemotherapy. Underpinned by a robust theoretical framework, we have developed an evidence-based resource that is perceived by both patients and health professionals as likely to enhance preparedness for chemotherapy.

Advances in the medical treatment of juvenile rheumatoid arthritis.

PubMed

Onel, K B

2000-02-01

Juvenile rheumatoid arthritis (JRA) remains a challenge for clinicians. Nonsteroidal anti-inflammatory drugs and corticosteroids remain the mainstays of therapy, but concerns persist about side effects and the ability of these agents to prevent progression of bony disease. In recent years, novel treatments have been developed and quickly discarded because of unexpected toxicities or lack of efficacy. However, recent studies have shown that methotrexate and sulfasalazine are relatively safe and effective for JRA. Newly developed drugs, such as selective cyclooxygenase-2 inhibitors and soluble tumor necrosis factor receptor, whose development has stemmed from a more basic understanding of pathophysiology, may provide better disease control with fewer side effects. Finally, novel therapies, such as stem cell transplantation, may offer hope for children with JRA, especially systemic-onset JRA, whose disease has been refractory to conventional therapy.

Exercise and prostate cancer: From basic science to clinical applications.

PubMed

Campos, Christian; Sotomayor, Paula; Jerez, Daniel; González, Javier; Schmidt, Camila B; Schmidt, Katharina; Banzer, Winfried; Godoy, Alejandro S

2018-06-01

Prostate cancer (PCa) is a disease of increasing medical significance worldwide. In developed countries, PCa is the most common non-skin cancer in men, and one of the leading causes of cancer-related deaths. Exercise is one of the environmental factors that have been shown to influence cancer risk. Moreover, systemic reviews and meta-analysis have suggested that total physical activity is related to a decrease in the risk of developing PCa. In addition, epidemiological studies have shown that exercise, after diagnosis, has benefits regarding PCa development, and positive outcome in patients under treatment. The standard treatment for locally advanced or metastatic PCa is Androgen deprivation therapy (ADT). ADT produces diverse side effects, including loss of libido, changes in body composition (increase abdominal fat), and reduced muscle mass, and muscle tone. Analysis of numerous research publications showed that aerobic and/or resistance training improve patient's physical condition, such us, cardiorespiratory fitness, muscle strength, physical function, body composition, and fatigue. Therefore, exercise might counteract several ADT treatment-induced side effects. In addition of the aforementioned benefits, epidemiological, and in vitro studies have shown that exercise might decrease PCa development. Thus, physical activity might attenuate the risk of PCa and supervised exercise intervention might improve deleterious effects of cancer treatment, such as ADT side effects. This review article provides evidence indicating that exercise could complement, and potentiate, the current standard treatments for advanced PCa, probably by creating an unfavorable microenvironment that can negatively affect tumor development, and progression. © 2018 Wiley Periodicals, Inc.

Reliability Stress-Strength Models for Dependent Observations with Applications in Clinical Trials

NASA Technical Reports Server (NTRS)

Kushary, Debashis; Kulkarni, Pandurang M.

1995-01-01

We consider the applications of stress-strength models in studies involving clinical trials. When studying the effects and side effects of certain procedures (treatments), it is often the case that observations are correlated due to subject effect, repeated measurements and observing many characteristics simultaneously. We develop maximum likelihood estimator (MLE) and uniform minimum variance unbiased estimator (UMVUE) of the reliability which in clinical trial studies could be considered as the chances of increased side effects due to a particular procedure compared to another. The results developed apply to both univariate and multivariate situations. Also, for the univariate situations we develop simple to use lower confidence bounds for the reliability. Further, we consider the cases when both stress and strength constitute time dependent processes. We define the future reliability and obtain methods of constructing lower confidence bounds for this reliability. Finally, we conduct simulation studies to evaluate all the procedures developed and also to compare the MLE and the UMVUE.

The Oxford Questionnaire on the Emotional Side-effects of Antidepressants (OQuESA): development, validity, reliability and sensitivity to change.

PubMed

Price, Jonathan; Cole, Victoria; Doll, Helen; Goodwin, Guy M

2012-09-01

Some patients with major depression report a restricted range of emotions that may appear to arise as a side-effect of treatment with antidepressants. It is uncertain whether this phenomenon, sometimes called emotional blunting, represents residual symptoms of depression or side-effects of antidepressant treatment. There is currently no adequate instrument to measure this phenomenon. A draft questionnaire was developed from patient-derived qualitative data, refined using cognitive interviewing, and administered on three occasions to patients taking antidepressants. Statistical methods including factor analysis were used to reduce the size of the draft questionnaire, and to assess the performance of the resulting Oxford Questionnaire on the Emotional Side-effects of Antidepressants (OQuESA). 207 patients completed the OQuESA on at least one occasion. Their BDI-II scores and self-reported emotional blunting were spread across the possible range. The factor analysis resulted in four dimensions: 'not caring', 'emotional detachment', 'reduction in positive emotions', and 'general reduction in emotions'. The OQuESA appears to be acceptable, valid, and reliable, with sensitivity to change. The OQuESA offers promise as an effective self-report measure of the symptoms of emotional blunting in patients with depression. It can be used as a clinical tool, to facilitate the identification of patients with the syndrome of emotional blunting. It should also be used in research studies, to advance our understanding of the nature, causes and treatment of this phenomenon. Copyright © 2012 Elsevier B.V. All rights reserved.

Exploring consumer opinions on the presentation of side-effects information in Australian Consumer Medicine Information leaflets.

PubMed

Tong, Vivien; Raynor, David K; Blalock, Susan J; Aslani, Parisa

2016-06-01

Consumer Medicine Information (CMI) is a brand-specific and standardized source of written medicine information available in Australia for all prescription medicines. Side-effect information is poorly presented in CMI and may not adequately address consumer information needs. To explore consumer opinions on (i) the presentation of side-effect information in existing Australian CMI leaflets and alternative study-designed CMIs and (ii) side-effect risk information and its impact on treatment decision making. Fuzzy trace, affect heuristic, frequency hypothesis and cognitive-experiential theories were applied when revising existing CMI side-effects sections. Together with good information design, functional linguistics and medicine information expertise, alternative ramipril and clopidogrel CMI versions were proposed. Focus groups were then conducted to address the study objectives. Three focus groups (n = 18) were conducted in Sydney, Australia. Mean consumer age was 58 years (range 50-65 years), with equal number of males and females. All consumers preferred the alternative CMIs developed as part of the study, with unequivocal preference for the side-effects presented in a simple tabular format, as it allowed quick and easy access to information. Consumer misunderstandings reflected literacy and numeracy issues inherent in consumer risk appraisal. Many preferred no numerical information and a large proportion preferred natural frequencies. One single method of risk presentation in CMI is unable to cater for all consumers. Consumer misunderstandings are indicative of possible health literacy and numeracy factors that influence consumer risk appraisal, which should be explored further. © 2014 The Authors Health Expectations Published by John Wiley & Sons Ltd.

The toxicology of cannabis and cannabis prohibition.

PubMed

Grotenhermen, Franjo

2007-08-01

The acute side effects caused by cannabis use are mainly related to psyche and cognition, and to circulation. Euphoria, anxiety, changes in sensory perception, impairment of memory and psychomotor performance are common effects after a dose is taken that exceeds an individually variable threshold. Cannabis consumption may increase heart rate and change blood pressure, which may have serious consequences in people with heart disease. Effects of chronic use may be induction of psychosis and development of dependency to the drug. Effects on cognitive abilities seem to be reversible after abstinence, except possibly in very heavy users. Cannabis exposure in utero may have negative consequences on brain development with subtle impairment of cognitive abilities in later life. Consequences of cannabis smoking may be similar to those of tobacco smoking and should be avoided. Use by young people has more detrimental effects than use by adults. There appear to be promising therapeutic uses of cannabis for a range of indications. Use of moderate doses in a therapeutic context is usually not associated with severe side effects. Current prohibition on cannabis use may also have harmful side effects for the individual and the society, while having little influence on prevalence of use. Harm is greatest for seriously ill people who may benefit from a treatment with cannabis. This makes it difficult to justify criminal penalties against patients.

Side Effect Perceptions and Their Impact on Treatment Decisions in Women.

PubMed

Waters, Erika A; Pachur, Thorsten; Colditz, Graham A

2017-04-01

Side effects prompt some patients to forego otherwise-beneficial therapies. This study explored which characteristics make side effects particularly aversive. We used a psychometric approach, originating from research on risk perception, to identify the factors (or components) underlying side effect perceptions. Women ( N = 149) aged 40 to 74 years were recruited from a patient registry to complete an online experiment. Participants were presented with hypothetical scenarios in which an effective and necessary medication conferred a small risk of a single side effect (e.g., nausea, dizziness). They rated a broad range of side effects on several characteristics (e.g., embarrassing, treatable). In addition, we collected 4 measures of aversiveness for each side effect: choosing to take the medication, willingness to pay to avoid the side effect (WTP), negative affective attitude associated with the side effect, and how each side effect ranks among others in terms of undesirability. A principal components analysis (PCA) was used to identify the components underlying side effect perceptions. Then, for each aversiveness measure separately, regression analyses were used to determine which components predicted differences in aversiveness among the side effects. The PCA revealed 4 components underlying side effect perceptions: affective challenge (e.g., frightening), social challenge (e.g., disfiguring), physical challenge (e.g., painful), and familiarity (e.g., common). Side effects perceived as affectively and physically challenging elicited the highest levels of aversiveness across all 4 measures. Understanding what side effect characteristics are most aversive may inform interventions to improve medical decisions and facilitate the translation of novel biomedical therapies into clinical practice.

Side Effect Perceptions and their Impact on Treatment Decisions in Women

PubMed Central

Waters, Erika A.; Pachur, Thorsten; Colditz, Graham A.

2016-01-01

Background Side effects prompt some patients to forego otherwise-beneficial therapies. This study explored which characteristics make side effects particularly aversive. Methods We used a psychometric approach, originating from research on risk perception, to identify the factors (or components) underlying side effect perceptions. Women (N=149) aged 40–74 were recruited from a patient registry to complete an online experiment. Participants were presented with hypothetical scenarios in which an effective and necessary medication conferred a small risk of a single side effect (e.g., nausea, dizziness). They rated a broad range of side effects on several characteristics (e.g., embarrassing, treatable). In addition, we collected four measures of aversiveness for each side effect: choosing to take the medication, willingness to pay to avoid the side effect (WTP), negative affective attitude associated with the side effect, and how each side effect ranks among others in terms of undesirability. A principle-components analysis (PCA) was used to identify the components underlying side effect perceptions. Then, for each aversiveness measure separately, regression analyses were used to determine which components predicted differences in aversiveness among the side effects. Results The PCA revealed four components underlying side effect perceptions: affective challenge (e.g., frightening), social challenge (e.g., disfiguring), physical challenge (e.g., painful), and familiarity (e.g., common). Side effects perceived as affectively and physically challenging elicited the highest levels of aversiveness across all four measures. Conclusions Understanding what side effect characteristics are most aversive may inform interventions to improve medical decisions and facilitate the translation of novel biomedical therapies into clinical practice. PMID:27216581

New findings in pharmacogenetics of schizophrenia.

PubMed

Zai, Clement C; Tiwari, Arun K; Zai, Gwyneth C; Maes, Miriam S; Kennedy, James L

2018-05-01

This review highlights recent advances in the investigation of genetic factors for antipsychotic response and side effects. Antipsychotics prescribed to treat psychotic symptoms are variable in efficacy and propensity for causing side effects. The major side effects include tardive dyskinesia, antipsychotic-induced weight gain (AIWG), and clozapine-induced agranulocytosis (CIA). Several promising associations of polymorphisms in genes including HSPG2, CNR1, and DPP6 with tardive dyskinesia have been reported. In particular, a functional genetic polymorphism in SLC18A2, which is a target of recently approved tardive dyskinesia medication valbenazine, was associated with tardive dyskinesia. Similarly, several consistent findings primarily from genes modulating energy homeostasis have also been reported (e.g. MC4R, HTR2C). CIA has been consistently associated with polymorphisms in the HLA genes (HLA-DQB1 and HLA-B). The association findings between glutamate system genes and antipsychotic response require additional replications. The findings to date are promising and provide us a better understanding of the development of side effects and response to antipsychotics. However, more comprehensive investigations in large, well characterized samples will bring us closer to clinically actionable findings.

Lead Phytochemicals for Anticancer Drug Development

PubMed Central

Singh, Sukhdev; Sharma, Bhupender; Kanwar, Shamsher S.; Kumar, Ashok

2016-01-01

Cancer is a serious concern at present. A large number of patients die each year due to cancer illnesses in spite of several interventions available. Development of an effective and side effects lacking anticancer therapy is the trending research direction in healthcare pharmacy. Chemical entities present in plants proved to be very potential in this regard. Bioactive phytochemicals are preferential as they pretend differentially on cancer cells only, without altering normal cells. Carcinogenesis is a complex process and includes multiple signaling events. Phytochemicals are pleiotropic in their function and target these events in multiple manners; hence they are most suitable candidate for anticancer drug development. Efforts are in progress to develop lead candidates from phytochemicals those can block or retard the growth of cancer without any side effect. Several phytochemicals manifest anticancer function in vitro and in vivo. This article deals with these lead phytomolecules with their action mechanisms on nuclear and cellular factors involved in carcinogenesis. Additionally, druggability parameters and clinical development of anticancer phytomolecules have also been discussed. PMID:27877185

Effect of Communication Style on Perceptions of Medication Side Effect Risk among Pharmacy Students.

PubMed

Sawant, Ruta V; Beatty, Collin R; Sansgiry, Sujit S

2016-10-25

Objective. To assess the effect of communication style, and frequency and severity of medication side-effects, on pharmacy students' perception of risk of experiencing side effects. Methods. One hundred responses from pharmacy students were obtained using an online survey. Participants were presented with a drug information box containing drug name, drug usage, and one side-effect associated with the drug. Information on side-effect for each drug was presented in one of eight experimental conditions, in a 2 (side-effect frequency: low, high), X2 (side-effect severity: mild, severe) X2 (communication style: verbal, verbal + natural frequency) factorial design. Risk perception of experiencing side effects was measured. Results. Communication style was found to have a significant impact on risk perception depending on the context of frequency and severity associated with the side effect. Conclusion. Communication style plays a significant role in formulating risk perceptions of medication side effects. Training in pharmaceutical counseling should include special emphasis on effective language use.

A comparison of the effects of visual deprivation and regular body weight support treadmill training on improving over-ground walking of stroke patients: a multiple baseline single subject design.

PubMed

Kim, Jeong-Soo; Kang, Sun-Young; Jeon, Hye-Seon

2015-01-01

The body-weight-support treadmill (BWST) is commonly used for gait rehabilitation, but other forms of BWST are in development, such as visual-deprivation BWST (VDBWST). In this study, we compare the effect of VDBWST training and conventional BWST training on spatiotemporal gait parameters for three individuals who had hemiparetic strokes. We used a single-subject experimental design, alternating multiple baselines across the individuals. We recruited three individuals with hemiparesis from stroke; two on the left side and one on the right. For the main outcome measures we assessed spatiotemporal gait parameters using GAITRite, including: gait velocity; cadence; step time of the affected side (STA); step time of the non-affected side (STN); step length of the affected side (SLA); step length of the non-affected side (SLN); step-time asymmetry (ST-asymmetry); and step-length asymmetry (SL-asymmetry). Gait velocity, cadence, SLA, and SLN increased from baseline after both interventions, but STA, ST-asymmetry, and SL-asymmetry decreased from the baseline after the interventions. The VDBWST was significantly more effective than the BWST for increasing gait velocity and cadence and for decreasing ST-asymmetry. VDBWST is more effective than BWST for improving gait performance during the rehabilitation for ground walking.

[Pregnancy and breastfeeding. Side effects of drugs used in the treatment of thyroid diseases, on the fetus and the newborn].

PubMed

Matos, L; Afonso, A

2003-01-01

The authors allude to the composed anti-thyroid drugs, blocking drugs, iodides, radioactive iodine, lithium carbonate and tyrosine side effects. The most common are composed anti-thyroid drugs and tyrosine. Anti-thyroid drugs risks are related to the tresspassing of the placenta barrier which can induce in goitre and hypothyroidism. Thyroid hormones are also very important for the fetus neural development during the first quarter when they cross the placenta.

Seizures associated with low-dose tramadol for chronic pain treatment

PubMed Central

Beyaz, Serbülent Gökhan; Sonbahar, Tuğba; Bayar, Fikret; Erdem, Ali Fuat

2016-01-01

The management of cancer pain still poses a major challenge for clinicians. Tramadol is a centrally acting synthetic opioid analgesic. Its well-known side effects include nausea, vomiting, and dizziness; seizures are a rare side effect. Some reports have found that tramadol triggers seizure activity at high doses, whereas a few preclinical studies have found that this seizure activity is not dose-related. We herein present a case involving a patient with laryngeal cancer who developed seizures while on low-dose oral tramadol. PMID:27212778

Yohimbine-induced cutaneous drug eruption, progressive renal failure, and lupus-like syndrome.

PubMed

Sandler, B; Aronson, P

1993-04-01

Yohimbine is an indole alkaloid obtained from the yohimbe tree, a common tree in West Africa. We describe a forty-two-year black man in whom a generalized erythrodermic skin eruption, progressive renal failure, and lupus-like syndrome developed following treatment with the drug, yohimbine. A literature review failed to reveal any reported association of these side effects. We review current information on yohimbine's use in male impotence, reported side effects, and its role as a drug allergen.

Transforming Biology Assessment with Machine Learning: Automated Scoring of Written Evolutionary Explanations

NASA Astrophysics Data System (ADS)

Nehm, Ross H.; Ha, Minsu; Mayfield, Elijah

2012-02-01

This study explored the use of machine learning to automatically evaluate the accuracy of students' written explanations of evolutionary change. Performance of the Summarization Integrated Development Environment (SIDE) program was compared to human expert scoring using a corpus of 2,260 evolutionary explanations written by 565 undergraduate students in response to two different evolution instruments (the EGALT-F and EGALT-P) that contained prompts that differed in various surface features (such as species and traits). We tested human-SIDE scoring correspondence under a series of different training and testing conditions, using Kappa inter-rater agreement values of greater than 0.80 as a performance benchmark. In addition, we examined the effects of response length on scoring success; that is, whether SIDE scoring models functioned with comparable success on short and long responses. We found that SIDE performance was most effective when scoring models were built and tested at the individual item level and that performance degraded when suites of items or entire instruments were used to build and test scoring models. Overall, SIDE was found to be a powerful and cost-effective tool for assessing student knowledge and performance in a complex science domain.

Family Caregiver Knowledge, Patient Illness Characteristics, and Unplanned Hospital Admissions in Older Adults With Cancer.

PubMed

Geddie, Patricia I; Wochna Loerzel, Victoria; Norris, Anne E

2016-07-01

To explore factors related to unplanned hospital admissions and determine if one or more factors are predictive of unplanned hospital admissions for older adults with cancer.
. A prospective longitudinal design and a retrospective chart review.
. Adult oncology outpatient infusion centers and inpatient units at Orlando Regional Medical Center in Florida.
. A convenience sample of 129 dyads of older adults with cancer and their family caregivers. 
. Family caregiver demographic and side effect knowledge data were collected prospectively during interviews with family caregivers using a newly developed tool, the Nurse Assessment of Family Caregiver Knowledge and Action Tool. Patient demographic and clinical data were obtained through a retrospective chart review. Descriptive statistics and logistic regression analyses were used to evaluate data and examine relationships among variables.
. Patient illness characteristics; impaired function; side effects, such as infection, fever, vomiting, and diarrhea; family caregiver knowledge; and unplanned hospital admissions.
. Unplanned hospital admissions were more likely to occur when older adults had impaired function and side effects, such as infection, fever, vomiting, and diarrhea. Impaired function and family caregiver knowledge did not moderate the effects of these side effects on unplanned hospital admissions. 
. Findings suggest that the presence of impaired function and side effects, such as infection, fever, vomiting, and diarrhea, predict unplanned hospital admissions in older adults with cancer during the active treatment phase. Side effects may or may not be related to chemotherapy and may be related to preexisting comorbidities. 
. Nurses can conduct targeted assessments to identify older adults and their family caregivers who will need additional follow-up and support during the cancer treatment trajectory. Information gained from these assessments will assist nurses to provide practical and tailored strategies to reduce the risk for unplanned admissions.

A survey on the knowledge, beliefs and behaviour of a general adult population in Malaysia with respect to the adverse effects of medicines.

PubMed

Jose, Jimmy; Chong, David; Lynn, Tay Szu; Jye, Goh Ee; Jimmy, Beena

2011-08-01

The aim of the study was to explore, in the Malaysian general population: knowledge and beliefs of the characteristics in general of medication-related side effects and side effects associated with different types of medicines; behaviour related to the safe use of drugs before and after taking a medication; and behaviour in the event of a medication-related side effect. A 24-item self-administered questionnaire was developed and used to survey the general public living or working in suburban Kuala Lumpur, Malaysia. Eight hundred questionnaires were distributed, face to face, by researchers using quota sampling. Respondents' knowledge, belief and behaviour were analysed and correlated with demographics, medical history and experience of side effects. Six hundred and ten respondents completed the questionnaire giving a response rate of 76.3%. The mean knowledge score for the respondents was 18.4±3.6 out of the maximum possible score of 26. Educational level and experience of side effect had an influence on the knowledge score obtained. Respondents had misconceptions regarding the safety of complementary and alternative medicines (CAMs) and over-the-counter medications. Medication history and previous experience with side effects had a significant influence on the higher behaviour score obtained. The survey has shown moderate results with regard to the knowledge of public regarding safety of medications, and there was evidence of under-estimating the risk of medications, especially CAMs. The misconceptions among the public, and inappropriate behaviour on drug safety-related aspects, is a concern which needs to be addressed in the interventions designed. © 2011 The Authors. IJPP © 2011 Royal Pharmaceutical Society.

Chitin Oligosaccharide (COS) Reduces Antibiotics Dose and Prevents Antibiotics-Caused Side Effects in Adolescent Idiopathic Scoliosis (AIS) Patients with Spinal Fusion Surgery.

PubMed

Qu, Yang; Xu, Jinyu; Zhou, Haohan; Dong, Rongpeng; Kang, Mingyang; Zhao, Jianwu

2017-03-14

Antibiotics are always considered for surgical site infection (SSI) in adolescent idiopathic scoliosis (AIS) surgery. However, the use of antibiotics often causes the antibiotic resistance of pathogens and side effects. Thus, it is necessary to explore natural products as drug candidates. Chitin Oligosaccharide (COS) has anti-inflammation and anti-bacteria functions. The effects of COS on surgical infection in AIS surgery were investigated. A total of 312 AIS patients were evenly and randomly assigned into control group (CG, each patient took one-gram alternative Azithromycin/Erythromycin/Cloxacillin/Aztreonam/Ceftazidime or combined daily), experiment group (EG, each patient took 20 mg COS and half-dose antibiotics daily), and placebo group (PG, each patient took 20 mg placebo and half-dose antibiotics daily). The average follow-up was one month, and infection severity and side effects were analyzed. The effects of COS on isolated pathogens were analyzed. SSI rates were 2%, 3% and 8% for spine wounds and 1%, 2% and 7% for iliac wound in CG, EG and PG ( p < 0.05), respectively. COS reduces the side effects caused by antibiotics ( p < 0.05). COS improved biochemical indexes and reduced the levels of interleukin (IL)-6 and tumor necrosis factor (TNF) alpha. COS reduced the antibiotics dose and antibiotics-caused side effects in AIS patients with spinal fusion surgery by improving antioxidant and anti-inflammatory activities. COS should be developed as potential adjuvant for antibiotics therapies.

Ketamine for Pain Management-Side Effects & Potential Adverse Events.

PubMed

Allen, Cheryl A; Ivester, Julius R

2017-12-01

An old anesthetic agent, ketamine is finding new use in lower doses for analgesic purposes. There are concerns stemming from its potential side effects-specifically psychomimetic effects. These side effects are directly related to dose amount. The doses used for analgesic purposes are much lower than those used for anesthesia purposes. A literature review was performed to ascertain potential side effects and/or adverse events when using ketamine for analgesia purposes. The search included CINAHL, PubMed, and Ovid using the search terms "ketamine," "ketamine infusion," "pain," "adverse events," "practice guideline," and "randomized controlled trial." Searches were limited to full-text, peer-reviewed articles and systematic reviews. Initially 1,068 articles were retrieved. The search was then narrowed by using the Boolean connector AND with various search term combinations. After adjusting for duplication, article titles and abstracts were reviewed, leaving 25 articles for an in-depth analysis. Specific exclusion criteria were then applied. The literature supports the use of ketamine for analgesic purposes, and ketamine offers a nonopioid option for the management of some pain conditions. Because ketamine is still classified as an anesthetic agent, health care institutions should develop their own set of policies and protocols for the administration of ketamine. By using forethought and understanding of the properties of ketamine, appropriate care may be planned to mitigate potential side effects and adverse events so that patients are appropriately cared for and their pain effectively managed. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Safety of Adrenaline Use in Anaphylaxis: A Multicentre Register.

PubMed

Cardona, Victòria; Ferré-Ybarz, Laia; Guilarte, Mar; Moreno-Pérez, Nuria; Gómez-Galán, Catalina; Alcoceba-Borràs, Eva; Delavalle, Maria Belén; Garriga-Baraut, Teresa

2017-01-01

The use of intramuscular adrenaline to treat anaphylaxis is suboptimal, despite being the first-line treatment recommended by national and international anaphylaxis guidelines. Fear of potentially severe side effects may be one of the underlying factors. The aim of this study was to assess the incidence and severity of adverse side effects after the use of adrenaline in anaphylaxis, as well as potential risk factors. Observational study based on a multicenter online registry of cases of adrenaline administration for suspected anaphylaxis. 277 registered valid cases were included: 138 (51.49%) female, median age 29 years (12-47), and 6 children under 2 years with a median age of 9 months (1-21). Side effects occurred in 58 cases (21.64%), with tremors, palpitations, and anxiety being the most frequent. There was a significant association of developing side effects with older age, higher dose of adrenaline, or use of the intravenous route. Potentially severe adverse effects (high blood pressure, chest discomfort, or ECG alterations) occurred only in 8 cases (2.99%); in these cases, no differences were found according to age or adrenaline dose, but again, intravenous administration was associated with more severe adverse events. This study shows that side effects affect less than 1 in 5 patients who receive adrenaline for an anaphylactic reaction, and are usually mild and transient. Therefore, in an emergency situation such as anaphylaxis, restricting adrenaline administration due to potential adverse effects would, in general, not be justified. © 2017 S. Karger AG, Basel.

Synthetic Studies of Neoclerodane Diterpenes from Salvia divinorum: Identification of a Potent and Centrally Acting μ Opioid Analgesic with Reduced Abuse Liability.

PubMed

Crowley, Rachel Saylor; Riley, Andrew P; Sherwood, Alexander M; Groer, Chad E; Shivaperumal, Nirajmohan; Biscaia, Miguel; Paton, Kelly; Schneider, Sebastian; Provasi, Davide; Kivell, Bronwyn M; Filizola, Marta; Prisinzano, Thomas E

2016-12-22

Opioids are widely used to treat millions suffering from pain, but their analgesic utility is limited due to associated side effects. Herein we report the development and evaluation of a chemical probe exhibiting analgesia and reduced opioid-induced side effects. This compound, kurkinorin (5), is a potent and selective μ-opioid receptor (MOR) agonist (EC 50 = 1.2 nM, >8000 μ/κ selectivity). 5 is a biased activator of MOR-induced G-protein signaling over β-arrestin-2 recruitment. Metadynamics simulations of 5's binding to a MOR crystal structure suggest energetically preferred binding modes that differ from crystallographic ligands. In vivo studies with 5 demonstrate centrally mediated antinociception, significantly reduced rewarding effects, tolerance, and sedation. We propose that this novel MOR agonist may represent a valuable tool in distinguishing the pathways involved in MOR-induced analgesia from its side effects.

Minimal contribution of severe hypertriglyceridemia in L-asparaginase-associated pancreatitis developed in a child with acute lymphocytic leukemia.

PubMed

Goto, Yoshinori; Nishimura, Ryosei; Nohara, Atsushi; Mase, Shintaro; Fujiki, Toshihiro; Irabu, Hitoshi; Kuroda, Rie; Araki, Raita; Ikawa, Yasuhiro; Maeba, Hideaki; Yachie, Akihiro

2016-08-01

A 10-year-old girl developed L-asparaginase (ASP)-associated pancreatitis during chemotherapy for acute lymphocytic leukemia. Her symptoms showed alleviation with continuous regional arterial infusion of protease inhibitor and systemic somatostatin analog therapy. She had intermittent and marked hypertriglyceridemia, an initial trigger for pancreatitis, probably as a side effect of ASP and steroids. However, we considered the pancreatitis to have developed mainly because of factors other than hypertriglyceridemia as lipoprotein analysis confirmed chylomicron levels to be nearly undetectable. Extremely large chylomicrons contribute directly to the onset of pancreatitis by causing blockage of small vessels. Although it is necessary to examine patients for dyslipidemia developing as a side effect of ASP, therapeutic intervention for hypertriglyceridemia is not considered to prevent the onset of ASP-associated pancreatitis.

Earth's future in the Anthropocene: Technological interventions between piecemeal and utopian social engineering

NASA Astrophysics Data System (ADS)

Schäfer, Stefan; Stelzer, Harald; Maas, Achim; Lawrence, Mark G.

2014-04-01

An extensive discussion in the academic and policy communities is developing around the possibility of climate engineering through stratospheric aerosol injection (SAI). In this contribution, we develop a perspective on this issue in the context of the wider setting of societal development in the Anthropocene. We draw on Karl Popper's concepts of piecemeal and utopian social engineering to examine how different visions of societal development relate to SAI. Based on this reflection, we argue that the debate on SAI is fueled not only by the inequitable distribution of its effects and potential atmospheric and climatic side effects, as disconcerting as some of these effects and side effects may be, but also, and perhaps primarily, by its apparent privileging of the status quo and incremental change over a more immediate and radical change in societal organization. Although differing ideological orientations might thus help explain the intensity of parts of the debate, the understanding from which they follow, in which societal development is deduced from postulated technological characteristics and assumptions about a technology's use, hides from view a more subtle understanding of the relationship between technology and politics.

Comparison of light and x-ray sensitometric responses of double-emulsion films for different processing conditions.

PubMed

Blendl, C; Buhr, E

2001-12-01

The effects of different film processing conditions on light and x-ray sensitometric responses were compared for a variety of double-emulsion x-ray films. The processing conditions were altered by changes of the developer temperature. Three different exposure variants were applied: x-ray sensitometry using two stepped neutral density attenuators between film and screens, simultaneous double-sided light sensitometry, and single-sided light sensitometry. 13 different types of double-emulsion x-ray films were investigated, among them three asymmetric films. In the special case of exposing the asymmetric films with the single-sided light sensitometer, a method was investigated where each side of the film is exposed at different locations and the sum effect is analyzed. From each sensitometric curve shape two parameters, the logarithmic speed (logS) and the average gradient (G), were evaluated. The results of this study can be summarized as follows: (1) Single-sided and double-sided light sensitometers revealed almost equal changes of logS when the processing conditions are altered. Thus, single-sided light sensitometers can serve as a substitute for double-sided light sensitometers provided that suited exposure methods are used and appropriate sensitometric parameters are evaluated. (2) Light sensitometry quantitatively indicated changes of the film processing that affect the x-ray speed. Hence, light sensitometry is a useful method to monitor changes in film processing.

New Language and Old Problems in Breast Cancer Radiotherapy.

PubMed

Chiricuţă, Ion Christian

2017-01-01

New developments in breast cancer radiotherapy make possible new standards in treatment recommandations based on international guidelines. Developments in radiotherapy irradiation techniques from 2D to 3D-Conformal RT and to IMRT (Intensity Modulated Arc Therapy) make possible to reduce the usual side effects on the organs at risk as: skin, lung, miocard, bone, esophagus and brahial plexus. Dispite of all these progresses acute and late side effects are present. Side effects are as old as the radiotherapy was used. New solutions are available now by improving irradiation techniques. New techniques as sentinel node procedure (SNP) or partial breast irradiation (PBRT) and immediate breast reconstruction with silicon implants (IBRIS) make necessary new considerations regarding the target volume delineations. A new language for definition of gross tumor volume (GTV), clinical target volume (CTV) based on the new diagnostic methods as PET/CT,nonaparticle MRI will have real impact on target delineation and irradiation techniques. "The new common language in breast cancer therapy" would be the first step to improve the endresults and finally the quality of life of the patients. Celsius.

Health Related Quality of Life in Patients with Side-Effects after Antimuscarinic Treatment for Overactive Bladder.

PubMed

Kim, Aram; Lee, Kyu-Sung; Jung, Rangrhee; Na, Selee; Kim, Joon-Chul; Kim, Hyeong Gon; Choo, Myung-Soo

2017-09-01

Drug therapy is the mainstay of treatment for overactive bladder (OAB), but antimuscarinic agents possess side-effects. These side-effects decrease the patients' quality of life. We therefore assessed the impact of side-effects on health-related quality of life (HR-QoL) through an analysis of EQ-5D questionnaire. This study was designed to investigate the patients' satisfaction by quality weight of health status as affected by the side-effects of OAB medications. Patients who had OAB symptoms lasting longer than 3 months and have experienced side-effects after any antimuscarinic treatments filled in the EQ-5D questionnaire. The enrolled patients had two EQ-5D questionnaires for two different health statuses, i.e., presence or absence of side-effects. Quality weight was calculated using the ED-5D health status score with Korean tariff. One hundred patients were enrolled and completed the HR-QoL questionnaire. The most prevalent side-effect was dry mouth (61%) and 28% patients had dry mouth and constipation concurrently. Most of the patients with side-effects tried to endure and overcome these side-effects (79%), but 10% desired a change in medication, and 6% stopped medication altogether. The quality weight of EQ-5D without side-effects was 0.863, while the quality weight with side-effects was 0.666 (P < 0.001). The VAS score was 79 in patient without side-effects and 57 in those with side-effects, supporting the results of quality weight assessment. Overactive bladder patients may enjoy a better quality of life if side-effects associated with antimuscarinic therapy are fewer. © 2016 John Wiley & Sons Australia, Ltd.

[Machine Learning-based Prediction of Seizure-inducing Action as an Adverse Drug Effect].

PubMed

Gao, Mengxuan; Sato, Motoshige; Ikegaya, Yuji

2018-01-01

　During the preclinical research period of drug development, animal testing is widely used to help screen out a drug's dangerous side effects. However, it remains difficult to predict side effects within the central nervous system. Here, we introduce a machine learning-based in vitro system designed to detect seizure-inducing side effects before clinical trial. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices that were bath-perfused with each of 14 different drugs, and at 5 different concentrations of each drug. For each of these experimental conditions, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs) that induced seizure-like events, and identified diphenhydramine, enoxacin, strychnine and theophylline as "seizure-inducing" drugs, which have indeed been reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to pre-clinically detect seizure-inducing side effects of drugs.

Machine learning-based prediction of adverse drug effects: An example of seizure-inducing compounds.

PubMed

Gao, Mengxuan; Igata, Hideyoshi; Takeuchi, Aoi; Sato, Kaoru; Ikegaya, Yuji

2017-02-01

Various biological factors have been implicated in convulsive seizures, involving side effects of drugs. For the preclinical safety assessment of drug development, it is difficult to predict seizure-inducing side effects. Here, we introduced a machine learning-based in vitro system designed to detect seizure-inducing side effects. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices, while 14 drugs were bath-perfused at 5 different concentrations each. For each experimental condition, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs) that induced seizure-like events and identified diphenhydramine, enoxacin, strychnine and theophylline as "seizure-inducing" drugs, which indeed were reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to detect the seizure-inducing side effects of preclinical drugs. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Effects of boundary-layer separation controllers on a desktop fume hood.

PubMed

Huang, Rong Fung; Chen, Jia-Kun; Hsu, Ching Min; Hung, Shuo-Fu

2016-10-02

A desktop fume hood installed with an innovative design of flow boundary-layer separation controllers on the leading edges of the side plates, work surface, and corners was developed and characterized for its flow and containment leakage characteristics. The geometric features of the developed desktop fume hood included a rearward offset suction slot, two side plates, two side-plate boundary-layer separation controllers on the leading edges of the side plates, a slanted surface on the leading edge of the work surface, and two small triangular plates on the upper left and right corners of the hood face. The flow characteristics were examined using the laser-assisted smoke flow visualization technique. The containment leakages were measured by the tracer gas (sulphur hexafluoride) detection method on the hood face plane with a mannequin installed in front of the hood. The results of flow visualization showed that the smoke dispersions induced by the boundary-layer separations on the leading edges of the side plates and work surface, as well as the three-dimensional complex flows on the upper-left and -right corners of the hood face, were effectively alleviated by the boundary-layer separation controllers. The results of the tracer gas detection method with a mannequin standing in front of the hood showed that the leakage levels were negligibly small (≤0.003 ppm) at low face velocities (≥0.19 m/s).

Application of side-oblique image-motion blur correction to Kuaizhou-1 agile optical images.

PubMed

Sun, Tao; Long, Hui; Liu, Bao-Cheng; Li, Ying

2016-03-21

Given the recent development of agile optical satellites for rapid-response land observation, side-oblique image-motion (SOIM) detection and blur correction have become increasingly essential for improving the radiometric quality of side-oblique images. The Chinese small-scale agile mapping satellite Kuaizhou-1 (KZ-1) was developed by the Harbin Institute of Technology and launched for multiple emergency applications. Like other agile satellites, KZ-1 suffers from SOIM blur, particularly in captured images with large side-oblique angles. SOIM detection and blur correction are critical for improving the image radiometric accuracy. This study proposes a SOIM restoration method based on segmental point spread function detection. The segment region width is determined by satellite parameters such as speed, height, integration time, and side-oblique angle. The corresponding algorithms and a matrix form are proposed for SOIM blur correction. Radiometric objective evaluation indices are used to assess the restoration quality. Beijing regional images from KZ-1 are used as experimental data. The radiometric quality is found to increase greatly after SOIM correction. Thus, the proposed method effectively corrects image motion for KZ-1 agile optical satellites.

Effect of Physician Tutorials on Prescribing Patterns of Graduate Physicians.

ERIC Educational Resources Information Center

Klein, Lawrence E.; And Others

1981-01-01

Physicians in an experimental group were surveyed to assess their knowledge of the effectiveness, cost, and side effects of antibiotics, and a tutorial was developed to modify some prescribing patterns. Prescribing patterns were statistically different. (Author/MLW)

A comparison of three methods to evaluate the position of an artificial ear on the deficient side of the face from a three-dimensional surface scan of patients with hemifacial microsomia.

PubMed

Coward, Trevor J; Watson, Roger M; Richards, Robin; Scott, Brendan J J

2012-01-01

Patients with hemifacial microsomia may have a missing ear on the deficient side of the face. The fabrication of an ear for such individuals usually has been accomplished by directly measuring the ear on the normal side to construct a prosthesis based on these dimensions, and the positioning has been, to a large extent, primarily operator-dependent. The aim of the present study was to compare three methods, developed from the identification of landmarks plotted on three-dimensional surface scans, to evaluate the position of an artificial ear on the deficient side of the face compared with the position of the natural ear on the normally developed side. Laser scans were undertaken of the faces of 14 subjects with hemifacial microsomia. Landmarks on the ear and face on the normal side were identified. Three methods of mirroring the normal ear on the deficient side of the face were investigated, which used either facial landmarks from the orbital area or a zero reference point generated from the intersection of three orthogonal planes on a frame of reference. To assess the methods, landmarks were identified on the ear situated on the normal side as well as on the face. These landmarks yielded paired dimensional measurements that could be compared between the normal and deficient sides. Mean differences and 95% confidence intervals were calculated. It was possible to mirror the normal ear image on to the deficient side of the face using all three methods. Generally only small differences between the dimensional measurements on the normal and deficient sides were observed. However, two-way analysis of variance revealed statistically significant differences between the three methods (P = .005). The method of mirroring using the outer canthi was found to result in the smallest dimensional differences between the anthropometric points on the ear and face between the normally developed and deficient sides. However, the effects of the deformity can result in limitations in relation to achieving a precise alignment of the ear to the facial tissues. This requires further study.

Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human.

PubMed

Morgan, Michael M; Christie, MacDonald J

2011-10-01

Opioid agonists are the most effective treatment for pain, but their use is limited by side effects, tolerance and fears of addiction and dependence. A major goal of opioid research is to develop agonists that have high analgesic efficacy and a low profile for side effects, tolerance, addiction and dependence. Unfortunately, there is a serious lack of experimental data comparing the degree to which different opioids produce these effects in humans. In contrast, a wide range of experimental techniques from heterologous expression systems to behaviour assessment in whole animals have been developed to study these problems. The objective of this review is to describe and evaluate these techniques as they are used to study opioid efficacy, tolerance, addiction and dependence. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Explanations for side effect aversion in preventive medical treatment decisions

PubMed Central

Waters, Erika A.; Weinstein, Neil D.; Colditz, Graham A.; Emmons, Karen

2008-01-01

Objective Many laypeople demonstrate excessive sensitivity to negative side effects of medical treatments, which may lead them to refuse beneficial therapies. This Internet-based experiment investigated three possible explanations for such “side effect aversion.” One was derived from mental accounting, one examined the mere presence of a side effect, and one focused on computational difficulties. Design Participants (N = 5,379) were presented with a hypothetical cancer preventive treatment situation that was or was not accompanied by one or two small side effects. The side effects were either beneficial or harmful. In all conditions the net absolute risk reduction associated with the treatment was 15%. Main Outcome Measures Participants indicated their willingness to accept treatment and their perceptions of the treatment’s effects on their overall cancer risk. Results Data were consistent only with the “mere presence” explanation of side effect aversion, the idea that side effects act as a strong negative cue that directly affects treatment appraisal. The number of negative side effects did not influence treatment willingness. Conclusion Side effect aversion is a challenge to informed decision making. Specific mechanisms that produce side effect aversion should be identified. PMID:19290712

Effects of brain-derived neurotrophic factor (BDNF) on the cochlear nucleus in cats deafened as neonates.

PubMed

Kandathil, Cherian K; Stakhovskaya, Olga; Leake, Patricia A

2016-12-01

Many previous studies have shown significant neurotrophic effects of intracochlear delivery of BDNF in preventing degeneration of cochlear spiral ganglion (SG) neurons after deafness in rodents and our laboratory has shown similar results in developing cats deafened prior to hearing onset. This study examined the morphology of the cochlear nucleus (CN) in a group of neonatally deafened cats from a previous study in which infusion of BDNF elicited a significant improvement in survival of the SG neurons. Five cats were deafened by systemic injections of neomycin sulfate (60 mg/kg, SQ, SID) starting one day after birth, and continuing for 16-18 days until auditory brainstem response (ABR) testing demonstrated profound bilateral hearing loss. The animals were implanted unilaterally at about 1 month of age using custom-designed electrodes with a drug-delivery cannula connected to an osmotic pump. BDNF (94 μg/ml; 0.25 μl/hr) was delivered for 10 weeks. The animals were euthanized and studied at 14-23 weeks of age. Consistent with the neurotrophic effects of BDNF on SG survival, the total CN volume in these animals was significantly larger on the BDNF-treated side than on the contralateral side. However, total CN volume, both ipsi- and contralateral to the implants in these deafened juvenile animals, was markedly smaller than the CN in normal adult animals, reflecting the severe effects of deafness on the central auditory system during development. Data from the individual major CN subdivisions (DCN, Dorsal Cochlear Nucleus; PVCN, Posteroventral Cochlear Nucleus; AVCN, Anteroventral Cochlear Nucleus) also were analyzed. A significant difference was observed between the BDNF-treated and control sides only in the AVCN. Measurements of the cross-sectional areas of spherical cells showed that cells were significantly larger in the AVCN ipsilateral to the implant than on the contralateral side. Further, the numerical density of spherical cells was significantly lower in the AVCN ipsilateral to the implant than on the contralateral side, consistent with the larger AVCN volume observed with BDNF treatment. Together, findings indicate significant neurotrophic effects of intracochlear BDNF infusion on the developing CN. Copyright © 2016 Elsevier B.V. All rights reserved.

Real World Data Driven Evolution of Volvo Cars’ Side Impact Protection Systems and their Effectiveness

PubMed Central

Jakobsson, Lotta; Lindman, Magdalena; Svanberg, Bo; Carlsson, Henrik

2010-01-01

This study analyses the outcome of the continuous improved occupant protection over the last two decades for front seat near side occupants in side impacts based on a real world driven working process. The effectiveness of four generations of improved side impact protection are calculated based on data from Volvo’s statistical accident database of Volvo Cars in Sweden. Generation I includes vehicles with a new structural and interior concept (SIPS). Generation II includes vehicles with structural improvements and a new chest airbag (SIPSbag). Generation III includes vehicles with further improved SIPS and SIPSbag as well as the new concept with a head protecting Inflatable Curtain (IC). Generation IV includes the most recent vehicles with further improvements of all the systems plus advanced sensors and seat belt pretensioner activation. Compared to baseline vehicles, vehicles of generation I reduce MAIS2+ injuries by 54%, generation II by 61% and generation III by 72%. For generation IV effectiveness figures cannot be calculated because of the lack of MAIS2+ injuries. A continuous improved performance is also seen when studying the AIS2+ pelvis, abdomen, chest and head injuries separately. By using the same real world driven working process, future improvements and possibly new passive as well as active safety systems, will be developed with the aim of further improved protection to near side occupants in side impacts. PMID:21050597

Subjective Report of Side Effects of Prescribed and Nonprescribed Psychostimulant Use in Young Adults.

PubMed

Smith, Tess E; Martel, Michelle M; DeSantis, Alan D

2017-03-21

Side effects of prescribed and nonprescribed psychostimulant use are understudied. The study examined side effects of prescribed and nonprescribed psychostimulant use in a college sample with attention to possible gender differences. 2716 undergraduates (1448 male) between the ages of 17 and 57 years (M = 19.43 years, SD = 1.7 years) completed an online survey that included questions about the subjective side effects of prescribed and nonprescribed psychostimulant use. Results suggested that prescribed users more frequently reported side effects, compared to nonprescribed users. For prescribed users, females more frequently reported appetite, somatic, and anxiety-related side effects compared to males. For nonprescribed users, while females reported more somatic and anxiety-related side effects, males more frequently reported loss of sex drive and sweating as side effects. Conclusions/Importance: These findings suggest prescribed users of psychostimulants more frequently report side effects with prominent gender differences in line with gender roles.

Sexual side effects associated with conventional and atypical antipsychotics.

PubMed

Compton, M T; Miller, A H

2001-01-01

The sexual side effects of psychotropic medications are becoming increasingly recognized in clinical psychiatry. The magnitude of the problem of sexual side effects associated with antipsychotic medications has yet to be fully elucidated, but a multitude of references in the literature demonstrate the importance of these side effects in both men and women. All currently used antipsychotic medications are associated with sexual side effects of various types. Although each antipsychotic medication may have a specific side effect profile determined by its various receptor affinities and by the degree to which it elevates serum prolactin, there is currently no evidence that specific side effects can be predicted. Sexual side effects can be categorized according to the phase of the sexual response cycle with which they interfere. Suggestions for clinical evaluation and treatment options are provided, including risk factor modification, dose reduction, switching agents, and addition of other agents. Sexual side effects associated with conventional and atypical antipsychotic medications represent an underestimated and understudied set of side effects that may diminish a patient's quality of life and lead to treatment noncompliance. Clinicians prescribing antipsychotic medications should be familiar with the classification, evaluation, and treatment of these side effects.

Normal tissue complication probability (NTCP) models for late rectal bleeding, stool frequency and fecal incontinence after radiotherapy in prostate cancer patients.

PubMed

Schaake, Wouter; van der Schaaf, Arjen; van Dijk, Lisanne V; Bongaerts, Alfons H H; van den Bergh, Alfons C M; Langendijk, Johannes A

2016-06-01

Curative radiotherapy for prostate cancer may lead to anorectal side effects, including rectal bleeding, fecal incontinence, increased stool frequency and rectal pain. The main objective of this study was to develop multivariable NTCP models for these side effects. The study sample was composed of 262 patients with localized or locally advanced prostate cancer (stage T1-3). Anorectal toxicity was prospectively assessed using a standardized follow-up program. Different anatomical subregions within and around the anorectum were delineated. A LASSO logistic regression analysis was used to analyze dose volume effects on toxicity. In the univariable analysis, rectal bleeding, increase in stool frequency and fecal incontinence were significantly associated with a large number of dosimetric parameters. The collinearity between these predictors was high (VIF>5). In the multivariable model, rectal bleeding was associated with the anorectum (V70) and anticoagulant use, fecal incontinence was associated with the external sphincter (V15) and the iliococcygeal muscle (V55). Finally, increase in stool frequency was associated with the iliococcygeal muscle (V45) and the levator ani (V40). No significant associations were found for rectal pain. Different anorectal side effects are associated with different anatomical substructures within and around the anorectum. The dosimetric variables associated with these side effects can be used to optimize radiotherapy treatment planning aiming at prevention of specific side effects and to estimate the benefit of new radiation technologies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Simultaneous confidence sets for several effective doses.

PubMed

Tompsett, Daniel M; Biedermann, Stefanie; Liu, Wei

2018-04-03

Construction of simultaneous confidence sets for several effective doses currently relies on inverting the Scheffé type simultaneous confidence band, which is known to be conservative. We develop novel methodology to make the simultaneous coverage closer to its nominal level, for both two-sided and one-sided simultaneous confidence sets. Our approach is shown to be considerably less conservative than the current method, and is illustrated with an example on modeling the effect of smoking status and serum triglyceride level on the probability of the recurrence of a myocardial infarction. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Clinical Significance of Repetitive Compound Muscle Action Potentials in Patients with Myasthenia Gravis: A Predictor for Cholinergic Side Effects of Acetylcholinesterase Inhibitors

PubMed Central

Lee, Hyo Eun; Kim, Yool-hee; Kim, Seung Min

2016-01-01

Background and Purpose Acetylcholinesterase inhibitors (AChEIs) are widely used to treat myasthenia gravis (MG). Although AChEIs are usually tolerated well, some MG patients suffer from side effects. Furthermore, a small proportion of MG patients show cholinergic hypersensitivity and cannot tolerate AChEIs. Because repetitive compound muscle action potentials (R-CMAPs) are an electrophysiologic feature of cholinergic neuromuscular hyperactivity, we investigated the clinical characteristics of MG patients with R-CMAPs to identify their clinical usefulness in therapeutic decision-making. Methods We retrospectively reviewed the clinical records and electrodiagnostic findings of MG patients who underwent electrodiagnostic studies and diagnostic neostigmine testing (NT). Results Among 71 MG patients, 9 could not tolerate oral pyridostigmine bromide (PB) and 17 experienced side effects of PB. R-CMAPs developed in 24 patients after NT. The highest daily dose of PB was lower in the patients with R-CMAPs (240 mg/day vs. 480 mg/day, p<0.001). The frequencies of PB intolerance and side effects were higher in the patients with R-CMAPs than in those without R-CMAPs [37.5% vs. 0% (p<0.001) and 45.8% vs. 12.8% (p=0.002), respectively]. The MG Foundation of America postintervention status did not differ significantly between MG patients with and without R-CMAPs, and the response to immunotherapy was also good in both groups. Conclusions Side effects of and intolerance to AChEIs are more common in MG patients with R-CMAPs than in those without R-CMAPs. AChEIs should be used carefully in MG patients with R-CMAPs. The presence of R-CMAPs after NT may be a good indicator of the risks of PB side effects and intolerance. PMID:27819419

Valium without dependence? Individual GABAA receptor subtype contribution toward benzodiazepine addiction, tolerance, and therapeutic effects.

PubMed

Cheng, Tianze; Wallace, Dominique Marie; Ponteri, Benjamin; Tuli, Mahir

2018-01-01

Benzodiazepines are one of the most prescribed medications as first-line treatment of anxiety, insomnia, and epilepsy around the world. Over the past two decades, advances in the neuropharmacological understanding of gamma aminobutyric acid (GABA) A receptors revealed distinct contributions from each subtype and produced effects. Recent findings have highlighted the importance of α 1 containing GABA A receptors in the mechanisms of addiction and tolerance in benzodiazepine treatments. This has shown promise in the development of tranquilizers with minimal side effects such as cognitive impairment, dependence, and tolerance. A valium-like drug without its side effects, as repeatedly demonstrated in animals, is achievable.

Translational strategies for therapeutic development in nicotine addiction: rethinking the conventional bench to bedside approach.

PubMed

Le Foll, Bernard; Pushparaj, Abhiram; Pryslawsky, Yaroslaw; Forget, Benoit; Vemuri, Kiran; Makriyannis, Alexandros; Trigo, Jose M

2014-07-03

Tobacco produces an impressive burden of disease resulting in premature death in half of users. Despite effective smoking cessation medications (nicotine replacement therapies, bupropion and varenicline), there is a very high rate of relapse following quit attempts. The use of efficient strategies for the development of novel treatments is a necessity. A 'bench to bedside strategy' was initially used to develop cannabinoid CB1 receptor antagonists for the treatment of nicotine addiction. Unfortunately, after being tested on experimental animals, what seemed to be an interesting approach for the treatment of nicotine addiction resulted in serious unwanted side effects when tested in humans. Current research is focusing again on pre-clinical models in an effort to eliminate unwanted side effects while preserving the initially observed efficacy. A 'bed side to bench strategy' was used to study the role of the insula (part of the frontal cortex) in nicotine addiction. This line of research started based on clinical observations that patients suffering stroke-induced lesions to the insula showed a greater likelihood to report immediate smoking cessation without craving or relapse. Subsequently, animal models of addiction are used to explore the role of insula in addiction. Due to the inherent limitations existing in clinical versus preclinical studies, the possibility of close interaction between both models seems to be critical for the successful development of novel therapeutic strategies for nicotine dependence. © 2013.

Cognitive science in the era of artificial intelligence: A roadmap for reverse-engineering the infant language-learner.

PubMed

Dupoux, Emmanuel

2018-04-01

Spectacular progress in the information processing sciences (machine learning, wearable sensors) promises to revolutionize the study of cognitive development. Here, we analyse the conditions under which 'reverse engineering' language development, i.e., building an effective system that mimics infant's achievements, can contribute to our scientific understanding of early language development. We argue that, on the computational side, it is important to move from toy problems to the full complexity of the learning situation, and take as input as faithful reconstructions of the sensory signals available to infants as possible. On the data side, accessible but privacy-preserving repositories of home data have to be setup. On the psycholinguistic side, specific tests have to be constructed to benchmark humans and machines at different linguistic levels. We discuss the feasibility of this approach and present an overview of current results. Copyright © 2017 Elsevier B.V. All rights reserved.

Right side neglect in right cerebellar lesion

PubMed Central

Silveri, M; Misciagna, S; Terrezza, G

2001-01-01

A patient is described who developed right side hemineglect after a right cerebellar lesion. This spatial disorder was interpreted as a secondary effect of a deficit of the motor organisation in the right hemispace due to left frontal diaschisis. The pathological base may be the interruption of a highly integrated system which includes the lateral cerebellum and the contralateral frontal lobe.

 PMID:11413276

Ten-year development of Douglas-fir and associated vegetation after different site preparation on coast range clearcuts.

Treesearch

William I. Stein

1995-01-01

Side-by-side comparisons were made in an operational-sized, replicated experiment, installed in 1980-81 on four areas in the Coast Ranges of Oregon, to determine the effects of six methods of site preparation on the subsequent survival and growth of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) and associated vegetation. A decade later, tree...

Chromium Elimination and Cannon Life Extension for Gun Tubes

DTIC Science & Technology

2012-08-30

the use of hexavalent chromium (VI) in the production of cannon barrels by developing a cost effective environmentally friendly Explosive Bonding...erosion- resistant chrome cobalt alloy matrix with 15% tungsten. Stellite is used as M60 machine gun barrel liner. Tantalum Cobalt Tungsten...Grounds (YPG) Preliminary proof of principle endurance testing at YPG shows promising results when conducted side by side to a chrome plated

An update on analgesics.

PubMed

Power, I

2011-07-01

Recent introduction of new analgesics into the clinic is best described as a slow process with activity classified into two main areas: improving analgesic efficacy/potency and reducing side-effect profile. This review article describes some of the recent advances with an emphasis on use in the acute setting. In this respect, opioids continue to be the mainstay (but not the only) analgesic and there have been important improvements in their clinical effect profile. For example, tapentadol has been introduced as a mixed opioid and norepinephrine uptake inhibitor which, unlike tramadol, does not require metabolic activation and does not suffer from isomer-dependent pharmacodynamics. Opioid antagonists have received much attention recently either used alone, methylnaltrexone (s.c) or alvimopan (p.o), or in combination, Targinact (oxycodone/naloxone), and appear to be effective in reducing opioid side-effects such as those in the gastrointestinal tract. Other agents where there has been recent development include the use of gabapentin, methylxanthines, and local anaesthetics. An interesting area of translation of basic research is in the inhibition of breakdown of endogenous opioids with opiorphin, targeting of the endocannabinoid system, and the use of ampakines to obtund opioid-induced side-effects. It is clear that there is still much work to be done, but the need for highly efficacious analgesics with good side-effect profile remains.

Physiological and skill demands of 'on-side' and 'off-side' games.

PubMed

Gabbett, Tim J; Jenkins, David G; Abernethy, Bruce

2010-11-01

This study investigated the physiological and skill demands of 'on-side' and 'off-side' games in elite rugby league players. Sixteen male rugby league players participated in 'on-side' and 'off-side' games. Both small-sided games were played in a 40- × 40-m playing area. The 'off-side' game permitted players to have 3 'plays' while in possession of the ball. Players were permitted to pass backward or forward (to an 'off-side' player). The 'on-side' game also permitted players to have 3 'plays' while in possession of the ball. However, players were only permitted to pass backward to players in an 'on-side' position. Heart rate and movement patterns (via global positioning system) were recorded continuously throughout both games. Data were collected on the distance covered, number of high-acceleration and velocity efforts, and recovery between efforts. Video footage was also taken to track the performance of the players. Post hoc inspection of the footage was undertaken to count the number of possessions and the number and quality of disposals. In comparison to 'on-side' games, 'off-side' games had a greater number of involvements ("touches"), passes, and effective passes. However, the cognitive demands of 'on-side' games were greater than 'off-side' games. 'Off-side' games resulted in a greater total distance covered, greater distance covered in mild and moderate accelerations, and greater distance covered in low, moderate, and high-velocity efforts. There were also a greater number of short duration recovery periods between efforts in 'off-side' games. The results of this study demonstrate that 'off-side' games provide greater physiological and skill demands than 'on-side' games. 'Off-side' games may provide a practical alternative to 'on-side' games for the development of skill and fitness in elite rugby league players.

