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.

Managing Chemotherapy Side Effects: Sexual and Fertility Changes in Men

MedlinePlus

... Chemotherapy Side Effects Sexual and Fertility Changes in Men “I talked with my doctor before treatment. I ... other health issues are also important. Questions from men about sexual problems: What sexual problems might I ...

Managing Chemotherapy Side Effects: Urination Changes

MedlinePlus

... how important it was to drink lots of water. She told me what changes to call about, such as a fever or ... when you urinate Managing Chemotherapy Side Effects: Urination ... Drink liquids such as water, soup, milkshakes, and cranberry juice. Add extra water ...

Side Effects of Immunosuppressant Medications as They Affect Physical Fitness: A Physical Therapist's Point of View

MedlinePlus

... Another side effect of immunosuppressant medications is hyperglycemia (high blood sugar) and secondary diabetes because they may alter the way your body manages glucose (sugar). It is important to routinely check your ...

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.

An Ensemble Approach for Drug Side Effect Prediction

PubMed Central

Jahid, Md Jamiul; Ruan, Jianhua

2014-01-01

In silico prediction of drug side-effects in early stage of drug development is becoming more popular now days, which not only reduces the time for drug design but also reduces the drug development costs. In this article we propose an ensemble approach to predict drug side-effects of drug molecules based on their chemical structure. Our idea originates from the observation that similar drugs have similar side-effects. Based on this observation we design an ensemble approach that combine the results from different classification models where each model is generated by a different set of similar drugs. We applied our approach to 1385 side-effects in the SIDER database for 888 drugs. Results show that our approach outperformed previously published approaches and standard classifiers. Furthermore, we applied our method to a number of uncharacterized drug molecules in DrugBank database and predict their side-effect profiles for future usage. Results from various sources confirm that our method is able to predict the side-effects for uncharacterized drugs and more importantly able to predict rare side-effects which are often ignored by other approaches. The method described in this article can be useful to predict side-effects in drug design in an early stage to reduce experimental cost and time. PMID:25327524

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

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

Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects

PubMed Central

Majumdar, Susruta; Grinnell, Steven; Le Rouzic, Valerie; Burgman, Maxim; Polikar, Lisa; Ansonoff, Michael; Pintar, John; Pan, Ying-Xian; Pasternak, Gavril W.

2011-01-01

Pain remains a pervasive problem throughout medicine, transcending all specialty boundaries. Despite the extraordinary insights into pain and its mechanisms over the past few decades, few advances have been made with analgesics. Most pain remains treated by opiates, which have significant side effects that limit their utility. We now describe a potent opiate analgesic lacking the traditional side effects associated with classical opiates, including respiratory depression, significant constipation, physical dependence, and, perhaps most important, reinforcing behavior, demonstrating that it is possible to dissociate side effects from analgesia. Evidence indicates that this agent acts through a truncated, six-transmembrane variant of the G protein-coupled mu opioid receptor MOR-1. Although truncated splice variants have been reported for a number of G protein-coupled receptors, their functional relevance has been unclear. Our evidence now suggests that truncated variants can be physiologically important through heterodimerization, even when inactive alone, and can comprise new therapeutic targets, as illustrated by our unique opioid analgesics with a vastly improved pharmacological profile. PMID:22106286

Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects.

PubMed

Majumdar, Susruta; Grinnell, Steven; Le Rouzic, Valerie; Burgman, Maxim; Polikar, Lisa; Ansonoff, Michael; Pintar, John; Pan, Ying-Xian; Pasternak, Gavril W

2011-12-06

Pain remains a pervasive problem throughout medicine, transcending all specialty boundaries. Despite the extraordinary insights into pain and its mechanisms over the past few decades, few advances have been made with analgesics. Most pain remains treated by opiates, which have significant side effects that limit their utility. We now describe a potent opiate analgesic lacking the traditional side effects associated with classical opiates, including respiratory depression, significant constipation, physical dependence, and, perhaps most important, reinforcing behavior, demonstrating that it is possible to dissociate side effects from analgesia. Evidence indicates that this agent acts through a truncated, six-transmembrane variant of the G protein-coupled mu opioid receptor MOR-1. Although truncated splice variants have been reported for a number of G protein-coupled receptors, their functional relevance has been unclear. Our evidence now suggests that truncated variants can be physiologically important through heterodimerization, even when inactive alone, and can comprise new therapeutic targets, as illustrated by our unique opioid analgesics with a vastly improved pharmacological profile.

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 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.

Medicinal chemistry and anti-inflammatory activity of nitric oxide-releasing NSAI drugs.

PubMed

Koç And, Esra; Küçükgüzel, S Güniz

2009-05-01

Nitric Oxide, which acts as a non-specific cytotoxic mediator and a biological messenger on immunological competence, has been gaining significantly increasing importance. As an alternative to conventional NSAIDs having significant side effects, pharmacologically improved and therapeutically enhanced NO releasing non-steroidal anti-inflammatory drugs with less side effects are being planned to produce.

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.

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.

The Need of Slanted Side Holes for Venous Cannulae

PubMed Central

Park, Joong Yull

2012-01-01

Well-designed cannulae must allow good flow rate and minimize nonphysiologic load. Venous cannulae generally have side holes to prevent the rupture of blood vessel during perfusion. Optimizing side hole angle will yield more efficient and safe venous cannulae. A numerical modeling was used to study the effect of the angle (0°–45°) and number (0–12) of side holes on the performance of cannulae. By only slanting the side holes, it increases the flow rate up to 6% (in our models). In addition, it was found that increasing the number of side holes reduces the shear rate up to 12% (in our models). A new parameter called “penetration depth” was introduced to describe the interfering effect of stream jets from side holes, and the result showed that the 45°-slanted side holes caused minimum interfering for the flow in cannula. Our quantitative hemodynamic analysis study provides important guidelines for venous cannulae design. PMID:22291856

An analysis of the diffusion of new antidepressants: variety, quality, and marketing efforts.

PubMed

Berndt, Ernst R; Bhattacharjya, Ashoke; Mishol, David N; Arcelus, Almudena; Lasky, Thomas

2002-03-01

We are not aware of any published research that quantifies and compares the importance of effectiveness and side effects for pharmaceutical sales, and that simultaneously incorporates the impacts of marketing efforts on the diffusion of new pharmaceutical agents in the U.S. The overall level and market share success of the various selective serotonin reuptake inhibitors ( SSRIs ) relative to a representative older generation tricyclic (such as amitriptyline) provides a useful focus for studying such issues. To model jointly the marketing and sales relationships of the SSRIs in the U.S., to quantify the extent to which marketing efforts are responsive to the availability of new scientific information accompanying changes in quality and increases in product variety, and in turn to assess how the new FDA indication approvals and the enhanced marketing initiatives involving product quality and variety affect sales of the SSRI and other novel antidepressants. Quarterly US sales, price, quantity and marketing data 1988Q1-1997Q4 are taken from IMS Health for the eight new antidepressants introduced into the US during this time period. Measures of physician-perceived quality attributes of the antidepressants are drawn from Market Measures, Inc., a medical survey research firm. These data are used to construct measures of product quality (effectiveness and side effect profile), and attribute variety across all antidepressants. Multivariate regression methods are used in estimating parameters of a marketing efforts model, a sales demand model encompassing the aggregate of the newer antidepressants, and a product share model. Simulation methods are employed to quantify elasticities. Since 1988, and relative to amitriptyline, there has been only a rather modest increase in the perceived average effectiveness of the SSRIs and related products, but the side effect profiles have improved substantially. Variety measures for effectiveness show greater increases over time than do those for side effects. Marketing efforts respond to science-based events, such as new FDA indication approvals, and to effectiveness and side-effect quality improvements. Total antidepressant sales are positively and significantly related to price reductions, increased marketing efforts, and the level and variety of side effect profiles involving antidepressants. The level and variety of effectiveness does not significantly affect total antidepressant sales. Order of entry effects are important in affecting product market shares, while marketing efforts and relative quality attributes (particularly a more favorable side effect profile) have positive and significant impacts on relative market shares. Since patient response to SSRIs and related products is idiosyncratic, greater product variety facilitates better matching of antidepressant with patient. Much of the growth of the SSRIs and related antidepressants since 1988 can be attributed to increased product attribute variety, to improved changes in side effect quality relative to that of the tricyclics, and to the marketing of those improvements. Marketing efforts play an important role in diffusing product information. Marketing efforts increase considerably following FDA approval for indications other than depression, and also increase with the average effectiveness and the average side effect rating of the products. Whether the relatively minor role that perceived effectiveness has in affecting sales relative to perceived side effect profile is unique to antidepressants, or generalizes to other therapeutic classes, merits further examination.

Effects of granulocyte-colony-stimulating factor on potential normal granulocyte donors.

PubMed

McCullough, J; Clay, M; Herr, G; Smith, J; Stroncek, D

1999-10-01

The use of granulocyte-colony-stimulating factor (G-CSF) to increase the granulocyte count and the yield from leukapheresis in normal donors is leading to renewed interest in granulocyte transfusion. Therefore, it is important to understand the side effects of G-CSF. We studied the effect of G-CSF on peripheral blood counts and recorded the side effects experienced 24 hours after an injection of G-CSF in normal subjects donating peripheral blood progenitor cells for research. Following administration of G-CSF to 261 donors, the neutrophil count increased to 20.6 to 24.5 x 10(9) per microL depending on the dose of G-CSF. This represented a 6.2 to 7.4-fold increase over the neutrophil count before G-CSF administration. Of all donors, 69 percent experienced one or more side effects. The most common effects were: muscle and bone pain, headache, fatigue, and nausea. There was a relationship between the dose of G-CSF and the likelihood of experiencing a side effect. Most side effects were mild, but about 75 percent of donors took analgesics because of them. In a granulocyte donation program involving G-CSF stimulation, about two-thirds of donors would experience one or more side effects, but these would usually be mild and well tolerated.

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.

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.

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.

A second international cooperative investigation into thioacetazone side effects

PubMed Central

Miller, A. B.; Nunn, A. J.; Robinson, D. K.; Fox, Wallace; Somasundaram, P. R.; Tall, Ruth

1972-01-01

As part of a large-scale international cooperative investigation into the side effects of thioacetazone-containing regimens in the treatment of tuberculosis, an evaluation has been made of the variation in the frequency of side effects between different countries and between different centres in the same country and of the likely reasons for this variation. In 3 countries patients of different racial origin were under observation in the same hospital. Over a 12-week period of treatment there was considerable variation between the countries and centres in the overall frequency of side effects and of those leading to a major departure from prescribed treatment, the variation being similar for the two thioacetazone-containing regimens and for the streptomycin plus isoniazid control regimen, though at a lower level for the latter. In Malaysia, Singapore, and Trinidad, where different racial groups were under treatment, there was no clear indication that race was an important factor in explaining the differences between countries, except for cutaneous side effects in Trinidad and possibly in Malaysia. It is concluded that the differences in the frequency of side effects to thioacetazone-containing regimens probably result from variation in the closeness of supervision of patients, in the recording and interpretation of side effects, and in environmental factors including the previous use of other medicaments or exposure to sensitizing substances. PMID:4118761

Rarefaction Effects in Hypersonic Aerodynamics

NASA Astrophysics Data System (ADS)

Riabov, Vladimir V.

2011-05-01

The Direct Simulation Monte-Carlo (DSMC) technique is used for numerical analysis of rarefied-gas hypersonic flows near a blunt plate, wedge, two side-by-side plates, disk, torus, and rotating cylinder. The role of various similarity parameters (Knudsen and Mach numbers, geometrical and temperature factors, specific heat ratios, and others) in aerodynamics of the probes is studied. Important kinetic effects that are specific for the transition flow regime have been found: non-monotonic lift and drag of plates, strong repulsive force between side-by-side plates and cylinders, dependence of drag on torus radii ratio, and the reverse Magnus effect on the lift of a rotating cylinder. The numerical results are in a good agreement with experimental data, which were obtained in a vacuum chamber at low and moderate Knudsen numbers from 0.01 to 10.

Interactions between antiepileptic drugs and hormones.

PubMed

Svalheim, Sigrid; Sveberg, Line; Mochol, Monika; Taubøll, Erik

2015-05-01

Antiepileptic drugs (AEDs) are known to have endocrine side effects in both men and women. These can affect fertility, sexuality, thyroid function, and bone health, all functions of major importance for well-being and quality of life. The liver enzyme inducing antiepileptic drugs (EIAEDs), like phenobarbital, phenytoin, and carbamazepine, and also valproate (VPA), a non-EIAED, are most likely to cause such side effects. AED treatment can alter the levels of different sex hormones. EIAEDs increase sex hormone binding globulin (SHBG) concentrations in both men and women. Over time, this elevation can lead to lower levels of bioactive testosterone and estradiol, which may cause menstrual disturbances, sexual problems, and eventually reduced fertility. VPA can cause weight gain in both men and women. In women, VPA can also lead to androgenization with increased serum testosterone concentrations, menstrual disturbances, and polycystic ovaries. Lamotrigine has not been shown to result in endocrine side effects. The newer AEDs have not yet been thoroughly studied, but case reports indicate that some of these drugs could also be suspected to cause such effects if endocrine changes commence after treatment initiation. It is important to be aware of possible endocrine side effects of AEDs as they can have a major impact on quality of life, and are, at least partly, reversible after AED discontinuation. Copyright © 2015. Published by Elsevier Ltd.

Terbinafine induced pityriasis rosea-like eruption.

PubMed

George, Anisha; Bhatia, Anuradha; Kanish, Bimal; Williams, Abhilasha

2015-01-01

Terbinafine is an allylamine antifungal agent which is widely used for the treatment of fungal infections. Cutaneous side effects have been reported in 2% of the patients on terbinafine therapy with many morphological patterns. We report a case of terbinafine induced pityriasis rosea, a very rare side effect of terbinafine. This report emphasizes the importance of counseling the patient to report immediately in the event of a cutaneous eruption.

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)

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

Clinical importance of voluntary and induced Bennett movement.

PubMed

Tupac, R G

1978-07-01

A total of 136 dentulous patients were divided into three groups for purposes of quantitative pantographic comparison of voluntary and induced Bennett movement. The effects of patient age and operator experience on recording the Bennett movement were also studied. The results indicates that for patients studied with Bennett movement iduced in the manner described: 1. Experienced operators can obtain more induced Bennett movement that inexperienced operators. 2. Inducing Bennett movement has a greater effect on the immediate side shift component than it has on the progressive side shift component. 3. For older individuals the amount and direction of induced immediate side shift is greater than for younger patients, statistically highly significant, and therefore clinically important. In conclusion, if the objective of a pantographic survey is to record the complete capacity of the joint to move, *lateral jaw movements must be induced.

Nurses' discourse in contraceptive prescribing: an analysis using Foucault's 'procedures of exclusion'.

PubMed

Hayter, Mark

2007-05-01

This paper is a report of an analysis of the discourse about contraceptive efficacy and side effects used by nurses when prescribing contraception. All women seeking contraception should be informed of the efficacy and potential adverse effects of the particular method they are considering. This information facilitates an informed choice. Women also require this information in order to monitor for any side effects. Paradoxically, side effects are also a key factor in reducing adherence with contraceptive regimens. However, there is no literature that explores specifically how this issue is addressed in clinical consultations, or places these practices in a theoretical context. Forty-nine consultations between nurses and women in sexual health clinics were audio-recorded during 2002. Data were subject to a discourse analysis using Foucault's 'procedures of exclusion' to explore the discursive construction of contraceptive efficacy and side effects The nurses employed specific discursive strategies when discussing contraception. When addressing efficacy, discourse centred on medico-statistical facts, but side effects were described in lay terms that minimized their severity. Nurses contextualized contraceptive side effects within potential problems that women might experience in pregnancy, and also attempted to 'normalize' contraceptive-related problems. Discourse and its deployment play a key role in practitioner-client relationships that sexual health nurses need to become more aware of how they discuss clinical issues about contraception with women. Clinical data on contraceptive side-effects are present in the literature, and it is important that sexual health nurses use this to help women make truly informed decisions.

[Supportive care during chemotherapy for lung cancer in daily practice].

PubMed

Müller, Veronika; Tamási, Lilla; Gálffy, Gabriella; Losonczy, György

2012-09-01

Active oncotherapy, combination chemotherapy of lung cancer is accompanied with many side effects which may impair patients' quality of life and compromise the effectiveness of chemotherapy. Most side effects of chemotherapy are preventable or treatable with optimal supportive care which enhances success in patient care and treatment. The aim of this review is to summarize the most important conditions that may be associated with combined chemotherapy of lung cancer from the practical point of view.

Terbinafine induced pityriasis rosea-like eruption

PubMed Central

George, Anisha; Bhatia, Anuradha; Kanish, Bimal; Williams, Abhilasha

2015-01-01

Terbinafine is an allylamine antifungal agent which is widely used for the treatment of fungal infections. Cutaneous side effects have been reported in 2% of the patients on terbinafine therapy with many morphological patterns. We report a case of terbinafine induced pityriasis rosea, a very rare side effect of terbinafine. This report emphasizes the importance of counseling the patient to report immediately in the event of a cutaneous eruption. PMID:26729964

Cognitive effects of radiation emitted by cellular phones: the influence of exposure side and time.

PubMed

Luria, Roy; Eliyahu, Ilan; Hareuveny, Ronen; Margaliot, Menachem; Meiran, Nachshon

2009-04-01

This study examined the time dependence effects of exposure to radiofrequency radiation (RFR) emitted by standard GSM cellular phones on the cognitive functions of humans. A total of 48 healthy right-handed male subjects performed a spatial working memory task (that required either a left-hand or a right-hand response) while being exposed to one of two GSM phones placed at both sides of the head. The subjects were randomly divided into three groups. Each group was exposed to one of three exposure conditions: left-side of the head, right-side, or sham-exposure. The experiment consisted of 12 blocks of trials. Response times (RTs) and accuracy of the responses were recorded. It was found that the average RT of the right-hand responses under left-side exposure condition was significantly longer than those of the right-side and sham-exposure groups averaged together during the first two time blocks. These results confirmed the existence of an effect of exposure on RT, as well as the fact that exposure duration (together with the responding hand and the side of exposure) may play an important role in producing detectable RFR effects on performance. Differences in these parameters might be the reason for the failure of certain studies to detect or replicate RFR effects. (c) 2008 Wiley-Liss, Inc.

The Risks of Chronic Corticosteroid Exposure.

PubMed

Money, Sarah

2017-06-01

Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. This article focuses on the use of corticosteroids to decrease inflammation and treat painful conditions as well as their long-term side effects and risks. Their long-term use can expose the body to side effects and can cause long-term health concerns. It therefore is important to be aware of the risks of long-term corticosteroid use.

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.

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.

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.

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

Challenges Evaluating Chemotherapy-Induced Peripheral Neuropathy in Childhood Cancer Survivors.

PubMed

Mohrmann, Caroline; Armer, Jane; Hayashi, Robert J

Children treated for cancer are exposed to a variety of chemotherapeutic agents with known toxicity to the peripheral nervous system. The side effect of peripheral neuropathy can cause changes in sensation, function, and even cause pain. Although peripheral neuropathy is recognized by pediatric oncology nurses as an important and significant side effect, measuring neuropathy can be quite complex for clinical care and research efforts. With more children surviving a cancer diagnosis today, this issue is increasingly important for childhood cancer survivors. This article has reviewed existing literature examining peripheral neuropathy in childhood cancer survivors with particular interest paid to measurement tools available and needs for future research. It is important for nurses to choose appropriate measures for clinical care and research methods in order to have an impact on patients experiencing this condition.

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

Determinants for drug survival of methotrexate in patients with psoriasis, split according to different reasons for discontinuation: results of the prospective MTX-CAPTURE.

PubMed

Otero, M E; van den Reek, J M; Seyger, M M; van de Kerkhof, P C; Kievit, W; de Jong, E M

2017-08-01

As methotrexate (MTX) is a widely used treatment for psoriasis, it is important to gain insight into the reasons for the discontinuation of MTX and to understand the determinants for drug survival. To describe 5-year drug survival for MTX in patients with psoriasis, split according to different reasons for discontinuation, and to identify the determinants for drug survival. Data were extracted from a prospective psoriasis registry of patients treated with MTX (MTX-CAPTURE). Drug survival was analysed using Kaplan-Meier estimates and the determinants for discontinuation were analysed using Cox regression analysis. Analyses were split according to the reason for discontinuation: side-effects or ineffectiveness. We included 85 patients treated with MTX, with a maximum treatment duration of 5·2 years. The overall drug survival rates were 63%, 30% and 15% after 1, 3 and 5 years, respectively. The median survival was 1·8 years. Overall, 55 patients (65%) discontinued MTX for the following reasons: side-effects (35%), ineffectiveness (26%), combination of side-effects and ineffectiveness (13%), other reasons (16%) and 11% were lost to follow-up. The most reported side-effects were gastrointestinal symptoms, despite the use of folic acid in 99% of patients. Based on univariate analysis, a high Psoriasis Area and Severity Index score and a high score on the visual analogue scale for disease severity at baseline were possible determinants for a short drug survival. Drug survival of MTX was low with 15% of patients 'on drug' after 5 years. Side-effects alone or in combination with inadequate disease control were more important in the context of treatment discontinuation than inadequate disease control alone. © 2017 British Association of Dermatologists.

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.

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.

Doxorubicin-induced second degree and complete atrioventricular block.

PubMed

Kilickap, Saadettin; Akgul, Ebru; Aksoy, Sercan; Aytemir, Kudret; Barista, Ibrahim

2005-05-01

Doxorubicin is one of the most effective chemotherapeutic agents used in the treatment of malignancies. Cardiotoxicity is the most important dose-limiting toxicity of doxorubicin. Although cardiomyopathy is the most well known side effect of doxorubicin, it usually occurs many years after the treatment and relates to cumulative doxorubicin dosage. Another form of doxorubicin cardiotoxicity is arrhythmia which may occur at any time and after any dosage. However, doxorubicin-induced arrhythmia is rarely a life-threatening side effect. In this report, we present a case in which there were doxorubicin-induced life-threatening arrhythmias.

Combining automatic table classification and relationship extraction in extracting anticancer drug-side effect pairs from full-text articles.

PubMed

Xu, Rong; Wang, QuanQiu

2015-02-01

Anticancer drug-associated side effect knowledge often exists in multiple heterogeneous and complementary data sources. A comprehensive anticancer drug-side effect (drug-SE) relationship knowledge base is important for computation-based drug target discovery, drug toxicity predication and drug repositioning. In this study, we present a two-step approach by combining table classification and relationship extraction to extract drug-SE pairs from a large number of high-profile oncological full-text articles. The data consists of 31,255 tables downloaded from the Journal of Oncology (JCO). We first trained a statistical classifier to classify tables into SE-related and -unrelated categories. We then extracted drug-SE pairs from SE-related tables. We compared drug side effect knowledge extracted from JCO tables to that derived from FDA drug labels. Finally, we systematically analyzed relationships between anti-cancer drug-associated side effects and drug-associated gene targets, metabolism genes, and disease indications. The statistical table classifier is effective in classifying tables into SE-related and -unrelated (precision: 0.711; recall: 0.941; F1: 0.810). We extracted a total of 26,918 drug-SE pairs from SE-related tables with a precision of 0.605, a recall of 0.460, and a F1 of 0.520. Drug-SE pairs extracted from JCO tables is largely complementary to those derived from FDA drug labels; as many as 84.7% of the pairs extracted from JCO tables have not been included a side effect database constructed from FDA drug labels. Side effects associated with anticancer drugs positively correlate with drug target genes, drug metabolism genes, and disease indications. Copyright © 2014 Elsevier Inc. All rights reserved.

Reducing side effects of hiding sensitive itemsets in privacy preserving data mining.

PubMed

Lin, Chun-Wei; Hong, Tzung-Pei; Hsu, Hung-Chuan

2014-01-01

Data mining is traditionally adopted to retrieve and analyze knowledge from large amounts of data. Private or confidential data may be sanitized or suppressed before it is shared or published in public. Privacy preserving data mining (PPDM) has thus become an important issue in recent years. The most general way of PPDM is to sanitize the database to hide the sensitive information. In this paper, a novel hiding-missing-artificial utility (HMAU) algorithm is proposed to hide sensitive itemsets through transaction deletion. The transaction with the maximal ratio of sensitive to nonsensitive one is thus selected to be entirely deleted. Three side effects of hiding failures, missing itemsets, and artificial itemsets are considered to evaluate whether the transactions are required to be deleted for hiding sensitive itemsets. Three weights are also assigned as the importance to three factors, which can be set according to the requirement of users. Experiments are then conducted to show the performance of the proposed algorithm in execution time, number of deleted transactions, and number of side effects.

Reducing Side Effects of Hiding Sensitive Itemsets in Privacy Preserving Data Mining

PubMed Central

Lin, Chun-Wei; Hong, Tzung-Pei; Hsu, Hung-Chuan

2014-01-01

Data mining is traditionally adopted to retrieve and analyze knowledge from large amounts of data. Private or confidential data may be sanitized or suppressed before it is shared or published in public. Privacy preserving data mining (PPDM) has thus become an important issue in recent years. The most general way of PPDM is to sanitize the database to hide the sensitive information. In this paper, a novel hiding-missing-artificial utility (HMAU) algorithm is proposed to hide sensitive itemsets through transaction deletion. The transaction with the maximal ratio of sensitive to nonsensitive one is thus selected to be entirely deleted. Three side effects of hiding failures, missing itemsets, and artificial itemsets are considered to evaluate whether the transactions are required to be deleted for hiding sensitive itemsets. Three weights are also assigned as the importance to three factors, which can be set according to the requirement of users. Experiments are then conducted to show the performance of the proposed algorithm in execution time, number of deleted transactions, and number of side effects. PMID:24982932

Who has a clue to preventing the flu? Unravelling supply and demand effects on the take-up of influenza vaccinations.

PubMed

Maurer, Jürgen

2009-05-01

Influenza is a serious disease, especially for older people, and incomplete vaccination take-up poses a major public health challenge. On both the side of physicians and patients, there could be promising channels for increasing immunization rates, but no attempt has yet been made to empirically unravel their respective influences. Using exclusion restrictions implied by an economic model of physician-patient interactions, our study quantifies the particular effects of supply and demand on influenza immunization. On the supply side, our estimates highlight the importance of physician agency and physician quality, while a patient's education and health behaviors are key demand side factors.

The Importance of Making the Well-Being of Children in Poverty a Priority

ERIC Educational Resources Information Center

Prince, Debra Lindsey; Pepper, Kaye; Brocato, Kay

2006-01-01

Hurricane Katrina exposed to the world the side of America that is often ignored or forgotten--the side of America where people live in poverty and struggle to meet their most basic needs. This article focuses primarily on children in Mississippi and highlights the effect that poverty has on children's well-being at an early age and future…

[Parkinson therapy 1985].