Gastrointestinal Side Effects of Antiarrhythmic Medications: A Review of Current Literature.

PubMed

Amjad, Waseem; Qureshi, Waqas; Farooq, Ali; Sohail, Umair; Khatoon, Salma; Pervaiz, Sarah; Narra, Pratyusha; Hasan, Syeda M; Ali, Farman; Ullah, Aman; Guttmann, Steven

2017-09-03

Antiarrhythmic drugs are commonly prescribed cardiac drugs. Due to their receptor mimicry with several of the gastrointestinal tract receptors, they can frequently lead to gastrointestinal side effects. These side effects are the most common reasons for discontinuation of these drugs by the patients. Knowledge of these side effects is important for clinicians that manage antiarrhythmic drugs. This review focuses on the gastrointestinal side effects of these drugs and provides a detailed up-to-date literature review of the side effects of these drugs. The review provides case reports reported in the literature as well as possible mechanisms that lead to gastrointestinal side effects.

Memory for Medication Side Effects in Younger and Older Adults: The Role of Subjective and Objective Importance

PubMed Central

Friedman, Michael C.; McGillivray, Shannon; Murayama, Kou; Castel, Alan D.

2014-01-01

Older adults often experience memory impairments, but can sometimes use selective processing and schematic support to remember important information. The current experiments investigate to what degree younger and healthy older adults remember medication side effects that were subjectively or objectively important to remember. Participants studied a list of common side effects, and rated how negative these effects were if they were to experience them, and were then given a free recall test. In Experiment 1, the severity of the side effects ranged from mild (e.g., itching) to severe (e.g., stroke), and in Experiment 2, certain side effects were indicated as critical to remember (i.e., “contact your doctor if you experience this”). There were no age differences in terms of free recall of the side effects, and older adults remembered more severe side effects relative to mild effects. However, older adults were less likely to recognize critical side effects on a later recognition test, relative to younger adults. The findings suggest that older adults can selectively remember medication side effects, but have difficulty identifying familiar but potentially critical side effects, and this has implications for monitoring medication use in older age. PMID:25331278

Zebrafish: A Model for the Study of Toxicants Affecting Muscle Development and Function

PubMed Central

Dubińska-Magiera, Magda; Daczewska, Małgorzata; Lewicka, Anna; Migocka-Patrzałek, Marta; Niedbalska-Tarnowska, Joanna; Jagla, Krzysztof

2016-01-01

The rapid progress in medicine, agriculture, and allied sciences has enabled the development of a large amount of potentially useful bioactive compounds, such as drugs and pesticides. However, there is another side of this phenomenon, which includes side effects and environmental pollution. To avoid or minimize the uncontrollable consequences of using the newly developed compounds, researchers seek a quick and effective means of their evaluation. In achieving this goal, the zebrafish (Danio rerio) has proven to be a highly useful tool, mostly because of its fast growth and development, as well as the ability to absorb the molecules diluted in water through its skin and gills. In this review, we focus on the reports concerning the application of zebrafish as a model for assessing the impact of toxicants on skeletal muscles, which share many structural and functional similarities among vertebrates, including zebrafish and humans. PMID:27869769

Neuropsychiatric manifestation after a stroke: newly developed symptoms or side-effect of drug?

PubMed Central

Tan, Eng Chai; Aziz, Noor Azah; Ahmad, Saharuddin

2012-01-01

A 55-year-old woman presented with sudden onset of left-sided body weakness and numbness, which was diagnosed as multifocal cerebral infarct with right thalamic bleed. She had concurrent hypertension, diabetes mellitus and chronic kidney disease. She suffered from central poststroke pain and reactive depression as poststroke complications, for which amitriptyline was prescribed. Unfortunately, she developed symptoms suggestive of mania and psychosis upon initiation of medications, which resolved upon withdrawal of amitriptyline. Amitriptyline is effective for treatment of poststroke pain and particularly useful in concomitant depression. Unexpectedly, this patient developed new psychopathologies after initiation of this medication. This case highlights the development of new psychopathologies that could be due to the antidepressant, underlying bipolar disorder or a complication of the stroke itself. Primary care providers need to actively enquire regarding neuropsychiatric symptoms because they can adversely affect the patient's quality of life as well as impede rehabilitation efforts. PMID:22907854

Inspection of cup-shaped steel parts from the I.D. side using eddy current

NASA Astrophysics Data System (ADS)

Griffiths, Erick W.; Pearson, Lee H.

2018-04-01

An eddy current method was developed to inspect cup-shaped steel parts from the I.D. side. During the manufacturing process of these parts, a thin Al tape foil is applied to the I.D. side of the part. One of the critical process parameters is that only one foil layer can be applied. An eddy current inspection system was developed to reject parts with more than one foil layer. The Al tape foil is cut to length to fit the inner diameter, however, after application of the foil there is a gap created between the beginning and end of the foil. It was found that this gap interfered with the eddy current inspection causing a false positive indication. To solve this problem a sensor design and data analysis process were developed to overcome the effects of these gaps. The developed system incorporates simultaneous measurements from multiple eddy current sensors and signal processing to achieve a reliable inspection.

Paclitaxel Nano-Delivery Systems: A Comprehensive Review

PubMed Central

Ma, Ping; Mumper, Russell J.

2013-01-01

Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles. PMID:24163786

The impact of an empowering Internet-based Breast Cancer Patient Pathway program on breast cancer patients' clinical outcomes: a randomised controlled trial.

PubMed

Ryhänen, Anne M; Rankinen, Sirkku; Siekkinen, Mervi; Saarinen, Maiju; Korvenranta, Heikki; Leino-Kilpi, Helena

2013-04-01

To evaluate the effect of the Breast Cancer Patient Pathway program on breast cancer patient's empowerment process. The results of earlier studies indicate that the use of tailored Internet-based patient education programs increased patient's knowledge level; however, other outcome measures differed. This randomised control trial studied the effect of the Internet-based patient educational program on breast cancer patients' empowerment. In this study, we measured the quality of life, anxiety and managing with treatment-related side effects as the outcomes of breast cancer patients' empowering process. Breast cancer patients who were Internet users in one Finnish university hospital during 2008-2010 were randomised to the control group (n=43) and the intervention group (n=47). Baseline data were collected first in the hospital and the following data seven times during the treatment process, the last time one year after breast cancer diagnosis. There were no statistically significant differences in the quality of life, anxiety or side effects of treatment between the groups. The amount of treatment-related side effects was connected to both physical and psychological well-being. In this study, the Breast Cancer Patient Pathway program did not decrease anxiety level or treatment-related side effects among breast cancer patients or improve subscales of quality of life when compared with controls. There is a need to relieve the side effects caused by patients' care with the help of patient education. Internet-based patient education programs need more focus when developing new patient education methods. © 2013 Blackwell Publishing Ltd.

Hormonal contraception and physiology: a research-based theory of discontinuation due to side effects.

PubMed

Vitzthum, Virginia J; Ringheim, Karin

2005-03-01

Side effects influence the acceptability and continuation of hormonal contraceptives. Counseling the client about the management of side effects is a principal approach advocated for increasing continuation. Evidence of a biological basis for variation in women's tolerance of hormonal contraceptives argues, however, that greater attention should be given to altering the product rather than principally attempting to alter a woman's ability to deal with the product. Discontinuation rates for hormonal contraceptives, largely attributable to side effects and health concerns, are high in nearly all less-developed countries for which Demographic and Health Survey data are available. Oral contraceptives appear to be particularly problematic for Latin American women, most notably in Bolivia. Clinical trials suggest substantial variation in the physiological response to exogenous hormones, and new evidence confirms the hypothesis that the normal hormonal profiles of Bolivian women are significantly lower than those of women in the United States. These findings suggest a need for more population-specific physiological research linked to analyses of the possible association between endogenous hormone differences and contraceptive continuation. Appropriately adjusting the level of the steroid delivered may benefit women's health and improve the acceptability and continuation of hormonal contraceptives.

The small miracle.

PubMed

Tiranti, D

1979-09-01

Although the standard argument for distributing birth control pills throughout the Third World is that they are less dangerous than pregnancy or abortion, irregular use of the pill increases riks of both. The irregularity of use can be attributed to both poor delivery systems and side effects. Side effects occur because of poor screening and lack of alternative dosages. Because of the lower price of buying in bulk, family planning groups distribute only 1 kind of pill. The woman who experiences side effects, e.g. headache, dizziness, weight gain, depression, has no choice but to discontinue use. Few women are screened by having their blood pressure taken, therefore the pill exacerbates illness in those with circulation problems. Breast-feeding mothers who take the pill provide less sustenance from their breastmilk, which can increase infant mortality rates. In Bangladesh a USAID-funded study on contractive distribution found that the "trained" family planning workers did not know what advice to give a woman who missed her pill on 5 consecutive days, or what type of side effects might be anticipated, or how many days after the onset of menstruation a woman should begin the pill. A more level headed approach to delivery of contraceptives in developing countries is needed.

“So far it’s been choosing which side effects I want or I can deal with”: A grounded theory of HIV treatment side effects among people living with HIV

PubMed Central

Holmes, Dave

2016-01-01

Despite the availability of new antiretroviral drugs and the simplification of treatment options, side effects continue to affect people living with HIV. In this paper, we present the findings of a grounded theory study designed to gain a critical understanding of the experience of side effects. Three main categories emerged from the data: the side effects, the experience, and the connections. The first category suggests that we need to change how we think about side effects in order to take into account the context in which they are experienced as well as the types and nature of side effects. The second category puts forward the idea that the experience of side effects is composed of three interrelated processes: becoming with, living with, and dealing with. Finally, the third category points to new connections that are formed with people, things and systems in the presence of side effects. PMID:27867446

Cutaneous side-effects of epidermal growth factor receptor-tyrosine kinase inhibitor (TKI) in the treatment of lung cancer: description and its management.

PubMed

Ong, C K; Tan, W C; Chan, L C; Abdul Razak, M

2012-04-01

Epidermal growth factor receptor (EGFR)--tyrosine kinase inhibitors (TKI) like erlotinib and gefitinib have been approved as monotherapy for the treatment of patients with locally advanced or metastatic non small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen. The use of EGFR-TKI is associated with unique and dramatic dermatologic side effects. We report 2 patients with NSCLC developing a typical acneiform (papulo-pustular) eruption shortly after initiation of EGFR-TKI.

Heat transfer in a conical porous medium due to inner and top surface heating: Effect of radius ratio

NASA Astrophysics Data System (ADS)

Ahamad, N. Ameer; Khan, T. M. Yunus

2018-05-01

The present study investigates the effect of radius ratio and Rayleigh number on beat transfer characteristics of an annular cone subjected to two side heating and one side cooling. Finite element method is used to convert the partial differential equations into algebraic equations. The resulting equations are solved with the help of in-house computer code developed for specific purpose of heat transfer in conical porous medium. The results are discussed with respect to the radius ratio and Rayleigh number.

Relation between therapeutic response and side effects induced by methylphenidate as observed by parents and teachers of children with ADHD.

PubMed

Lee, James; Grizenko, Natalie; Bhat, Venkataramana; Sengupta, Sarojini; Polotskaia, Anna; Joober, Ridha

2011-04-21

The desired (therapeutic) and undesired (side) effects of methylphenidate might have underlying correlations. The aim of this study was to explore the strength and the possible sources of these correlations. One hundred and fifty-seven children with ADHD (6-12 years) were administered placebo and methylphenidate (0.5 mg/kg in a divided b.i.d. dose), each for a one-week period, in a double-blind, crossover trial. Therapeutic response was assessed using the Conners' Global Index for parents (CGI-Parents) and teachers (CGI-Teachers), while side effects were assessed using the Barkley Side Effects Rating Scale (SERS). The side effect profile as assessed by the SERS was similar to that of previous studies with insomnia, decreased appetite, and headaches showing significant treatment effects (p < 0.005). These "somatic/physical" side effects did not correlate with CGI-Parents or CGI-Teachers. However, the side effects of "irritability", "proneness to crying", and "anxiousness" showed significant relationships with CGI-Parents. These "mood/anxiety" side effects showed no significant correlations with the CGI-Teachers. The greater "mood/anxiety" side effects on methylphenidate and placebo, the less the parents observe improvement of their children while treated with methylphenidate. This suggests that the correlations between "mood/anxiety" side effects and poor response to treatment may be driven by observer effects rather than biological commonalities between therapeutic and side effects of methylphenidate.

Biopolymers Containing Unnatural Amino Acids

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

Schultz, Peter

Although the main chain structure of polymers has a profound effect on their materials properties, the side groups can also have dramatic effects on their properties including conductivity, liquid crystallinity, hydrophobicity, elasticity and biodegradability. Unfortunately control over the side chain structure of polymers remains a challenge – it is difficult to control the sequence of chain elongation when mixtures of monomers are polymerized, and postpolymerization side chain modification is made difficult by polymer effects on side chain reactivity. In contrast, the mRNA templated synthesis of polypeptides on the ribosome affords absolute control over the primary sequence of the twenty aminomore » acid monomers. Moreover, the length of the biopolymer is precisely controlled as are sites of crosslinking. However, whereas synthetic polymers can be synthesized from monomers with a wide range of chemically defined structures, ribosomal biosynthesis is largely limited to the 20 canonical amino acids. For many applications in material sciences, additional building blocks would be desirable, for example, amino acids containing metallocene, photoactive, and halogenated side chains. To overcome this natural constraint we have developed a method that allows unnatural amino acids, beyond the common twenty, to be genetically encoded in response to nonsense or frameshift codons in bacteria, yeast and mammalian cells with high fidelity and good yields. Here we have developed methods that allow identical or distinct noncanonical amino acids to be incorporated at multiple sites in a polypeptide chain, potentially leading to a new class of templated biopolymers. We have also developed improved methods for genetically encoding unnatural amino acids. In addition, we have genetically encoded new amino acids with novel physical and chemical properties that allow selective modification of proteins with synthetic agents. Finally, we have evolved new metal-ion binding sites in proteins using a novel metal-ion binding amino acid, which may facilitate our ability to generate new protein based sensors and catalysts.« less

Biopolymers Containing Unnatural Building Blocks

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

Schultz, Peter G.

2013-06-30

Although the main chain structure of polymers has a profound effect on their materials properties, the side groups can also have dramatic effects on their properties including conductivity, liquid crystallinity, hydrophobicity, elasticity and biodegradability. Unfortunately control over the side chain structure of polymers remains a challenge – it is difficult to control the sequence of chain elongation when mixtures of monomers are polymerized, and postpolymerization side chain modification is made difficult by polymer effects on side chain reactivity. In contrast, the mRNA templated synthesis of polypeptides on the ribosome affords absolute control over the primary sequence of the twenty aminomore » acid monomers. Moreover, the length of the biopolymer is precisely controlled as are sites of crosslinking. However, whereas synthetic polymers can be synthesized from monomers with a wide range of chemically defined structures, ribosomal biosynthesis is largely limited to the 20 canonical amino acids. For many applications in material sciences, additional building blocks would be desirable, for example, amino acids containing metallocene, photoactive, and halogenated side chains. To overcome this natural constraint we have developed a method that allows unnatural amino acids, beyond the common twenty, to be genetically encoded in response to nonsense or frameshift codons in bacteria, yeast and mammalian cells with high fidelity and good yields. Here we have developed methods that allow identical or distinct noncanonical amino acids to be incorporated at multiple sites in a polypeptide chain, potentially leading to a new class of templated biopolymers. We have also developed improved methods for genetically encoding unnatural amino acids. In addition, we have genetically encoded new amino acids with novel physical and chemical properties that allow selective modification of proteins with synthetic agents. Finally, we have evolved new metal-ion binding sites in proteins using a novel metal-ion binding amino acid, which may facilitate our ability to generate new protein based sensors and catalysts.« less

A Proposal of Product Development Collaboration Method Using User Support Information and its Experimental Evaluation

NASA Astrophysics Data System (ADS)

Tanaka, Mitsuru; Kataoka, Masatoshi; Koizumi, Hisao

As the market changes more rapidly and new products continue to get more complex and multifunctional, product development collaboration with competent partners and leading users is getting more important to come up with new products that are successful in the market in a timely manner. ECM (engineering chain management) and SCM (supply chain management) are supply-side approaches toward this collaboration. In this paper, we propose a demand-side approach toward product development collaboration with users based on the information gathered through user support interactions. The approach and methodology proposed here was applied to a real data set, and its effectiveness was verified.

Developing instrumentation to characterize thermoelectric generator modules.

PubMed

Liu, Dawei; Li, Qiming; Peng, Wenbo; Zhu, Lianjun; Gao, Hu; Meng, Qingsen; Jin, A J

2015-03-01

Based on the law of physics, known as "Seebeck effect," a thermoelectric generator (TEG) produces electricity when the temperature differential is applied across the TEG. This article reports a precision method in characterizing TEG modules. A precision instrument is constructed to study thermoelectric conversion in terms of output power and efficiency of TEG modules. The maximum allowable TEG module size is 150 mm, and the preferred size is from 30 mm to 60 mm. During measurements, the highest hot side temperature is 500 °C and the cold side temperature can be adjusted from room temperature to 100 °C. A mechanical structure is developed to control the pressure and parallelism of the clamping force of the TEG on both its hot and cold sides. A heat flux measurement module is installed at its cold side, and the heat flux through TEGs can be measured in position. Finally, the energy conversion efficiency of TEGs is calculated from experimental data of both an output power and a heat flux.

Development of robust building energy demand-side control strategy under uncertainty

NASA Astrophysics Data System (ADS)

Kim, Sean Hay

The potential of carbon emission regulations applied to an individual building will encourage building owners to purchase utility-provided green power or to employ onsite renewable energy generation. As both cases are based on intermittent renewable energy sources, demand side control is a fundamental precondition for maximizing the effectiveness of using renewable energy sources. Such control leads to a reduction in peak demand and/or in energy demand variability, therefore, such reduction in the demand profile eventually enhances the efficiency of an erratic supply of renewable energy. The combined operation of active thermal energy storage and passive building thermal mass has shown substantial improvement in demand-side control performance when compared to current state-of-the-art demand-side control measures. Specifically, "model-based" optimal control for this operation has the potential to significantly increase performance and bring economic advantages. However, due to the uncertainty in certain operating conditions in the field its control effectiveness could be diminished and/or seriously damaged, which results in poor performance. This dissertation pursues improvements of current demand-side controls under uncertainty by proposing a robust supervisory demand-side control strategy that is designed to be immune from uncertainty and perform consistently under uncertain conditions. Uniqueness and superiority of the proposed robust demand-side controls are found as below: a. It is developed based on fundamental studies about uncertainty and a systematic approach to uncertainty analysis. b. It reduces variability of performance under varied conditions, and thus avoids the worst case scenario. c. It is reactive in cases of critical "discrepancies" observed caused by the unpredictable uncertainty that typically scenario uncertainty imposes, and thus it increases control efficiency. This is obtainable by means of i) multi-source composition of weather forecasts including both historical archive and online sources and ii) adaptive Multiple model-based controls (MMC) to mitigate detrimental impacts of varying scenario uncertainties. The proposed robust demand-side control strategy verifies its outstanding demand-side control performance in varied and non-indigenous conditions compared to the existing control strategies including deterministic optimal controls. This result reemphasizes importance of the demand-side control for a building in the global carbon economy. It also demonstrates a capability of risk management of the proposed robust demand-side controls in highly uncertain situations, which eventually attains the maximum benefit in both theoretical and practical perspectives.

Effects of diabetic peripheral neuropathy on gait in vascular trans-tibial amputees.

PubMed

Nakajima, Hiroshi; Yamamoto, Sumiko; Katsuhira, Junji

2018-07-01

Patients with diabetes often develop diabetic peripheral neuropathy, which is a distal symmetric polyneuropathy, so foot function on the non-amputated side is expected to affect gait in vascular trans-tibial amputees. However, there is little information on the kinematics and kinetics of gait or the effects of diabetic peripheral neuropathy in vascular trans-tibial amputees. This study aimed to clarify these effects, including the biomechanics of the ankle on the non-amputated side. Participants were 10 vascular trans-tibial amputees with diabetic peripheral neuropathy (group V) and 8 traumatic trans-tibial amputees (group T). Each subject's gait was analyzed at a self-selected speed using a three-dimensional motion analyzer and force plates. Ankle plantarflexion angle, heel elevation angle, and peak and impulse of anterior ground reaction force were smaller on the non-amputated side during pre-swing in group V than in group T. Center of gravity during pre-swing on the non-amputated side was lower in group V than in group T. Hip extension torque during loading response on the prosthetic side was greater in group V than in group T. These findings suggest that the biomechanical function of the ankle on the non-amputated side during pre-swing is poorer in vascular trans-tibial amputees with DPN than in traumatic trans-tibial amputees; the height of the center of gravity could not be maintained during this phase in vascular trans-tibial amputees with diabetic peripheral neuropathy. The hip joint on the prosthetic side compensated for this diminished function at the ankle during loading response. Copyright © 2018 Elsevier Ltd. All rights reserved.

Side Effects

Cancer.gov

Side effects are problems that occur when cancer treatment affects healthy tissues or organs. Learn about side effects caused by cancer treatment. Know what signs and symptoms to call your doctor about. Learn about treatments for side effects.

Asymmetrical development of root endodermis and exodermis in reaction to abiotic stresses

PubMed Central

Líška, Denis; Martinka, Michal; Kohanová, Jana; Lux, Alexander

2016-01-01

Background and Aims In the present study, we show that development of endodermis and exodermis is sensitively regulated by water accessibility. As cadmium (Cd) is known to induce xeromorphic effects in plants, maize roots were exposed also to Cd to understand the developmental process of suberin lamella deposition in response to a local Cd source. Methods In a first experiment, maize roots were cultivated in vitro and unilaterally exposed to water-containing medium from one side and to air from the other. In a second experiment, the roots were placed between two agar medium layers with a strip of Cd-containing medium attached locally and unilaterally to the root surface. Key Results The development of suberin lamella (the second stage of exodermal and endodermal development) started asymmetrically, preferentially closer to the root tip on the side exposed to the air. In the root contact with Cd in a spatially limited area exposed to one side of the root, suberin lamella was preferentially developed in the contact region and additionally along the whole length of the root basipetally from the contact area. However, the development was unilateral and asymmetrical, facing the treated side. The same pattern occurred irrespective of the distance of Cd application from the root apex. Conclusions These developmental characteristics indicate a sensitive response of root endodermis and exodermis in the protection of vascular tissues against abiotic stresses. PMID:27112163

A successful renal transplantation for renal failure after dasatinib-induced thrombotic thrombocytopenic purpura in a patient with imatinib-resistant chronic myelogenous leukaemia on nilotinib.

PubMed

Martino, Suella; Daguindau, Etienne; Ferrand, Christophe; Bamoulid, Jamal; Hayette, Sandrine; Nicolini, F-E; Capellier, G; Deconinck, Eric; Larosa, Fabrice

2013-01-01

Second-generation tyrosine kinase inhibitors (TKI2) often induce molecular remission, and prolonged survival with a better tolerance in imatinib-resistant chronic myelogenous leukaemia (CML) patients. We report the case of a CML in first chronic phase who was diagnosed in August 2003 in a young 24 year-old Caucasian woman. Our patient received first imatinib and then dasatinib and nilotinib. Imatinib was well tolerated and she developed TTP/HUS on dasatinib without documented evolution of CML and finally obtained MR5.0 with nilotinib and without any side effect. This case also illustrates the absence of cross-resistance and side-effects between the different TKIs and the feasibility of kidney transplantation associated with a nilotinib treatment of CML allowing a continuing MR5.0 and no further side effects.

Sexual Dysfunction in a Patient Taking Ledipasvir/Sofosbuvir for the Treatment of Hepatitis C: A Case Report.

PubMed

Lenz, Destin U; Crutcher, Effie L; Greene, Elisa M

2017-01-01

Sexual dysfunction is a bothersome side effect of several medications, though it has not yet been reported with the use of ledipasvir/sofosbuvir for the treatment of hepatitis C. However, sexual dysfunction is a potentially unrecognized side effect of ledipasvir/sofosbuvir that could result in nonadherence and treatment failure. We report a case of a 42-year-old man with a sudden onset of sexual dysfunction with the initiation of ledipasvir/sofosbuvir for the treatment of hepatitis C. The patient had no prior history or risk factors for the development of sexual dysfunction. His symptoms resolved upon discontinuation of ledipasvir/sofosbuvir after a successful 12-week course. Clinicians should be aware that sexual dysfunction is a possible side effect of ledipasvir/sofosbuvir and educate patients appropriately. Adherence should be emphasized as the risks of untreated hepatitis C virus far outweigh transient sexual dysfunction.

Cardiac side effects of bruton tyrosine kinase (BTK) inhibitors.

PubMed

Tang, Chloe Pek Sang; McMullen, Julie; Tam, Constantine

2017-09-13

The development of bruton tyrosine kinase inhibitors (BTKi) has been a significant advancement in the treatment of chronic lymphocytic leukemia and related B-cell malignancies. As experience in using ibrutinib increased, the first drug to be licensed in its class, atrial fibrillation (AF) emerged as an important side effect. The intersection between BTKi therapy for B-cell malignancies and AF represents a complex area of management with scant evidence for guidance. Consideration needs to be taken regarding the interplay of increased bleeding risk versus thromboembolic complications of AF, drug interactions between ibrutinib and anticoagulants and antiarrhythmic agents, and the potential for other, as yet seldom reported cardiac side effects. This review describes the current knowledge regarding BTKi and potential pathophysiologic mechanisms of AF and discusses the management of BTKi-associated AF. Finally, a review of the second generation BTKi is provided and gaps in knowledge in this evolving field are highlighted.

Efficient hiding of confidential high-utility itemsets with minimal side effects

NASA Astrophysics Data System (ADS)

Lin, Jerry Chun-Wei; Hong, Tzung-Pei; Fournier-Viger, Philippe; Liu, Qiankun; Wong, Jia-Wei; Zhan, Justin

2017-11-01

Privacy preserving data mining (PPDM) is an emerging research problem that has become critical in the last decades. PPDM consists of hiding sensitive information to ensure that it cannot be discovered by data mining algorithms. Several PPDM algorithms have been developed. Most of them are designed for hiding sensitive frequent itemsets or association rules. Hiding sensitive information in a database can have several side effects such as hiding other non-sensitive information and introducing redundant information. Finding the set of itemsets or transactions to be sanitised that minimises side effects is an NP-hard problem. In this paper, a genetic algorithm (GA) using transaction deletion is designed to hide sensitive high-utility itemsets for PPUM. A flexible fitness function with three adjustable weights is used to evaluate the goodness of each chromosome for hiding sensitive high-utility itemsets. To speed up the evolution process, the pre-large concept is adopted in the designed algorithm. It reduces the number of database scans required for verifying the goodness of an evaluated chromosome. Substantial experiments are conducted to compare the performance of the designed GA approach (with/without the pre-large concept), with a GA-based approach relying on transaction insertion and a non-evolutionary algorithm, in terms of execution time, side effects, database integrity and utility integrity. Results demonstrate that the proposed algorithm hides sensitive high-utility itemsets with fewer side effects than previous studies, while preserving high database and utility integrity.

Modulation of p-Cyanophenylalanine Fluorescence by Amino Acid Side-chains and Rational Design of Fluorescence Probes of α-Helix Formation

PubMed Central

Taskent-Sezgin, Humeyra; Marek, Peter; Thomas, Rosanne; Goldberg, Daniel; Chung, Juah; Carrico, Isaac; Raleigh, Daniel P.

2011-01-01

p-Cyanophenylalanine is an extremely useful fluorescence probe of protein structure which can be recombinantly and chemically incorporated into proteins. The probe has been used to study protein folding, protein-membrane interactions, protein-peptide interactions and amyloid formation, however the factors that control its fluorescence are not fully understood. Hydrogen bonding to the cyano group is known to play a major role in modulating the fluorescence quantum yield, but the role of potential side-chain quenchers has not yet been elucidated. A systematic study on the effects of different side-chains on p-cyanophenylalanine fluorescence is reported. Tyr is found to have the largest effect followed by deprotonated His, Met, Cys, protonated His, Asn, Arg, and protonated Lys. Deprotonated amino groups are much more effective fluorescence quenchers than protonated amino groups. Free neutral imidazole and hydroxide ion are also effective quenchers of p-cyanophenylalanine fluorescence with Stern-Volmer constants of 39.8 M−1 and 22.1 M−1, respectively. The quenching of p-cyanophenylalanine fluorescence by specific side-chains is exploited to develop specific, high sensitivity, fluorescence probes of helix formation. The approach is demonstrated with Ala based peptides that contain a p-cyanophenylalanine-His or a p-cyanophenylalanine-Tyr pair located at positions i and i+4. The p-cyanophenylalanine-His pair is most useful when the His side-chain is deprotonated and is, thus, complimentary to Trp-His pair which is most sensitive when the His side-chain is protonated. PMID:20565125

Side Effects of HIV Medicines: HIV and Lactic Acidosis

MedlinePlus

... Drugs Clinical Trials Apps skip to content Side Effects of HIV Medicines Home Understanding HIV/AIDS Fact ... and Immunizations What is a Drug Interaction? Side Effects of HIV Medicines HIV Medicines and Side Effects ...

The C-2 derivatives of salvinorin A, ethoxymethyl ether Sal B and β-tetrahydropyran Sal B, have anti-cocaine properties with minimal side effects.

PubMed

Ewald, Amy W M; Bosch, Peter J; Culverhouse, Aimee; Crowley, Rachel Saylor; Neuenswander, Benjamin; Prisinzano, Thomas E; Kivell, Bronwyn M

2017-08-01

Kappa-opioid receptor (KOPr) agonists have pre-clinical anti-cocaine and analgesic effects. However, side effects including sedation, dysphoria, aversion, anxiety and depression limit their therapeutic development. The unique structure of salvinorin A has been used to develop longer acting KOPr agonists. We evaluate two novel C-2 analogues of salvinorin A, ethoxymethyl ether Sal B (EOM Sal B) and β-tetrahydropyran Sal B (β-THP Sal B) alongside U50,488 for their ability to modulate cocaine-induced behaviours and side effects, pre-clinically. Anti-cocaine properties of EOM Sal B were evaluated using the reinstatement model of drug seeking in self-administering rats. EOM Sal B and β-THP Sal B were evaluated for effects on cocaine-induced hyperactivity, spontaneous locomotor activity and sucrose self-administration. EOM Sal B and β-THP Sal B were evaluated for aversive, anxiogenic and depressive-like effects using conditioned place aversion (CPA), elevated plus maze (EPM) and forced swim tests (FSTs), respectively. EOM Sal B (0.1, 0.3 mg/kg, intraperitoneally (i.p.)) dose dependently attenuated drug seeking, and EOM Sal B (0.1 mg/kg, i.p.) and β-THP Sal B (1 mg/kg, i.p.) attenuated cocaine-induced hyperactivity. No effects on locomotor activity, open arm times (EPM) or swimming behaviours (FST) were seen with EOM (0.1 or 0.3 mg/kg, i.p.) or β-THP Sal B (1 or 2 mg/kg, i.p.). However, β-THP Sal B decreased time spent in the drug-paired chamber. EOM Sal B is more potent than Sal A and β-THP Sal B in reducing drug-seeking behaviour with fewer side effects. EOM Sal B showed no effects on sucrose self-administration (0.1 mg/kg), locomotor, depressive-like, aversive-like or anxiolytic effects.

Framing effects on expectations, decisions, and side effects experienced: the case of influenza immunization.

PubMed

O'Connor, A M; Pennie, R A; Dales, R E

1996-11-01

To examine the effects of using positive or negative frames to describe influenza vaccine benefits and side effects on patients' expectations, decisions, decisional conflict, and reported side effects. 292 previously unimmunized patients with chronic respiratory or cardiac disease were randomly assigned to receive benefit/risk information that was framed: (1) positively as the percentage who remain free of influenza and have no vaccine side effects, or (2) negatively as the percentage who acquire influenza and have vaccine side effects. Questionnaires elicited expectations, decisions, and decisional conflict. Vaccines were telephoned 3 days later for a self-report of local and systemic side effects and work absenteeism. Both groups had similar immunization rates and decisional conflict scores. The positive frame group had lower and more realistic expectations of vaccine side effects, fewer systemic side effects, and less work absenteeism (p < 0.05). In contrast to previous studies of health care workers, framing did not influence patients' decisions, possibly due to the patients' awareness of their higher risk of influenza complications and greater desire to follow recommendations. The common practice of using negative frames when describing probabilities of side effects may need to be reexamined, considering its deleterious influence on self-reported side effects and work absenteeism.

The Bright Elusive Butterfly of Value in Health Technology Development

PubMed Central

Greenhalgh, Trisha; Fahy, Nick; Shaw, Sara

2018-01-01

The current system of health technology development is characterised by multiple misalignments. The "supply" side (innovation policy-makers, entrepreneurs, investors) and the "demand" side (health policy-makers, regulators, health technology assessment, purchasers) operate under different – and conflicting – logics. The system is less a "pathway" than an unstable ecosystem of multiple interacting sub-systems. "Value" means different things to each of the numerous actors involved. Supply-side dynamics are built on fictions; regulatory checks and balances are designed to assure quality, safety and efficacy, not to ensure that technologies entering the market are either desirable or cost-effective. Assessment of comparative and cost-effectiveness usually comes too late in the process to shape an innovation’s development. We offer no simple solutions to these problems, but in the spirit of commencing a much-needed public debate, we suggest some tentative ways forward. First, universities and public research funders should play a more proactive role in shaping the system. Second, the role of industry in forging long-term strategic partnerships for public benefit should be acknowledged (though not uncritically). Third, models of "responsible innovation" and public input to research priority-setting should be explored. Finally, the evidence base on how best to govern inter-sectoral health research partnerships should be developed and applied. PMID:29325407

A review method for UML requirements analysis model employing system-side prototyping.

PubMed

Ogata, Shinpei; Matsuura, Saeko

2013-12-01

User interface prototyping is an effective method for users to validate the requirements defined by analysts at an early stage of a software development. However, a user interface prototype system offers weak support for the analysts to verify the consistency of the specifications about internal aspects of a system such as business logic. As the result, the inconsistency causes a lot of rework costs because the inconsistency often makes the developers impossible to actualize the system based on the specifications. For verifying such consistency, functional prototyping is an effective method for the analysts, but it needs a lot of costs and more detailed specifications. In this paper, we propose a review method so that analysts can verify the consistency among several different kinds of diagrams in UML efficiently by employing system-side prototyping without the detailed model. The system-side prototype system does not have any functions to achieve business logic, but visualizes the results of the integration among the diagrams in UML as Web pages. The usefulness of our proposal was evaluated by applying our proposal into a development of Library Management System (LMS) for a laboratory. This development was conducted by a group. As the result, our proposal was useful for discovering the serious inconsistency caused by the misunderstanding among the members of the group.

Side Effects of Leukotriene Receptor Antagonists in Asthmatic Children.

PubMed

Erdem, Semiha Bahceci; Nacaroglu, Hikmet Tekin; Unsal Karkiner, Canan Sule; Gunay, Ilker; Can, Demet

2015-10-01

Leukotriene receptor antagonists (LTRAs) are drugs which have been widely used more than ten years. As the use of LTRAs increases, our knowledge with respect to their side effects increases as well. The objective of our study was to evaluat the observed side effects of LTRAs used in patients with astma. 1024 patients treated only with LTRAs owing to asthma or early wheezing were included in the study for a five-year period. The observed side effects of LTRAs in these patients were retrospectively investigated. The side effects were divided into two parts as psychiatric and non-psychiatric. Among the 1024 cases included in the study, 67.5% of the patients out of 41 with side effects were male, 32.5% were female and the average age was 6.5 years. The rate of patients with asthma was 63.41% and 36.58% of the patients had early wheezing. It was determined that sex, age and diagnosis (early wheezing or asthma) of the patients were ineffective in the emergence of side effects. The average period for the emergence of side effects was the first month. It was observed that hyperactivity was the most frequently observed psychiatric side effect and that abdominal pain was the non-psychiatric side effect. The side effects of LTRAs were common in children. Therefore, patients must be informed at the beginning of the treatment and they must be evaluated at certain intervals.

Effects of small-sided games on physical conditioning and performance in young soccer players.

PubMed

Katis, Athanasios; Kellis, Eleftherios

2009-01-01

The purpose of this study was to examine, first, the movement actions performed during two different small-sided games and, second, their effects on a series of field endurance and technical tests. Thirty-four young soccer players (age: 13 ± 0.9 yrs; body mass: 62.3 ± 15.1 kg; height: 1.65 ± 0.06 m) participated in the study. Small-sided games included three-a-side (3 versus 3 players) and six-a-side (6 versus 6 players) games consisting of 10 bouts of 4 min duration with 3 min active recovery between bouts. Soccer player performance was evaluated using five field tests: a) 30m sprint, b) throw-in for distance, c) Illinois Agility Test, d) dribbling the ball and e) horizontal jump before, in the middle and after the implementation of both game situations. Heart rate was monitored during the entire testing session. Each game was also filmed to measure soccer movements within the game. The ANOVA analysis indicated that the three-a- side games displayed significantly higher heart rate values compared with the six-a-side games (p < 0.05). The number of short passes, kicks, tackles, dribbles and scoring goals were significantly higher during the three-a-side compared with the six-a-side game condition (p < 0. 05) while players performed more long passes and headed the ball more often during the six-a-side (p < 0.05). After the three-a-side games, there was a significant decline in sprint and agility performance (p < 0.05), while after both game conditions significant alterations in the throw-in and the horizontal jump performance were observed (p < 0.05). The results of the present study indicated that three-a-side games provide higher stimulus for physical conditioning and technical improvement than six-a-side games and their use for training young soccer players is recommended. Key pointsThree-a-side games display higher HR compared with six-a-side games.In the three-a-side games players performed more short passes, kicks, dribbles, tackles and scored more goals compared with the six-a-side games.Impairment in endurance and field test performance was observed mainly after three-a-side games.The use of the three-a-side games to develop physical fitness and technique in young soccer players is recommended.

Identification of IFN-γ-producing T cells as the main mediators of the side effects associated to mouse interleukin-15 sustained exposure

PubMed Central

Scala, Marianna Di; Gil-Fariña, Irene; Olagüe, Cristina; Vales, Africa; Sobrevals, Luciano; Fortes, Puri; Corbacho, David; González-Aseguinolaza, Gloria

2016-01-01

Interleukin-15 (IL-15) is a cell growth-factor that regulates lymphocyte function and homeostasis. Its strong immunostimulatory activity coupled with an apparent lack of toxicity makes IL-15 an exciting candidate for cancer therapy, somehow limited by its short half-life in circulation. To increase IL-15 bioavailability we constructed a recombinant adeno-associated vector expressing murine IL-15 (AAV-mIL15) in the liver. Mice injected with AAV-mIL15 showed sustained and vector dose-dependent levels of IL-15/IL-15Rα complexes in serum, production of IFN-γ and activation of CD8+ T-cells and macrophages. The antitumoral efficacy of AAV-mIL15 was tested in a mouse model of metastatic colorectal cancer established by injection of MC38 cells. AAV-mIL15 treatment slightly inhibits MC38 tumor-growth and significantly increases the survival of mice. However, mIL-15 sustained expression was associated with development of side effects like hepatosplenomegaly, liver damage and the development of haematological stress, which results in the expansion of hematopoietic precursors in the bone marrow. To elucidate the mechanism, we treated IFN-γ receptor-, RAG1-, CD1d- and μMT-deficient mice and performed adoptive transfer of bone marrow cells from WT mice to RAG1-defcient mice. We demonstrated that the side effects of murine IL-15 administration were mainly mediated by IFN-γ-producing T-cells. Conclusion IL-15 induces the activation and survival of effector immune cells that are necessary for its antitumoral activity; but, long-term exposure to IL-15 is associated with the development of important side effects mainly mediated by IFN-γ-producing T-cells. Strategies to modulate T-cell activation should be combined with IL-15 administration to reduce secondary adverse events while maintaining its antitumoral effect. PMID:27356750

Developing an Instrument to Measure Socioeconomic Disparities in Quality of Care for Men with Early-Stage Prostate Cancer

DTIC Science & Technology

2011-09-01

Cystorrhaphy, suture of bladder wound), 52332 (Insertion of ureteral stent ) Diagnosis of urinary incontinence: ICD-9: 599.82 (Intrinsic...first outcome measure we will investigate will be urinary side effects of prostate cancer treatment. Because urinary continence and urinary side...initial findings have been quite striking. Most patients who undergo treatment for prostate cancer are diagnosed with some type of urinary

A Comparison of Sexual Side Effects of Antidepressants With and Without Naltrexone.

PubMed

Thapa, Mona; Petrakis, Ismene; Ralevski, Elizabeth

2017-01-01

The aim of the study was to compare the rate of sexual side effects of the selective serotonin reuptake inhibitor paroxetine versus the tricyclic antidepressant desipramine and to examine the effect of co-prescription of naltrexone on sexual side effects among participants in a randomized clinical trial. This was a secondary analysis (N = 88) of veterans who participated in a 12-week trial. All veterans were randomized into one of four treatment groups: (a) desipramine/naltrexone, (b) desipramine/placebo, (c) paroxetine/naltrexone, and (d) paroxetine/placebo. The main outcome measure was the frequency of sexual side effects consisting of "decreased sex drive" and/or "impotence" reported by veterans at each weekly visit. Approximately 61% of the veterans reported sexual side effects at least once during the trial, and 26.4% reported sexual side effects throughout the study. There were no significant differences in the frequency of sexual side effects among the four treatment groups. The results were similar when the comparison was made between the two antidepressant groups. There were no significant differences in the reporting of sexual side effects between those receiving desipramine and paroxetine. Also, the comparison between naltrexone and placebo did not alter the results. This is the first study to compare frequency of sexual side effect reporting between paroxetine and desipramine. We found no statistically significant differences in sexual side effect reporting between the two antidepressants. Also, the addition of naltrexone did not show any beneficial effect on the sexual side effect profile.

Principles of a multistack electrochemical wastewater treatment design

NASA Astrophysics Data System (ADS)

Elsahwi, Essam S.; Dawson, Francis P.; Ruda, Harry E.

2018-02-01

Electrolyzer stacks in a bipolar architecture (cells connected in series) are desirable since power provided to a stack can be transferred at high voltages and low currents and thus the losses in the power bus can be reduced. The anode electrodes (active electrodes) considered as part of this study are single sided but there are manufacturing cost advantages to implementing double side anodes in the future. One of the main concerns with a bipolar stack implementation is the existence of leakage currents (bypass currents). The leakage current is associated with current paths that are not between adjacent anode and cathode pairs. This leads to non uniform current density distributions which compromise the electrochemical conversion efficiency of the stack and can also lead to unwanted side reactions. The objective of this paper is to develop modelling tools for a bipolar architecture consisting of two single sided cells that use single sided anodes. It is assumed that chemical reactions are single electron transfer rate limited and that diffusion and convection effects can be ignored. The design process consists of the flowing two steps: development of a large signal model for the stack, and then the extraction of a small signal model from the large signal model. The small signal model facilitates the design of a controller that satisfies current or voltage regulation requirements. A model has been developed for a single cell and two cells in series but can be generalized to more than two cells in series and to incorporate double sided anode configurations in the future. The developed model is able to determine the leakage current and thus provide a quantitative assessment on the performance of the cell.

How does the side-effect information in patient information leaflets influence peoples' side-effect expectations? A cross-sectional national survey of 18- to 65-year-olds in England.

PubMed

Webster, Rebecca K; Weinman, John; Rubin, G James

2017-12-01

To establish how the terms recommended by the European Commission to describe side-effect risk in patient information leaflets (PILs) influences expectations of side-effects and to identify factors associated with these side-effect expectations. A cross-sectional online survey was carried out by a market research company. Data were collected in England between 18th March and 1st April 2016. A total of 1003 adults aged between 18 and 65. Self-reported expectation that the described side-effects would affect participants if they took the medicine, measured on a likelihood scale from 1 (very unlikely) to 5 (very likely). Participants formed high expectations of side-effects for "very common" and "common" side-effects, with 51.9% and 45.0% of participants rating these as "very likely" or "likely" to happen to them, respectively. This fell to 8.1% for "uncommon," 5.8% for "rare" and 4.1% for "very rare." For each descriptor, higher expectations of side-effects were more associated with women or being from an ethnic minority, or having less education, a household illness, high perceived sensitivity to medicines or negative beliefs about medicines. The current use of verbal descriptors to communicate side-effect risk in PILs leads to high side-effect expectations. These expectations could contribute to nocebo-induced medication side-effects experienced by patients. Additional work is required to identify ways to improve the way risk information is conveyed in PILs. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

Right-sided infective endocarditis: recent epidemiologic changes

PubMed Central

Yuan, Shi-Min

2014-01-01

Background: Infective endocarditis (IE) has been increasingly reported, however, little is available regarding recent development of right-sided IE. Methods: Right-sided IE was comprehensively analyzed based on recent 5⅓-year literature. Results: Portal of entry, implanted foreign material, and repaired congenital heart defects were the main predisposing risk factors. Vegetation size on the right-sided valves was much smaller than those beyond the valves. Multiple logistic regression analysis revealed that predisposing risk factors, and vegetation size and locations were independent predictive risks of patients’ survival. Conclusions: Changes of right-sided IE in the past 5⅓ years included younger patient age, and increased vegetation size, but still prominent Staphylococcus aureus infections. Complication spectrum has changed into more valve insufficiency, more embolic events, reduced abscess formation, and considerably decreased valve perforations. With effective antibiotic regimens, prognoses of the patients seemed to be better than before. PMID:24482708

Terbinafine: novel formulations that potentiate antifungal activities.

PubMed

Ma, Y; Chen, X; Guan, S

2015-03-01

Terbinafine, an orally and topically active antifungal agent, has been available for the treatment of dermatophytic infections and onychomycosis for more than a decade. In addition, oral administration has been shown to be associated with drug-drug interactions, hepatotoxicity, low concentration at the infected sites, gastrointestinal and systemic side effects and other adverse effects. Since topical drug delivery can provide higher patient compliance, allow immediate access to the infected site and reduce unwanted systemic drug exposure, an improved topical drug delivery approach with high permeability, sustained release and prolonged retainment could overcome the limitations and side effects caused by oral administration. Conventional topical formulations cannot keep the drug in the targeted sites for a long duration of time and hence a novel drug delivery that can avoid the side effects while still providing sustained efficacy in treatment should be developed. This brief review of novel formulations based on polymers and nanostructure carriers provides insight into the efficacy and topical delivery of terbinafine. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

[Functional selectivity of opioid receptors ligands].

PubMed

Audet, Nicolas; Archer-Lahlou, Elodie; Richard-Lalonde, Mélissa; Piñeyro-Filpo, Graciela

2010-01-01

Opiates are the most effective analgesics available for the treatment of severe pain. However, their clinical use is restricted by unwanted side effects such as tolerance, physical dependence and respiratory depression. The strategy to develop new opiates with reduced side effects has mainly focused on the study and production of ligands that specifically bind to different opiate receptors subtypes. However, this strategy has not allowed the production of novel therapeutic ligands with a better side effects profile. Thus, other research strategies need to be explored. One which is receiving increasing attention is the possibility of exploiting ligand ability to stabilize different receptor conformations with distinct signalling profiles. This newly described property, termed functional selectivity, provides a potential means of directing the stimulus generated by an activated receptor towards a specific cellular response. Here we summarize evidence supporting the existence of ligand-specific active conformations for two opioid receptors subtypes (delta and mu), and analyze how functional selectivity may contribute in the production of longer lasting, better tolerated opiate analgesics. double dagger.

High versus moderate energy use of bipolar fractional radiofrequency in the treatment of acne scars: a split-face double-blinded randomized control trial pilot study.

PubMed

Phothong, Weeranut; Wanitphakdeedecha, Rungsima; Sathaworawong, Angkana; Manuskiatti, Woraphong

2016-02-01

Bipolar fractional radiofrequency (FRF) device was firstly FDA-approved for treating atrophic acne scar in 2008 through the process of dermal coagulation and minimal epidermal ablation. The average energy at 60 mJ/pin was widely used to treat atrophic acne scars. However, the higher energy was delivered, the deeper ablation and coagulation were found. At present, the new generation of a device with bipolar FRF technology with electrode-pin tip was developed to maximize ability to deliver energy up to 100 mJ/pin. The objective of the study was to explore and compare the efficacy of utilizing high energy (100 mJ/pin) and moderate energy (60 mJ/pin) of bipolar fractional radiofrequency in treatment of atrophic acne scar in Asians. This is a split-face, double-blinded, randomized control trial, pilot study by using parallel group design technique. Thirty healthy subjects with Fitzpatrick skin phototype III-IV diagnosed as atrophic acne scares were enrolled. All subjects received four monthly sessions of bipolar FRF treatment. Left and right facial sides of individual patients were randomly assigned for different energy (high energy at 100 mJ/pin versus moderate energy at 60 mJ/pin). Acne scars improvement was blinded graded by dermatologist using global acne scarring score (GASS) which was subjectively evaluated at baseline, 1-, 3-, and 6-month follow-up. Objective scar analysis was also done using UVA-light video camera to measure scar volume, skin smoothness, and wrinkle at baseline, 3-, and 6-month follow-up after the last treatment. Side effects including pain, erythema, swelling, and crusting were also recorded. Thirty subjects completed the study with full 4-treatment course. The mean GASS of high energy side and moderate energy side was significantly reduced at 1-, 3-, and 6-month follow-up visits. At 1 month follow-visit, high energy side demonstrated significant improvement compared with moderate energy side (p = 0.03). Postinflammatory hyperpigmentation (PIH) developed in 21/120 sessions in high energy side (17.5 %) and 16/120 sessions in moderate energy side (13.3 %). Pain score and the duration of erythema after treatments were significant higher on the side that was treated with high energy. Bipolar FRF device was safe and effective in the treatment of atrophic acne scars in Asians. High energy setting demonstrated significant higher efficacy at 1 month follow-visit. However, the efficacy of both energy settings was comparable at 3- and 6-month follow-up. In addition, side effects were significantly more intense on the side treated with high energy.

Transporter Protein-Coupled DPCPX Nanoconjugates Induce Diaphragmatic Recovery after SCI by Blocking Adenosine A1 Receptors.

PubMed

Minic, Zeljka; Zhang, Yanhua; Mao, Guangzhao; Goshgarian, Harry G

2016-03-23

Respiratory complications in patients with spinal cord injury (SCI) are common and have a negative impact on the quality of patients' lives. Systemic administration of drugs that improve respiratory function often cause deleterious side effects. The present study examines the applicability of a novel nanotechnology-based drug delivery system, which induces recovery of diaphragm function after SCI in the adult rat model. We developed a protein-coupled nanoconjugate to selectively deliver by transsynaptic transport small therapeutic amounts of an A1 adenosine receptor antagonist to the respiratory centers. A single administration of the nanoconjugate restored 75% of the respiratory drive at 0.1% of the systemic therapeutic drug dose. The reduction of the systemic dose may obviate the side effects. The recovery lasted for 4 weeks (the longest period studied). These findings have translational implications for patients with respiratory dysfunction after SCI. The leading causes of death in humans following SCI are respiratory complications secondary to paralysis of respiratory muscles. Systemic administration of methylxantines improves respiratory function but also leads to the development of deleterious side effects due to actions of the drug on nonrespiratory sites. The importance of the present study lies in the novel drug delivery approach that uses nanotechnology to selectively deliver recovery-inducing drugs to the respiratory centers exclusively. This strategy allows for a reduction in the therapeutic drug dose, which may reduce harmful side effects and markedly improve the quality of life for SCI patients. Copyright © 2016 the authors 0270-6474/16/363441-12$15.00/0.

Review Article: Fabricated Microparticles: An Innovative Method to Minimize the Side Effects of NSAIDs in Arthritis.

PubMed

Abadi, Shaivad Shabee Hulhasan; Moin, Afrasim; Veerabhadrappa, Gangadharappa Hosahalli

2016-01-01

Microparticles are polymeric bodies ranging 1-1000 µm that constitute a variety of forms such as microcapsules, microspheres, microcages, microshells, microrods, biosensors microparticles, radiolabeled microparticles, and so forth. This review focuses on general microparticles, mainly microcapsules and microspheres. Nonsteriodal anti-inflammatory drugs (NSAIDs) are one of the mostcommonly prescribed medications in the world. Most of the NSAIDs available have severe side effects. With increased awareness of NSAID-induced gastrointestinal (GI) side effects, safety has become a priority in treatment of arthritis and other inflammatory diseases with NSAIDs. A trend in NSAID development has been to improve therapeutic efficacy while reducing the severity of GI side effects by altering dosage through modified release to optimize drug delivery. One such approach is the use of fabricated microparticles such as microcapsules and microspheres as carriers of drugs. Microparticles provide delivery of macromolecules and micromolecules via different routes and effectively control the release profile of such drugs. Microcapsules and microspheres are compatible with most natural and synthetic polymers and can be used for several routes of administration, including parenteral, oral, nasal, intra-ocular, topical, and the like. Because of greater stability and multiple manufacturing techniques, microspheres and microcapsules are preferred as drug carriers over other colloidal drug delivery systems. Microparticles provide effective protection of the encapsulated agent against degradation by enzymatic activities, controlled and confined delivery of drugs from a few hours to months, and ingenious administration compared to alternative forms of controlled-release parenteral dosages, such as macro-sized implants. This comprehensive overview of fabricated microparticles describes microencapsulation technologies to produce microparticles for targeted therapy of arthritis and other inflammatory diseases which provide constant and prolonged therapeutic effects that reduce dosing frequency and thereby minimize potential adverse effects of NSAIDs such as GI irritation and insufficient patient compliance. The present review describes the latest developments in microparticulate drug delivery systems and the best alternatives for safe and effective microcapsular systems in a controlled manner for the delivery of NSAIDs.

Pharmacokinetic and pharmacodynamic profile of dronedarone , a new antiarrhythmic agent for the treatment of atrial fibrillation.

PubMed

Rosa, Gian Marco; Bianco, Daniele; Parodi, Antonello; Valbusa, Alberto; Zawaideh, Camilla; Bizzarri, Nicolò; Ferrero, Simone; Brunelli, Claudio

2014-12-01

Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased morbidity and mortality. Dronedarone is a recent antiarrhythmic drug that has been developed for treatment of AF, with electrophysiological properties similar to amiodarone but with a lower incidence of side effects. This review evaluates the efficacy, safety, tolerability and side effects of dronedarone in the treatment of AF. In particular, the review includes studies comparing: dronedarone and placebo (ANDROMEDA, ATHENA, DAFNE, ERATO, EURIDIS/ADONIS, HESTIA, PALLAS trials), dronedarone and amiodarone (DIONYSOS trial), ranolazine and dronedarone given alone and in combination (HARMONY trial). Dronedarone is an interesting antiarrhythmic agent in well-selected groups of patients. It also has several other pleiotropic effects that may potentially be beneficial in clinical practice, such as the reduction of the risk of stroke and acute coronary syndromes. In addition, combination therapies such as those with dronedarone and ranolazine, currently being investigated in the HARMONY trial, may provide another interesting approach to increase the antiarrhythmic efficacy and further reduce the incidence of side effects. A better understanding of the mechanisms underlying dronedarone's pleiotropic actions is expected to facilitate the selection of patients benefiting from dronedarone, as well as the development of novel antiarrhythmic drugs for AF.

Side Effects to Antidepressant Treatment in Patients With Depression and Comorbid Panic Disorder.

PubMed

Shankman, Stewart A; Gorka, Stephanie M; Katz, Andrea C; Klein, Daniel N; Markowitz, John C; Arnow, Bruce A; Manber, Rachel; Rothbaum, Barbara O; Thase, Michael E; Schatzberg, Alan F; Keller, Martin B; Trivedi, Madhukar H; Kocsis, James H

2017-04-01

Side effects to antidepressant medication can affect the efficacy of treatment, but few predictors foretell who experiences side effects and which side effects they experience. This secondary data analysis examined whether depressed patients with comorbid panic disorder were more likely to experience side effects than those without panic disorder. The study also examined whether greater burden of side effects predicted a poorer treatment course for patients with panic disorder than those without panic disorder. To examine the specificity of these effects, analyses also examined 2 other anxiety disorders-social phobia and generalized anxiety disorder (GAD). Between 2002 and 2006, a large sample (N = 808) of chronically depressed individuals (assessed using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders [SCID-IV]) received antidepressants according to a predetermined algorithm for 12 weeks. Every 2 weeks, depressive symptoms (per the Hamilton Depression Rating Scale) and side effects (specific side effects as well as several indicators of side effect burden) were assessed. Lifetime diagnosis of panic disorder (assessed using the SCID-IV) at baseline was associated with higher likelihood of gastrointestinal (OR = 1.6 [95% CI, 1.0-2.6]), cardiac (OR = 1.8 [95% CI, 1.1-3.1]), neurologic (OR = 2.6 [95% CI, 1.6-4.2]), and genitourinary side effects (OR = 3.0 [95% CI, 1.7-5.3]) during treatment. Increases in side effect frequency, intensity, and impairment over time were more strongly associated with increases in depressive symptoms for patients with panic disorder compared to those without panic disorder. Neither social phobia nor GAD was associated with these effects. Potentially due to heighte​ned interoceptive awareness of changes in their body, chronically depressed individuals with panic disorder may be at greater risk than those without panic disorder for antidepressant side effects and to experience a worsening of depressive symptoms as a result of these side effects over time. ClinicalTrials.gov identifier: NCT00057551​. © Copyright 2017 Physicians Postgraduate Press, Inc.

Medications and Side Effects

MedlinePlus

... to fully work. You might feel some side effects of your medication before your feel the benefits – ... as sleepiness, anxiety or headache) is a side effect or a symptom of your illness. Many side ...

Cancer Treatment for Women: Possible Sexual Side Effects

MedlinePlus

... the clitoris. These play a major part in sexual arousal in women. Removing the vulva and the clitoris ... www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/fertility-and-sexual-side-effects/sexuality-for-women-with-cancer.html. ...

Patient-provider communication and hormonal therapy side effects in breast cancer survivors.

PubMed

Lin, Jenny J; Chao, Jennifer; Bickell, Nina A; Wisnivesky, Juan P

2017-09-01

Side effects from hormonal therapy (HT) for breast cancer treatment occur frequently and are associated with worse quality of life and HT non-adherence. Whether improved patient-physician communication is associated with patients' reporting of side effects is unknown. We undertook this study to assess factors associated with women's reports of HT side effects. Between December 2012 and April 2013, we conducted a cross-sectional survey of breast cancer patients undergoing HT in an urban medical center. Descriptive statistics, univariate analyses, and multivariate analyses were used to evaluate associations. Of the 100 participants, 67% reported having HT side effects. However, when prompted, an additional 9% reported experiencing specific HT-related symptoms. Despite very high communication scores, one-third of participants reported they had not discussed side effects with providers. Multivariate analysis showed that after controlling for age, education, race, and medication beliefs, women who had difficulty asking providers for more information were more likely to report side effects (odds ratio 8.27, 95% confidence interval 1.01-69.88). Although HT side effects often occur and are bothersome, patient-provider discussions about side effects remain suboptimal. Providers should actively ask patients about medication side effects so that they can be addressed to improve quality of life and potentially, medication adherence.

Side effect burden of antipsychotic drugs in real life - Impact of gender and polypharmacy.

PubMed

Iversen, Trude Seselie Jahr; Steen, Nils Eiel; Dieset, Ingrid; Hope, Sigrun; Mørch, Ragni; Gardsjord, Erlend Strand; Jørgensen, Kjetil Nordbø; Melle, Ingrid; Andreassen, Ole A; Molden, Espen; Jönsson, Erik G

2018-03-02

Antipsychotic-associated side effects are well known and represent a significant treatment challenge. Still, few large studies have investigated the overall side effect burden of antipsychotics in real-life settings. To describe the occurrence of side effects and perceived burden of antipsychotics in a large naturalistic sample, taking polypharmacy and patient characteristics into account. Patients (n=1087) with psychotic disorders were assessed for side effects using the Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale in addition to assessment of clinical and pharmacological data. Statistical analyses were performed controlling for possible confounding factors. Use of antipsychotics showed significant associations to neurologic and sexual symptoms, sedation and weight gain, and >75% of antipsychotics-users reported side effects. More side effects were observed in patients using several antipsychotics (p=0.002), with increasing total dose (p=0.021) and with antipsychotics in combinations with other psychotropic drugs. Patients and investigators evaluated the side effect burden differently, particularly related to severity, gender and antipsychotics dose. Twice as many females described side effect burden as severe (p=0.004). Patients with psychotic disorders have a high occurrence of symptoms associated with use of antipsychotics, and polypharmacy and female gender are seemingly risk factors for reporting a severe side effect burden. Due to the cross-sectional design evaluation of causality is tentative, and these findings should be further investigated in prospective studies. Copyright © 2017 Elsevier Inc. All rights reserved.

The Glasgow antipsychotic side-effects scale for clozapine in inpatients and outpatients with schizophrenia or schizoaffective disorder.

PubMed

Ignjatović Ristić, Dragana; Cohen, Dan; Obradović, Andrea; Nikić-Đuričić, Katarina; Drašković, Marija; Hinić, Darko

2018-02-01

The inconsistency in clinician and patient ratings of clozapine-induced side effects underscore the need to supplement clinician-based estimates of side effects with patient-reported ones. The main aims of the study are validation of the Glasgow antipsychotic side-effects scale for clozapine (GASS-C) in Serbian inpatients/outpatients with schizophrenia or schizo-affective disorder and recommendations for its future use, based on common and rare clozapine-associated side-effects. The GASS-C was administered to 95 outpatients/inpatients diagnosed with schizophrenia, schizoaffective, or chronic psychotic disorder. The scale showed good overall reliability, with an internal consistency coefficient of α = 0.84, an average retest coefficient of rho = 0.76, and a Spearman-Brown coefficient of validity of 0.81. Side effects were absent or mild in 64.2% of the patients, moderate in 31.6%, severe in 4.2%; 14% of the subjects considered their symptoms distressing. The most commonly reported side-effects were drowsiness, thirst, frequent urination, and dry mouth. Women reported more side effects than men, and patients not in a relationship reported significantly fewer side effects than patients in a relationship. Results indicate a weak positive correlation (rho = 0.231; p = .025) between severity of side effects and clozapine dose. The GASS-C showed good psychometric characteristics in clinical population of patients on clozapine. In future studies, clozapine serum concentrations should be measured when using the GASS-C to monitor side effects.

Development of a 2 MHz Sonar Sensor for Inspection of Bridge Substructures.

PubMed

Park, Chul; Kim, Youngseok; Lee, Heungsu; Choi, Sangsik; Jung, Haewook

2018-04-16

Hydraulic factors account for a large part of the causes of bridge collapse. Due to the nature of the underwater environment, quick and accurate inspection is required when damage occurs. In this study, we developed a 2 MHz side scan sonar sensor module and effective operation technique by improving the limitations of existing sonar. Through field tests, we analyzed the correlation of factors affecting the resolution of the sonar data such as the angle of survey, the distance from the underwater structure and the water depth. The effect of the distance and the water depth and the structure on the survey angle was 66~82%. We also derived the relationship between these factors as a regression model for effective operating techniques. It is considered that application of the developed 2 MHz side scan sonar and its operation method could contribute to prevention of bridge collapses and disasters by quickly and accurately checking the damage of bridge substructures due to hydraulic factors.

Development of a 2 MHz Sonar Sensor for Inspection of Bridge Substructures

PubMed Central

Park, Chul; Lee, Heungsu; Choi, Sangsik; Jung, Haewook

2018-01-01

Hydraulic factors account for a large part of the causes of bridge collapse. Due to the nature of the underwater environment, quick and accurate inspection is required when damage occurs. In this study, we developed a 2 MHz side scan sonar sensor module and effective operation technique by improving the limitations of existing sonar. Through field tests, we analyzed the correlation of factors affecting the resolution of the sonar data such as the angle of survey, the distance from the underwater structure and the water depth. The effect of the distance and the water depth and the structure on the survey angle was 66~82%. We also derived the relationship between these factors as a regression model for effective operating techniques. It is considered that application of the developed 2 MHz side scan sonar and its operation method could contribute to prevention of bridge collapses and disasters by quickly and accurately checking the damage of bridge substructures due to hydraulic factors. PMID:29659557

Update on pharmacology of obesity: benefits and risks.

PubMed

Cabrerizo García, Lucio; Ramos-Leví, Ana; Moreno Lopera, Carmen; Rubio Herrera, Miguel A

2013-09-01

The prevalence of obesity in Western countries has increased at a much greater pace than the development of new efficient and safe drugs, beyond mere lifestyle changes, for the treatment of overweight. Numerous different types of drugs which had been used in the past for the treatment of obesity have currently been withdrawn due to undesirable long-term side effects. The only available drug in Europe is orlistat, which serves only as an aid for the treatment of obesity. In the USA, however, a few central adrenergic-mediators, for instance, diethylpropion and phentermine, have been available for decades to treat obesity during a short-term period (less than 12 weeks). The Food and Drug Administration (FDA) has recently approved lorcaserin and the combination phentermine/ topiramate for the treatment of obesity. The first one is a selective serotonin 2C receptor agonist that works by decreasing food intake with few side effects. Its outcomes on weight are modest, but may be helpful in certain selected patients. The phentermine/topiramate combination has proved to be highly effective, achieving a 10% reduction in weight in the majority of patients, although attention must be drawn to the possible development of side effects in both the short and the long-term follow-up. Further investigation regarding the mechanisms involved in weight balance will anticipate the development of new expectations for the treatment of obesity in the near future. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

Systemic hypertension and the right-sided cardiovascular system: a review of the available evidence.

PubMed

Pedrinelli, Roberto; Dell'Omo, Giulia; Talini, Enrica; Canale, Maria Laura; Di Bello, Vitantonio

2009-02-01

Abnormal vasoconstriction of the lesser circulation characterizes a subset of patients with essential hypertension, a possible effect of mechanisms, such as enhanced sympathetic tone, increased delivery of blood-borne vasoconstrictor substances or abnormal local release of vasoactive factors, acting on both sides of the circulation or to backward transmission of increased pressure due to stiffer left ventricles with more advanced diastolic dysfunction. Elevated systemic pressure also associates with thickening of the right ventricle, a central element of the low-pressure system. Right ventricular remodelling develops in parallel with a similar process occurring at the left side, likely as a result of ventricular interdependence under the influence of trophic factors targeting both ventricles, though other mechanisms, including increased pulmonary afterload, may also be operative. By and large independent of the extent of structural remodelling of both ventricles, systemic hypertension also conditions an impaired filling rate of the right ventricle that accompanies a similar phenomenon at the left side. Thus, quite in contrast with the common and simplistic assumption of a separate behaviour of the two ventricles, the right-sided cardiovascular system is not immune to the effect of systemic hypertension, a concept whose clinical and pathophysiological implications require further studies.

Decreasing the Burden of Side Effects Through Positive Message Framing: an Experimental Proof-of-Concept Study.

PubMed

Wilhelm, Marcel; Rief, Winfried; Doering, Bettina K

2018-05-21

Informing patients about treatment side effects increases the occurrence and intensity of side effects. Since the obligatory informed consent procedure in drug treatments requires transparency and nocebo research suggests that the informed consent of a drug leads to an increased occurrence of the mentioned side effects, the aim of this proof of concept study was to determine the effect of two different framings of informed consent on the occurrence, intensity, and perceived threat of side effects. Healthy male participants (n = 80) were randomized to one of two framing groups. The positive framing group was informed that the common side effect dizziness was a sign that the drug had started to work, while the neutral framing group was told that dizziness is an unpleasant but well-known side effect. Side effects were measured after the administration of metoprolol, an antihypertensive agent. Post hoc moderator analyses investigated the effect of pre-existing negative beliefs about the general harm of medication on the framing manipulation. Metoprolol-specific drug-attributed side effects were rated significantly less threatening in the positive framing group. The between-group effect size (Cohen's d) was small (d = 0.38, p = 0.049). Exploratory post hoc moderator analyses suggest that participants who believed that medication is a source of harmful effects benefited from positive framing, compared to neutral framing of drug-attributed side effects. Positive framing was partially effective in decreasing specific side effect measures, particularly among participants with a tendency to believe that medicine is harmful. Informed consent procedures should therefore be personalized, focusing on patients with negative treatment beliefs.

Combined use of alcohol and energy drinks: Dose relationship with self-reported physiological stimulation and sedation side effects.

PubMed

Droste, Nicolas; Peacock, Amy; Bruno, Raimondo; Pennay, Amy; Zinkiewicz, Lucy; Lubman, Dan I; Miller, Peter

2017-08-01

Negative physiological stimulation and sedation side effects are experienced by a significant proportion of consumers who consume alcohol mixed with energy drinks (AmED). Few studies have compared the frequency of side effects between sessions of AmED and sessions of alcohol only within-subject, and none have explored a dose relationship. Explore the occurrence of self-reported physiological stimulant and sedative side effects between sessions of AmED and alcohol only, and at varying ED dosage levels within AmED sessions. A convenience sample of 2953 residents of New South Wales, Australia completed an online survey. N=731 AmED users reported daily caffeine intake, typical alcohol and AmED consumption, and past 12-month experience of physiological stimulation and sedation side effects during AmED and alcohol only sessions. Within-subject analyses compared occurrence of side effects between session types. Hierarchical binary logistic regression analyses explored the association of ED dose during AmED sessions with the experience of physiological side effects. There were greater odds of most stimulant side effects, and lower odds of sedation side effects, during AmED sessions compared to alcohol only sessions. Compared to one ED, consumption of three or more EDs was significantly associated with the majority of both stimulant and alcohol intoxication side effects after controlling for demographics and consumption covariates. AmED is associated with perceived changes in physiological stimulant and sedation side effects of alcohol. Experience of side effects is positively associated with ED dosage. Future research should account for varying ED dosage, and reflect real world consumption levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metabolomics Based Profiling of Dexamethasone Side Effects in Rats

PubMed Central

Malkawi, Abeer K.; Alzoubi, Karem H.; Jacob, Minnie; Matic, Goran; Ali, Asmaa; Al Faraj, Achraf; Almuhanna, Falah; Dasouki, Majed; Abdel Rahman, Anas M.

2018-01-01

Dexamethasone (Dex) is a synthetic glucocorticoid that has anti-inflammatory and immunosuppressant effects and is used in several conditions such as asthma and severe allergy. Patients receiving Dex, either at a high dose or for a long time, might develop several side effects such as hyperglycemia, weight change, or osteoporosis due to its in vivo non-selectivity. Herein, we used liquid chromatography-tandem mass spectrometry-based comprehensive targeted metabolomic profiling as well as radiographic imaging techniques to study the side effects of Dex treatment in rats. The Dex-treated rats suffered from a ∼20% reduction in weight gain, hyperglycemia (145 mg/dL), changes in serum lipids, and reduction in total serum alkaline phosphatase (ALP) (∼600 IU/L). Also, compared to controls, Dex-treated rats showed a distinctive metabolomics profile. In particular, serum amino acids metabolism showed six-fold reduction in phenylalanine, lysine, and arginine levels and upregulation of tyrosine and hydroxyproline reflecting perturbations in gluconeogenesis and protein catabolism which together lead to weight loss and abnormal bone metabolism. Sorbitol level was markedly elevated secondary to hyperglycemia and reflecting activation of the polyol metabolism pathway causing a decrease in the availability of reducing molecules (glutathione, NADPH, NAD+). Overexpression of succinylacetone (4,6-dioxoheptanoic acid) suggests a novel inhibitory effect of Dex on hepatic fumarylacetoacetate hydrolase. The acylcarnitines, mainly the very long chain species (C12, C14:1, C18:1) were significantly increased after Dex treatment which reflects degradation of the adipose tissue. In conclusion, long-term Dex therapy in rats is associated with a distinctive metabolic profile which correlates with its side effects. Therefore, metabolomics based profiling may predict Dex treatment-related side effects and may offer possible novel therapeutic interventions. PMID:29503615

Metabolomics Based Profiling of Dexamethasone Side Effects in Rats.

PubMed

Malkawi, Abeer K; Alzoubi, Karem H; Jacob, Minnie; Matic, Goran; Ali, Asmaa; Al Faraj, Achraf; Almuhanna, Falah; Dasouki, Majed; Abdel Rahman, Anas M

2018-01-01

Dexamethasone (Dex) is a synthetic glucocorticoid that has anti-inflammatory and immunosuppressant effects and is used in several conditions such as asthma and severe allergy. Patients receiving Dex, either at a high dose or for a long time, might develop several side effects such as hyperglycemia, weight change, or osteoporosis due to its in vivo non-selectivity. Herein, we used liquid chromatography-tandem mass spectrometry-based comprehensive targeted metabolomic profiling as well as radiographic imaging techniques to study the side effects of Dex treatment in rats. The Dex-treated rats suffered from a ∼20% reduction in weight gain, hyperglycemia (145 mg/dL), changes in serum lipids, and reduction in total serum alkaline phosphatase (ALP) (∼600 IU/L). Also, compared to controls, Dex-treated rats showed a distinctive metabolomics profile. In particular, serum amino acids metabolism showed six-fold reduction in phenylalanine, lysine, and arginine levels and upregulation of tyrosine and hydroxyproline reflecting perturbations in gluconeogenesis and protein catabolism which together lead to weight loss and abnormal bone metabolism. Sorbitol level was markedly elevated secondary to hyperglycemia and reflecting activation of the polyol metabolism pathway causing a decrease in the availability of reducing molecules (glutathione, NADPH, NAD + ). Overexpression of succinylacetone (4,6-dioxoheptanoic acid) suggests a novel inhibitory effect of Dex on hepatic fumarylacetoacetate hydrolase. The acylcarnitines, mainly the very long chain species (C12, C14:1, C18:1) were significantly increased after Dex treatment which reflects degradation of the adipose tissue. In conclusion, long-term Dex therapy in rats is associated with a distinctive metabolic profile which correlates with its side effects. Therefore, metabolomics based profiling may predict Dex treatment-related side effects and may offer possible novel therapeutic interventions.

Adverse reactions and interactions with beta-adrenoceptor blocking drugs.

PubMed

Lewis, R V; McDevitt, D G

1986-01-01

beta-Blocking drugs are widely used throughout the world and serious adverse reactions are relatively uncommon. Most of those which do occur are pharmacologically predictable and may be avoided by ensuring that patients who are to be given beta-blockers do not have a predisposition to the development of bronchospasm, cardiac failure or peripheral ischaemia. In some situations, the use of a beta 1-selective blocking drug may reduce the risk of a severe adverse reaction, but there is little evidence that other ancillary properties such as partial agonist activity are of relevance in this context. Long term experience with many of the beta-blockers in current use suggests that unpredictable major adverse reactions such as the practolol oculomucocutaneous syndrome are unlikely to be repeated, although some of these drugs may be associated with immunological disturbances and some have been implicated in the development of retroperitoneal fibrosis. beta-Blocking drugs appear to be associated with a number of subjective side effects including muscle fatigue, peripheral coldness and some neurological symptoms. These side effects are highly subjective and are therefore difficult to quantify and it is not known whether they are of major importance in terms of their effect upon patients' overall well-being. It cannot be assumed that simply because such side effects can be elicited that they do, in fact, matter. However, because beta-blockers are often prescribed for patients who have no symptoms and for whom the benefits of therapy are generally small, such side effects would be of considerable importance if they had an overall effect upon quality of life. There are theoretical reasons to suppose that the incidence and severity of such side effects may be related to the ancillary properties of the individual drugs, but there is little evidence that parameters such as beta 1-selectivity, or partial agonist activity are clinically important determinants of the severity of these side effects. Lipophilicity, however, may be associated with an increased incidence of neurological symptoms. beta-Blocking drugs may cause a variety of metabolic disturbances including an increase in serum VLDL-cholesterol concentrations. However, long term studies have not shown that such disturbances are associated with an increased risk of cardiovascular disease, indicating that such metabolic changes may not be of major importance in practice. beta-Blocking drugs may be involved in a number of interactions with other drugs, but few of these have been shown to be of clinical significance.(ABSTRACT TRUNCATED AT 400 WORDS)

Treatment factors affecting longitudinal quality of life in new onset pediatric epilepsy.

PubMed

Modi, Avani C; Ingerski, Lisa M; Rausch, Joseph R; Glauser, Tracy A

2011-05-01

Recognizing the importance of patient-reported outcomes, this longitudinal, prospective study examined: Changes in health-related quality of life (HRQOL) over seven months following antiepileptic drug (AED) initiation and the relationship of seizures, AED side-effects, and AED type to HRQOL. Parents of 124 children with newly diagnosed epilepsy completed measures of HRQOL and side-effects at each clinic visit. Treatment information was also collected. HRQOL remained stable over time; however, seizures and AED side-effects significantly affected multiple HRQOL domains. Higher seizure activity was associated with decreased Physical HRQOL. Side-effects were negatively associated with all HRQOL domains. Children taking carbamazepine who experienced higher side-effects early in therapy demonstrated declining emotional functioning compared to children experiencing no/some side-effects. AED side-effects, AED type, and seizure frequency were associated with longitudinal HRQOL in children with newly-diagnosed epilepsy. Routine assessment of AED side-effects and HRQOL may be useful for clinical decision making.

Development and pilot testing of an online monitoring tool of depression symptoms and side effects for young people being treated for depression.

PubMed

Hetrick, Sarah E; Dellosa, Maria Kristina; Simmons, Magenta B; Phillips, Lisa

2015-02-01

To develop and examine the feasibility of an online monitoring tool of depressive symptoms, suicidality and side effects. The online tool was developed based on guideline recommendations, and employed already validated and widely used measures. Quantitative data about its use, and qualitative information on its functionality and usefulness were collected from surveys, a focus group and individual interviews. Fifteen young people completed the tool between 1 and 12 times, and reported it was easy to use. Clinicians suggested it was too long and could be completed in the waiting room to lessen impact on session time. Overall, clients and clinicians who used the tool found it useful. Results show that an online monitoring tool is potentially useful as a systematic means for monitoring symptoms, but further research is needed including how to embed the tool within clinical practice. © 2014 Wiley Publishing Asia Pty Ltd.

[Treatment side effects and compliance in patients with depression].

PubMed

Petrova, N N; Kucher, E O

2012-01-01

The impact of treatment side-effects on the compliance was studied in 85 depressive patients with different mental disorders - recurrent depressive disorder, postschizophrenic depression and organic affective disorder. The comparison of objective and subjective evaluations of compliance and a comparative analysis of the level of compliance, with its dependence on the treatment specifics, in different diseases were done. A significant role of efficacy and treatment side-effects was identified. The levels of "mental" and "autonomous" side-effects were highest in the treatment of depression: patients with postschizophrenic depression had the highest risk in respect of maintenance treatment; patients with recurrent depressive disorder and organic (affective) disorder were more tolerant to the treatment side-effects and their treatment, including the maintenance therapy, was rather effective. The compliance of all patients with depression was negatively correlated with the severity of side-effects of pharmacotherapy. The greatest side-effects and the lowest level of compliance were observed in the complex treatment with antidepressants and atypical neuroleptics. The effect of side-effects on the compliance was dependent on their severity and subjective tolerability and, to a lesser extent, on the amount of drugs.

Endovenous ablation of refluxing saphenous and perforating veins.

PubMed

Proebstle, Thomas; van den Bos, Renate

2017-05-01

Since the end of the nineties endovenous thermal ablation and more recently non-thermal, non-tumescent techniques have been developed and improved. Until now, because of their favourable side effect profile in conjunction to sustained efficacy, in many countries they already replaced high ligation and stripping in the treatment of refluxing saphenous veins as well as for treatment of perforators and selected tributaries. Now, studies and comparative trials are available with long-term follow-ups for most of the techniques, providing valid data on occlusion and reflux rates, side effect profiles, and health related quality of life.

The International Applied Military Psychology Symposium (27th): A Focus on Decision Making Research

DTIC Science & Technology

1992-08-04

kinds of elements that need to be con- sidered: goals , actions , side effects and processes to be controlled. Thus, complexity would be related to the...number of processes to be controlled, the number of goals , the number of action alternatives, and the number of side effects. In the case of the fire...t FOA, d~~s~ I decisio ~nsuppo rt system called vih ’Yais developeIt ir responding !i A;cta"m ic iiui’aI1 (NJW’, attacks. This "endrti in use. serv

Development of a carbazole-based fluorescence probe for G-quadruplex DNA: The importance of side-group effect on binding specificity

NASA Astrophysics Data System (ADS)

Wang, Ming-Qi; Ren, Gui-Ying; Zhao, Shuang; Lian, Guang-Chang; Chen, Ting-Ting; Ci, Yang; Li, Hong-Yao

2018-06-01

G-quadruplex DNAs are highly prevalent in the human genome and involved in many important biological processes. However, many aspects of their biological mechanism and significance still need to be elucidated. Therefore, the development of fluorescent probes for G-quadruplex detection is important for the basic research. We report here on the development of small molecular dyes designed on the basis of carbazole scaffold by introducing styrene-like substituents at its 9-position, for the purpose of G-quadruplex recognition. Results revealed that the side group on the carbazole scaffold was very important for their ability to selectively recognize G-quadruplex DNA structures. 1a with the pyridine side group displayed excellent fluorescence signal turn-on property for the specific discrimination of G-quadruplex DNAs against other nucleic acids. The characteristics of 1a were further investigated with UV-vis spectrophotometry, fluorescence, circular dichroism, FID assay and molecular docking to validate the selectivity, sensitivity and detailed binding mode toward G-quadruplex DNAs.

Research on Operation Strategy for Bundled Wind-thermal Generation Power Systems Based on Two-Stage Optimization Model

NASA Astrophysics Data System (ADS)

Sun, Congcong; Wang, Zhijie; Liu, Sanming; Jiang, Xiuchen; Sheng, Gehao; Liu, Tianyu

2017-05-01

Wind power has the advantages of being clean and non-polluting and the development of bundled wind-thermal generation power systems (BWTGSs) is one of the important means to improve wind power accommodation rate and implement “clean alternative” on generation side. A two-stage optimization strategy for BWTGSs considering wind speed forecasting results and load characteristics is proposed. By taking short-term wind speed forecasting results of generation side and load characteristics of demand side into account, a two-stage optimization model for BWTGSs is formulated. By using the environmental benefit index of BWTGSs as the objective function, supply-demand balance and generator operation as the constraints, the first-stage optimization model is developed with the chance-constrained programming theory. By using the operation cost for BWTGSs as the objective function, the second-stage optimization model is developed with the greedy algorithm. The improved PSO algorithm is employed to solve the model and numerical test verifies the effectiveness of the proposed strategy.

Development of the My Medicines and Me (M3Q) side effect questionnaire for mental health patients: a qualitative study

PubMed Central

Ashoorian, Deena M.; Davidson, Rowan M.; Rock, Daniel J. T.; Seubert, Liza J.; Clifford, Rhonda M.

2015-01-01

Objective: The objective of this study was to assess the acceptability, content validity and usability of the My Medicines and Me (M3Q) self-report side effect questionnaire. Methods: Eight focus groups consisting of mental health patients, carers, general practitioners, psychiatrists, mental health nurses and pharmacists were conducted, involving 78 participants. Two researchers independently examined the transcriptions and analysed the data thematically using an inductive method. Results: The findings supported changes to the formatting, length and phrasing of questions in the original version of the questionnaire. Although the groups provided differing views on the usability of the M3Q in clinical practice, the patient and carer groups were unconditionally in favour of such a tool to be used systematically to describe patients’ subjective experiences with side effects. Conclusion: The differing contribution made by all groups involved in the administration and completion of the M3Q assisted with content validity of the questionnaire. The acceptability and usability of this novel side effect questionnaire was also explored, with many participants agreeing it was a necessary tool for a patient centred approach to treatment. Following implementation of the changes to the current format of the questionnaire, investigation into the uptake and use in clinical practice should be carried out. PMID:26557985

Development of universal antidotes to control aptamer activity

PubMed Central

Oney, Sabah; Lam, Ruby T S; Bompiani, Kristin M; Blake, Charlene M; Quick, George; Heidel, Jeremy D; Liu, Joanna Yi-Ching; Mack, Brendan C; Davis, Mark E; Leong, Kam W; Sullenger, Bruce A

2010-01-01

With an ever increasing number of people taking numerous medications, the need to safely administer drugs and limit unintended side effects has never been greater. Antidote control remains the most direct means to counteract acute side effects of drugs, but, unfortunately, it has been challenging and cost prohibitive to generate antidotes for most therapeutic agents. Here we describe the development of a set of antidote molecules that are capable of counteracting the effects of an entire class of therapeutic agents based upon aptamers. These universal antidotes exploit the fact that, when systemically administered, aptamers are the only free extracellular oligonucleotides found in circulation. We show that protein-and polymer-based molecules that capture oligonucleotides can reverse the activity of several aptamers in vitro and counteract aptamer activity in vivo. The availability of universal antidotes to control the activity of any aptamer suggests that aptamers may be a particularly safe class of therapeutics. PMID:19801990

[Doping. High-tech cheating in sport].

PubMed

Striegel, H; Simon, P

2007-07-01

Today, doping is no longer limited to the classical drugs with well known effects and side effects. Older generation anabolic steroids are used mainly in fitness and recreational sports. In contrast, due to doping tests, substances used in competitive sports include peptide hormones, medications not yet approved, and even specially developed drugs, such as designer steroids. Of the peptide hormones, particularly growth hormones (human growth hormone), erythropoietin and generics, insulin, and presumably insulin-like growth factor 1 are used. Substance groups potentially relevant for doping are selective androgen receptor modulators and gene therapy drugs. For most of these, there is no knowledge about side effects in healthy individuals, and no adequate doping tests. Therefore, anti-doping measures cannot rely solely on the continual improvement of doping analyses, but should include increased measures for doping prevention. Not only sports organizations, but also governmental agencies should be involved in developing and implementing these measures.

Cutaneous resurfacing with CO2 and erbium: YAG lasers: preoperative, intraoperative, and postoperative considerations.

PubMed

Alster, T S

1999-02-01

The development and integration of pulsed and scanned CO2 and erbium:YAG laser systems into mainstream surgical practice over the past years has revolutionized cutaneous resurfacing. These lasers are capable of delivering to skin high peak fluences to effect controlled tissue vaporization, while leaving an acceptably narrow zone of residual thermal damage. The inherent technological differences that exist between the two distant laser systems in terms of ablation depths, degree of thermal coagulation, and postoperative side-effects and complications guide patient selection and management. This article reviews the basic principles of CO2 and erbium:YAG laser resurfacing, including preoperative, intraoperative, and postoperative patient considerations. Side-effects and complications encountered after laser resurfacing are discussed with specific guidelines provided on their appropriate management. Anticipated future developments and cutting-edge research endeavors in cutaneous laser resurfacing are also briefly outlined.

Parental Expectation of Side Effects Following Vaccination Is Self-fulfilling: A Prospective Cohort Study.

PubMed

Smith, Louise E; Weinman, John; Amlôt, Richard; Yiend, Jenny; Rubin, G James

2018-06-02

One of the major factors contributing to parental refusal of vaccinations is the perception that vaccines cause side effects. Although symptoms are commonly reported following vaccinations, their causes are not always straightforward. Although some may be directly attributable to the vaccine itself, others may reflect pre-existing or coincidental symptoms that are misattributed to the vaccine. To investigate psychological factors associated with parental report of side effects following vaccination with the child influenza vaccine, and parental intention to re-vaccinate one's child the following year. A prospective cohort study was run in primary care practices in London in the 2016-2017 influenza season (ClinicalTrials.gov number NCT02909855). Two hundred seventy parents from 14 practices completed a questionnaire before their child's vaccination. Follow-up questionnaires were completed 3 days after vaccination and one month after vaccination. Parental report of side effects and vaccination intention for the subsequent year were measured. Parental report of side effects was strongly associated with pre-vaccination expectation of side effects. Suggestions received from the media, National Health Service (NHS) vaccination leaflet, and health care workers, as well as uncertainty-related beliefs, perceived sensitivity of the child to medicines, pessimism, and anxiety were also associated with reporting side effects. Side effect report was associated with lower vaccination intention for the following influenza season. Side effect perception following vaccination is influenced by psychological factors, in particular expectations. Perceiving side effects reduces future vaccination intention. Future public health communications should aim to decrease unrealistic expectations of side effects to increase vaccine uptake.

Endocrine therapy toxicity: management options.

PubMed

Henry, N Lynn

2014-01-01

Treatment with adjuvant endocrine therapy, including tamoxifen and the aromatase inhibitors, has resulted in notable improvements in disease-free and overall survival for patients with hormone receptor-positive breast cancer. Despite their proven benefit, however, adherence to and persistence with the medications is poor in part because of bothersome side effects that can negatively affect quality of life. Retrospective analyses have identified possible predictors of development of toxicity. Reports have also suggested that development of toxicity may be a biomarker of better response to therapy. In addition, there has been considerable research investment into the management of these side effects, which may lead to improved adherence and persistence with therapy. However, although notable advances have been made, much more remains to be done to provide patients with truly personalized therapy for hormone receptor-positive breast cancer.

"Herbal seizures"--atypical symptoms after ibogaine intoxication: a case report.

PubMed

Breuer, Lorenz; Kasper, Burkhard S; Schwarze, Bernd; Gschossmann, Juergen M; Kornhuber, Johannes; Müller, Helge H

2015-10-31

Misuse of various new psychotropic substances such as ibogaine is increasing rapidly. Knowledge of their negative side effects is sparse. We present a case of intoxication with the herbal substance ibogaine in a 22-year-old white man. After taking a cumulative dose of 38 g (taken in two doses), he developed visual memories, nausea and vomiting. He developed a generalized tonic-clonic seizure with additional grand mal seizures. He was treated with midazolam and levetiracetam. Extended drug screenings and computed tomography and magnetic resonance imaging findings were all negative. Knowledge of the side effects of ibogaine has mainly come from reports of cardiovascular complications; seizures are rarely mentioned and experimental findings are inconsistent. It seems that ibogaine acts like a proconvulsive drug at high doses.

Radiation Therapy Side Effects

Cancer.gov

Radiation therapy has side effects because it not only kills or slows the growth of cancer cells, it can also affect nearby healthy cells. Many people who get radiation therapy experience fatigue. Other side effects depend on the part of the body that is being treated. Learn more about possible side effects.

Influence of opioid-related side effects on disability, mood, and opioid misuse risk among patients with chronic pain in primary care.

PubMed

Jamison, Robert N; Dorado, Kathleen; Mei, Anna; Edwards, Robert R; Martel, Marc O

2017-03-01

There is increasing concern among primary care practitioners about the use of opioids for chronic pain, including their adverse effects, but little attention has been given to how reports of side effects from prescription medication can contribute to outcomes among patients with chronic pain. The aim of this study was to investigate the impact of frequently reported side effects on mood, disability, and opioid misuse in patients with chronic pain prescribed opioids within primary care. Two hundred (N = 200) patients with chronic pain taking opioids for pain were recruited into the study. All patients completed baseline measures and a monthly side effects checklist once a month for 6 months. Patients were divided evenly based on a median split of the number of endorsed side effects over 6 months. The subjects repeated the baseline measures at the end of the study period. Over time, reports of medication side effects tended to decrease, but differences in frequency of reported side effects from baseline to follow-up (6-month time) were not significant, and the order of the frequency of the reported side effects remained similar. Patients who reported significant medication-related adverse effects reported significantly greater activity interference, negative affect, and catastrophizing compared with those with fewer side effects ( P < 0.01). In addition, those patients with pain who reported more side effects showed significantly higher scores on opioid misuse risk ( P < 0.001). This study demonstrates the important role of monitoring medication-related side effects among patients with chronic pain who are prescribed opioid medication for pain within primary care.

Influence of opioid-related side effects on disability, mood, and opioid misuse risk among patients with chronic pain in primary care

PubMed Central

Jamison, Robert N.; Dorado, Kathleen; Mei, Anna; Edwards, Robert R.; Martel, Marc O.

2017-01-01

Abstract Background: There is increasing concern among primary care practitioners about the use of opioids for chronic pain, including their adverse effects, but little attention has been given to how reports of side effects from prescription medication can contribute to outcomes among patients with chronic pain. The aim of this study was to investigate the impact of frequently reported side effects on mood, disability, and opioid misuse in patients with chronic pain prescribed opioids within primary care. Methods: Two hundred (N = 200) patients with chronic pain taking opioids for pain were recruited into the study. All patients completed baseline measures and a monthly side effects checklist once a month for 6 months. Patients were divided evenly based on a median split of the number of endorsed side effects over 6 months. The subjects repeated the baseline measures at the end of the study period. Results: Over time, reports of medication side effects tended to decrease, but differences in frequency of reported side effects from baseline to follow-up (6-month time) were not significant, and the order of the frequency of the reported side effects remained similar. Patients who reported significant medication-related adverse effects reported significantly greater activity interference, negative affect, and catastrophizing compared with those with fewer side effects (P < 0.01). In addition, those patients with pain who reported more side effects showed significantly higher scores on opioid misuse risk (P < 0.001). Discussion: This study demonstrates the important role of monitoring medication-related side effects among patients with chronic pain who are prescribed opioid medication for pain within primary care. PMID:29392205

Side effects of low-dose pyridostigmine bromide are not related to cholinesterase inhibition.

PubMed

Cook, M R; Gerkovich, M M; Sastre, A; Graham, C

2001-12-01

Pretreatment with pyridostigmine bromide (PB) has become part of standard military procedures for protection against the effects of possible chemical warfare attack. The purpose of the work reported here was to quantify the type, intensity and frequency of side effects of low-dose PB, and to examine factors that predict the intensity and frequency of side effects. A double-blind, cross-over, placebo (PL)-controlled design was used. Of the 67 subjects, 33 received 30 mg PB every 8 h for 13 doses, and 34 received 60 mg on the same schedule. Order of PB and PL administration was counterbalanced. Overall, side effects were mild, even at the 60-mg dose level. More side effects were reported when volunteers were taking PB than when they were taking placebo. Women reported more symptoms than men. Neither cholinesterase inhibition nor plasma levels of PB predicted side effect scores during the PB week; the best predictor of side effect scores during the PB week was side effect scores during the PL week. PB is well tolerated by healthy young people, even when twice the recommended military dose is administered.

Transient Three-Dimensional Startup Side Load Analysis of a Regeneratively Cooled Nozzle

NASA Technical Reports Server (NTRS)

Wang, Ten-See

2008-01-01

The objective of this effort is to develop a computational methodology to capture the startup side load physics and to anchor the computed aerodynamic side loads with the available data from a regeneratively cooled, high-aspect-ratio nozzle, hot-fired at sea level. The computational methodology is based on an unstructured-grid, pressure-based, reacting flow computational fluid dynamics and heat transfer formulation, a transient 5 s inlet history based on an engine system simulation, and a wall temperature distribution to reflect the effect of regenerative cooling. To understand the effect of regenerative wall cooling, two transient computations were performed using the boundary conditions of adiabatic and cooled walls, respectively. The results show that three types of shock evolution are responsible for side loads: generation of combustion wave; transitions among free-shock separation, restricted-shock separation, and simultaneous free-shock and restricted shock separations; along with the pulsation of shocks across the lip, although the combustion wave is commonly eliminated with the sparklers during actual test. The test measured two side load events: a secondary and lower side load, followed by a primary and peak side load. Results from both wall boundary conditions captured the free-shock separation to restricted-shock separation transition with computed side loads matching the measured secondary side load. For the primary side load, the cooled wall transient produced restricted-shock pulsation across the nozzle lip with peak side load matching that of the test, while the adiabatic wall transient captured shock transitions and free-shock pulsation across the lip with computed peak side load 50% lower than that of the measurement. The computed dominant pulsation frequency of the cooled wall nozzle agrees with that of a separate test, while that of the adiabatic wall nozzle is more than 50% lower than that of the measurement. The computed teepee-like formation and the tangential motion of the shocks during lip pulsation also qualitatively agree with those of test observations. Moreover, a third transient computation was performed with a proportionately shortened 1 s sequence, and lower side loads were obtained with the higher ramp rate.

Factors affecting patient's perception of anticancer treatments side-effects: an observational study.

PubMed

Russo, Stefania; Cinausero, Marika; Gerratana, Lorenzo; Bozza, Claudia; Iacono, Donatella; Driol, Pamela; Deroma, Laura; Sottile, Roberta; Fasola, Gianpiero; Puglisi, Fabio

2014-02-01

Analysis of relative importance of side effects of anticancer therapy is extremely useful in the process of clinical decision making. There is evidence that patients' perception of the side effects of anticancer treatments changes over time. Aim of this study was to evaluate the cancer patients' perceptions of physical and non-physical side effects of contemporary anticancer therapy. Four hundred and sixty-four patients entered the study (153 men and 311 women). Participants were asked to rank their side effects in order of distress by using two sets of cards naming physical and non-physical effects, respectively. Influencing factors, including treatment and patient characteristics, were also analysed. Patients ranked the non-physical side effect 'Affects my family or partner' first. 'Constantly tired' and 'Loss of hair' were ranked second and third, respectively. Significant differences from previous studies on this topic emerged. In particular, 'Vomiting', a predominant concern in previous studies, almost disappeared, whereas 'Nausea' and 'Loss of hair' remained important side effects in the patients' perception. Interestingly, marital status was predominant in driving patients' perception, being associated with several side effects ('Constantly tired', 'Loss of appetite', 'Affects my work/Home duties', 'Affects my social activities', 'Infertility'). Other significant factors influencing patient's perception of side effects included age, disease characteristics and ongoing anticancer therapy. This study provided information on current status of patients' perceptions of side effects of anticancer treatment. These results could be used in pre-treatment patient education and counselling.

Perceived risk of tamoxifen side effects: a study of the use of absolute frequencies or frequency bands, with or without verbal descriptors.

PubMed

Knapp, Peter; Gardner, Peter H; Raynor, David K; Woolf, Elizabeth; McMillan, Brian

2010-05-01

To investigate the effectiveness of presenting medicine side effect risk information in different forms, including that proposed by UK guidelines [[1] Medicines and Healthcare products Regulatory Agency. Always read the leaflet-Getting the best information with every medicine. (Report of the Committee on Safety of Medicines Working Group on Patient Information). London: The Stationery Office, 2005.]. 134 Cancer Research UK (CRUK) website users were recruited via a 'pop-up'. Using a 2x2 factorial design, participants were randomly allocated to one of four conditions and asked to: imagine they had to take tamoxifen, estimate the risks of 4 side effects, and indicate a presentation mode preference. Those presented with absolute frequencies demonstrated greater accuracy in estimating 2 of 4 side effects, and of any side effect occurring, than those presented with frequency bands. Those presented with combined descriptors were more accurate at estimating the risk of pulmonary embolism than those presented with numeric descriptors only. Absolute frequencies outperform frequency bands when presenting side effect risk information. However, presenting such exact frequencies for every side effect may be much less digestible than all side effects listed under 5 frequency bands. Combined numerical and verbal descriptors may be better than numeric only descriptors when describing infrequent side effects. Information about side effects should be presented in ways that patients prefer, and which result in most accurate risk estimates. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Comparison of molindone and tranylcypromine in the treatment of refractory depression.

PubMed

Small, J G; Kellams, J J; Dennis, J L; Milstein, V

1981-01-01

A single-blind parallel study of 20 treatment-resistant hospitalized depressed patients showed that 10-30 mg/day molindone was more effective and less toxic than 20-30 mg tranylcypromine. Molindone-treated patients responded during the first week with particular improvement in anxiety symptoms and agitation. Extrapyramidal symptoms developed in half of the patients on molindone, which were effectively managed with amantadine. Early termination from the study because of clinical worsening or side effects occurred in seven patients on tranylcypromine and in none on molindone. These results suggest that molindone in low dosage may be helpful in the management of refractory depression and may have the further advantage of producing a more rapid response to treatment with fewer disabling side effects.

Frontal Plane Knee Moments in Golf: Effect of Target Side Foot Position at Address

PubMed Central

Lynn, Scott K.; Noffal, Guillermo J.

2010-01-01

Golf has the potential to keep people active well into their later years. Injuries to the target side knee have been reported in golfers, yet no mechanisms for these injuries have been proposed. The loads on the knee during the golf swing may be insufficient to cause acute injury, yet they may be a factor in the progression of overuse/degenerative conditions; therefore, research developing swing modifications that may alter loading of the knee is warranted. It has been suggested that the proper golf set-up position has the target-side foot externally rotated but no reasoning for this modification has been provided. Frontal plane knee moments have been implicated in many knee pathologies. Therefore, this study used a 3-dimensional link segment model to quantify the frontal plane knee moments during the golf swing in a straight (STR) and externally rotated (EXT) target-side foot position. Subjects were 7 collegiate golfers and knee moments were compared between conditions using repeated measures T-tests. The golf swing knee moment magnitudes were also descriptively compared to those reported for two athletic maneuvers (drop jump landing, side-step cutting) and activities of daily living (gait, stair ascent). The EXT condition decreased the peak knee adduction moment as compared to the STR condition; however, foot position had no effect on the peak knee abduction moment. Also, the magnitude of the knee adduction moments during the two activities of daily living were 9-33% smaller than those experienced during the two different golfing conditions. The drop jump landing and golf swing knee moments were of similar magnitude (STR= - 5%, EXT= + 8%); however, the moments associated with side- step cutting were 50-71% larger than those on the target side knee during the golf swing. The loading of the target side knee during the golf swing may be a factor in the development and progression of knee pathologies and further research should examine ways of attenuating these loads through exercise and swing modifications. Key points An externally rotated front foot position at address would be recommended for those with medial knee pathology in the target side limb. There is a large valgus moment on the target side knee during the golf swing that is not decreased with external rotation of the foot at address. The potential of the knee moments on the target side limb to lead to knee pathologies in golfers needs to be further investigated. PMID:24149696

Anticancer Effects of Sandalwood (Santalum album).

PubMed

Santha, Sreevidya; Dwivedi, Chandradhar

2015-06-01

Effective management of tumorigenesis requires development of better anticancer agents with greater efficacy and fewer side-effects. Natural products are important sources for the development of chemotherapeutic agents and almost 60% of anticancer drugs are of natural origin. α-Santlol, a sesquiterpene isolated from Sandalwood, is known for a variety of therapeutic properties including anti-inflammatory, anti-oxidant, anti-viral and anti-bacterial activities. Cell line and animal studies reported chemopreventive effects of sandalwood oil and α-santalol without causing toxic side-effects. Our laboratory identified its anticancer effects in chemically-induced skin carcinogenesis in CD-1 and SENCAR mice, ultraviolet-B-induced skin carcinogenesis in SKH-1 mice and in vitro models of melanoma, non-melanoma, breast and prostate cancer. Its ability to induce cell-cycle arrest and apoptosis in cancer cells is its most reported anticancer mechanism of action. The present review discusses studies that support the anticancer effect and the mode of action of sandalwood oil and α-santalol in carcinogenesis. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Further Investigations of the Passive Optical Sample Assembly (POSA) - I Flight Experiment

NASA Technical Reports Server (NTRS)

Finckenor, Miria M.; Kamenetzky, Rachel R.; Vaughn, Jason A.; Mell, Richard; Deshpande, M. S.

2001-01-01

The Passive Optical Sample Assembly-I (POSA-I), part of the Mir Environmental Effects Payload (MEEP), was designed to study the combined effects of contamination, atomic oxygen, ultraviolet radiation, vacuum, then-nal cycling, and other constituents of the space environment on spacecraft materials. The MEEP program is a Phase I International Space Station Risk Mitigation Experiment. Candidate materials for the International Space Station (ISS) were exposed in a specially designed "suitcase" carrier, with identical specimens facing either Mir or space. The payload was attached by EVA to the exterior of the Mir docking module during the STS-76 mission (f'ig. 1). It was removed during the STS-86 mission after an 18-month exposure. During the mission, it received approximately 7 x 1019 atoMS/CM2 atomic oxygen, as calculated by polymer mass loss, and 413 ESH of solar ultraviolet radiation on the Mir-facing side. The side facing away from Mir received significant contaminant deposition, so atomic oxygen fluence has not been reliably determined. The side facing away from Mir received 571 ESH of solar UV. Contamination was observed on both the Mir-facing and space-facing sides of the POSA-I experiment , with a greater amount of deposition on the space facing side than the Mir side. The contamination has been determined to be outgassed silicone photofixed by ultraviolet radiation and converted to silicate by atomic oxygen interaction. Electron spectroscopy for chemical analysis (ESCA) with depth profiling indicated the presence of 26 - 31 nm silicate on the Mir-facing side and 500 - 1000 nm silicate on the space-facing side. The depth profiling also showed that the contaminant layer was uniform, with a small amount of carbon present on the surface and trace amounts of nitrogen, phosphorus, sulfur, and tin. The surface carbon layer is likely due to post-flight exposure in the laboratory and is similar to carbonaceous deposits on control samples. EDAX and FTIR analysis concurred with ESCA for the presence of silicon, oxygen, and carbon. Nearly 400 samples were exposed on POSA-I, which included materials such as thermal control coatings polymeric films, optical materials, and multi-layer insulation blankets. A previous paper discussed the effects of the space environment exposure and contaminant deposition on candidate materials for ISS, including Z93P inorganic thermal control coating, various anodizes, and multi-layer insulation blankets. This paper details the investigation of environmental effects on the remainder of POSA-I samples, particularly the innovative conductive thermal control coatings developed by AZ Technology of Huntsville, AL and HT Research Institute of Chicago, IL. The silicone/silicate contamination had a significant impact on the solar absorptance of white inorganic thermal control coatings on the space-facing side of POSA-I. The effect of contamination on electrical conductivity is discussed. Samples of conductive anodized aluminum developed by Boundary Technologies of Buffalo Grove, IL were also exposed on POSA-I. The effects of the space environment and contaminant deposition on the optical and electrical properties of the conductive anodized aluminum are discussed.

Kerato-lenticular ocular deposits and visual impairment with prolonged chlorpromazine use: A case series.

PubMed

Gowda, Guru S; Hegde, Aditya; Shanbhag, Vandita; Narayanaswamy, Janardhanan C; Jaisoorya, T S

2017-02-01

Chlorpromazine is a low potency "typical" antipsychotic agent used to treat schizophrenia. It continues to be prescribed frequently in India owing to its lower cost. There have been previous reports of ocular adverse effects with prolonged use of chlorpromazine. We report three patients who developed corneal and lenticular opacities secondary to prolonged chlorpromazine use leading to visual impairment. Early detection of ocular deposits and switching over to risperidone from chlorpromazine helped in the reversal of chlorpromazine- induced ocular side effects in one of them. The case series further adds evidence to the causative relationship between chlorpromazine and ocular side effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Second-generation corticosteroids for the treatment of Crohn's disease and ulcerative colitis: more effective and less side effects?

PubMed

De Cassan, Chiara; Fiorino, Gionata; Danese, Silvio

2012-01-01

Systemic corticosteroids are highly effective at inducing clinical remission in cases of acute exacerbation of Crohn's disease (CD) and ulcerative colitis (UC); however, their use is limited by their frequent and sometimes severe side effects. Thus, a second generation of corticosteroids with less systemic effects has been developed. This review analyzed all of the studies on the new formulations of steroids with limited absorption (budesonide, budesonide MMX®, beclomethasone dipropionate and erythrocyte-mediated delivery of dexamethasone) in patients with CD and UC. All relevant articles published in English between September 1960 and April 2011 were reviewed. Budesonide is superior to placebo, and as effective as systemic corticosteroids in inducing clinical remission in patients with ileo-colonic CD, but evidence of mucosal healing is limited. When administered as an MMX formula, budesonide can also effectively induce clinical remission in patients with UC, but budesonide alone is not effective in maintaining clinical remission in CD or UC. Beclomethasone dipropionate seems to be effective in patients with mild-to-moderate left-sided and extensive UC, while data on erythrocyte-mediated delivery of dexamethasone are encouraging but still limited. The safety profile for all these products is good but more studies are needed. Steroids remain the mainstay for the induction of clinical remission in cases of acute relapse of both CD and UC. Second-generation corticosteroids are an interesting alternative, with the advantage of high topical activity, less systemic toxicity and limited side effects. Copyright © 2012 S. Karger AG, Basel.

Medication Side Effects among People with Epilepsy Taking Phenobarbital in Zambia

PubMed Central

Elafros, Melissa A.; Bui, Esther; Birbeck, Gretchen L.

2014-01-01

Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool Adverse Events Profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman’s correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1 mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4–8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the WHO report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional investigations regarding phenobarbital side effects in routine care in low income settings is warranted. PMID:25219354

Medication side effects among people with epilepsy taking phenobarbital in Zambia.

PubMed

Elafros, Melissa A; Bui, Esther; Birbeck, Gretchen L

2014-11-01

Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool adverse events profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman's correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4-8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the World Health Organization report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional investigations regarding phenobarbital side effects during routine care in low income settings is warranted. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of side group functionality and molecular weight on the activity of synthetic antimicrobial polypeptides.

PubMed

Engler, Amanda C; Shukla, Anita; Puranam, Sravanthi; Buss, Hilda G; Jreige, Nina; Hammond, Paula T

2011-05-09

The rapid emergence of antibiotic-resistant bacteria along with increasing difficulty in biofilm treatment has caused an immediate need for the development of new classes of antimicrobial therapeutics. We have developed a library of antimicrobial polypeptides, prepared by the ring-opening polymerization of γ-propargyl-L-glutamate N-carboxyanhydride and the alkyne-azide cycloaddition click reaction, which mimic the favorable characteristics of naturally occurring antimicrobial peptides (AmPs). AmPs are known not to cause drug resistance as well as prevent bacteria attachment on surfaces. The ease and scale of synthesis of the antimicrobial polypeptides developed here are significantly improved over the traditional Merrifield synthetic peptide approaches needed for naturally occurring antimicrobial peptides and avoids the unique challenges of biosynthetic pathways. The polypeptides range in length from 30 to 140 repeat units and can have varied side group functionality, including primary, secondary, tertiary, and quaternary amines with hydrocarbon side chains ranging from 1 to 12 carbons long. Overall, we find these polypeptides to exhibit broad-spectrum activity against both Gram positive and Gram negative bacteria, namely, S. aureus and E. coli , while having very low hemolytic activity. Many of the polypeptides can also be used as surface coatings to prevent bacterial attachment. The polypeptide library developed in this work addresses the need for effective biocompatible therapeutics for drug delivery and medical device coatings.

Reducing Aversion to Side Effects in Preventive Medical Treatment Decisions

ERIC Educational Resources Information Center

Waters, Erika A.; Weinstein, Neil D.; Colditz, Graham A.; Emmons, Karen M.

2007-01-01

Laypeople tend to be overly sensitive to side effects of treatments that prevent illness, possibly leading them to refuse beneficial therapies. This Internet-based study attempted to reduce such side effect aversion by adding graphic displays to the numerical risk probabilities. It also explored whether graphics reduce side effect aversion by…

Systematic identification of proteins that elicit drug side effects

PubMed Central

Kuhn, Michael; Al Banchaabouchi, Mumna; Campillos, Monica; Jensen, Lars Juhl; Gross, Cornelius; Gavin, Anne-Claude; Bork, Peer

2013-01-01

Side effect similarities of drugs have recently been employed to predict new drug targets, and networks of side effects and targets have been used to better understand the mechanism of action of drugs. Here, we report a large-scale analysis to systematically predict and characterize proteins that cause drug side effects. We integrated phenotypic data obtained during clinical trials with known drug–target relations to identify overrepresented protein–side effect combinations. Using independent data, we confirm that most of these overrepresentations point to proteins which, when perturbed, cause side effects. Of 1428 side effects studied, 732 were predicted to be predominantly caused by individual proteins, at least 137 of them backed by existing pharmacological or phenotypic data. We prove this concept in vivo by confirming our prediction that activation of the serotonin 7 receptor (HTR7) is responsible for hyperesthesia in mice, which, in turn, can be prevented by a drug that selectively inhibits HTR7. Taken together, we show that a large fraction of complex drug side effects are mediated by individual proteins and create a reference for such relations. PMID:23632385

Prediction of Central Nervous System Side Effects Through Drug Permeability to Blood-Brain Barrier and Recommendation Algorithm.

PubMed

Fan, Jun; Yang, Jing; Jiang, Zhenran

2018-04-01

Drug side effects are one of the public health concerns. Using powerful machine-learning methods to predict potential side effects before the drugs reach the clinical stages is of great importance to reduce time consumption and protect the security of patients. Recently, researchers have proved that the central nervous system (CNS) side effects of a drug are closely related to its permeability to the blood-brain barrier (BBB). Inspired by this, we proposed an extended neighborhood-based recommendation method to predict CNS side effects using drug permeability to the BBB and other known features of drug. To the best of our knowledge, this is the first attempt to predict CNS side effects considering drug permeability to the BBB. Computational experiments demonstrated that drug permeability to the BBB is an important factor in CNS side effects prediction. Moreover, we built an ensemble recommendation model and obtained higher AUC score (area under the receiver operating characteristic curve) and AUPR score (area under the precision-recall curve) on the data set of CNS side effects by integrating various features of drug.

Goal Format in Small-Sided Soccer Games: Technical Actions and Offensive Scenarios of Prepubescent Players

PubMed Central

Pulling, Craig; Twitchen, Alex; Pettefer, Carl

2016-01-01

The aim of this study was to investigate the influence of the number of goal-posts and the positioning of goal-posts used within small-sided games on the frequency of technical actions and offensive scenarios performed by prepubescent players within soccer. The participants were eight male prepubescent soccer players (12.1 ± 0.5 years). The participants were video recorded for 20 min playing four different formats of 4v4 small-sided games: (1) standard two goal game; (2) four goal game, one goal in each corner; (3) two goal game with goal-posts positioned 9.14 m/10 yd infield, scoring only through the back of the goal; (4) four goal-game, one goal positioned 9.14 m/10 yd infield in each corner, scoring through either the front or back of each goal. Chi-squared tests of independence were utilized to statistically explore the impact of the different small-sided game formats. There were significant associations (p < 0.05) observed between the different small-sided game formats and the frequency of turns, dribbles, shots, goals and overlaps performed. For example, players performed more turns in small-sided game format two and more shots during small-sided game format four. It is suggested coaches should consider using a variation of the number and positioning of goal-posts in small-sided games as an effective training tool in the development of prepubescent soccer players. This will enable coaches to vary the focus of sessions, and develop specific technical and tactical actions within a situation similar to that of real match-play. PMID:29910301

The Dark Side of Resilience and Burnout: A Moderation-Mediation Model

PubMed Central

Treglown, Luke; Palaiou, Kat; Zarola, Anthony; Furnham, Adrian

2016-01-01

This study tested whether specific dark-side traits may be beneficial in manifesting and maintaining Resilience, whilst others are vulnerability factors for Burnout. Four hundred and fifty-one (50 female) ambulance personnel completed three questionnaires as a part of a selection and development assessment. The study utilised the Hogan Development survey as a measure of dark side personality, the Copenhagen Burnout Inventory to assess work-related burnout, and the Resilience Scale– 14 to measure resilience levels. Those high on Excitable and Cautious but low on Bold and Reserved were linked to an increased vulnerability to Burnout. Also those high on Bold and Diligent yet low on the Excitable, Cautious, and Imaginative scales were more resilient. Structural Equation Modelling revealed that resilience plays both a mediating and moderating role on personality and burnout. Theoretical implications suggest future research assessing the predictive capacity of psychological variables on burnout should account the indirect effect of resilience. PMID:27336304

The Dark Side of Resilience and Burnout: A Moderation-Mediation Model.

PubMed

Treglown, Luke; Palaiou, Kat; Zarola, Anthony; Furnham, Adrian

2016-01-01

This study tested whether specific dark-side traits may be beneficial in manifesting and maintaining Resilience, whilst others are vulnerability factors for Burnout. Four hundred and fifty-one (50 female) ambulance personnel completed three questionnaires as a part of a selection and development assessment. The study utilised the Hogan Development survey as a measure of dark side personality, the Copenhagen Burnout Inventory to assess work-related burnout, and the Resilience Scale- 14 to measure resilience levels. Those high on Excitable and Cautious but low on Bold and Reserved were linked to an increased vulnerability to Burnout. Also those high on Bold and Diligent yet low on the Excitable, Cautious, and Imaginative scales were more resilient. Structural Equation Modelling revealed that resilience plays both a mediating and moderating role on personality and burnout. Theoretical implications suggest future research assessing the predictive capacity of psychological variables on burnout should account the indirect effect of resilience.

Numerical simulation of flow path in the oxidizer side hot gas manifold of the Space Shuttle main engine

NASA Technical Reports Server (NTRS)

Lin, S. J.; Yang, R. J.; Chang, James L. C.; Kwak, D.

1987-01-01

The purpose of this study is to examine in detail incompressible laminar and turbulent flows inside the oxidizer side Hot Gas Manifold of the Space Shuttle Main Engine. To perform this study, an implicit finite difference code cast in general curvilinear coordinates is further developed. The code is based on the method of pseudo-compressibility and utilize ADI or implicit approximate factorization algorithm to achieve computational efficiency. A multiple-zone method is developed to overcome the complexity of the geometry. In the present study, the laminar and turbulent flows in the oxidizer side Hot Gas Manifold have been computed. The study reveals that: (1) there exists large recirculation zones inside the bowl if no vanes are present; (2) strong secondary flows are observed in the transfer tube; and (3) properly shaped and positioned guide vanes are effective in eliminating flow separation.