PubMed

Kaeser, H E

1986-06-14

The problems of long term treatment with antiparkinson drugs are numerous, involving increased involuntary movements, painful dystonic cramps, decrease or loss of therapeutic benefit, wearing-off, episodes of akinesia (on-off) and long periods of "freezing". Important side effects are also mental changes with heavy dreams, hallucinations, nocturnal confusional states and paranoid psychosis. As most of these side effects are dose-related, they are postponed and lessened by small daily doses of L-dopa and decarboxylase inhibitor. Frequent small doses may decrease the wearing-off effect but may cause unpredictable episodes of on-off. The addition of or partial replacement by bromocriptine may decrease fluctuations and dyskinesias in many patients. To reduce the side effects such as nausea, orthostatic hypotension and mental disturbances, daily doses of 15-30 mg should be built up very slowly. Painful dystonias are related to the off period and respond well to baclofen. For the treatment of severe psychic disturbances tranquilizers with little or no extrapyramidal side effects, such as clomethiazole, benzodiazepine derivatives and (if necessary) thioridazine, are recommended. Bromocriptine may also be useful in occasional cases which do not, or no longer, respond to L-dopa.

Tuning the thermal conductivity of solar cell polymers through side chain engineering.

PubMed

Guo, Zhi; Lee, Doyun; Liu, Yi; Sun, Fangyuan; Sliwinski, Anna; Gao, Haifeng; Burns, Peter C; Huang, Libai; Luo, Tengfei

2014-05-07

Thermal transport is critical to the performance and reliability of polymer-based energy devices, ranging from solar cells to thermoelectrics. This work shows that the thermal conductivity of a low band gap conjugated polymer, poly(4,8-bis-alkyloxybenzo[1,2-b:4,5-b']dithiophene-2,6-diyl-alt-(alkylthieno[3,4-b]thiophene-2-carboxylate)-2,6-diyl) (PBDTTT), for photovoltaic applications can be actively tuned through side chain engineering. Compared to the original polymer modified with short branched side chains, the engineered polymer using all linear and long side chains shows a 160% increase in thermal conductivity. The thermal conductivity of the polymer exhibits a good correlation with the side chain lengths as well as the crystallinity of the polymer characterized using small-angle X-ray scattering (SAXS) experiments. Molecular dynamics simulations and atomic force microscopy are used to further probe the molecular level local order of different polymers. It is found that the linear side chain modified polymer can facilitate the formation of more ordered structures, as compared to the branched side chain modified ones. The effective medium theory modelling also reveals that the long linear side chain enables a larger heat carrier propagation length and the crystalline phase in the bulk polymer increases the overall thermal conductivity. It is concluded that both the length of the side chains and the induced polymer crystallization are important for thermal transport. These results offer important guidance for actively tuning the thermal conductivity of conjugated polymers through molecular level design.

[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.

An Investigation of the Facets for Converting Military Authorizations for Maintenance Personnel to Civilian Positions

DTIC Science & Technology

1984-03-01

have a significant effect on the worker whether military or civilian, but the primary impact 4 may occur while both types work side by side. Performance ...32 - . - - have important consequences for the organization’s members (3:226). Performance appraisals can effect the worker at any time but the impact ... employee (3:227). There are a large number of variables related to personnel performance including "training, experience, skill-level and rank distribution

The evolution of spinal/epidural neostigmine in clinical application: Thoughts after two decades

PubMed Central

Lauretti, Gabriela Rocha

2015-01-01

Since the first clinical application of analgesia following spinal anticholinesterase by 1940's, several clinical double-blind studies have been conducted to date, where intrathecal doses of neostigmine in humans ranged from 750 to 1 μg, due to side-effects. Conversely, epidural neostigmine has been evaluated in proportionally higher doses and represents an alternative, but still deserves more investigation concerning both acute and chronic pain, as it seems devoid of important side-effects. PMID:25558203

Longitudinal perceptions of the side effects of chemotherapy in patients with gynecological cancer.

PubMed

Hsu, Hui-Chun; Tsai, Su-Yu; Wu, Shang-Liang; Jeang, Shiow-Roug; Ho, Mei-Yao; Liou, Wen-Shiung; Chiang, An-Jen; Chang, Tsung-Hsien

2017-11-01

This study aimed to assess the incidence and difference of side effects among six courses of chemotherapy (C/T) in gynecological cancer patients. The study period was from Sep. 2010 to Dec. 2011 at the Kaohsiung Veterans General Hospital in Taiwan. The treating protocols, courses, and drugs of C/T in patient were considered according to the different malignant cancers and clinical conditions. The patient data of age, marriage status, education, religion, and experiences of C/T were collected. The patients' or their families' reported side effects of C/T were recorded daily from the beginning of C/T to the 10th day after C/T in each cycle and every course of C/T. Total 89 patients enrolled into the study received total 450 courses of C/T. The mean age was 54.52 ± 11.02. Ovarian cancer was the most common malignant disease (64.0%). The most often combination of drugs used was Taxol and carboplatin (40.9%). Patients complained peripheral numbness of limbs, with the highest incidence of 58.6%. The side effects with incidence about 50% were decreased fatigue (55.0%) and hair loss (49.9%). Other side effects with different levels of incidence were also noticed, such as lack of appetite, changes in taste, and muscle ache. The incidences of peripheral limb numbness and hair loss were increased with following courses of C/T. The high incidence of fatigue did not show variation between different courses of C/T. This study revealed the incidence of side effects and occurrence timing during C/T in patients with gynecological cancer. These data provide substantial information to patients and their families to understand the potential side effects of C/T courses, which might increase their compliance in receiving adjuvant C/T. Relieving the side effects in C/T would be important to improve their quality of daily life and treatment willingness.

Patient Experience of Symptoms and Side Effects when Treated with Osimertinib for Advanced Non-Small-Cell Lung Cancer: A Qualitative Interview Substudy.

PubMed

Rydén, Anna; Blackhall, Fiona; Kim, Hye Ryun; Pillai, Rathi N; Braam, Lauren; Martin, Mona L; Walding, Andrew

2017-10-01

Capturing the patient experience during treatment is important to both regulatory authorities and to patients starting treatment. We identified the symptoms and side effects experienced by patients with advanced non-small-cell lung cancer during osimertinib treatment, to understand treatment expectations, satisfaction, and the level of difficulty coping with the side effects experienced during treatment. Qualitative interviews (approximately 4-6 weeks after treatment initiation and again after approximately 4 months of treatment) were conducted during the phase I/II AURA clinical trial of osimertinib, a tyrosine kinase inhibitor of epidermal growth factor receptor-sensitizing and T790M resistance mutations. During the first interview (23 patients), the most commonly reported symptoms/side effects were coughing, itching, tiredness (each reported by 56.5% of patients), and rash (43.5%). During the second interview (21 patients), compared with the first interview, shortness of breath and diarrhea were reported by more patients (57.1 and 38.1%, respectively; both increased from 34.8%); tiredness remained predominant (42.9%); and itching (38.1%), coughing (38.1%), and rash (14.3%) were reported by fewer patients. At both interviews, the most frequently reported symptoms/side effects were also those most often rated by patients for bothersomeness and severity, and generally received mean scores in the low-to-moderate range. However, several rarely expressed symptoms/side effects (e.g., abdominal pain, frequent day time urination) received high bothersomeness ratings. At the second interview, patients were highly satisfied with osimertinib and had a low level of difficulty in coping with side effects during treatment. These data enhance our understanding of patients' experiences of symptoms/side effects, which could increase the accuracy of the osimertinib benefit-risk assessment, guide management of adverse events, and improve the information given to patients receiving the drug.

Side Effects of Chloroquine and Primaquine and Symptom Reduction in Malaria Endemic Area (Mâncio Lima, Acre, Brazil)

PubMed Central

Braga, Cássio Braga e; Martins, Antonio Camargo; Cayotopa, Athaid David Escalante; Klein, Wagner Werner; Schlosser, Andreus Roberto; da Silva, Aline Ferreira; de Souza, Mardelson Nery; Andrade, Breno Wilson Benevides; Filgueira-Júnior, José Alcântara; Pinto, Wagner de Jesus; da Silva-Nunes, Mônica

2015-01-01

Side effects of antimalarial drug can overlap with malaria symptoms. We evaluated 50 patients with vivax malaria in Mâncio Lima, Acre, treated with chloroquine and primaquine. Patients were evaluated for the presence of 21 symptoms before and after treatment and for reported side effects of these drugs after treatment was started. The most frequent symptoms before medication were headache, fever, chills, sweating, arthralgia, back pain, and weakness, which were present in between 40% and 76% of respondents. The treatment reduced the occurrence of these symptoms and reduced the lack of appetite, but gastrointestinal symptoms and choluria increased in frequency. There were no reports of pale stools before medication, but 12% reported the occurrence of this symptom after treatment started. Other symptoms such as blurred vision (54%), pruritus (22%), paresthesia (6%), insomnia (46%), and “stings” into the skin (22%) were reported after chloroquine was taken. The antimalarial drugs used to treat P. vivax malaria reduce much of the systemic and algic symptoms but cause mainly gastrointestinal side effects that may lead to lack of adherence to drug treatment. It is important to guide the patient for the appearance and the transience of such side effects in order to avoid abandoning treatment. PMID:26357512

Deciphering Front-Side Complex Formation in SN2 Reactions via Dynamics Mapping.

PubMed

Szabó, István; Olasz, Balázs; Czakó, Gábor

2017-07-06

Due to their importance in organic chemistry, the atomistic understanding of bimolecular nucleophilic substitution (S N 2) reactions shows exponentially growing interest. In this publication, the effect of front-side complex (FSC) formation is uncovered via quasi-classical trajectory computations combined with a novel analysis method called trajectory orthogonal projection (TOP). For both F - + CH 3 Y [Y = Cl,I] reactions, the lifetime distributions of the F - ···YCH 3 front-side complex revealed weakly trapped nucleophiles (F - ). However, only the F - + CH 3 I reaction features strongly trapped nucleophiles in the front-side region of the prereaction well. Interestingly, both back-side and front-side attack show propensity to long-lived FSC formation. Spatial distributions of the nucleophile demonstrate more prominent FSC formation in case of the F - + CH 3 I reaction compared to F - + CH 3 Cl. The presence of front-side intermediates and the broad spatial distribution in the back-side region may explain the indirect nature of the F - + CH 3 I reaction.

Side Flow Effect on Surface Generation in Nano Cutting

NASA Astrophysics Data System (ADS)

Xu, Feifei; Fang, Fengzhou; Zhang, Xiaodong

2017-05-01

The side flow of material in nano cutting is one of the most important factors that deteriorate the machined surface quality. The effects of the crystallographic orientation, feed, and the cutting tool geometry, including tool edge radius, rake angle and inclination angle, on the side flow are investigated employing molecular dynamics simulation. The results show that the stagnation region is formed in front of tool edge and it is characterized by the stagnation radius R s and stagnation height h s . The side flow is formed because the material at or under the stagnation region is extruded by the tool edge to flow to the side of the tool edge. Higher stagnation height would increase the size of the side flow. The anisotropic nature of the material which partly determines the stagnation region also influences the side flow due to the different deformation mechanism under the action of the tool edge. At different cutting directions, the size of the side flow has a great difference which would finally affect the machined surface quality. The cutting directions of {100} < 011>, {110} < 001>, and {110} < 1-10 > are beneficial to obtain a better surface quality with small side flow. Besides that, the side flow could be suppressed by reducing the feed and optimizing the cutting tool geometry. Cutting tool with small edge radius, large positive rake angle, and inclination angle would decrease the side flow and consequently improve the machined surface quality.

Side Flow Effect on Surface Generation in Nano Cutting.

PubMed

Xu, Feifei; Fang, Fengzhou; Zhang, Xiaodong

2017-12-01

The side flow of material in nano cutting is one of the most important factors that deteriorate the machined surface quality. The effects of the crystallographic orientation, feed, and the cutting tool geometry, including tool edge radius, rake angle and inclination angle, on the side flow are investigated employing molecular dynamics simulation. The results show that the stagnation region is formed in front of tool edge and it is characterized by the stagnation radius R s and stagnation height h s . The side flow is formed because the material at or under the stagnation region is extruded by the tool edge to flow to the side of the tool edge. Higher stagnation height would increase the size of the side flow. The anisotropic nature of the material which partly determines the stagnation region also influences the side flow due to the different deformation mechanism under the action of the tool edge. At different cutting directions, the size of the side flow has a great difference which would finally affect the machined surface quality. The cutting directions of {100} < 011>, {110} < 001>, and {110} < 1-10 > are beneficial to obtain a better surface quality with small side flow. Besides that, the side flow could be suppressed by reducing the feed and optimizing the cutting tool geometry. Cutting tool with small edge radius, large positive rake angle, and inclination angle would decrease the side flow and consequently improve the machined surface quality.

An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies

PubMed Central

Iffland, Kerstin; Grotenhermen, Franjo

2017-01-01

Abstract Introduction: This literature survey aims to extend the comprehensive survey performed by Bergamaschi et al. in 2011 on cannabidiol (CBD) safety and side effects. Apart from updating the literature, this article focuses on clinical studies and CBD potential interactions with other drugs. Results: In general, the often described favorable safety profile of CBD in humans was confirmed and extended by the reviewed research. The majority of studies were performed for treatment of epilepsy and psychotic disorders. Here, the most commonly reported side effects were tiredness, diarrhea, and changes of appetite/weight. In comparison with other drugs, used for the treatment of these medical conditions, CBD has a better side effect profile. This could improve patients' compliance and adherence to treatment. CBD is often used as adjunct therapy. Therefore, more clinical research is warranted on CBD action on hepatic enzymes, drug transporters, and interactions with other drugs and to see if this mainly leads to positive or negative effects, for example, reducing the needed clobazam doses in epilepsy and therefore clobazam's side effects. Conclusion: This review also illustrates that some important toxicological parameters are yet to be studied, for example, if CBD has an effect on hormones. Additionally, more clinical trials with a greater number of participants and longer chronic CBD administration are still lacking. PMID:28861514

Protein side chain conformation predictions with an MMGBSA energy function.

PubMed

Gaillard, Thomas; Panel, Nicolas; Simonson, Thomas

2016-06-01

The prediction of protein side chain conformations from backbone coordinates is an important task in structural biology, with applications in structure prediction and protein design. It is a difficult problem due to its combinatorial nature. We study the performance of an "MMGBSA" energy function, implemented in our protein design program Proteus, which combines molecular mechanics terms, a Generalized Born and Surface Area (GBSA) solvent model, with approximations that make the model pairwise additive. Proteus is not a competitor to specialized side chain prediction programs due to its cost, but it allows protein design applications, where side chain prediction is an important step and MMGBSA an effective energy model. We predict the side chain conformations for 18 proteins. The side chains are first predicted individually, with the rest of the protein in its crystallographic conformation. Next, all side chains are predicted together. The contributions of individual energy terms are evaluated and various parameterizations are compared. We find that the GB and SA terms, with an appropriate choice of the dielectric constant and surface energy coefficients, are beneficial for single side chain predictions. For the prediction of all side chains, however, errors due to the pairwise additive approximation overcome the improvement brought by these terms. We also show the crucial contribution of side chain minimization to alleviate the rigid rotamer approximation. Even without GB and SA terms, we obtain accuracies comparable to SCWRL4, a specialized side chain prediction program. In particular, we obtain a better RMSD than SCWRL4 for core residues (at a higher cost), despite our simpler rotamer library. Proteins 2016; 84:803-819. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Focused Study on the Quiet Side Effect in Dwellings Highly Exposed to Road Traffic Noise

PubMed Central

Renterghem, Timothy Van; Botteldooren, Dick

2012-01-01

This study provides additional evidence for the positive effect of the presence of a quiet façade at a dwelling and aims at unraveling potential mechanisms. Locations with dominant road traffic noise and high Lden-levels at the most exposed façade were selected. Dwellings both with and without a quiet façade were deliberately sought out. Face-to-face questionnaires (N = 100) were taken to study the influence of the presence of a quiet side in relation to noise annoyance and sleep disturbance. As a direct effect, the absence of a quiet façade in the dwelling (approached as a front-back façade noise level difference smaller than 10 dBA) leads to an important increase of at least moderately annoyed people (odds-ratio adjusted for noise sensitivity equals 3.3). In an indirect way, a bedroom located at the quiet side leads to an even stronger reduction of the self-reported noise annoyance (odds-ratio equal to 10.6 when adjusted for noise sensitivity and front façade Lden). The quiet side effect seems to be especially applicable for noise sensitive persons. A bedroom located at the quiet side also reduces noise-induced sleep disturbances. On a loud side, bedroom windows are more often closed, however, conflicting with the preference of dwellers. PMID:23330222

Critical side channel effects in random bit generation with multiple semiconductor lasers in a polarization-based quantum key distribution system.

PubMed

Ko, Heasin; Choi, Byung-Seok; Choe, Joong-Seon; Kim, Kap-Joong; Kim, Jong-Hoi; Youn, Chun Ju

2017-08-21

Most polarization-based BB84 quantum key distribution (QKD) systems utilize multiple lasers to generate one of four polarization quantum states randomly. However, random bit generation with multiple lasers can potentially open critical side channels that significantly endangers the security of QKD systems. In this paper, we show unnoticed side channels of temporal disparity and intensity fluctuation, which possibly exist in the operation of multiple semiconductor laser diodes. Experimental results show that the side channels can enormously degrade security performance of QKD systems. An important system issue for the improvement of quantum bit error rate (QBER) related with laser driving condition is further addressed with experimental results.

Psychiatric side effects of ketamine in hospitalized medical patients administered subanesthetic doses for pain control.

PubMed

Rasmussen, Keith G

2014-08-01

To assess the psychiatric side effects of ketamine when administered in subanesthetic doses to hospitalized patients. It is hypothesized that such effects occur frequently. In this retrospective study, the medical records of 50 patients hospitalized on medical and surgical units at our facility who had continuous intravenous infusions of ketamine for pain or mild sedation were reviewed. Patient progress in the days following the start of ketamine infusion was reviewed and response to ketamine was noted. Twenty-two percent of the patients were noted to have some type of psychiatric reaction to ketamine, including agitation, confusion, and hallucinations. These reactions were relatively short lived, namely, occurring during or shortly after the infusions. No association was found between patient response to ketamine and gender, age, or infusion rate. Awareness of the psychiatric side effects of ketamine is an important consideration for clinicians administering this medication either for pain control or for depressive illness.

A novel approach to surveying sturgeon using side-scan sonar and occupancy modeling

USGS Publications Warehouse

Flowers, H. Jared; Hightower, Joseph E.

2013-01-01

Technological advances represent opportunities to enhance and supplement traditional fisheries sampling approaches. One example with growing importance for fisheries research is hydroacoustic technologies such as side-scan sonar. Advantages of side-scan sonar over traditional techniques include the ability to sample large areas efficiently and the potential to survey fish without physical handling-important for species of conservation concern, such as endangered sturgeons. Our objectives were to design an efficient survey methodology for sampling Atlantic Sturgeon Acipenser oxyrinchus by using side-scan sonar and to developmethods for analyzing these data. In North Carolina and South Carolina, we surveyed six rivers thought to contain varying abundances of sturgeon by using a combination of side-scan sonar, telemetry, and video cameras (i.e., to sample jumping sturgeon). Lower reaches of each river near the saltwater-freshwater interface were surveyed on three occasions (generally successive days), and we used occupancy modeling to analyze these data.We were able to detect sturgeon in five of six rivers by using these methods. Side-scan sonar was effective in detecting sturgeon, with estimated gear-specific detection probabilities ranging from 0.2 to 0.5 and river-specific occupancy estimates (per 2-km river segment) ranging from 0.0 to 0.8. Future extensions of this occupancy modeling framework will involve the use of side-scan sonar data to assess sturgeon habitat and abundance in different river systems.

Yellow fever vaccination in organ transplanted patients: is it safe? A multicenter study.

PubMed

Azevedo, L S; Lasmar, E P; Contieri, F L C; Boin, I; Percegona, L; Saber, L T S; Selistre, L S; Netto, M V P; Moreira, M C V; Carvalho, R M; Bruno, R M; Ferreira, T C A; David-Neto, E

2012-06-01

Yellow fever (YF) may be very serious, with mortality reaching 50%. Live attenuated virus YF vaccine (YFV) is effective, but may present, although rare, life-threatening side effects and is contraindicated in immunocompromised patients. However, some transplant patients may inadvertently receive the vaccine. A questionnaire was sent to all associated doctors to the Brazilian Organ Transplantation Association through its website, calling for reports of organ transplanted patients who have been vaccinated against YF. Twelve doctors reported 19 cases. None had important side effects. Only one had slight reaction at the site of YFV injection. Eleven patients were male. Organs received were 14 kidneys, 3 hearts, and 2 livers. Twelve patients received organs from deceased donors. Mean age at YFV was 45.6 ± 13.6 years old (range 11-69); creatinine: 1.46 ± 0.62 mg/dL (range 0.8-3.4); post-transplant time: 65 ± 83.9 months (range 3-340); and time from YFV at the time of survey: 45 ± 51 months (range 3-241). Immunosuppression varied widely with different drug combinations: azathioprine (7 patients), cyclosporine (8), deflazacort (1), mycophenolate (10), prednisone (11), sirolimus (3), and tacrolimus (4). YFV showed no important side effects in this cohort of solid organ transplanted patients. However, owing to the small number of studied patients, it is not possible to extend these findings to the rest of the transplanted population, assuring safety. Therefore, these data are not strong enough to safely recommend YFV in organ transplanted recipients, as severe, even life-threatening side effects may occur. © 2011 John Wiley & Sons A/S.

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.

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.

Acetylcholinesterase inhibitors for electroconvulsive therapy-induced cognitive side effects: a systematic review.

PubMed

Henstra, Marieke J; Jansma, Elise P; van der Velde, Nathalie; Swart, Eleonora L; Stek, Max L; Rhebergen, Didi

2017-05-01

Electroconvulsive therapy (ECT) is an effective treatment for severe late-life depression; however, ECT-induced cognitive side effects frequently occur. The cholinergic system is thought to play an important role in the pathogenesis. We systematically reviewed the evidence for acetylcholinesterase inhibitors (Ache-I) to prevent or reduce ECT-induced cognitive side effects. A systematic search was performed in Pubmed, EMBASE, PsychINFO, and the Cochrane database to identify clinical trials investigating the effect of Ache-I on ECT-induced cognitive side effects. Key search terms included all synonyms for ECT and Ache-I. Risk of bias assessment was conducted by using the Cochrane Collaboration's tool. Five clinical trials were eligible for inclusion. All studies focused on cognitive functioning as primary endpoint, but assessment of cognitive functioning varied widely in time point of assessment and in cognitive tests that were used. There was also great variety in study medication, route and time of administration and dosages, duration of drug administration, and ECT techniques. Finally, only two out of five studies were considered at low risk of bias. Despite the aforementioned shortcomings, without exception, all studies demonstrated significantly better cognitive performance in individuals treated with Ache-I. Despite large heterogeneity in studies, Ache-I appear to have beneficial effects on ECT-induced cognitive side effects, supporting an association with the cholinergic system in ECT-induced cognitive impairment. Methodological sound studies controlling for putative confounders are warranted. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes

PubMed Central

Karagiannis, Tom C; Lin, Ann JE; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam

2010-01-01

Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by γH2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer. PMID:20930262

Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes.

PubMed

Karagiannis, Tom C; Lin, Ann J E; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam

2010-10-01

Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by γH2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer.

The alcohol supply: its importance to public health and safety, and essential research questions.

PubMed

Edwards, G; Holder, H D

2000-12-01

This paper seeks to identify the main questions which have emerged from the preceding papers concerning the supply side of alcohol. On any rational analysis these issues are of thoroughly legitimate concern to public health researchers. We list them under seven headings: (1) what drives the alcohol supply side? (2) What is the impact of alcohol supply on demand? (3) What are the benefits and risks to health and safety stemming from deregulation and what are the possibilities to avoid negative effects? (4) What is the size and significance of the alcohol supply which may derive from other than the officially approved channels? (5) Who are the important actors in the alcohol supply system? (6) What are local influences on alcohol supply and its distribution throughout communities? (7) What is to be learned from tobacco and other risky commodities about the importance of supply? Finally, we outline a series of possible next steps for a supply side initiative.

Central neurotoxicity of immunomodulatory drugs in multiple myeloma.

PubMed

Patel, Urmeel H; Mir, Muhammad A; Sivik, Jeffrey K; Raheja, Divisha; Pandey, Manoj K; Talamo, Giampaolo

2015-02-24

Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient), lenalidomide (4 patients), and pomalidomide (1 patient) was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.

Central Neurotoxicity of Immunomodulatory Drugs in Multiple Myeloma

PubMed Central

Patel, Urmeel H.; Mir, Muhammad A.; Sivik, Jeffrey K.; Raheja, Divisha; Pandey, Manoj K.; Talamo, Giampaolo

2015-01-01

Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient), lenalidomide (4 patients), and pomalidomide (1 patient) was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy. PMID:25852850

Atenolol versus pindolol: side-effects in hypertension.

PubMed

Foerster, E C; Greminger, P; Siegenthaler, W; Vetter, H; Vetter, W

1985-01-01

This randomized crossover out-patient study was designed to compare the antihypertensive effects of atenolol and pindolol. After a wash-out period of two weeks in pretreated cases, 107 patients with essential hypertension were given either atenolol 100 mg once-daily or pindolol 20 mg slow release (SR) once-daily. Both atenolol and pindolol lowered blood pressure over the 24 week period. The diastolic blood pressure reduction was significantly greater (p less than 0.01) with atenolol than with pindolol. Before beta-blocker therapy, many patients had already experienced side-effects such as fatigue, sleep disturbances and dreams. This probably relates to the high sensitivity of the analogue scale used to assess side-effects, and to the high incidence of such symptoms in untreated patients. As the study progressed there was a reduction in the frequency of fatigue (p less than 0.03) and dreams (p less than 0.05) in both groups, whereas sleep disturbances significantly increased under pindolol (p less than 0.05) but decreased under atenolol (p less than 0.05). The only important side-effect difference between the two beta-blockers was the higher incidence of sleep disturbances with pindolol which may be due to the higher lipophilicity of this beta-blocker.

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 ".

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.

[Towards an improvement of the quality of life after radiotherapy in children].