A new early cognitive screening measure to detect cognitive side-effects of electroconvulsive therapy?

PubMed

Martin, Donel M; Katalinic, Natalie; Ingram, Anna; Schweitzer, Isaac; Smith, Deidre J; Hadzi-Pavlovic, Dusan; Loo, Colleen K

2013-12-01

Cognitive side-effects from electroconvulsive therapy (ECT) can be distressing for patients and early detection may have an important role in guiding treatment decisions over the ECT course. This prospective study examined the utility of an early cognitive screening battery for predicting cognitive side-effects which develop later in the ECT course. The screening battery, together with the Mini Mental Status Examination (MMSE), was administered to 123 patients at baseline and after 3 ECT treatments. A more detailed cognitive battery was administered at baseline, after six treatments (post ECT 6) and after the last ECT treatment (post treatment) to assess cognitive side-effects across several domains: global cognition, anterograde memory, executive function, speed and concentration, and retrograde memory. Multivariate analyses examined the predictive utility of change on items from the screening battery for later cognitive changes at post ECT 6 and post treatment. Results showed that changes on a combination of items from the screening battery were predictive of later cognitive changes at post treatment, particularly for anterograde memory (p < 0.01), after controlling for patient and treatment factors. Change on the MMSE predicted cognitive changes at post ECT 6 but not at post treatment. A scoring method for the new screening battery was tested for discriminative ability in a sub-sample of patients. This study provides preliminary evidence that a simple and easy-to-administer measure may potentially be used to help guide clinical treatment decisions to optimise efficacy and cognitive outcomes. Further development of this measure and validation in a more representative ECT clinical population is required. Copyright © 2013 Elsevier Ltd. All rights reserved.

Transient Two-Dimensional Analysis of Side Load in Liquid Rocket Engine Nozzles

NASA Technical Reports Server (NTRS)

Wang, Ten-See

2004-01-01

Two-dimensional planar and axisymmetric numerical investigations on the nozzle start-up side load physics were performed. The objective of this study is to develop a computational methodology to identify nozzle side load physics using simplified two-dimensional geometries, in order to come up with a computational strategy to eventually predict the three-dimensional side loads. The computational methodology is based on a multidimensional, finite-volume, viscous, chemically reacting, unstructured-grid, and pressure-based computational fluid dynamics formulation, and a transient inlet condition based on an engine system modeling. The side load physics captured in the low aspect-ratio, two-dimensional planar nozzle include the Coanda effect, afterburning wave, and the associated lip free-shock oscillation. Results of parametric studies indicate that equivalence ratio, combustion and ramp rate affect the side load physics. The side load physics inferred in the high aspect-ratio, axisymmetric nozzle study include the afterburning wave; transition from free-shock to restricted-shock separation, reverting back to free-shock separation, and transforming to restricted-shock separation again; and lip restricted-shock oscillation. The Mach disk loci and wall pressure history studies reconfirm that combustion and the associated thermodynamic properties affect the formation and duration of the asymmetric flow.

Nilotinib Induced Recurrent Gastric Polyps: Case Report and Review of Literature.

PubMed

Kassem, Nancy; Ismail, Omar M; Elomri, Halima; Yassin, Mohamad A

2017-07-14

BACKGROUND Tyrosine kinase inhibitors (TKIs) are currently an important targeted drug class in the treatment of chronic myeloid leukemia (CML). Imatinib was the first approved TKI for CML in 2001. Nilotinib is a second-generation TKI, approved in 2007; it inhibits BCR-ABL, PDGFR, and c-KIT, and is 30 times more potent than imatinib. Tyrosine kinase enzymes are expressed in multiple tissues and are involved in several signaling pathways; they have been shown to have several off-target side effects. CASE REPORT We report a case of an elderly male with CML and no history of gastrointestinal diseases, treated with nilotinib, and developed recurrent gastric polyps after three years of treatment. We excluded common causes of gastric polyps and therefore considered nilotinib as a probable cause of recurrent gastric polyps. CONCLUSIONS Recurrent gastric polyps could be a potential side effect of nilotinib treatment. Careful long-term monitoring of patients on TKI therapy is necessary and further long-term studies of TKI side effects are needed.

Discovery, clinical development, and therapeutic uses of bisphosphonates.

PubMed

Licata, Angelo A

2005-04-01

To review the literature concerning the history, development, and therapeutic uses of bisphosphonates. English-language articles were identified through a search of MEDLINE (through December 2004) using the key word bisphosphonate. Reference lists of pivotal studies, reviews, and full prescribing information for the approved agents were also examined. Selected studies included those that discussed the discovery and initial applications of bisphosphonates, as well as their historical development, pharmacokinetic and pharmacodynamic properties, and current therapeutic uses. Bisphosphonates structurally resemble pyrophosphates (naturally occurring polyphosphates) and have demonstrated similar physicochemical effects to pyrophosphates. In addition, bisphosphonates reduce bone turnover and resist hydrolysis when administered orally. The information gained from initial work with etidronate generated a considerable scientific effort to design new and more effective bisphosphonates. The PCP moiety in the general bisphosphonate structure is essential for binding to hydroxyapatite and allows for a number of chemical variations by changing the 2 lateral side chains (designated R(1) and R(2)). The R(1) side chain determines binding affinity to hydroxyapatite, and the R(2) side chain determines antiresorptive potency. Accordingly, each bisphosphonate has its own characteristic profile of activity. The bisphosphonates reduce bone turnover, increase bone mass, and decrease fracture risk and therefore have a significant place in the management of skeletal disorders including osteoporosis, Paget's disease, bone metastases, osteogenesis imperfecta, and heterotopic ossification.

Installation of a groundwater monitoring-well network on the east side of the Uncompahgre River in the Lower Gunnison River Basin, Colorado, 2012

USGS Publications Warehouse

Thomas, Judith C.; Arnold, Larry R. Rick

2015-07-06

The east side of the Uncompahgre River Basin has been a known contributor of dissolved selenium to recipient streams. Discharge of groundwater containing dissolved selenium contributes to surface-water selenium concentrations and loads; however, the groundwater system on the east side of the Uncompahgre River Basin is not well characterized. The U.S. Geological Survey, in cooperation with the Colorado Water Conservation Board and the Bureau of Reclamation, has established a groundwater-monitoring network on the east side of the Uncompahgre River Basin. Ten monitoring wells were installed during October and November 2012. This report presents location data, lithologic logs, well-construction diagrams, and well-development information. Understanding the groundwater system will provide managers with an additional metric for evaluating the effectiveness of salinity and selenium control projects.

Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human

PubMed Central

Morgan, Michael M; Christie, MacDonald J

2011-01-01

Opioid agonists are the most effective treatment for pain, but their use is limited by side effects, tolerance and fears of addiction and dependence. A major goal of opioid research is to develop agonists that have high analgesic efficacy and a low profile for side effects, tolerance, addiction and dependence. Unfortunately, there is a serious lack of experimental data comparing the degree to which different opioids produce these effects in humans. In contrast, a wide range of experimental techniques from heterologous expression systems to behaviour assessment in whole animals have been developed to study these problems. The objective of this review is to describe and evaluate these techniques as they are used to study opioid efficacy, tolerance, addiction and dependence. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21434879

Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity – A Case Report

PubMed Central

GERASIMOU, CHARILAOS; PHAEDRA VITALI, GEORGIA; D. VAVOUGIOS, GEORGE; PAPAGEORGIOU, CHARALABOS; DOUZENIS, ATHANASIOS; I. KOKORIS, STYLIANI; LIAPPAS, IOANNIS; RIZOS, EMMANOUIL

2017-01-01

Background: Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. Case Report: We present the case of a 31- year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug. Discussion: This case hints at the presence of initially subclinical cardiotoxicity as an underlying factor in patients developing fever. Conclusion: Taking advantage of more sensitive methods for measuring troponin, clinicians would be promptly aware of this possible side-effect. This would allow for significant reduction of the risk of cardiac dysfunction, further attained by carefully monitoring the patient. PMID:28064233

Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity - A Case Report.

PubMed

Gerasimou, Charilaos; Vitali, Georgia Phaedra; Vavougios, George D; Papageorgiou, Charalabos; Douzenis, Athanasios; Kokoris, Styliani I; Liappas, Ioannis; Rizos, Emmanouil

2017-01-02

Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. We present the case of a 31-year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug. This case hints at the presence of initially subclinical cardiotoxicity as an underlying factor in patients developing fever. Taking advantage of more sensitive methods for measuring troponin, clinicians would be promptly aware of this possible side-effect. This would allow for significant reduction of the risk of cardiac dysfunction, further attained by carefully monitoring the patient. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

When 1+1=1: the unification of independent actors revealed through joint Simon effects in crossed and uncrossed effector conditions.

PubMed

Welsh, Timothy N

2009-12-01

The "Simon effect" describes a pattern of reaction times (RTs) where responses to symbolic information are shorter when the information is presented on the same side of space as the desired response than when it is on the opposite side of space. For example, if right hand responses are required for green targets and left hand responses for red targets, RTs with the right hand are shorter when the green target appears on the right side than on the left side. It has been reported that Simon effects also appear when two individuals perform independent components of a Simon effect task. It has been suggested that such joint Simon effects occur because participants represent the action of their partner. It is unclear, however, if the joint Simon effect emerges because: (1) each partner represents the other's action; (2) each partner is using the other person or their response as an environmental reference; or (3) an intra-hemispheric processing advantage due to the lateralized cerebral organization of perceptual and motor systems. The present study distinguished between these possibilities by asking pairs of participants to perform in conditions in which they crossed their arms into the other person's space. Consistent with within-person Simon effects, joint Simon effects were observed in uncrossed- and crossed limb conditions. These results support a response co-representation explanation of joint Simon effects. It is suggested that the processes underlying the evoked representations have developed to allow two independent agents to form temporary synergies to facilitate efficient task completion. 2009 Elsevier B.V. All rights reserved.

GLYX-13, a NMDA Receptor Glycine-Site Functional Partial Agonist, Induces Antidepressant-Like Effects Without Ketamine-Like Side Effects

PubMed Central

Burgdorf, Jeffrey; Zhang, Xiao-lei; Nicholson, Katherine L; Balster, Robert L; David Leander, J; Stanton, Patric K; Gross, Amanda L; Kroes, Roger A; Moskal, Joseph R

2013-01-01

Recent human clinical studies with the NMDA receptor (NMDAR) antagonist ketamine have revealed profound and long-lasting antidepressant effects with rapid onset in several clinical trials, but antidepressant effects were preceded by dissociative side effects. Here we show that GLYX-13, a novel NMDAR glycine-site functional partial agonist, produces an antidepressant-like effect in the Porsolt, novelty induced hypophagia, and learned helplessness tests in rats without exhibiting substance abuse-related, gating, and sedative side effects of ketamine in the drug discrimination, conditioned place preference, pre-pulse inhibition and open-field tests. Like ketamine, the GLYX-13-induced antidepressant-like effects required AMPA/kainate receptor activation, as evidenced by the ability of NBQX to abolish the antidepressant-like effect. Both GLYX-13 and ketamine persistently (24 h) enhanced the induction of long-term potentiation of synaptic transmission and the magnitude of NMDAR-NR2B conductance at rat Schaffer collateral-CA1 synapses in vitro. Cell surface biotinylation studies showed that both GLYX-13 and ketamine led to increases in both NR2B and GluR1 protein levels, as measured by Western analysis, whereas no changes were seen in mRNA expression (microarray and qRT-PCR). GLYX-13, unlike ketamine, produced its antidepressant-like effect when injected directly into the medial prefrontal cortex (MPFC). These results suggest that GLYX-13 produces an antidepressant-like effect without the side effects seen with ketamine at least in part by directly modulating NR2B-containing NMDARs in the MPFC. Furthermore, the enhancement of ‘metaplasticity' by both GLYX-13 and ketamine may help explain the long-lasting antidepressant effects of these NMDAR modulators. GLYX-13 is currently in a Phase II clinical development program for treatment-resistant depression. PMID:23303054

Respiratory dyskinesia--an under-recognized side-effect of neuroleptic medications.

PubMed

Bhimanil, Mukesh Mohan; Bhimani, Mukesh; Khan, Murad Moosa; Khan, Muhammad Faheem Ashraf; Waris, Muhammad Shiraz

2011-09-01

Respiratory dyskinesia is an under-recognized side effect of neuroleptic administration. There are only few studies that have addressed the prevalence of respiratory dyskinesia in patients with tardive dyskinesia. Our case report highlights the need to regularly examine patients on antipsychotics for any evidence of dyskinetic movements including respiratory musculature. Since RD is underrecognized and misdiagnosed, early detection can improve long term prognosis as treatment options are few and usually of only limited effect. A 62-year-old Asian male, retired civil engineer, had more than 20 years history of depressive illness, developed antidepressant induced hypomania, and was given risperidone upto 1 mg per day. He developed extrapyrmidal side effects as tremors, rigidity and later dyskinetic movements of lips with shortness of breathing, dyspnoea, grunting or gasping. He was referred to the pulmonologist who got the neccessary medical work up done, which was normal. A diagnosis of respiratory dyskinesia was made. Respiratory dyskinesia is an under-recognised and distressing condition that clinicians need to be aware of when treating patients with anti-psychotic medications. And also there is a need to regularly examine patients on antipsychotics for any evidence of dyskinetic movements including respiratory musculature for early diagnosis and better outcome. This case report also is worth reading for professionals of other specialties also because of the presentation of this patient, it can be easily misdiagnosed and result in poor outcome.

Role of parenteral testosterone in hypospadias: A study from a teaching hospital in India

PubMed Central

Ahmad, Reyaz; Chana, Rajendra Singh; Ali, Syed Manazir; Khan, Shehtaj

2011-01-01

Objectives: To evaluate the effect of parenteral testosterone on penile length, preputial skin and side effects in patients with hypospadias. Materials and Methods: 23 patients with hypospadias were included in this study. An oily solution, each ml of which contained testosterone propionate 25 mg, and testosterone enanthate 110 mg, equivalent to 100 mg of testosterone was given deep intramuscularly 4, 3 and 2 weeks before reconstructive surgery at the dose of 2 mg/kg body weight. Increase in penile length, transverse preputial diameter, and diameter at the base of penis were noted. Basal testosterone levels were obtained before the institution of therapy and on the day of operation. In addition, side effect such as development of pubic hair and delay in bone age was noted. Results: Following parenteral testosterone administration, the mean increase in penile length, transverse preputial diameter and diameter at the base of penis was 1.35±0.40 cm (P<0.001), 1.40±0.47 cm (P<0.001), and 0.72±0.47 cm (P<0.001), respectively. Serum testosterone level after injection was well within normal range for that age. Minimal side effects were noted in form of development of fine pubic hair. Conclusion: We conclude that parenteral testosterone can be safely used to improve the surgical outcome of hypospadias repair. PMID:21976926

Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence.

PubMed

Rohleder, Cathrin; Müller, Juliane K; Lange, Bettina; Leweke, F M

2016-01-01

There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ 9 -THC), cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although, results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in both rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial demonstrated that in acute schizophrenia cannabidiol exerts antipsychotic properties comparable to the antipsychotic drug amisulpride while being accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. Although, a plethora of mechanisms of action has been suggested, their potential relevance for the antipsychotic effects of cannabidiol still needs to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol's antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials.

Variations in judgments of intentional action and moral evaluation across eight cultures.

PubMed

Robbins, Erin; Shepard, Jason; Rochat, Philippe

2017-07-01

Individuals tend to judge bad side effects as more intentional than good side effects (the Knobe or side-effect effect). Here, we assessed how widespread these findings are by testing eleven adult cohorts of eight highly contrasted cultures on their attributions of intentional action as well as ratings of blame and praise. We found limited generalizability of the original side-effect effect, and even a reversal of the effect in two rural, traditional cultures (Samoa and Vanuatu) where participants were more likely to judge the good side effect as intentional. Three follow-up experiments indicate that this reversal of the side-effect effect is not due to semantics and may be linked to the perception of the status of the protagonist. These results highlight the importance of factoring cultural context in our understanding of moral cognition. Copyright © 2017. Published by Elsevier B.V.

Side-effects of topical steroids: A long overdue revisit.

PubMed

Coondoo, Arijit; Phiske, Meghana; Verma, Shyam; Lahiri, Koushik

2014-10-01

The introduction of topical steroids (TS) of varying potency have rendered the therapy of inflammatory cutaneous disorders more effective and less time-consuming. However the usefulness of these has become a double edged sword with constantly rising instances of abuse and misuse leading to serious local, systemic and psychological side effects. These side effects occur more with TS of higher potency and on particular areas of the body like face and genitalia. The article reviews the side effects of TS with special mention about peadiatric age group, also includes the measures for preventing the side effects.

Small for Gestational Age (SGA)

MedlinePlus

... Throat (ENT) Dental/Orthodontics Urology Orthopedics Child Development Psychology Special Education Services DO WE NEED TO IMPROVE ... body proportions and head circumference Improved psychological and cognitive function Possible Adverse Side Effects of GHT for ...

Molecular modeling of calmodulin: a comparison with crystallographic data

NASA Technical Reports Server (NTRS)

McDonald, J. J.; Rein, R.

1989-01-01

Two methods of side-chain placement on a modeled protein have been examined. Two molecular models of calmodulin were constructed that differ in the treatment of side chains prior to optimization of the molecule. A virtual bond analysis program developed by Purisima and Scheraga was used to determine the backbone conformation based on 2.2 angstroms resolution C alpha coordinates for the molecules. In the first model, side chains were initially constructed in an extended conformation. In the second model, a conformational grid search technique was employed. Calcium ions were treated explicitly during energy optimization using CHARMM. The models are compared to a recently published refined crystal structure of calmodulin. The results indicate that the initial choices for side-chains, but also significant effects on the main-chain conformation and supersecondary structure. The conformational differences are discussed. Analysis of these and other methods makes possible the formulation of a methodology for more appropriate side-chain placement in modeled proteins.

Side-chain Engineering of Benzo[1,2-b:4,5-b’]dithiophene Core-structured Small Molecules for High-Performance Organic Solar Cells

PubMed Central

Yin, Xinxing; An, Qiaoshi; Yu, Jiangsheng; Guo, Fengning; Geng, Yongliang; Bian, Linyi; Xu, Zhongsheng; Zhou, Baojing; Xie, Linghai; Zhang, Fujun; Tang, Weihua

2016-01-01

Three novel small molecules have been developed by side-chain engineering on benzo[1,2-b:4,5-b’]dithiophene (BDT) core. The typical acceptor-donor-acceptor (A-D-A) structure is adopted with 4,8-functionalized BDT moieties as core, dioctylterthiophene as π bridge and 3-ethylrhodanine as electron-withdrawing end group. Side-chain engineering on BDT core exhibits small but measurable effect on the optoelectronic properties of small molecules. Theoretical simulation and X-ray diffraction study reveal the subtle tuning of interchain distance between conjugated backbones has large effect on the charge transport and thus the photovoltaic performance of these molecules. Bulk-heterojunction solar cells fabricated with a configuration of ITO/PEDOT:PSS/SM:PC71BM/PFN/Al exhibit a highest power conversion efficiency (PCE) of 6.99% after solvent vapor annealing. PMID:27140224

Side-chain Engineering of Benzo[1,2-b:4,5-b']dithiophene Core-structured Small Molecules for High-Performance Organic Solar Cells.

PubMed

Yin, Xinxing; An, Qiaoshi; Yu, Jiangsheng; Guo, Fengning; Geng, Yongliang; Bian, Linyi; Xu, Zhongsheng; Zhou, Baojing; Xie, Linghai; Zhang, Fujun; Tang, Weihua

2016-05-03

Three novel small molecules have been developed by side-chain engineering on benzo[1,2-b:4,5-b']dithiophene (BDT) core. The typical acceptor-donor-acceptor (A-D-A) structure is adopted with 4,8-functionalized BDT moieties as core, dioctylterthiophene as π bridge and 3-ethylrhodanine as electron-withdrawing end group. Side-chain engineering on BDT core exhibits small but measurable effect on the optoelectronic properties of small molecules. Theoretical simulation and X-ray diffraction study reveal the subtle tuning of interchain distance between conjugated backbones has large effect on the charge transport and thus the photovoltaic performance of these molecules. Bulk-heterojunction solar cells fabricated with a configuration of ITO/PEDOT:PSS/SM:PC71BM/PFN/Al exhibit a highest power conversion efficiency (PCE) of 6.99% after solvent vapor annealing.

Effectiveness and side-effect profile of stimulant therapy as monotherapy and in combination in the central hypersomnias in clinical practice.

PubMed

Thakrar, Chiraag; Patel, Kishankumar; D'ancona, Grainne; Kent, Brian D; Nesbitt, Alexander; Selsick, Hugh; Steier, Joerg; Rosenzweig, Ivana; Williams, Adrian J; Leschziner, Guy D; Drakatos, Panagis

2017-10-19

Effectiveness and side-effect profile data on pharmacotherapy for daytime sleepiness in central hypersomnias are based largely upon randomized controlled trials. Evidence regarding the use of combination therapy is scant. The aim of this study was to examine the effectiveness and occurrence of drug-related side effects of these drugs in routine clinical practice. Adult patients diagnosed with a central hypersomnia during a 54-month period at a tertiary sleep disorders centre were identified retrospectively. Side effects were recorded at every follow-up visit. A total of 126 patients, with 3275 patient-months of drug exposure, were categorized into narcolepsy type 1 (n = 70), narcolepsy type 2 (n = 47) and idiopathic hypersomnia (n = 9). Modafinil was the most common drug used as a first-line treatment (93%) and in combination therapy (70%). Thirty-nine per cent of the patients demonstrated a complete, 25% partial and 36% a poor response to treatment. Combination treatment improved daytime sleepiness in 55% of the patients with residual symptoms despite monotherapy. Sixty per cent of patients reported side effects, and 30% reported treatment-limiting side effects. Drugs had similar side-effect incidence (P = 0.363) and their side-effect profile met those reported in the literature. Twenty-seven per cent of the patients received combination treatment and had fewer side effects compared to monotherapy (29.4% versus 60%, respectively, P = 0.001). Monotherapy appears to achieve satisfactory symptom control in most patients with central hypersomnia, but significant side effects are common. Combination therapy appears to be a useful and safe option in patients with refractory symptoms. © 2017 European Sleep Research Society.

Use of Biologics in Private Practice: Nine Years of Lessons and Learning.

PubMed

Correa-Selm, Lilia M; Alamgir, Mahin; Rao, Babar K

2017-03-01

Over a decade ago, the FDA approved biologics for psoriasis, which changed how the disease is treated and, in most cases, has a significant positive impact on the lives of patients. Side effects primarily identified during the investigational and research phase led to the development of specific guidelines for treatment. The treatment guidelines have been amended to incorporate better understandings of side-effects over the years that the disease has been treated. In this study, we focused on a chart review that included assessing the current guidelines and their alignment with modern patient management and the recent side effects presented. This life-cycle evaluation included over 100 patients, management of their treatment, laboratory abnormalities, criteria for choosing or changing to a different biologic, and the effects of the treatments management throughout the years. The review identified some recommended changes in the application and treatment of psoriasis with biologics. To further evidence our findings, we hope to expand this study to a larger scale with more patients.

J Drugs Dermatol. 2017;16(3):215-217.

A multifunctional metal-organic framework based tumor targeting drug delivery system for cancer therapy

NASA Astrophysics Data System (ADS)

Wang, Xiao-Gang; Dong, Zhi-Yue; Cheng, Hong; Wan, Shuang-Shuang; Chen, Wei-Hai; Zou, Mei-Zhen; Huo, Jia-Wei; Deng, He-Xiang; Zhang, Xian-Zheng

2015-09-01

Drug delivery systems (DDSs) with biocompatibility and precise drug delivery are eagerly needed to overcome the paradox in chemotherapy that high drug doses are required to compensate for the poor biodistribution of drugs with frequent dose-related side effects. In this work, we reported a metal-organic framework (MOF) based tumor targeting DDS developed by a one-pot, and organic solvent-free ``green'' post-synthetic surface modification procedure, starting from the nanoscale MOF MIL-101. Owing to the multifunctional surface coating, premature drug release from this DDS was prevented. Due to the pH responsive benzoic imine bond and the redox responsive disulfide bond at the modified surface, this DDS exhibited tumor acid environment enhanced cellular uptake and intracellular reducing environment triggered drug release. In vitro and in vivo results showed that DOX loaded into this DDS exhibited effective cancer cell inhibition with much reduced side effects.Drug delivery systems (DDSs) with biocompatibility and precise drug delivery are eagerly needed to overcome the paradox in chemotherapy that high drug doses are required to compensate for the poor biodistribution of drugs with frequent dose-related side effects. In this work, we reported a metal-organic framework (MOF) based tumor targeting DDS developed by a one-pot, and organic solvent-free ``green'' post-synthetic surface modification procedure, starting from the nanoscale MOF MIL-101. Owing to the multifunctional surface coating, premature drug release from this DDS was prevented. Due to the pH responsive benzoic imine bond and the redox responsive disulfide bond at the modified surface, this DDS exhibited tumor acid environment enhanced cellular uptake and intracellular reducing environment triggered drug release. In vitro and in vivo results showed that DOX loaded into this DDS exhibited effective cancer cell inhibition with much reduced side effects. Electronic supplementary information (ESI) available: Synthesis procedure, 1HNMR, ESI-MS and additional data. See DOI: 10.1039/c5nr04045k

RF313, an orally bioavailable neuropeptide FF receptor antagonist, opposes effects of RF-amide-related peptide-3 and opioid-induced hyperalgesia in rodents.

PubMed

Elhabazi, Khadija; Humbert, Jean-Paul; Bertin, Isabelle; Quillet, Raphaelle; Utard, Valérie; Schneider, Séverine; Schmitt, Martine; Bourguignon, Jean-Jacques; Laboureyras, Emilie; Ben Boujema, Meric; Simonnet, Guy; Ancel, Caroline; Simonneaux, Valérie; Beltramo, Massimiliano; Bucher, Bernard; Sorg, Tania; Meziane, Hamid; Schneider, Elodie; Petit-Demoulière, Benoit; Ilien, Brigitte; Bihel, Frédéric; Simonin, Frédéric

2017-05-15

Although opiates represent the most effective analgesics, their use in chronic treatments is associated with numerous side effects including the development of pain hypersensitivity and analgesic tolerance. We recently identified a novel orally active neuropeptide FF (NPFF) receptor antagonist, RF313, which efficiently prevents the development of fentanyl-induced hyperalgesia in rats. In this study, we investigated the properties of this compound into more details. We show that RF313 exhibited a pronounced selectivity for NPFF receptors, antagonist activity at NPFF1 receptor (NPFF1R) subtype both in vitro and in vivo and no major side effects when administered in mice up to 30 mg/kg. When co-administered with opiates in rats and mice, it improved their analgesic efficacy and prevented the development of long lasting opioid-induced hyperalgesia. Moreover, and in marked contrast with the dipeptidic NPFF receptor antagonist RF9, RF313 displayed negligible affinity and no agonist activity (up to 100 μM) toward the kisspeptin receptor. Finally, in male hamster, RF313 had no effect when administered alone but fully blocked the increase in LH induced by RFRP-3, while RF9 per se induced a significant increase in LH levels which is consistent with its ability to activate kisspeptin receptors. Altogether, our data indicate that RF313 represents an interesting compound for the development of therapeutic tools aiming at improving analgesic action of opiates and reducing adverse side effects associated with their chronic administration. Moreover, its lack of agonist activity at the kisspeptin receptor indicates that RF313 might be considered a better pharmacological tool, when compared to RF9, to examine the regulatory roles of RF-amide-related peptides and NPFF1R in reproduction. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reirradiation on recurrent cervical cancer case: Treatment response and side effects

NASA Astrophysics Data System (ADS)

Siregar, M. F.; Supriana, N.; Nuranna, L.; Prihartono, J.

2017-08-01

Management of recurrent cervical cancer by reirradiation after radiation treatment remains controversial. In Indonesia, there is currently no data about reirradiation tumor response and side effects. This study aims to assess the tumor response to and side effects of reirradiation, the effect of time interval between first radiation treatment and cancer recurrence on the tumor response and side effects, and the effect of tumor size on tumor response. A cohort retrospective study with no comparison was done with the Radiotherapy Department at Cipto Mangunkusumo General Hospital, Jakarta. Participants were recurrent cervical cancer patients undergoing reirradiation. Data was collected from patients’ medical records and follow-up phone calls. Twenty-two patients participated in this study. Nine patients (40.9%) had complete responses, 10 patients (45.5%) had partial responses, 1 patient (4.5%) had a stable response, and 2 patients (9.1%) had tumor progressions. In general, 15 patients (68.2%) had no to light side effects (grade 0-2 RTOG) and 7 patients (31.8%) had severe side effects (grade 3-4 RTOG). Four patients (18.1%) had severe gastrointestinal acute side effects, 6 patients (27.3%) had severe gastrointestinal late side effects, 2 patients (9.1%) had severe urogenital side effects, and there were no patients had severe urogenital late side effects. There was no significant difference in tumor response between patients with time interval between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was no significant difference in tumor response between patients with tumor size ≤4 cm vs. >4 cm. Reirradiation can be considered as a modality in recurrent cervical cancer management since good tumor response was achieved and the majority of patients had no to light side effects (grade 0-2 RTOG). This study found no correlation between tumor response, side effects, and time gap between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was also no correlation between tumor response and tumor size of ≤4 cm vs. > 4 cm.

Comparison of Pathway and Center of Gravity of the Calcaneus on Non-Involved and Involved Sides According to Eccentric and Concentric Strengthening in Patients With Achilles Tendinopathy

PubMed Central

Yu, JaeHo; Lee, GyuChang

2012-01-01

This study compares the changes in pathway and center of gravity (COG) on the calcaneus of non-involved and involved sides according to eccentric and concentric strengthening in patients with unilateral Achilles tendinopathy. The goal was to define the biomechanical changes according to eccentric strengthening for the development of clinical guidelines. Eighteen patients with Achilles tendinopathy were recruited at the K Rehabilitation Hospital in Seoul. The subjects were instructed to perform 5 sessions of concentric strengthening. The calcaneal pathway was measured using a three-dimensional (3D) motion analyzer, and COG was measured by a force plate. Subsequently, eccentric strengthening was implemented, and identical variables were measured. Concentric and eccentric strengthening was carried out on both the involved and non-involved sides. There was no significant difference in the calcaneal pathway in patients with Achilles tendinopathy during concentric and eccentric strengthening. However, during eccentric strengthening, the calcaneal pathway significantly increased on the involved side compared to the non-involved side for all variables excluding the z-axis. COG significantly decreased on the involved side when compared to the non-involved side in patients with Achilles tendinopathy during eccentric and concentric strengthening. During concentric strengthening, all variables of the COG significantly increased on the involved side compared to the non-involved side. Compared with eccentric strengthening, concentric strengthening decreased the stability of ankle joints and increased the movement distance of the calcaneus in patients with Achilles tendinopathy. Furthermore, eccentric strengthening was verified to be an effective exercise method for prevention of Achilles tendinopathy through the reduction of forward and backward path length of foot pressure. The regular application of eccentric strengthening was found to be effective in the secondary prevention of Achilles tendinopathy in a clinical setting. Key point Compared with eccentric strengthening, concentric strengthening decreased the stability of ankle joints, increasing movement of the calcaneus in patients with Achilles tendinopathy. Eccentric strengthening was shown to be an effective exercise method for preventing Achilles tendinopathy through the reduction of forward and backward path length of foot pressure. It was verified that regular application of eccentric strengthening is effective in secondary prevention of Achilles tendinopathy in the clinical setting. PMID:24149129

Health care resource use and costs associated with possible side effects of high oral corticosteroid use in asthma: a claims-based analysis.

PubMed

Luskin, Allan T; Antonova, Evgeniya N; Broder, Michael S; Chang, Eunice Y; Omachi, Theodore A; Ledford, Dennis K

2016-01-01

The objective of this study was to estimate the prevalence of possible oral corticosteroid (OCS)-related side effects and health care resource use and costs in patients with asthma. This was a cross-sectional, matched-cohort, retrospective study using a commercial claims database. Adults with asthma diagnosis codes and evidence of asthma medication use were studied. Patients with high OCS use (≥30 days of OCS annually) were divided into those who did versus those who did not experience OCS-related possible side effects. Their health care resource use and costs were compared using linear regression or negative binomial regression models, adjusting for age, sex, geographic region, Charlson Comorbidity Index score, and chronic obstructive pulmonary disease status. After adjustment, high OCS users with possible side effects were more likely to have office visits (23.0 vs 19.6; P <0.001) and hospitalizations (0.44 vs 0.22; P <0.001) than those without possible side effects. Emergency department visits were similar between the groups. High OCS users with possible side effects had higher adjusted total annual mean health care costs ($25,168) than those without such side effects ($21,882; P =0.009). Among high OCS users, patients with possible OCS-related side effects are more likely to use health care services than those without such side effects. Although OCS may help control asthma and manage exacerbations, OCS side effects may result in additional health care resource use and costs, highlighting the need for OCS-sparing asthma therapies.

From clinically relevant outcome measures to quality of life in epilepsy: A time trade-off study.

PubMed

de Kinderen, Reina J A; Wijnen, Ben F M; van Breukelen, Gerard; Postulart, Debby; Majoie, Marian H J M; Aldenkamp, Albert P; Evers, Silvia M A A

2016-09-01

A proposed method for bridging the gap between clinically relevant epilepsy outcome measures and quality-adjusted life years is to derive utility scores for epilepsy health states. The aim of this study is to develop such a utility-function and to investigate the impact of the epilepsy outcome measures on utility. Health states, based on clinically important epilepsy attributes (e.g. seizure frequency, seizure severity, side-effects), were valued by a sample of the Dutch population (N=525) based on the time trade-off method. In addition to standard demographics, every participant was asked to rate 10 or 11 different health state scenarios. A multilevel regression analysis was performed to account for the nested structure of the data. Results show that the best health state (no seizures and no side-effects) is estimated at 0.89 and the worst state (seizures type 5 twice a day plus severe side-effects) at 0.22 (scale: 0-1). An increase in seizure frequency, occurrence of side-effects, and seizure severity were all significantly associated with lower utility values. Furthermore, seizure severity has the largest impact on quality of life compared with seizure frequency and side-effects. This study provides a utility-function for transforming clinically relevant epilepsy outcome measures into utility estimates. We advise using our utility-function in economic evaluations, when quality of life is not directly measured in a study and hence, no health state utilities are available, or when there is convincing empirical evidence of the insensitivity of a generic quality-of-life-instrument within epilepsy. Copyright © 2016 Elsevier B.V. All rights reserved.

Relieving Oral Mucositis - Palifermin Discovery

Cancer.gov

Painful mouth and throat sores can be a side effect of intensive cancer treatments for many patients. Learn how NCI scientists developed the drug, Palifermin, which vastly improves the quality of life for cancer patients.

Chemotherapy-induced peripheral neuropathy: an update on the current understanding.

PubMed

Addington, James; Freimer, Miriam

2016-01-01

Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects.

TNF and cancer: the two sides of the coin.

PubMed

Mocellin, Simone; Nitti, Donato

2008-01-01

Despite its name, discovery history and approval as anticancer agent, tumor necrosis factor (TNF) has been implicated in both cancer development and progression in some preclinical models. In particular, as a central mediator of inflammation, TNF might represent one of the molecular links between chronic inflammation and the subsequent development of malignant disease. Furthermore, deregulated TNF expression within the tumor microenvironment appears to favor malignant cell tissue invasion, migration and ultimately metastasis formation. On the other side, TNF clearly possesses antitumor effects not only in preclinical models but also in the clinical setting. In order to reconcile these conflicting findings, we provide readers with an overview on the most relevant available evidence supporting anticancer as well as cancer-promoting TNF effects; on the basis of these data, we propose a model to explain the coexistence of these apparently paradoxical TNF activities.

Segmental Bile Duct-Targeted Liver Resection for Right-Sided Intrahepatic Stones.

PubMed

Li, Shao-Qiang; Hua, Yun-Peng; Shen, Shun-Li; Hu, Wen-Jie; Peng, Bao-Gang; Liang, Li-Jian

2015-07-01

Hepatectomy is a safe and effective treatment for intrahepatic stones (IHSs). However, the resection plane for right-sided stones distributed within 2 segments is obstacle because of atrophy-hypertrophy complex formation of the liver and difficult dissection of segmental pedicle within the Glissonean plate by conventional approach. Thus, we devised segmental bile duct-targeted liver resection (SBDLR) for IHS, which aimed at completely resection of diseased bile ducts. This study aimed to evaluate the outcomes of SBDLR for right-sided IHSs. From January 2009 to December 2013, 107 patients with IHS treated by SBDLR in our center were reviewed in a prospective database. Patients' intermediate and long-term outcomes after SBDLR were analyzed. A total of 40 (37.4%) patients with localized right-sided stone and 67 (62.7%) patients with bilateral stones underwent SBDLR alone and SBDLR combined with left-sided hepatectomy, respectively. There was no hospital mortality of this cohort of patients. The postoperative morbidity was 35.5%. The mean intraoperative blood loss was 414  mL (range: 100-2500). Twenty-one (19.6%) patients needed red blood cells transfusion. The intermediate stone clearance rate was 94.4%; the final clearance rate reached 100% after subsequent postoperative cholangioscopic lithotomy. Only 2.8% patients developed stone recurrence in a median follow-up period of 38.3 months. SBDLR is a safe and effective treatment for right-sided IHS distributed within 2 segments. It is especially suitable for a subgroup of patients with bilateral stones whose right-sided stones are within 2 segments and bilateral liver resection is needed.

Current and Potential Tree Locations in Tree Line Ecotone of Changbai Mountains, Northeast China: The Controlling Effects of Topography

PubMed Central

Zong, Shengwei; Wu, Zhengfang; Xu, Jiawei; Li, Ming; Gao, Xiaofeng; He, Hongshi; Du, Haibo; Wang, Lei

2014-01-01

Tree line ecotone in the Changbai Mountains has undergone large changes in the past decades. Tree locations show variations on the four sides of the mountains, especially on the northern and western sides, which has not been fully explained. Previous studies attributed such variations to the variations in temperature. However, in this study, we hypothesized that topographic controls were responsible for causing the variations in the tree locations in tree line ecotone of the Changbai Mountains. To test the hypothesis, we used IKONOS images and WorldView-1 image to identify the tree locations and developed a logistic regression model using topographical variables to identify the dominant controls of the tree locations. The results showed that aspect, wetness, and slope were dominant controls for tree locations on western side of the mountains, whereas altitude, SPI, and aspect were the dominant factors on northern side. The upmost altitude a tree can currently reach was 2140 m asl on the northern side and 2060 m asl on western side. The model predicted results showed that habitats above the current tree line on the both sides were available for trees. Tree recruitments under the current tree line may take advantage of the available habitats at higher elevations based on the current tree location. Our research confirmed the controlling effects of topography on the tree locations in the tree line ecotone of Changbai Mountains and suggested that it was essential to assess the tree response to topography in the research of tree line ecotone. PMID:25170918

Current and potential tree locations in tree line ecotone of Changbai Mountains, Northeast China: the controlling effects of topography.

PubMed

Zong, Shengwei; Wu, Zhengfang; Xu, Jiawei; Li, Ming; Gao, Xiaofeng; He, Hongshi; Du, Haibo; Wang, Lei

2014-01-01

Tree line ecotone in the Changbai Mountains has undergone large changes in the past decades. Tree locations show variations on the four sides of the mountains, especially on the northern and western sides, which has not been fully explained. Previous studies attributed such variations to the variations in temperature. However, in this study, we hypothesized that topographic controls were responsible for causing the variations in the tree locations in tree line ecotone of the Changbai Mountains. To test the hypothesis, we used IKONOS images and WorldView-1 image to identify the tree locations and developed a logistic regression model using topographical variables to identify the dominant controls of the tree locations. The results showed that aspect, wetness, and slope were dominant controls for tree locations on western side of the mountains, whereas altitude, SPI, and aspect were the dominant factors on northern side. The upmost altitude a tree can currently reach was 2140 m asl on the northern side and 2060 m asl on western side. The model predicted results showed that habitats above the current tree line on the both sides were available for trees. Tree recruitments under the current tree line may take advantage of the available habitats at higher elevations based on the current tree location. Our research confirmed the controlling effects of topography on the tree locations in the tree line ecotone of Changbai Mountains and suggested that it was essential to assess the tree response to topography in the research of tree line ecotone.

Superiority of stapled side-to-side gastrojejunostomy over conventional hand-sewn end-to-side gastrojejunostomy for reducing the risk of primary delayed gastric emptying after subtotal stomach-preserving pancreaticoduodenectomy.

PubMed

Murata, Yasuhiro; Tanemura, Akihiro; Kato, Hiroyuki; Kuriyama, Naohisa; Azumi, Yoshinori; Kishiwada, Masashi; Mizuno, Shugo; Usui, Masanobu; Sakurai, Hiroyuki; Isaji, Shuji

2017-08-01

Delayed gastric emptying (DGE) is the most common complication following pancreaticoduodenectomy (PD). The clinical efficacy of stapled side-to-side anastomosis using a laparoscopic stapling device during alimentary reconstruction in PD is not well understood and its superiority over conventional hand-sewn end-to-side anastomosis remains controversial. The objective of this study was to evaluate the effectiveness of the stapled side-to-side anastomosis in preventing the development of DGE after PD. The subjects of this retrospective study were 137 patients who underwent pancreaticoduodenectomy, as subtotal stomach-preserving pancreaticoduodenectomy (SSPPD; n = 130), or conventional whipple procedure (n = 7) with Child reconstruction, between January 2010 and May 2014. The patients were divided into two groups according to whether they had had a stapled side-to-side anastomosis (SA group; n = 57) or a conventional hand-sewn end-to-side anastomosis (HA group; n = 80). SA reduced the operative time (SA vs. HA: 508 vs. 557 min, p = 0.028) and the incidence of delayed gastric emptying (SA vs. HA: 21.1 vs. 46.3%, p = 0.003) and was associated with shorter hospitalization (SA vs. HA: 33 vs. 39.5 days, p = 0.007). In this cohort, SA was the only significant factor contributing to a reduction in the incidence of DGE (p = 0.002). Stapled side-to-side gastrojejunostomy reduced the operative time and the incidence of DGE following PD with Child reconstruction, thereby also reducing the length of hospitalization.

Input and output constraints affecting irrigation development

NASA Astrophysics Data System (ADS)

Schramm, G.

1981-05-01

In many of the developing countries the expansion of irrigated agriculture is used as a major development tool for bringing about increases in agricultural output, rural economic growth and income distribution. Apart from constraints imposed by water availability, the major limitations considered to any acceleration of such programs are usually thought to be those of costs and financial resources. However, as is shown on the basis of empirical data drawn from Mexico, in reality the feasibility and effectiveness of such development programs is even more constrained by the lack of specialized physical and human factors on the input and market limitations on the output side. On the input side, the limited availability of complementary factors such as, for example, truly functioning credit systems for small-scale farmers or effective agricultural extension services impose long-term constraints on development. On the output side the limited availability, high risk, and relatively slow growth of markets for high-value crops sharply reduce the usually hoped-for and projected profitable crop mix that would warrant the frequently high costs of irrigation investments. Three conclusions are drawn: (1) Factors in limited supply have to be shadow-priced to reflect their high opportunity costs in alternative uses. (2) Re-allocation of financial resources from immediate construction of projects to longer-term increase in the supply of scarce, highly-trained manpower resources are necessary in order to optimize development over time. (3) Inclusion of high-value, high-income producing crops in the benefit-cost analysis of new projects is inappropriate if these crops could potentially be grown in already existing projects.

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

Del Bianco, M.; Wiehagen, J.

This project evaluated the effectiveness and affordability of integrating retrofit insulated panels into a re-siding project. The Partnership for Home Innovation (PHI) teamed with New York State Energy Research and Development Authority (NYSERDA), the Albany Housing Authority (AHA), and the New York State Weatherization Assistance Program (WAP) administered by Albany Community Action Partnership to demonstrate an energy retrofit and siding upgrade on a two-story, seven unit, multifamily building in Albany New York (CZ 5). The project focused on accomplishing three goals - doubling the existing wall thermal resistance (from approximately R-13 to a weighted average of R-27), reduction of buildingmore » air leakage, and completion of the retrofit within a budget where the additional cost for upgrading wall's thermal resistance is equal to the cost of the standard re-siding effort (i.e., the total cost of the energy efficient re-siding scope of work is not more than double the cost of the standard re-siding effort). Lessons learned from the project strongly indicate that the retrofit panel technology can be installed using common installation practices and with minimal training. Other lessons learned include limitation on the use of standard air sealing materials during cold weather installations and the need to develop better installation guidance for trades working with the level of tolerances that may be present in the existing structure. This technology demonstration showed that exterior retrofit panels provide a viable and reasonable option for the siding trades to increase market opportunities and achieve synergistic benefits for aesthetic upgrades to a building's exterior.« less

A Case of Chronic Total Occlusion of the Left Anterior Descending Artery Successfully Treated with Side Branch Technique Using the Soutenir CV

PubMed Central

Niizeki, Takeshi; Ikeno, Eiichiro; Kubota, Isao

2017-01-01

Patient: Male, 54 Final Diagnosis: Old myocardial infarction Symptoms: Lower extremity swelling • respiratory distress Medication: — Clinical Procedure: Success Specialty: Cardiology Objective: Unusual setting of medical care Background: Success rates for treatment of chronic total occlusion (CTO) have dramatically improved in recent years with the development of new CTO guidewires and development of new techniques such as the retrograde approach. In the antegrade approach, a guidewire is occasionally passed through a side branch despite successful wire crossing of the CTO lesion. In order to pass a wire through the main artery, there are a few side branch techniques such as a reverse wire technique. Case Report: A 54-year-old man with symptoms of heart failure was admitted to our hospital. Coronary angiography showed CTO of the proximal left anterior descending artery. Percutaneous coronary intervention with an antegrade approach was started. We succeeded in passing the wire through a side branch but not the main artery. Unfortunately, a reverse wire technique failed in this case. Next, the wire passed through a side branch was exchanged with the Soutenir CV, and a retrograde approach was started. The wire crossing from retrograde was entwined around the Soutenir CV. After that, the retrograde wire was snared and guided to the antegrade guiding catheter, which resulted in successful wiring into the main artery easily. Conclusions: The side branch technique using the Soutenir CV may be an effective strategy in some cases. PMID:28082733

Treatment Options for Primary Refractory/Recurrent Hodgkin Lymphoma in Children and Adolescents

MedlinePlus

... back). The treatment options also depend on: The child's age and sex. The risk of long-term side effects . Most ... Physical problems that affect the following: Development of sex and reproductive organs . Fertility (ability to have children). Bone and muscle growth and development. Thyroid , heart, ...

A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia.

PubMed

Dibonaventura, Marco; Gabriel, Susan; Dupclay, Leon; Gupta, Shaloo; Kim, Edward

2012-03-20

Antipsychotic medications often have a variety of side effects, however, it is not well understood how the presence of specific side effects correlate with adherence in a real-world setting. The aim of the current study was to examine the relationship between these variables among community-dwelling patients with schizophrenia. Data were analyzed from a 2007-2008 nationwide survey of adults who self-reported a diagnosis of schizophrenia and were currently using an antipsychotic medication (N = 876). The presence of side effects was defined as those in which the patient reported they were at least "somewhat bothered". Adherence was defined as a score of zero on the Morisky Medication Adherence Scale. To assess the relationship between side effects and adherence, individual logistic regression models were fitted for each side effect controlling for patient characteristics. A single logistic regression model assessed the relationship between side effect clusters and adherence. The relationships between adherence and health resource use were also examined. A majority of patients reported experiencing at least one side effect due to their medication (86.19%). Only 42.5% reported complete adherence. Most side effects were associated with a significantly reduced likelihood of adherence. When grouped as side effect clusters in a single model, extra pyramidal symptoms (EPS)/agitation (odds ratio (OR) = 0.57, p = 0.0007), sedation/cognition (OR = 0.70, p = 0.033), prolactin/endocrine (OR = 0.69, p = 0.0342), and metabolic side effects (OR = 0.64, p = 0.0079) were all significantly related with lower rates of adherence. Those who reported complete adherence to their medication were significantly less likely to report a hospitalization for a mental health reason (OR = 0.51, p = 0.0006), a hospitalization for a non-mental health reason (OR = 0.43, p = 0.0002), and an emergency room (ER) visit for a mental health reason (OR = 0.60, p = 0.008). Among patients with schizophrenia, medication side effects are highly prevalent and significantly associated with medication nonadherence. Nonadherence is significantly associated with increased healthcare resource use. Prevention, identification, and effective management of medication-induced side effects are important to maximize adherence and reduce health resource use in schizophrenia.

A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia

PubMed Central

2012-01-01

Background Antipsychotic medications often have a variety of side effects, however, it is not well understood how the presence of specific side effects correlate with adherence in a real-world setting. The aim of the current study was to examine the relationship between these variables among community-dwelling patients with schizophrenia. Methods Data were analyzed from a 2007-2008 nationwide survey of adults who self-reported a diagnosis of schizophrenia and were currently using an antipsychotic medication (N = 876). The presence of side effects was defined as those in which the patient reported they were at least "somewhat bothered". Adherence was defined as a score of zero on the Morisky Medication Adherence Scale. To assess the relationship between side effects and adherence, individual logistic regression models were fitted for each side effect controlling for patient characteristics. A single logistic regression model assessed the relationship between side effect clusters and adherence. The relationships between adherence and health resource use were also examined. Results A majority of patients reported experiencing at least one side effect due to their medication (86.19%). Only 42.5% reported complete adherence. Most side effects were associated with a significantly reduced likelihood of adherence. When grouped as side effect clusters in a single model, extra pyramidal symptoms (EPS)/agitation (odds ratio (OR) = 0.57, p = 0.0007), sedation/cognition (OR = 0.70, p = 0.033), prolactin/endocrine (OR = 0.69, p = 0.0342), and metabolic side effects (OR = 0.64, p = 0.0079) were all significantly related with lower rates of adherence. Those who reported complete adherence to their medication were significantly less likely to report a hospitalization for a mental health reason (OR = 0.51, p = 0.0006), a hospitalization for a non-mental health reason (OR = 0.43, p = 0.0002), and an emergency room (ER) visit for a mental health reason (OR = 0.60, p = 0.008). Conclusions Among patients with schizophrenia, medication side effects are highly prevalent and significantly associated with medication nonadherence. Nonadherence is significantly associated with increased healthcare resource use. Prevention, identification, and effective management of medication-induced side effects are important to maximize adherence and reduce health resource use in schizophrenia. PMID:22433036

[Pharmacotherapy of hyperthyreosis--adverse drug reactions].

PubMed

Perger, Ludwig; Bürgi, Ulrich; Fattinger, Karin

2011-06-01

The antithyroid drugs mainly include thioimidazole (carbimazole, methimazole=thiamazole) and propylthiouracil. After absorption, carbimazole is rapidly metabolized to methimazole and thus switching between these two drugs should not be considered in case of side effects. Furthermore, in case of side effects, sometimes even cross reactions between thioimidazoles and propylthiouracil occur. Common and typical adverse reactions of antithyroid drugs include dose dependent hypothyroidism and thus thyroid function should be repeatedly checked while the patient is on antithyroid drugs. Furthermore, pruritus and rash may develop. In this case, one might try to switch from thioimidazoles to propylthiouracil or vice versa. Antithyroid drugs may cause mild dose dependent neutropenia or severe allergy-mediated agranulocytosis, which typically occurs during the first three months of treatment, has an incidence of 3 per 10,000 patients and cross reactivity between thioimidazoles to propylthiouracil may occur. Rarely, antithyroid drugs can cause aplastic anemia. Mainly propylthiouracil, but sometimes also methimazole may lead to an asymptomatic transient increase in liver enzymes or to severe, even lethal liver injury of cholestatic or hepatocellular pattern. Since propylthiouracil associated liver injury was observed increasingly among children and adolescent, it has been suggested to prefer thioimidazoles for these patients. Because of these potential serious adverse effects, physicians should advise patients to immediately seek medical help if they get a fever or sore throat or malaise, abdominal complaints or jaundice, respectively. Furthermore, arthralgias may develop in 1-5% of patients under both antithyroid drugs. Since arthralgias may be the first symptom of more serious immunologic side effects, it is recommended to stop the antithyroid drug in this case. Drug induced polyarthritis mainly develops during the first month of therapy, whereas ANCA-positive vasculitis is generally observed only after long term exposure to propylthiouracil or very rarely with the thioimidazoles. The teratogenic risk of the thioimidazoles is somewhat higher (Aplasia cutis congenita), that is why one generally recommends preferring propylthiouracil during pregnancy. During breast feeding both, thioimidazoles or propylthiouracil, may be administered. Nowadays, perchlorate is only used short term in case of latent hyperthyroidism before administering iodine-containing contrast agents. Therefore, the known side effects, which usually are only observed after long term treatment, are not an issue any more.

"Side effects affected my daily activities a lot": a qualitative exploration of the impact of contraceptive side effects in Bangladesh.

PubMed

Jain, Aparna; Reichenbach, Laura; Ehsan, Iqbal; Rob, Ubaidur

2017-01-01

In a country like Bangladesh that has made great progress in contraceptive use with one of the lowest levels of fertility and highest levels of contraceptive use, understanding what factors influence women's decisions to discontinue a contraceptive method and not switch to a new method is critical in designing interventions and programs that will help enable Bangladesh to reach its FP2020 goals. Research on side effects has focused on physical manifestations like headaches, moodiness, abdominal pain, and menstrual irregularities. While physical effects alone may stop women from continuing a contraceptive method, less is known about how side effects influence women's daily activities and lives. The purpose of this study is to understand the ways that side effects affect Bangladeshi women's participation in different social settings. Thirty-five in-depth interviews with married women who recently discontinued or switched to a different contraceptive method were conducted in Sylhet and Khulna Divisions. Interviews explored reasons for discontinuation including experience of side effects and impact of side effects on women's lives. Key themes emerged including that side effects are not only experienced physically but are barriers to women's participation in many aspects of their lives. The spheres of life that most commonly appeared to be influenced by side effects include religion, household, and sexual intimacy irrespective of method used or residence. Family planning providers need to be aware of these additional consequences associated with contraceptive side effects to provide tailored counseling that recognizes these issues and helps women to mitigate them. For Bangladesh to achieve its FP2020 goals, understanding the broader context in which family planning decisions are made vis-à-vis side effects is critical to design programs and interventions that meet all the needs of women beyond just their fertility intentions.

Effects of buspirone on the immediate positive and delayed negative properties of intravenous cocaine as measured in the conditioned place preference test

PubMed Central

Ettenberg, Aaron; Bernardi, Rick E.

2007-01-01

In prior work, we have demonstrated that the behavioral effects of cocaine adhere to the predictions of the opponent-process theory of drug action. Animals develop conditioned place preferences for distinct locations paired with the immediate effects of IV cocaine, but learn to avoid places paired with the effects present 15-min post injection. It was of interest to assess the putative role of 5-HT in producing the negative properties of cocaine since cocaine acts to inhibit the reuptake of serotonin (5-HT) and since such actions have been associated with anxiogenic consequences. Male rats were administered a reinforcing dose of cocaine (1.0 mg/kg IV) and then placed – either immediately or after a 15-min delay -- into one side of a two-compartment (black-white) Conditioned Place Preference (CPP) box for 5-min. On alternate days, the animals received IV saline injections and were placed in the opposite side of the CPP box. This continued for eight days after which animals had experienced 4 pairings of cocaine with one side (black or white) of the CPP apparatus, and 4 saline pairings with the opposite side. Other groups of rats were treated identically except that 30-min prior to placement into the apparatus, these animals received an IP injection of saline or buspirone (a partial 5-HT1A agonist) at a dose that we have shown to be anxiolytic (2.5 mg/kg IP). Control animals experienced either buspirone or saline pretreatments without cocaine. Our results confirm that animals increase the time spent on the side paired with the immediate effects of cocaine (compared to baseline), but tend to avoid the side paired with effects present 15-min post-injection. Buspirone had no effect on the immediate rewarding properties of cocaine, but completely reversed the negative properties present 15-min post-cocaine. These results are consistent with the view that attenuation of 5-HT neurotransmission (via the autoreceptor agonist properties of buspirone) can reverse the negative impact of IV cocaine. PMID:17524462

Combining Pharmacological Countermeasures to Attenuate the Acute Radiation Syndrome-A Concise Review.

PubMed

Hofer, Michal; Hoferová, Zuzana; Depeš, Daniel; Falk, Martin

2017-05-19

The goal of combined pharmacological approaches in the treatment of the acute radiation syndrome (ARS) is to obtain an effective therapy producing a minimum of undesirable side effects. This review summarizes important data from studies evaluating the efficacy of combining radioprotective agents developed for administration prior to irradiation and therapeutic agents administered in a post-irradiation treatment regimen. Many of the evaluated results show additivity, or even synergism, of the combined treatments in comparison with the effects of the individual component administrations. It can be deduced from these findings that the research in which combined treatments with radioprotectors/radiomitigators are explored, tested, and evaluated is well-founded. The requirement for studies highly emphasizing the need to minimize undesirable side effects of the radioprotective/radiomitigating therapies is stressed.

Side Effects (Management)

MedlinePlus

... cancer care is relieving side effects, called symptom management, palliative care, or supportive care. It is important ... treat them. To learn about the symptoms and management of the long-term side effects of cancer ...

Effectiveness of Citrus Fruits on Helicobacter pylori

PubMed Central

2017-01-01

It is known that Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, and gastric carcinoma. Due to the increased side effects of the treatment regimens and the development of antimicrobial resistance, a number of natural compounds have been tested as potential alternatives. In this review, we will examine the current knowledge on the effect of Citrus fruits and their derivatives against H. pylori, highlighting the remaining outstanding questions on the development of novel therapeutic strategies. PMID:28408943

Numerical Approach for Goaf-Side Entry Layout and Yield Pillar Design in Fractured Ground Conditions

NASA Astrophysics Data System (ADS)

Jiang, Lishuai; Zhang, Peipeng; Chen, Lianjun; Hao, Zhen; Sainoki, Atsushi; Mitri, Hani S.; Wang, Qingbiao

2017-11-01

Entry driven along goaf-side (EDG), which is the development of an entry of the next longwall panel along the goaf-side and the isolation of the entry from the goaf with a small-width yield pillar, has been widely employed in China over the past several decades . The width of such a yield pillar has a crucial effect on EDG layout in terms of the ground control, isolation effect and resource recovery rate. Based on a case study, this paper presents an approach for evaluating, designing and optimizing EDG and yield pillar by considering the results from numerical simulations and field practice. To rigorously analyze the ground stability, the numerical study begins with the simulation of goaf-side stress and ground conditions. Four global models with identical conditions, except for the width of the yield pillar, are built, and the effect of pillar width on ground stability is investigated by comparing aspects of stress distribution, failure propagation, and displacement evolution during the entire service life of the entry. Based on simulation results, the isolation effect of the pillar acquired from field practice is also considered. The suggested optimal yield pillar design is validated using a field test in the same mine. Thus, the presented numerical approach provides references and can be utilized for the evaluation, design and optimization of EDG and yield pillars under similar geological and geotechnical circumstances.