PubMed

Demoor-Goldschmidt, Charlotte; Bernier, Valérie

2015-01-01

Pediatric radiotherapy did not differ technically from adult radiotherapy but its characteristics, its difficulties and challenges are specific. Thanks in part to this treatment, overall survival of French children with cancer is around 80%. It is therefore important to integrate in the elaboration of the treatment planning potential side long-term effects. Indeed, whatever the technique is, even the most sophisticated, it is usually inevitable that healthy nearby organs receive a dose of radiation. Dose limits on organs at risk come from adult data and are adapted for children. After the treatment, it is important to graduate the potential risks of side effects to propose a personalized monitoring protocol avoiding excessive medicalization. This article presents the medical thinking concerning radiotherapy in different anatomical areas (brain, head and neck, chest, abdomen) including concepts of dose level corresponding to side effects usually described. In parallel, we present follow-up recommendations with the aim to preserve an optimal quality of life for the adults cured of a childhood cancer, currently called survivors. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

A Weighty Matter: Heaviness Influences the Evaluation of Disease Severity, Drug Effectiveness, and Side Effects

PubMed Central

Kaspar, Kai

2013-01-01

Peoples' perception of diseases and pharmaceutical drugs is a critical issue in health research. Beliefs about disease severity influence the compliance with recommendations for convalescence and the motivation to perform proper health-behavior. The estimated effectiveness of drugs and severity of side effects influence medication adherence and contribute to placebo effects. The present paper closes the gap between these effects and the concept of embodied cognition from a metaphor-enriched perspective. In five studies, we demonstrate that the bodily sensation of weight influences our evaluations of diseases and drugs. The experience of heaviness enhanced the estimated seriousness of diseases and the estimated effectiveness of drugs. The perceived seriousness of drug side effects was also affected by weight but only when drug effectiveness was not attended to. Moreover, the incidental sensation of weight shows a novel effect when evaluating weight-related drugs. The results are in line with the idea of embodied metaphors and reveal important boundary conditions which contribute to a better understanding of the underlying mechanisms. PMID:24244302

Preferences for a potential longer-acting injectable contraceptive: perspectives from women, providers, and policy makers in Kenya and Rwanda.

PubMed

Tolley, Elizabeth E; McKenna, Kevin; Mackenzie, Caroline; Ngabo, Fidele; Munyambanza, Emmanuel; Arcara, Jennet; Rademacher, Kate H; Lendvay, Anja

2014-05-01

Between 1995 and 2005, injectable use doubled worldwide. However, discontinuation rates remain high, partly because of side effects but also because of missed appointments for reinjection. A longer-acting injectable (LAI) may improve compliance by reducing the required number of reinjection visits, thereby reducing unintentional discontinuation. This study examined acceptability of LAI characteristics comprising the target product profile (TPP). In 2012, we conducted qualitative case studies in Kenya and Rwanda, consisting of 19 focus group discussions (FGDs) with 177 current, previous, or never users of injectables and 46 in-depth interviews (IDIs) with providers, program implementers, and policy makers. FGDs and IDIs assessed current injectable experiences; attitudes toward potential LAI products; and perceptions of TPP attributes, including ranking preferences for the most and least important characteristics. In addition, we obtained completed electronic surveys from 28 international family planning opinion leaders about the perceived need for an LAI, important product characteristics, and challenges to LAI development or introduction. Many FGD participants and interviewees spontaneously expressed strong interest in an LAI, but there was some variation in TPP preferences. The majority of participants ranked effectiveness as the most important TPP attribute. Providers were generally more concerned about side effects than potential users; some potential users suggested that side effects were related less to the product than to their own body chemistry and that side effects were acceptable as long as they did not last a long time or disrupt daily activities. Women and providers, especially in Kenya, preferred a method with a predictable return to fertility. Some participants associated amenorrhea with delayed or reduced fertility. Most women and providers preferred delivery of the LAI in a single, prepackaged, disposable injection system to facilitate injections by providers and to reduce the risk of pain or discomfort for women. While providers and policy makers ranked cost as one of the most important issues, it was among the least important issues for most potential users. Many Kenyan, but few Rwandan, participants appeared willing to pay for an LAI, with some presuming cost savings from reduced menstruation and fewer clinic visits. Some TPP preferences for an LAI have implications for product development decisions about formulation, delivery mechanism, or presentation, while others point to the need for tailored communication and counseling approaches to ensure acceptability and adherence within clinical trials and beyond.

Pharmacogenetic study of second-generation antipsychotic long-term treatment metabolic side effects (the SLiM Study): rationale, objectives, design and sample description.

PubMed

Pina-Camacho, Laura; Díaz-Caneja, Covadonga M; Saiz, Pilar A; Bobes, Julio; Corripio, Iluminada; Grasa, Eva; Rodriguez-Jimenez, Roberto; Fernández, Miryam; Sanjuán, Julio; García-López, Aurelio; Tapia-Casellas, Cecilia; Álvarez-Blázquez, María; Fraguas, David; Mitjans, Marina; Arias, Bárbara; Arango, Celso

2014-01-01

Weight gain is an important and common side effect of second generation antipsychotics (SGAs). Furthermore, these drugs can induce other side effects associated with higher cardiovascular morbidity and mortality, such as insulin resistance, diabetes or metabolic syndrome. Preliminary studies show that inter-individual genetic differences produce varying degrees of vulnerability to the different SGA-induced side effects. The Second-generation antipsychotic Long-term treatment Metabolic side effects (SLiM) study aims to identify clinical, environmental and genetic factors that explain inter-individual differences in weight gain and metabolic changes in drug-naïve patients after six months of treatment with SGAs. The SLIM study is a multicenter, observational, six-month pharmacogenetic study where a cohort of 307 drug-naïve paediatric and adult patients (age range 8.8-90.1 years) and a cohort of 150 age- and sex- matched healthy controls (7.8-73.2 years) were recruited. This paper describes the rationale, objectives and design of the study and provides a description of the sample at baseline. Results from the SLiM study will provide a better understanding of the clinical, environmental, and genetic factors involved in weight gain and metabolic disturbances associated with SGA treatment. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

[Side effects of biologic therapies in psoriasis].

PubMed

Altenburg, A; Augustin, M; Zouboulis, C C

2018-04-01

The introduction of biologics has revolutionized the treatment of moderate to severe plaque psoriasis. Due to the continuous expansion of biological therapies for psoriasis, it is particularly important to acknowledge efficacy and safety of the compounds not only in clinical trials but also in long-term registry-based observational studies. Typical side effects and significant risks of antipsoriatic biologic therapies considering psoriatic control groups are presented. A selective literature search was conducted in PubMed and long-term safety studies of the psoriasis registries PsoBest, PSOLAR and BADBIR were evaluated. To assess the long-term safety of biologics, the evaluation of the course of large patient cohorts in long-term registries is of particular medical importance. Newer biologic drugs seem to exhibit a better safety profile than older ones.

Context as a drug: some consequences of placebo research for primary care.

PubMed

Lucassen, P; Olesen, F

2016-12-01

On the basis of emerging research evidence, this review aims to discuss the importance of the context surrounding the doctor-patient encounter for the success of treatment. Discussion paper based on placebo-nocebo and pain studies conducted in the western world. Literature-based theory about impact of communication elements on seriousness of symptoms in clinical practice. The therapeutic outcome seems to be impacted by rituals around a clinical encounter and by the doctor patient communication and relation. A warm, friendly and empathic attitude is crucial in the first contact with the practice and during the consultation as it influences the patient's perceived outcome. It is important to raise positive expectations when discussing the prognosis, conducting treatment and prescribing medications as the effect may be reduced if the physician expresses doubt about the effectiveness of the medication. Additionally, overly focus on side effects in the doctor-patient conversation about proposed treatments seems to influence the magnitude of perceived side effects in the patient. Thus, shared decision-making might be a desirable tool for ensuring better expectations in the patient and successful symptom relief. The context of the doctor-patient interplay matters. Placebo-nocebo research provides strong evidence for this link. The therapeutic context induces biomedical processes in the patient's brain that may enhance or reduce the effects of chosen interventions. The context thus works as a drug, with real effects and side effects. KEY POINTS Increased awareness of the context drug may help GPs alleviate symptoms and better motivate patients for treatment. Treatment is affected by multiple types of context, as also confirmed by placebo-nocebo research. The therapeutic context influences the biomedical processes, which may enhance or reduce intervention effects on symptoms. The impact of context should be considered in daily general practice as it may serve as a drug, with real effects and side effects.

Religious Involvement, Social Support, and Health Among African-American Women on the East Side of Detroit

PubMed Central

Van Olphen, Juliana; Schulz, Amy; Israel, Barbara; Chatters, Linda; Klem, Laura; Parker, Edith; Williams, David

2003-01-01

BACKGROUND A significant body of research suggests that religious involvement is related to better mental and physical health. Religion or spirituality was identified as an important health protective factor by women participating in the East Side Village Health Worker Partnership (ESVHWP), a community-based participatory research initiative on Detroit's east side. However, relatively little research to date has examined the mechanisms through which religion may exert a positive effect on health. OBJECTIVE The research presented here examines the direct effects of different forms of religious involvement on health, and the mediating effects of social support received in the church as a potential mechanism that may account for observed relationships between church attendance and health. DESIGN This study involved a random sample household survey of 679 African-American women living on the east side of Detroit, conducted as part of the ESVHWP. MAIN RESULTS Results of multivariate analyses show that respondents who pray less often report a greater number of depressive symptoms, and that faith, as an important source of strength in one's daily life, is positively associated with chronic conditions such as asthma or arthritis. Tests of the mediating effect of social support in the church indicated that social support received from church members mediates the positive relationship between church attendance and specific indicators of health. CONCLUSIONS These findings are consistent with the hypothesis that one of the major ways religious involvement benefits health is through expanding an individual's social connections. The implications of these findings for research and practice are discussed. PMID:12848838

Hypersensitivity lo local anesthetics.

PubMed

Grzanka, Alicja; Wasilewska, Iwona; Śliwczyńska, Magdalena; Misiołek, Hanna

2016-01-01

Using local anaesthetics in daily practice, particularly by anaesthetists and dentists, is connected with the risk of side effects. Therefore, the observation of side effects, carrying out detailed research (according to the chart proposed in this study) and conducting specialist examinations is of the highest importance. There is a variety of side effects that could occur during local anaesthesia procedures, with the intensity ranging from clinically unimportant to life threatening. Clinicians' major concerns are the appearance of various hypersensitivity reactions, including anaphylaxis. Healthcare providers responsible for the administration of local anaesthetics should be able to detect hypersensitivity reactions to implement appropriate treatment and then choose highly selected diagnostic procedures. The final diagnosis should be based on specific medical history; documentation, including a description of the case and measurement of tryptase activity; skin tests; and provocation trials. Screening tests are not recommended in populations without hypersensitivity to local anaesthestics in their medical history.

[Pharmacogenetics in primary health care: implementation and future expectations].

PubMed

Houwink, Elisa J F; Rigter, Tessel; Swen, Jesse J; Cornel, Martina C; Kienhuis, Anne; Rodenburg, Wendy; Weda, Marjolein

2015-01-01

Personalised medicine is a targeted approach to the prevention, diagnosis and treatment of disorders on the basis of the specific genetic profile of the patient. Pharmacogenetics research shows that differences in the genetic profile of patients explain the interindividual differences in efficacy and side effects of medicines. Although there are high expectations of personalised medicine and pharmacogenetics in healthcare, both are only used to a limited extent to date. Pharmacogenetics seems particularly important in diseases with a poor prognosis and treatments with potentially serious side effects. Pharmacogenetics testing is reimbursed in the case of serious side effects or unexpected ineffectiveness. 95% of patients in the Netherlands have at least one abnormality in the panel of genes for which guidance is available. The KNMP (Royal Dutch Pharmacists' Association) provides dosing advice based on genotype for 80 medicines, 27 of which are regularly prescribed in primary health care.

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.

Life After Breast Cancer Treatment

MedlinePlus

... pregnancy. A woman who is concerned about the effects of chemotherapy on fertility should ask her doctor about options before she ... from medicines. Weight gain is a common side effect of ... loss and may help to relieve stress. It is also important to eat a healthy ...

A discrete choice experiment to explore patients' willingness to risk disease relapse from treatment withdrawal in psoriatic arthritis.

PubMed

Rothery, Claire; Bojke, Laura; Richardson, Gerry; Bojke, Chris; Moverley, Anna; Coates, Laura; Thorp, Liz; Waxman, Robin; Helliwell, Philip

2016-12-01

The objective of this study is to assess patient preferences for treatment-related benefits and risk of disease relapse in the management of low disease states of psoriatic arthritis (PsA). Focus groups with patients and a literature review were undertaken to determine the characteristics of treatment and symptoms of PsA important to patients. Patient preferences were assessed using a discrete choice experiment which compared hypothetical treatment profiles of the risk and benefits of treatment withdrawal. The risk outcome included increased risk of disease relapse, while benefit outcomes included reduced sickness/nausea from medication and changes in health-related quality of life. Each patient completed 12 choice sets comparing treatment profiles. Preference weights were estimated using a logic regression model, and the maximum acceptable risk in disease relapse for a given improvement in benefit outcomes was elicited. Final sample included 136 patients. Respondents attached the greatest importance to eliminating severe side effects of sickness/nausea and the least importance to a change in risk of relapse. Respondents were willing to accept an increase in the risk of relapse of 32.6 % in order to eliminate the side effects of sickness/nausea. For improvements in health status, the maximum acceptable risk in relapse was comparable to a movement from some to no sickness/nausea. The study suggests that patients in low disease states of PsA are willing to accept greater risks of relapse for improvements in side effects of sickness/nausea and overall health status, with the most important benefit attribute being the elimination of severe sickness or nausea.

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.

Characterization and bioactivity of novel calcium antagonists - N-methoxy-benzyl haloperidol quaternary ammonium salt

PubMed Central

Chen, Yi-Cun; Zhu, Wei; Zhong, Shu-Ping; Zheng, Fu-Chun; Gao, Fen-Fei; Zhang, Yan-Mei; Xu, Han; Zheng, Yan-Shan; Shi, Gang-Gang

2015-01-01

BACKGROUND AND PURPOSE Calcium antagonists play an important role in clinical practice. However, most of them have serious side effects. We have synthesized a series of novel calcium antagonists, quaternary ammonium salt derivatives of haloperidol with N-p-methoxybenzyl (X1), N-m-methoxybenzyl (X2) and N-o-methoxybenzyl (X3) groups. The objective of this study was to investigate the bioactivity of these novel calcium antagonists, especially the vasodilation activity and cardiac side-effects. The possible working mechanisms of these haloperidol derivatives were also explored. EXPERIMENTAL APPROACH Novel calcium antagonists were synthesized by amination. Compounds were screened for their activity of vasodilation on isolated thoracic aortic ring of rats. Their cardiac side effects were explored. The patch-clamp, confocal laser microscopy and the computer-fitting molecular docking experiments were employed to investigate the possible working mechanisms of these calcium antagonists. RESULTS The novel calcium antagonists, X1, X2 and X3 showed stronger vasodilation effect and less cardiac side effect than that of classical calcium antagonists. They blocked L-type calcium channels with an potent effect order of X1 > X2 > X3. Consistently, X1, X2 and X3 interacted with different regions of Ca2+-CaM-CaV1.2 with an affinity order of X1 > X2 > X3. CONCLUSIONS The new halopedidol derivatives X1, X2 and X3 are novel calcium antagonists with stronger vasodilation effect and less cardiac side effect. They could have wide clinical application. PMID:26544729

A qualitative analysis of women's explanations for changing contraception: the importance of non-contraceptive effects.

PubMed

Wigginton, Britta; Harris, Melissa L; Loxton, Deborah; Lucke, Jayne C

2016-10-01

Women commonly report changing contraceptive methods because of side-effects. However, there is a lack of literature that has thoroughly examined women's perspectives, including why they changed contraception. Using qualitative data from a contraceptive survey of young Australian women, we explored women's explanations for their recent changes in contraception. A thematic analysis of 1051 responses to a question about why women recently changed contraception was conducted. Themes reflected reasons for changing contraception which included: both contraceptive and non-contraceptive (4%); relationship/sexual (9%); medical (11%); contraceptive (18%); non-contraceptive (41%). A minority of responses were uncoded (17%). Non-contraceptive effects (effects unrelated to pregnancy prevention) featured most frequently in women's reasons for changing contraception. While cessation of various contraceptives due to unwanted side-effects is a well-known phenomenon, this analysis provides evidence of the changing of contraception for its non-contraceptive effects and reframes the notion of 'side-effects'. 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/.

Study on collision resistance characteristics of the side tanks with water inside

NASA Astrophysics Data System (ADS)

Liu, Yuxi; Hu, Jinwen; Liu, Ting; Wu, Can

2018-05-01

When we evaluate the safety performance of ships against external events, one of the most important indicator is the collision resistance to which water inside the side tanks also make some contributions because of the water effect. To further analyze the interaction mechanism, different collision velocities and side tank waterlines are set for the analysis model. Results indicate the outside shell and the inner shell of the side structure significantly enhanced the collision resistance performance to a certain extension. The water effect on the failure of the outside shell is unobvious, while, it performs a great influence on the destructive reaction force of the inner shell. When the velocity of the coming bulbous bow gradually increases, the destructive reaction forces of the outside shell and the inner shell increase with a decreasing rate. Besides, water influence the collision characteristics of the inner shell a lot when the waterlines are below the upper rib of the strong frame.

Impact of scaling voltage and size on the performance of Side-contacted Field Effect Diode

NASA Astrophysics Data System (ADS)

Touchaei, Behnam Jafari; Manavizadeh, Negin

2018-05-01

Side-contacted Fild Effect Diode (S-FED), with low leakage current and high Ion/Ioff ratio, has been recently introduced to suppress short channel effects in nanoscale regime. The voltage and size scalability of S-FEDs and effects on the power consumption, propagation delay time, and power delay product have been studied in this article. The most attractive properties are related to channel length to channel thickness ratio in the S-FED which reduces in comparison with MOSFET significantly, while gates control over the channel improve and the off-state current reduces dramatically. This promising advantage is not only capable to improve important S-FED's characteristics such as subthreshold slope but also eliminate Latch-up and floating body effect.

Off-Label Drug Use

MedlinePlus

... their drugs for off-label uses. Off-label marketing is very different from off-label use. Why ... at a higher risk for medication errors, side effects, and unwanted drug reactions. It’s important that the ...

Seizure Disorders: A Review for School Psychologists.

ERIC Educational Resources Information Center

Sachs, Henry T.; Barrett, Rowland P.

1995-01-01

Recognizing possible seizure disorders, medication side-effects, behavioral and cognitive effects of seizures, and their treatments are important skills for school psychologists because they affect 500,000 United States school-aged children attending regular education. A knowledgeable school professional serves a critical role in integrating…

Hepatic manifestations of non-steroidal inflammatory bowel disease therapy

PubMed Central

Hirten, Robert; Sultan, Keith; Thomas, Ashby; Bernstein, David E

2015-01-01

Inflammatory bowel disease (IBD) is composed of Crohn’s disease and ulcerative colitis and is manifested by both bowel-related and extraintestinal manifestations. Recently the number of therapeutic options available to treat IBD has dramatically increased, with each new medication having its own mechanism of action and side effect profile. A complete understanding of the hepatotoxicity of these medications is important in order to distinguish these complications from the hepatic manifestations of IBD. This review seeks to evaluate the hepatobiliary complications of non-steroid based IBD medications and aide providers in the recognition and management of these side-effects. PMID:26644815

Current concepts for chronochemotherapy of cancer.

PubMed

Laerum, O D; Smaaland, R; Abrahamsen, J F

1995-01-01

In this article, a survey on the concepts and scientific basis for applying chemotherapy against malignant tumors on a circadian schedule is given. The idea is to give the cytostatic drugs at times of the day when optimal effect on the tumor is achieved, but at the same time causing minimal toxic side effects. Following a brief description of the complexity of cancer tissue, some aspects of the present status of cancer chemotherapy in general are reviewed. Applications of chronobiology in cancer treatment are then surveyed together with possibilities to increase cytostatic doses and reduce side effects. When optimal tumor cell kill is achieved, the next step is to address the circadian aspects of normal organs, including the proliferative behavior of tissues with rapid cell renewal. Finally, the question of how regulatory mechanisms responsible for normal circadian rhythms can be interfered with is addressed. Cancer chronochemotherapy today combined with modern infusional technology is a promising field for improving cancer treatment in general and reducing side effects and is expected to make important progress in the near future.

Efavirenz, Emtricitabine, and Tenofovir

MedlinePlus

... nervous abnormally happy mood unusual dreams joint or back pain itching Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately ...

Tachykinin NK-1 and NK-3 selective agonists induce analgesia in the formalin test for tonic pain following intra-VTA or intra-accumbens microinfusions.

PubMed

Altier, N; Stewart, J

1997-12-01

Experiments were designed to examine the analgesic effects induced by selective tachykinin receptor agonists microinfused into either the ventral tegmental area (VTA) or nucleus accumbens septi (NAS). Rats were tested in the formalin test for tonic pain following an injection of 0.05 ml of 2.5% formalin into one hind paw immediately after bilateral intra-VTA infusions of either the NK-1 agonist, GR-73632 (0.005, 0.05 or 0.5 nmol/side), the NK-3 agonist, senktide (0.005, 0.5 or 1.5 nmol/side), or saline. Two weeks later, the saline-treated rats were assessed in the tail-flick test for phasic pain after infusions of the tachykinin agonists. Tail-flick latencies were recorded following immersion of the tail in 55 degrees C hot water at 10 min intervals for 1 h immediately after intra-VTA infusions of either GR-73632 (0.5 nmol/side), senktide (1.5 nmol/side) or saline. In a second group of rats, the same effects were studied after infusions into the nucleus accumbens (NAS) of GR-73632 (0.005, 0.5 or 1.5 nmol/side), senktide (0.005, 0.5 or 1.5 nmol/side), or saline. In both the VTA and NAS, the NK-1 and the NK-3 agonists caused significant analgesia in the formalin test, although the NK-1 agonist appeared to be more effective. Naltrexone (2.0 mg/kg) pretreatment failed to reverse the analgesic effects in the formalin test induced by intra-VTA infusions of the substance P (SP) analog, DiMe-C7 (3.0 microg/side), GR-73632 (0.5 nmol/side), or senktide (1.5 nmol/side). Neither compound given at either site was effective in the tail-flick test. These findings suggest that SP-dopamine (DA) interactions within the mesolimbic DA system play an important role in the inhibition of tonic pain. Furthermore, they support our earlier ideas that activation of midbrain DA systems by SP might play a role in stress- and/or pain-induced analgesia.

[Drug management for coronary artery disease in the elderly].

PubMed

Meune, C

2006-11-01

The incidence of side effects increases dramatically with age. It is estimated that almost one third of side effects could be avoided by an appropriate prescription. On the other hand, age is the main factor associated to the non-prescription of major pharmacological classes, which have evidenced their efficacy in younger patients with coronary artery disease. The estimation of the benefit/risk ratio is therefore highly important in the old/very old patient. It seems important to integrate the results of studies and registries including old patients, evidencing the efficacy of the majority of pharmacological classes validated in younger patients, especially antiplatelets, beta-blockers and statins. The assessment of the benefit/risk ratio should also take into account the tolerance profile of the drug and the patient. The prescription should be adapted to the "age-related" changes of pharmacokinetics and pharmacodynamics.

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.

Oncology providers' perspectives on endocrine therapy prescribing and management.

PubMed

Wheeler, Stephanie B; Roberts, Megan C; Bloom, Diane; Reeder-Hayes, Katherine E; Espada, Maya; Peppercorn, Jeffrey; Golin, Carol E; Earp, Jo Anne

2016-01-01

Adjuvant endocrine therapy (ET) can reduce the risk of recurrence among females with hormone receptor-positive breast cancer. Overall, initiation and adherence to ET are suboptimal, though reasons are not well described. The study's objective was to better understand ET decision making, prescribing, and patient management from oncology providers' perspectives. Using purposive sampling, we recruited oncology providers who saw five or more breast cancer patients per week (n=20). We conducted 30-45-minute telephone interviews, using a semistructured guide to elicit perspectives on ET use. We used thematic content analysis to systematically identify categories of meaning and double-coded transcripts using Atlas.ti. Providers recommend ET to all eligible patients except those with contraindications or other risk factors. Providers base their ET prescribing decisions on the patient's menopausal status, side effects, and comorbidities. ET is typically discussed multiple times: at the onset of breast cancer treatment and in more detail after other treatment completion. Providers felt that the associated recurrence risk reduction is the most compelling argument for patients during ET decision making. While providers rarely perceived noninitiation as a problem, nonadherence was prevalent, often due to unresolvable side effects. From the clinicians' perspectives, side effects from ET are the dominant factor in nonadherence. Efforts to improve adherence should focus on strategies to minimize side effects and ensure clinicians and patients are well informed regarding optimal side effect management. This finding has important implications for novel endocrine regimens that offer improved outcomes through longer duration or more intensive therapy.

Perceptions of coping behaviors by persons with cancer and health care providers.

PubMed

Merluzzi, T V; Martinez Sanchez, M A

1997-09-01

We studied perceptions of the importance and difficulty of coping behaviors, from the perspectives of cancer patients (n = 33) and health care providers (i.e. nursing and technical personnel, n = 24). They rated the importance and difficulty of 43 behaviors that correspond to six domains of coping with cancer. Generally, ratings of importance were similar for both patients and providers. However, patients rated the domains of Coping with Treatment Related Side Effects and Seeking Support as less important than staff. Ratings of difficulty were quite divergent. Patients perceived coping as less difficult than the medical staff in the following domains: Maintenance of Activity and Independence, Coping With Treatment-Related Side-Effects, Accepting Cancer/Maintaining Positive Attitude, and Seeking Support. These differences in difficulty ratings between patients and health care providers may reflect distinct perspectives or schemas about coping. That is, patients may hold 'positive illusions' about their coping capacity and, therefore, rate coping as less difficult. Health care providers may overestimate patients' distress and, therefore, underestimate patients' coping capacity. An understanding of these different perspectives may assist medical staff in fostering self-efficacy expectations for coping behaviors.

Side effect profile similarities shared between antidepressants and immune-modulators reveal potential novel targets for treating major depressive disorders.

PubMed

Sun, Yu; Narayan, Vaibhav A; Wittenberg, Gayle M

2016-10-21

Side effects, or the adverse effects of drugs, contain important clinical phenotypic information that may be useful in predicting novel or unknown targets of a drug. It has been suggested that drugs with similar side-effect profiles may share common targets. The diagnostic class, Major Depressive Disorder, is increasingly viewed as being comprised of multiple depression subtypes with different biological root causes. One 'type' of depression generating substantial interest today focuses on patients with high levels of inflammatory burden, indicated by elevated levels of C-reactive proteins (CRP) and pro-inflammatory cytokines such as interleukin 6 (IL-6). It has been suggested that drugs targeting the immune system may have beneficial effect on this subtype of depressed patients, and several studies are underway to test this hypothesis directly. However, patients have been treated with both anti-inflammatory and antidepressant compounds for decades. It may be possible to exploit similarities in clinical readouts to better understand the antidepressant effects of immune-related drugs. Here we explore the space of approved drugs by comparing the drug side effect profiles of known antidepressants and drugs targeting the immune system, and further examine the findings by comparing the human cell line expression profiles induced by them with those induced by antidepressants. We found 7 immune-modulators and 14 anti-inflammatory drugs sharing significant side effect profile similarities with antidepressants. Five of the 7 immune modulators share most similar side effect profiles with antidepressants that modulate dopamine release and/or uptake. In addition, the immunosuppressant rapamycin and the glucocorticoid alclometasone induces transcriptional changes similar to multiple antidepressants. These findings suggest that some antidepressants and some immune-related drugs may affect common molecular pathways. Our findings support the idea that certain medications aimed at the immune system may be helpful in relieving depressive symptoms, and suggest that it may be of value to test immune-modulators for antidepressant-like activity in future proof-of-concept studies.

Sleep Disturbance During Smoking Cessation: Withdrawal or Side Effect of Treatment?

PubMed

Ashare, Rebecca L; Lerman, Caryn; Tyndale, Rachel F; Hawk, Larry W; George, Tony P; Cinciripini, Paul; Schnoll, Robert A

2017-06-01

The nicotine-metabolite ratio (NMR) predicts treatment response and is related to treatment side effect severity. Sleep disturbance may be one important side effect, but understanding sleep disturbance effects on smoking cessation is complicated by the fact that nicotine withdrawal also produces sleep disturbance. To evaluate the effects of withdrawal and treatment side effects on sleep disturbance. This is a secondary analysis of data from a clinical trial (Lerman et al., 2015) of 1,136 smokers randomised to placebo ( n = 363), transdermal nicotine (TN; n = 381), or varenicline ( n = 392) and stratified based on NMR (559 slow metabolisers; 577 normal metabolisers). Sleep disturbance was assessed at baseline and at 1-week following the target quit date (TQD). We also examined whether sleep disturbance predicted 7-day point-prevalence abstinence at end-of-treatment (EOT). The varenicline and TN groups exhibited greater increases in sleep disturbance (vs. placebo; treatment × time interaction; p = 0.005), particularly among those who quit smoking at 1-week post-TQD. There was a main effect of NMR ( p = 0.04), but no interactions with treatment. TN and varenicline attenuated withdrawal symptoms unrelated to sleep (vs. placebo). Greater baseline sleep disturbance predicted relapse at EOT ( p = 0.004). Existing treatments may not mitigate withdrawal-related sleep disturbance and adjunctive treatments that target sleep disturbance may improve abstinence rates.

POTENTIAL OF HERBAL MEDICINES IN MODERN MEDICAL THERAPY

PubMed Central

Said, Hakim Mohammed

1984-01-01

The author discusses in this paper the potentialities of Herbal medicine in modern therapy. Also he throws some light on the importance of natural drugs which bring about cure without generation side-effects. PMID:22557447

Pre-Surgery Psychological Factors Predict Pain, Nausea and Fatigue One Week Following Breast Cancer Surgery

PubMed Central

Montgomery, Guy H.; Schnur, Julie B.; Erblich, Joel; Diefenbach, Michael A.; Bovbjerg, Dana H.

2010-01-01

Prior to scheduled surgery, breast cancer surgical patients frequently experience high levels of distress and expect a variety of post-surgery symptoms. Previous literature has supported the view that pre-surgery distress and response expectancies are predictive of post-surgery outcomes. However, the contributions of distress and response expectancies to post-surgical side effect outcomes have rarely been examined together within the same study. Furthermore, studies on the effects of response expectancies in the surgical setting have typically focused on the immediate post-surgical setting rather than the longer term. The purpose of the present study was to test the contribution of pre-surgery distress and response expectancies to common post-surgery side effects (pain, nausea, fatigue). Female patients (n=101) undergoing breast cancer surgery were recruited to a prospective study. Results indicated that pre-surgery distress uniquely contributed to patients’ post-surgery pain severity (P<0.05) and fatigue (P<0.003) one week following surgery. Response expectancies uniquely contributed to pain severity (P<0.001), nausea (P<0.012) and fatigue (P<0.010) one week following surgery. Sobel tests indicated that response expectancies partially mediated the effects of distress on pain severity (P<0.03) and fatigue (P<0.03). Response expectancies also mediated the effects of age on pain severity, nausea and fatigue. Results highlight the contribution of pre-surgery psychological factors to post-surgery side effects, the importance of including both emotional and cognitive factors within studies as predictors of post-surgery side effects, and suggest pre-surgical clinical targets for improving patients’ postoperative experiences of side effects. PMID:20538186

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.

Pharmacogenetics of clozapine treatment response and side-effects in schizophrenia: an update.

PubMed

Sriretnakumar, Venuja; Huang, Eric; Müller, Daniel J

2015-01-01

Clozapine (CLZ) is the most effective treatment for treatment-resistant schizophrenia (SCZ) patients, with potential added benefits of reduction in suicide risk and aggression. However, CLZ is also mainly underused due to its high risk for the potentially lethal side-effect of agranulocytosis as well as weight gain and related metabolic dysregulation. Pharmacogenetics promises to enable the prediction of patient treatment response and risk of adverse effects based on patients' genetics, paving the way toward individualized treatment. This article reviews pharmacogenetics studies of CLZ response and side-effects with a focus on articles from January 2012 to February 2015, as an update to the previous reviews. Pharmacokinetic genes explored primarily include CYP1A2, while pharmacodynamic genes consisted of traditional pharmacogenetic targets such as brain-derived neurotrophic factor as well novel mitochondrial genes, NDUFS-1 and translocator protein. Pharmacogenetics is a promising avenue for individualized medication of CLZ in SCZ, with several consistently replicated gene variants predicting CLZ response and side-effects. However, a large proportion of studies have yielded mixed results. Large-scale Genome-wide association studies (e.g., CRESTAR) and targeted gene studies with standardized designs (response measurements, treatment durations, plasma level monitoring) are required for further progress toward clinical translation. Additionally, in order to improve study quality, we recommend accounting for important confounders, including polypharmacy, baseline measurements, treatment duration, gender, and age at onset.

Experimental Studies on Wave Interactions of Partially Perforated Wall under Obliquely Incident Waves

PubMed Central

Lee, Jong-In; Kim, Young-Taek; Shin, Sungwon

2014-01-01

This study presents wave height distribution in terms of stem wave evolution phenomena on partially perforated wall structures through three-dimensional laboratory experiments. The plain and partially perforated walls were tested to understand their effects on the stem wave evolution under the monochromatic and random wave cases with the various wave conditions, incident angle (from 10 to 40 degrees), and configurations of front and side walls. The partially perforated wall reduced the relative wave heights more effectively compared to the plain wall structure. Partially perforated walls with side walls showed a better performance in terms of wave height reduction compared to the structure without the side wall. Moreover, the relative wave heights along the wall were relatively small when the relative chamber width is large, within the range of the chamber width in this study. The wave spectra showed a frequency dependency of the wave energy dissipation. In most cases, the existence of side wall is a more important factor than the porosity of the front wall in terms of the wave height reduction even if the partially perforated wall was still effective compared to the plain wall. PMID:25254260

Experimental studies on wave interactions of partially perforated wall under obliquely incident waves.

PubMed

Lee, Jong-In; Kim, Young-Taek; Shin, Sungwon

2014-01-01

This study presents wave height distribution in terms of stem wave evolution phenomena on partially perforated wall structures through three-dimensional laboratory experiments. The plain and partially perforated walls were tested to understand their effects on the stem wave evolution under the monochromatic and random wave cases with the various wave conditions, incident angle (from 10 to 40 degrees), and configurations of front and side walls. The partially perforated wall reduced the relative wave heights more effectively compared to the plain wall structure. Partially perforated walls with side walls showed a better performance in terms of wave height reduction compared to the structure without the side wall. Moreover, the relative wave heights along the wall were relatively small when the relative chamber width is large, within the range of the chamber width in this study. The wave spectra showed a frequency dependency of the wave energy dissipation. In most cases, the existence of side wall is a more important factor than the porosity of the front wall in terms of the wave height reduction even if the partially perforated wall was still effective compared to the plain wall.

Medication non-adherence and uncertainty: Information-seeking and processing in the Danish LIFESTAT survey.

PubMed

Kriegbaum, Margit; Lau, Sofie Rosenlund

2017-09-23

Statins are widely prescribed to lower cardiovascular morbidity and mortality. However, statin non-adherence is very high. The aim of this paper was to investigate reasons for stopping statin treatment in the general population and to study how aspects of information-seeking and processing is associated with statin non-adherence. This study used a population survey on 3050 Danish residents aged 45-65 years. Reasons for statin discontinuation was studied among those who were previous statin users. The association between information seeking and processing and statin discontinuation were analysed using multivariate logistical regression models. Experience of side effects and fear of side effects played an important role in the discontinuation of statin treatment. Feelings of uncertainty and confusion regarding information on statins predicted statin discontinuation. This applied to information from both mass media and from general practitioners. There was no clear pattern of information seeking and statin non-adherence. The article point to the impact of information-seeking on the decision to take cholesterol-lowering medication. This included contributions from information disseminated by media outlets. Side effects and fear of side effects should be addressed in clinical practice. Health care professionals should pay attention to emotional aspects of how information is disseminated and perceived by statin users. Copyright © 2017. Published by Elsevier Inc.

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.

Co2 Laser Resurfacing for Facial Rhytides

PubMed Central

Jain, Vinod K; Ghiya, B C; Gupta, Dhruv; Singhi, Mahendra K

2008-01-01

Resurfacing of facial rhytides (periorbital crow-feet wrinkles) was performed in three cases by carbon dioxide laser (Sharplan® 1030 machine). Good to excellent results were observed. However, erythema and postinflammatory pigmentation were important side effects. PMID:20300334

Electric field effects on ion currents in satellite wakes

NASA Technical Reports Server (NTRS)

Parks, D. E.; Katz, I.

1985-01-01

Small currents associated with satellite spin, dielectric conduction, or trace concentrations of H+, can have a substantial effect on the potential of a satellite and the particle currents reaching its surface. The importance of such small currents at altitudes below about 300 km stems from the extremely small 0+ currents impinging on the wake-side of the spacecraft. The particle current on the downstream side of the AE-C satellite is considered. Theoretical estimates based on a newly described constant of the motion of a particle indicate that accounting for small concentrations of H+ remove a major discrepancy between calculated and measured currents.

Patients' perspectives about why they have their contraceptive Implanon NXT device removed early.

PubMed

Flore, Meike; Chen, Xiaoshuang Lilly; Bonney, Andrew; Mullan, Judy; Dijkmans-Hadley, Bridget; Hodgkins, Adam; Evans, Gina; Frew, Haley; Lloyd, Gail

2016-10-01

Women with long-acting, reversible contraceptive devices inserted may choose to remove them prior to their planned expiry dates. The objective of this study was to explore Australian women's experiences with the etonogestrel subdermal contraceptive implant (Implanon NXT) and why they had it removed early. Semi-structured interviews were conducted with 18 women between June 2013 and January 2014. Transcriptions of the audio-taped interviews were analysed using a constant comparative analysis framework. Two core themes of participants' responses that were identified in this study were influences on choice of contraception, which included convenience and information sources; and influences on removal of contraception, which included side effects and their negative impacts on relationships and financial costs. This study highlights that women's experiences with side effects contribute to the early removal of long-acting contraceptive devices such as Implanon NXT. This study emphasises the importance of general practitioners (GPs) in providing comprehensive information about the benefits and potential side effects associated with using these implants.

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.

Side effects from intense pulsed light: Importance of skin pigmentation, fluence level and ultraviolet radiation-A randomized controlled trial.

PubMed

Thaysen-Petersen, Daniel; Erlendsson, Andres M; Nash, J F; Beerwerth, Frank; Philipsen, Peter A; Wulf, Hans C; Paasch, Uwe; Haedersdal, Merete

2017-01-01

Intense pulsed light (IPL) is a mainstream treatment for hair removal. Side effects after IPL are known, but risk factors remain to be investigated. The objective of this study was to assess the contribution of skin pigmentation, fluence level, and ultraviolet radiation (UVR) on IPL-induced side effects. The study was a blinded, randomized intra-individual controlled trial including 16 healthy subjects with Fitzpatrick Skin Types (FST) II-V. Three test areas were each divided into four sites, randomized to a single IPL exposure of 22, 34, 46 J/cm 2 or triple stacking of 46 J/cm 2 . Areas were subsequently randomized to no UVR or single solar-simulated UVR exposure of 3 Standard Erythema Dose at 30 minutes or 24 hours after IPL. Each area had a corresponding control, resulting in 15 treatment sites. Follow-up visits were scheduled up to 4 weeks after IPL. Outcome measures were: (i) blinded clinical skin reactions; (ii) objectively measured erythema and pigmentation; (iii) pain measured by visual analog scale (VAS); (iv) histology (H&E, Fontana-Masson); and (v) mRNA-expression of p53. Fifteen subjects with FST II-IV completed the protocol. IPL induced a wide range of skin reactions, including erythema (87% of subjects), purpura (27%), blisters (20%), edema (13%), crusting (13%), hyper- (60%), and hypopigmentation (20%). Darker skin pigmentation and increasing IPL fluence were determinants for IPL-induced side effects (P ≤ 0.002), while a single exposure of UVR did not exacerbate side effects (P ≥ 0.180). Clinical findings were confirmed objectively by reflectance spectrometry and qualitatively by histological changes in skin architecture, inflammatory infiltration, and pigmentation. Marker of cellular DNA damage, that is, p53, did not increase after IPL (P ≥ 0.24). Skin pigmentation and IPL fluence are major determinants of side effects after IPL exposure, while a single exposure to three SED of UVR at 30 minutes or 24 hours after IPL, does not amplify such side effects. Lasers Surg. Med. 49:88-96, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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.

Is side-viewing endoscope assisted balloon dilatation better for corrosive gastric outlet obstruction?

PubMed

Katiyar, Prashant; Nijhawan, Sandeep; Saradava, Vimal; Nagaich, Neeraj; Gupta, Gaurav; Mathur, Amit; Nepalia, Subhash

2013-11-01

Endoscopic balloon dilatation (EBD) is an effective therapy for caustic-induced gastric outlet obstruction (GOO). Gaining access to the stricture site is the most important step. It is sometimes difficult to negotiate a balloon through the stricture with a front-viewing endoscope due to deformed anatomy of stomach. To overcome this technical difficulty, a side-viewing endoscope can be used. There is limited data regarding the use of side-viewing endoscopes in EBD. We here report on the short-term efficacy and safety of EBD in caustic-induced GOO. In technically difficult cases, a side-viewing endoscope was used for EBD and its efficacy and safety were assessed. The study included 25 patients with caustic-induced GOO. Patients underwent EBD using a through-the-scope balloon. Initial balloon dilatation was performed with a front-viewing endoscope. A side-viewing endoscope was used where negotiation across the stricture failed with a front-viewing endoscope. Dilatation was started at 8 mm diameter and was performed at 1-week intervals. The end point of dilatation was 15 mm diameter. In 18 patients successful balloon dilatation was possible with a front-viewing endoscope. A side-viewing endoscope was used in six patients as negotiation across the stricture was not possible with a front-viewing endoscope. In all six patients negotiation across the stricture followed by successful dilatation was successful with a side-viewing endoscope. Of the 25 patients included in this study, 24 (96%) achieved procedural success (18 with a front-viewing endoscope and 6 with a side-viewing endoscope) in 3-9 sessions. Our results show that EBD is a safe and effective option for caustic-induced GOO and in difficult cases a side-viewing endoscope can be used to achieve technical success.

The effect of acute hypoxia on short-circuit current and epithelial resistivity in biopsies from human colon.

PubMed

Carra, Graciela E; Ibáñez, Jorge E; Saraví, Fernando D

2013-09-01

In isolated colonic mucosa, decreases in short-circuit current (ISC) and transepithelial resistivity (RTE) occur when hypoxia is either induced at both sides or only at the serosal side of the epithelium. We assessed in human colon biopsies the sensitivity to serosal-only hypoxia and mucosal-only hypoxia and whether Na, K-ATPase blockade with ouabain interacts with hypoxia. Biopsy material from patients undergoing colonoscopy was mounted in an Ussing chamber for small samples (1-mm2 window). In a series of experiments we assessed viability and the electrical response to the mucolytic, dithiothreitol (1 mmol/l). In a second series, we explored the effect of hypoxia without and with ouabain. In a third series, we evaluated the response to a cycle of hypoxia and reoxygenation induced at the serosal or mucosal side while keeping the oxygenation of the opposite side. 1st series: Dithiothreitol significantly decreased the unstirred layer and ISC but increased RTE. 2nd series: Both hypoxia and ouabain decreased ISC, but ouabain increased RTE and this effect on RTE prevailed even during hypoxia. 3rd series: Mucosal hypoxia caused lesser decreases of ISC and RTE than serosal hypoxia; in the former, but not in the latter, recovery was complete upon reoxygenation. In mucolytic concentration, dithiothreitol modifies ISC and RTE. Oxygen supply from the serosal side is more important to sustain ISC and RTE in biopsy samples. The different effect of hypoxia and Na, K-ATPase blockade on RTE suggests that their depressing effect on ISC involves different mechanisms.

Leakage and field emission in side-gate graphene field effect transistors

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

Di Bartolomeo, A., E-mail: dibant@sa.infn.it; Iemmo, L.; Romeo, F.

We fabricate planar graphene field-effect transistors with self-aligned side-gate at 100 nm from the 500 nm wide graphene conductive channel, using a single lithographic step. We demonstrate side-gating below 1 V with conductance modulation of 35% and transconductance up to 0.5 mS/mm at 10 mV drain bias. We measure the planar leakage along the SiO{sub 2}/vacuum gate dielectric over a wide voltage range, reporting rapidly growing current above 15 V. We unveil the microscopic mechanisms driving the leakage, as Frenkel-Poole transport through SiO{sub 2} up to the activation of Fowler-Nordheim tunneling in vacuum, which becomes dominant at higher voltages. We report a field-emission current densitymore » as high as 1 μA/μm between graphene flakes. These findings are important for the miniaturization of atomically thin devices.« less

Viscous Fingering on an Immiscible Reactive Interface with Variation of Interfacial Tension

NASA Astrophysics Data System (ADS)

Tsuzuki, Reiko; Nagatsu, Yuichiro; Li, Qian; Chen, Ching-Yao

2017-11-01

The effects of chemical reaction, in which surfactants are produced on the interface of two immiscible fluids, on viscous fingering in a radial Hele-Shaw flow are numerically investigated. The presence of surfactants reduces interfacial tension, which is an important factor to the fingering pattern formation. In the present study, influences of reaction rate and dispersion of produced surfactants, represented respectively by dimensionless parameters of Damkohler number and Peclet number, are evaluated systematically. Secondary fingering instability, e.g., tip-splitting and side-branching, is triggered by chemical reactions. Weaker surface tension generally induces tip-splitting. For the case of high Damkohler number, because of the vortex pairs generated within each finger, surfactant tends to accumulate significantly on the side of finger, so that side-branching is preferred. Nevertheless, side-branching is suppressed in the cases associated with low Peclet number, in which strong dispersion reduces the local variation of surfactant concentration. Considering the coupled effects by Damkohler number and Peclet number, the patterns obtained by the simulations qualitatively agree with the observations in the experiments.

Drug side effect extraction from clinical narratives of psychiatry and psychology patients

PubMed Central

Kocher, Jean-Pierre A; Chute, Christopher G; Savova, Guergana K

2011-01-01

Objective To extract physician-asserted drug side effects from electronic medical record clinical narratives. Materials and methods Pattern matching rules were manually developed through examining keywords and expression patterns of side effects to discover an individual side effect and causative drug relationship. A combination of machine learning (C4.5) using side effect keyword features and pattern matching rules was used to extract sentences that contain side effect and causative drug pairs, enabling the system to discover most side effect occurrences. Our system was implemented as a module within the clinical Text Analysis and Knowledge Extraction System. Results The system was tested in the domain of psychiatry and psychology. The rule-based system extracting side effects and causative drugs produced an F score of 0.80 (0.55 excluding allergy section). The hybrid system identifying side effect sentences had an F score of 0.75 (0.56 excluding allergy section) but covered more side effect and causative drug pairs than individual side effect extraction. Discussion The rule-based system was able to identify most side effects expressed by clear indication words. More sophisticated semantic processing is required to handle complex side effect descriptions in the narrative. We demonstrated that our system can be trained to identify sentences with complex side effect descriptions that can be submitted to a human expert for further abstraction. Conclusion Our system was able to extract most physician-asserted drug side effects. It can be used in either an automated mode for side effect extraction or semi-automated mode to identify side effect sentences that can significantly simplify abstraction by a human expert. PMID:21946242

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.

Financing pharmaceuticals in transition economies.

PubMed

Kanavos, P

1999-06-01

This paper (a) provides a methodological taxonomy of pricing, financing, reimbursement, and cost containment methodologies for pharmaceuticals; (b) analyzes complex agency relationships and the health versus industrial policy tradeoff; (c) pinpoints financing measures to balance safety and effectiveness of medicines and their affordability by publicly funded systems in transition; and (d) highlights viable options for policy-makers for the financing of pharmaceuticals in transition. Three categories of measures and their implications for pharmaceutical policy cost containing are analyzed: supply-side measures, targeting manufacturers, proxy demand-side measures, targeting physicians and pharmacists, and demand-side measures, targeting patients. In pursuing supply side measures, we explore free pricing for pharmaceuticals, direct price controls, cost-plus and cost pricing, average pricing and international price comparisons, profit control, reference pricing, the introduction of a fourth hurdle, positive and negative lists, and other price control measures. The analysis of proxy-demand measures includes budgets for physicians, generic policies, practice guidelines, monitoring the authorizing behavior of physicians, and disease management schemes. Demand-side measures explore the effectiveness of patient co-payments, the impact of allowing products over-the-counter and health promotion programs. Global policies should operate simultaneously on the supply, the proxy demand, and the demand-side. Policy-making needs to have a continuous long-term planning. The importation of policies into transition economy may require extensive and expensive adaptation, and/or lead to sub-optimal policy outcomes.

New insights in the use of immunoglobulins for the management of immune deficiency (PID) patients

PubMed Central

Krivan, Gergely; Jolles, Stephen; Granados, Eduardo Lopes; Paolantonacci, Phillipe; Ouaja, Rabye; Cissé, Ousmane Alfa; Bernatowska, Ewa

2017-01-01

Immunoglobulin replacement therapy (IRT) is standard treatment for patients with primary immunodeficiency (PID). Because most of the patients with PID will require long life-time immunoglobulin replacement therapy, the quality of the prescribed products is of utmost importance. The IRT is generally administered either intravenously (abbreviated IVIG), or subcutaneously (abbreviated SCIG). Both routes have been demonstrated to be effective. The preferred route may vary at different times during a given patient’s life. Options are therefore not fixed and the choice of route for immunoglobulin therapy will depend on several factors, including patient characteristics, clinical indication, venous access, side effects, rural or remote location, treatment compliance and patient preference. Many years ago, immunoglobulin therapy was associated with side effects which may compromise patient’s compliance and quality of life of the patients. Most of the side effects were related to impurities. Recently, major advances in the manufacturing process have been made and new processes, such as the Quality by design (QbD) approach were added into the manufacturing steps to ensure patients tolerability and safety. Due to the improved purity of the immunoglobulin products obtained by these processes, the incidence of side effects is lower, while the ways of administration of Ig therapy and the choice of the regimen has widened to suit patient’s preference and needs. PMID:29181272

Rhinoscintigraphic analysis of nasal mucociliary function in patients with Bell's palsy.

PubMed

Boynuegri, S; Ozer, S; Peksoy, I; Acikalin, A; Tuna, E Ü; Dursun, E; Eryilmaz, A

2016-01-01

Mucociliary transport (MCT) is an important defense mechanism of the respiratory tract. One of the major factors determining MCT is the ciliary activity of the respiratory epithelium. Rhinoscintigraphy is the most commonly used method for the analysis of mucociliary activity. The aim of this study was to investigate the effect of facial paralysis on the nasal mucociliary clearance. This study included 38 Bell's palsy patients as the study group and 10 subjects without any history of paranasal sinus disease or facial paralysis as the control group. A drop of technetium 99m-labeled macroaggregated albumin (Tc-99m MAA) was placed posterior to the head of the inferior turbinate and followed with a gamma camera. MCT rate was measured as the velocity of Tc-99m MAA drop. The mean MCT rate was 4.27 ± 0.76 millimeters per minute (mm/min) on 20 sides of 10 healthy controls, 4.11 ± 2.91 mm/min on the affected sides of the patients with Bell's palsy, and 6.03 ± 3.13 mm/min on the nonparalyzed sides of the patients. MCT rate was statistically significantly faster in the nonparalyzed side when compared to the paralyzed side in Bell's palsy patients (P = 0.001). MCT rates were not significantly different in the control group and paralyzed sides of the Bell's palsy patients (P = 0.810). The MCT rate was statistically significantly faster in the nonparalyzed sides of Bell's palsy patients when compared to the controls (P = 0.017). This study showed a faster MCT rate on the nonparalyzed side in Bell's palsy patients when compared to the paralyzed side and the control subjects. A compensatory mechanism could be the underlying reason for faster MCT on the nonparalyzed side. Further studies on larger patient groups are needed to investigate the effect of facial paralysis on the MCT and changes of facial nerve function on the opposite, nonparalyzed side of the face.

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.

Life-threatening complications of ibogaine: three case reports.

PubMed

Paling, F P; Andrews, L M; Valk, G D; Blom, H J

2012-11-01

Ibogaine is a naturally occurring psychoactive alkaloid extracted from the roots of the Tabernanthe iboga plant, which in alternative medicine is used to treat drug dependency. However, this upcoming, online advocated therapy can be dangerous due to its potentially lethal adverse effects. We present three cases in which toxic side effects were noted. We used the Naranjo scale to estimate the probability of a causal relationship between these effects and ibogaine. Findings in these three cases are suggestive of a causal relationship between the use of ibogaine and serious respiratory and cardiac problems (including lengthening of the QT interval). In our opinion it is of great importance that clinicians are aware of these potentially serious side effects and realise that widespread online marketing practices will give many more people access to ibogaine.