[Investigation of glucocorticoid-induced side effects in patients with autoimmune diseases].

PubMed

Nakajima, Aya; Doki, Kosuke; Homma, Masato; Sagae, Terumi; Saito, Reiko; Ito, Satoshi; Sumida, Takayuki; Kohda, Yukinao

2009-04-01

High dose glucocorticoids (GC) are commonly used for the treatment of autoimmune diseases. The frequencies, occurrence day and dose-dependency for side effects may be different among the events such as diabetes mellitus, hyperlipidemia, infectious disease, osteoporosis, and peptic ulcer. We investigated GC-induced side effects in 68 patients treated with GC for autoimmune diseases. Initial dose of GC (prednisolone equivalent) was 0.67+/-0.35 mg/kg/d. Hypercholesterolemia (66%), hypertension (62%), insomnia (50%), hypertriglyceridemia (44%), excessive appetite (38%), hyperglycemia (18%), digestive symptom (16%), moon-shaped face (13%) and oral candidiasis (12%) were observed in 63 patients treated with GC. Hypercholesterolemia, excessive appetite, digestive symptom, moon-shaped face, and oral candidiasis were associated with the initial dose of prednisolone greater than 0.80 mg/kg/d. Insomnia [median 6 days (range 1-88)], excessive appetite [7 days (2-57)], hypertension [8 days (1-37)], digestive symptom [15 days (1-87)] and hypercholesterolemia [19 days (3-77)] were observed early after 6-19 days starting GC. On the other hand, hypertriglyceridemia [33 days (2-131)], oral candidiasis [35 days (7-52)] and hyperglycemia [60 days (4-134)] were developed after 33-60 days starting GC. Since the frequencies, dose-dependency and occurrence day were different among the side effects of GC, medical staffs including physicians and pharmacists should pay attention such features of the events in the treatment of autoimmune diseases.

Dental changes evaluated with a 3D computer-assisted model analysis after long-term tongue retaining device wear in OSA patients.

PubMed

Chen, Hui; Lowe, Alan A; Strauss, Arthur M; de Almeida, Fernanda Riberiro; Ueda, Hiroshi; Fleetham, John A; Wang, Bangkang

2008-05-01

Oral appliances (OAs) have been used to treat obstructive sleep apnea (OSA) patients for decades. However, detailed dental side effects in long-term OA cases analyzed with an accurate three-dimensional (3D) measurement tool have seldom been reported. The purpose of this study is to evaluate dental side effects in five OSA patients, who had used a tongue retaining device (TRD) (with occasional other OA wear) for an average of 6 years and 4 months. The baseline and follow-up orthodontic study models were measured with a newly developed MicroScribe-3DX analysis system. High compliance of TRD wear was confirmed in all cases and different patterns and amounts of dental changes were observed. The most common appliance-induced dental changes included anterior and/or unilateral posterior open-bites and reduced anterior overjets. It was hypothesized that there might be two possible mechanisms for the TRD side effects--one is the forward pressure of the tongue upon the anterior dental arch and the other is the lateral pressure of the tongue upon the posterior arch. Considerations to correct the TRD dental side effects should be guided by these different mechanisms of the tongue on the dental arch. Possible solutions to minimize occlusal changes and maximize the benefits for OSA patients are also discussed.

Effect of flomoxef on blood coagulation and alcohol metabolism.

PubMed

Uchida, K; Matsubara, T

1991-01-01

The effect of flomoxef, a newly developed oxacephem antibiotic with an N-hydroxyethyltetrazolethiol (HTT) side chain, on blood coagulation and alcohol metabolism was compared with that of a series of cephalosporin antibiotics with N-methyltetrazolethiol (NMTT), thiadiazolethiol (TDT) or methylthiadiazolethiol (MTDT) side chains in position 3' of the cephalosporin nucleus known to cause hypoprothrombinemia and bleeding in patients who are malnourished, debilitated and/or of high age. A disulfiram-like effect caused by inhibition of aldehyde dehydrogenase was observed for NMTT-containing antibiotics. Studies were carried out on healthy volunteers and on rats. Eight-day treatment with 2 g flomoxef i.v. once or twice daily in five and six healthy male volunteers, respectively, did not cause any significant changes in prothrombin time (PT), coagulation factors II, VII, IX or X, in hepaplastin values or fibrinogen levels, activated partial thromboplastin time (APTT), platelet counts, bleeding time, or collagen- and ADP-induced platelet aggregation. Inhibition of vitamin K epoxide reductase was observed in rats treated with flomoxef, yet to a much lesser extent than observed for cephalosporins with NMTT, TDT or MTDT side chains. This defect was quickly normalized by vitamin K injection. There were no differences between oxacephem (1-O) and cephem (1-S) compounds with respect to effects on blood clotting and platelet aggregation. Flomoxef and its side chain HTT showed no influence on alcohol metbolism.

From idea to implementation: creation of an educational picture book for radiation therapy patients.

PubMed

Osmar, Kari; Webb, Deborah

2015-03-01

Patient education is an integral part of the cancer patient's journey. Radiation therapists strive to provide timely, effective, and evidence-based information on care processes, side effects, and side effect management treatment strategies. Patient satisfaction surveys in health-care settings can guide new interventions and strategies to provide the right education to patients at the right time. Courses offered in adult education and patient education to practicing health-care providers allow for a unique opportunity to look at the current provision of health-care education to patients. This paper explores the development and implementation of a new visual aid for radiation therapy patients in an acute health-care setting with a diversity of languages spoken using principles of adult education.

The Effect of Hock Injury Laterality and Lameness on Lying Behaviors and Lying Laterality in Holstein Dairy Cows

PubMed Central

Krawczel, Peter D.

2017-01-01

Simple Summary Dairy cattle may experience discomfort in a myriad of ways throughout their life cycle, particularly when sustaining hock injuries or suboptimal locomotion. Lactating dairy cattle divide their lying time equally between left and right sides; however, discomfort experienced during pregnancy or following cannulation can cause a shift in the normal lying laterality. The objective of this study was to determine the effect of hock injuries and lameness on the lying behaviors of dairy cattle, particularly lying laterality. Lying laterality did not differ from the expected 50% (left side lying time) in cattle with hock injuries, lameness, or both. The current results suggest that lying laterality does not differ between varying levels of hock injury or lameness severity. Going forward, further research could determine if lying laterality shifts over the course of the animal developing a hock injury or lameness. Abstract Lactating dairy cattle divide their lying equally between their left side and their right side. However, discomfort, such as pregnancy and cannulation, can cause a cow to shift lying side preference. The objective of this study was to determine the effect of lameness and hock injuries on lying behaviors, particularly lying laterality, of lactating dairy cows. Cows from four commercial farms in eastern Croatia that had lying behavior data, health score data, and production records were used in the study. Health scores including hock injuries and locomotion were collected once per cow. Severely lame cows had greater daily lying time compared to sound cows and moderately lame cows. Overall, cows spent 51.3 ± 1.2% of their daily lying time on the left side. Maximum hock score, locomotion score, hock injury laterality, or parity did not result in lying laterality differing from 50%. PMID:29149044

Wind Tunnel Results of Pneumatic Forebody Vortex Control Using Rectangular Slots a Chined Forebody

NASA Technical Reports Server (NTRS)

Alexander, Michael; Meyn, Larry A.

1994-01-01

A subsonic wind tunnel investigation of pneumatic vortex flow control on a chined forebody using slots was accomplished at a dynamic pressure of 50 psf resulting in a R(n)/ft of 1.3 x 10(exp 6). Data were acquired from angles of attack ranging from -4deg to +34deg at side slips of +0.4deg and +10.4deg. The test article used in this study was the 10% scale Fighter Lift and Control (FLAC) advanced diamond winged, vee-tailed fighter configuration. Three different slot blowing concepts were evaluated; outward, downward, and tangential with ail blowing accomplished asymmetrically. The results of three different mass flows (0.067, 0.13, and 0.26 lbm/s; C(sub mu)'s of less than or equal to 0.006, 0.011. and 0.022 respectively) were analyzed and reported. Test data are presented on the effects of mass flows, slot lengths and positions and blowing concepts on yawing moment and side force generation. Results from this study indicate that the outward and downward blowing slots developed yawing moment and side force increments in the direction opposite of the blowing side while the tangential blowing slots generated yawing moment and side force increments in the direction towards the blowing side. The outward and downward blowing slots typically produced positive pitching moment increments while the tangential blowing slots typically generated negative pitching moment increments. The slot blowing nearest the forebody apex was most effective at generating the largest increments and as the slot was moved aft or increased in length, its effectiveness at generating forces and moments diminished.

EFFECTS OF SEDIMENT TYPE ON BENTHIC MACROINFAUNAL COLONIZATION OF LABORATORY MICROCOSMS

EPA Science Inventory

We tested the effects of four different sediment types on macroinfaunal colonization and community development in our laboratory flow-thru microcosm system (all microcosms were 20 cm side-1 and sediment depth was 5 cm) over a period of 41 days. Sediments included Santa Rosa Islan...

The Price of a Token.

ERIC Educational Resources Information Center

Yoder, Janice D.; And Others

As women enter nontraditional occupations and training programs, tokenism may develop and its side-effects of visibility, contrast, and assimilation may appear. Each of these effects was encountered by the first class of women cadets at the United States Military Academy, West Point, in 1976, who received great visibility from the news media. This…

New developments in the management of periocular capillary hemangioma in children.

PubMed

Ni, Nina; Wagner, Rudolph S; Langer, Paul; Guo, Suqin

2011-01-01

The authors describe the theories of pathogenesis for capillary hemangioma and discuss the benefits and side effects of current treatment options, such as systemic and intralesional corticosteroids, laser therapy, and surgical excision. They also evaluate the recent systemic and topical applications of beta-blockers to treat infantile hemangioma. Although no major adverse events from beta-blocker treatment have been reported, the incidence of potential side effects such as bronchospasm, hypoglycemia, heart block, bradycardia, and congestive heart failure is unknown due to the novelty of the treatment. It has been postulated that topical application for localized superficial tumor may reduce systemic effects. Further research is necessary to compare the effectiveness of different treatments and to find the optimal dosing and delivery methods to minimize adverse effects in the treatment of this disorder. Copyright 2011, SLACK Incorporated.

Developing Server-Side Infrastructure for Large-Scale E-Learning of Web Technology

ERIC Educational Resources Information Center

Simpkins, Neil

2010-01-01

The growth of E-business has made experience in server-side technology an increasingly important area for educators. Server-side skills are in increasing demand and recognised to be of relatively greater value than comparable client-side aspects (Ehie, 2002). In response to this, many educational organisations have developed E-business courses,…

Does creating a subperiosteal tunnel influence the periorbital edema and ecchymosis in rhinoplasty?

PubMed

Kara, Cüneyt Orhan; Kara, Inci Gökalan; Topuz, Bülent

2005-08-01

The study goal was to determine whether creating a subperiosteal tunnel before lateral osteotomy had an effect on postoperative periorbital edema, ecchymosis, and subconjunctival ecchymosis. Eighteen consecutive patients who underwent septorhinoplasty were included in the study. In all patients lateral osteotomies were carried out bilaterally, after creating a subperiosteal tunnel on a randomly chosen side and without creating a subperiosteal tunnel on the other side. The patients were seen on the second postoperative day, and a different surgeon who was unaware of the side with the periosteal tunnel determined the side of the face with more edema and ecchymosis. Subconjunctival ecchymosis was evaluated and recorded, as well. Creating subperiosteal tunnels before lateral osteotomy statistically increased periorbital ecchymosis. Although there was no statistically significant difference, creating subperiosteal tunnels also increased development and severity of subconjunctival ecchymosis and edema. We suggest performing lateral osteotomy without creating subperiosteal tunnels.

Experimental treatment of antipsychotic-induced movement disorders

PubMed Central

Shireen, Erum

2016-01-01

Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs. PMID:27540314

Managing Chemotherapy Side Effects: Constipation

MedlinePlus

... ational C ancer I nstitute Managing Chemotherapy Side Effects Constipation Take these steps: Eat high-fiber foods ... SERVICES National Institutes of Health Managing Chemotherapy Side Effects: Constipation These foods may help if you are ...

HIV Medicines and Side Effects

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... Apps skip to content Side Effects of HIV Medicines Home Understanding HIV/AIDS Fact Sheets HIV Medicines ... p.m. ET) Send us an email HIV Medicines and Side Effects Last Reviewed: October 9, 2017 ...

Matrix formalism of electromagnetic wave propagation through multiple layers in the near-field region: application to the flat panel display.

PubMed

Lee, C Y; Lee, D E; Hong, Y K; Shim, J H; Jeong, C K; Joo, J; Zang, D S; Shim, M G; Lee, J J; Cha, J K; Yang, H G

2003-04-01

We have developed an electromagnetic (EM) wave propagation theory through a single layer and multiple layers in the near-field and far-field regions, and have constructed a matrix formalism in terms of the boundary conditions of the EM waves. From the shielding efficiency (SE) against EM radiation in the near-field region calculated by using the matrix formalism, we propose that the effect of multiple layers yields enhanced shielding capability compared to a single layer with the same total thickness in conducting layers as the multiple layers. We compare the intensities of an EM wave propagating through glass coated with conducting indium tin oxide (ITO) on one side and on both sides, applying it to the electromagnetic interference (EMI) shielding filter in a flat panel display such as a plasma display panel (PDP). From the measured intensities of EMI noise generated by a PDP loaded with ITO coated glass samples, the two-side coated glass shows a lower intensity of EMI noise compared to the one-side coated glass. The result confirms the enhancement of the SE due to the effect of multiple layers, as expected in the matrix formalism of EM wave propagation in the near-field region. In the far-field region, the two-side coated glass with ITO in multiple layers has a higher SE than the one-side coated glass with ITO, when the total thickness of ITO in both cases is the same.

Nature versus nurture in determining athletic ability.

PubMed

Brutsaert, Tom D; Parra, Esteban J

2009-01-01

This chapter provides an overview of the truism that both nature and nurture determine human athletic ability. The major thesis developed is that environmental effects work through the process of growth and development and interact with an individual's genetic background to produce a specific adult phenotype, i.e. an athletic or nonathletic phenotype. On the nature side (genetics), a brief historical review is provided with emphasis on several areas that are likely to command future attention including the rise of genome-wide association as a mapping strategy, the problem of false positives using association approaches, as well as the relatively unknown effects of gene-gene interaction(epistasis), gene-environment interaction, and genome structure on complex trait variance. On the nurture side (environment), common environmental effects such as training-level and sports nutrition are largely ignored in favor of developmental environmental effects that are channeled through growth and development processes. Developmental effects are difficult to distinguish from genetic effects as phenotypic plasticity in response to early life environmental perturbation can produce lasting effects into adulthood. In this regard, the fetal programming (FP) hypothesis is reviewed in some detail as FP provides an excellent example of how developmental effects work and also interact with genetics. In general, FP has well-documented effects on adult body composition and the risk for adult chronic disease, but there is emerging evidence that FP affects human athletic performance as well. 2009 S. Karger AG, Basel

Recent developments in Helicobacter pylori vaccination.

PubMed

Kusters, J G

2001-01-01

This reviews discusses the recent progress in the development of a vaccine against Helicobacter pylori. To date, this gram-negative, spiral-shaped bacterium is one of the most common infections of mankind. Infection usually occurs during childhood, and when left untreated results in lifelong colonization of the stomach. Helicobacter pylori infection is a chronic gastritis that can lead to peptic ulcer disease, gastric adenocarcinoma and gastric B-cell lymphoma. Antimicrobial therapy is currently the method of choice for curing H. pylori infection, but complex dosing, inconsistent efficiency, development of antibiotic resistance, costs and various side effects compromise widespread use. As a consequence, new strategies for the prevention and eradication of H. pylori infections are being explored. Vaccines are an attractive option, because they are both effective and economic in use. Natural infection with H. pylori usually results in a strong inflammatory Th1-type CD4(+)T-cell response that does not seem to have any protective effects. Successful vaccination studies indicate that a Th2-type response is required for protection, but the exact mechanisms involved in protective immunization are still poorly understood. Although commercial development of products for clinical trial is underway, many important issues, such as lack of a suitable mucosal adjuvant, and prevention of potential side effects, such as postimmunization gastritis, need to be resolved.

Development of a carbazole-based fluorescence probe for G-quadruplex DNA: The importance of side-group effect on binding specificity.

PubMed

Wang, Ming-Qi; Ren, Gui-Ying; Zhao, Shuang; Lian, Guang-Chang; Chen, Ting-Ting; Ci, Yang; Li, Hong-Yao

2018-06-15

G-quadruplex DNAs are highly prevalent in the human genome and involved in many important biological processes. However, many aspects of their biological mechanism and significance still need to be elucidated. Therefore, the development of fluorescent probes for G-quadruplex detection is important for the basic research. We report here on the development of small molecular dyes designed on the basis of carbazole scaffold by introducing styrene-like substituents at its 9-position, for the purpose of G-quadruplex recognition. Results revealed that the side group on the carbazole scaffold was very important for their ability to selectively recognize G-quadruplex DNA structures. 1a with the pyridine side group displayed excellent fluorescence signal turn-on property for the specific discrimination of G-quadruplex DNAs against other nucleic acids. The characteristics of 1a were further investigated with UV-vis spectrophotometry, fluorescence, circular dichroism, FID assay and molecular docking to validate the selectivity, sensitivity and detailed binding mode toward G-quadruplex DNAs. Copyright © 2018 Elsevier B.V. All rights reserved.

Probiotics: Safety and Side Effects

MedlinePlus

... of this page please turn JavaScript on. Feature: Probiotics Safety and Side Effects Past Issues / Winter 2016 ... Says About the Safety and Side Effects of Probiotics Whether probiotics are likely to be safe for ...

Managing Chemotherapy Side Effects: Pain

MedlinePlus

N ational C ancer I nstitute Managing Chemotherapy Side Effects Pain It’s important to treat pain. If ... help to pay for pain medicine. Managing Chemotherapy Side Effects: Pain Keep track of the pain. Each ...

Managing Chemotherapy Side Effects: Memory Changes

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... C ancer I nstitute Managing Chemotherapy Side Effects Memory Changes What is causing these changes? Your doctor ... thinking or remembering things Managing Chemotherapy Side Effects: Memory Changes Get help to remember things. Write down ...

The Influence of Social Modeling, Gender, and Empathy on Treatment Side Effects.

PubMed

Faasse, Kate; Parkes, Bryony; Kearney, James; Petrie, Keith J

2018-05-31

Social modeling has the capacity to shape treatment outcomes, including side effects. This study investigated the influence of social modeling of treatment side effects, gender, and participant empathy, on side effects of a placebo treatment. Ninety-six participants (48 females) completed a study purportedly investigating the influence of modafinil (actually placebo) on alertness and fatigue. The participants were randomly seated with a male or female confederate and saw this confederate report experiencing side effects or no side effects. Participant empathy was assessed at baseline. Changes in modeled and general symptoms, and misattribution of symptoms, were assessed during the session and at 24-hr follow-up. During the experimental session, seeing side effect modeling significantly increased modeled symptoms (p = .023, d = 0.56) but not general or misattributed symptoms. Regardless of modeling condition, female participants seated with a female model reported significantly more general symptoms during the session. However, response to social modeling did not differ significantly by model or participant gender. At follow-up, the effect of social modeling of side effects had generalized to other symptoms, resulting in significantly higher rates of modeled symptoms (p = .023, d = 0.48), general symptoms (p = .013, d = 0.49), and misattributed symptoms (p = .022, d = 0.50). The experience of modeled symptoms in response to social modeling was predicted by participants' levels of baseline empathy. Social modeling of symptoms can increase the side effects following treatment, and this effect appears to generalize to a broader range of symptoms and symptom misattribution over time. Higher baseline empathy seems to increase response to social modeling.

A hierarchical anatomical classification schema for prediction of phenotypic side effects

PubMed Central

Kanji, Rakesh

2018-01-01

Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a ‘hierarchical anatomical classification schema’ which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects. PMID:29494708

A hierarchical anatomical classification schema for prediction of phenotypic side effects.

PubMed

Wadhwa, Somin; Gupta, Aishwarya; Dokania, Shubham; Kanji, Rakesh; Bagler, Ganesh

2018-01-01

Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a 'hierarchical anatomical classification schema' which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects.

Comparison of pathway and center of gravity of the calcaneus on non-involved and involved sides according to eccentric and concentric strengthening in patients with achilles tendinopathy.

PubMed

Yu, Jaeho; Lee, Gyuchang

2012-01-01

This study compares the changes in pathway and center of gravity (COG) on the calcaneus of non-involved and involved sides according to eccentric and concentric strengthening in patients with unilateral Achilles tendinopathy. The goal was to define the biomechanical changes according to eccentric strengthening for the development of clinical guidelines. Eighteen patients with Achilles tendinopathy were recruited at the K Rehabilitation Hospital in Seoul. The subjects were instructed to perform 5 sessions of concentric strengthening. The calcaneal pathway was measured using a three-dimensional (3D) motion analyzer, and COG was measured by a force plate. Subsequently, eccentric strengthening was implemented, and identical variables were measured. Concentric and eccentric strengthening was carried out on both the involved and non-involved sides. There was no significant difference in the calcaneal pathway in patients with Achilles tendinopathy during concentric and eccentric strengthening. However, during eccentric strengthening, the calcaneal pathway significantly increased on the involved side compared to the non-involved side for all variables excluding the z-axis. COG significantly decreased on the involved side when compared to the non-involved side in patients with Achilles tendinopathy during eccentric and concentric strengthening. During concentric strengthening, all variables of the COG significantly increased on the involved side compared to the non-involved side. Compared with eccentric strengthening, concentric strengthening decreased the stability of ankle joints and increased the movement distance of the calcaneus in patients with Achilles tendinopathy. Furthermore, eccentric strengthening was verified to be an effective exercise method for prevention of Achilles tendinopathy through the reduction of forward and backward path length of foot pressure. The regular application of eccentric strengthening was found to be effective in the secondary prevention of Achilles tendinopathy in a clinical setting.

Impact of adherence on the outcome of antiviral therapy for chronic hepatitis C.

PubMed

Mulhall, Brian P; Younossi, Zobair

2005-01-01

Nearly 4 million people in the United States have evidence of hepatitis C infection (HCV), representing a significant cause of cirrhosis and liver cancer as well a major burden to our healthcare systems and society. Antiviral therapy can successfully eradicate HCV over the long term, potentially reducing the risk of progression and improving patients' quality of life. The currently preferred HCV treatment is a combination of pegylated interferon alfa and ribavirin, which can achieve an overall sustained viral eradication rate of 55%. The duration of this treatment is typically determined by HCV genotype and the patient's early virologic response to the antiviral regimen. Evidence has accumulated over the past few years to indicate that close adherence to the optimal antiviral regimen can enhance sustained virologic response. But optimal treatment outcomes require diligence and careful management of side effects related to combination therapy. Although reducing the dose of pegylated interferon alfa, ribavirin, or both can effectively treat side effects, suboptimal doses of this regimen, especially ribavirin, may negatively affect virologic response. An alternative strategy is to use growth factors to treat cytopenias. This strategy can obviate dose reductions while potentially improving patients' quality of life. Patient support seems especially important early after the initiation of antiviral therapy. Encouraging study findings involving the growth factors, epoetin alfa and darbepoetin alfa, suggest improved anemia and quality of life while maintaining the optimal ribavirin dose. Future work should be aimed at providing stronger evidence for the use of these "supportive products" during anti-HCV therapy. As we strive to develop better treatment options for our HCV patients, the importance of adhering to the treatment regimen continues to play a central role. Effective side effect management is crucial for the success of this treatment because adherence is negatively affected by side effects related to the antiviral regimen. By identifying and addressing the important side effects of combination therapy for HCV, adherence to treatment can be improved and optimal outcomes can be achieved.

Fat, demented and stupid: An unrecognized legacy of pediatric urology?

PubMed

Cooper, Christopher S

2017-08-01

The human body is an unfathomably intricate structure consisting of many connected and intertwined systems. This makes it impossible for therapeutic interventions to selectively target only one physiologic system without some impact or side effects on all the other systems. The resiliency of the human body modifies and disguises side effects, some of which may be undetectable for years and not apparent without scientific investigation. Pediatric urologists employ relatively few medications for the common conditions they treat and in general these consist of antibiotics, anticholinergics, and anesthetics. Although harm from early side effects is well recognized, recent medical literature suggests there may be other side effects of these common interventions that aren't as well recognized. Antibiotics have been added to livestock feed as growth promoters for three-quarters of a century. Antibiotics alter the microbiota of the intestinal tract and these alterations have been demonstrated to impact growth, metabolism, and the risk of obesity in animals and humans. To date, the long-term impact of daily antibiotic prophylaxis in children with such pediatric urology conditions as vesicoureteral reflux or prenatal hydronephrosis have not been published. Similarly, there are no studies assessing long-term effects of anticholinergic use on cognition in children despite research demonstrating an increased risk of dementia in adults using anticholinergics. Research in animals and children recently led the FDA to issue a warning regarding the risk of lengthy use of general anesthesia on cognitive development in children. This review raises the possibility that antibiotics in children may alter growth, anticholinergics may increase their risk of dementia later in life, and anesthetics may impair their cognitive development. The possibility of such an unrecognized legacy from current therapeutic interventions should give all physicians, including pediatric urologists, pause for consideration before electing any intervention, no matter how routine or currently well accepted. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

An Examination of Psychotropic Medication Side Effects: Does Taking a Greater Number of Psychotropic Medications from Different Classes Affect Presentation of Side Effects in adults with ID?

ERIC Educational Resources Information Center

Mahan, Sara; Holloway, Jodie; Bamburg, Jay W.; Hess, Julie A.; Fodstad, Jill C.; Matson, Johnny L.

2010-01-01

This study examined whether the number of psychotropic medications an individual is taking across classes influences side effects among adults with Intellectual Disability (ID). Participants were 80 adults diagnosed with ID. Dependent variables were the composite score and domain scores of the "Matson Evaluation of Drug Side-Effects" ("MEDS"),…

A side-effect free method for identifying cancer drug targets.

PubMed

Ashraf, Md Izhar; Ong, Seng-Kai; Mujawar, Shama; Pawar, Shrikant; More, Pallavi; Paul, Somnath; Lahiri, Chandrajit

2018-04-27

Identifying effective drug targets, with little or no side effects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side effect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identification of effective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying effective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as effective candidates for drug development.

Bumper and grille airbags concept for enhanced vehicle compatibility in side impact: phase II.

PubMed

Barbat, Saeed; Li, Xiaowei; Prasad, Priya

2013-01-01

Fundamental physics and numerous field studies have shown a higher injury and fatality risk for occupants in smaller and lighter vehicles when struck by heavier, taller and higher vehicles. The consensus is that the significant parameters influencing compatibility in front-to-side crashes are geometric interaction, vehicle stiffness, and vehicle mass. The objective of this research is to develop a concept of deployable bumper and grille airbags for improved vehicle compatibility in side impact. The external airbags, deployed upon signals from sensors, may help mitigate the effect of weight, geometry and stiffness differences and reduce side intrusions. However, a highly reliable pre-crash sensing system is required to enable the reliable deployment, which is currently not technologically feasible. Analytical and numerical methods and hardware testing were used to help develop the deployable external airbags concept. Various Finite Element (FE) models at different stages were developed and an extensive number of iterations were conducted to help optimize airbag and inflator parameters to achieve desired targets. The concept development was executed and validated in two phases. This paper covers Phase II ONLY, which includes: (1) Re-design of the airbag geometry, pressure, and deployment strategies; (2) Further validation using a Via sled test of a 48 kph perpendicular side impact of an SUV-type impactor against a stationary car with US-SID-H3 crash dummy in the struck side; (3) Design of the reaction surface necessary for the bumper airbag functionality. The concept was demonstrated through live deployment of external airbags with a reaction surface in a full-scale perpendicular side impact of an SUV against a stationary passenger car at 48 kph. This research investigated only the concept of the inflatable devices since pre-crash sensing development was beyond the scope of this research. The concept design parameters of the bumper and grille airbags are presented in this paper. Full vehicle-to-vehicle crash test results, Via sled test, and simulation results are also presented. Head peak acceleration, Head Injury Criteria (HIC), Thoracic Trauma Index (TTI), and Pelvic acceleration for the SID-H3 dummy and structural intrusion profiles were used as performance metrics for the bumper and grille airbags. Results obtained from the Via sled tests and the full vehicle-to-vehicle tests with bumper and grille airbags were compared to those of baseline test results with no external airbags.

[Understanding chair-side digital technology for stomatology from an engineering viewpoint].

PubMed

Zhao, Y J; Wang, Y

2018-04-09

In recent years with the rapid development of digital technology for stomatology, the application field, application model, technical features and technical connotation of the chair-side digital technology has got development and change. The open modular system has gradually replaced the traditional closed system, and the application field of digital technology is no longer limited to chair-side dental restoration, it also has been extend to various kinds of chair-side digital treatment-assisted technology. In this paper, from the engineering point of view, the up to date general connotation of chair-side digital technology was explained, the characteristics and the development of each unit in chair-side digital technology were analyzed, and the application pattern and the localization status were also discussed in this paper. The aim of this paper was to introduce the trend of chair-side digital technological to readers and to better guide clinical application.

Comparıson of the Heart Rate and Blood Lactate Responses of Different Small Sided Games in Young Soccer Players.

PubMed

Köklü, Yusuf; Alemdaroğlu, Utku

2016-09-29

The purpose of this study was to compare the percentage of maximum heart rate (%HRmax), blood lactate (La - ), and rating of perceived exertion (RPE, CR-10) responses across different formats of small-sided games (SSG) in elite young soccer players. Fourteen players (average age 16.7 ± 0.6 years; height 177.6 ± 4.1 cm; body mass 66.3 ± 4.7 kg; average training age 6.7 ± 1.6 years; percentage of body fat 8.4 ± 2.6%) volunteered to perform the YoYo intermittent recovery test (level 1) and eight bouts of soccer drills including 2-a-side, 3-a-side, and 4-a-side games without goalkeepers in random order at two-day intervals. Heart rates were monitored throughout the SSGs, whereas the RPE and venous blood lactate were determined at the end of the last bout of each SSG. The differences in La - , %HRmax, and RPE either across the different SSGs or between the bouts were identified using 3 × 8 (games × exercise bouts) two-way analysis of variance with repeated measures. Significant differences were found in terms of La - , RPE, and %HRmax among the different types of SSG ( p ≤ 0.05). 3-a-side and 4-a-side games elicited significantly higher responses than 2-a-side games in terms of %HRmax ( p ≤ 0.05), whereas 4-a-side games resulted in significantly lower La - and RPE responses compared to 2-a-side and 3-a-side games. The results of this study show that physiological responses differ according to the numbers of players involved in small-sided games. Therefore, it can be concluded that 3-a-side and 4-a-side games could be more effective in improving high intensity aerobic performance than 2-a-side games, which in turn are more appropriate for developing anaerobic performance.

Pathogenesis of solitary right aortic arch: a mass effect hypothesis based on observations of serial human embryonic sections.

PubMed

Jin, Zhe W; Yamada, Tomonori; Kim, Ji H; Rodríguez-Vázquez, José F; Murakami, Gen; Arakawa, Keiji

2017-03-01

In general, solitary right aortic arch carries the left-sided ductus arteriosus communicating between the left subclavian and pulmonary arteries or the right-sided ductus connecting the descending aorta to the left pulmonary artery. Serial sections of fifteen 5- to 6-week-old embryos and ten 8- to 9-week-old fetuses suggested that the pathogenesis was unrelated to inversion due to dysfunction in gene cascades that control the systemic left/right axis. With inversion, conversely, the ductus or the sixth pharyngeal arch artery should connect to the right pulmonary artery. The disappearance of the right aortic arch started before the caudal migration of the aortic attachment of the ductus. Sympathetic nerve ganglia developed immediately posterior to both aortae, with a single embryonic specimen showing a large ganglion at the midline close to the union of the aortic arches. These ganglia may interfere with blood flow through the distal left arch, resulting in the ductus ending at the descending aorta behind the oesophagus. In another fetus examined, a midline shift of the ductus course resulted in the trachea curving posteriorly. Therefore, solitary right arch is likely to accompany abnormalities of the surrounding structures. The timing and site of the obstruction should be different between types: an almost midline obstruction near the aortic union needed for the development of the left-sided ductus and a distal obstruction near the left subclavian arterial origin needed for the development of the right-sided ductus. A mass effect of the sympathetic ganglia may explain the pathogenesis of any type of anomalous ductus arteriosus shown in previous reports of the solitary right arch.

Managing Chemotherapy Side Effects: Anemia

MedlinePlus

... ational C ancer I nstitute Managing Chemotherapy Side Effects Anemia “I told my doctor that I was ... exercise a little every day. Managing Chemotherapy Side Effects: Anemia Eat and drink well. ● ● Talk with your ...

Chemotherapy Side Effects: A Cause of Heart Disease?

MedlinePlus

... Can chemotherapy side effects increase the risk of heart disease? Answers from Timothy J. Moynihan, M.D. Chemotherapy side effects may increase the risk of heart disease, including weakening of the heart muscle (cardiomyopathy) and ...

Managing Chemotherapy Side Effects: Skin and Nail Changes

MedlinePlus

... ational C ancer I nstitute Managing Chemotherapy Side Effects Skin and Nail Changes “I was glad to ... services national institutes of health Managing Chemotherapy Side Effects: Skin and Nail Changes Protect your skin from ...

Multiple-dose safety study of ibuprofen/codeine and aspirin/codeine combinations.

PubMed

Friedman, H; Seckman, C; Stubbs, C; Oster, H; Royer, G

1990-01-01

This multiple-dose, double-blind, placebo-controlled, randomized, normal volunteer study compared formulations of ibuprofen/codeine and aspirin/codeine for systemic safety. Vital signs, hematologic, biochemical and urinary parameters, side effects, mood and mental alertness, were monitored. The placebo group had less gastrointestinal side effects and more frequent stools than the active treatment groups. There was statistical evidence for greater adverse effects of aspirin/codeine on mood and mental alertness in comparison to ibuprofen/codeine and placebo. Ibuprofen/codeine had a more favorable adverse effect profile than aspirin/codeine. A mild respiratory and cardiac depressant effect attributable to codeine was evident in all active treatment groups after 7 days of frequent therapy. More work needs to be done to elucidate the factors regulating the development of tolerance to the respiratory and cardiovascular depressant effects of opiates in general, and for codeine in particular.

Effect of Chronic Administration of Low Dose Rapamycin on Development and Immunity in Young Rats.

PubMed

Lu, Zhenya; Liu, Furong; Chen, Linglin; Zhang, Huadan; Ding, Yuemin; Liu, Jianxiang; Wong, Michael; Zeng, Ling-Hui

2015-01-01

Mammalian target of rapamycin (mTOR) regulates cell growth, cell differentiation and protein synthesis. Rapamycin, an inhibitor of mTOR, has been widely used as an immunosuppressant and anti-cancer drug. Recently, mTOR inhibitors have also been reported to be a potential anti-epileptic drug, which may be effective when used in young patients with genetic epilepsy. Thus, a suitable dose of rapamycin which can maintain the normal function of mTOR and has fewer side effects ideally should be identified. In the present study, we first detected changes in marker proteins of mTOR signaling pathway during development. Then we determined the dose of rapamycin by treating rats of 2 weeks of age with different doses of rapamycin for 3 days and detected its effect on mTOR pathway. Young rats were then treated with a suitable dose of rapamycin for 4 weeks and the effect of rapamycin on mTOR, development and immunity were investigated. We found that the expression of the marker proteins of mTOR pathway was changed during development in brain hippocampus and neocortex. After 3 days of treanent, 0.03 mg/kg rapamycin had no effect on phospho-S6, whereas 0.1, 0.3, 1.0 and 3.0 mg/kg rapamycin inhibited phospho-S6 in a dose-dependent manner. However, only 1.0 mg/kg and 3.0 mg/kg rapamycin inhibited phospho-S6 after 4 weeks treatment of rapamycin. Parallel to this result, rats treated with 0.1 and 0.3 mg/kg rapamycin had no obvious adverse effects, whereas rats treated with 1.0 and 3.0 mg/kg rapamycin showed significant decreases in body, spleen and thymus weight. Additionally, rats treated with 1.0 and 3.0 mg/kg rapamycin exhibited cognitive impairment and anxiety as evident by maze and open field experiments. Furthermore, the content of IL-1β, IL-2, IFN-γ, TNF-α in serum and cerebral cortex were significantly decreased in 1.0 and 3.0 mg/kg rapamycin-treated rats. The expression of DCX was also significantly decreased in 1.0 and 3.0 mg/kg rapamycin-treated rats. However, rats treated with 1.0 mg/kg rapamycin exhibited fewer and milder side effects than those treated with 3.0 mg/kg. In summary, all these data suggest that there is not a rapamycin dose that can inhibit mTOR for epilepsy without causing any side effects, but 1 mg/kg may be the optimal dose for young rats for suppressing mTOR with relatively few side effects.

Effect of Chronic Administration of Low Dose Rapamycin on Development and Immunity in Young Rats

PubMed Central

Lu, Zhenya; Liu, Furong; Chen, Linglin; Zhang, Huadan; Ding, Yuemin; Liu, Jianxiang; Wong, Michael; Zeng, Ling-Hui

2015-01-01

Mammalian target of rapamycin (mTOR) regulates cell growth, cell differentiation and protein synthesis. Rapamycin, an inhibitor of mTOR, has been widely used as an immunosuppressant and anti-cancer drug. Recently, mTOR inhibitors have also been reported to be a potential anti-epileptic drug, which may be effective when used in young patients with genetic epilepsy. Thus, a suitable dose of rapamycin which can maintain the normal function of mTOR and has fewer side effects ideally should be identified. In the present study, we first detected changes in marker proteins of mTOR signaling pathway during development. Then we determined the dose of rapamycin by treating rats of 2 weeks of age with different doses of rapamycin for 3 days and detected its effect on mTOR pathway. Young rats were then treated with a suitable dose of rapamycin for 4 weeks and the effect of rapamycin on mTOR, development and immunity were investigated. We found that the expression of the marker proteins of mTOR pathway was changed during development in brain hippocampus and neocortex. After 3 days of treanent, 0.03 mg/kg rapamycin had no effect on phospho-S6, whereas 0.1, 0.3, 1.0 and 3.0 mg/kg rapamycin inhibited phospho-S6 in a dose-dependent manner. However, only 1.0 mg/kg and 3.0 mg/kg rapamycin inhibited phospho-S6 after 4 weeks treatment of rapamycin. Parallel to this result, rats treated with 0.1 and 0.3 mg/kg rapamycin had no obvious adverse effects, whereas rats treated with 1.0 and 3.0 mg/kg rapamycin showed significant decreases in body, spleen and thymus weight. Additionally, rats treated with 1.0 and 3.0 mg/kg rapamycin exhibited cognitive impairment and anxiety as evident by maze and open field experiments. Furthermore, the content of IL-1β, IL-2, IFN-γ, TNF-α in serum and cerebral cortex were significantly decreased in 1.0 and 3.0 mg/kg rapamycin-treated rats. The expression of DCX was also significantly decreased in 1.0 and 3.0 mg/kg rapamycin-treated rats. However, rats treated with 1.0 mg/ kg rapamycin exhibited fewer and milder side effects than those treated with 3.0 mg/kg. In summary, all these data suggest that there is not a rapamycin dose that can inhibit mTOR for epilepsy without causing any side effects, but 1 mg /kg may be the optimal dose for young rats for suppressing mTOR with relatively few side effects. PMID:26248290

Influence of Side Effects on ART Adherence Among PLWH in China: The Moderator Role of ART-Related Knowledge.

PubMed

Zhou, Guangyu; Li, Xiaoming; Qiao, Shan; Shen, Zhiyong; Zhou, Yuejiao

2018-03-01

Despite the medical advancements in HIV treatment, realities of side effects are faced by people living with HIV (PLWH) who receive antiretroviral therapy (ART). Mixed findings have been reported on the association between side effects and ART adherence. However, few studies have explored the combined side effects and behavior-related information on medication adherence. The aim of the current study is to examine moderator role of ART-related knowledge between side effects and ART adherence. A cross-sectional survey was conducted among 2987 PLWH from October 2012 to August 2013 in China. Of the total sample, 2095 patients had received ART and provided ART adherence. Side effects, ART-related knowledge, and ART adherence, as well as potential covariates were assessed. The results revealed that there was a negative relationship of side effects and ART adherence existed among low and medium levels of ART-related knowledge, but not among high level of knowledge. Future interventions to promote HIV medication adherence should focus on providing behavior-related information education among PLWH.

A versatile genetic tool for post-translational control of gene expression in Drosophila melanogaster

PubMed Central

Sethi, Sachin

2017-01-01

Several techniques have been developed to manipulate gene expression temporally in intact neural circuits. However, the applicability of current tools developed for in vivo studies in Drosophila is limited by their incompatibility with existing GAL4 lines and side effects on physiology and behavior. To circumvent these limitations, we adopted a strategy to reversibly regulate protein degradation with a small molecule by using a destabilizing domain (DD). We show that this system is effective across different tissues and developmental stages. We further show that this system can be used to control in vivo gene expression levels with low background, large dynamic range, and in a reversible manner without detectable side effects on the lifespan or behavior of the animal. Additionally, we engineered tools for chemically controlling gene expression (GAL80-DD) and recombination (FLP-DD). We demonstrate the applicability of this technology in manipulating neuronal activity and for high-efficiency sparse labeling of neuronal populations. PMID:29140243

Corticosteroid treatment in Sydenham's chorea.

PubMed

Fusco, C; Spagnoli, C

2018-03-01

Sydenham's chorea (SC) is an immune-mediated hyperkinetic movement disorder, developing after group A Beta-hemolytic streptococcal (GABHS) infection. Aside from conventional symptomatic treatment (carbamazepine, valproate, neuroleptics), the use of steroids has also been advocated, mainly in severe, drug-resistant cases or if clinically disabling side effects develop with first line therapies. Based on the description of 5 cases followed in the Child Neurology Unit of Santa Maria Nuova Hospital in Reggio Emilia and on the available medical literature on this topic, we propose considering the use of corticosteroids therapy in children with SC, with the administration of IV methyl-prednisolone followed by oral deflazacort in severe cases and of oral deflazacort alone in mild and moderate degrees of involvement. In our experience this therapy is effective both in the short and long-term period, in different clinical presentations (chorea paralytica, distal chorea, hemichorea, "classic" chorea, association with mood disorder or dyspraxia) and very well tolerated (no significant side effects were recorded). Copyright © 2017. Published by Elsevier Ltd.

Cancer Treatment Side Effects: A Meta-analysis of the Relationship Between Response Expectancies and Experience.

PubMed

Devlin, Elise J; Denson, Linley A; Whitford, Hayley S

2017-08-01

Although previous research has, overall, suggested a moderate relationship between response expectancies (REs) and cancer treatment-related side effects, empirical results have been mixed. We aimed to further explore these relationships, hypothesizing that REs would predict subsequent toxicities with the inclusion of more recent studies, across a broader range of side effects, while incorporating the impact of potential moderators including patients' experience with treatment and measurement methods. We further investigated the impact of REs across individual toxicities. A systematic search and analysis were conducted across four databases (PsychInfo, PubMed, CINAHL, and Embase) and reference lists, from 1985 to February 2016. This provided 27 eligible studies with 4474 participants, through which the main analysis, moderator analyses, and individual side-effect analyses were explored. REs were moderately related to side effects overall (r = 0.26), and effect sizes were significantly influenced by sample diagnostic homogeneity, whereas differences between type and timing of measurement showed trends. Of the 16 toxicities examined, 15 demonstrated significant relationships between REs and side-effect experience, with hair loss (r = 0.48) the strongest. No clear difference emerged between objective and subjective side effects; however, significant differences across individual toxicities were revealed. Findings support a relationship between REs and a wide range of subsequent side effects, yet differences between individual RE-toxicity associations emerged. These findings provide direction for the measurement of side effects and REs and support REs as potential targets for intervention during the informed consent process. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Anaesthesiological considerations on tocolytic and uterotonic therapy in obstetrics.

PubMed

Vercauteren, M; Palit, S; Soetens, F; Jacquemyn, Y; Alahuhta, S

2009-07-01

Significant side effects of tocolytic and uterotonic substances may be of concern to the anaesthesiologist. Recently, new drugs have been introduced having less side effects for both the mother and the neonate. A literature search was undertaken mainly focusing on meta-analyses, to review the possible side effects that might affect the course of anaesthesia and to suggest which precautions should be considered to prevent the occurrence of significant interactions with anaesthetic manipulations and drugs. Magnesium sulphate has a proven benefit in lowering systolic blood pressure and preventing the occurrence of eclampsia, but not as a tocolytic. beta-adrenergic agonists are being abandoned due to the availability of tocolytic agents causing less side effects. Calcium channel blockers (CCB) are frequently used but can cause major maternal cardiovascular complications. Nitroglycerin seems to be appreciated as an acute tocolytic rather than a routine substance during pre-term labour. Cyclo-oxygenase-2 inhibitors are still under investigation but their tocolytic benefit is questionable mainly due to foetal side effects. Atosiban is considered the first-choice tocolytic. With respect to oxytocic drugs, oxytocine, prostaglandines and methylergometrine may all cause serious side effects especially when combined. The cardiovascular side effects of prostaglandins and methylergometrine can be life-threatening. Both oxytocin and carbetocin have a rather low risk for maternal complications. Atosiban and CCB are at least as effective tocolytic agents as beta-mimetics but have significantly less side effects. Magnesium sulphate can cause neuromuscular blockade, especially when combined with CCB. Concerning oxytocic agents, short-acting oxyctocin and long-acting carbetocin have the least side effects as compared with prostaglandins and methylergometrine.

Depressive symptoms as a side effect of the sustained release form of methylphenidate in a 7-year-old boy with attention-deficit hyperactivity disorder.

PubMed

Lakić, Aneta

2012-02-01

Hyperkinetic disorder or attention-deficit hyperactivity disorder (ADHD) is a clinical entity consisting of a cluster of symptoms including hyperactivity, attention disorder and impulse control disorder group. In the context of ADHD etiology we may say that genetic, clinical and imaging studies point out a disruption of the brain dopamine system, which is corroborated by the clinical effectiveness of stimulant drugs, which increase extracellular dopamine in the brain. Basically, it is a biological and not psychological disorder, which is important both for the comprehension and therapeutical approach to this problem. Today, the best recommended approach regarding children with ADHD is a combination of two therapeutic modalities: pharmacotherapy and behavioral treatment. The first-choice drugs for this disorder belong to the group of sympathomimetics--psychostimulants and atomoxetine (more recently). As the first-choice therapy, methylphenydate in sustained release form has numerous advantages. Like all drugs, methylphenidate has its unwanted side effects. Most common are: loss of appetite, weight loss, sleeping disorders, irritability, headache. These side effects are well-known and documented in the literature. By analysing the available literature we have found cases of psychiatric side effects such as: psychosis, mania, visual hallucinations, agitation, suicidal ideas. We have not found examples of ADHD in children who use increased dosage of sustained release of methylphenidate leading to depressive symptomatology. On the other side, methylphenidate may be prescribed for off-label use in treatment-resistant cases of depression. The case of a 7-year-old boy diagnosed with ADHD was on a minimal dose of sustained release form of methylphenidate. After initial titration of the drug, i.e. after raising the dose to the next level the boy developed clinical signs of depression. The treatment was ceased and depressive symptoms were withdrawed. Manifestation of depressive symptomatology after dose increasement of sustained release form of methylphenidate in a 7-year-old boy with ADHD represents an uncommon side effect. Precise drug activity mechanisms responsible for the appearance of these symptoms remains to be explained.

Firebrand Production from Building Components Fitted with Siding Treatments

PubMed Central

Suzuki, Sayaka; Manzello, Samuel L.

2016-01-01

Firebrand production from real-scale building components under well-controlled laboratory conditions was investigated. Re-entrant corner assemblies were ignited and during the combustion process, firebrands were collected to determine the size/mass distribution generated from such real-scale building components under varying wind speed. In prior work, a unique ignition methodology was developed to generate firebrands from re-entrant corner assemblies constructed of wood studs and oriented strand board (OSB). In this study, this ignition methodology was applied to re-entrant corners constructed from wood studs/OSB but fitted with actual siding treatments (tar paper and cedar siding) to determine the influence of siding treatments on firebrand generation from wall assemblies. Firebrands were collected with pans filled with water, and then the size and mass of firebrands were measured after drying. The size and mass distributions of firebrands collected in this study were compared with the data from prior component tests as well as the limited studies available in the literature on this topic. Some firebrands were found to be lighter for a given projected area than others, likely produced from cedar siding or tar paper. The effects of applied siding treatments on firebrand production are discussed in detail. PMID:27114643

Firebrand Production from Building Components Fitted with Siding Treatments.

PubMed

Suzuki, Sayaka; Manzello, Samuel L

2016-02-01

Firebrand production from real-scale building components under well-controlled laboratory conditions was investigated. Re-entrant corner assemblies were ignited and during the combustion process, firebrands were collected to determine the size/mass distribution generated from such real-scale building components under varying wind speed. In prior work, a unique ignition methodology was developed to generate firebrands from re-entrant corner assemblies constructed of wood studs and oriented strand board (OSB). In this study, this ignition methodology was applied to re-entrant corners constructed from wood studs/OSB but fitted with actual siding treatments (tar paper and cedar siding) to determine the influence of siding treatments on firebrand generation from wall assemblies. Firebrands were collected with pans filled with water, and then the size and mass of firebrands were measured after drying. The size and mass distributions of firebrands collected in this study were compared with the data from prior component tests as well as the limited studies available in the literature on this topic. Some firebrands were found to be lighter for a given projected area than others, likely produced from cedar siding or tar paper. The effects of applied siding treatments on firebrand production are discussed in detail.

Diuretics and salt transport along the nephron.

PubMed

Bernstein, Paul L; Ellison, David H

2011-11-01

The clinical use of diuretics almost uniformly predated the localization of their site of action. The consequence of diuretic specificity predicts clinical application and side effect, and the proximity of the sodium transporters, one to the next, often dictates potency or diuretic efficiency. All diuretics function by inhibiting the normal transport of sodium from the filtrate into the renal tubular cells. This movement of sodium into the renal epithelial cells on the apical side is facilitated by a series of transporters whose function is, in turn, dependent on the adenosine triphosphate (ATP)-dependent Na-K cotransporter on the basolateral side of the cell. Our growing understanding of the physiology of sodium transport has spawned new possibilities for diuretic development. Copyright © 2011 Elsevier Inc. All rights reserved.

Direct torque control method applied to the WECS based on the PMSG and controlled with backstepping approach

NASA Astrophysics Data System (ADS)

Errami, Youssef; Obbadi, Abdellatif; Sahnoun, Smail; Ouassaid, Mohammed; Maaroufi, Mohamed

2018-05-01

This paper proposes a Direct Torque Control (DTC) method for Wind Power System (WPS) based Permanent Magnet Synchronous Generator (PMSG) and Backstepping approach. In this work, generator side and grid-side converter with filter are used as the interface between the wind turbine and grid. Backstepping approach demonstrates great performance in complicated nonlinear systems control such as WPS. So, the control method combines the DTC to achieve Maximum Power Point Tracking (MPPT) and Backstepping approach to sustain the DC-bus voltage and to regulate the grid-side power factor. In addition, control strategy is developed in the sense of Lyapunov stability theorem for the WPS. Simulation results using MATLAB/Simulink validate the effectiveness of the proposed controllers.

Effect of defect creation and migration on hump characteristics of a-InGaZnO thin film transistors under long-term drain bias stress with light illumination

NASA Astrophysics Data System (ADS)

Cho, Yong-Jung; Kim, Woo-Sic; Lee, Yeol-Hyeong; Park, Jeong Ki; Kim, Geon Tae; Kim, Ohyun

2018-06-01

We investigated the mechanism of formation of the hump that occurs in the current-voltage I-V characteristics of amorphous InGaZnO (a-IGZO) thin film transistors (TFTs) that are exposed to long-term drain bias stress under illumination. Transfer characteristics showed two-stage degradation under the stress. At the beginning of the stress, the I-V characteristics shifted in the negative direction with a degradation of subthreshold slope, but the hump phenomenon developed over time in the I-V characteristics. The development of the hump was related to creation of defects, especially ionized oxygen vacancies which act as shallow donor-like states near the conduction-band minimum in a-IGZO. To further investigate the hump phenomenon we measured a capacitance-voltage C-V curve and performed two-dimensional device simulation. Stretched-out C-V for the gate-to-drain capacitance and simulated electric field distribution which exhibited large electric field near the drain side of TFT indicated that VO2+ were generated near the drain side of TFT, but the hump was not induced when VO2+ only existed near the drain side. Therefore, the degradation behavior under DBITS occurred because VO2+ were created near the drain side, then were migrated to the source side of the TFT.

Hyponatremia associated with repeated use of levetiracetam.

PubMed

Nasrallah, Khalil; Silver, Brian

2005-06-01

Levetiracetam (LEV) is increasingly used as adjunctive anticonvulsant therapy because of apparent low toxicity. Somnolence, asthenia, headache, dizziness, and nervousness are the most frequently reported side effects (1). We describe a patient, predisposed to the development of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), in whom hyponatremia developed after two challenges of LEV.

Psychological Development and Educational Problems of Left-Behind Children in Rural China

ERIC Educational Resources Information Center

Sun, Xiaojun; Tian, Yuan; Zhang, Yongxin; Xie, Xiaochun; Heath, Melissa A.; Zhou, Zongkui

2015-01-01

With China's rapidly developing economy and increasing urbanization, many adults from rural areas migrate to urban areas for better paid jobs. A side effect of this migration is that parents frequently leave their children behind (left-behind children). This research investigated left-behind children's and non-left-behind children's psychological,…

Type and frequency of side effects during PC6 acupuncture: observations from therapists and patients participating in clinical efficacy trials of acupuncture.

PubMed

Enblom, Anna; Johnsson, Anna

2017-12-01

Many therapists practise PC6 acupuncture for emesis (nausea and vomiting) during pregnancy, different cancer therapies, palliative care, after surgery, or to induce relaxing effects in general. Knowledge of side effects is central to shared decision-making. To describe the type and frequency of side effects and the level of needle-induced pain during PC6 acupuncture. We included 1298 PC6 acupuncture treatments, delivered to 221 participants (77% women, mean age 52.5, range 18-91 years). The subjects had received genuine PC6 acupuncture, in one of two previous randomised controlled trials, aimed at inducing antiemetic (n=100, with 100 providing data on side effects and 94 on needle-induced pain, respectively) or relaxing (n=121, with 120 providing data) effects. Side effects during and after the acupuncture treatments were registered in structured treatment protocols and study diaries. No serious complications occurred. Side effects during the acupuncture sessions included minor bleeding in 5.0%, tiredness in 4.9%, numbness in 4.5% and dizziness in 1.4% of the 1298 treatments. After treatment, the mean proportions of participants reporting side effects each week were: tiredness 25.8%; feeling cold 17.8%; dizziness 9.7%; sweating 9.3%; haematoma 8.8%; and soreness at the needling sites 4.3%. Participants perceived the needling to be not painful (47.4% of participants), or mildly (39.1%), moderately (11.6%) or very painful (1.4%). Few side effects occurred and those that did were mild. Nearly 90% found PC6 acupuncture to be not painful or only mildly painful. Healthcare professionals may consider the observed levels of side effects when informing patients about side effects of PC6 acupuncture. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comparison of High Aspect Ratio Cooling Channel Designs for a Rocket Combustion Chamber with Development of an Optimized Design

NASA Technical Reports Server (NTRS)

Wadel, Mary F.

1998-01-01

An analytical investigation on the effect of high aspect ratio (height/width) cooling channels, considering different coolant channel designs, on hot-gas-side wall temperature and coolant pressure drop for a liquid hydrogen cooled rocket combustion chamber, was performed. Coolant channel design elements considered were: length of combustion chamber in which high aspect ratio cooling was applied, number of coolant channels, and coolant channel shape. Seven coolant channel designs were investigated using a coupling of the Rocket Thermal Evaluation code and the Two-Dimensional Kinetics code. Initially, each coolant channel design was developed, without consideration for fabrication, to reduce the hot-gas-side wall temperature from a given conventional cooling channel baseline. These designs produced hot-gas-side wall temperature reductions up to 22 percent, with coolant pressure drop increases as low as 7.5 percent from the baseline. Fabrication constraints for milled channels were applied to the seven designs. These produced hot-gas-side wall temperature reductions of up to 20 percent, with coolant pressure drop increases as low as 2 percent. Using high aspect ratio cooling channels for the entire length of the combustion chamber had no additional benefit on hot-gas-side wall temperature over using high aspect ratio cooling channels only in the throat region, but increased coolant pressure drop 33 percent. Independent of coolant channel shape, high aspect ratio cooling was able to reduce the hot-gas-side wall temperature by at least 8 percent, with as low as a 2 percent increase in coolant pressure drop. ne design with the highest overall benefit to hot-gas-side wall temperature and minimal coolant pressure drop increase was the design which used bifurcated cooling channels and high aspect ratio cooling in the throat region. An optimized bifurcated high aspect ratio cooling channel design was developed which reduced the hot-gas-side wall temperature by 18 percent and reduced the coolant pressure drop by 4 percent. Reductions of coolant mass flow rate of up to 50 percent were possible before the hot-gas-side wall temperature reached that of the baseline. These mass flow rate reductions produced coolant pressure drops of up to 57 percent.

Living with Fibromyalgia, Drugs Approved to Manage Pain

MedlinePlus

... that can happen in people with diabetes (diabetic peripheral neuropathy) and in those who develop pain following the ... previously approved to treat depression, anxiety, and diabetic peripheral neuropathy. Cymbalta's side effects include nausea, dry mouth, sleepiness, ...

Phytochemical and pharmacological properties of essential oils from Cedrus species.