Active learning for semi-supervised clustering based on locally linear propagation reconstruction.

PubMed

Chang, Chin-Chun; Lin, Po-Yi

2015-03-01

The success of semi-supervised clustering relies on the effectiveness of side information. To get effective side information, a new active learner learning pairwise constraints known as must-link and cannot-link constraints is proposed in this paper. Three novel techniques are developed for learning effective pairwise constraints. The first technique is used to identify samples less important to cluster structures. This technique makes use of a kernel version of locally linear embedding for manifold learning. Samples neither important to locally linear propagation reconstructions of other samples nor on flat patches in the learned manifold are regarded as unimportant samples. The second is a novel criterion for query selection. This criterion considers not only the importance of a sample to expanding the space coverage of the learned samples but also the expected number of queries needed to learn the sample. To facilitate semi-supervised clustering, the third technique yields inferred must-links for passing information about flat patches in the learned manifold to semi-supervised clustering algorithms. Experimental results have shown that the learned pairwise constraints can capture the underlying cluster structures and proven the feasibility of the proposed approach. Copyright © 2014 Elsevier Ltd. All rights reserved.

Radiation effect of neutrons produced by D-D side reactions on a D-3He fusion reactor

NASA Astrophysics Data System (ADS)

Bahmani, J.

2017-04-01

One of the most important characteristics in D-3He fusion reactors is neutron production via D-D side reactions. The neutrons can activate structural material, degrading them and ultimately converting them into high-level radioactive waste, while it is really costly and difficult to remove them. The neutrons from a fusion reactor could also be used to make weapons-grade nuclear material, rendering such types of fusion reactors a serious proliferation hazard. A related problem is the presence of radioactive elements such as tritium in D-3He plasma, either as fuel for or as products of the nuclear reactions; substantial quantities of radioactive elements would not only pose a general health risk, but tritium in particular would also be another proliferation hazard. The problems of neutron radiation and radioactive element production are especially interconnected because both would result from the D-D side reaction. Therefore, the presentation approach for reducing neutrons via D-D nuclear side reactions in a D-3He fusion reactor is very important. For doing this research, energy losses and neutron power fraction in D-3He fusion reactors are investigated. Calculations show neutrons produced by the D-D nuclear side reaction could be reduced by changing to a more 3He-rich fuel mixture, but then the bremsstrahlung power loss fraction would increase in the D-3He fusion reactor.

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 ...

Neglected environmental health impacts of China's supply-side structural reform.

PubMed

Zhang, Wei; Zhang, Lei; Li, Ying; Tian, Yuling; Li, Xiaoran; Zhang, Xue; Mol, Arthur P J; Sonnenfeld, David A; Liu, Jianguo; Ping, Zeyu; Chen, Long

2018-06-01

"Supply-side structural reform" (SSSR) has been the most important ongoing economic reform in China since 2015, but its important environmental health effects have not been properly assessed. The present study addresses that gap by focusing on reduction of overcapacity in the coal, steel, and iron sectors, combined with reduction of emissions of sulfur dioxide (SO 2 ), nitrogen oxide (NO x ), and fine particulate matter (PM 2.5 ), and projecting resultant effects on air quality and public health across cities and regions in China. Modeling results indicate that effects on air quality and public health are visible and distributed unevenly across the country. This assessment provides quantitative evidence supporting projections of the transregional distribution of such effects. Such uneven transregional distribution complicates management of air quality and health risks in China. The results challenge approaches that rely solely on cities to improve air quality. The article concludes with suggestions on how to integrate SSSR measures with cities' air quality improvement attainment planning and management performance evaluation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Beliefs regarding medication and side effects influence treatment adherence in adolescents with attention deficit hyperactivity disorder.

PubMed

Emilsson, Maria; Gustafsson, Per A; Öhnström, Gisela; Marteinsdottir, Ina

2017-05-01

Adherence to attention deficit hyperactivity disorder (ADHD) treatment is important because, when untreated, it may have serious consequences with lifelong effects. In the case of adolescents on long-term medicine prescription, more knowledge is needed regarding adherence and factors influencing adherence, which was the purpose of this study. Adolescents (n = 101) on ADHD medication ≥6 months were administrated questionnaires at a monitoring appointment: Medication Adherence Report Scale (MARS), beliefs about medicines (BMQ) and the Brief Illness Perception Questionnaire (B-IPQ). Adherence was high, the mean value was 88% of the maximum MARS score, and correlated positively with the "BMQ-necessity-concerns differential" but negatively with "BMQ-concerns" and "BMQ-side effects". Adolescents with more belief in the necessity of the medication, less concerns and less experience of side effects tended to be more adherent to medication prescription ("intentional non-adherence"), while "unintentional non-adherence" (forgetfulness) was associated with how much they perceived that their ADHD affected their lives. In a multiple regression model, the variance of MARS total (R 2  = 0.21) and "intentional non-adherence" (R 2  = 0.24) was explained by the "BMQ-necessity-concern differential" and "BMQ-experienced side effects". The variance of "unintentional non-adherence" (R 2  = 0.12) was explained by the "BMQ-necessity-concern differential" and "B-IPQ-consequences of ADHD". In conclusion, adolescents on long-term medication reported good adherence, mainly influenced by more beliefs in the necessity versus concerns of the medications, less experienced side effects and more perceived consequences of ADHD. BMQ could be useful to identify risks of low adherence, which should be counteracted by partially gender-specific interventions.

Side effects associated with anti-HIV drugs.

PubMed

Highleyman, L

1998-04-01

Many side effects are associated with the use of anti-HIV drugs, impacting the development of drug resistance and the quality of life for HIV-patients. Concern about side effects is a primary factor in deterring people from beginning HIV therapy. Frequency and severity of side effects vary greatly, but they are frequently more common and severe in people who are taking a new drug or who have advanced HIV disease. Information on side effects comes largely from clinical trials; however, many side effects are not discovered until the drug has been approved and used by larger numbers of people. Side effects vary from serious toxicities that require stopping treatment to uncomfortable or annoying side effects that interfere with daily life. A table categorizes the four major side effects (nausea, fever, skin rash, and fatigue) and divides them into grades that describe their intensity. A chart lists the side effects associated with specific anti-HIV drugs. Suggestions for managing side effects are included.

Artificial reef effect in relation to offshore renewable energy conversion: state of the art.

PubMed

Langhamer, Olivia

2012-01-01

The rapid worldwide growth of offshore renewable energy production will provide marine organisms with new hard substrate for colonization, thus acting as artificial reefs. The artificial reef effect is important when constructing, for example, scour protections since it can generate an enhanced habitat. Specifically, artificial structures can create increased heterogeneity in the area important for species diversity and density. Offshore energy installations also have the positive side effect as they are a sanctuary area for trawled organisms. Higher survival of fish and bigger fish is an expected outcome that can contribute to a spillover to outer areas. One negative side effect is that invasive species can find new habitats in artificial reefs and thus influence the native habitats and their associated environment negatively. Different scour protections in offshore wind farms can create new habitats compensating for habitat loss by offshore energy installations. These created habitats differ from the lost habitat in species composition substantially. A positive reef effect is dependent on the nature and the location of the reef and the characteristics of the native populations. An increase in surface area of scour protections by using specially designed material can also support the reef effect and its productivity.

Artificial Reef Effect in relation to Offshore Renewable Energy Conversion: State of the Art

PubMed Central

2012-01-01

The rapid worldwide growth of offshore renewable energy production will provide marine organisms with new hard substrate for colonization, thus acting as artificial reefs. The artificial reef effect is important when constructing, for example, scour protections since it can generate an enhanced habitat. Specifically, artificial structures can create increased heterogeneity in the area important for species diversity and density. Offshore energy installations also have the positive side effect as they are a sanctuary area for trawled organisms. Higher survival of fish and bigger fish is an expected outcome that can contribute to a spillover to outer areas. One negative side effect is that invasive species can find new habitats in artificial reefs and thus influence the native habitats and their associated environment negatively. Different scour protections in offshore wind farms can create new habitats compensating for habitat loss by offshore energy installations. These created habitats differ from the lost habitat in species composition substantially. A positive reef effect is dependent on the nature and the location of the reef and the characteristics of the native populations. An increase in surface area of scour protections by using specially designed material can also support the reef effect and its productivity. PMID:23326215

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

Treatment of gastro-esophageal reflux disease: the new kids to block.

PubMed

Blondeau, K

2010-08-01

Refractory gastro-esophageal reflux disease (GERD), defined as persistent symptoms despite proton pump inhibitor (PPI) therapy, is an increasingly prevalent condition and is becoming a major challenge for the clinician. Since non-acidic reflux may be associated with symptoms persisting during PPI treatment, the lower esophageal sphincter (LES), the most important barrier protecting against reflux, has become an important target for the treatment of (refractory) GERD. Preclinical research has identified several receptors that are involved in the control of transient lower esophageal sphincter relaxations (TLESRs), the predominant mechanism of both acid and non-acidic reflux events, and several drugs have now been tested in humans. The GABA(B) agonist baclofen has demonstrated to effectively reduce the rate of TLESRs and the amount of reflux in both GERD patients and healthy volunteers. Nevertheless, the occurrence of central side effects limits its clinical use for the treatment of GERD. Several analogues are being developed to overcome this limitation and have shown promising results. Additionally, metabotropic glutamate receptor 5 (mGluR5) receptor antagonists have shown to reduce both acid and non-acidic reflux in GERD patients and several molecules are currently being evaluated. Although CB(1) antagonists have been shown to reduce TLESRs, they are also associated with central side effects, limiting their clinical applicability. Despite the identification of several potentially interesting drugs, the main challenge for the future remains the reduction of central side effects. Moreover, future studies will need to demonstrate the efficacy of these treatments in patients with refractory GERD.

Investigation of the novel attributes in double recessed gate SiC MESFETs at drain side

NASA Astrophysics Data System (ADS)

Orouji, Ali A.; Razavi, S. M.; Ebrahim Hosseini, Seyed; Amini Moghadam, Hamid

2011-11-01

In this paper, the potential impact of drain side-double recessed gate (DS-DRG) on silicon carbide (SiC)-based metal semiconductor field effect transistors (MESFETs) is studied. We investigate the device performance focusing on breakdown voltage, threshold voltage, drain current and dc output conductance with two-dimensional and two-carrier device simulation. Our simulation results demonstrate that the channel thickness under the gate in the drain side is an important factor in the breakdown voltage. Also, the positive shift in the threshold voltage for the DS-DRG structure is larger in comparison with that for the source side-double recessed gate (SS-DRG) SiC MESFET. The saturated drain current for the DS-DRG structure is larger compared to that for the SS-DRG structure. The maximum dc output conductance in the DS-DRG structure is smaller than that in the SS-DRG structure.

Shock wave boundary layer interaction on suction side of compressor profile in single passage test section

NASA Astrophysics Data System (ADS)

Flaszynski, Pawel; Doerffer, Piotr; Szwaba, Ryszard; Kaczynski, Piotr; Piotrowicz, Michal

2015-11-01

The shock wave boundary layer interaction on the suction side of transonic compressor blade is one of the main objectives of TFAST project (Transition Location Effect on Shock Wave Boundary Layer Interaction). In order to investigate the flow structure on the suction side of a profile, a design of a generic test section in linear transonic wind tunnel was proposed. The experimental and numerical results for the flow structure investigations are shown for the flow conditions as the existing ones on the suction side of the compressor profile. Near the sidewalls the suction slots are applied for the corner flow structure control. It allows to control the Axial Velocity Density Ratio (AVDR), important parameter for compressor cascade investigations. Numerical results for Explicit Algebraic Reynolds Stress Model with transition modeling are compared with oil flow visualization, schlieren and Pressure Sensitive Paint. Boundary layer transition location is detected by Temperature Sensitive Paint.

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.

Issues in hypertension: drug tolerability and special populations.

PubMed

Gavras, H P

2001-07-01

Improvements in the death rate from coronary heart disease and in the control of hypertension have leveled off in recent years, reversing a trend toward steady improvement that began in 1972. Of the roughly 20% of Americans who suffer from hypertension, only 29% achieve adequate control (<140/90 mm Hg) with treatment and nearly half receive no treatment at all. Poor adherence to therapy doubtless plays a key role in this failure. As a major cause of poor adherence, tolerability becomes an extremely important element in any discussion of effective antihypertensive treatment. Despite their efficacy in treating hypertension, diuretics, beta-blockers, and calcium channel blockers have all been associated with numerous side effects, including increased serum lipid levels, insulin resistance, and edema. With the introduction of the angiotensin converting enzyme (ACE) inhibitors, patients were able to achieve blood pressure goals with fewer side effects. These agents, however, cause an irritating cough in up to 19% of patients. A newer class of drugs, the angiotensin receptor blockers (ARB), have similar effects to the ACE inhibitors, but their highly selective nature produces even fewer side effects. Eprosartan is a structurally unique ARB. Like the other ARB, this promising new agent has a side effect profile similar to placebo, and its response rate rivals or exceeds that of enalapril. Although it remains to be seen whether the ARB can significantly reduce morbidity and mortality from cardiovascular disease, preliminary data from the Evaluation of Losartan in the Elderly (ELITE) trial appear to be promising.

Demand-side financing measures to increase maternal health service utilisation and improve health outcomes: a systematic review of evidence from low- and middle-income countries.

PubMed

Murray, Susan F; Hunter, Benjamin M; Bisht, Ramila; Ensor, Tim; Bick, Debra

2012-01-01

In many countries financing for health services has traditionally been disbursed directly from governmental and non-governmental funding agencies to providers of services: the 'supply-side' of healthcare markets. Demand-side financing offers a supplementary model in which some funds are instead channelled through, or to, prospective users. In this review we considered evidence on five forms of demand-side financing that have been used to promote maternal health in developing countries: OBJECTIVES: The overall review objective was to assess the effects of demand-side financing interventions on maternal health service utilisation and on maternal health outcomes in low- and middle-income countries. Broader effects on perinatal and infant health, the situation of underprivileged women and the health care system were also assessed. This review considered poor, rural or socially excluded women of all ages who were either pregnant or within 42 days of the conclusion of pregnancy, the limit for postnatal care as defined by the World Health Organization. The review also considered the providers of services.The intervention of interest was any programme that incorporated demand-side financing as a mechanism to increase the consumption of goods and services that could impact on maternal health outcomes. This included the direct consumption of maternal health care goods and services as well as related 'merit goods' such as improved nutrition. We included systems in which potential users of maternal health services are financially empowered to make restricted decisions on buying maternal health-related goods or services - sometimes known as consumer-led demand-side financing. We also included programmes that provided unconditional cash benefits to pregnant women (for example in the form of maternity allowances), or to families with children under five years of age where there was evidence concerning maternal health outcomes.We aimed to include quantitative studies (experimental, observational and descriptive), qualitative studies (including designs based on phenomenology, grounded theory, ethnography, action research and feminist research), and economic studies (cost-effectiveness, cost-utility and costs studies). The Joanna Briggs Institute methodology for mixed-method systematic reviews was adopted. A three-step systematic search strategy was used to: 1) identify key terms, 2) search bibliographic databases and 3) retrieve additional publications from reference lists and sources of grey literature. Data were extracted from papers included in the review using the standardised data extraction tools for quantitative, qualitative and economic data from the Joanna Briggs Institute System for the Unified Management, Assessment and Review of Information. The quantitative and economic findings are presented in narrative form. Qualitative research findings were pooled using the Joanna Briggs Institute Qualitative Assessment and Review Instrument. This involved the aggregation or synthesis of findings to generate a set of statements that represent that aggregation, through assembling the findings (Level 1 findings), and categorising these findings on the basis of similarity in meaning (Level 2 findings). These categories were then subjected to a meta-synthesis in order to produce a single comprehensive set of synthesised findings (Level 3 findings) that can be used as a basis for evidence-based practice or policy. Seventy-two studies were included in the review. Drawing on work from several continents, many of the included studies were reports and evaluations for relevant government or funding agencies and represented important lesson-learning about implementation issues. However, fewer than half were published in peer reviewed journals and few were of high research quality.For three modes of demand-side financing (conditional cash transfers, payments to offset costs of access to maternal healthcare, and vouchers for maternity services) we found evidence relevant to review questions on the utilisation of maternal health services, barriers to the provision of demand-side financing and supply-side preconditions to implementing demand-side financing schemes. There was insufficient evidence to provide comprehensive answers for review questions on the effect of demand-side financing interventions on maternal, perinatal and infant health outcomes and on the social and financial situation of underprivileged women. There was also insufficient evidence on the cost-effectiveness of demand-side financing interventions and preconditions for sustainability and scale-up of demand-side financing schemes.Salient recommendations for policymakers regarding demand-side financing for maternal health derived from the current evidence are:There is a pressing need for large, robust studies on the short- and longer-term impact of demand-side financing on maternal and infant mortality and morbidity, which should also reflect 'good practice' indicators such as the uptake and duration of exclusive breastfeeding and compliance with infant immunisation programmes. It is also important that the impact on outcomes of subsequent pregnancies is evaluated. Moderate and large-sized demand-side financing programmes that have recently or will soon be scaled up, such as those in Kenya, Uganda and Bangladesh, represent the most obvious sites for such evaluations, and lessons may be learnt from Mexico's PROGRESA/ Oportunidades about how to establish a well-embedded monitoring and rigorous evaluation structure.Other important areas that require further study include.

Effect of charged amino acid side chain length on lateral cross-strand interactions between carboxylate- and guanidinium-containing residues in a β-hairpin.

PubMed

Kuo, Hsiou-Ting; Liu, Shing-Lung; Chiu, Wen-Chieh; Fang, Chun-Jen; Chang, Hsien-Chen; Wang, Wei-Ren; Yang, Po-An; Li, Jhe-Hao; Huang, Shing-Jong; Huang, Shou-Ling; Cheng, Richard P

2015-05-01

β-Sheet is one of the major protein secondary structures. Oppositely charged residues are frequently observed across neighboring strands in antiparallel sheets, suggesting the importance of cross-strand ion pairing interactions. The charged amino acids Asp, Glu, Arg, and Lys have different numbers of hydrophobic methylenes linking the charged functionality to the backbone. To investigate the effect of side chain length of guanidinium- and carboxylate-containing residues on lateral cross-strand ion pairing interactions at non-hydrogen-bonded positions, β-hairpin peptides containing Zbb-Agx (Zbb = Asp, Glu, Aad in increasing length; Agx = Agh, Arg, Agb, Agp in decreasing length) sequence patterns were studied by NMR methods. The fraction folded population and folding energy were derived from the chemical shift deviation data. Peptides with high fraction folded populations involved charged residue side chain lengths that supported high strand propensity. Double mutant cycle analysis was used to determine the interaction energy for the potential lateral ion pairs. Minimal interaction was observed between residues with short side chains, most likely due to the diffused positive charge on the guanidinium group, which weakened cross-strand electrostatic interactions with the carboxylate side chain. Only the Aad-Arg/Agh interactions with long side chains clearly exhibited stabilizing energetics, possibly relying on hydrophobics. A survey of a non-redundant protein structure database revealed that the statistical sheet pair propensity followed the trend Asp-Arg < Glu-Arg, implying the need for matching long side chains. This suggested the need for long side chains on both guanidinium-bearing and carboxylate-bearing residues to stabilize the β-hairpin motif.

Shields for protecting cables from the effects of electromagnetic noise and interference

NASA Astrophysics Data System (ADS)

Hoeft, L. O.; Hofstra, J. S.; Karaskiewicz, R. J.; Torres, B. W.

1988-12-01

The intrinsic electromagnetic property of a cable or connector shield is its surface transfer impedance. This is the ratio of the longitudinal open circuit voltage measured on one side of the shield (normally the inside) to the axial current on the other side (normally the outside). In cases where a high electric field is present at the surface of the shield, the transfer admittance or charge transfer elastance is also important. Measurements of typical cables, connectors, backshells and cable terminations are presented and explained in terms of simple models.

Age-related changes in the antidepressant-like effect of desipramine and fluoxetine in the rat forced-swim test.

PubMed

Olivares-Nazario, Maribel; Fernández-Guasti, Alonso; Martínez-Mota, Lucía

2016-02-01

Some reports suggest that older patients are less responsive to antidepressants than young adults, but this idea has not been fully supported. Here, we investigated the role of aging in the behavioral effects of the antidepressants, desipramine (DMI) (5, 10, and 20 mg/kg) and fluoxetine (FLX) (5, 10, and 20 mg/kg) in young adults (3-5 months), middle-aged (MA, 12-15 months), and senescent (SE, 23-25 months) male rats in the forced-swim test. In addition, locomotor activity and motor coordination were assessed as side-effects. DMI and fluoxetine produced an antidepressant-like effect in YA and MA animals, although in the latter group, a shift to the right in the dose-response curve was found for DMI. Importantly, neither drug was effective in SE animals. Motor side-effects were produced mainly by DMI in MA and SE rats. Therefore, a decrease in the antidepressant-like effect is associated strongly with senescence as well as an increased vulnerability to motor side-effects, particularly of tricyclics. This study is significant because SE animals are scarcely studied in pharmacological screening tests, and our findings might be useful for improving antidepressant treatments for the increasing aged population.

Antiepileptic drug therapy: clinical laboratory significance.

PubMed

Naradzay, J F; Olshaker, J S

1996-01-01

When evaluating a patient who is taking an antiepileptic medication, it is important for the emergency physician to correlate the clinical presentation with the antiepileptic drug level. Therapeutic ranges have been suggested for most antiepileptic medications, but these must be interpreted in light of clinical efficacy and patient tolerance. When considering the efficacy of anti-epileptic medications, it is necessary to consider the patient's unique metabolism, side-effect tolerance, and overall response to therapy. Suggested therapeutic ranges should be the first reference for the emergency physician. The purpose of this report is to discuss the laboratory values of commonly prescribed antiepileptic medications. Therapeutic ranges, side-effects, and common medication interactions are discussed concerning phenytoin, phenobarbital, carbamezapine, and valproic acid.

Landscape assessment of side channel plugs and associated cumulative side channel attrition across a large river floodplain.

PubMed

Reinhold, Ann Marie; Poole, Geoffrey C; Bramblett, Robert G; Zale, Alexander V; Roberts, David W

2018-04-24

Determining the influences of anthropogenic perturbations on side channel dynamics in large rivers is important from both assessment and monitoring perspectives because side channels provide critical habitat to numerous aquatic species. Side channel extents are decreasing in large rivers worldwide. Although riprap and other linear structures have been shown to reduce side channel extents in large rivers, we hypothesized that small "anthropogenic plugs" (flow obstructions such as dikes or berms) across side channels modify whole-river geomorphology via accelerating side channel senescence. To test this hypothesis, we conducted a geospatial assessment, comparing digitized side channel areas from aerial photographs taken during the 1950s and 2001 along 512 km of the Yellowstone River floodplain. We identified longitudinal patterns of side channel recruitment (created/enlarged side channels) and side channel attrition (destroyed/senesced side channels) across n = 17 river sections within which channels were actively migrating. We related areal measures of recruitment and attrition to the density of anthropogenic side channel plugs across river sections. Consistent with our hypothesis, a positive spatial relationship existed between the density of anthropogenic plugs and side channel attrition, but no relationship existed between plug density and side channel recruitment. Our work highlights important linkages among side channel plugs and the persistence and restoration of side channels across floodplain landscapes. Specifically, management of small plugs represents a low-cost, high-benefit restoration opportunity to facilitate scouring flows in side channels to enable the persistence of these habitats over time.

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.

Nurses’ knowledge of blood transfusion in medical training centers of Shahrekord University of Medical Science in 2004

PubMed Central

Aslani, Yosef; Etemadyfar, Shahram; Noryan, Kobra

2010-01-01

BACKGROUND: Using blood and blood components is a common therapeutic procedure in hospitals. Nurses have an important role in a safe blood transfusion. Therefore, it is crucial for nurses to have sufficient knowledge of situations, amount and methods of using blood components, possible side effects and necessary cares. This study investigated nurses’ knowledge of blood transfusion. METHODS: This was a cross-sectional descriptive study on 117 nurses in medical training hospitals of Shahrekord University of Medical Sciences in 2004, aiming to evaluate their knowledge of blood transfusion. Data were collected using a questionnaire including 4 sections and 29 questions. Sections included demographic data, nurses’ knowledge of blood components, nurses’ knowledge of blood components infusion techniques, and nurses’ knowledge of indication and side effects of blood components infusion. Knowledge scores were first coded and then categorized in three levels of good, average, and poor. Data were analyzed using SPSS software. RESULTS: The nurses’ knowledge of blood and blood component, techniques of blood components infusion, and its indication and side effects was average (66.7%, 65.8% and 59%, respectively). CONCLUSIONS: The findings showed that the nurses’ knowledge of blood and blood component was average and insufficient. Therefore, it is recommended to activate the blood transfusion committees in hospitals to increase the quality of this common procedure and prevent side effects by in-service trainings of nurses. PMID:21589778

Effect of side-chain structure of rigid polyimide dispersant on mechanical properties of single-walled carbon nanotube/cyanate ester composite.

PubMed

Yuan, Wei; Li, Weifeng; Mu, Yuguang; Chan-Park, Mary B

2011-05-01

Three kinds of polymer, polyimide without side-chain (PI), polyimide-graft-glyceryl 4-nonylphenyl ether (PI-GNE), and polyimide-graft-bisphenol A diglyceryl acrylate (PI-BDA), have been synthesized and used to disperse single-walled carbon nanotubes (SWNTs) and to improve the interfacial bonding between SWNTs and cyanate ester (CE) matrix. Visual observation, UV-vis-near-IR (UV-vis-NIR) spectra, and atomic force microscopy (AFM) images show that both PI-GNE and PI-BDA are highly effective at dispersing and debundling SWNTs in DMF, whereas PI is less effective. Interaction between SWNTs and PI, PI-GNE or PI-BDA was confirmed by computer simulation and Raman spectra. A series of CE-based composite films reinforced with different loadings of SWNTs, SWNTs/PI, SWNTs/PI-GNE and SWNTs/PI-BDA were prepared by solution casting. It was found that, because of the unique side-chain structure of PI-BDA, SWNTs/PI-BDA disperse better in CE matrix than do SWNTs/PI-GNE, SWNTs/PI, and SWNTs. As a result, SWNTs/PI-BDA/CE composites have the greatest improvement in mechanical properties of the materials tested. These results imply that the choice of side-chain on a dispersant is very important to the dispersion of SWNTs in matrix and the filler/matrix interfacial adhesion, which are two key requirements for achieving effective reinforcement.