PubMed

Saab, Antoine M; Gambari, Roberto; Sacchetti, Gianni; Guerrini, Alessandra; Lampronti, Ilaria; Tacchini, Massimo; El Samrani, Antoine; Medawar, Samir; Makhlouf, Hassane; Tannoury, Mona; Abboud, Jihad; Diab-Assaf, Mona; Kijjoa, Anake; Tundis, Rosa; Aoun, Jawad; Efferth, Thomas

2018-06-01

Natural products frequently exert pharmacological activities. The present review gives an overview of the ethnobotany, phytochemistry and pharmacology of the Cedrus genus, e.g. cytotoxic, spasmolytic immunomodulatory, antiallergic, anti-inflammatory and analgesic activities. Cancer patients frequently seek remedies from traditional medicinal plants that are believed to exert less side effects than conventional therapy with synthetic drugs. A long-lasting goal of anti-cancer and anti-microbial therapy research is to find compounds with reduced side effects compared to currently approved drugs. In this respect, Cedrus species might be of interest. The essential oil isolated from Cedrus libani leaves may bear potential for drug development due to its high concentrations of germacrene D and β-caryophyllene. The essential oils from Cedrus species also show bioactivity against bacteria and viruses. More preclinical analyses (e.g. in vivo experiments) as well as clinical trials are required to evaluate the potential of essential oils from Cedrus species for drug development.

Randomized controlled trial of the cognitive side-effects of magnetic seizure therapy (MST) and electroconvulsive shock (ECS).

PubMed

Moscrip, Tammy D; Terrace, Herbert S; Sackeim, Harold A; Lisanby, Sarah H

2006-02-01

Magnetic seizure therapy (MST) is under development as a means of improving the cognitive side-effect profile of electroconvulsive therapy (ECT) by inducing more spatially delimited seizures that spare cortical regions involved in memory. We tested whether MST had a cognitive side-effect profile distinct from electroconvulsive shock (ECS) in a non-human primate model, using the Columbia University Primate Cognitive Profile, which has been shown to be sensitive to the cognitive effects of ECS. Using a within-subject cross-over design, daily ECS, MST, and sham (anaesthesia-only) interventions were administered in 5-wk blocks. Rhesus macaques (n = 2) were trained on a long-term memory task, an anterograde learning and memory task, and a combined anterograde and retrograde task where learning and memory were evaluated for new and previously learned 3-item lists. Acutely following each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-h retention interval. Overall, monkeys were least accurate following ECS (p's < 0.05) compared to sham and MST. This effect was most marked for long-term memory of a constant target, short-term memory of a variable target and recall of previously learned 3-item lists. Monkeys were slowest to complete all tasks following ECS (p's = 0.0001). Time to task completion following MST did not differ from sham. These findings suggest that MST results in a more benign acute cognitive side-effect profile than ECS in this model, consistent with initial observations with human MST.

Side-gate modulation effects on high-quality BN-Graphene-BN nanoribbon capacitors

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

Wang, Yang; Chen, Xiaolong; Ye, Weiguang

High-quality BN-Graphene-BN nanoribbon capacitors with double side-gates of graphene have been experimentally realized. The double side-gates can effectively modulate the electronic properties of graphene nanoribbon capacitors. By applying anti-symmetric side-gate voltages, we observed significant upward shifting and flattening of the V-shaped capacitance curve near the charge neutrality point. Symmetric side-gate voltages, however, only resulted in tilted upward shifting along the opposite direction of applied gate voltages. These modulation effects followed the behavior of graphene nanoribbons predicted theoretically for metallic side-gate modulation. The negative quantum capacitance phenomenon predicted by numerical simulations for graphene nanoribbons modulated by graphene side-gates was not observed,more » possibly due to the weakened interactions between the graphene nanoribbon and side-gate electrodes caused by the Ga{sup +} beam etching process.« less

Track and track-side video survey technology development.

DOT National Transportation Integrated Search

2015-05-01

Researchers at HiDef/Createc have completed prototype development and testing of a novel track video surveying technology : called Track and Track-Side Video Survey (TTVS). TTVS is designed to capture clear video images of the track and track side : ...

Double side read-out technique for mitigation of radiation damage effects in PbWO 4 crystals

DOE PAGES

Lucchini, Marco Toliman; Auffray, E.; Benaglia, A.; ...

2016-04-18

Test beam results of a calorimetric module based on 3×3×22 cm 3 PbWO 4 crystals, identical to those used in the CMS ECAL Endcaps, read out by a pair of photodetectors coupled to the two opposite sides (front and rear) of each crystal are presented. Nine crystals with different level of induced absorption, from 0 to 20 m -1, have been tested using electrons in the 50–200 GeV energy range. Photomultiplier tubes have been chosen as photodetectors to allow for a precise measurement of highly damaged crystals. The information provided by this double side read-out configuration allows to correct formore » event-by-event fluctuations of the longitudinal development of electromagnetic showers. By strongly mitigating the effect of non-uniform light collection efficiency induced by radiation damage, the double side read-out technique significantly improves the energy resolution with respect to a single side read-out configuration. The non-linearity of the response arising in damaged crystals is also corrected by a double side read-out configuration and the response linearity of irradiated crystals is restored. In high radiation environments at future colliders, as it will be the case for detectors operating during the High Luminosity phase of the Large Hadron Collider, defects can be created inside the scintillator volume leading to a non-uniform response of the calorimetric cell. As a result, the double side read-out technique presented in this study provides a valuable way to improve the performance of calorimeters based on scintillators whose active volumes are characterized by high aspect ratio cells similar to those used in this study.« less

Double side read-out technique for mitigation of radiation damage effects in PbWO 4 crystals

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

Lucchini, Marco Toliman; Auffray, E.; Benaglia, A.

Test beam results of a calorimetric module based on 3×3×22 cm 3 PbWO 4 crystals, identical to those used in the CMS ECAL Endcaps, read out by a pair of photodetectors coupled to the two opposite sides (front and rear) of each crystal are presented. Nine crystals with different level of induced absorption, from 0 to 20 m -1, have been tested using electrons in the 50–200 GeV energy range. Photomultiplier tubes have been chosen as photodetectors to allow for a precise measurement of highly damaged crystals. The information provided by this double side read-out configuration allows to correct formore » event-by-event fluctuations of the longitudinal development of electromagnetic showers. By strongly mitigating the effect of non-uniform light collection efficiency induced by radiation damage, the double side read-out technique significantly improves the energy resolution with respect to a single side read-out configuration. The non-linearity of the response arising in damaged crystals is also corrected by a double side read-out configuration and the response linearity of irradiated crystals is restored. In high radiation environments at future colliders, as it will be the case for detectors operating during the High Luminosity phase of the Large Hadron Collider, defects can be created inside the scintillator volume leading to a non-uniform response of the calorimetric cell. As a result, the double side read-out technique presented in this study provides a valuable way to improve the performance of calorimeters based on scintillators whose active volumes are characterized by high aspect ratio cells similar to those used in this study.« less

Large Eddy Simulation of Crashback in Marine Propulsors

NASA Astrophysics Data System (ADS)

Jang, Hyunchul

Crashback is an operating condition to quickly stop a propelled vehicle, where the propeller is rotated in the reverse direction to yield negative thrust. The crashback condition is dominated by the interaction of the free stream flow with the strong reverse flow. This interaction forms a highly unsteady vortex ring, which is a very prominent feature of crashback. Crashback causes highly unsteady loads and flow separation on the blade surface. The unsteady loads can cause propulsor blade damage, and also affect vehicle maneuverability. Crashback is therefore well known as one of the most challenging propeller states to analyze. This dissertation uses Large-Eddy Simulation (LES) to predict the highly unsteady flow field in crashback. A non-dissipative and robust finite volume method developed by Mahesh et al. (2004) for unstructured grids is applied to flow around marine propulsors. The LES equations are written in a rotating frame of reference. The objectives of this dissertation are: (1) to understand the flow physics of crashback in marine propulsors with and without a duct, (2) to develop a finite volume method for highly skewed meshes which usually occur in complex propulsor geometries, and (3) to develop a sliding interface method for simulations of rotor-stator propulsor on parallel platforms. LES is performed for an open propulsor in crashback and validated against experiments performed by Jessup et al. (2004). The LES results show good agreement with experiments. Effective pressures for thrust and side-force are introduced to more clearly understand the physical sources of thrust and side-force. Both thrust and side-force are seen to be mainly generated from the leading edge of the suction side of the propeller. This implies that thrust and side-force have the same source---the highly unsteady leading edge separation. Conditional averaging is performed to obtain quantitative information about the complex flow physics of high- or low-amplitude events. The events for thrust and side force show the same tendency. The conditional averages show that during high amplitude events, the vortex ring core is closer to the propeller blades, the reverse flow induced by the propeller rotation is lower, the forward flow is higher at the root of the blades, and leading and trailing edge flow separations are larger. The instantaneous flow field shows that during low amplitude events, the vortex ring is more axisymmetric and the stronger reverse flow induced by the vortex ring suppresses the forward flow so that flow separation on the blades is smaller. During high amplitude events, the vortex ring is less coherent and the weaker reverse flow cannot overcome the forward flow. The stronger forward flow makes flow separation on the blades larger. The effect of a duct on crashback is studied with LES. Thrust mostly arises from the blade surface, but most of side-force is generated from the duct surface. Both mean and RMS of pressure are much higher on inner surface of duct, especially near blade tips. This implies that side-force on the ducted propulsor is caused by the blade-duct interaction. Strong tip leakage flow is observed behind the suction side at the tip gap. The physical source of the tip leakage flow is seen to be the large pressure difference between pressure and suction sides. The conditional average for high amplitude event shows consistent results; the tip leakage flow and pressure difference are significantly higher when thrust and side-force are higher. A sliding interface method is developed to allow simulations of rotor-stator propulsor in crashback. The method allows relative rotations between different parts of the computational grid. Search algorithm for sliding elements, data structures for message passing, and accurate interpolation scheme at the sliding interface are developed for arbitrary shaped unstructured grids on parallel computing platforms. Preliminary simulations of open propulsor in crashback show reasonable performance.

Cyclic AMP-specific phosphodiesterase-4 as a target for the development of antidepressant drugs.

PubMed

Zhang, Han-Ting

2009-01-01

Phosphodiesterase-4 (PDE4), one of eleven PDE enzyme families, specifically catalyzes hydrolysis of cyclic AMP (cAMP); it has four subtypes (PDE4A-D) with at least 25 splice variants. PDE4 plays a critical role in the control of intracellular cAMP concentrations. PDE4 inhibitors produce antidepressant actions in both animals and humans via enhancement of cAMP signaling in the brain. However, their clinical utility has been hampered by side effects, in particular nausea and emesis. While there is still a long way to go before PDE4 inhibitors with high therapeutic indices are available for treatment of depressive disorders, important advances have been made in the development of PDE4 inhibitors as antidepressants. First, limited, but significant studies point to PDE4D as the major PDE4 subtype responsible for antidepressant-like effects of PDE4 inhibitors, although the role of PDE4A cannot be excluded. Second, PDE4D may contribute to emesis, the major side effect of PDE4 inhibitors. For this reason, identification of roles of PDE4D splice variants in mediating antidepressant activity is particularly important. Recent studies using small interfering RNAs (siRNAs) have demonstrated the feasibility to identify cellular functions of individual PDE4 variants. Third, mixed inhibitors of PDE4 and PDE7 or PDE4 and serotonin reuptake have been developed and may be potential antidepressants with minimized side effects. Finally, relatively selective inhibitors of one or two PDE4 subtypes have been synthesized using structure- and scaffold-based design. This review also discusses the relationship between PDE4 and antidepressant activity based on structures, brain distributions, and pharmacological properties of PDE4 and its isoforms.

Subjective experience and mental side-effects of antipsychotic treatment.

PubMed

Gerlach, J; Larsen, E B

1999-01-01

Many schizophrenic patients have a negative attitude towards antipsychotic drugs. This attitude is not only due to lack of insight into the disease, lack of recognition of the beneficial effects of the drugs, and to objective side-effects. The negative attitude is to a high degree due to mental side-effects and a sceptical opinion about antipsychotic medication in general. In a study of 53 chronic schizophrenic out-patients receiving maintenance depot antipsychotic treatment, we found that 60% were positive about the treatment, 32% were ambivalent and 8% had a negative attitude. Only 60% complained of side-effects, even though 94% had objective side-effects. Mental side-effects such as subjective akathisia, dysphoria and emotional indifference were most often observed by the patients, while hypokinesia and hyperkinesia were least noticed by them, but most often observed by the physician. No correlation was found between the patients' subjective assessment of their quality of life and the degree of psychosis and side-effects. With the new atypical antipsychotics this situation seems to be changing. These new drugs are primarily characterized by a lower level of motor extrapyramidal side-effects (EPS), and with fewer motor EPS, fewer mental EPS can be expected. In recent studies comparing the new antipsychotics with haloperidol, better effects have been observed with regard to negative symptoms and depression, and this may at least in part be a reflection of a lower level of mental side-effects of the atypical antipsychotics. This improved clinical profile of new antipsychotics is extremely valuable in the context of an integrated treatment in schizophrenia, consisting of early intervention, psychosocial rehabilitation and family/patient psycho-education.

Ayurveda for chemo-radiotherapy induced side effects in cancer patients.

PubMed

Metri, Kashinath; Bhargav, Hemant; Chowdhury, Praerna; Koka, Prasad S

2013-01-01

Chemotherapy drugs and radiotherapy are highly toxic and both damage adjacent healthy cells. Side effects may be acute (occurring within few weeks after therapy), intermediate or late (occurring months or years after the therapy). Some important side effects of chemotherapy are: nausea, vomiting, diarrhea, mucositis, alopecia, constipation etc; whereas radiation therapy though administered locally, can produce systemic side effects such as fatigue, anorexia, nausea, vomiting, alteration in the taste, sleep disturbance, headache, anemia, dry skin, constipation etc. Late complications of these therapies also include pharyngitis, esophagitis, laryngitis, persistent dysphagia, fatigue, hepatotoxicity, infertility and cognitive deficits. These arrays of side effects have a devastating effect on the quality of life of cancer survivors. Due to the inadequacy of most of the radio-protectors and chemo-protectors in controlling the side effects of conventional cancer therapy the complementary and alternative medicines have attracted the view of researchers and medical practitioners more recently. This review aims at providing a comprehensive management protocol of above mentioned chemo-radiotherapy induced side effects based on Ayurveda, which is an ancient system of traditional medicine practiced in Indian peninsula since 5000 BC. When the major side effects of chemo-radiotherapy are looked through an ayurvedic perspective, it appears that they are the manifestations of aggravated pitta dosha, especially under the group of disorders called Raktapitta (haemorrhage) or Raktadushti (vascular inflammation). Based on comprehensive review of ancient vedic literature and modern scientific evidences, ayurveda based interventions are put forth. This manuscript should help clinicians and people suffering from cancer to combat serious chemo-radiotherapy related side effects through simple but effective home-based ayurveda remedies. The remedies described are commonly available and safe. These simple ayurveda based solutions may act as an important adjuvant to chemo-radiotherapy and enhance the quality of life of cancer patients.

[Pharmacological approaches for correction of thyroid dysfunctions in diabetes mellitus].

PubMed

Shpakov, A O

2017-05-01

Thyroid diseases are closely associated with the development of types 1 and 2 diabetes mellitus (DM), and as a consequence, the development of effective approaches for their treatment is one of the urgent problems of endocrinology. Traditionally, thyroid hormones (TH) are used to correct functions of the thyroid system. However, they are characterized by many side effects, such as their negative effect on the cardiovascular system as well as the ability of TH to enhance insulin resistance and to disturb insulin-producing function of pancreas, exacerbating thereby diabetic pathology. Therefore, the analogues of TH, selective for certain types of TH receptors, that do not have these side effects, are being developed. The peptide and low-molecular weight regulators of thyroid-stimulating hormone receptor, which regulate the activity of the thyroid axis at the stage of TH synthesis and secretion in thyrocytes, are being created. Systemic and intranasal administration of insulin, metformin therapy and drugs with antioxidant activity are effective for the treatment of thyroid pathology in types 1 and 2 DM. In the review, the literature data and the results of own investigations on pharmacological approaches for the treatment and prevention of thyroid diseases in patients with types 1 and 2 DM are summarized and analyzed.

Single dose regorafenib-induced hypertensive crisis.

PubMed

Yilmaz, B; Kemal, Y; Teker, F; Kut, E; Demirag, G; Yucel, I

2014-06-01

Gastrointestinal stromal tumors (GISTs) are uncommon tumors of the gastrointestinal (GI) tract. Regorafenib is a new multikinase inhibitor and is approved for the treatment of GISTs in patients who develop resistance to imatinib and sunitinib. The most common drug-related adverse events with regorafenib are hypertension, hand-foot skin reactions, and diarrhea. Grade IV hypertensive side effect has never been reported after a single dose. In this report, we present a case of Grade IV hypertensive side effect (hypertensive crisis and seizure) after a single dose of regorafenib. A 54-year-old male normotensive GIST patient was admitted to the emergency department with seizure and encephalopathy after the first dosage of regorafenib. His blood pressure was 240/140 mmHg upon admission. After intensive treatment with nitrate and nitroprusside, his blood pressure returned to normal levels in five days. Regorafenib was discontinued, and he did not experience hypertension again. This paper reports the first case of Grade IV hypertension after the first dosage of regorafenib. We can suggest that hypertension is an idiosyncratic side effect unrelated to the dosage.

Selective serotonin reuptake inhibitor discontinuation: side effects and other factors that influence medication adherence.

PubMed

Goethe, John W; Woolley, Stephen B; Cardoni, Alex A; Woznicki, Brenda A; Piez, Deborah A

2007-10-01

Patients with major depression discontinue taking their antidepressants for many reasons. Although side effects are often cited as the reason for discontinuation, few prospective studies have addressed this question, and none has specifically examined discontinuation in patients with severe depression. Inpatients and outpatients treated with a selective serotonin reuptake inhibitor for major depressive disorder were identified after admission. Three months later, patients were contacted and interviewed to determine antidepressant usage and the side effects experienced, including when these were experienced and their severity. Between October 2001 and April 2003, 406 English- or Spanish-speaking patients aged 18 to 75 years were followed up. One in 4 patients discontinued the index antidepressant. Among specific side effects noted, only "change in weight" and "anxiety" were significant predictors of discontinuation after controlling for confounders. Experiencing 1 or more "extremely" bothersome side effects was associated with more than a doubling of the risk of discontinuation, but the presence of side effects and side effects less severe than "extremely" bothersome were not significant predictors. There were no differences among selective serotonin reuptake inhibitor antidepressants in either the presence/absence of side effects or in the discontinuation rates. The results suggest that the contribution of side effects to antidepressant discontinuation is more complex than previously suggested. Disparate findings from earlier studies may reflect aspects of study design, such as examining populations whose severity of depression varied widely or not controlling for important confounding factors. Future research should separately examine high-risk groups (or control for severity of depression) and carefully rule out other potential contributors to discontinuation.

Virtual identification of novel PPARα/γ dual agonists by scaffold hopping of saroglitazar.

PubMed

Jia, Wen-Qing; Jing, Zhi; Liu, Xin; Feng, Xiao-Yan; Liu, Ya-Ya; Wang, Shu-Qing; Xu, Wei-Ren; Liu, Jian-Wen; Cheng, Xian-Chao

2017-10-28

The thiazolidinedione class PPARγ agonists as antidiabetic agents are restricted in clinical use because of the side effects such as edema, weight gain, and heart failure. The single and selective agonism of PPARγ is the main cause of side effects. The multi-target cooperative PPARα/γ dual agonist development is a hot topic in the antidiabetic medicinal chemistry field. Saroglitazar is the first approved PPARα/γ dual agonist, available in India for the treatment of diabetic dyslipidemia. It got rid of these side effects. With the aim of finding more protent PPARα/γ dual agonists, the scaffold hopping was used to replace α-o phenylpropionic acid skeleton of saroglitazar with L-tyrosine skeleton. Then, the structural modification was carried out designing 72 compounds. Considering the importance of chirality, opposite configuration of 72 compounds was also studied. 12 compounds with better -cdocker energy were screened by molecular docking. Subsequently, the pharmacokinetic properties and toxicity evaluated by ADMET prediction, 11 of them showed better properties. Comp#L-17-1 and comp#L-3-1 were regarded as representatives to study the binding stability by molecular dynamics (MD) simulations. The MD simulation results of comp#L-17-1-PPARs (α, γ) and comp#L-3-1-PPARs (α, γ) provided structure reference for the research and development of novel PPARα/γ dual agonists.

Pharmacological profiling of zebrafish behavior using chemical and genetic classification of sleep-wake modifiers.

PubMed

Nishimura, Yuhei; Okabe, Shiko; Sasagawa, Shota; Murakami, Soichiro; Ashikawa, Yoshifumi; Yuge, Mizuki; Kawaguchi, Koki; Kawase, Reiko; Tanaka, Toshio

2015-01-01

Sleep-wake states are impaired in various neurological disorders. Impairment of sleep-wake states can be an early condition that exacerbates these disorders. Therefore, treating sleep-wake dysfunction may prevent or slow the development of these diseases. Although many gene products are likely to be involved in the sleep-wake disturbance, hypnotics and psychostimulants clinically used are limited in terms of their mode of action and are not without side effects. Therefore, there is a growing demand for developing new hypnotics and psychostimulants with high efficacy and few side effects. Toward this end, animal models are indispensable for use in genetic and chemical screens to identify sleep-wake modifiers. As a proof-of-concept study, we performed behavioral profiling of zebrafish treated with chemical and genetic sleep-wake modifiers. We were able to demonstrate that behavioral profiling of zebrafish treated with hypnotics or psychostimulants from 9 to 10 days post-fertilization was sufficient to identify drugs with specific modes of action. We were also able to identify behavioral endpoints distinguishing GABA-A modulators and hypocretin (hcrt) receptor antagonists and between sympathomimetic and non-sympathomimetic psychostimulants. This behavioral profiling can serve to identify genes related to sleep-wake disturbance associated with various neuropsychiatric diseases and novel therapeutic compounds for insomnia and excessive daytime sleep with fewer adverse side effects.

Effects of side lying on lung function in older individuals.

PubMed

Manning, F; Dean, E; Ross, J; Abboud, R T

1999-05-01

Body positioning exerts a strong effect on pulmonary function, but its effect on other components of the oxygen transport pathway are less well understood, especially the effects of side-lying positions. This study investigated the interrelationships between side-lying positions and indexes of lung function such as spirometry, alveolar diffusing capacity, and inhomogeneity of ventilation in older individuals. Nineteen nonsmoking subjects (mean age=62.8 years, SD=6.8, range=50-74) with no history of cardiac or pulmonary disease were tested over 2 sessions. The test positions were sitting and left side lying in one session and sitting and right side lying in the other session. In each of the positions, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), single-breath pulmonary diffusing capacity (DLCO/VA), and the slope of phase III (DN2%/L) of the single-breath nitrogen washout test to determine inhomogeneity of ventilation were measured. Compared with measurements obtained in the sitting position, FVC and FEV1 were decreased equally in the side-lying positions, but no change was observed in DLCO/VA or DN2%/L. Side-lying positions resulted in decreases in FVC and FEV1, which is consistent with the well-documented effects of the supine position. These findings further support the need for prescriptive rather than routine body positioning of patients with risks of cardiopulmonary compromise and the need to use upright positions in which lung volumes and capacities are maximized.

Renal thrombotic microangiopathy caused by interferon beta-1a treatment for multiple sclerosis

PubMed Central

Mahe, Julien; Meurette, Aurélie; Moreau, Anne; Vercel, Caroline; Jolliet, Pascale

2013-01-01

Interferon beta-1a is available as an immunomodulating agent for relapsing forms of multiple sclerosis. Common side effects include flu-like symptoms, asthenia, anorexia, and administration site reaction. Kidney disorders are rarely reported. In this study we describe the case of a woman who has been undergoing treatment with interferon beta-1a for multiple sclerosis for 5 years. She developed a hemolytic-uremic syndrome with intravascular hemolysis in a context of severe hypertension. A kidney biopsy showed a thrombotic microangiopathy. This observation highlights an uncommon side effect of long-term interferon beta-1a therapy. Pathophysiological mechanisms leading to this complication might be explained by the antiangiogenic activity of interferon. PMID:23950639

Effects and Side Effects of Flemish School Inspection

ERIC Educational Resources Information Center

Penninckx, Maarten; Vanhoof, Jan; De Maeyer, Sven; Van Petegem, Peter

2016-01-01

Despite the increased importance of school inspection in recent years, the current knowledge base does not provide a clear view on the effects and side effects of being inspected. More evidence is needed in more diverse educational contexts. This article responds to this need with a quantitative study on the effects and side effects of school…

Chemotherapy

MedlinePlus

... cells to get better. Because everyone's different, some people will have fewer side effects than others. Common side effects of chemo are ... infections easily. Medicines are available that can help people feel better if they have side effects from chemo. Doctors, nurses, and other members of ...

Detection of infectious haematopoietic necrosis virus in river water and demonstration of waterborne transmission

USGS Publications Warehouse

Mulcahy, D.; Pascho, R.J.; Jenes, C.K.

1983-01-01

In a study of the possible role of waterborne infectious haematopoietic necrosis virus in transmission of the disease among spawning sockeye salmon, Oncorhynchus nerka (Walbaum), both infection rates and virus titres were higher in fish held at high density in a side channel than in fish in the adjacent river. Virus was never isolated from river water, but was found in water from the side channel at levels ranging from 32.5 to 1600 plaque-forming units (p.f.u.)/ml. Uninfected yearling sockeye salmon held in a box in the side channel developed localized gill infections with IHN virus. The disease did not progress to the viscera until a threshold titre of about 105 p.f.u./g was reached in the gill. The effectiveness of the gill as a barrier limiting development of systemic infections means that waterborne IHN virus probably does not greatly increase the infection rate in a sockeye salmon population during spawning.

Detection of infectious hematopoietic necrosis virus in river water and demonstration of waterborne transmission

USGS Publications Warehouse

Mulcahy, Daniel M.; Pascho, Ronald J.; Jenes, C.K.

1983-01-01

In a study of the possible role of waterborne infectious haematopoietic necrosis virus in transmission of the disease among spawning sockeye salmon, Oncorhynchus nerka (Walbaum), both infection rates and virus titres were higher in fish held at high density in a side channel than in fish in the adjacent river. Virus was never isolated from river water, but was found in water from the side channel at levels ranging from 32.5 to 1600 plaque-forming units (p.f.u.)/ml. Uninfected yearling sockeye salmon held in a box in the side channel developed localized gill infections with IHN virus. The disease did not progress to the viscera until a threshold titre of about 105 p.f.u./g was reached in the gill. The effectiveness of the gill as a barrier limiting development of systemic infections means that waterborne IHN virus probably does not greatly increase the infection rate in a sockeye salmon population during spawning.

Electrorheological effect and electro-optical properties of side-on liquid crystalline polysiloxane in a nematic solvent.

PubMed

Kaneko, Kosuke; Oto, Kodai; Kawai, Toshiaki; Choi, Hyunseok; Kikuchi, Hirotsugu; Nakamura, Naotake

2013-08-26

The electrorheological (ER) effect and the electro-optical properties of a ''side-on'' liquid crystalline polysiloxane (PS) are investigated. A large ER effect is observed and the response to the shear stress of neat PS in the nematic phase is shown to be affected by the shear rate. PS is also mixed with a low-molar nematic liquid crystal (5CB) in order to improve the response behavior to the applied electric field. The rheological properties of such mixtures are highly dependent on the concentration of 5CB. The composites respond faster to the applied electric field and have improved electro-optical properties. This study offers a new perspective on the development of liquid crystal materials for the ER effect. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Building America Case Study: Trade-Friendly Retrofit Insulated Panels for Existing Buildings, Albany, New York

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

This project evaluated the effectiveness and affordability of integrating retrofit insulated panels into a re-siding project. The Partnership for Home Innovation (PHI) teamed with New York State Energy Research and Development Authority (NYSERDA), the Albany Housing Authority (AHA), and the New York State Weatherization Assistance Program (WAP) administered by Albany Community Action Partnership to demonstrate an energy retrofit and siding upgrade on a two-story, seven unit, multifamily building in Albany New York (CZ 5). The project focused on accomplishing three goals - doubling the existing wall thermal resistance (from approximately R-13 to a weighted average of R-27), reduction of buildingmore » air leakage, and completion of the retrofit within a budget where the additional cost for upgrading wall's thermal resistance is equal to the cost of the standard re-siding effort (i.e., the total cost of the energy efficient re-siding scope of work is not more than double the cost of the standard re-siding effort). Lessons learned from the project strongly indicate that the retrofit panel technology can be installed using common installation practices and with minimal training. Other lessons learned include limitation on the use of standard air sealing materials during cold weather installations and the need to develop better installation guidance for trades working with the level of tolerances that may be present in the existing structure. This technology demonstration showed that exterior retrofit panels provide a viable and reasonable option for the siding trades to increase market opportunities and achieve synergistic benefits for aesthetic upgrades to a building's exterior.« less

Application Side Casing on Open Deck RoRo to Improve Ship Stability

NASA Astrophysics Data System (ADS)

Hasanudin; K. A. P Utama, I.; Chen, Jeng-Horng

2018-03-01

RoRo is a vessel that can transport passengers, cargo, container and cars. Open Car Deck is favourite RoRo Vessel in developing countries due to its small GT, small tax and spacious car deck, but it has poor survival of stability. Many accident involve Open Car Deck RoRo which cause fatalities and victim. In order to ensure the safety of the ship, IMO had applied intact stability criteria IS Code 2008 which adapted from Rahola’s Research, but since 2008 IMO improved criteria become probabilistic damage stability SOLAS 2009. The RoRo type Open Car Deck has wide Breadth (B), small Draft (D) and small freeboard. It has difficulties to satisfy the ship’s stability criteria. Side Casings which has been applied in some RoRo have be known reduce freeboard or improve ship’s safety. In this paper investigated the effect side casings to survival of intact dan damage ship’s stability. Calculation has been conducted for four ships without, existing and full side casings. The investigation results shows that defect stability of Open Deck RoRo can be reduce with fitting side casing.

Predicting new drug indications from network analysis

NASA Astrophysics Data System (ADS)

Mohd Ali, Yousoff Effendy; Kwa, Kiam Heong; Ratnavelu, Kurunathan

This work adapts centrality measures commonly used in social network analysis to identify drugs with better positions in drug-side effect network and drug-indication network for the purpose of drug repositioning. Our basic hypothesis is that drugs having similar phenotypic profiles such as side effects may also share similar therapeutic properties based on related mechanism of action and vice versa. The networks were constructed from Side Effect Resource (SIDER) 4.1 which contains 1430 unique drugs with side effects and 1437 unique drugs with indications. Within the giant components of these networks, drugs were ranked based on their centrality scores whereby 18 prominent drugs from the drug-side effect network and 15 prominent drugs from the drug-indication network were identified. Indications and side effects of prominent drugs were deduced from the profiles of their neighbors in the networks and compared to existing clinical studies while an optimum threshold of similarity among drugs was sought for. The threshold can then be utilized for predicting indications and side effects of all drugs. Similarities of drugs were measured by the extent to which they share phenotypic profiles and neighbors. To improve the likelihood of accurate predictions, only profiles such as side effects of common or very common frequencies were considered. In summary, our work is an attempt to offer an alternative approach to drug repositioning using centrality measures commonly used for analyzing social networks.

Lipo-PGE1, a new lipid-encapsulated preparation of prostaglandin E1: placebo-and prostaglandin E1-controlled multicenter trials in patients with diabetic neuropathy and leg ulcers.

PubMed

Toyota, T; Hirata, Y; Ikeda, Y; Matsuoka, K; Sakuma, A; Mizushima, Y

1993-11-01

Several clinical trials have shown that prostaglandin E1 (PGE1) is effective in treating peripheral occlusive vascular disease, but not definitely for diabetic neuropathy. We developed a new preparation of PGE1 incorporated in lipid microspheres (lipo-PGE1) that was designed to accumulate at vascular lesions. The effect of lipo-PGE1 (10 micrograms/day) was compared with placebo and the normal dose of a free PGE1 preparation (PGE1-CD, 40 micrograms/day) in two studies (double-blind and well-controlled) which enrolled 364 diabetic patients with neuropathy and/or leg ulcers. The drugs were given intravenously (bolus or drip infusion) for 4 weeks. Clinical improvement was noted in 61.6% of the lipo-PGE1 group and 30.0% of the placebo group in Trial 1 (p < 0.01), while the figures were 58.3% in the lipo-PGE1 group and 37.1% in the PGE1-CD group in Trial 2 (p < 0.01). Leg ulcers became smaller in the lipo-PGE1 groups in both trials (p < 0.01). In Trial 2, motor conduction velocity improved in the lipo-PGE1 group (p = 0.016). Side effects occurred in few patients receiving lipo-PGE1 or placebo, but more patients developed local side effects in the PGE1-CD group (p < 0.01). Thus, bolus intravenous injection of lipo-PGE1 improved diabetic neuropathy and leg ulcers with minimal side effects.

Drug safety evaluation of dronedarone in atrial fibrillation.

PubMed

De Ferrari, Gaetano M; Dusi, Veronica

2012-11-01

Dronedarone was developed with the intent of replicating the antiarrhythmic effects of amiodarone, while minimizing its side effects. Side effects reported in eight randomized clinical trials are discussed, comparing dronedarone and placebo (DAFNE, EURIDIS, ADONIS, ERATO, ANDROMEDA, ATHENA, PALLAS, total number of patients treated with dronedarone 5347), or dronedarone and amiodarone (DIONYSOS, total number of patients treated with dronedarone 249). The results of the first trials, including ATHENA, set high expectations by suggesting that dronedarone may decrease the risk of hospitalization (and even cardiovascular mortality) among patients with paroxysmal and persistent atrial fibrillation (AF), and that it could be regarded as an easy-to-use drug that could be prescribed by general practitioners; unfortunately, dronedarone has not met these expectations. Dronedarone may increase mortality and heart failure hospitalization in patients with advanced NYHA class and in patients with permanent AF, preventing its use in these settings. In addition to gastrointestinal side effects that may lead to discontinuation in 5 - 10% of patients, dronedarone may induce very rare but severe liver and lung toxicity. Despite these limitations and its relatively limited antiarrhythmic potency, dronedarone may still be a useful drug for well-selected patients.

The impact of tamoxifen brand switch on side effects and patient compliance in hormone receptor positive breast cancer patients.

PubMed

Zeidan, B; Anderson, K; Peiris, L; Rainsbury, D; Laws, S

2016-10-01

In 2006 Nolvadex was discontinued and replaced by a variety of alternative generic tamoxifen brands for the adjuvant treatment of breast cancer. Anecdotally, patients are switching brands and taking alternative medications to reduce treatment related symptoms. Nevertheless, more severe side effects may equate to better relapse prevention. This study evaluates generic tamoxifen adherence and its correlation with side effects and brand switch. Consecutive disease free ER positive patients (stage I-III) were invited to respond to a questionnaire. 165 of 327 questionnaires were returned (50% response). Pearson's Chi Square test was used for data analysis. 63 patients (38%) reported a switch between generic tamoxifen. 59% of all patients experienced side effects associated with tamoxifen treatment of which 53% were severe. Patients experiencing differential symptoms dependent on tamoxifen brand reported more severe side effects (p = 0.02). Non-prescribed supplements were taken by 42% of all patients with no significant improvement in climacteric symptoms (p = 0.05). The concomitant use of SSRIs appeared to have no effect on symptoms. A significant number of patients considered discontinuing tamoxifen because of the side effects (p = 0.001), yet this did not translate into discontinuation or non-adherence (p = 0.8 and 0.08 respectively). Severe tamoxifen side effects are commonly experienced by breast cancer patients and can be significantly altered by change in tamoxifen brand. Most patients will continue to take tamoxifen, despite side effects to avoid cancer relapse. Supplementation and antidepressants did not improve tamoxifen related side effects in our cohort. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Investigating Climate Compatible Development Outcomes and their Implications for Distributive Justice: Evidence from Malawi

NASA Astrophysics Data System (ADS)

Wood, Benjamin T.; Quinn, Claire H.; Stringer, Lindsay C.; Dougill, Andrew J.

2017-09-01

Governments and donors are investing in climate compatible development in order to reduce climate and development vulnerabilities. However, the rate at which climate compatible development is being operationalised has outpaced academic enquiry into the concept. Interventions aiming to achieve climate compatible development "wins" (for development, mitigation, adaptation) can also create negative side-effects. Moreover, benefits and negative side-effects may differ across time and space and have diverse consequences for individuals and groups. Assessments of the full range of outcomes created by climate compatible development projects and their implications for distributive justice are scarce. This article develops a framework using a systematic literature review that enables holistic climate compatible development outcome evaluation over seven parameters identified. Thereafter, we explore the outcomes of two donor-funded projects that pursue climate compatible development triple-wins in Malawi using this framework. Household surveys, semi-structured interviews and documentary material are analysed. Results reveal that uneven outcomes are experienced between stakeholder groups and change over time. Although climate compatible development triple-wins can be achieved through projects, they do not represent the full range of outcomes. Ecosystem—and community-based activities are becoming popularised as approaches for achieving climate compatible development goals. However, findings suggest that a strengthened evidence base is required to ensure that these approaches are able to meet climate compatible development goals and further distributive justice.

Selecting Random Distributed Elements for HIFU using Genetic Algorithm

NASA Astrophysics Data System (ADS)

Zhou, Yufeng

2011-09-01

As an effective and noninvasive therapeutic modality for tumor treatment, high-intensity focused ultrasound (HIFU) has attracted attention from both physicians and patients. New generations of HIFU systems with the ability to electrically steer the HIFU focus using phased array transducers have been under development. The presence of side and grating lobes may cause undesired thermal accumulation at the interface of the coupling medium (i.e. water) and skin, or in the intervening tissue. Although sparse randomly distributed piston elements could reduce the amplitude of grating lobes, there are theoretically no grating lobes with the use of concave elements in the new phased array HIFU. A new HIFU transmission strategy is proposed in this study, firing a number of but not all elements for a certain period and then changing to another group for the next firing sequence. The advantages are: 1) the asymmetric position of active elements may reduce the side lobes, and 2) each element has some resting time during the entire HIFU ablation (up to several hours for some clinical applications) so that the decreasing efficiency of the transducer due to thermal accumulation is minimized. Genetic algorithm was used for selecting randomly distributed elements in a HIFU array. Amplitudes of the first side lobes at the focal plane were used as the fitness value in the optimization. Overall, it is suggested that the proposed new strategy could reduce the side lobe and the consequent side-effects, and the genetic algorithm is effective in selecting those randomly distributed elements in a HIFU array.

Acute hemifacial dystonia possibly induced by clebopride.

PubMed

Bosco, Domenico; Plastino, Massimiliano; Marcello, Maria Giovanna; Mungari, Pasquale; Fava, Antonietta

2009-01-01

Dystonic reactions produce twisting and repetitive movements or abnormal posturing. Severe dystonic reactions have been shown to occur in concert with numerous medications. This report details the case of a patient who developed hemifacial dystonia as acute side reaction from administration of clebopride for dyspeptic prophylaxis. When the drug was immediately stopped, the dystonic posture disappeared completely within 2 weeks. The use of clebopride may be associated with not only a reversible or persistent parkinsonism syndrome but also hemifacial dystonia; therefore, attention must be drawn to this possible side effect.

Statin Side Effects: Weigh the Benefits and Risks

MedlinePlus

... your skin or eyes. Increased blood sugar or type 2 diabetes It's possible your blood sugar (blood glucose) level ... take a statin, which may lead to developing type 2 diabetes. The risk is small but important enough that ...

The Association of Long-term Treatment-related Side Effects With Cancer-specific and General Quality of Life Among Prostate Cancer Survivors

PubMed Central

Davis, Kimberly M.; Kelly, Scott P.; Luta, George; Tomko, Catherine; Miller, Anthony B.; Taylor, Kathryn L.

2018-01-01

OBJECTIVE To examine the association between treatment-related side effects and cancer-specific and general quality of life (QOL) among long-term prostate cancer survivors. MATERIALS AND METHODS Within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we conducted telephone interviews with prostate cancer survivors (N = 518) who were 5-10 years after diagnosis. We assessed demographic and clinical information, sexual, urinary, and bowel treatment-related side effects (Expanded Prostate Cancer Index Composite), cancer-specific QOL (Functional Assessment of Cancer Therapy—total score), and general QOL (the Medical Outcomes Study Short Form 12’s physical and mental subscales). RESULTS Participants were aged 74.6 years on average, primarily White (88.4%), and married (81.7%). Pearson correlation coefficients between the 3 treatment-related side effect domains (urinary, sexual, and bowel) and QOL ranged between 0.14 and 0.42 (P <.0001). Multivariable linear regression analyses revealed that poorer urinary and sexual functioning and greater bowel side effects were independently associated with poorer cancer-specific QOL (P <.0001). Bowel and urinary functions were also associated with poorer general QOL on the Medical Outcomes Study Short Form 12’s physical component summary and mental component summary (P <.05). Bowel side effects demonstrated the strongest association with all QOL outcomes. CONCLUSION Treatment-related side effects persisted for up to 10 years after diagnosis and continued to be associated with men’s QOL. These results suggest that each of the treatment-related side effects was independently associated with cancer-specific QOL. Compared with the other Expanded Prostate Cancer Index Composite domains, bowel side effects had the strongest association with cancer-specific and general QOL. These associations emphasize the tremendous impact that bowel side effects continue to have for men many years after their initial diagnosis. PMID:24975711

Consumer confusion between prescription drug precautions and side effects.

PubMed

Amoozegar, Jacqueline B; Rupert, Douglas J; Sullivan, Helen W; O'Donoghue, Amie C

2017-06-01

Multiple studies have identified consumers' difficulty correctly interpreting risk information provided about prescription drugs, whether in printed format or online. This study's purpose was to explore whether consumers can distinguish between prescription drug precautions and side effects presented on brand-name drug websites. Participants (n=873) viewed fictitious drug websites that presented both precautions and side effects for one of four drugs, and they completed a survey assessing recall and comprehension. We coded open-ended recall data to identify whether drug precautions were mentioned and, if so, how they were interpreted. Approximately 15% of participants mentioned at least one drug precaution. The majority (59.7%) misinterpreted precautions as potential side effects. Participants who misinterpreted precautions rated the drugs as significantly more likely to cause side effects than participants who accurately interpreted the precautions. Age, education, literacy, and other factors did not appear to predict precaution interpretation. At least some consumers are likely to interpret precautions on drug websites as potential side effects, which might affect consumer preferences, treatment decisions, and medication safety. Healthcare providers should be aware of this potential confusion, assess patients' understanding of precautions and potential side effects, and address any misunderstandings. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Fast image decompression for telebrowsing of images

NASA Technical Reports Server (NTRS)

Miaou, Shaou-Gang; Tou, Julius T.

1993-01-01

Progressive image transmission (PIT) is often used to reduce the transmission time of an image telebrowsing system. A side effect of the PIT is the increase of computational complexity at the viewer's site. This effect is more serious in transform domain techniques than in other techniques. Recent attempts to reduce the side effect are futile as they create another side effect, namely, the discontinuous and unpleasant image build-up. Based on a practical assumption that image blocks to be inverse transformed are generally sparse, this paper presents a method to minimize both side effects simultaneously.

A potential role for adjunctive vitamin D therapy in the management of weight gain and metabolic side effects of second-generation antipsychotics

PubMed Central

Nwosu, Benjamin U.; Meltzer, Bruce; Maranda, Louise; Ciccarelli, Carol; Reynolds, Daniel; Curtis, Laura; King, Jean; Frazier, Jean A.; Lee, Mary M.

2014-01-01

Second-generation antipsychotic (SGA) medications introduced about 20 years ago are increasingly used to treat psychiatric illnesses in children and adolescents. There has been a five-fold increase in the use of these medications in U.S. children and adolescents in the past decade. However, there has also been a parallel rise in the incidence of side effects associated with these medications, such as obesity, dyslipidemia, insulin resistance, and diabetes mellitus. Despite the severity of these complications and their financial impact on the national healthcare budget, there is neither a clear understanding of the mechanisms contributing to these side effects nor the best ways to address them. Studies that examined lifestyle modification and pharmaceutical agents have yielded mixed results. Therefore, clinical studies using agents, such as vitamin D, which are inexpensive, readily available, with low side effects profile, and have mechanisms to counteract the metabolic side effects of SGA agents, are warranted. Vitamin D is a prohormone with skeletal and extraskeletal properties that could potentially reduce the severity of these metabolic side effects. Its role as an adjunctive therapy for the management of metabolic side effects of SGA agents has not been adequately studied. Effective strategies to curb these side effects will improve the overall health of youths with psychiatric illnesses who receive SGAs. Herein we present a pilot study on the use of vitamin D in patients on treatment with SGAs. PMID:22145446

Choreatic Side Effects of Deep Brain Stimulation of the Anteromedial Subthalamic Nucleus for Treatment-Resistant Obsessive-Compulsive disorder.

PubMed

Mulders, Anne E P; Leentjens, Albert F G; Schruers, Koen; Duits, Annelien; Ackermans, Linda; Temel, Yasin

2017-08-01

Patients with treatment-resistant obsessive-compulsive disorder (OCD) are potential candidates for deep brain stimulation (DBS). The anteromedial subthalamic nucleus (STN) is among the most commonly used targets for DBS in OCD. We present a patient with a 30-year history of treatment-resistant OCD who underwent anteromedial STN-DBS. Despite a clear mood-enhancing effect, stimulation caused motor side effects, including bilateral hyperkinesia, dyskinesias, and sudden large amplitude choreatic movements of arms and legs when stimulating at voltages greater than approximately 1.5 V. DBS at lower amplitudes and at other contact points failed to result in a significant reduction of obsessions and compulsions without inducing motor side effects. Because of this limitation in programming options, we decided to reoperate and target the ventral capsule/ventral striatum (VC/VS), which resulted in a substantial reduction in key obsessive and compulsive symptoms without serious side effects. Choreatic movements and hemiballismus have previously been linked to STN dysfunction and have been incidentally reported as side effects of DBS of the dorsolateral STN in Parkinson disease (PD). However, in PD, these side effects were usually transient, and they rarely interfered with DBS programming. In our patient, the motor side effects were persistent, and they made optimal DBS programming impossible. To our knowledge, such severe and persistent motor side effects have not been described previously for anteromedial STN-DBS. Copyright © 2017 Elsevier Inc. All rights reserved.

The Zero-vision: potential side effects of communicating health perfection and zero risk.

PubMed

Fugelli, Per

2006-03-01

Public health education may have harmful side effects: generate fear, give rise to healthism and contribute to a medical sorting society. To prevent these adverse reactions a new deal for public health communication is presented. It is commended to move public health from omnipotence to moderation, from life style to living conditions, from risk to the bright sides of health, from statistical clone to the holy individual. Furthermore public health communication ought to include uncertainty as authoritarian truth mongering erodes trust. The public health educator must convey compassion and dedication. Rational techno-info is not sufficient. The last golden rule for a new public health is to respect the people. The people are not an inferior mass subjected to basic instincts and irrational fears. Common sense and lay experiences may contribute to the wise management of risk. Therefore public health should develop a people-centered method, recognizing people's own values, perceptions and potentials for preventing disease and promoting health.

Land development under regulation: comparison between the east and the west sides of the Cascade Range in Oregon, Washington, and California.

Treesearch

Seong-Hoo Cho; JunJie Wu; Ralph J. Alig

2005-01-01

We compare how socioeconomic factors, physical landscape, profit uncertainty, and local land use policies have affected land development on the east and west sides of the Cascade Range in Oregon, Washington, and California. It is found that the west side has more actively planned and regulated land use than the east side. Consequently, the more intense land use...

Measurement of Side Effects of Drugs

PubMed Central

Huskisson, E. C.; Wojtulewski, J. A.

1974-01-01

In a clinical trial of two antirheumatic agents two methods of collection of side effects were used, one with and the other without a check list of possible symptoms. Findings suggested that the use of a check list interfered with the collection of side effects. Known side effects of aspirin—tinnitus, deafness, and gastrointestinal disturbance—were more efficiently shown and symptoms not included in the check list were more likely to be reported when a check list was not used. PMID:4853118

Comparison of hair removal efficacy and side effect of neodymium:Yttrium-aluminum-garnet laser and intense pulsed light systems (18-month follow-up).

PubMed

Szima, Georgina Zita; Janka, Eszter Anna; Kovács, Anikó; Bortély, Blanka; Bodnár, Edina; Sawhney, Irina; Szabó, Éva; Remenyik, Éva

2017-06-01

Photothermal destruction of hair shaft melanin with intense pulsed light (IPL) and neodymium:yttrium-aluminum-garnet (Nd:YAG) laser has become an effective treatment of hair removal. Our aim was to compare efficacy, satisfactory levels, safety, and side effects of Nd:YAG and IPL in hair reduction. This was a prospective randomized intrapatient, right-left, assessor-blinded comparison of Nd:YAG vs IPL. There were 38 volunteers recruited. Seven sessions were performed. Hair count, efficacy, and side effects were compared before and after each treatment and 6 months after the last treatment. In respect of 12 volunteers, we have examined the reduction in hair after 18 months. Initially, there was no significant difference between the numbers of hair follicles. There was significant hair reduction after each treatment on the Nd:YAG-treated side. The hair reduction became significant after the third treatment with IPL. Comparison of the efficacy of the two devices on each visits showed no significant difference. There was statistically lower pain score on the IPL-treated side and statistically higher erythema, burning sensation, and edema on the Nd:YAG-treated side. Statistically lower side effect score was observed on the IPL-treated side. Eight months after the last treatment, there was significant hair reduction both on the Nd:YAG and on the IPL-treated side, and there was no difference between the efficacy. The patient satisfaction scores were higher with the IPL. Unwanted hair can be reduced by both systems safely and effectively; however, IPL has less side effects and higher satisfaction scores. © 2017 Wiley Periodicals, Inc.

Side effects during subcutaneous immunotherapy in children with allergic diseases.

PubMed

Tophof, Max A; Hermanns, Anne; Adelt, Thomas; Eberle, Peter; Gronke, Christine; Friedrichs, Frank; Knecht, Roland; Mönter, Ernst; Schöpfer, Helmut; Schwerk, Nicolaus; Steinbach, Jörg; Umpfenbach, Hans-Ulrich; Weißhaar, Christian; Wilmsmeyer, Brigitte; Bufe, Albrecht

2018-05-01

Allergen-specific immunotherapy is the only causal form of therapy for IgE-mediated allergic diseases. Subcutaneous immunotherapy (SCIT) is considered safe and well tolerated in adults, yet there is less evidence of safety in the pediatric population. A non-interventional prospective observing longitudinal study was carried out to determine the incidence of local and systemic side effects by SCIT, routinely performed in pediatric patients. A total of 581 pediatric patients were observed in 18 study centers between March 2012 and October 2014, recording 8640 treatments and 10 015 injections. A total of 54.6% of the patients experienced immediate local side effects at least once; delayed local side effects were seen in 56.1%. Immediate systemic adverse reactions occurred in 2.2% of patients; 7.4% experienced delayed systemic side effects. However, severe systemic side effects (grade III in the classification of Ring and Messmer) were seen in 0.03% of all treatments, all appearing within 30 minutes after the injections. No grade IV reactions were observed. In addition, many potential risk factors were investigated, yet only a few were found to be associated with the occurrence of side effects. Subcutaneous immunotherapy is a safe form of therapy in pediatric patients, with similar rates of local side effects compared to adult patients and low rates of severe systemic side effects. However, local and systemic reactions occurring later than 30 minutes after injection were observed more often than expected, which makes it essential to be attentive on behalf of pediatricians, patients, and parents. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Specific expectancies are associated with symptomatic outcomes and side effect burden in a trial of chamomile extract for Generalized Anxiety Disorder

PubMed Central

Keefe, John R.; Amsterdam, Jay; Li, Qing S; Soeller, Irene; DeRubeis, Robert; Mao, Jun J

2017-01-01

Objective Patient expectancies are hypothesized to contribute to the efficacy and side effects of psychiatric treatments, but little research has investigated this hypothesis in the context of psychopharmacological therapies for anxiety. We prospectively investigated whether expectancies predicted efficacy and adverse events in oral therapy for Generalized Anxiety Disorder (GAD), controlling for confounding patient characteristics correlating with outcomes. Methods Expectancies regarding treatment efficacy and side effects were assessed at baseline of an eight week open-label phase of a trial of chamomile for Generalized Anxiety Disorder (GAD). The primary outcome was patient-reported GAD-7 scores, with clinical response and treatment-emergent side-effects as secondary outcomes. Expectancies were used to predict symptomatic and side-effect outcomes. Results Very few baseline patient characteristics predicted either type of expectancy. Controlling for a patient’s predicted recovery based on their baseline characteristics, higher efficacy expectancies at baseline predicted greater change on the GAD-7 (adjusted β = −0.19, p = 0.011). Efficacy expectancies also predicted a higher likelihood of attaining clinical response (adjusted odds ratio = 1.69, p = 0.002). Patients with higher side effect expectancies reported more side effects (adjusted log expected count = 0.26, p = 0.038). Efficacy expectancies were unrelated to side effect reports (log expected count = −0.05, p = 0.680), and side effect expectancies were unrelated to treatment efficacy (β = 0.08, p = 0.306). Conclusions Patients entering chamomile treatment for GAD with more favorable self-generated expectancies for the treatment experience greater improvement and fewer adverse events. Aligning patient expectancies with treatment selections may optimize outcomes. PMID:27716513

[Extrapyramidal side-effects: avoidance, diagnosis and treatment].

PubMed

Fleischhacker, W Wolfgang; Widschwendter, Christian

2005-04-01

Acute extrapyramidal side-effects (EPS) are a common phenomenon of treatment with antipsychotics. They are associated with a substantial reduction of the patient's quality of life and of compliance with the treatment. This article gives an overview of the different forms of EPS. It outlines strategies to avoid these side-effects and discusses problems in diagnosis and treatment. In comparison to conventional compounds, the clearest advantage of new generation antipsychotics is a reduced risk of the occurrence of extrapyramidal side-effects (EPS). Many studies have found that newer antipsychotics have a lesser propensity to causes EPS. Nevertheless, there are some conflicting results on this topic. This article discusses some of these results and sheds light on methodological problems in the evaluation of side-effects of antipsychotic treatment.

Chemosensitization as a Means to Augment Commercial Antifungal Agents

PubMed Central

Campbell, Bruce C.; Chan, Kathleen L.; Kim, Jong H.

2012-01-01

Antimycotic chemosensitization and its mode of action are of growing interest. Currently, use of antifungal agents in agriculture and medicine has a number of obstacles. Foremost of these is development of resistance or cross-resistance to one or more antifungal agents. The generally high expense and negative impact, or side effects, associated with antifungal agents are two further issues of concern. Collectively, these problems are exacerbated by efforts to control resistant strains, which can evolve into a treadmill of higher dosages for longer periods. This cycle in turn, inflates cost of treatment, dramatically. A further problem is stagnation in development of new and effective antifungal agents, especially for treatment of human mycoses. Efforts to overcome some of these issues have involved using combinations of available antimycotics (e.g., combination therapy for invasive mycoses). However, this approach has had inconsistent success and is often associated with a marked increase in negative side effects. Chemosensitization by natural compounds to increase effectiveness of commercial antimycotics is a somewhat new approach to dealing with the aforementioned problems. The potential for safe natural products to improve antifungal activity has been observed for over three decades. Chemosensitizing agents possess antifungal activity, but at insufficient levels to serve as antimycotics, alone. Their main function is to disrupt fungal stress response, destabilize the structural integrity of cellular and vacuolar membranes or stimulate production of reactive oxygen species, augmenting oxidative stress and apoptosis. Use of safe chemosensitizing agents has potential benefit to both agriculture and medicine. When co-applied with a commercial antifungal agent, an additive or synergistic interaction may occur, augmenting antifungal efficacy. This augmentation, in turn, lowers effective dosages, costs, negative side effects and, in some cases, countermands resistance. PMID:22393330

Motion of spin label side chains in cellular retinol-binding protein: correlation with structure and nearest-neighbor interactions in an antiparallel beta-sheet.

PubMed

Lietzow, Michael A; Hubbell, Wayne L

2004-03-23

A goal in the development of site-directed spin labeling in proteins is to correlate the motion of a nitroxide side chain with local structure, interactions, and dynamics. Significant progress toward this goal has been made using alpha-helical proteins of known structure, and the present study is the first step in a similar exploration of a beta-sheet protein, cellular retinol-binding protein (CRBP). Nitroxide side chains were introduced along both interior and edge strands. At sites in interior strands, the side-chain motion is strongly influenced by interactions with side chains of neighboring strands, giving rise to a rich variety of dynamic modes (weakly ordered, strongly ordered, immobilized) and complex electron paramagnetic resonance spectra that are modulated by strand twist. The interactions giving rise to the dynamic modes are explored using mutagenesis, and the results demonstrate the particular importance of the non-hydrogen-bonded neighbor residue in giving rise to highly ordered states. Along edge strands of the beta-sheet, the motion of the side chain is simple and weakly ordered, resembling that at solvent-exposed surfaces of an alpha-helix. A simple working model is proposed that can account for the wide variety of dynamic modes encountered. Collectively, the results suggest that the nitroxide side chain is an effective probe of side-chain interactions, and that site-directed spin labeling should be a powerful means of monitoring conformational changes that involve changes in beta-sheet topology.

Airport emissions quantification: Impacts of electrification. Final report

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

Geba, V.

1998-07-01

Four airports were assessed to demonstrate that electrification of economically viable air- and land-side vehicles and equipment can significantly reduce total airport emissions. Assessments were made using the FAA`s Emissions and Dispersion Modeling System and EPRI Airport Electrification Project data. Development and implementation of cost-effective airport emissions reduction strategies can be complex, requiring successful collaboration of local, state, and federal regulatory agencies with airport authorities. The methodology developed in this study helps to simplify this task. The objectives of this study were: to develop a methodology to quantify annual emissions at US airports from all sources--aircraft, vehicles, and infrastructure; andmore » to demonstrate that electrification of economically viable air- and land-side vehicles and equipment can significantly reduce total airport emissions on-site, even when allowing for emissions from the generation of electricity.« less

Oral health impacts of medications used to treat mental illness.

PubMed

Cockburn, N; Pradhan, A; Taing, M W; Kisely, S; Ford, P J

2017-12-01

Many psychotropic medications affect oral health. This review identified oral side effects for antidepressant, antipsychotic, anticonvulsant, antianxiety and sedative drugs that are recommended in Australia for the management of common mental illnesses and provides recommendations to manage these side-effects. The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat common mental health conditions. For each medication, the generic name, class, and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (eMIMs) and UpToDate databases. Meyler's Side Effect of Drugs Encyclopaedia was used to identify additional oral adverse reactions to these medications. Fifty-seven drugs were identified: 23 antidepressants, 22 antipsychotics or mood stabilisers, and 12 anxiolytic or sedative medications. Xerostomia (91%) the most commonly reported side effect among all classes of medications of the 28 identified symptoms. Other commonly reported adverse effects included dysguesia (65%) for antidepressants, and tardive dyskinesia (94%) or increased salivation (78%) for antipsychotic medications. While xerostomia has often been reported as a common adverse effect of psychotropic drugs, this review has identified additional side effects including dysguesia from antidepressants and tardive dyskinesia and increased salivation from antipsychotics. Clinicians should consider oral consequences of psychotropic medication in addition to other side-effects when prescribing. For antidepressants, this would mean choosing duloxetine, agomelatine and any of the serotonin re-uptake inhibitors except sertraline. In the case of antipsychotics and mood stabilisers, atypical agents have less oral side effects than older alternatives. Copyright © 2017 Elsevier B.V. All rights reserved.

Surgical scheduling: a lean approach to process improvement.

PubMed

Simon, Ross William; Canacari, Elena G

2014-01-01

A large teaching hospital in the northeast United States had an inefficient, paper-based process for scheduling orthopedic surgery that caused delays and contributed to site/side discrepancies. The hospital's leaders formed a team with the goals of developing a safe, effective, patient-centered, timely, efficient, and accurate orthopedic scheduling process; smoothing the schedule so that block time was allocated more evenly; and ensuring correct site/side. Under the resulting process, real-time patient information is entered into a database during the patient's preoperative visit in the surgeon's office. The team found the new process reduced the occurrence of site/side discrepancies to zero, reduced instances of changing the sequence of orthopedic procedures by 70%, and increased patient satisfaction. Copyright © 2014 AORN, Inc. Published by Elsevier Inc. All rights reserved.

Glutamate Receptors in the Central Nucleus of the Amygdala Mediate Cisplatin-Induced Malaise and Energy Balance Dysregulation through Direct Hindbrain Projections

PubMed Central

Alhadeff, Amber L.; Holland, Ruby A.; Nelson, Alexandra; Grill, Harvey J.

2015-01-01

Cisplatin chemotherapy is used commonly to treat a variety of cancers despite severe side effects such as nausea, vomiting, and anorexia that compromise quality of life and limit treatment adherence. The neural mechanisms mediating these side effects remain elusive despite decades of clinical use. Recent data highlight the dorsal vagal complex (DVC), lateral parabrachial nucleus (lPBN), and central nucleus of the amygdala (CeA) as potential sites of action in mediating the side effects of cisplatin. Here, results from immunohistochemical studies in rats identified a population of cisplatin-activated DVC neurons that project to the lPBN and a population of cisplatin-activated lPBN calcitonin gene-related peptide (CGRP, a marker for glutamatergic neurons in the lPBN) neurons that project to the CeA, outlining a neuroanatomical circuit that is activated by cisplatin. CeA gene expressions of AMPA and NMDA glutamate receptor subunits were markedly increased after cisplatin treatment, suggesting that CeA glutamate receptor signaling plays a role in mediating cisplatin side effects. Consistent with gene expression results, behavioral/pharmacological data showed that CeA AMPA/kainate receptor blockade attenuates cisplatin-induced pica (a proxy for nausea/behavioral malaise in nonvomiting laboratory rodents) and that CeA NMDA receptor blockade attenuates cisplatin-induced anorexia and body weight loss in addition to pica, demonstrating that glutamate receptor signaling in the CeA is critical for the energy balance dysregulation caused by cisplatin treatment. Together, these data highlight a novel circuit and CGRP/glutamatergic mechanism through which cisplatin-induced malaise and energy balance dysregulation are mediated. SIGNIFICANCE STATEMENT To treat cancer effectively, patients must follow prescribed chemotherapy treatments without interruption, yet most cancer treatments produce side effects that devastate quality of life (e.g., nausea, vomiting, anorexia, weight loss). Although hundreds of thousands of patients undergo chemotherapies each year, the neural mechanisms mediating their side effects are unknown. The current data outline a neural circuit activated by cisplatin chemotherapy and demonstrate that glutamate signaling in the amygdala, arising from hindbrain projections, is required for the full expression of cisplatin-induced malaise, anorexia, and body weight loss. Together, these data help to characterize the neural circuits and neurotransmitters mediating chemotherapy-induced energy balance dysregulation, which will ultimately provide an opportunity for the development of well tolerated cancer and anti-emetic treatments. PMID:26245970

The Bmp signaling pathway regulates development of left-right asymmetry in amphioxus.

PubMed

Soukup, Vladimir; Kozmik, Zbynek

2018-02-01

Establishment of asymmetry along the left-right (LR) body axis in vertebrates requires interplay between Nodal and Bmp signaling pathways. In the basal chordate amphioxus, the left-sided activity of the Nodal signaling has been attributed to the asymmetric morphogenesis of paraxial structures and pharyngeal organs, however the role of Bmp signaling in LR asymmetry establishment has not been addressed to date. Here, we show that Bmp signaling is necessary for the development of LR asymmetric morphogenesis of amphioxus larvae through regulation of Nodal signaling. Loss of Bmp signaling results in loss of the left-sided expression of Nodal, Gdf1/3, Lefty and Pitx and in gain of ectopic expression of Cerberus on the left side. As a consequence, the larvae display loss of the offset arrangement of axial structures, loss of the left-sided pharyngeal organs including the mouth, and ectopic development of the right-sided organs on the left side. Bmp inhibition thus phenocopies inhibition of Nodal signaling and results in the right isomerism. We conclude that Bmp and Nodal pathways act in concert to specify the left side and that Bmp signaling plays a fundamental role during LR development in amphioxus. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of present and past antipsychotic side effects on attitude toward typical antipsychotic treatment and adherence.

PubMed

Lambert, M; Conus, P; Eide, P; Mass, R; Karow, A; Moritz, S; Golks, D; Naber, D

2004-11-01

(1) determine which antipsychotic side effects (SE) schizophrenic patients consider the most distressing during treatment with typical antipsychotics, (2) measure the impact of actual and past SE on patients' attitude toward antipsychotics and (3) assess the influence of both on adherence. The 213 schizophrenics, treated with conventional antipsychotics, were recruited in two psychiatric hospitals in Hamburg. Subjects were assessed about type and severity of present and past side effects and their attitude and adherence to antipsychotic treatment. The 82 (39%) patients presented present SE while 131 (61%) did not. Sexual dysfunctions (P < 0.001), extrapyramidal (P < 0.05) and psychic side effects (P < 0.05) were rated as significantly subjectively more distressing than sedation or vegetative side effects. Patients presenting with present SE compared with patients without present SE had a significantly more negative general attitude toward antipsychotics (P < 0.05), were more doubtful about their efficacy (P < 0.01) and were less likely to encourage a relative to take such a medication in case of need (P < 0.001). A regression analysis indicated that nonadherence was mainly influenced by negative general and efficacy attitudes toward antipsychotics and the experience of past or present antipsychotic side effects. All antipsychotic side effects, present or past, can have a durable negative impact on patient's attitude toward antipsychotic treatment and adherence. Non-adherence is mainly determined, among other factors, by these negative attitudes, which are partly influenced by the experience of past or present antipsychotic-induced side effects.

Investigation of the flow in the impeller side clearances of a centrifugal pump with volute casing

NASA Astrophysics Data System (ADS)

Will, Björn-Christian; Benra, Friedrich-Karl; Dohmen, Hans-Josef

2012-06-01

The paper is concerned with the fluid flow in the impeller side clearances of a centrifugal pump with volute casing. The flow conditions in these small axial gaps are of significant importance for a number of effects such as disk friction, leakage losses or hydraulic axial thrust to name but a few. In the investigated single stage pump, the flow pattern in the volute turns out to be asymmetric even at design flow rate. To gain a detailed insight into the flow structure, numerical simulations of the complete pump including the impeller side clearances are accomplished. Additionally, the hydraulic head and the radial pressure distributions in the impeller side clearances are measured and compared with the numerical results. Two configurations of the impeller, either with or without balancing holes, are examined. Moreover, three different operating points, i.e.: design point, part load or overload conditions are considered. In addition, analytical calculations are accomplished to determine the pressure distributions in the impeller side clearances. If accurate boundary conditions are available, the 1D flow models used in this paper can provide reasonable results for the radial static pressure distribution in the impeller side clearances. Furthermore, a counter rotating wake region develops in the rear impeller side clearances in absence of balancing holes which severely affects the inflow and outflow conditions of the cavity in circumferential direction.

Black hairy tongue associated with olanzapine treatment: a case report.

PubMed

Tamam, Lut; Annagur, Bilge Burcak

2006-10-01

Olanzapine is an atypical antipsychotic drug approved for acute and long-term treatment of bipolar disorder. Although relatively safe as compared to other classical antipsychotic medications, there are a number of uncommon adverse effects of olanzapine such as oral cavity lesions. In addition to the relatively common side effect of dry mouth, several articles have reported an association between olanzapine treatment and the development of oral lesions such as apthous stomatitis, pharyngitis, glossitis and oral ulceration. Although there are several cases in which the tongue was affected in conjunction with stomatitis or pharyngitis, we could not find a case report indicating a direct relationship between olanzapine use and a tongue lesion. We present here the case of a patient with bipolar disorder, who developed recurrent black hairy tongue on two different occasions following the addition of olanzapine to lithium treatment. In the present case, xerostomia (dry mouth), which is an adverse reaction of both olanzapine and lithium, may have played a role in the development of black hairy tongue. All agents with a possible side effect of xerostomia may predispose patients to black hairy tongue, especially when they are administered in combination. To preclude the development of this complication with such drugs, extra time and effort should be given to improving oral hygiene.

2D trajectory estimation during free walking using a tiptoe-mounted inertial sensor.

PubMed

Sagawa, Koichi; Ohkubo, Kensuke

2015-07-16

An estimation method for a two-dimensional walking trajectory during free walking, such as forward walking, side stepping and backward walking, was investigated using a tiptoe-mounted inertial sensor. The horizontal trajectory of the toe-tip is obtained by double integration of toe-tip acceleration during the moving phase in which the sensor is rotated before foot-off or after foot-contact, in addition to the swing phase. Special functions that determine the optimum moving phase as the integral duration in every one step are developed statistically using the gait cycle and the resultant angular velocity of dorsi/planter flexion, pronation/supination and inversion/eversion so that the difference between the estimated trajectory and actual one gives a minimum value during free walking with several cadences. To develop the functions, twenty healthy volunteers participated in free walking experiments in which subjects performed forward walking, side stepping to the right, side stepping to the left, and backward walking at 39 m down a straight corridor with several predetermined cadences. To confirm the effect of the developed functions, five healthy subjects participated in the free walking experiment in which each subject performed free walking with different velocities of normal, fast, and slow based on their own assessment in a square course with 7 m side. The experimentally obtained results of free walking with a combination of forward walking, backward walking, and side stepping indicate that the proposed method produces walking trajectory with high precision compared with the constant threshold method which determines swing phase using the size of the angular velocity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Numerical simulation of heat transfer and fluid flow during double-sided laser beam welding of T-joints for aluminum aircraft fuselage panels

NASA Astrophysics Data System (ADS)

Yang, Zhibin; Tao, Wang; Li, Liqun; Chen, Yanbin; Shi, Chunyuan

2017-06-01

In comparison with conventional laser beam welding, double-sided laser beam welding has two laser heat sources simultaneously and symmetrically loaded from both sides makes it to be a more complicated coupled heat transport and fluid flow process. In this work, in order to understand the heat transfer and fluid flow, a three-dimensional model was developed and validated with the experimental results. The temperature field, fluid flow field, and keyhole characteristic were calculated using the developed model by FLUENT software. Calculated results indicated that the temperature and fluid flow fields were bilateral symmetry along the stringer center, and the molten pool maximum length was located near the keyhole intersection position. The skin side had higher temperature and faster cooling speed. Several characteristic flow patterns in the weld pool cross section, including the vortexes flows near the keyhole opening position, the convection flows above the keyhole intersection location, the regularity downward flows at the molten pool bottom. And in the lengthwise section, a distinct vortex flow below the keyhole, and the liquid metal behind the keyhole first flowed to near the molten pool maximum length location and then to the molten pool surface. Perpendicular to and along welding direction the keyhole liquid metal flowed to the weld molten pool surface and around the keyhole, respectively. The special temperature fields and fluid flow patterns were closely related to the effects of the double sides' laser energy coupling and enhancement. The calculated weld pool geometry basically in good agreement with the experimental results indicated that the developed model was validity and reasonable.

[CANNABIS AND GLAUCOMA: AN ANCIENT LEGEND OR A NOVEL THERAPEUTIC HORIZON?].

PubMed

Mathalone, Nurit; Wolf, Alvit; Geyer, Orna

2015-06-01

Glaucoma causes damage to the optic nerve and compromises the visual field. The main risk factor of the disease is the level of the intra-ocular pressure. Therapeutic options include medical and surgical treatment, aimed to lower the intra-ocular pressure. Consumption of the cannabis plant (Cannabis Satival has been known since ancient times. It can be consumed orally, topically, intra-venous or by inhalation. The main active ingredient of cannabis is THC (Tetra-Hydro-Cannabinol). One of THC's reported effects is the reduction of intra-ocular pressure. Several studies have demonstrated temporary intra-ocular pressure decrease in both healthy subjects and glaucoma patients following topical application or systemic consumption. The effect was a short term one. It was followed by the development of resistance to the drug after prolonged intake and it was also accompanied by topical and systemic side effects. Cannabis may be considered as a therapeutic option in glaucoma. Its limited effect, development of resistance, acquired side effects and the accompanying psycho-active influence limit its advantage and cause its efficacy to be dubious. Therefore, cannabis treatment for glaucoma currently seems impractical and is not recommended by either the Israeli or the American glaucoma societies.

Automicroneedle therapy system combined with topical tretinoin shows better regenerative effects compared with each individual treatment.

PubMed

Kim, J H; Park, H Y; Jung, M; Choi, E H

2013-01-01

Regenerative therapy is a relatively new dermatological field. However, the currently available topical agents are unsuitable for transdermal drug delivery because of their high molecular weight and low liposolubility. Therefore, a more effective transdermal drug delivery system is needed in order to achieve better therapeutic effects with these agents. A recently introduced microneedle therapy system (MTS), which is a mechanical method for making minute holes in the skin, improves transdermal delivery. A recently developed refinement of this technique, the automicroneedle therapy system (AMTS), has several advantages over the traditional MTS, as it can achieve consistent results because of its automatic punching method. To evaluate the cutaneous effects of an AMTS in combination with topical tretinoin. Twelve hairless mice were divided into two groups, and the dorsal skin of each mouse was marked down the centre. The first group was treated with the AMTS plus 0.025% tretinoin on one side of the back, and with 0.025% tretinoin only on the other side. The other group was treated with the AMTS and vehicle on one side, while the other side was left untreated. The effects on cutaneous regeneration and the treatment side-effects were evaluated by functional assessment including transepidermal water loss and skin hydration, and by histopathology including epidermal and dermal thickness, and density of collagen fibres. Western blotting and real-time reverse transcriptase PCR were also performed to determine protein and mRNA expression of procollagen type 1 and matrix metalloproteinase-13. Compared with the individual treatments (the AMTS alone or tretinoin alone) the combination of tretinoin plus the AMTS produced greater dermal regeneration as a result of increased proliferation of collagen fibres. This combination therapy did not result in treatment-related adverse effects. An AMTS combined with topical tretinoin is a safe and effective method for skin regeneration, which works by increasing collagen production, and might be a new therapeutic option for regenerative therapy. © The Author(s). CED © 2012 British Association of Dermatologists.

Antithyroid Drug Side Effects in the Population and in Pregnancy.

PubMed

Andersen, Stine Linding; Olsen, Jørn; Laurberg, Peter

2016-04-01

Methimazole (MMI) and propylthiouracil (PTU) are both associated with birth defects and may also rarely be associated with agranulocytosis and liver failure. The frequency of these side effects when antithyroid drugs (ATDs) are used in the population in general or in pregnancy remains to be elucidated. All individuals registered as the parent of a live-born child in Denmark, 1973–2008, were identified (n = 2 299 952) and studied from 1995 through 2010 for the use of ATDs. Outcomes were agranulocytosis, liver failure, and birth defects in their offspring. To evaluate the frequency of these side effects associated with the use of ATDs in pregnancy, all live-born pregnancies (n = 830 680), 1996–2008, were identified in a subanalysis. In the population studied, 28 998 individuals redeemed prescriptions of ATDs (exposure in 2115 pregnancies), which was associated with 45 cases of agranulocytosis (one in pregnancy) and 10 cases of liver failure (one in pregnancy). This corresponded to 41 and 11 cases of agranulocytosis and liver failure per 5 million inhabitants during a 10-year period (agranulocytosis: 0.16% of ATDs exposed [MMI: 0.11% vs PTU: 0.27%, P = .02]; liver failure: 0.03% of ATDs exposed [MMI: 0.03% vs PTU: 0.05%, P = .4]). The majority (83%) developed the side effect within 3 months of ATD treatment and 25% during hyperthyroidism relapse. The use of ATDs in pregnancy was associated with birth defects in 3.4% of exposed children (44 cases per 5 million inhabitants per 10 y), and the frequency of birth defects after ATD exposure was 75 times higher than both maternal agranulocytosis and liver failure in pregnancy. In the Danish population in general, ATDs associated birth defects and agranulocytosis had similar frequencies and were more common than liver failure, whereas for the use of ATDs in pregnancy, birth defects were dominant. The burden of side effects to the use of ATDs can be reduced by restricting the use of ATDs in early pregnancy.

Blood RNA biomarker panel detects both left- and right-sided colorectal neoplasms: a case-control study.

PubMed

Chao, Samuel; Ying, Jay; Liew, Gailina; Marshall, Wayne; Liew, Choong-Chin; Burakoff, Robert

2013-07-23

Colonoscopy is widely regarded to be the gold standard for colorectal cancer (CRC) detection. Recent studies, however, suggest that the effectiveness of colonoscopy is mostly confined to tumors on the left side of the colon (descending, sigmoid, rectum), and that the technology has poor tumor detection for right-sided (cecum, ascending, transverse) lesions. A minimally invasive test that can detect both left-sided and right-sided lesions could increase the effectiveness of screening colonoscopy by revealing the potential presence of neoplasms in the right-sided "blind spot". We previously reported on a seven-gene, blood-based biomarker panel that effectively stratifies a patient's risk of having CRC. For the current study, we assessed the effectiveness of the seven-gene panel for the detection of left- and right-sided CRC lesions. Results were evaluated for 314 patients with CRC (left-sided: TNM I, 65; TNM II, 57; TNM III, 60; TNM IV, 17; unknown, 9. right-sided: TNM I, 28; TNM II, 29; TNM III, 38; TNM IV, 12; unknown, 1 and including two samples with both left and right lesions) and 328 control samples. Blood samples were obtained prior to clinical staging and therapy. Most CRC subjects had localized disease (stages I and II, 58%); regional (stage III) and systemic (stage IV) disease represented 32% and 9%, respectively, of the study population. The panel detected left-sided (74%, 154/208) and right-sided (85%, 92/108) lesions with an overall sensitivity of 78% (215/316) at a specificity of 66% (215/328). Treatable cancer (stages I to III) was detected with left-sided lesion sensitivity of 76% (138/182) and right-sided sensitivity of 84% (80/95). This seven-gene biomarker panel detected right-sided CRC lesions across all cancer stages with a sensitivity that is at least equal to that for left-sided lesions. This study supports the use of this panel as the basis for a patient-friendly, blood-based test that can be easily incorporated into a routine physical examination in advance of colonoscopy to provide a convenient companion diagnostic and a pre-screening alert, ultimately leading to enhanced CRC screening effectiveness.

Work Related Stress: Application of a Special Study to the General Business Community.

ERIC Educational Resources Information Center

Gallagher, Denise M.; And Others

There has been much recent attention given to stress and the negative side effects associated with excessive stress. Employers need to recognize the effect that stress can have on the productivity and attitudes of their employees. To examine work-related stress and to develop stress management strategies, a study was conducted of flight attendants…

On the mass function of stars growing in a flocculent medium

NASA Astrophysics Data System (ADS)

Maschberger, Th.

2013-12-01

Stars form in regions of very inhomogeneous densities and may have chaotic orbital motions. This leads to a time variation of the accretion rate, which will spread the masses over some mass range. We investigate the mass distribution functions that arise from fluctuating accretion rates in non-linear accretion, ṁ ∝ mα. The distribution functions evolve in time and develop a power-law tail attached to a lognormal body, like in numerical simulations of star formation. Small fluctuations may be modelled by a Gaussian and develop a power-law tail ∝ m-α at the high-mass side for α > 1 and at the low-mass side for α < 1. Large fluctuations require that their distribution is strictly positive, for example, lognormal. For positive fluctuations the mass distribution function develops the power-law tail always at the high-mass hand side, independent of α larger or smaller than unity. Furthermore, we discuss Bondi-Hoyle accretion in a supersonically turbulent medium, the range of parameters for which non-linear stochastic growth could shape the stellar initial mass function, as well as the effects of a distribution of initial masses and growth times.

From Semi- to Full-Two-Dimensional Conjugated Side-Chain Design: A Way toward Comprehensive Solar Energy Absorption

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

Chao, Pengjie; Wang, Huan; Qu, Shiwei

Two polymers with fully two-dimensional (2D) conjugated side chains, 2D-PTB-Th and 2D-PTB-TTh, were synthesized and characterized through simultaneously integrating the 2D-TT and the 2D-BDT monomers onto the polymer backbone. Resulting from the synergistic effect from the conjugated side chains on both monomers, the two polymers showed remarkably efficient absorption of the sunlight and improved pi-pi intermolecular interactions for efficient charge carrier transport. The optimized bulk heterojunction device based on 2D-PTB-Th and PC71BM shows a higher PCE of 9.13% compared to PTB7-Th with a PCE of 8.26%, which corresponds to an approximately 10% improvement in solar energy conversion. The fully 2D-conjugatedmore » side-chain concept reported here developed a new molecular design strategy for polymer materials with enhanced sunlight absorption and efficient solar energy conversion.« less

A Rodent Model of Dynamic Facial Reanimation Using Functional Electrical Stimulation

PubMed Central

Attiah, Mark A.; de Vries, Julius; Richardson, Andrew G.; Lucas, Timothy H.

2017-01-01

Facial paralysis can be a devastating condition, causing disfiguring facial droop, slurred speech, eye dryness, scarring and blindness. This study investigated the utility of closed-loop functional electric stimulation (FES) for reanimating paralyzed facial muscles in a quantitative rodent model. The right buccal and marginal mandibular branches of the rat facial nerve were transected for selective, unilateral paralysis of whisker muscles. Microwire electrodes were implanted bilaterally into the facial musculature for FES and electromyographic (EMG) recording. With the rats awake and head-fixed, whisker trajectories were tracked bilaterally with optical micrometers. First, the relationship between EMG and volitional whisker movement was quantified on the intact side of the face. Second, the effect of FES on whisker trajectories was quantified on the paralyzed side. Third, closed-loop experiments were performed in which the EMG signal on the intact side triggered FES on the paralyzed side to restore symmetric whisking. The results demonstrate a novel in vivo platform for developing control strategies for neuromuscular facial prostheses. PMID:28424583

Installation of a groundwater monitoring-well network on the east side of the Uncompahgre River in the Lower Gunnison River Basin, Colorado, 2014

USGS Publications Warehouse

Thomas, Judith C.

2015-10-07

The east side of the Uncompahgre River Basin has been a known contributor of dissolved selenium to recipient streams. Discharge of groundwater containing dissolved selenium contributes to surface-water selenium concentrations and loads; however, the groundwater system on the east side of the Uncompahgre River Basin is not well characterized. The U.S. Geological Survey, in cooperation with the Colorado Water Conservation Board and the Bureau of Reclamation, has established a groundwater-monitoring network on the east side of the Uncompahgre River Basin. Thirty wells total were installed for this project: 10 in 2012 (DS 923, http://dx.doi.org/10.3133/ds923), and 20 monitoring wells were installed during April and June 2014 which are presented in this report. This report presents location data, lithologic logs, well-construction diagrams, and well-development information. Understanding the groundwater system can provide managers with an additional metric for evaluating the effectiveness of salinity and selenium control projects.

Association between septal deviation and sinonasal papilloma.

PubMed

Nomura, Kazuhiro; Ogawa, Takenori; Sugawara, Mitsuru; Honkura, Yohei; Oshima, Hidetoshi; Arakawa, Kazuya; Oshima, Takeshi; Katori, Yukio

2013-12-01

Sinonasal papilloma is a common benign epithelial tumor of the sinonasal tract and accounts for 0.5% to 4% of all nasal tumors. The etiology of sinonasal papilloma remains unclear, although human papilloma virus has been proposed as a major risk factor. Other etiological factors, such as anatomical variations of the nasal cavity, may be related to the pathogenesis of sinonasal papilloma, because deviated nasal septum is seen in patients with chronic rhinosinusitis. We, therefore, investigated the involvement of deviated nasal septum in the development of sinonasal papilloma. Preoperative computed tomography or magnetic resonance imaging findings of 83 patients with sinonasal papilloma were evaluated retrospectively. The side of papilloma and the direction of septal deviation showed a significant correlation. Septum deviated to the intact side in 51 of 83 patients (61.4%) and to the affected side in 18 of 83 patients (21.7%). Straight or S-shaped septum was observed in 14 of 83 patients (16.9%). Even after excluding 27 patients who underwent revision surgery and 15 patients in whom the papilloma touched the concave portion of the nasal septum, the concave side of septal deviation was associated with the development of sinonasal papilloma (p = 0.040). The high incidence of sinonasal papilloma in the concave side may reflect the consequences of the traumatic effects caused by wall shear stress of the high-velocity airflow and the increased chance of inhaling viruses and pollutants. The present study supports the causative role of human papilloma virus and toxic chemicals in the occurrence of sinonasal papilloma.

Societal preferences for rheumatoid arthritis treatments: evidence from a discrete choice experiment.

PubMed

Harrison, Mark; Marra, Carlo; Shojania, Kam; Bansback, Nick

2015-10-01

There is a concern that cost-effectiveness analysis using quality-adjusted life years does not capture all valuable benefits of treatments. The objective of this study was to determine the value society places on aspects of RA treatment to inform policymaking. A discrete choice experiment was administered to a representative sample of the Canadian general population. The discrete choice experiment, developed using focus groups, had seven attributes (route and frequency of administration, chance of benefit, chance of serious and minor side effects, confidence in evidence and life expectancy). A conditional logit regression model was used to estimate the significance and relative importance of attributes in influencing preferences on the quality-adjusted life years scale. Responses from 733 respondents who provided rational responses were analysed. Six attribute levels within four attributes significantly influenced preferences for treatments: a willingness to trade a year of life expectancy over a 10-year period to increase the probability of benefiting from treatment, or two-thirds of a year to reduce minor or serious side effects to the lowest level or improve the confidence in benefit/side-effect estimates. There was also some evidence of a preference for oral drug delivery, though a subgroup analysis suggested this preference was restricted to injection-naive respondents. Our results suggest society values the degree of confidence in the estimates of risks and benefits of RA treatments and the route of administration, as well as benefits and side effects. This study provides important evidence to policymakers determining the cost-effectiveness of treatments in arthritis. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Enquiry into the Side Effects of School Inspection in a "Low-Stakes" Inspection Context

ERIC Educational Resources Information Center

Penninckx, Maarten; Vanhoof, Jan; De Maeyer, Sven; Van Petegem, Peter

2016-01-01

This article describes a qualitative study into the occurrence of the side effects of school inspection through in-depth interviews in five case schools. The study investigates the extent to which strategic activities, disturbing effects and emotional side effects occur in the case schools. The study also aims to understand features that may…

Inferring protein domains associated with drug side effects based on drug-target interaction network.

PubMed

Iwata, Hiroaki; Mizutani, Sayaka; Tabei, Yasuo; Kotera, Masaaki; Goto, Susumu; Yamanishi, Yoshihiro

2013-01-01

Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions. In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, which we call "pharmacogenomic features," based on the drug-target interaction network. We detect drug side effects and protein domains that appear jointly in known drug-target interactions, which is made possible by using classifiers with sparse models. It is shown that the inferred pharmacogenomic features can be used for predicting potential drug-target interactions. We also discuss advantages and limitations of the pharmacogenomic features, compared with the chemogenomic features that are the associations between drug chemical substructures and protein domains. The inferred side effect-domain association network is expected to be useful for estimating common drug side effects for different protein families and characteristic drug side effects for specific protein domains.

Vedolizumab is an effective alternative in inflammatory bowel disease patients with anti-TNF-alpha therapy-induced dermatological side effects.

PubMed

Pijls, Philippe A R R; Gilissen, Lennard P L

2016-11-01

The treatment of patients with inflammatory bowel diseases has been revolutionized by the introduction of biological therapy with TNF-alpha blockers. However, TNF-alpha blockers are also associated with a wide variety of dermatological side effects, such as local skin infections, psoriasis and eczema. A new biological therapy, targeting the gut-specific adhesion molecule alpha4beta7 integrin, is the humanized monoclonal IgG1 antibody vedolizumab. Vedolizumab prevents leukocyte migration to the gastrointestinal tract, thereby reducing inflammation. This gut-specific therapy has the potential to reduce systemic side effects, including dermatological ones. We describe 3 inflammatory bowel disease patients who experience anti-TNF-alpha therapy-induced dermatological side effects, consisting of hidradenitis suppurativa, a folliculitis, scalp psoriasis and a dissecting folliculitis. In all patients, anti-TNF-alpha therapy-induced dermatological side effects diminished after switching to vedolizumab. Vedolizumab may be a viable alternative biological therapy in inflammatory bowel disease patients who experience anti-TNF-alpha therapy-induced dermatological side effects. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Experimental Study of Wake / Flap Interaction Noise and the Reduction of Flap Side Edge Noise

NASA Technical Reports Server (NTRS)

Hutcheson, Florence V.; Stead, Daniel J.; Plassman, Gerald E.

2016-01-01

The effects of the interaction of a wake with a half-span flap on radiated noise are examined. The incident wake is generated by bars of various widths and lengths or by a simplified landing gear model. Single microphone and phased array measurements are used to isolate the effects of the wake interaction on the noise radiating from the flap side edge and flap cove regions. The effects on noise of the wake generator's geometry and relative placement with respect to the flap are assessed. Placement of the wake generators upstream of the flap side edge is shown to lead to the reduction of flap side edge noise by introducing a velocity deficit and likely altering the instabilities in the flap side edge vortex system. Significant reduction in flap side edge noise is achieved with a bar positioned directly upstream of the flap side edge. The noise reduction benefit is seen to improve with increased bar width, length and proximity to the flap edge. Positioning of the landing gear model upstream of the flap side edge also leads to decreased flap side edge noise. In addition, flap cove noise levels are significantly lower than when the landing gear is positioned upstream of the flap mid-span. The impact of the local flow velocity on the noise radiating directly from the landing gear is discussed. The effects of the landing gear side-braces on flap side edge, flap cove and landing gear noise are shown.

Effect of muscle injection site on preanaesthetic sedation in dogs.

PubMed

Self, I A; Hughes, J M L; Kenny, D A; Clutton, R E

2009-03-14

The demeanour of 122 dogs was assessed, and a mixture of 0.025 mg/kg acepromazine and 0.3 mg/kg morphine was injected intramuscularly into one of four randomly assigned muscle sites (cervical epaxial, triceps brachii, middle gluteal and quadriceps femoris) and the dogs' reactions to the injections were assessed. The development of sedation and the occurrence of side effects were assessed after 10, 20 and 30 minutes, and each dog's reaction to venous catheterisation was scored. All the dogs became similarly sedated after 30 minutes. The degree of sedation and the incidence of side effects were independent of the injection site, but the dogs receiving intragluteal injections had lower sedation scores after 10 minutes. The dogs' demeanour had no effect on their response to venous catheterisation. The dogs receiving an injection into the postural quadriceps and triceps muscles showed more marked reactions than those injected into the non-postural cervical epaxial and gluteal muscles.

Evaluating the use of side-scan sonar for detecting freshwater mussel beds in turbid river environments

USGS Publications Warehouse

Powers, Jarrod; Brewer, Shannon K.; Long, James M.; Campbell, Thomas

2015-01-01

Side-scan sonar is a valuable tool for mapping habitat features in many aquatic systems suggesting it may also be useful for locating sedentary biota. The objective of this study was to determine if side-scan sonar could be used to identify freshwater mussel (unionid) beds and the required environmental conditions. We used side-scan sonar to develop a series of mussel-bed reference images by placing mussel shells within homogenous areas of fine and coarse substrates. We then used side-scan sonar to map a 32-km river reach during spring and summer. Using our mussel-bed reference images, several river locations were identified where mussel beds appeared to exist in the scanned images and we chose a subset of sites (n = 17) for field validation. The validation confirmed that ~60% of the sites had mussel beds and ~80% had some mussels or shells present. Water depth was significantly related to our ability to predict mussel-bed locations: predictive ability was greatest at depths of 1–2 m, but decreased in water >2-m deep. We determined side-scan sonar is an effective tool for preliminary assessments of mussel presence during times when they are located at or above the substrate surface and in relatively fine substrates excluding fine silt.

Diagnosing the Causes and Severity of One-sided Message Contention

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

Tallent, Nathan R.; Vishnu, Abhinav; van Dam, Hubertus

Two trends suggest network contention for one-sided messages is poised to become a performance problem that concerns application developers: an increased interest in one-sided programming models and a rising ratio of hardware threads to network injection bandwidth. Unfortunately, it is difficult to reason about network contention and one-sided messages because one-sided tasks can either decrease or increase contention. We present effective and portable techniques for diagnosing the causes and severity of one-sided message contention. To detect that a message is affected by contention, we maintain statistics representing instantaneous (non-local) network resource demand. Using lightweight measurement and modeling, we identify themore » portion of a message's latency that is due to contention and whether contention occurs at the initiator or target. We attribute these metrics to program statements in their full static and dynamic context. We characterize contention for an important computational chemistry benchmark on InfiniBand, Cray Aries, and IBM Blue Gene/Q interconnects. We pinpoint the sources of contention, estimate their severity, and show that when message delivery time deviates from an ideal model, there are other messages contending for the same network links. With a small change to the benchmark, we reduce contention up to 50% and improve total runtime as much as 20%.« less

UDE-based control of variable-speed wind turbine systems

NASA Astrophysics Data System (ADS)

Ren, Beibei; Wang, Yeqin; Zhong, Qing-Chang

2017-01-01

In this paper, the control of a PMSG (permanent magnet synchronous generator)-based variable-speed wind turbine system with a back-to-back converter is considered. The uncertainty and disturbance estimator (UDE)-based control approach is applied to the regulation of the DC-link voltage and the control of the RSC (rotor-side converter) and the GSC (grid-side converter). For the rotor-side controller, the UDE-based vector control is developed for the RSC with PMSG control to facilitate the application of the MPPT (maximum power point tracking) algorithm for the maximum wind energy capture. For the grid-side controller, the UDE-based vector control is developed to control the GSC with the power reference generated by a UDE-based DC-link voltage controller. Compared with the conventional vector control, the UDE-based vector control can achieve reliable current decoupling control with fast response. Moreover, the UDE-based DC-link voltage regulation can achieve stable DC-link voltage under model uncertainties and external disturbances, e.g. wind speed variations. The effectiveness of the proposed UDE-based control approach is demonstrated through extensive simulation studies in the presence of coupled dynamics, model uncertainties and external disturbances under varying wind speeds. The UDE-based control is able to generate more energy, e.g. by 5% for the wind profile tested.

Antipsychotic Drug Side Effects for Persons with Intellectual Disability

ERIC Educational Resources Information Center

Matson, Johnny L.; Mahan, Sara

2010-01-01

Antipsychotic drugs are the most frequently prescribed of the psychotropic drugs among the intellectually disabled (ID) population. Given their widespread use, efforts to systematically assess and report side effects are warranted. Specific scaling methods such as the "Matson Evaluation of Side Effects" ("MEDS"), the "Abnormal Inventory Movement…

CHECKPOINT INHIBITOR IMMUNE THERAPY: Systemic Indications and Ophthalmic Side Effects.

PubMed

Dalvin, Lauren A; Shields, Carol L; Orloff, Marlana; Sato, Takami; Shields, Jerry A

2018-06-01

To review immune checkpoint inhibitor indications and ophthalmic side effects. A literature review was performed using a PubMed search for publications between 1990 and 2017. Immune checkpoint inhibitors are designed to treat system malignancies by targeting one of three ligands, leading to T-cell activation for attack against malignant cells. These ligands (and targeted drug) include cytotoxic T-lymphocyte antigen-4 (CTLA-4, ipilimumab), programmed death protein 1 (PD-1, pembrolizumab, nivolumab), and programmed death ligand-1 (PD-L1, atezolizumab, avelumab, durvalumab). These medications upregulate the immune system and cause autoimmune-like side effects. Ophthalmic side effects most frequently manifest as uveitis (1%) and dry eye (1-24%). Other side effects include myasthenia gravis (n = 19 reports), inflammatory orbitopathy (n = 11), keratitis (n = 3), cranial nerve palsy (n = 3), optic neuropathy (n = 2), serous retinal detachment (n = 2), extraocular muscle myopathy (n = 1), atypical chorioretinal lesions (n = 1), immune retinopathy (n = 1), and neuroretinitis (n = 1). Most inflammatory side effects are managed with topical or periocular corticosteroids, but advanced cases require systemic corticosteroids and cessation of checkpoint inhibitor therapy. Checkpoint inhibitors enhance the immune system by releasing inhibition on T cells, with risk of autoimmune-like side effects. Ophthalmologists should include immune-related adverse events in their differential when examining cancer patients with new ocular symptoms.

Body-drug assemblages: theorizing the experience of side effects in the context of HIV treatment.

PubMed

Gagnon, Marilou; Holmes, Dave

2016-10-01

Each of the antiretroviral drugs that are currently used to stop the progression of HIV infection causes its own specific side effects. Despite the expansion, multiplication, and simplification of treatment options over the past decade, side effects continue to affect people living with HIV. Yet, we see a clear disconnect between the way side effects are normalized, routinized, and framed in clinical practice and the way they are experienced by people living with HIV. This paper builds on the premise that new approaches are needed to understand side effects in a manner that is more reflective of the subjective accounts of people living with HIV. Drawing on the work of Deleuze and Guattari, it offers an original application of the theory of 'assemblage'. This theory offers a new way of theorizing side effects, and ultimately the relationship between the body and antiretroviral drugs (as technologies). Combining theory with examples derived from empirical data, we examine the multiple ways in which the body connects not only to the drugs but also to people, things, and systems. Our objective is to illustrate how this theory dares us to think differently about side effects and allows us to originally (re)think the experience of taking antiretroviral drugs. © 2016 The Authors. Nursing Philosophy Published by John Wiley & Sons Ltd.

Osteoporosis treatment: recent developments and ongoing challenges

PubMed Central

Khosla, Sundeep; Hofbauer, Lorenz C

2018-01-01

Osteoporosis is an enormous and growing public health problem. Once considered an inevitable consequence of ageing, it is now eminently preventable and treatable. Ironically, despite tremendous therapeutic advances, there is an increasing treatment gap for patients at high fracture risk. In this Series paper, we trace the evolution of drug therapy for osteoporosis, which began in the 1940s with the demonstration by Fuller Albright that treatment with oestrogen could reverse the negative calcium balance that developed in women after menopause or oophorectomy. We note a watershed in osteoporosis drug discovery around the year 2000, when the approach to developing novel therapeutics shifted from one driven by discoveries in animal studies and clinical observations (eg, oestrogen, calcitonin, and teriparatide) or opportunistic repurposing of existing compounds (eg, bisphosphonates) to one driven by advances in fundamental bone biology (eg, denosumab) coupled with clues from patients with rare bone diseases (eg, romosozumab, odanacatib). Despite these remarkable advances, concerns about rare side-effects of anti-resorptive drugs, particularly bisphosphonates, and the absence of clear evidence in support of their long-term efficacy is leading many patients who could benefit from drug therapy to not take these drugs. As such, there remains an important clinical need to develop ways to enhance patient acceptance and compliance with these effective drugs, and to continue to develop new drugs that do not cause these side-effects and have prolonged anabolic effects on bone. Such changes could lead to a true reversal of this potentially devastating disease of ageing. PMID:28689769

The Coordinated Noninvasive Studies (CNS) Project. Phase 1

DTIC Science & Technology

1991-12-01

may reveal functional asymmetries that represent the influence of two factors: 1) the "contralateral effect ," based on the side -of-space source of...asymmetries, where processing on that side of the CNS opposite the side of input is favored, and 2) an effect based J.L. Lauter [CNS Project/AFOSR 88-0352...extent that these exist over and above sidedness bias as well as side -of-space asymmetries -- since in these experiments, contralateral effects are

Dose-dependent valproate-induced alopecia in patients with mental disorders.

PubMed

Tomita, Takashi; Goto, Hidekazu; Yoshida, Tadashi; Tanaka, Katsuya; Sumiya, Kenji; Kohda, Yukinao

2015-01-01

Drug-induced hair loss may occur as a side effect in patients treated with valproate. However, few studies have reported a relationship between the blood levels of valproate and the occurrence of hair loss. We report three cases of alopecia that occurred in patients who received sodium valproate for mental disorders. In all three cases, alopecia appeared after long-term valproate exposure with a plasma concentration of 100 µg/ml approximately. However, the alopecia resolved in all cases after dose reduction or treatment discontinuation. Therefore, alopecia may develop in patients with chronic exposure to high plasma concentrations of valproate. Based on these findings, we believe that patients with high plasma concentrations of valproate should be closely monitored for the occurrence of side effects, particularly alopecia.

Flow boiling with enhancement devices for cold plate coolant channel design

NASA Technical Reports Server (NTRS)

Boyd, Ronald D.; Turknett, Jerry C.; Smith, Alvin

1989-01-01

The effects of enhancement devices on flow boiling heat transfer in circular coolant channels, which are heated over a fraction of their perimeters, are studied. The variations were examined in both the mean and local (axial, and circumferential) heat transfer coefficients for a circular coolant channel with either smooth walls or with both a twisted tape and spiral finned walls. Improvements were initiated in the present data reduction analysis. These efforts should lead to the development of heat transfer correlations which include effects of single side heat flux and enhancement device configuration. It is hoped that a stage will be set for the study of heat transfer and pressure drop in single sided heated systems under zero gravity conditions.

Hydroxyurea-induced oral ulceration.

PubMed

Badawi, Maha; Almazrooa, Soulafa; Azher, Fatima; Alsayes, Fatin

2015-12-01

Hydroxyurea is an antimetabolite that is widely used in the treatment of many benign and malignant conditions. This drug is usually well tolerated but has a number of side effects that vary in incidence. In cases of clinically significant adverse events, hydroxyurea is usually discontinued either temporarily or permanently, depending on treatment need versus harm caused by side effects. Here, we report a case of oral ulceration associated with hydroxyurea treatment in a patient who had chronic myelogenous leukemia. The patient rapidly developed an oral ulcer 12 days after administration of the drug. Hydroxyurea was discontinued, and the oral lesion appreciably decreased in size and severity. Physicians and dentists should be aware of the association between hydroxyurea and oral lesions. Copyright © 2015 Elsevier Inc. All rights reserved.

Novel four-sided neural probe fabricated by a thermal lamination process of polymer films.

PubMed

Shin, Soowon; Kim, Jae-Hyun; Jeong, Joonsoo; Gwon, Tae Mok; Lee, Seung-Hee; Kim, Sung June

2017-02-15

Ideally, neural probes should have channels with a three-dimensional (3-D) configuration to record the activities of 3-D neural circuits. Many types of 3-D neural probes have been developed; however, most of them were designed as an array of multiple shanks with electrodes located along one side of the shanks. We developed a novel liquid crystal polymer (LCP)-based neural probe with four-sided electrodes. This probe has electrodes on four sides of the shank, i.e., the front, back and two sidewalls. To generate the proposed configuration of the electrodes, we used a thermal lamination process involving LCP films and laser micromachining. The proposed novel four-sided neural probe, was used to successfully perform in vivo multichannel neural recording in the mouse primary somatosensory cortex. The multichannel neural recording showed that the proposed four-sided neural probe can record spiking activities from a more diverse neuronal population than single-sided probes. This was confirmed by a pairwise Pearson correlation coefficient (Pearson's r) analysis and a cross-correlation analysis. The developed four-sided neural probe can be used to record various signals from a complex neural network. Copyright © 2016 Elsevier B.V. All rights reserved.

Evolving Clinical Cancer Radiotherapy: Concerns Regarding Normal Tissue Protection and Quality Assurance

PubMed Central

Choi, Won Hoon

2016-01-01

Radiotherapy, which is one of three major cancer treatment methods in modern medicine, has continued to develop for a long period, more than a century. The development of radiotherapy means allowing the administration of higher doses to tumors to improve tumor control rates while minimizing the radiation doses absorbed by surrounding normal tissues through which radiation passes for administration to tumors, thereby reducing or removing the incidence of side effects. Such development of radiotherapy was accomplished by the development of clinical radiation oncology, the development of computers and machine engineering, the introduction of cutting-edge imaging technology, a deepened understanding of biological studies on the effects of radiation on human bodies, and the development of quality assurance (QA) programs in medical physics. The development of radiotherapy over the last two decades has been quite dazzling. Due to continuous improvements in cancer treatment, the average five-year survival rate of cancer patients has been close to 70%. The increases in cancer patients’ complete cure rates and survival periods are making patients’ quality of life during or after treatment a vitally important issue. Radiotherapy is implemented in approximately 1/3 to 2/3s of all cancer patients; and has improved the quality of life of cancer patients in the present age. Over the last century, as a noninvasive treatment, radiotherapy has unceasingly enhanced complete tumor cure rates and the side effects of radiotherapy have been gradually decreasing, resulting in a tremendous improvement in the quality of life of cancer patients. PMID:26908993

My Brother’s Keeper: Forging SOF Operators Through Developmental Relationships

DTIC Science & Technology

2016-06-01

85 2. Formal development effectiveness (Q30) ...................................85 3. Formal development drawbacks (Q31...experience, does formal (mandated) development work in the military? 31. What would be the top one or two drawbacks you would foresee with a formal...figuring out the direction of the team. The pendulum has swung too far to one side. Where’s our focus? Regionally? Skill set? All that changes who you get

Prevention of palmar-plantar erythrodysesthesia with an antiperspirant in breast cancer patients treated with pegylated liposomal doxorubicin (SAKK 92/08).

PubMed

Templeton, Arnoud J; Ribi, Karin; Surber, Christian; Sun, Hong; Hsu Schmitz, Shu-Fang; Beyeler, Michael; Dietrich, Daniel; Borner, Markus; Winkler, Annette; Müller, Andreas; von Rohr, Lukas; Winterhalder, Ralph C; Rochlitz, Christoph; von Moos, Roger; Zaman, Khalil; Thürlimann, Beat J K; Ruhstaller, Thomas

2014-06-01

Elevated concentrations of doxorubicin are found in eccrine sweat glands of the palms and soles. We therefore evaluated an antiperspirant as preventive treatment for palmar-plantar erythrodysesthesia (hand-foot syndrome) in patients with metastatic breast cancer treated with pegylated liposomal doxorubicin. An antiperspirant containing aluminum chlorohydrate or placebo cream was applied to the left or right hand and foot in a double-blinded manner (intra-patient randomization). The primary endpoint was the rate of grade 2 or 3 palmar-plantar erythrodysesthesia. A secondary endpoint was the patient-reported symptom burden (tingling, numbness, pain, or skin problems). Using McNemar's matched pairs design, 53 patients were needed to detect a 20% difference between the treatment and placebo sides with a significance level of 5% and power of 90%. Grade 2 or 3 PPE occurred in 30 (58%) of 52 evaluable patients; in six patients adverse effects occurred on the placebo side but not on the treatment side, whereas one patient developed palmar-plantar erythrodysesthesia on the treatment side only (P = 0.07). Four patients developed grade 2 or 3 palmar-plantar erythrodysesthesia on their foot on the placebo side but not on the treatment side (P = 0.05). In the cohort with grade 2 or 3 palmar-plantar erythrodysesthesia there was a trend towards fewer dermatologic symptomatologies with the active treatment (P = 0.05), and no difference for other adverse events. Using topical aluminum chlorohydrate as an antiperspirant appears to reduce the incidence of grade 2 or 3 palmar-plantar erythrodysesthesia following pegylated liposomal doxorubicin chemotherapy for metastatic breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

A novel treatment for management of a trapped placenta using intracervical nitroglycerin tablets

PubMed Central

Rodgers, Blake Conley; Pasternak, Adam; Gray, Richard

2013-01-01

A 34-year-old gravida 2, para 1 woman delivered a viable male infant and developed retained placenta due to entrapment. A nitroglycerin tablet was used to relax the lower uterine segment and cervix, which allowed the placenta to pass through the cervix for delivery. The nitroglycerin tablet was placed in the cervix and held in place by the delivering physician as it dissolved. Soon after administration, the intact placenta delivered. The patient did not experience the typical side effects of headache, asymptomatic decrease in blood pressure, hypotension, palpitations or dizziness that can be associated with administration of nitroglycerin. We suspect that this novel localised route of nitroglycerin administration may be an effective management strategy to treat trapped placenta while minimising side effects. However, the outcomes of this treatment would require further study. PMID:24014558

Strategies to minimize cognitive side effects with ECT: aspects of ECT technique.

PubMed

Prudic, Joan

2008-03-01

The adverse cognitive effects of electroconvulsive therapy are important limitations in the use of this treatment that continues to be a significant therapeutic strategy after 7 decades of use. Among the approaches to mitigation of these side effects are considerations involving the prescription and manipulation of the electrical stimulus itself. The impact of the following electrical factors on the cognitive outcomes of electroconvulsive therapy are surveyed: efficiency of the stimulus as expressed in electrical waveform; targeting of the stimulus, the major concept underlying electrode placement; stimulus dosing; and frequency and number of treatments. The current state of development of knowledge in these areas is summarized, and methods to achieve the best cognitive outcomes without sacrificing clinical efficacy are discussed. Future trends in the further optimization of the electrical stimulus are briefly mentioned.

Psychological factors associated with uptake of the childhood influenza vaccine and perception of post-vaccination side-effects: A cross-sectional survey in England.

PubMed

Smith, Louise E; Webster, Rebecca K; Weinman, John; Amlôt, Richard; Yiend, Jenny; Rubin, G James

2017-04-04

To identify predictors of: uptake of the childhood influenza vaccine in the 2015-2016 influenza season, parental perceptions of side-effects from the influenza vaccine and intention to vaccinate one's child for influenza in the 2016-2017 influenza season. Cross-sectional online survey. Data were collected in England shortly after the end of the 2015-2016 immunization campaign. 1001 parents or guardians of children aged between two and seven. Self-reported uptake of the childhood influenza vaccine in the 2015-2016 influenza season, perception of side-effects from the influenza vaccine and intention to vaccinate one's child in the 2016-2017 influenza season. Self-reported uptake of the childhood influenza vaccine was 52.8%. Factors strongly positively associated with uptake included the child having previously been vaccinated against influenza, perceiving the vaccine to be effective and perceiving the child to be susceptible to flu. Factors strongly negatively associated with uptake included perceiving the vaccine to be unsafe, to cause short-term side-effects or long-term health problems and believing that yearly vaccination may overload the immune system. Predictors of intended vaccine uptake in 2016-2017 were similar. Participants who perceived side-effects after the 2015-2016 vaccination reported being less likely to vaccinate their child next year. Side-effects were more likely to be reported in first-born children, by participants who knew another child who had side-effects, those who thought that the vaccine would interact with medication that the child was currently taking, and those who believed the vaccine causes short-term side-effects. Perceptions about the childhood influenza vaccine show strong associations with uptake, intended uptake and perception of side-effects. Attempts to improve uptake rates from their current low levels must address these perceptions. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Persuading drivers to refrain from speeding: Effects of message sidedness and regulatory fit.

PubMed

Pierro, Antonio; Giacomantonio, Mauro; Pica, Gennaro; Giannini, Anna Maria; Kruglanski, Arie W; Higgins, E Tory

2013-01-01

Building on regulatory fit theory (Higgins, 2000, 2005), we tested whether two-sided ads were more effective than one-sided ads in changing intentions toward driving behavior when message recipients were high in assessment orientation rather than locomotion orientation. In one study either a locomotion or an assessment orientation were situationally induced (Study 1) and in another study these different orientations were chronic predispositions (Study 2). As predicted, both studies found that for participants high in assessment, two-sided ads were more effective than one-sided ads, as reflected in stronger engagement with the persuasive message and stronger intentions to reduce driving speed. In contrast, for participants high in locomotion, one-sided ads were more effective than two-sided ads. There was also evidence that the fit effect on intentions to comply was mediated by strength of engagement with the message. Implications for persuasion concerning driving behaviors are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Side effects of methylphenidate in childhood cancer survivors: a randomized placebo-controlled trial.

PubMed

Conklin, Heather M; Lawford, Joanne; Jasper, Bruce W; Morris, E Brannon; Howard, Scott C; Ogg, Susan W; Wu, Shengjie; Xiong, Xiaoping; Khan, Raja B

2009-07-01

To investigate the frequency and severity of side effects of methylphenidate among childhood survivors of acute lymphoblastic leukemia and brain tumors and identify predictors of higher adverse effect levels. Childhood cancer survivors (N = 103) identified as having attention and learning problems completed a randomized, double-blind, 3-week, home-crossover trial of placebo, low-dose methylphenidate (0.3 mg/kg; 10 mg twice daily maximum) and moderate-dose methylphenidate (0.6 mg/kg; 20 mg twice daily maximum). Caregivers completed the Barkley Side Effects Rating Scale (SERS) at baseline and each week during the medication trial. Siblings of cancer survivors (N = 49) were recruited as a healthy comparison group. There was a significantly higher number and severity of symptoms endorsed on the SERS when patients were taking moderate dose compared with placebo or low dose, but not low dose compared with placebo. The number of side effects endorsed on the SERS was significantly lower during all 3 home-crossover weeks (placebo, low dose, moderate dose) when compared with baseline symptom scores. The severity of side effects was also significantly lower, compared with baseline screening, during placebo and low-dose weeks but not moderate-dose weeks. Both the number and severity of symptoms endorsed at baseline were significantly higher for patients compared with siblings. Female gender and lower IQ were associated with higher adverse effect levels. Methylphenidate is generally well tolerated by childhood cancer survivors. There is a subgroup at increased risk for side effects that may need to be closely monitored or prescribed a lower medication dose. The seemingly paradoxical findings of increased "side effects" at baseline must be considered when monitoring side effects and designing clinical trials.

Switching effect of the side chain on quantum walks on triple graphs

NASA Astrophysics Data System (ADS)

Du, Yi-Mu; Lu, Li-Hua; Li, You-Quan

2015-07-01

We consider a continuous-time quantum walk on a triple graph and investigate the influence of the side chain on propagation in the main chain. Calculating the interchange of the probabilities between the two parts of the main chain, we find that a switching effect appears if there is an odd number of points in the side chain when concrete conditions between the length of the main chain and the position of the side chain are satisfied. However, such an effect does not occur if there is an even number of points in the side chain. We also suggest two proposals for experiments to demonstrate this effect, which may be employed to design a new type of switching device.

Side-scan sonar and submersible observations: New techniques for gleaning more information from sea-floor outcrops

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

Kendall, J.; Hams, J.E.; Buck, S.P.

1990-05-01

Advances in high resolution side-scan sonar imaging technology are so effective at imaging sea-floor geology that they have greatly improved the efficiency of a bottom sampling program The traditional sea-floor geology methodology of shooting a high-resolution seismic survey and sampling along the seismic grid was considered successful if outcrops were sampled on 20% of the attempts. A submersible was used sparingly because of the inability to consistently locate sea-floor outcrops. Side-scan sonar images have increased the sampling success ratio to 70-95% and allow the cost-effective use of a submersible even in areas of sparse sea-floor outcrops. In offshore basins thismore » new technology has been used in consolidated and semiconsolidated rock terranes. When combined with observations from a two-man submersible, SCUBA traverses, seismic data, and traditional sea-floor bottom sampling techniques, enough data are provided to develop an integrated sea-floor geologic interpretation. On individual prospects, side-scan sonar has aided the establishment of critical dip in poor seismic data areas, located seeps and tar mounds, and determined erosional breaching of a prospect. Over a mature producing field, side-scan sonar has influenced the search for field extension by documenting the orientation and location of critical trapping cross faults. These relatively inexpensive techniques can provide critical data in any marine basin where rocks crop out on the sea floor.« less

The Relationship among Side Effects Associated with Anti-Epileptic Medications in Those with Intellectual Disability

ERIC Educational Resources Information Center

Sipes, Megan; Matson, Johnny L.; Belva, Brian; Turygin, Nicole; Kozlowski, Alison M.; Horovitz, Max

2011-01-01

Seizures are fairly common in those with intellectual disabilities. In order to treat these seizures, antiepileptic drugs (AEDs) are often used and in many cases are effective. However, these medications often create a variety of associated side effects. In order to monitor these side effects, measures such as the SEIZES-B have been used. While…

Developing effective messages about potable recycled water: The importance of message structure and content

NASA Astrophysics Data System (ADS)

Price, J.; Fielding, K. S.; Gardner, J.; Leviston, Z.; Green, M.

2015-04-01

Community opposition is a barrier to potable recycled water schemes. Effective communication strategies about such schemes are needed. Drawing on social psychological literature, two experimental studies are presented, which explore messages that improve public perceptions of potable recycled water. The Elaboration-Likelihood Model of information processing and attitude change is tested and supported. Study 1 (N = 415) premeasured support for recycled water, and trust in government information at Time 1. Messages varied in complexity and sidedness were presented at Time 2 (3 weeks later), and support and trust were remeasured. Support increased after receiving information, provided that participants received complex rather than simple information. Trust in government was also higher after receiving information. There was tentative evidence of this in response to two-sided messages rather than one-sided messages. Initial attitudes to recycled water moderated responses to information. Those initially neutral or ambivalent responded differently to simple and one-sided messages, compared to participants with positive or negative attitudes. Study 2 (N = 957) tested the effectiveness of information about the low relative risks, and/or benefits of potable recycled water, compared to control groups. Messages about the low risks resulted in higher support when the issue of recycled water was relevant. Messages about benefits resulted in higher perceived issue relevance, but did not translate into greater support. The results highlight the importance of understanding people's motivation to process information, and need to tailor communication to match attitudes and stage of recycled water schemes' development.

Technology versus humanism: how patients perceive the use of electronic health records in physicians' offices--a qualitative study.