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.

Hippocampal histone acetylation regulates object recognition and the estradiol-induced enhancement of object recognition

PubMed Central

Zhao, Zaorui; Fan, Lu; Fortress, Ashley M.; Boulware, Marissa I.; Frick, Karyn M.

2012-01-01

Histone acetylation has recently been implicated in learning and memory processes, yet necessity of histone acetylation for such processes has not been demonstrated using pharmacological inhibitors of histone acetyltransferases (HATs). As such, the present study tested whether garcinol, a potent HAT inhibitor in vitro, could impair hippocampal memory consolidation and block the memory-enhancing effects of the modulatory hormone 17β-estradiol (E2). We first showed that bilateral infusion of garcinol (0.1, 1, or 10 μg/side) into the dorsal hippocampus (DH) immediately after training impaired object recognition memory consolidation in ovariectomized female mice. A behaviorally effective dose of garcinol (10 μg/side) also significantly decreased DH HAT activity. We next examined whether DH infusion of a behaviorally subeffective dose of garcinol (1 ng/side) could block the effects of DH E2 infusion on object recognition and epigenetic processes. Immediately after training, ovariectomized female mice received bilateral DH infusions of vehicle, E2 (5 μg/side), garcinol (1 ng/side), or E2 plus garcinol. Forty-eight hours later, garcinol blocked the memory-enhancing effects of E2. Garcinol also reversed the E2-induced increase in DH histone H3 acetylation, HAT activity, and levels of the de novo methyltransferase DNMT3B, as well as the E2-induced decrease in levels of the memory repressor protein histone deacetylase 2 (HDAC2). Collectively, these findings suggest that histone acetylation is critical for object recognition memory consolidation and the beneficial effects of E2 on object recognition. Importantly, this work demonstrates that the role of histone acetylation in memory processes can be studied using a HAT inhibitor. PMID:22396409

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

Childhood Vaccine Acceptance and Refusal among Warao Amerindian Caregivers in Venezuela; A Qualitative Approach.

PubMed

Burghouts, Jochem; Del Nogal, Berenice; Uriepero, Angimar; Hermans, Peter W M; de Waard, Jacobus H; Verhagen, Lilly M

2017-01-01

Acceptance of childhood vaccination varies between societies, affecting worldwide vaccination coverage. Low coverage rates are common in indigenous populations where parents often choose not to vaccinate their children. We aimed to gain insight into reasons for vaccine acceptance or rejection among Warao Amerindians in Venezuela. Based on records of vaccine acceptance or refusal, in-depth interviews with 20 vaccine-accepting and 11 vaccine-declining caregivers were performed. Parents' attitudes were explored using a qualitative approach. Although Warao caregivers were generally in favor of vaccination, fear of side effects and the idea that young and sick children are too vulnerable to be vaccinated negatively affected vaccine acceptance. The importance assigned to side effects was related to the perception that these resembled symptoms/diseases of another origin and could thus harm the child. Religious beliefs or traditional healers did not influence the decision-making process. Parental vaccine acceptance requires educational programs on the preventive nature of vaccines in relation to local beliefs about health and disease. Attention needs to be directed at population-specific concerns, including explanation on the nature of and therapeutic options for side effects.

Increasing AR by HIF-2α inhibitor (PT-2385) overcomes the side-effects of sorafenib by suppressing hepatocellular carcinoma invasion via alteration of pSTAT3, pAKT and pERK signals

PubMed Central

Xu, Junjie; Zheng, Longbo; Chen, Jiang; Sun, Yin; Lin, Hui; Jin, Ren-an; Tang, Minyue; Liang, Xiao; Cai, Xiujun

2017-01-01

Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR. Importantly, In vitro and In vivo studies suggested a specific and potent HIF-2α inhibitor, PT-2385, could significantly enhance sorafenib efficacy by suppressing HIF-2α, increasing AR and suppressing downstream pSTAT3/pAKT/pERK pathways. Clinical samples further confirmed the role of HIF-2α and AR. It is promising that PT-2385 could alleviate the undesirable side-effects of sorafenib treatment by sorafenib-PT-2385 combination therapy, which may shed light for late-stage HCC patients. PMID:29022906

Increasing AR by HIF-2α inhibitor (PT-2385) overcomes the side-effects of sorafenib by suppressing hepatocellular carcinoma invasion via alteration of pSTAT3, pAKT and pERK signals.

PubMed

Xu, Junjie; Zheng, Longbo; Chen, Jiang; Sun, Yin; Lin, Hui; Jin, Ren-An; Tang, Minyue; Liang, Xiao; Cai, Xiujun

2017-10-12

Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR. Importantly, In vitro and In vivo studies suggested a specific and potent HIF-2α inhibitor, PT-2385, could significantly enhance sorafenib efficacy by suppressing HIF-2α, increasing AR and suppressing downstream pSTAT3/pAKT/pERK pathways. Clinical samples further confirmed the role of HIF-2α and AR. It is promising that PT-2385 could alleviate the undesirable side-effects of sorafenib treatment by sorafenib-PT-2385 combination therapy, which may shed light for late-stage HCC patients.

Distribution and feeding ecology of dolphins along the Mid-Atlantic Ridge between Iceland and the Azores

NASA Astrophysics Data System (ADS)

Doksæter, L.; Olsen, E.; Nøttestad, L.; Fernö, A.

2008-01-01

During Leg 1 of the MAR-ECO expedition on the R.V. G.O. Sars in June 2004 four main species of dolphins were observed along the Mid-Atlantic Ridge from Iceland to the Azores: pilot whale ( Globicephala melas) ( n=326), short-beaked common dolphin ( Delphinus delphis) ( n=273), white-sided dolphin ( Lagenorhynchus acutus) ( n=103), and striped dolphin ( Stenella coeruleoalba) ( n=86). Pilot whales and white-sided dolphins were found in cold (5-16 °C) and less-saline (34.6-35.8‰) water masses in the northern part of the study area, whereas common and striped dolphins inhabited warmer (12-22 °C) and more-saline (34.8-36.7‰) waters in the south. Dolphins tended to aggregate in areas of steep slopes, but actual bottom depth appeared to be less important. Based on spatial correlations between dolphin occurrence and candidate prey organisms recorded acoustically and by midwater trawling, mesopelagic fishes and squids were assumed to be important prey items, with Benthosema glaciale probably being the most important prey for pilot whales and white-sided dolphins, while Lampanyctus macdonaldi, Stomias boa ferox and Chauliodus sloani were probably of particular importance for common dolphins. Cephalopods, especially Gonatus sp. and Teuthowenia megalops were the most likely prey species of pilot whales and striped dolphins, respectively. The difference in physical habitat north and south of the Sub-polar Frontal Zone seemed to have important effects on prey distribution, in turn influencing dolphin distribution.

Daily baseline skin care in the prevention, treatment, and supportive care of skin toxicity in oncology patients: recommendations from a multinational expert panel

PubMed Central

Bensadoun, René-Jean; Humbert, Phillipe; Krutman, Jean; Luger, Thomas; Triller, Raoul; Rougier, André; Seite, Sophie; Dreno, Brigitte

2013-01-01

Skin reactions due to radiotherapy and chemotherapy are a significant problem for an important number of cancer patients. While effective for treating cancer, they disturb cutaneous barrier function, causing a reaction soon after initiation of treatment that impacts patient quality of life. Managing these symptoms with cosmetics and nonpharmaceutical skin care products for camouflage or personal hygiene may be important for increasing patient self-esteem. However, inappropriate product choice or use could worsen side effects. Although recommendations exist for the pharmaceutical treatment of skin reactions, there are no recommendations for the choice or use of dermatologic skin care products for oncology patients. The present guidelines were developed by a board of European experts in dermatology and oncology to provide cancer care professionals with guidance for the appropriate use of non-pharmaceutical, dermocosmetic skin care management of cutaneous toxicities associated with radiotherapy and systemic chemotherapy, including epidermal growth factor inhibitors and monoclonal antibodies. The experts hope that these recommendations will improve the management of cutaneous side effects and hence quality of life for oncology patients. PMID:24353440

Landscape assessment of side channel plugs and associated cumulative side channel attrition across a large river floodplain

USGS Publications Warehouse

Reinhold, Ann Marie; Poole, Geoffrey C.; Bramblett, Robert G.; Zale, Alexander V.; Roberts, David W.

2018-01-01

Determining the influences of anthropogenic perturbations on side channel dynamics in large rivers is important from both assessment and monitoring perspectives because side channels provide critical habitat to numerous aquatic species. Side channel extents are decreasing in large rivers worldwide. Although riprap and other linear structures have been shown to reduce side channel extents in large rivers, we hypothesized that small “anthropogenic plugs” (flow obstructions such as dikes or berms) across side channels modify whole-river geomorphology via accelerating side channel senescence. To test this hypothesis, we conducted a geospatial assessment, comparing digitized side channel areas from aerial photographs taken during the 1950s and 2001 along 512 km of the Yellowstone River floodplain. We identified longitudinal patterns of side channel recruitment (created/enlarged side channels) and side channel attrition (destroyed/senesced side channels) across n = 17 river sections within which channels were actively migrating. We related areal measures of recruitment and attrition to the density of anthropogenic side channel plugs across river sections. Consistent with our hypothesis, a positive spatial relationship existed between the density of anthropogenic plugs and side channel attrition, but no relationship existed between plug density and side channel recruitment. Our work highlights important linkages among side channel plugs and the persistence and restoration of side channels across floodplain landscapes. Specifically, management of small plugs represents a low-cost, high-benefit restoration opportunity to facilitate scouring flows in side channels to enable the persistence of these habitats over time.

Pupillary correlates of covert shifts of attention during working memory maintenance.

PubMed

Unsworth, Nash; Robison, Matthew K

2017-04-01

The pupillary light reflex (PLR) was used to track covert shifts of attention to items maintained in visual working memory (VWM). In three experiments, participants performed a change detection task in which rectangles appeared on either side of fixation and at test participants indicated if the cued rectangle changed its orientation. Prior to presentation or during the delay, participants were cued to the light or dark side of the screen. When cued to the light side, the pupil constricted, and when cued to the dark side, the pupil dilated, suggesting that the PLR tracked covert shifts of attention. Similar covert shifts of attention were seen when the target stimuli remained onscreen and during a blank delay period, suggesting similar effects for attention to perceptual stimuli and attention to stimuli maintained in VWM. Furthermore, similar effects were demonstrated when participants were pre-cued or retro-cued to the prioritized location, suggesting that shifts of covert attention can occur both before and after target presentation. These results are consistent with prior research, suggesting an important role of covert shifts of attention during VWM maintenance and that the PLR can be used to track these covert shifts of attention.

Research on electricity market operation mechanism and its benefit of demand side participation

NASA Astrophysics Data System (ADS)

Han, Shuai; Yan, Xu; Qin, Li-juan; Lin, Xi-qiao; Zeng, Bo

2017-08-01

Demand response plays an important role in maintaining the economic stability of the system, and has the characteristics of high efficiency, low cost, fast response, good environmental benefits and so on. Demand side resource is an important part of electricity market. The research of demand side resources in our country is still in the initial stage, but the opening of the electricity sales side provides a broad prospect for the development of electricity market. This paper summarizes the main types of demand side resources in our country, analyzes the economic principle of demand response from the micro perspective, puts forward some suggestions on the operation mechanism of China’s demand side resources participating in the electricity market under the condition of electricity sales side opening, analyzes the current situation of pricing in the electricity wholesale market and sets up the pricing strategy of the centralized wholesale market with the demand side power supply participating in quotation, which makes the social and economic benefits reach the maximum.

Free Energy Perturbation Calculations of the Thermodynamics of Protein Side-Chain Mutations.

PubMed

Steinbrecher, Thomas; Abel, Robert; Clark, Anthony; Friesner, Richard

2017-04-07

Protein side-chain mutation is fundamental both to natural evolutionary processes and to the engineering of protein therapeutics, which constitute an increasing fraction of important medications. Molecular simulation enables the prediction of the effects of mutation on properties such as binding affinity, secondary and tertiary structure, conformational dynamics, and thermal stability. A number of widely differing approaches have been applied to these predictions, including sequence-based algorithms, knowledge-based potential functions, and all-atom molecular mechanics calculations. Free energy perturbation theory, employing all-atom and explicit-solvent molecular dynamics simulations, is a rigorous physics-based approach for calculating thermodynamic effects of, for example, protein side-chain mutations. Over the past several years, we have initiated an investigation of the ability of our most recent free energy perturbation methodology to model the thermodynamics of protein mutation for two specific problems: protein-protein binding affinities and protein thermal stability. We highlight recent advances in the field and outline current and future challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

Promoting innovation in small markets: Evidence from the market for rare and intractable diseases.

PubMed

Iizuka, Toshiaki; Uchida, Gyo

2017-07-01

In many medical care markets with limited profit potential, firms often have little incentive to innovate. These include the market for rare diseases, "neglected" tropical diseases, and personalized medicine. Governments and not-for-profit organizations promote innovation in such markets but empirical evidence on the policy effect is limited. We study this issue by analyzing the impact of a demand-side policy in Japan, which reduces the cost sharing of patients with some rare and intractable diseases and attempts to establish and promote the treatment of those diseases. Using clinical trials data taken from public registries, we identify the effect of the policy using a difference-in-difference approach. We find that the demand-side policy increased firms' incentive to innovate: firm-sponsored clinical trials increased 181% (0.16 per disease per year) when covered by the policy. This result indicates that the demand-side policy can be an important part of innovation policies in markets with limited profit potential. Copyright © 2017 Elsevier B.V. All rights reserved.

The German fibromyalgia consumer reports - a cross-sectional survey.

PubMed

Häuser, Winfried; Jung, Eva; Erbslöh-Möller, Brigitte; Gesmann, Mechthild; Kühn-Becker, Hedi; Petermann, Franz; Langhorst, Jost; Thoma, Reinhard; Weiss, Thomas; Wolfe, Frederick; Winkelmann, Andreas

2012-05-18

Consumer surveys provide information on effectiveness and side effects of medical interventions in routine clinical care. A report of fibromyalgia syndrome (FMS) consumers has not been carried out in Europe. The study was carried out from November 2010 to April 2011. Participants diagnosed with FMS rated the effectiveness and side effects of pharmacological and non-pharmacological FMS interventions on a 0 to 10 scale, with 10 being most efficacious (harmful). The questionnaire was distributed by the German League for people with Arthritis and Rheumatism and the German Fibromyalgia Association to their members and to all consecutive FMS patients of nine clinical centers of different levels of care. 1661 questionnaires (95% women, mean age 54 years, mean duration since FMS diagnosis 6.8 years) were analysed. The most frequently used therapies were self-management strategies, prescription pain medication and aerobic exercise. The highest average effectiveness was attributed to whole body and local warmth therapies, thermal bathes, FMS education and resting. The highest average side effects were attributed to strong opioids, local cold therapy, gamma-amino-butyric acid analogues (pregabalin and gabapentin), tramadol and opioid transdermal systems. The German fibromyalgia consumer reports highlight the importance of non-pharmcological therapies in the long-term management of FMS, and challenges the strong recommendations for drug therapies given by FMS-guidelines.

Photothermal effects in phase shifted FBG with varied light wavelength and intensity.

PubMed

Ding, Meng; Chen, Dijun; Fang, Zujie; Wang, Di; Zhang, Xi; Wei, Fang; Yang, Fei; Ying, Kang; Cai, Haiwen

2016-10-31

The intensity enhancement effect of a phase-shifted fiber Bragg grating (PSFBG) is investigated theoretically and experimentally in this paper. Due to the effect, both of the FBG reflection bands and the transmission peak show red-shift with the increase of pump light wavelength from the shorter side to the longer side of the Bragg wavelength. The transmission peak shifts in pace with the pump's wavelength, which is much faster than the reflection band. The maximum shift increases with the pump power. In contrast, the red-shift is very small when the pump light deceases from the longer side of the Bragg wavelength. Such asymmetric behavior is checked dynamically by using a frequency modulated laser in a serrated wave, showing push-pull behavior. The effect of the characteristics of thermal dissipation conditions is also measured. The fiber loss coefficient of FBG being tested is estimated from the measured data to be about 0.001 mm^-1, which may be attributed to the H₂-loading and UV exposure in FBG fabrication. The observed phenomena are believed of importance in application where PSFBG is utilized as a narrow linewidth filter.

The effect of depression and side effects of antiepileptic drugs on injuries in patients with epilepsy.

PubMed

Gur-Ozmen, S; Mula, M; Agrawal, N; Cock, H R; Lozsadi, D; von Oertzen, T J

2017-09-01

People with epilepsy are at increased risk of accidents and injuries but, despite several studies on this subject, data regarding preventable causes are still contradictory. The aim of this study was to investigate the relationship between injuries, side effects of antiepileptic drugs (AEDs) and depression. Data from a consecutive sample of adult patients with epilepsy attending the outpatient clinics at St George's University Hospital in London were included. All patients were asked if they had had any injury since the last clinic appointment and completed the Liverpool Adverse Event Profile (LAEP) and Neurological Disorders Depression Inventory for Epilepsy. Among 407 patients (243 females, mean age 43.1 years), 71 (17.4%) reported injuries since the last appointment. A two-step cluster analysis revealed two clusters with the major cluster (53.5% of the injured group) showing a total score for LAEP ≥45, a positive Neurological Disorders Depression Inventory for Epilepsy screening and presence of AED polytherapy. A total score for LAEP ≥45 was the most important predictor. Antiepileptic drug treatment should be reviewed in patients reporting injuries in order to evaluate the potential contribution and burden of AED side effects. © 2017 EAN.

The Janus effect on superhydrophilic Cu mesh decorated with Ni-NiO/Ni(OH)2 core-shell nanoparticles for oil/water separation

NASA Astrophysics Data System (ADS)

Luo, Zhi-Yong; Lyu, Shu-Shen; Fu, Yuan-Xiang; Heng, Yi; Mo, Dong-Chuan

2017-07-01

Janus effect has been studied for emerging materials like Janus membranes, Janus nanoparticles, etc., and the applications including fog collection, oil/water separation, CO2 removal and stabilization of multiphasic mixtures. However, the Janus effect on oil/water separation is still unclear. Herein, Janus Cu mesh decorated with Ni-NiO/Ni(OH)2 core-shell nanoparticles is synthesized via selective electrodeposition, in which we keep one side of Cu mesh (Janus A) to be superhydrophilic, while manipulate the wettability of another side (Janus B) from hydrophobic to superhydrophilic. Experimental results indicate that Cu mesh with both-side superhydrophilic shows the superior oil/water separation performance (separation efficiency >99.5%), which is mainly due to its higher water capture percentage as well as larger oil intrusion pressure. Further, we demonstrate the orientation of Janus membranes for oil/water separation, and summarize that the wettability of the upper surface plays a more important role than the lower surface to achieve remarkable performance. Our work provides a clear insight of Janus effect on oil/water separation, it is significative to design high-performance membranes for oil/water separation and many other applications.

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.

The glaucoma research foundation patient survey: patient understanding of glaucoma and its treatment.

PubMed

Herndon, Leon W; Brunner, Thomas M; Rollins, Jane Neff

2006-01-01

Determine patients' understanding of glaucoma and its treatment, their sources of information about glaucoma, their preferences for treatment, their experience with medication side effects, and their reasons for changing eye doctors. Prospective, nonrandomized patient survey study. A questionnaire was developed and sent to the 22,000 subscribers of the Gleams newsletter who have glaucoma. Questionnaires were returned by 4310 glaucoma patients. Most respondents received glaucoma information from their eye doctor. Only 28% of respondents reported having changed eye doctors for reasons related to their glaucoma. Of those who had, 60% cited poor communication as the reason. When queried about specific side effects associated with their medication, over 85% of responding patients were never or rarely bothered by headaches and eyelid darkening. Most respondents (67% and 55%, respectively) were rarely or never disturbed by red eye or burning and stinging. Most respondents understood the importance of intraocular pressure (IOP) lowering in glaucoma, and of those patients who expressed a preference, 92% reported that they would prefer the medication that lowers IOP the most, even if it caused red eye for a few weeks, over a medication that caused no red eye but did not get IOP as low. Patients who subscribe to Gleams and responded to the survey rely most on their doctors for information about glaucoma and its treatment. Most understand the importance of maintaining low IOP to decrease the risk of vision loss, and most will tolerate temporary ocular side effects to achieve low IOP.

“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

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.

Nature versus Nurture in Determining Athletic Ability.

PubMed

Yan, Xu; Papadimitriou, Ioannis; Lidor, Ronnie; Eynon, Nir

2016-01-01

This overview provides a general discussion of the roles of nature and nurture in determining human athletic ability. On the nature (genetics) side, a review is provided with emphasis on the historical research and on several areas which are likely to be important for future research, including next-generation sequencing technologies. In addition, a number of well-designed training studies that could possibly reveal the biological mechanism ('cause') behind the association between gene variants and athletic ability are discussed. On the nurture (environment) side, we discuss common environmental variables including deliberate practice, family support, and the birthplace effect, which may be important in becoming an elite athlete. Developmental effects are difficult to disassociate with genetic effects, because the early life environment may have long-lasting effects in adulthood. With this in mind, the fetal programming hypothesis is also briefly reviewed, as fetal programming provides an excellent example of how the environment interacts with genetics. We conclude that the traditional argument of nature versus nurture is no longer relevant, as it has been clearly established that both are important factors in the road to becoming an elite athlete. With the availability of the next-generation genetics (sequencing) techniques, it is hoped that future studies will reveal the relevant genes influencing performance, as well as the interaction between those genes and environmental (nurture) factors. © 2016 S. Karger AG, Basel.

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.

Impact of Doxorubicin Treatment on the Physiological Functions of White Adipose Tissue

PubMed Central

Cruz, Maysa Mariana; Cunha, Roberta D. C.; Alonso-Vale, Maria Isabel; Oyama, Lila Missae; Nascimento, Claudia M. Oller; Pimentel, Gustavo Duarte; dos Santos, Ronaldo V. T.; Lira, Fabio Santos

2016-01-01

White adipose tissue (WAT) plays a fundamental role in maintaining energy balance and important endocrine functions. The loss of WAT modifies adipokine secretion and disrupts homeostasis, potentially leading to severe metabolic effects and a reduced quality of life. Doxorubicin is a chemotherapeutic agent used clinically because of its good effectiveness against various types of cancer. However, doxorubicin has deleterious effects in many healthy tissues, including WAT, liver, and skeletal and cardiac muscles. Our objective was to investigate the effects of doxorubicin on white adipocytes through in vivo and in vitro experiments. Doxorubicin reduced the uptake of glucose by retroperitoneal adipocytes and 3T3-L1 cells via the inhibition of AMP-activated protein kinase Thr172 phosphorylation and glucose transporter 4 content. Doxorubicin also reduced the serum level of adiponectin and, to a greater extent, the expression of genes encoding lipogenic (Fas and Acc) and adipogenic factors (Pparg, C/ebpa, and Srebp1c) in retroperitoneal adipose tissue. In addition, doxorubicin inhibited both lipogenesis and lipolysis and reduced the hormone-sensitive lipase and adipose tissue triacylglycerol lipase protein levels. Therefore, our results demonstrate the impact of doxorubicin on WAT. These results are important to understand some side effects observed in patients receiving chemotherapy and should encourage new adjuvant treatments that aim to inhibit these side effects. PMID:27015538

Identification and Prioritization of Important Attributes of Disease-Modifying Drugs in Decision Making among Patients with Multiple Sclerosis: A Nominal Group Technique and Best-Worst Scaling.

PubMed

Kremer, Ingrid E H; Evers, Silvia M A A; Jongen, Peter J; van der Weijden, Trudy; van de Kolk, Ilona; Hiligsmann, Mickaël

2016-01-01

Understanding the preferences of patients with multiple sclerosis (MS) for disease-modifying drugs and involving these patients in clinical decision making can improve the concordance between medical decisions and patient values and may, subsequently, improve adherence to disease-modifying drugs. This study aims first to identify which characteristics-or attributes-of disease-modifying drugs influence patients´ decisions about these treatments and second to quantify the attributes' relative importance among patients. First, three focus groups of relapsing-remitting MS patients were formed to compile a preliminary list of attributes using a nominal group technique. Based on this qualitative research, a survey with several choice tasks (best-worst scaling) was developed to prioritize attributes, asking a larger patient group to choose the most and least important attributes. The attributes' mean relative importance scores (RIS) were calculated. Nineteen patients reported 34 attributes during the focus groups and 185 patients evaluated the importance of the attributes in the survey. The effect on disease progression received the highest RIS (RIS = 9.64, 95% confidence interval: [9.48-9.81]), followed by quality of life (RIS = 9.21 [9.00-9.42]), relapse rate (RIS = 7.76 [7.39-8.13]), severity of side effects (RIS = 7.63 [7.33-7.94]) and relapse severity (RIS = 7.39 [7.06-7.73]). Subgroup analyses showed heterogeneity in preference of patients. For example, side effect-related attributes were statistically more important for patients who had no experience in using disease-modifying drugs compared to experienced patients (p < .001). This study shows that, on average, patients valued effectiveness and unwanted effects as most important. Clinicians should be aware of the average preferences but also that attributes of disease-modifying drugs are valued differently by different patients. Person-centred clinical decision making would be needed and requires eliciting individual preferences.

Identification and Prioritization of Important Attributes of Disease-Modifying Drugs in Decision Making among Patients with Multiple Sclerosis: A Nominal Group Technique and Best-Worst Scaling

PubMed Central

Kremer, Ingrid E. H.; van der Weijden, Trudy; van de Kolk, Ilona

2016-01-01

Objectives Understanding the preferences of patients with multiple sclerosis (MS) for disease-modifying drugs and involving these patients in clinical decision making can improve the concordance between medical decisions and patient values and may, subsequently, improve adherence to disease-modifying drugs. This study aims first to identify which characteristics–or attributes–of disease-modifying drugs influence patients´ decisions about these treatments and second to quantify the attributes’ relative importance among patients. Methods First, three focus groups of relapsing-remitting MS patients were formed to compile a preliminary list of attributes using a nominal group technique. Based on this qualitative research, a survey with several choice tasks (best-worst scaling) was developed to prioritize attributes, asking a larger patient group to choose the most and least important attributes. The attributes’ mean relative importance scores (RIS) were calculated. Results Nineteen patients reported 34 attributes during the focus groups and 185 patients evaluated the importance of the attributes in the survey. The effect on disease progression received the highest RIS (RIS = 9.64, 95% confidence interval: [9.48–9.81]), followed by quality of life (RIS = 9.21 [9.00–9.42]), relapse rate (RIS = 7.76 [7.39–8.13]), severity of side effects (RIS = 7.63 [7.33–7.94]) and relapse severity (RIS = 7.39 [7.06–7.73]). Subgroup analyses showed heterogeneity in preference of patients. For example, side effect-related attributes were statistically more important for patients who had no experience in using disease-modifying drugs compared to experienced patients (p < .001). Conclusions This study shows that, on average, patients valued effectiveness and unwanted effects as most important. Clinicians should be aware of the average preferences but also that attributes of disease-modifying drugs are valued differently by different patients. Person-centred clinical decision making would be needed and requires eliciting individual preferences. PMID:27812117

Survey of healthcare workers' attitudes, beliefs and willingness to receive the 2009 pandemic influenza A (H1N1) vaccine and the impact of educational campaigns.

PubMed

Thoon, Koh Cheng; Chong, Chia Yin

2010-04-01

Vaccination against the 2009 pandemic influenza A (H1N1) represents the best method of controlling spread, morbidity and mortality due to the pandemic. While this has been recommended for all healthcare-workers locally, it is unclear if they are willing to accept the vaccination. A cross-sectional survey was conducted before and after an educational talk on pandemic influenza and vaccines to ascertain responses and stated reasons, as well as identify associated factors. For 235 returned forms prior to the talk, 182 (77.4%) responded positively, while 161 of 192 (83.8%) who returned forms after the talk responded positively. Importantly, 12 of 47 (25.5%) initially negative responses turned positive after education. The desire to protect family, self and patients were the 3 most important reasons for staff wanting to receive the vaccine, while the concern regarding potential side effects was the most important reason for refusal. A high rate of willingness to receive pandemic influenza vaccine was found, which was in contrast to acceptance rates elsewhere and during previous influenza seasons. Education can play an important role in altering vaccine acceptance behaviour, with an emphasis on addressing concerns with regard to potential side effects.

Side-specific effects by cadmium exposure: Apical and basolateral treatment in a coculture model of the blood-air barrier

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

Papritz, Mirko, E-mail: papritz@uni-mainz.d; Institute of Pathology, Johannes Gutenberg University Mainz; Pohl, Christine

2010-06-15

Cadmium (Cd{sup 2+}) is a widespread environmental pollutant, which is associated with a wide variety of cytotoxic and metabolic effects. Recent studies showed that intoxication with the heavy metal most importantly targets the integrity of the epithelial barrier. In our study, the lung epithelial cell line, NCI H441, was cultured with the endothelial cell line, ISO-HAS-1, as a bilayer on a 24-well HTS-Transwell (registered) filter plate. This coculture model was exposed to various concentrations of CdCl{sub 2}. The transepithelial electrical resistance decreased on the apical side only after treatment with high Cd{sup 2+} concentrations after 48 h. By contrast, amore » breakdown of TER to less than 5% of baseline could be observed much earlier (after 24 h) when Cd{sup 2+} was administered from the basal side. Observations of cell layer fragmentation and widening of intercellular spaces confirmed the barrier breakdown only for the basolaterally treated samples. Furthermore, the cytotoxicity and release of proinflammatory markers was enhanced if samples were exposed to Cd{sup 2+} from the basal side compared to treatment from the apical side. Moreover, we could demonstrate that a high concentration of Ca{sup 2+} could prevent the barrier-disrupting effect of Cd{sup 2+}. In conclusion, the exposure of Cd{sup 2+} to cocultures of lung cells caused a decrease in TER, major morphological changes, a reduction of cell viability and an increase of cytokine release, but the effects markedly differed between the two modes of exposure. Therefore, our results suggest that intact epithelial TJs may play a major role in protecting the air-blood barrier from inhaled Cd{sup 2+}.« less

Induced interaction in a Fermi gas with a BEC-BCS crossover

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

Yu Zengqiang; Huang Kun; Yin Lan

2009-05-15

We study the effect of the induced interaction on the superfluid transition temperature of a Fermi gas with a Bose-Einstein condensation-Bardeen-Cooper-Schrieffer (BEC-BCS) crossover. The Gorkov-Melik-Barkhudarov theory about the induced interaction is extended from the BCS side to the entire crossover and the pairing fluctuation is treated in the approach by Nozieres and Schmitt-Rink. At unitarity, the induced interaction reduces the transition temperature by about 20%. In the BCS limit, the transition temperature is reduced by a factor of about 2.22, as found by Gorkov and Melik-Barkhudarov. Our result shows that the effect of the induced interaction is important both onmore » the BCS side and in the unitary region.« less

Predictors of long-term compliance in attending a worksite hypertension programme.

PubMed

Landers, R; Riccobene, A; Beyreuther, M; Neusy, A J

1993-12-01

Variables such as patient's anxiety, knowledge, number of medication changes, medication-induced side-effects and programme-derived benefits and conveniences have been reported or theorised to be important determinants of patient's attendance at worksite hypertension programmes. This study investigates whether these variables have predictive value in differentiating compliers from noncompliers attending a union-sponsored worksite hypertension programme for at least five years. Scores were created from a questionnaire distributed to 243 patients with a response rate of 98%. Compliance was defined as missing < or = 25% of scheduled clinic appointments. By discriminant statistical analysis scores for patient's anxiety, knowledge, number of medication changes, medication side-effects, perceived benefits and conveniences failed to show any predictive value for patient's compliance with appointment keeping.

Transient Three-Dimensional Side Load Analysis of Out-of-Round Film Cooled Nozzles

NASA Technical Reports Server (NTRS)

Wang, Ten-See; Lin, Jeff; Ruf, Joe; Guidos, Mike

2010-01-01

The objective of this study is to investigate the effect of nozzle out-of-roundness on the transient startup side loads at a high altitude, with an anchored computational methodology. The out-of-roundness could be the result of asymmetric loads induced by hardware attached to the nozzle, asymmetric internal stresses induced by previous tests, and deformation, such as creep, from previous tests. The rocket engine studied encompasses a regeneratively cooled thrust chamber and a film cooled nozzle extension with film coolant distributed from a turbine exhaust manifold. The computational methodology is based on an unstructured-grid, pressure-based computational fluid dynamics formulation, and a transient inlet history based on an engine system simulation. Transient startup computations were performed with the out-of-roundness achieved by four different degrees of ovalization: one perfectly round, one slightly out-of-round, one more out-of-round, and one significantly out-of-round. The results show that the separation-line-jump is the peak side load physics for the round, slightly our-of-round, and more out-of-round cases, and the peak side load increases as the degree of out-of-roundness increases. For the significantly out-of-round nozzle, however, the peak side load reduces to comparable to that of the round nozzle and the separation line jump is not the peak side load physics. The counter-intuitive result of the significantly out-of-round case is found to be related to a side force reduction mechanism that splits the effect of the separation-line-jump into two parts, not only in the circumferential direction and most importantly in time.

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 ...

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.

Male osteoporosis and androgenic therapy: from testosterone to SARMs

PubMed Central

Cilotti, Antonio; Falchetti, Alberto

2009-01-01

As in the women, male osteoporosis represents an important social problem, amplified by the increasing life expectance. Differently from women, 50% of male osteoporosis is secondary to treatments and/or diseases that make mandatory their search through an accurate clinical investigations in every newly diagnosed osteoporotic men. Male osteoporosis is frequently underdiagnosed and consequently undertreated, and too often it is revealed only after the occurrence of a fragility fracture. Androgens may prevent the loss of cancellous bone and stimulate periosteal cortical bone apposition. The anabolic effect of testosterone on both bone and muscle, is limited by the high incidence of androgenic side effects. Hypogonadism is the only situation where the benefits of the use of testosterone formulations exceed the side effects. Selective androgen receptor modulators can dissociate androgenic and anabolic effect on different tissues with various strategies. Many compounds have been studied with positive results in vivo and in clinical trials. PMID:22461251

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.

Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression

PubMed Central

Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J.; Schoevers, Robert A.; Klein, Hans C.

2017-01-01

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects. PMID:28910337

Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression.

PubMed

van Buel, Erin M; Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J; Schoevers, Robert A; Klein, Hans C; Pryce, Christopher R; Eisel, Ulrich Lm

2017-01-01

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects.

Patient Preferences and Urologist Judgments on Prostate Cancer Therapy in Japan.

PubMed

Nakayama, Masahiko; Kobayashi, Hisanori; Okazaki, Masateru; Imanaka, Keiichiro; Yoshizawa, Kazutake; Mahlich, Jörg

2018-05-01

The purpose of the present study is to investigate the concordance of treatment preferences between patients and physicians in prostate cancer (PCa) in Japan. An internet-based discrete choice experiment was conducted. Patients and physicians were asked to select their preferred treatment from a pair of hypothetical treatments consisting of four attributes: quality of life (QOL), treatment effectiveness, side effects, and accessibility of treatment. The data were analyzed using a conditional logistic regression model to calculate coefficients and the relative importance (RI) of each attribute. A total of 103 PCa patients and 127 physicians responded. The study looked at 37 patients considered as advanced PCa and 66 who were non-advanced PCa. All of the physicians were urologists. Advanced PCa patients ranked the attributes as follows: treatment effectiveness (RI: 32%), accessibility of treatment (RI: 26%), QOL (RI: 23%), and side effects (RI: 19%). For physicians, the RI ranking was the same as for advanced PCa patients; treatment effectiveness (RI: 29%), accessibility of treatment (RI: 27%), QOL (RI: 26%), and side effects (RI: 18%). For non-advanced PCa patients, accessibility of treatment ranked the highest RI (27%) and treatment effectiveness ranked as the lowest RI (14%). Our study suggests that the ranking of the attributes was consistent between advanced PCa patients and physicians. The most influential attribute was treatment effectiveness. Treatment preferences also vary by disease stage.

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.

An analysis of induced pressure fields in electroosmotic flows through microchannels.

PubMed

Zhang, Yonghao; Gu, Xiao-Jun; Barber, Robert W; Emerson, David R

2004-07-15

Induced pressure gradients are found to cause band-broadening effects which are important to the performance of microfluidic devices, such as capillary electrophoresis and capillary chromatography. An improved understanding of the underlying mechanisms causing an induced pressure gradient in electroosmotic flows is presented. The analysis shows that the induced pressure distribution is the key to understanding the experimentally observed phenomena of leakage flows. A novel way of determining the static pressures at the inlet and outlet of microchannels is also presented that takes account of the pressure losses due to flow contraction and expansion. These commonly neglected pressure losses at the channel entrance and outlet are shown to be important in accurately describing the flow. The important parameters that define the effect of induced pressure on the flows are discussed, which may facilitate the design of improved microfluidic devices. The present model clearly identifies the mechanism behind the experimentally observed leakage flows, which is further confirmed by numerical simulations. Not only can the leakage flow occur from the electric-field-free side channel to the main channel, but also the fluid in the main channel can be attracted into the side channel by the induced pressure gradient. Copyright 2004 Elsevier Inc.

Investigation of the Effects of High-Intensity, Intermittent Exercise and Unanticipation on Trunk and Lower Limb Biomechanics During a Side-Cutting Maneuver Using Statistical Parametric Mapping.

PubMed

Whyte, Enda F; Richter, Chris; OʼConnor, Siobhan; Moran, Kieran A

2018-06-01

Whyte, EF, Richter, C, O'Connor, S, and Moran, KA. Investigation of the effects of high-intensity, intermittent exercise and unanticipation on trunk and lower limb biomechanics during a side-cutting maneuver using statistical parametric mapping. J Strength Cond Res 32(6): 1583-1593, 2018-Anterior cruciate ligament (ACL) injuries frequently occur during side-cutting maneuvers when fatigued or reacting to the sporting environment. Trunk and hip biomechanics are proposed to influence ACL loading during these activities. However, the effects of fatigue and unanticipation on the biomechanics of the kinetic chain may be limited by traditional discrete point analysis. We recruited 28 male, varsity, Gaelic footballers (21.7 ± 2.2 years; 178.7 ± 14.6 m; 81.8 ± 11.4 kg) to perform anticipated and unanticipated side-cutting maneuvers before and after a high-intensity, intermittent exercise protocol (HIIP). Statistical parametric mapping (repeated-measures analysis of varience) identified differences in phases of trunk and stance leg biomechanics during weight acceptance. Unanticipation resulted in less trunk flexion (p < 0.001) and greater side flexion away from the direction of cut (p < 0.001). This led to smaller (internal) knee flexor and greater (internal) knee extensor (p = 0.002-0.007), hip adductor (p = 0.005), and hip external rotator (p = 0.007) moments. The HIIP resulted in increased trunk flexion (p < 0.001) and side flexion away from the direction of cut (p = 0.038), resulting in smaller (internal) knee extensor moments (p = 0.006). One interaction effect was noted demonstrating greater hip extensor moments in the unanticipated condition post-HIIP (p = 0.025). Results demonstrate that unanticipation resulted in trunk kinematics considered an ACL injury risk factor. A subsequent increase in frontal and transverse plane hip loading and sagittal plane knee loading was observed, which may increase ACL strain. Conversely, HIIP-induced trunk kinematic alterations resulted in reduced sagittal plane knee and subsequent ACL loading. Therefore, adequate hip and knee control is important during unanticipated side-cutting maneuvers.

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.

Perceptual load in central and peripheral regions and its effects on driving performance: advertizing billboards.

PubMed

Marciano, Hadas; Yeshurun, Yaffa

2012-01-01

A broadened version of the perceptual load model was utilized to explore systematically the influence of four variables on driver's behavior: a. levels of load on the road; b. levels of load at the sides of the road; c. event's initial location (on the road vs. at the sides of the road); and d. the presence and size of advertizing billboards. 18 participants participated in two experimental sessions in a driving simulator. One of the sessions contained advertizing billboards and the other session did not. The results indicated that billboards can have a considerable effect on various aspects of driving like the time required responding to a potentially dangerous event or simply the number of accidents occurring during driving, but importantly the effect of billboards on driving was modulated by the levels of perceptual load.

Patient's Knowledge and Perception Towards the use of Non-steroidal Anti-Inflammatory Drugs in Rheumatology Clinic Northern Malaysia.

PubMed

Sulaiman, Wahinuddin; Seung, Ong Ping; Ismail, Rosli

2012-11-01

In Rheumatology, non-steroidal anti-inflammatory drugs (NSAIDs) has been widely prescribed and used. However, despite their clinical benefits in the management of inflammatory and degenerative joint disease, NSAIDs have considerable side effects, mostly affecting the upper gastrointestinal system, which therefore, limit their use. This study was conducted to determine the patients' knowledge and perception regarding the used of NSAIDS. A total of 120 patients who attended the rheumatology clinic Hospital, Raja Permaisuri Bainun, Malaysia, and received NSAIDs more than 3 months were interviewed irrespective of their rheumatological conditions. Patient's knowledge and perception on the side effects of NSAIDs were recorded. Fifty-four percent of the patients obtained information regarding the side effect of NSAIDs either from the rheumatologist, rheumatology staff nurse or other medical staffs (75.4%). The remaining 45.8% were naive of such knowledge. Fifteen percent obtained the information by surfing the internet and 9.2% from printed media. Twenty-four (24.2%) patients, experienced indigestion and/or stomach discomfort attributed to NSAIDs used. Two patients (1.7%) had hematemesis and malena once. This study shows that half of the patients who attended the rheumatology clinic were unaware of the side effect of NSAIDs. Available data showed that most of the knowledgeable patients are more conscience and self-educated. This study also reveals the important roles of clinicians, trained staff nurses as well as the pharmacist in providing the guidance and knowledge of any medication taken by patients.

Cellular internalization, transcellular transport, and cellular effects of silver nanoparticles in polarized Caco-2 cells following apical or basolateral exposure

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

Imai, Shunji; Morishita, Yuki; Hata, Tomoyuki

When considering the safety of ingested nanomaterials, it is important to quantitate their transfer across intestinal cells; however, little information exists about the effects of nanomaterial size or exposure side (apical versus basolateral epithelial surface) on nanomaterial transfer. Here, we examined cellular internalization and transcellular transport, and the effects of nanomaterials on Caco-2 monolayers after apical or basolateral exposure to Ag or Au nanoparticles with various sizes. After apical treatment, both internalization and transfer to the basolateral side of the monolayers were greater for smaller Ag nanoparticles than for larger Ag nanoparticles. In contrast, after basolateral treatment, larger Ag nanoparticlesmore » were more internalized than smaller Ag nanoparticles, but the transfer to the apical side was greater for smaller Ag nanoparticles. Au nanoparticles showed different rules of internalization and transcellular transport compared with Ag nanoparticles. Furthermore, the paracellular permeability of the Caco-2 monolayers was temporarily increased by Ag nanoparticles (5 μg/mL; diameters, ≤10 nm) following basolateral but not apical exposure. We conclude that the internalization, transfer, and effects of nanomaterials in epithelial cell monolayers depend on the size and composition of nanomaterials, and the exposure side. - Highlights: • Ag and Au nanoparticles can transfer across Caco-2 monolayers. • Cellular uptake of nanoparticles change between apical and basolateral exposure. • Basolateral Ag nanoparticle exposure increases the permeability of Caco-2 monolayers.« less

Effect of the computational domain size and shape on the self-diffusion coefficient in a Lennard-Jones liquid.

PubMed

Kikugawa, Gota; Ando, Shotaro; Suzuki, Jo; Naruke, Yoichi; Nakano, Takeo; Ohara, Taku

2015-01-14

In the present study, molecular dynamics (MD) simulations on the monatomic Lennard-Jones liquid in a periodic boundary system were performed in order to elucidate the effect of the computational domain size and shape on the self-diffusion coefficient measured by the system. So far, the system size dependence in cubic computational domains has been intensively investigated and these studies showed that the diffusion coefficient depends linearly on the inverse of the system size, which is theoretically predicted based on the hydrodynamic interaction. We examined the system size effect not only in the cubic cell systems but also in rectangular cell systems which were created by changing one side length of the cubic cell with the system density kept constant. As a result, the diffusion coefficient in the direction perpendicular to the long side of the rectangular cell significantly increases more or less linearly with the side length. On the other hand, the diffusion coefficient in the direction along the long side is almost constant or slightly decreases. Consequently, anisotropy of the diffusion coefficient emerges in a rectangular cell with periodic boundary conditions even in a bulk liquid simulation. This unexpected result is of critical importance because rectangular fluid systems confined in nanospace, which are present in realistic nanoscale technologies, have been widely studied in recent MD simulations. In order to elucidate the underlying mechanism for this serious system shape effect on the diffusion property, the correlation structures of particle velocities were examined.

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.

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.

A Review on the Traditional Chinese Medicinal Herbs and Formulae with Hypolipidemic Effect

PubMed Central

Sham, Tung-Ting; Chan, Chi-On; Wang, You-Hua; Yang, Jian-Mei; Mok, Daniel Kam-Wah; Chan, Shun-Wan

2014-01-01

Hyperlipidemia, characterized by the abnormal blood lipid profiles, is one of the dominant factors of many chronic diseases such as diabetes, obesity, and cardiovascular diseases (CVD). For the low cost, effectiveness, and fewer side effects, the popularity of using traditional Chinese medicine (TCM) to handle hyperlipidemia is increasing and its role in health care has been recognized by the public at large. Despite the importance of TCM herbs and formulations, there is no comprehensive review summarizing their scientific findings on handling hyperlipidemia. This review summarizes the recent experimental and clinical results of nine representative single Chinese herbs and seven classic TCM formulae that could improve lipid profiles so as to help understand and compare their underlying mechanisms. Most of single herbs and formulae demonstrated the improvement of hyperlipidemic conditions with multiple and diverse mechanisms of actions similar to conventional Western drugs in spite of their mild side effects. Due to increasing popularity of TCM, more extensive, well-designed preclinical and clinical trials on the potential synergistic and adverse side effects of herb-drug interactions as well as their mechanisms are warranted. Hyperlipidemic patients should be warned about the potential risks of herb-drug interactions, particularly those taking anticoagulants and antiplatelet drugs. PMID:25110708

A comparative evaluation of in-vehicle side view displays layouts in critical lane changing situation.

PubMed

Beck, Donghyun; Lee, Minho; Park, Woojin

2017-12-01

This study conducted a driving simulator experiment to comparatively evaluate three in-vehicle side view displays layouts for camera monitor systems (CMS) and the traditional side view mirror arrangement. The three layouts placed two electronic side view displays near the traditional mirrors positions, on the dashboard at each side of the steering wheel and on the centre fascia with the two displays joined side-by-side, respectively. Twenty-two participants performed a time- and safety-critical driving task that required rapidly gaining situation awareness through the side view displays/mirrors and making a lane change to avoid collision. The dependent variables were eye-off-the-road time, response time, and, ratings of perceived workload, preference and perceived safety. Overall, the layout placing the side view displays on the dashboard at each side of the steering wheel was found to be the best. The results indicated that reducing eye gaze travel distance and maintaining compatibility were both important for the design of CMS displays layout. Practitioner Summary: A driving simulator study was conducted to comparatively evaluate three in-vehicle side view displays layouts for camera monitor systems (CMS) and the traditional side view mirror arrangement in critical lane changing situation. Reducing eye movement and maintaining compatibility were found to be both important for the ergonomics design of CMS displays layout.

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.

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.

Managing Chemotherapy Side Effects: Fatigue (Feeling Weak and Very Tired)

MedlinePlus

... Make a plan to feel less tired. Do less. Let others help you. ● ● Do activities that are most important first. ● ● Ask others for help. ● ● Take time off from your job, or work fewer hours. “I was so tired. It was hard to ...

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 ...

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.

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. ...

"There is a chain of connections": using syndemics theory to understand HIV treatment side effects.

PubMed

Gagnon, Marilou

2018-03-12

Side effects are central to the experience of living longer with HIV but rarely have they been studied alone. Unlike other aspects of that experience, like quality of life, treatment adherence, chronicity, episodic disability, aging, health, and viral load suppression, side effects have not benefited from the same level of empirical and theoretical engagement from qualitative researchers. In this paper, we draw on syndemics theory and 50 qualitative interviews to better understand the experience of HIV treatment side effects. Two main categories were identified in the data: side effects as a product and side effects as a risk factor. The first category suggests that side effects are not just the product of taking antiretroviral drugs. They are also the product of particular conditions and tend to cluster with other health problems. The second category puts forward the idea that side effects can act as a syndemic risk factor by exposing PLWH to a greater risk of developing health problems and creating conditions in which psychosocial issues are more likely to emerge. The paper concludes by calling for more research on the complex nature of side effects and for the development of comprehensive approaches for the assessment and management of side effects.

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.

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.

Boat Hull Blisters: Repair Techniques and Long Term Effects on Hull Degradation

DTIC Science & Technology

1988-08-01

Swelling Stresses Produced by Diffusion; Long Term Damage by Water Absorption ; Effects of Gel Coat on Leaching of Water Soluble Material from...leinforcesents 5. Swelling Stresses Produced by Diffusion 6. Long Term Damage by Water Absorption 7. Effects of Gel Coat on Leaching of Water Soluble...the importance of bilge side water pick-up is emphasized. A second method for preventing blister formation is to eliminate or minimize the water soluble

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

Positive and negative tropic curvature induced by microbeam irradiation of protonemal tip cells of the moss Ceratodon purpureus.

PubMed

Lamparter, T; Kagawa, T; Brücker, G; Wada, M

2004-01-01

The photoreceptor phytochrome mediates tropic responses in protonemata of the moss Ceratodon purpureus. Under standard conditions the tip cells grow towards unilateral red light, or perpendicular to the electrical vector of polarized light. In this study the response of tip cells to partial irradiation of the apical region was analysed using a microbeam apparatus. The fluence response curve gave an unexpected pattern: whereas a 15-min microbeam with light intensities around 3 micro mol m (-2) s (-1) induced a growth curvature towards the irradiated side, higher light intensities around 100 micro mol m (-2) s (-1) caused a negative response, the cells grew away from the irradiated side. This avoidance response is explained by two effects: the light intensity is high enough to induce photoconversion into the active Pfr form of phytochrome, not only on the irradiated but also on the non-irradiated side by stray light. At the same time, the strong light on the irradiated side acts antagonistically to Pfr. As a result of this inhibition, the growth direction is moved to the light-avoiding side. Such a Pfr-independent mechanism might be important for the phototropic response to distinguish between the light-directed and light-avoiding side under unilateral light.

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.

Learning to experience side effects after antidepressant intake - Results from a randomized, controlled, double-blind study.

PubMed

Rheker, Julia; Winkler, Alexander; Doering, Bettina K; Rief, Winfried

2017-02-01

Side effects play a key role in patients' failure to take antidepressants. There is evidence that verbal suggestions and informed consent elicit expectations that can in turn trigger the occurrence of side effects. Prior experience or learning mechanisms are also assumed to contribute to the development of side effects, although their role has not been thoroughly investigated. In this study, we examined whether an antidepressant's side effects can be learned via Pavlovian conditioning. Participants (n = 39) were randomly allocated to one of two groups and were exposed to a classical conditioning procedure. During acquisition, 19 participants received amitriptyline and 20 participants received a placebo pill. Pills were taken for four nights together with a novel-tasting drink. After a washout phase, both groups received a placebo pill together with the novel-tasting drink (evocation). Side effects were assessed via the Generic Assessment of Side Effects Scale prior to acquisition (baseline), after acquisition, and after evocation. A score of antidepressant-specific side effects was calculated. Participants taking amitriptyline reported significantly more antidepressant-specific side effects after acquisition compared to both baseline and the placebo group. After evocation, participants who underwent the conditioning procedure with amitriptyline reported significantly more antidepressant-specific side effects than those who never received amitriptyline, even though both groups received a placebo. Our results indicate that antidepressant side effects can be learned using a conditioning paradigm and evoked via a placebo pill when applied with the same contextual factors as the verum.

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.

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.

Right Versus Left Colon Cancer Biology: Integrating the Consensus Molecular Subtypes.

PubMed

Lee, Michael S; Menter, David G; Kopetz, Scott

2017-03-01

Although clinical management of colon cancer generally has not accounted for the primary tumor site, left-sided and right-sided colon cancers harbor different clinical and biologic characteristics. Right-sided colon cancers are more likely to have genome-wide hypermethylation via the CpG island methylator phenotype (CIMP), hypermutated state via microsatellite instability, and BRAF mutation. There are also differential exposures to potential carcinogenic toxins and microbiota in the right and left colon. Gene expression analyses further shed light on distinct biologic subtypes of colorectal cancers (CRCs), with 4 consensus molecular subtypes (CMSs) identified. Importantly, these subtypes are differentially distributed between right- and left-sided CRCs, with greater proportions of the "microsatellite unstable/immune" CMS1 and the "metabolic" CMS3 subtypes found in right-sided colon cancers. This review summarizes important biologic distinctions between right- and left-sided CRCs that likely impact prognosis and may predict for differential responses to biologic therapy. Given the inferior prognosis of stage III-IV right-sided CRCs and emerging data suggesting that anti-epidermal growth factor receptor antibody therapy is associated with worse survival in right-sided stage IV CRCs compared with left-sided cancers, these biologic differences between right- and left-sided CRCs provide critical context and may provide opportunities to personalize therapy. Copyright © 2017 by the National Comprehensive Cancer Network.