PubMed

Mwachofi, Ari K; Khaliq, Amir A; Carrillo, Estevan R; Winfree, William

2016-01-01

Electronic Health Records (EHRs) have the potential to improve the quality of care. In view of the accelerated adoption of EHRs, there is a need to understand conditions necessary for their effective use. Patients are the focus of healthcare and their perceptions and expectations need to be included in developing and implementing EHRs. The purpose of this study was to gather exploratory qualitative information from patients about their experiences and perceptions regarding the effects of EHRs on healthcare quality in physicians' offices. We conducted five focus groups with patients representing a random mix of diverse socio-demographic backgrounds in Oklahoma. Related to EHRs, patients reported improvements on the technical side of care but no change on the human side. They expressed concerns about the potential for breach of confidentiality and security of medical records. They were also concerned about the possibility of governmental agencies or insurance companies having unauthorized access to patient records. Patients differentiated between the human and technical sides of care and reported no change or improvement in the doctor-patient interaction. Patients have an important perspective on the use of EHRs and their perceptions and experiences should be considered in the development, adoption and implementation of EHRs. Otherwise, the use of EHRs may not be fully effective. There is also a need to educate patients about the potential benefits and risks of EHRs and the steps being taken to mitigate such risks.

[Side Effects of Occupational Group Therapy].

PubMed

Flöge, B; Fay, D; Jöbges, M; Linden, M; Muschalla, B

2016-12-01

Background: Occupational therapy is an important co-therapy in psychiatric therapy. It is a common belief that no risks are associated with occupational therapy. Negative effects caused by group therapy, especially occupational therapy, have not been in the focus of research yet. In this study we want to illustrate possible types and intensities of group side effects through occupational therapy. Patients and Methods: Patients of an inpatient rehabilitation facility filled out the Adverse Treatment Reaction Group Checklist. The checklist contains 47 items divided in six dimensions: group size, content, group participants, group outcome and global. The self-rating used a 5-point likert scale (0 = not at all; 4 = very much, extremely stressful) and gives information about types and intensities of the side effects. Results: 88.9 % of 45 patients reported negative effects of occupational group therapy. 28.9 % of the patients rated the side effect as at least severe. Discussion: Occupational therapy is associated with side effects as every other group therapy. Possible side effects caused by group therapy should be considered while planning and implementing occupational therapy. © Georg Thieme Verlag KG Stuttgart · New York.

The effect of qualifying language on perceptions of drug appeal, drug experience, and estimates of side-effect incidence in DTC advertising.

PubMed

Davis, Joel

2007-01-01

This study examined how the use of qualifying language in direct-to-consumer (DTC) pharmaceutical advertising affects consumers' perceptions of drug appeal, anticipated pleasantness of drug usage, and the expected incidence of side-effect occurrence. A sample of 669 individuals participated in a 2 x 8 complete factorial design. The design manipulated the number of side effects associated with drug use and the type of qualifying language used to describe the side effects. The eight experimental qualifying language cells represented one control condition (no qualifying language), three cells where each of three types of qualifying language were presented individually, and four cells where qualifying language was combined. The results indicate that qualifying language has a profound effect on drug perceptions, especially when used in combination. Drug appeal and the anticipated drug-using experience almost always were more positive in the presence of qualifying language. Qualifying language appears to exert its influence by causing individuals to reduce their estimate of the likelihood of experiencing individual side effects. Policy implications of the research, particularly for evaluation of "fair balance" and the reporting of side effects, are presented.

The differences in the assessments of side effects at an oncology outpatient clinic.

PubMed

Bayraktar-Ekincioglu, A; Kucuk, E

2018-04-01

Background There is a growing interest in the use of targeted and immunotherapies in oncology. However, the assessment of side effects can be different due to interpretation of patients' health status by healthcare professionals in oncology outpatient clinics. Objective To demonstrate the differences in the assessments of side effects conducted independently by a clinical pharmacist and nurses in patients who receive targeted therapies at an oncology outpatient clinic. Setting The study was conducted at the University Oncology Hospital in an outpatient clinic from October 2015 to March 2016. Method Patients receiving ipilimumab, nivolumab, pembrolizumab, bevacizumab, panitumumab or cetuximab during study period were included. The assessment of side effects was conducted by a pharmacist and nurse independently using the NCI-CTCAE version-2. Main outcome measure To compare the severity assessments of side effects between a clinical pharmacist and nurses in an outpatient clinic. Results During the study, 204 visits for 43 patients with a total of 5508 side effect assessments were recorded where 1137 (20.64%) assessments were graded differently. Out of 1137 assessments, 473 of them were graded higher by a clinical pharmacist whereas 664 were graded higher by nurses. Statistically significant differences were detected in the assessment of vomiting, taste changes, sense changes, alopecia, fatigue, mood changes, anxiety, hearing impairment, and allergic reactions. Conclusion An assessment of side effects by healthcare providers in patients with cancer may be challenging due to an increased workload in clinics and undistinguishable symptoms of side effects and cancer itself. Therefore, a new care model which increases an interprofessional communication may improve pharmaceutical care in oncology outpatient clinics.

Period Prevalence and Perceived Side Effects of Hormonal Contraceptive Use and the Menstrual Cycle in Elite Athletes.

PubMed

Martin, Daniel; Sale, Craig; Cooper, Simon B; Elliott-Sale, Kirsty J

2017-12-28

To identify the period prevalence of hormonal contraceptive (HC) use and characterise the perceived side effects associated with the menstrual cycle and HC use. 430 elite female athletes completed a questionnaire to assess; the period prevalence of HC use, the reasons for initiation and discontinuation of HCs and the side effects experienced by HC and non-HC users. Descriptive statistics, between-group comparisons and associations between categorical variables were calculated. 49.5% of athletes were currently using HCs and 69.8% had used HCs at some point. Combined oral contraceptives were most commonly used (68.1%), with 30.0% using progestin-only contraceptives (implant = 13.1%; injection = 3.7%; intrauterine system = 2.8%). Perceived negative side effects were more common with progestin-only HC use (39.1%) compared to combined HC use (17.8%; P = 0.001) and were most prevalent in implant users (53.6%; P = 0.004). HC users reported perceived positive side effects relating to the ability to predict and/or manipulate the timing, frequency and amount of menstrual bleeding. Non-HC users had a menstrual cycle length of 29 ± 5 d and 77.4% reported negative side effects during their menstrual cycle, primarily during days 1-2 of menstruation (81.6%). Approximately half of elite athletes used HCs and progestin-only contraceptive users reported greater incidences of negative side effects, especially with the implant. Due to the high inter-individual variability in reported side effects, athletes and practitioners should maintain an open dialogue to pursue the best interests of the athlete.

Non-injection routes for allergen immunotherapy: focus on sublingual immunotherapy.

PubMed

Passalacqua, Giovanni; Guerra, Laura; Pasquali, Mercedes; Canonica, Giorgio Walter

2006-01-01

Allergen specific immunotherapy, together with drugs and allergen avoidance, is a cornerstone in the management of respiratory allergy. The non-injection or local routes were developed with the main goal of improving the safety and minimizing the risk of those side effects, which can accompany the injection route. The pure oral route and the bronchial route showed, in the clinical trials, only a marginal efficacy with not negligible side effects. Therefore, these routes are no longer recommended for clinical use. The nasal route proved effective and safe, but its efficacy is strictly limited to the nose. Moreover, the practical problems with administration have made the use of nasal immunotherapy progressively declining. The efficacy of the sublingual route is confirmed by numerous controlled trials, and a meta analysis (in allergic rhinitis). The safety profile, as derived from clinical trials and post marketing surveillance studies, is satisfactory, with mild gastrointestinal complaints being the more frequent side effect reported. Recent studies have also demonstrated that SLIT has a long-lasting effect and a preventive effect on the onset of new skin sensitizations, and interesting data on adherence and mechanisms of action have become recently available. Based on these experimental data, SLIT is now officially accepted as a viable alternative to the subcutaneous route in adults and children. Several points still need to be elucidated, including: mechanisms of action, optimal dosages, and indications in pediatric patients.

Knowledge and perceptions of the intrauterine device among family planning providers in Nepal: a cross-sectional analysis by cadre and sector.

PubMed

Chakraborty, Nirali M; Murphy, Caitlin; Paudel, Mahesh; Sharma, Sriju

2015-01-28

Nepal has high unmet need for family planning and low use of intrauterine devices (IUDs). While clients' attitudes toward the IUD are known in a variety of contexts, little is known about providers' knowledge and perceptions of the IUD in developing countries. Nepal's liberal IUD service provision policies allow the opportunity to explore provider knowledge and perceptions across cadres and sectors. This research contributes to an understanding of providers' IUD perceptions in low-resource environments, and increases evidence for IUD task-sharing and private sector involvement. A questionnaire was administered to 345 nurses and auxiliary nurse midwives (ANMs) affiliated with the private Mahila Swastha Sewa (MSS) franchise, public sector, or private non-franchise sector. All providers had been trained in TCu 380A IUD insertion and removal. The questionnaire captured providers' IUD experience, knowledge, and perceived barriers to recommendation. Descriptive, multivariate linear, and multinomial logistic regression was conducted, comparing providers between cadre and sector. On average, providers answered 21.5 of 35 questions correctly, for a score of 61.4%. Providers scored the lowest on IUD medical eligibility, answering 5.9 of 14 questions correctly. Over 50% of providers were able to name the four side effects most frequently associated with the IUD; however, one-third of all providers found at least one of these side effects unacceptable. Adjusted results show that cadre does not significantly impact provider's IUD knowledge scores or side effect perceptions. Public sector affiliation was associated with higher knowledge scores regarding personal characteristic eligibility and more negative perceptions of two normal IUD side effects. IUD knowledge is significantly associated with provider's recent training and employment at multiple facilities, and side effect perceptions are significantly associated with client volume, range of family planning methods, and region. Provider knowledge and attitudes towards IUD provision are similar across cadre and sector, supporting WHO task-sharing guidelines and validating Nepal's family planning policies. However, overall provider knowledge is low. We recommend that providers need to receive further training and support to improve knowledge, manage side effects, and recognize women in periods of high unmet need--such as post-partum or post-abortion women--as suitable candidates for IUDs.

Medical tourism-A New Arena.

PubMed

Puri, S; Singh, A; Yashik

2010-01-01

Globalisation has given birth to medical tourism. Health and medical tourism are the fastest growing segments in not only developed nations but in developing countries too. India has become a hot destination, as the Indian medical standards match up to the highly prescribed international standards at a very low cost. However, it is an unmixed blessing; along with advantages, it has many unintended side effects also.

Cationic Albumin Nanoparticles for Enhanced Drug Delivery to Treat Breast Cancer: Preparation and In Vitro Assessment

PubMed Central

Abbasi, Sana; Paul, Arghya; Shao, Wei; Prakash, Satya

2012-01-01

Most anticancer drugs are greatly limited by the serious side effects that they cause. Doxorubicin (DOX) is an antineoplastic agent, commonly used against breast cancer. However, it may lead to irreversible cardiotoxicity, which could even result in congestive heart failure. In order to avoid these harmful side effects to the patients and to improve the therapeutic efficacy of doxorubicin, we developed DOX-loaded polyethylenimine- (PEI-) enhanced human serum albumin (HSA) nanoparticles. The formed nanoparticles were ~137 nm in size with a surface zeta potential of ~+15 mV, prepared using 20 μg of PEI added per mg of HSA. Cytotoxicity was not observed with empty PEI-enhanced HSA nanoparticles, formed with low-molecular weight (25 kDa) PEI, indicating biocompatibility and safety of the nanoparticle formulation. Under optimized transfection conditions, approximately 80% of cells were transfected with HSA nanoparticles containing tetramethylrhodamine-conjugated bovine serum albumin. Conclusively, PEI-enhanced HSA nanoparticles show potential for developing into an effective carrier for anticancer drugs. PMID:22187654

Nanotechnology in the management of cervical cancer.

PubMed

Chen, Jiezhong; Gu, Wenyi; Yang, Lei; Chen, Chen; Shao, Renfu; Xu, Kewei; Xu, Zhi Ping

2015-03-01

Cervical cancer is a major disease with high mortality. All cervical cancers are caused by infection with human papillomaviruses (HPV). Although preventive vaccines for cervical cancer are successful, treatment of cervical cancer is far less satisfactory because of multidrug resistance and side effects. In this review, we summarize the recent application of nanotechnology to the diagnosis and treatment of cervical cancer as well as the development of HPV vaccines. Early detection of cervical cancer enables tumours to be efficiently removed by surgical procedures, leading to increased survival rate. The current method of detecting cervical cancer by Pap smear can only achieve 50% sensitivity, whereas nanotechnology has been used to detect HPVs with greatly improved sensitivity. In cervical cancer treatment, nanotechnology has been used for the delivery of anticancer drugs to increase treatment efficacy and decrease side effects. Nanodelivery of HPV preventive and therapeutic vaccines has also been investigated to increase vaccine efficacy. Overall, these developments suggest that nanoparticle-based vaccine may become the most effective way to prevent and treat cervical cancer, assisted or combined with some other nanotechnology-based therapy. Copyright © 2015 John Wiley & Sons, Ltd.

Photosensitivity: a current biological overview.

PubMed

Elkeeb, Dena; Elkeeb, Laila; Maibach, Howard

2012-12-01

The level of interest in photoirritation (phototoxicity) has increased because of the awareness among the scientific community of the increase in the UV portion of the solar spectrum reaching the earth. The need of new chemicals and drugs puts pressure on pre-test methods for side effects, especially interactive adverse effects with UV light. So pre-marketing clinical trials conducted before a new drug is licensed are essential, as such, at the early phases of the discovery process of the drug/chemical, developing an efficacious photosensitivity testing system is prudent to avoid such potential side effects. To review published literature and provide an overview on exogenous photosensitivity and assays used to evaluate the photosensitivity potential of drugs/chemicals. As well as testing considerations by the Regulatory bodies (namely, the Organization for Economic Cooperation and Development, the U.S Food and Drug Administration and the European Union regulatory agencies). We searched medical and scientific search engines as well as websites of the EU and US Regulatory agencies and used keywords such as cutaneous phototoxicity, phototoxicity in vitro assays, phototoxicity in vivo assays and other related terms.

Tip-enhanced near-field Raman spectroscopy with a scanning tunneling microscope and side-illumination optics.

PubMed

Yi, K J; He, X N; Zhou, Y S; Xiong, W; Lu, Y F

2008-07-01

Conventional Raman spectroscopy (RS) suffers from low spatial resolution and low detection sensitivity due to the optical diffraction limit and small interaction cross sections. It has been reported that a highly localized and significantly enhanced electromagnetic field could be generated in the proximity of a metallic tip illuminated by a laser beam. In this study, a tip-enhanced RS system was developed to both improve the resolution and enhance the detection sensitivity using the tip-enhanced near-field effects. This instrument, by combining RS with a scanning tunneling microscope and side-illumination optics, demonstrated significant enhancement on both optical sensitivity and spatial resolution using either silver (Ag)-coated tungsten (W) tips or gold (Au) tips. The sensitivity improvement was verified by observing the enhancement effects on silicon (Si) substrates. Lateral resolution was verified to be below 100 nm by mapping Ag nanostructures. By deploying the depolarization technique, an apparent enhancement of 175% on Si substrates was achieved. Furthermore, the developed instrument features fast and reliable optical alignment, versatile sample adaptability, and effective suppression of far-field signals.

A hidden Markov model to assess drug-induced sleep fragmentation in the telemetered rat.

PubMed

Diack, C; Ackaert, O; Ploeger, B A; van der Graaf, P H; Gurrell, R; Ivarsson, M; Fairman, D

2011-12-01

Drug-induced sleep fragmentation can cause sleep disturbances either via their intended pharmacological action or as a side effect. Examples of disturbances include excessive daytime sleepiness, insomnia and nightmares. Developing drugs without these side effects requires insight into the mechanisms leading to sleep disturbance. The characterization of the circadian sleep pattern by EEG following drug exposure has improved our understanding of these mechanisms and their translatability across species. The EEG shows frequent transitions between specific sleep states leading to multiple correlated sojourns in these states. We have developed a Markov model to consider the high correlation in the data and quantitatively compared sleep disturbance in telemetered rats induced by methylphenidate, which is known to disturb sleep, and of a new chemical entity (NCE). It was assumed that these drugs could either accelerate or decelerate the transitions between the sleep states. The difference in sleep disturbance of methylphenidate and the NCE were quantitated and different mechanisms of action on rebound sleep were identified. The estimated effect showed that both compounds induce sleep fragmentation with methylphenidate being fivefold more potent compared to the NCE.

Roles of urea and TMAO on the interaction between extended non-polar peptides

NASA Astrophysics Data System (ADS)

Su, Zhaoqian; Dias, Cristiano

Urea and trimethylamine n-oxide (TMAO) are small molecules known to destabilize and stabilize, respectively, the structure of proteins when added to aqueous solution. To unravel the molecular mechanisms of these cosolvents on protein structure we perform explicit all-atom molecular dynamics simulations of extended poly-alanine and polyleucine dimers. We use an umbrella sampling protocol to compute the potential of mean force (PMF) of dimers at different concentrations of urea and TMAO. We find that the large non-polar side chain of leucine is affected by urea whereas backbone atoms and alanine's side chain are not. Urea is found to occupy positions between leucine's side chains that are not accessible to water. This accounts for extra Lennard-Jones bonds between urea and side chains that favors the unfolded state. These bonds compete with urea-solvent interactions that favor the folded state. The sum of these two energetic terms provide the enthalpic driving force for unfolding. We show here that this enthalpy correlate with the potential of mean force of poly-leucine dimers. Moreover, the framework developed here is general and may be used to provide insights into effects of other small molecules on protein interactions. The effect of the TMAO will be in the presentation. Department of Physics, University Heights, Newark, New Jersey, 07102-1982.

The underlying number-space mapping among kindergarteners and its relation with early numerical abilities.

PubMed

Chan, Winnie Wai Lan; Wong, Terry Tin-Yau

2016-08-01

People map numbers onto space. The well-replicated SNARC (spatial-numerical association of response codes) effect indicates that people have a left-sided bias when responding to small numbers and a right-sided bias when responding to large numbers. This study examined whether such spatial codes were tagged to the ordinal or magnitude information of numbers among kindergarteners and whether it was related to early numerical abilities. Based on the traditional magnitude judgment task, we developed two variant tasks-namely the month judgment task and dot judgment task-to elicit ordinal and magnitude processing of numbers, respectively. Results showed that kindergarteners oriented small numbers toward the left side and large numbers toward the right side when processing the ordinal information of numbers in the month judgment task but not when processing the magnitude information in the number judgment task and dot judgment task, suggesting that the left-to-right spatial bias was probably tagged to the ordinal but not magnitude property of numbers. Moreover, the strength of the SNARC effect was not related to early numerical abilities. These findings have important implications for the early spatial representation of numbers and its role in numerical performance among kindergarteners. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhancing Electromagnetic Side-Channel Analysis in an Operational Environment

NASA Astrophysics Data System (ADS)

Montminy, David P.

Side-channel attacks exploit the unintentional emissions from cryptographic devices to determine the secret encryption key. This research identifies methods to make attacks demonstrated in an academic environment more operationally relevant. Algebraic cryptanalysis is used to reconcile redundant information extracted from side-channel attacks on the AES key schedule. A novel thresholding technique is used to select key byte guesses for a satisfiability solver resulting in a 97.5% success rate despite failing for 100% of attacks using standard methods. Two techniques are developed to compensate for differences in emissions from training and test devices dramatically improving the effectiveness of cross device template attacks. Mean and variance normalization improves same part number attack success rates from 65.1% to 100%, and increases the number of locations an attack can be performed by 226%. When normalization is combined with a novel technique to identify and filter signals in collected traces not related to the encryption operation, the number of traces required to perform a successful attack is reduced by 85.8% on average. Finally, software-defined radios are shown to be an effective low-cost method for collecting side-channel emissions in real-time, eliminating the need to modify or profile the target encryption device to gain precise timing information.

Complementary velocity and heat transfer measurements in a rotating turbine cooling passage

NASA Astrophysics Data System (ADS)

Bons, Jeffrey Peter

An experimental investigation was conducted on the internal flowfield of a simulated turbine blade cooling passage. The passage is of a square cross-section and was manufactured from quartz for optical accessibility. Velocity measurements were taken using Particle Image Velocimetry for both heated and non-heated cases. Thin film resistive heaters on the four passage walls allow heat to be added to the coolant flow without obstructing laser access. Under the same conditions, an infrared detector with associated optics collected wall temperature data for use in calculating local Nusselt number. The test section was operated with radial outward flow and at values of Reynolds number, Rotation number, and density ratio typical of applications. Velocity data for the non-heated case document the evolution of the Coriolis-induced double vortex. The vortex has the effect of increasing the leading side boundary layer thickness while decreasing the trailing side boundary layer thickness. Also, the streamwise component of the Coriolis acceleration creates a thinned side wall boundary layer. These data reveal an unsteady, turbulent flowfield in the cooling passage. Velocity data for the heated case show a strongly distorted streamwise profile indicative of a buoyancy effect on the leading side. The Coriolis vortex is the mechanism for the accumulation of stagnant flow on the leading side of the passage. Heat transfer data show a maximum factor of two difference in the Nusselt number from trailing side to leading side. An estimate of this heat transfer disparity based on the measured boundary layer edge velocity yields approximately the same factor of two. A momentum integral model was developed for data interpretation which accounts for Coriolis and buoyancy effects. Calculated streamwise profiles and secondary flows match the experimental data well. The model, the velocity data, and the heat transfer data combine to suggest the presence of separated flow on the leading wall starting at about five passage widths for the conditions studied. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.)

Upper extremity interaction with a helicopter side airbag: injury criteria for dynamic hyperextension of the female elbow joint.

PubMed

Duma, Stefan M; Hansen, Gail A; Kennedy, Eric A; Rath, Amber L; McNally, Craig; Kemper, Andrew R; Smith, Eric P; Brolinson, P Gunnar; Stitzel, Joel D; Davis, Martin B; Bass, Cameron R; Brozoski, Frederick T; McEntire, B Joseph; Alem, Nabih M; Crowley, John S

2004-11-01

This paper describes a three part analysis to characterize the interaction between the female upper extremity and a helicopter cockpit side airbag system and to develop dynamic hyperextension injury criteria for the female elbow joint. Part I involved a series of 10 experiments with an original Army Black Hawk helicopter side airbag. A 5(th) percentile female Hybrid III instrumented upper extremity was used to demonstrate side airbag upper extremity loading. Two out of the 10 tests resulted in high elbow bending moments of 128 Nm and 144 Nm. Part II included dynamic hyperextension tests on 24 female cadaver elbow joints. The energy source was a drop tower utilizing a three-point bending configuration to apply elbow bending moments matching the previously conducted side airbag tests. Post-test necropsy showed that 16 of the 24 elbow joint tests resulted in injuries. Injury severity ranged from minor cartilage damage to more moderate joint dislocations and severe transverse fractures of the distal humerus. Peak elbow bending moments ranged from 42.4 Nm to 146.3 Nm. Peak bending moment proved to be a significant indicator of any elbow injury (p = 0.02) as well as elbow joint dislocation (p = 0.01). Logistic regression analyses were used to develop single and multiple variate injury risk functions. Using peak moment data for the entire test population, a 50% risk of obtaining any elbow injury was found at 56 Nm while a 50% risk of sustaining an elbow joint dislocation was found at 93 Nm for the female population. These results indicate that the peak elbow bending moments achieved in Part I are associated with a greater than 90% risk for elbow injury. Subsequently, the airbag was re-designed in an effort to mitigate this as well as the other upper extremity injury risks. Part III assessed the redesigned side airbag module to ensure injury risks had been reduced prior to implementing the new system. To facilitate this, 12 redesigned side airbag deployments were conducted using the same procedures as Part I. Results indicate that the re-designed side airbag has effectively mitigated elbow injury risks induced by the original side airbag design. It is anticipated that this study will provide researchers with additional injury criteria for assessing upper extremity injury risk caused by both military and automotive side airbag deployments.

A Combined Finite-Element/Discrete-Particle Analysis of a Side-Vent-Channel-Based Concept for Improved Blast-Survivability of Light Tactical Vehicles

DTIC Science & Technology

2013-01-01

design of side- vent-channels. The results obtained confirmed the beneficial effects of the side-vent-channels in reducing the blast momentum , although...confirmed the beneficial effects of the side-vent-channels in reducing the blast momentum , although the extent of these effects is relatively small (3...products against the surrounding medium is associated with exchange of linear momentum and various energy components (e.g. potential, thermal

Antiepileptic Drug Behavioral Side Effects in Individuals with Mental Retardation and the Use of Behavioral Measurement Techniques.

ERIC Educational Resources Information Center

Kalachnik, John E.; And Others

1995-01-01

Behavioral psychology measurement methods helped assess antiepileptic drug behavioral side effects in five individuals with mental retardation who could not verbally communicate presence of side effects. When the suspected antiepileptic drug was altered, an 81% reduction of maladaptive behaviors occurred. The measurement methods enabled systematic…

Current Status of the Matson Evaluation of Drug Side Effects (MEDS)

ERIC Educational Resources Information Center

Matson, Johnny L.; Cervantes, Paige E.

2013-01-01

The Matson Evaluation of Drug Side Effects (MEDS) is currently the best established and most researched measure of drug side effects in the intellectual disability (ID) literature. Initial research was conducted on its psychometric properties such as reliability and validity. More recent research studies have used the measure to determine the…

Staff Knowledge of the Side Effects of Anti-Psychotic Medication

ERIC Educational Resources Information Center

Fretwell, Christine; Felce, David

2007-01-01

Background: Anti-psychotic medications are widely prescribed to people with intellectual disabilities and have a range of negative side effects. The aim was to identify the level of knowledge of anti-psychotic medications and their side effects among key carers or home managers of adults with intellectual disabilities living in residential group…

Use of a 22-gauge Whitacre needle to reduce the incidence of side effects after lumbar myelography: a prospective randomised study comparing Whitacre and Quincke spinal needles.

PubMed

Pedersen, O N

1996-01-01

In a prospective study lumbar iohexol myelography was performed in 107 consecutive patients, randomised for lumbar puncture with a Quincke or Whitacre spinal needle. All patients answered a questionnaire about possible side effects. Data from 100 patients (58 men, 42 women) were evaluated. In the Quincke group (n = 53), 23 (43%) reported no side effects. In the 30 patients who reported various side effects, post-dural puncture headache (PDPH) occurred in 22 (42%), of whom 9 had mild, 6 moderate and 7 (13%) severe cephalalgia, 18 (34%) reported increased low back pain/sciatica, 5 nausea and 7 dizziness. In the Whitacre group (n = 47), 33 (70%) had no side effects. PDPH was reported by 9 patients (19%), of whom 2 had mild, 6 moderate and only 1 (2%) severe cephalalgia, 4 (9%) reported increased low back pain/sciatica, 5 nausea and 4 dizziness. The conclusion drawn from this study is that lumbar myelography performed with the Whitacre spinal needle reduces postspinal side effects.

The role side effects play in the choice of antiepileptic therapy in brain tumor-related epilepsy: a comparative study on traditional antiepileptic drugs versus oxcarbazepine

PubMed Central

Maschio, Marta; Dinapoli, Loredana; Vidiri, Antonello; Pace, Andrea; Fabi, Alessandra; Pompili, Alfredo; Carapella, Maria Carmine; Jandolo, Bruno

2009-01-01

Background Seizure control doesn't represent the only challenging goal in patients with brain tumor-related epilepsy. Side effects have often taken precedence for patients' quality of life. Methods We performed an observational retrospective study on patients with brain tumor-related epilepsy: 35 who had assumed oxcarbazepine monotherapy and 35 patients who had undergone treatment with traditional antiepileptic drugs. Primary variable of efficacy was the mean seizure frequency per month and safety variables were the drop-out for side effects and total incidence of side effects. We applied the Propensity Score technique to minimize selection bias. Results Our results showed a similar efficacy of oxcarbazepine and traditional antiepileptic drugs over time, but the difference in safety and tolerability between the two groups was significant: traditional AEDs caused more side effects, both serious and non serious. Conclusion This study highlights the importance of taking into consideration not only seizure control but also the appearance of side effects when choosing antiepileptic drugs in this patients population. PMID:19419544

Side effects induced by the acute levodopa challenge in Parkinson's Disease and atypical parkinsonisms.

PubMed

Vasta, Rosario; Nicoletti, Alessandra; Mostile, Giovanni; Dibilio, Valeria; Sciacca, Giorgia; Contrafatto, Donatella; Cicero, Calogero Edoardo; Raciti, Loredana; Luca, Antonina; Zappia, Mario

2017-01-01

Acute levodopa challenge may be performed to predict levodopa chronic responsiveness. The aim of the study was to investigate frequency of side effects during the acute levodopa challenge in PD and atypical parkinsonisms. We enrolled 34 de novo PD patients and 29 patients affected by atypical parkinsonisms (Multiple System Atrophy, MSA, n = 10; Progressive Supranuclear Palsy, PSP, n = 12 and Corticobasal Degeneration, CBD, n = 7) who underwent an acute levodopa challenge. Side effects occurring during test were recorded. Side effects were more frequent among atypical parkinsonisms as unique group when compared to PD patients (64.3% versus 23.5%; p-value 0.002) with an adjusted OR of 4.36 (95%CI 1.40-13.5). Each atypical parkinsonisms showed almost double occurrence of side effects (MSA 90%, PSP 41.7% and CBD 57%). Side effects during acute levodopa challenge may be frequent in atypical parkinsonisms. This information could be useful in order to better prepare the patient for the test. Furthermore, it could represent a useful cue in differential diagnosis with PD.

Cataplexy as a side effect of modafinil in a patient without narcolepsy☆

PubMed Central

Lopes, Eduardo; Pereira, Danielle; da Silva Behrens, Nilce Sanny Costa; de Almeida Fonseca, Hassana; Calvancanti, Paola Oliveira; de Araújo Lima, Taís Figueiredo; Pradella-Hallinan, Marcia; Castro, Juliana; Tufik, Sergio; Coelho, Fernando Morgadinho Santos

2014-01-01

Narcolepsy is a disease in which there is diurnal excessive sleepiness with sleep attacks and a prevalence in the general population of 1/4000 individuals. Classically, it is characterized by cataplexy, sleep paralysis, hypnagogic hallucinations and fragmented sleep. The use of modafinil in the treatment of narcolepsy is the first option of treatment for diurnal excessive sleepiness. Although considered a safe drug for use in patients with narcolepsy, being utilized for more than 20 years, modafinil possesses a series of side effects, some of them still not fully researched or described. Side effects such as headache, nausea, anxiety, insomnia, lumbago, diarrhea, dyspepsia, rhinitis and vertigo are the most frequent. However, the clinical follow-up of patients under treatment with modafinil must be intensive and the side effects ought to be noted and evaluated. The under-response to treatment or the unexpected side effects must always be directed to differential diagnostics. The objective of this article is to describe an unexpected side effect of the use of modafinil in a patient with incorrect diagnosis of narcolepsy. PMID:26483900

Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS) as a subjective measure of drug-induced parkinsonism and akathisia.

PubMed

Jung, Hee-Yeon; Kim, Jong-Hoon; Ahn, Yong-Min; Kim, Seong-Chan; Hwang, Samuel S; Kim, Yong-Sik

2005-01-01

The Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS) was examined for its usefulness as a subjective measure of drug-induced parkinsonism and akathisia. Eighty-three subjects were assessed using the LUNSERS, the Simpson-Angus Scale (SAS) and the Barnes Akathisia Rating Scale (BARS), before and after a 6-week treatment with olanzapine. Significant correlations were found between the changes in scores of parkinsonism items of LUNSERS and SAS. The changes in scores of akathisia item (restlessness), extrapyramidal side effects (EPS) subscale and psychic side-effects subscale of LUNSERS were significantly correlated with those of the BARS. 'Shakiness', one item of the EPS subscale of LUNSERS, correctly classified between parkinsonism and non-parkinsonism groups with 81.0% accuracy. A combination of four items included in EPS and psychic side-effect subscales of LUNSERS identified akathisia and non-akathisia groups with 76.2% accuracy. These results suggest that the EPS and psychic side-effect subscales of LUNSERS may be useful in screening for drug-induced parkinsonism and akathisia. Copyright (c) 2004 John Wiley & Sons, Ltd.

Photo-thermal nanosystems for diseased cell treatment

NASA Astrophysics Data System (ADS)

Raeesi, Vahid

The prevalence of cancer and infectious disease demands for development of more effective treatment technologies. Current standard chemo- and radiotherapy for cancer offer only relative therapeutic efficacy at the cost of significant side-effects. On the other hand, resistance of microbes to current antibiotics has raised serious concern in public health sectors such as hospitals. Thermal therapy is an alternative technique that employs high temperatures to treat diseased cells via direct and indirect heat effects. Owing to its nature, this technique can offer enhanced therapeutic efficacy in local diseased regions via either mono- or combinatorial platforms and very minimal side-effects. However, existing bulk heating systems are limited in providing selective and controlled temperature rise in the desired region at tissue/cellular scales. This compromises the therapeutic efficacy of the treatment and increases the risk of off-target heating in healthy tissues. In this thesis, we propose the use of heat-generating nanoparticles to precisely target heat into small regions and study how they can be applied in cancer and bacteria treatment. Our model nanoparticle system generates heat by light stimulation. Different nanosystems based on this particle are developed and their thermal effects on therapeutic distribution are explored at tumor tissue and cellular scales. In addition, the thermal effect of these nanoparticles is utilized to overcome microbial resistance. By mechanistic understanding of nanoparticle thermal effects at different length scales, this research helps to rationalize proper design and development of heat- generating nanomedicine for cancer and microbial treatments.

Seeing is believing: Impact of social modeling on placebo and nocebo responding.

PubMed

Faasse, Kate; Grey, Andrew; Jordan, Rachel; Garland, Stacie; Petrie, Keith J

2015-08-01

This study investigated the impact of the social modeling of side effects following placebo medication ingestion on the nocebo and placebo effect. It also investigated whether medication branding (brand or generic labeling) moderated social modeling effects. Eighty-two university students took part in the study which was purportedly investigating the impact of fast-acting beta-blocker medications (actually placebos) on preexamination anxiety. After taking the medication, participants were randomized to either witness a female confederate report experiencing side effects or no side effects after taking the same medication. Differences in symptom reporting, blood pressure, heart rate, and anxiety were assessed between the social modeling of side effects and no modeling groups. Seeing a female confederate report side effects reduced the placebo effect in systolic (p = .009) and diastolic blood pressure (p = .033). Seeing a female confederate report side effects also increased both total reported symptoms (mean [SE] 7.35 [.54] vs. 5.16 [0.53] p = .005) and symptoms attributed to the medication (5.27 [0.60] vs. 3.04 [0.59] p = .01), although the effect on symptoms was only seen in female participants. Females who saw the confederate report side effects reported approximately twice the number of symptoms as those in the no modeling group. Social modeling did not affect heart rate or anxiety. Medication branding did not influence placebo or nocebo outcomes. The social modeling of symptoms can substantially reduce or eliminate the placebo effect. Viewing a female confederate display symptoms after taking the same medication increases symptom reporting in females. (c) 2015 APA, all rights reserved).

Transient Three-Dimensional Analysis of Nozzle Side Load in Regeneratively Cooled Engines

NASA Technical Reports Server (NTRS)

ng, Ten-See

2005-01-01

Nozzle side loads are potentially detrimental to the integrity and life of almost all launch vehicles. the lack of a detailed prediction capability results in reducing life and increased weight for reusable nozzle systems. A clear understanding of the mechanism that contribute to side loads during engine startup, shutdown, and steady-state operations must be established. A CFD based predictive tool must be developed to aid the understanding of side load physics and development of future reusable engine.

Moffatt eddies at an interface

NASA Astrophysics Data System (ADS)

Shtern, Vladimir

2014-12-01

It is shown that an infinite set of eddies can develop near the interface-wall intersection in a two-fluid flow. A striking feature is that the eddy occurrence depends on from what side of the interface the flow is driven. In air-water flows where the viscosity ratio is 0.018, the eddies develop if a driving source is located on (i) the air side for , (ii) any side for , and (iii) the water side for , where is the upper interface-wall angle.

[Gestrinone in pelvic endometriosis. A one-year evaluation].

PubMed

Cervantes Villarreal, E; García Zamarripa, H R; Herrera Prado, E; Barrón Vallejo, J

1995-08-01

The therapeutical effectiveness of gestrinone in endometriosis treatment, as well as its long term side effects, were evaluated. Prospective, clinical trial. At "Dr. Alejandro Castanedo Kimball" Hospital (PEMEX). Salamanca, Guanajuato. México. Thirty women with laparoscopically confirmed endometriosis, were studied. Subjects received 2.5 mg. of gestrinone two times per week for 6 months. Laparoscopy was performed before treatment, and clinical response was determined by second laparoscopy after 6 months. The pregnancy rate, frequency of side effects and recurrence of symptoms were determined. Median total endometriosis scores and symptoms decreased significantly after treatment. Four pregnancies were observed after treatment. The principal side effects were: ponderal increase, changes in the voice and hirsutism. However, the side effects disappeared after one year of clinical survey. The results indicate that gestrinone is effective in the treatment of pelvic endometriosis. In despite of a clear benefic effect on stage of the disease and symptoms; the use of gestrinone should weigh the risk-benefit (cost versus metabolic side effects) of treatment.

Recent progress in the development of polysaccharide conjugates of docetaxel and paclitaxel

PubMed Central

Roy, Aniruddha; Bhattacharyya, Mousumi; Ernsting, Mark J.; May, Jonathan P; Li, Shyh-Dar

2014-01-01

Taxanes are one of the most potent and broadest spectrum chemotherapeutics used clinically, but also induce significant side effects. Different strategies have been developed to produce a safer taxane formulation. Development of polysaccharide drug conjugates has increased in the recent years due to the demonstrated biocompatibility, biodegradability, safety and low cost of the biopolymers. This review focuses on polysaccharide taxane conjugates and provides an overview on various conjugation strategies and their effect on the efficacy. Detailed analyses on the designing factors of an effective polysaccharide drug conjugate are provided with a discussion on the future direction of this field. PMID:24652678

A Multidimensional Strategy to Detect Polypharmacological Targets in the Absence of Structural and Sequence Homology

PubMed Central

Durrant, Jacob D.; Amaro, Rommie E.; Xie, Lei; Urbaniak, Michael D.; Ferguson, Michael A. J.; Haapalainen, Antti; Chen, Zhijun; Di Guilmi, Anne Marie; Wunder, Frank; Bourne, Philip E.; McCammon, J. Andrew

2010-01-01

Conventional drug design embraces the “one gene, one drug, one disease” philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional strategy for the identification of secondary targets of known small-molecule inhibitors in the absence of global structural and sequence homology with the primary target protein. To demonstrate the utility of the strategy, we identify several targets of 4,5-dihydroxy-3-(1-naphthyldiazenyl)-2,7-naphthalenedisulfonic acid, a known micromolar inhibitor of Trypanosoma brucei RNA editing ligase 1. As it is capable of identifying potential secondary targets, the strategy described here may play a useful role in future efforts to reduce drug side effects and/or to increase polypharmacology. PMID:20098496

A multidimensional strategy to detect polypharmacological targets in the absence of structural and sequence homology.

PubMed

Durrant, Jacob D; Amaro, Rommie E; Xie, Lei; Urbaniak, Michael D; Ferguson, Michael A J; Haapalainen, Antti; Chen, Zhijun; Di Guilmi, Anne Marie; Wunder, Frank; Bourne, Philip E; McCammon, J Andrew

2010-01-22

Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional strategy for the identification of secondary targets of known small-molecule inhibitors in the absence of global structural and sequence homology with the primary target protein. To demonstrate the utility of the strategy, we identify several targets of 4,5-dihydroxy-3-(1-naphthyldiazenyl)-2,7-naphthalenedisulfonic acid, a known micromolar inhibitor of Trypanosoma brucei RNA editing ligase 1. As it is capable of identifying potential secondary targets, the strategy described here may play a useful role in future efforts to reduce drug side effects and/or to increase polypharmacology.

Retrospective study of canine nasal tumor treated with hypofractionated radiotherapy.

PubMed

Maruo, Takuya; Shida, Takuo; Fukuyama, Yasuhiro; Hosaka, Soshi; Noda, Masashi; Ito, Tetsuro; Sugiyama, Hiroki; Ishikawa, Takeshi; Madarame, Hiroo

2011-02-01

The object of this study was to evaluate hypofractionated multiportal field and two-portion (rostral and caudal portions divided by the eyelid) radiation therapy for canine nasal tumors. Sixty-three dogs underwent multiportal hypofractionated radiation therapy. The radiation field was divided into rostral and caudal portions by the eyelid. Treatments were performed four times for 57 dogs. The median irradiation dose/fraction was 8 Gy (range, 5-10 Gy); the median total dose was 32 Gy (10-40 Gy). Improvement of clinical symptoms was achieved in 53 (84.1%) of 63 cases. Median survival time was 197 days (range, 2-1,080 days). Median survival times with and without destruction of the cribriform plate before radiotherapy were 163 and 219 days, respectively. There was no significant difference between them. No other factors were related to survival according to a univariate analysis. All radiation side effects, except one, were grade I according to the VRTOG classification. It was not necessary to treat any dogs for skin side effects. One dog (1.6%) developed an oronasal fistula 1 year after completion of radiation therapy. This radiation protocol may be useful in reducing radiation side effects in dogs with cribriform plate destruction.

Women's perceptions of iron deficiency and anemia prevention and control in eight developing countries.

PubMed

Galloway, Rae; Dusch, Erin; Elder, Leslie; Achadi, Endang; Grajeda, Ruben; Hurtado, Elena; Favin, Mike; Kanani, Shubhada; Marsaban, Julie; Meda, Nicolas; Moore, K Mona; Morison, Linda; Raina, Neena; Rajaratnam, Jolly; Rodriquez, Javier; Stephen, Chitra

2002-08-01

The World Health Organization estimates that 58% of pregnant women in developing countries are anemic. In spite of the fact that most ministries of health in developing countries have policies to provide pregnant women with iron in a supplement form, maternal anemia prevalence has not declined significantly where large-scale programs have been evaluated. During the period 1991-98, the MotherCare Project and its partners conducted qualitative research to determine the major barriers and facilitators of iron supplementation programs for pregnant women in eight developing countries. Research results were used to develop pilot program strategies and interventions to reduce maternal anemia. Across-region results were examined and some differences were found but the similarity in the way women view anemia and react to taking iron tablets was more striking than differences encountered by region, country or ethnic group. While women frequently recognize symptoms of anemia, they do not know the clinical term for anemia. Half of women in all countries consider these symptoms to be a priority health concern that requires action and half do not. Those women who visit prenatal health services are often familiar with iron supplements, but commonly do not know why they are prescribed. Contrary to the belief that women stop taking iron tablets mainly due to negative side effects, only about one-third of women reported that they experienced negative side effects in these studies. During iron supplementation trials in five of the countries, only about one-tenth of the women stopped taking the tablets due to side effects. The major barrier to effective supplementation programs is inadequate supply. Additional barriers include inadequate counseling and distribution of iron tablets, difficult access and poor utilization of prenatal health care services, beliefs against consuming medications during pregnancy, and in most countries, fears that taking too much iron may cause too much blood or a big baby, making delivery more difficult. Facilitators include women's recognition of improved physical well being with the alleviation of symptoms of anemia, particularly fatigue, a better appetite, increased appreciation of benefits for the fetus, and subsequent increased demand for prevention and treatment of iron deficiency and anemia.

Experimental aerodynamic characteristics for a cylindrical body of revolution with side strakes and various noses at angles of attack from 0 degrees to 58 degrees and Mach numbers from 0.6 to 2.0

NASA Technical Reports Server (NTRS)

Jorgensen, L. H.; Nelson, E. R.

1975-01-01

For a body of revolution with afterbody side strakes, an experimental investigation was conducted in the Ames 6- by 6-Foot Wind Tunnel to determine the effects on the aerodynamic characteristics of forebody geometry, nose strakes, body side strakes, Reynolds number, Mach number, and angle of attack. Aerodynamic force and moment characteristics were measured for the straked cylindrical afterbody (cylinder fineness ratio of 7) with tangent ogive noses of fineness ratio 2.5 to 5.0. In addition, the straked cylinder afterbody was tested with an ogive nose having a rounded tip and an ogive nose with two different nose strake arrangements. The data demonstrate that the aerodynamic characteristics for a body of revolution with side strakes can be significantly affected by changes in nose fineness ratio, nose bluntness, Reynolds number, Mach number, and, of course, angle of attack. Removing the strakes from the cylindrical aftersection greatly decreased the lift, but this removal hardly changed the maximum magnitudes of the undesirable side forces that developed at angles of attack greater than about 25 deg for subsonic Mach numbers.

Operating Experience and Lessons Learned in the Use of Soft-Sided Packaging for Transportation and Disposal of Low Activity Radioactive Waste

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

Kapoor, A.; Gordon, S.; Goldston, W.

2013-07-08

This paper describes the operating experience and lessons learned at U.S. Department of Energy (DOE) sites as a result of an evaluation of potential trailer contamination and soft-sided packaging integrity issues related to the disposal of low-level and mixed low-level (LLW/MLLW) radioactive waste shipments. Nearly 4.3 million cubic meters of LLW/MLLW will have been generated and disposed of during fiscal year (FY) 2010 to FY 2015—either at commercial disposal sites or disposal sites owned by DOE. The LLW/MLLW is packaged in several different types of regulatory compliant packaging and transported via highway or rail to disposal sites safely and efficientlymore » in accordance with federal, state, and local regulations and DOE orders. In 1999, DOE supported the development of LLW containers that are more volumetrically efficient, more cost effective, and easier to use as compared to metal or wooden containers that existed at that time. The DOE Idaho National Engineering and Environmental Laboratory (INEEL), working in conjunction with the plastic industry, tested several types of soft-sided waste packaging systems that meet U.S. Department of Transportation requirements for transport of low specific activity and surface contaminated objects. Since then, soft-sided packaging of various capacities have been used successfully by the decontamination and decommissioning (D&D) projects to package, transport, and dispose D&D wastes throughout the DOE complex. The joint team of experts assembled by the Energy Facility Contractors Group from DOE waste generating sites, DOE and commercial waste disposal facilities, and soft-sided packaging suppliers conducted the review of soft-sided packaging operations and transportation of these packages to the disposal sites. As a result of this evaluation, the team developed several recommendations and best practices to prevent or minimize the recurrences of equipment contamination issues and proper use of soft-sided packaging for transport and disposal of waste.« less

Investigating the Effects of Side Airbag Deployment in Real-World Crashes Using Crash Comparison Techniques

PubMed Central

Loftis, Kathryn L.; Weaver, Ashley A.; Stitzel, Joel D.

2011-01-01

The objective of this study was to investigate side airbag (SAB) deployment in near side crashes and compare injuries and contact points between occupants with and without SAB deployment. Using NASS 2000–2008 and selecting for near side cases, with PDOF ± 20 degrees from 90 or 270, for non-pregnant adult belted occupants, there were 20,253 (weighted) SAB deployments. NASS showed that SABs have been increasing within the fleet, comprising 2% of airbags in 2000 and increasing to 33% of airbags in 2008. To investigate deployed SABs, we developed a three-step methology to pair CIREN cases to study the effects of deployment on occupant outcome. The first step involved extracting near side impacts from CIREN with adult, non-pregnant occupants seated in row 1 (drivers or right front passengers). In the second step, each case was quantitatively compared to FMVSS 214 barrier test standards using a 6 point similarity scoring system. Cases scoring at least 3 points were then qualitatively analyzed and 33 pairs of cases of the same vehicle make/model but opposite SAB status were chosen. Occupants with deployed SAB had reduced occurrences and severity of head and face, neck and cervical spine, and thoracic injuries and fewer injurious contacts to side components including the door, a-pillar, and window sill. SAB deployment was statistically significant for reducing occupant MAIS and ISS and thorax airbags were statistically significant for reducing thoracic and neck/cervical spine injury severity. The average ISS with SAB deployment was 21, while the average ISS of those without was 33. This study establishes methods for performing comparisons between CIREN cases based on regulatory conditions and shows injury reduction in key body regions with SAB deployment. PMID:22105386

Dentoalveolar growth inhibition induced by bone denudation on palates: a study of two isolated cleft palates with asymmetric scar tissue distribution.

PubMed

Ishikawa, H; Iwasaki, H; Tsukada, H; Chu, S; Nakamura, S; Yamamoto, K

1999-09-01

This report presents two cases of isolated cleft palate with asymmetric distribution of postsurgical scar tissue determined by laser Doppler flowmetry. To determine the effect of mucoperiosteal denudation of the bone on maxillary alveolar growth, the analysis of dentoalveolar structures compared the affected side to the unaffected side of each case. Two Japanese girls with isolated cleft palates were examined. Both subjects had undergone pushback operations (a modified version of the procedure of Wardill) for palatal repair at 18 months of age. Palatal blood flow was examined by laser Doppler flowmetry when the girls were 12 years old to determine the extent of postsurgical scar tissue over the denuded bone. To analyze the maxillary dentoalveolar structures three dimensionally, the whole surface of the upper dental cast was measured and recorded by an optical measuring device when the girls were 7 years old. Analysis via flowmetry showed that the palatal scar tissue area was limited to the anterior tooth region on the right (unaffected) side but extended posteriorly to the premolar region on the left (affected) side in both subjects. The two girls had similar dentoalveolar structures, with the dental and alveolar arches deflected lingually at the deciduous molar area on the affected side. There were no differences in the buccolingual inclination of deciduous molars or in the vertical growth of the alveolar processes between the affected and unaffected sides. In both girls, bone denudation in the premolar region appeared to result in less than 3 mm of displacement of the teeth palatally, with no change in lingual inclination. Any effects of scar tissue on the vertical development of the alveolus were not substantiated.

Immunization with Small Amyloid-β-derived Cyclopeptide Conjugates Diminishes Amyloid-β-Induced Neurodegeneration in Mice.

PubMed

Mulder, Cornelis K; Dong, Yun; Brugghe, Humphrey F; Timmermans, Hans A M; Tilstra, Wichard; Westdijk, Janny; van Riet, Elly; van Steeg, Harry; Hoogerhout, Peter; Eisel, Ulrich L M

2016-01-01

Soluble oligomeric (misfolded) species of amyloid-β (Aβ) are the main mediators of toxicity in Alzheimer's disease (AD). These oligomers subsequently form aggregates of insoluble fibrils that precipitate as extracellular and perivascular plaques in the brain. Active immunization against Aβ is a promising disease modifying strategy. However, eliciting an immune response against Aβ in general may interfere with its biological function and was shown to cause unwanted side-effects. Therefore, we have developed a novel experimental vaccine based on conformational neo-epitopes that are exposed in the misfolded oligomeric Aβ, inducing a specific antibody response. Here we investigate the protective effects of the experimental vaccine against oligomeric Aβ1-42-induced neuronal fiber loss in vivo. C57BL/6 mice were immunized or mock-immunized. Antibody responses were measured by enzyme-linked immunosorbent assay. Next, mice received a stereotactic injection of oligomeric Aβ1-42 into the nucleus basalis of Meynert (NBM) on one side of the brain (lesion side), and scrambled Aβ1-42 peptide in the contralateral NBM (control side). The densities of choline acetyltransferase-stained cholinergic fibers origination from the NBM were measured in the parietal neocortex postmortem. The percentage of fiber loss in the lesion side was determined relative to the control side of the brain. Immunized responders (79%) showed 23% less cholinergic fiber loss (p = 0.01) relative to mock-immunized mice. Moreover, fiber loss in immunized responders correlated negatively with the measured antibody responses (R2 = 0.29, p = 0.02). These results may provide a lead towards a (prophylactic) vaccine to prevent or at least attenuate (early onset) AD symptoms.

Evaluation of patients’ experiences with antidepressants reported by means of a medicine reporting system

PubMed Central

van Geffen, E. C. G.; van der Wal, S. W.; van Hulten, R.; de Groot, M. C. H.; Egberts, A. C. G.

2007-01-01

Objective To assess experiences related to antidepressant use reported to an internet-based medicine reporting system and to compare the nature of the side effects reported by patients with those reported by health care professionals (HCPs). Methods All reports submitted from May 2004 to May 2005 to an internet-based medicine reporting system in The Netherlands related to the use of antidepressants were analysed. Spontaneous reports of adverse drug reactions on antidepressants from HCPs received by The Netherlands Pharmacovigilance Centre Lareb from May 2004 to May 2005 were included for comparison. Results Of the 2232 individuals who submitted a report to the internet-based medicine reporting system, 258 submitted a report on antidepressants. Of these, 92 individuals (36%) reported on effectiveness, 40 (16%) of whom reported on ineffectiveness, and 217 (84%) submitted a report on side effects, with 202 (78%) reporting a total of 630 side effects that were experienced as negative. Fourteen individuals (5%) reported a practical issue and four (2%) reported a reimbursement issue. Of all 630 side effects reported, 48% resulted in the patient discontinuing the antidepressant therapy; of these 29% did not inform their HCP. Of all the side effects reported, 52% were perceived as “very negative”. In comparison to the side effects reported by HCPs, patients more often reported apathy, excessive sweating, ineffectiveness, somnolence, insomnia, sexual problems and weight increase. Conclusion Patients report the ineffectiveness and side effects of antidepressant therapy as negative and leading to discontinuation of the therapy. Patients and HCPs differ in the nature of the reported side effects. Patient experiences should be included in the evaluation of antidepressant treatment in clinical practice. PMID:17874086

Patient perceptions of glucocorticoid side effects: a cross-sectional survey of users in an online health community.

PubMed

Costello, Ruth; Patel, Rikesh; Humphreys, Jennifer; McBeth, John; Dixon, William G

2017-04-03

To identify the side effects most important to glucocorticoid (GC) users through a survey of a UK online health community (Healthunlocked.com). Online cross-sectional survey. Participants were recruited through Healthunlocked.com, an online social network for health. Adults who were currently taking GCs, or had taken GCs in the past month. Responders scored the importance of listed side effects from 1 to 10, with 10 being of high importance to them. For each side effect, histograms were plotted, and the median rating and IQR were determined. Side effects were ranked by median ranking (largest to smallest) and then IQR (smallest to largest). The scores were categorised as low (scores 1-3), medium (scores 4-7) and high (scores 8-10) importance. 604 responders completed the survey. Histograms of side effect scores showed a skew towards high importance for weight gain, a U-shaped distribution for cardiovascular disease (CVD), diabetes, eye disease and infections, and a skew towards low importance for acne. When ranked, the side effect of most importance to responders was weight gain (median score=9, IQR 6-10) followed by insomnia and moon face with equal median score (8) and IQR (5-10). Three serious side effects, CVD, diabetes and infections, were ranked of lower importance overall but had wide ranging scores (median score=8, IQR 1-10). The three most highly rated side effects were not clinically serious but remained important to patients, perhaps reflecting their impact on quality of life and high prevalence. This should be taken into consideration when discussing treatment options and planning future GC safety studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Specific expectancies are associated with symptomatic outcomes and side effect burden in a trial of chamomile extract for generalized anxiety disorder.

PubMed

Keefe, John R; Amsterdam, Jay; Li, Qing S; Soeller, Irene; DeRubeis, Robert; Mao, Jun J

2017-01-01

Patient expectancies are hypothesized to contribute to the efficacy and side effects of psychiatric treatments, but little research has investigated this hypothesis in the context of psychopharmacological therapies for anxiety. We prospectively investigated whether expectancies predicted efficacy and adverse events in oral therapy for Generalized Anxiety Disorder (GAD), controlling for confounding patient characteristics correlating with outcomes. Expectancies regarding treatment efficacy and side effects were assessed at baseline of an eight week open-label phase of a trial of chamomile for Generalized Anxiety Disorder (GAD). The primary outcome was patient-reported GAD-7 scores, with clinical response and treatment-emergent side-effects as secondary outcomes. Expectancies were used to predict symptomatic and side-effect outcomes. Very few baseline patient characteristics predicted either type of expectancy. Controlling for a patient's predicted recovery based on their baseline characteristics, higher efficacy expectancies at baseline predicted greater change on the GAD-7 (adjusted β = -0.19, p = 0.011). Efficacy expectancies also predicted a higher likelihood of attaining clinical response (adjusted odds ratio = 1.69, p = 0.002). Patients with higher side effect expectancies reported more side effects (adjusted log expected count = 0.26, p = 0.038). Efficacy expectancies were unrelated to side effect reports (log expected count = -0.05, p = 0.680), and side effect expectancies were unrelated to treatment efficacy (β = 0.08, p = 0.306). Patients entering chamomile treatment for GAD with more favorable self-generated expectancies for the treatment experience greater improvement and fewer adverse events. Aligning patient expectancies with treatment selections may optimize outcomes. Trial Number NCT01072344 at ClinicalTrials.gov. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exploring the role of drug-metabolising enzymes in antidepressant side effects.

PubMed

Hodgson, Karen; Tansey, Katherine E; Uher, Rudolf; Dernovšek, Mojca Zvezdana; Mors, Ole; Hauser, Joanna; Souery, Daniel; Maier, Wolfgang; Henigsberg, Neven; Rietschel, Marcella; Placentino, Anna; Craig, Ian W; Aitchison, Katherine J; Farmer, Anne E; Dobson, Richard J B; McGuffin, Peter

2015-07-01

Cytochrome P450 enzymes are important in the metabolism of antidepressants. The highly polymorphic nature of these enzymes has been linked to variability in antidepressant metabolism rates, leading to hope regarding the use of P450 genotyping to guide treatment. However, evidence that P450 genotypic differences underlie the variation in treatment outcomes is inconclusive. We explored the links between both P450 genotype and serum concentrations of antidepressant with antidepressant side effects, using data from the Genome-Based Therapeutic Drugs for Depression Project (GENDEP), which is a large (n = 868), pharmacogenetic study of depressed individuals treated with escitalopram or nortriptyline. Patients were genotyped for the enzymes CYP2C19 and CYP2D6, and serum concentrations of both antidepressant and primary metabolite were measured after 8 weeks of treatment. Side effects were assessed weekly. We investigated associations between P450 genotypes, serum concentrations of antidepressants and side effects, as well as the relationship between P450 genotype and study discontinuation. P450 genotype did not predict total side effect burden (nortriptyline: n = 251, p = 0.5638, β = -0.133, standard error (SE) = 0.229; escitalopram: n = 340, p = 0.9627, β = -0.004, SE = 0.085), study discontinuation (nortriptyline n = 284, hazard ratio (HR) = 1.300, p = 0.174; escitalopram n = 376, HR = 0.870, p = 0.118) or specific side effects. Serum concentrations of antidepressant were only related to a minority of the specific side effects measured: dry mouth, dizziness and diarrhoea. In this sample where antidepressant dosage is titrated using clinical judgement, P450 genotypes do not explain differences between patients in side effects with antidepressants. Serum drug concentrations appear to only explain variability in the occurrence of a minority of specific side effects.