Structural and dynamic properties of the C-terminal region of the Escherichia coli RNA chaperone Hfq: integrative experimental and computational studies.

PubMed

Wen, Bin; Wang, Weiwei; Zhang, Jiahai; Gong, Qingguo; Shi, Yunyu; Wu, Jihui; Zhang, Zhiyong

2017-08-09

In Escherichia coli, hexameric Hfq is an important RNA chaperone that facilitates small RNA-mediated post-transcriptional regulation. The Hfq monomer consists of an evolutionarily conserved Sm domain (residues 1-65) and a flexible C-terminal region (residues 66-102). It has been recognized that the existence of the C-terminal region is important for the function of Hfq, but its detailed structural and dynamic properties remain elusive due to its disordered nature. In this work, using integrative experimental techniques, such as nuclear magnetic resonance spectroscopy and small-angle X-ray scattering, as well as multi-scale computational simulations, new insights into the structure and dynamics of the C-terminal region in the context of the Hfq hexamer are provided. Although the C-terminal region is intrinsically disordered, some residues (83-86) are motionally restricted. The hexameric core may affect the secondary structure propensity of the C-terminal region, due to transient interactions between them. The residues at the rim and the proximal side of the core have significantly more transient contacts with the C-terminal region than those residues at the distal side, which may facilitate the function of the C-terminal region in the release of double-stranded RNAs and the cycling of small non-coding RNAs. Structure ensembles constructed by fitting the experimental data also support that the C-terminal region prefers to locate at the proximal side. From multi-scale simulations, we propose that the C-terminal region may play a dual role of steric effect (especially at the proximal side) and recruitment (at the both sides) in the binding process of RNA substrates. Interestingly, we have found that these motionally restricted residues may serve as important binding sites for the incoming RNAs that is probably driven by favorable electrostatic interactions. These integrative studies may aid in our understanding of the functional role of the C-terminal region of Hfq.

[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.

A numerical study of some potential sources of error in side-by-side seismometer evaluations

USGS Publications Warehouse

Holcomb, L. Gary

1990-01-01

This report presents the results of a series of computer simulations of potential errors in test data, which might be obtained when conducting side-by-side comparisons of seismometers. These results can be used as guides in estimating potential sources and magnitudes of errors one might expect when analyzing real test data. First, the derivation of a direct method for calculating the noise levels of two sensors in a side-by-side evaluation is repeated and extended slightly herein. This bulk of this derivation was presented previously (see Holcomb 1989); it is repeated here for easy reference.This method is applied to the analysis of a simulated test of two sensors in a side-by-side test in which the outputs of both sensors consist of white noise spectra with known signal-tonoise ratios (SNR's). This report extends this analysis to high SNR's to determine the limitations of the direct method for calculating the noise levels at signal-to-noise levels which are much higher than presented previously (see Holcomb 1989). Next, the method is used to analyze a simulated test of two sensors in a side-by-side test in which the outputs of both sensors consist of bandshaped noise spectra with known signal-tonoise ratios. This is a much more realistic representation of real world data because the earth's background spectrum is certainly not flat.Finally, the results of the analysis of simulated white and bandshaped side-by-side test data are used to assist in interpreting the analysis of the effects of simulated azimuthal misalignment in side-by-side sensor evaluations. A thorough understanding of azimuthal misalignment errors is important because of the physical impossibility of perfectly aligning two sensors in a real world situation. The analysis herein indicates that alignment errors place lower limits on the levels of system noise which can be resolved in a side-by-side measurement It also indicates that alignment errors are the source of the fact that real data noise spectra tend to follow the earth's background spectra in shape.

Anti-diabetic and hypolipidemic effects of Sargassum yezoense in db/db mice

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

Kim, Su-Nam, E-mail: snkim@kist.re.kr; Lee, Woojung; Bae, Gyu-Un

2012-08-10

Highlights: Black-Right-Pointing-Pointer Sargassum yezoense (SY) treatment improved glucose and lipid impairment in vivo. Black-Right-Pointing-Pointer This pharmacological action is associated with PPAR{alpha}/{gamma} dual activation. Black-Right-Pointing-Pointer It decreases the expression of G6Pase for gluconeogenesis in liver. Black-Right-Pointing-Pointer It increases the expression of UCP3 for lipid metabolism in adipose tissue. Black-Right-Pointing-Pointer There are no significant side effects such as body weight gain and hepatomegaly. -- Abstract: Peroxisome proliferator-activated receptors (PPARs) have been considered to be desirable targets for metabolic syndrome, even though their specific agonists have several side effects including body weight gain, edema and tissue failure. Previously, we have reported in vitromore » effects of Sargassum yezoense (SY) and its ingredients, sargaquinoic acid (SQA) and sargahydroquinoic acid (SHQA), on PPAR{alpha}/{gamma} dual transcriptional activation. In this study, we describe in vivo pharmacological property of SY on metabolic disorders. SY treatment significantly improved glucose and lipid impairment in db/db mice model. More importantly, there are no significant side effects such as body weight gain and hepatomegaly in SY-treated animals, indicating little side effects of SY in liver and lipid metabolism. In addition, SY led to a decrease in the expression of G6Pase for gluconeogenesis in liver responsible for lowering blood glucose level and an increase in the expression of UCP3 in adipose tissue for the reduction of total and LDL-cholesterol level. Altogether, our data suggest that SY would be a potential therapeutic agent against type 2 diabetes and related metabolic disorders by ameliorating the glucose and lipid metabolism.« less

Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis)

PubMed Central

BANERJI, JULIAN

2015-01-01

The present treatment of childhood T-cell leukemias involves the systemic administration of prokary-otic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved. In humans, misfunctions of genes encoding N-hCR are associated with a cluster of disorders that mimic ASNase therapy side-effects which include impaired glycemic control, dislipidemia, pancreatitis, compromised vascular integrity, and neurological dysfunction. This paper proposes that dysregulation of Asn homeostasis, potentially even by ASNase produced by the microbiome, may contribute to several clinically important syndromes by altering expression of N-hCR bearing genes. By altering amino acid abundance and modulating ribosome translocation rates at codon repeats, the microbiomic environment may contribute to genome decoding and to shaping the proteome. We suggest that impaired translation at poly Asn codons elevates diabetes risk and severity. PMID:26178806

Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis).

PubMed

Banerji, Julian

2015-09-01

The present treatment of childhood T-cell leukemias involves the systemic administration of prokaryotic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved. In humans, misfunctions of genes encoding N-hCR are associated with a cluster of disorders that mimic ASNase therapy side-effects which include impaired glycemic control, dislipidemia, pancreatitis, compromised vascular integrity, and neurological dysfunction. This paper proposes that dysregulation of Asn homeostasis, potentially even by ASNase produced by the microbiome, may contribute to several clinically important syndromes by altering expression of N-hCR bearing genes. By altering amino acid abundance and modulating ribosome translocation rates at codon repeats, the microbiomic environment may contribute to genome decoding and to shaping the proteome. We suggest that impaired translation at poly Asn codons elevates diabetes risk and severity.

Childhood Vaccine Acceptance and Refusal among Warao Amerindian Caregivers in Venezuela; A Qualitative Approach

PubMed Central

Burghouts, Jochem; Del Nogal, Berenice; Uriepero, Angimar; Hermans, Peter W. M.; de Waard, Jacobus H.; Verhagen, Lilly M.

2017-01-01

Objectives Acceptance of childhood vaccination varies between societies, affecting worldwide vaccination coverage. Low coverage rates are common in indigenous populations where parents often choose not to vaccinate their children. We aimed to gain insight into reasons for vaccine acceptance or rejection among Warao Amerindians in Venezuela. Methods Based on records of vaccine acceptance or refusal, in-depth interviews with 20 vaccine-accepting and 11 vaccine-declining caregivers were performed. Parents’ attitudes were explored using a qualitative approach. Results Although Warao caregivers were generally in favor of vaccination, fear of side effects and the idea that young and sick children are too vulnerable to be vaccinated negatively affected vaccine acceptance. The importance assigned to side effects was related to the perception that these resembled symptoms/diseases of another origin and could thus harm the child. Religious beliefs or traditional healers did not influence the decision-making process. Conclusions Parental vaccine acceptance requires educational programs on the preventive nature of vaccines in relation to local beliefs about health and disease. Attention needs to be directed at population-specific concerns, including explanation on the nature of and therapeutic options for side effects. PMID:28107501

[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.

Fatal hypermagnesemia in a child treated with megavitamin/megamineral therapy.

PubMed

McGuire, J K; Kulkarni, M S; Baden, H P

2000-02-01

We report a case of fatal hypermagnesemia resulting from the unsupervised use of high doses of magnesium oxide administered as part of a regimen of megavitamin and megamineral therapy to a child with mental retardation, spastic quadriplegia, and seizures. The treatment regimen was given at the recommendation of a dietician working as a private nutritional consultant without the involvement or notification of the child's pediatrician. Hypermagnesemia is an uncommon but serious side effect of the use of magnesium containing compounds. These compounds are widely used as laxatives and dietary supplements, and serious side effects are uncommon when used in appropriate dosages and with adequate supervision. The use of alternative medical therapies, including megavitamin/megamineral therapy, is widespread. Many patients use alternative medicine or seek care from alternative medicine practitioners without the recommendation or knowledge of their primary physicians. Despite unproved benefit, many alternative therapies may be safe. However, unsupervised use of generally safe treatments can result in serious side effects. This case report serves to illustrate the characteristic pathophysiologic changes of severe hypermagnesemia, an entity rarely seen in pediatric practice, and more importantly, it alerts primary care and subspecialty pediatricians to be aware of and monitor the use of alternative medical therapies in their patients.

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.

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,…

Genetics-Based Population Pharmacokinetics and Pharmacodynamics of Risperidone in a Psychiatric Cohort.

PubMed

Vandenberghe, Frederik; Guidi, Monia; Choong, Eva; von Gunten, Armin; Conus, Philippe; Csajka, Chantal; Eap, Chin B

2015-12-01

High interindividual variability in plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, may lead to suboptimal drug concentration. Using a population pharmacokinetic approach, we aimed to characterize the genetic and non-genetic sources of variability affecting risperidone and 9-hydroxyrisperidone pharmacokinetics, and relate them to common side effects. Overall, 150 psychiatric patients (178 observations) treated with risperidone were genotyped for common polymorphisms in NR1/2, POR, PPARα, ABCB1, CYP2D6 and CYP3A genes. Plasma risperidone and 9-hydroxyrisperidone were measured, and clinical data and common clinical chemistry parameters were collected. Drug and metabolite concentrations were analyzed using non-linear mixed effect modeling (NONMEM(®)). Correlations between trough concentrations of the active moiety (risperidone plus 9-hydroxyrisperidone) and common side effects were assessed using logistic regression and linear mixed modeling. The cytochrome P450 (CYP) 2D6 phenotype explained 52% of interindividual variability in risperidone pharmacokinetics. The area under the concentration-time curve (AUC) of the active moiety was found to be 28% higher in CYP2D6 poor metabolizers compared with intermediate, extensive and ultrarapid metabolizers. No other genetic markers were found to significantly affect risperidone concentrations. 9-hydroxyrisperidone elimination was decreased by 26% with doubling of age. A correlation between trough predicted concentration of the active moiety and neurologic symptoms was found (p = 0.03), suggesting that a concentration >40 ng/mL should be targeted only in cases of insufficient, or absence of, response. Genetic polymorphisms of CYP2D6 play an important role in risperidone, 9-hydroxyrisperidone and active moiety plasma concentration variability, which were associated with common side effects. These results highlight the importance of a personalized dosage adjustment during risperidone treatment.

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.

The German fibromyalgia consumer reports – a cross-sectional survey

PubMed Central

2012-01-01

Background Consumer surveys provide information on effectiveness and side effects of medical interventions in routine clinical care. A report of fibromyalgia syndrome (FMS) consumers has not been carried out in Europe. Methods The study was carried out from November 2010 to April 2011. Participants diagnosed with FMS rated the effectiveness and side effects of pharmacological and non-pharmacological FMS interventions on a 0 to 10 scale, with 10 being most efficacious (harmful). The questionnaire was distributed by the German League for people with Arthritis and Rheumatism and the German Fibromyalgia Association to their members and to all consecutive FMS patients of nine clinical centers of different levels of care. Results 1661 questionnaires (95% women, mean age 54 years, mean duration since FMS diagnosis 6.8 years) were analysed. The most frequently used therapies were self-management strategies, prescription pain medication and aerobic exercise. The highest average effectiveness was attributed to whole body and local warmth therapies, thermal bathes, FMS education and resting. The highest average side effects were attributed to strong opioids, local cold therapy, gamma-amino-butyric acid analogues (pregabalin and gabapentin), tramadol and opioid transdermal systems. Conclusion The German fibromyalgia consumer reports highlight the importance of non-pharmcological therapies in the long-term management of FMS, and challenges the strong recommendations for drug therapies given by FMS-guidelines. PMID:22607517

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.

Pharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis

PubMed Central

Zielinski, Daniel C.; Filipp, Fabian V.; Bordbar, Aarash; Jensen, Kasper; Smith, Jeffrey W.; Herrgard, Markus J.; Mo, Monica L.; Palsson, Bernhard O.

2015-01-01

Drug side effects cause a significant clinical and economic burden. However, mechanisms of drug action underlying side effect pathogenesis remain largely unknown. Here, we integrate pharmacogenomic and clinical data with a human metabolic network and find that non-pharmacokinetic metabolic pathways dysregulated by drugs are linked to the development of side effects. We show such dysregulated metabolic pathways contain genes with sequence variants affecting side effect incidence, play established roles in pathophysiology, have significantly altered activity in corresponding diseases, are susceptible to metabolic inhibitors and are effective targets for therapeutic nutrient supplementation. Our results indicate that metabolic dysregulation represents a common mechanism underlying side effect pathogenesis that is distinct from the role of metabolism in drug clearance. We suggest that elucidating the relationships between the cellular response to drugs, genetic variation of patients and cell metabolism may help managing side effects by personalizing drug prescriptions and nutritional intervention strategies. PMID:26055627

Bridging the boundaries between scientists and clinicians-mechanistic hypotheses and patient stories in risk assessment of drugs.

PubMed

Rocca, Elena

2017-02-01

The cultural divide between scientists and clinicians has been described as undermining the advance of medical science, by hindering the production of practice-relevant research and of research-informed clinical decisions. Here, I consider the field of post-marketing risk assessment of drugs as an example of strict interdependence between basic biomedical research, clinical research, and clinical evaluation and show how it would benefit from a closer collaboration between scientists and clinicians. The risk assessment of drugs after their marketing relies on spontaneous adverse effect reports to drug agencies and on peer-reviewed case reports. I emphasize the importance of qualitative analysis of such reports for the improvement of mechanistic understanding of harmful effects of drugs. I argue that mechanistic explanations of drug effects are at least as important as determination of their frequency, in order to establish causation. An ideal risk assessment, then, verifies not only the frequency of undesired effects but also why and how the harm happens. For this purpose, the frequency or novelty of the unintended outcome, although contextually indicative, should not determine the epistemic value of a report. Details about the context that generated an unexpected outcome, instead, can offer the chance of improving causal understanding about how the intervention works. This is illustrated through examples from medical research. Mechanistic understanding is a domain of joint collaboration among (1) clinicians, in charge of detailed, qualitative reporting of patient stories about side effects, (2) qualitative clinical researchers, in charge of analyzing clinical contexts or harmful effects and formulating explanatory hypotheses, and (3) basic biomedical researchers, in charge of verifying such hypotheses. In addition, direct information flow can on one side focus clinicians' attention on knowledge gaps about drugs/effects where more research is needed, while on the other side create a more contextualized concept of mechanism among scientists. © 2016 John Wiley & Sons, Ltd.

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.

Neurotoxicity Associated with Platinum-Based Anti-Cancer Agents: What are the Implications of Copper Transporters?

PubMed

Stojanovska, Vanesa; McQuade, Rachel; Rybalka, Emma; Nurgali, Kulmira

2017-01-01

Platinum-based anti-cancer agents, which include cisplatin, carboplatin and oxaliplatin, are an important class of drugs used in clinical setting to treat a variety of cancers. The cytotoxic efficacy of these drugs is mediated by the formation of inter-strand and intrastrand crosslinks, or platinum adducts on nuclear DNA. There is also evidence demonstrating that mitochondrial DNA is susceptible to platinum-adduct damage in dorsal root ganglia neurons. Although all platinum-based agents form similar DNA adducts, they are quite different in terms of activation, systemic toxicity and tolerance. Platinum-based agents are well known for their neurotoxicity and gastrointestinal side-effects which are major causes for dose limitation and treatment discontinuation compromising the efficacy of anti-cancer treatment. Accumulating evidence in non-neuronal cells shows that the copper transport system is associated with platinum drug sensitivity and resistance. There is minimal research concerning the role of copper transporters within the central and peripheral nervous systems. It is unclear whether neurons are more sensitive to platinum-based drugs, are insufficient in drug clearance, or whether platinum accumulation affects intracellular copper status and coppermediated functions. Understanding these mechanisms is important as neurotoxicity is the predominant side-effect of platinum-based chemotherapy. This review highlights the role of copper transpor ters in drug influx, differences in drug activation and side-effects caused by platinum-based agents, as well as their association with central and peripheral neuropathies and gastrointestinal toxicities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Patient Preferences for Pain Management in Advanced Cancer: Results from a Discrete Choice Experiment.

PubMed

Meads, David M; O'Dwyer, John L; Hulme, Claire T; Chintakayala, Phani; Vinall-Collier, Karen; Bennett, Michael I

2017-10-01

Pain from advanced cancer remains prevalent, severe and often under-treated. The aim of this study was to conduct a discrete choice experiment with patients to understand their preferences for pain management services and inform service development. Focus groups were used to develop the attributes and levels of the discrete choice experiment. The attributes were: waiting time, type of healthcare professional, out-of-pocket costs, side-effect control, quality of communication, quality of information and pain control. Patients completed the discrete choice experiment along with clinical and health-related quality of life questions. Conditional and mixed logit models were used to analyse the data. Patients with cancer pain (n = 221) and within palliative care services completed the survey (45% were female, mean age 64.6 years; age range 21-92 years). The most important aspects of pain management were: good pain control, zero out-of-pocket costs and good side-effect control. Poor or moderate pain control and £30 costs drew the highest negative preferences. Respondents preferred control of side effects and provision of better information and communication, over access to certain healthcare professionals. Those with lower health-related quality of life were less willing to wait for treatment and willing to incur higher costs. The presence of a carer influenced preferences. Outcome attributes were more important than process attributes but the latter were still valued. Thus, supporting self-management, for example by providing better information on pain may be a worthwhile endeavour. However, service provision may need to account for individual characteristics given the heterogeneity in preferences.

Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology.

PubMed

Eschenhagen, Thomas; Force, Thomas; Ewer, Michael S; de Keulenaer, Gilles W; Suter, Thomas M; Anker, Stefan D; Avkiran, Metin; de Azambuja, Evandro; Balligand, Jean-Luc; Brutsaert, Dirk L; Condorelli, Gianluigi; Hansen, Arne; Heymans, Stephane; Hill, Joseph A; Hirsch, Emilio; Hilfiker-Kleiner, Denise; Janssens, Stefan; de Jong, Steven; Neubauer, Gitte; Pieske, Burkert; Ponikowski, Piotr; Pirmohamed, Munir; Rauchhaus, Mathias; Sawyer, Douglas; Sugden, Peter H; Wojta, Johann; Zannad, Faiez; Shah, Ajay M

2011-01-01

The reductions in mortality and morbidity being achieved among cancer patients with current therapies represent a major achievement. However, given their mechanisms of action, many anti-cancer agents may have significant potential for cardiovascular side effects, including the induction of heart failure. The magnitude of this problem remains unclear and is not readily apparent from current clinical trials of emerging targeted agents, which generally under-represent older patients and those with significant co-morbidities. The risk of adverse events may also increase when novel agents, which frequently modulate survival pathways, are used in combination with each other or with other conventional cytotoxic chemotherapeutics. The extent to which survival and growth pathways in the tumour cell (which we seek to inhibit) coincide with those in cardiovascular cells (which we seek to preserve) is an open question but one that will become ever more important with the development of new cancer therapies that target intracellular signalling pathways. It remains unclear whether potential cardiovascular problems can be predicted from analyses of such basic signalling mechanisms and what pre-clinical evaluation should be undertaken. The screening of patients, optimization of therapeutic schemes, monitoring of cardiovascular function during treatment, and the management of cardiovascular side effects are likely to become increasingly important in cancer patients. This paper summarizes the deliberations of a cross-disciplinary workshop organized by the Heart Failure Association of the European Society of Cardiology (held in Brussels in May 2009), which brought together clinicians working in cardiology and oncology and those involved in basic, translational, and pharmaceutical science.

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.

Neuroprotective Effects of Drug-Induced Therapeutic Hypothermia in Central Nervous System Diseases.

PubMed

Ma, Junwei; Wang, Yibin; Wang, Zhong; Li, Haiying; Wang, Zhimin; Chen, Gang

2017-01-01

This review article focuses on the neuroprotective effect of drug-induced hypothermia in cerebrovascular diseases and discusses its related side effects. A systematic literature search was performed using Pubmed and Embase electronic databases for a retrospective analysis. Experimental studies have shown that drug-induced hypothermia alleviates brain damage and plays a neuroprotective role, thereby reducing mortality and ameliorating neurological deficits. Therefore, drug-induced hypothermia has an important research value and is worth further consideration in the clinical setting. However, drug-induced hypothermia is also associated with side effects, such as ventricular tachycardia, ventricular fibrillation, suppressed immune function, infection, electrolyte imbalance, glucose metabolism disorders, and skeletal muscle tremor. Existing drugs with cooling effects belong to the following categories: (1) dopamine receptor agonists; (2) cannabis; (3) opioid receptors; (4) vanilloid receptors; (5) vasopressins (potent neurotensin receptor agonists); (6) thyroid drugs; (7) adenosine drugs; and (8) purine drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Hypercholesterolemia: a look at low-cost treatment and treatment adherence.

PubMed

Flannery, J; Raulerson, A

2000-11-01

To determine whether a positive cholesterol-lowering effect could be achieved with a psyllium dose of 6 grams per day instead of the usual 10 grams per day as advocated by other researchers. Randomized trial of 46 males and females with hypercholesterolemia; multivariate analysis of variance with repeated measures on 1 factor done on 28 subjects (18 in treatment group, 10 in control group) remaining after 16 weeks of treatment. Lipoprotein analysis at 2, 8, and 16 weeks indicated that a daily dose of 6 grams of psyllium hydrophilic mucilloid did not significantly affect serum total cholesterol nor low-density lipoproteins in either men or women with hypercholesterolemia. The effects of psyllium on hypercholesterolemia appear to be dose dependent. Although it is a low cost option, the addition of psyllium to the diet has unpleasant side-effects, including abdominal distention, flatulence, and discomfort. Because these side effects are troublesome, the lowest effective dose of psyllium may be an important factor in improving treatment adherence.

Applications of XRF, NAA and low-kV radiographic techniques in the study of body composition and diseased tissue

NASA Astrophysics Data System (ADS)

Bradley, D. A.; Ng, K. H.; Green, S.; Mountford, P. J.; Shukri, A.; Evans, J.

1996-05-01

Members of this group have responded to a number of challenging health issues by attempting to devise sensitive XRF, NAA and low-kV radiographic measurement systems foboth in vivo and in vitro applications. These studies are generally either of toxicological importance, examine potential for diagnosing the presence of disease, or offer effective means for monitoring potentially harmful side-effects of therapy. Particular examples include the in vivo XRF investigation of human skeletal uptake of Pb in working and living environments, in vivo XRF monitoring of elevated levels of Fe in skin (indicating the presence of an undesirable side-effect of the treatment of thalassaemia), in vivo NAA monitoring of elevated levels of Al in bone (indicating an undesirable side-effect of the treatment of chronic renal failure) and in vitro characterization, by means of low-kV imaging, of a range of calcification parameters in healthy and diseased breast tissue. The latter investigation has been conducted in association with an in vitro NAA study of concentrations of trace elements in the same types of tissue. Figures of merit for the various measurement systems have been obtained in terms of minimum detectable levels and concentrations (MDL's and MDC's) and where applicable, image related parameters.

Potential of Eucalyptus Oil as Repellent against House Rat, Rattus rattus

PubMed Central

Thind, Ramandeep Kaur; Mahal, Amrit Kaur

2014-01-01

Rodent repellents are chemicals which by taste or odour or possibly by both will prevent animal from feeding or gnawing. Such substances may be used in protecting an area from rodent infestation or in protecting packaged food, packing materials, electric cables, and other important vulnerable materials. Mature and healthy house rat, Rattus rattus of both sexes, was exposed to 5, 10, and 20% eucalyptus oil applied as spray in laboratory pens in bichoice tests. Each concentration was applied through three different modes of application, that is, daily, once, and alternatively in a week. Repellent effect of the oil was assessed based on food consumption from treated and untreated sides for four days. In overall, food consumption was significantly (P < 0.0001) low from treatment side compared to the untreated side indicating significant repellent effect of the oil at all the three concentrations tested. Repellent effect of the oil was, however, not found to differ significantly between the two sexes. Percent repellency in both male and female rats was apparently more with daily application of 5 and 10% eucalyptus oil. Present studies reveal the potential of eucalyptus oil in repelling away R. rattus; however, further studies may be conducted to enhance the persistence of repellent effect for longer period of time. PMID:24523633

Continuous subcutaneous infusion of lidocaine for persistent hiccup in advanced cancer.

PubMed

Kaneishi, Keisuke; Kawabata, Masahiro

2013-03-01

Persistent hiccup can cause anorexia, weight loss, disabling sleep deprivation, anxiety, and depression. Therefore, relief of persistent hiccup is important for advanced cancer patients and their family. Most reports on this condition are case series reports advocating the use of baclofen, haloperidol, gabapentin, and midazolam. However, these medications are occasionally ineffective or accompanied by intolerable side effects. The sodium channel blocker lidocaine has been shown to be effective in treating a variety of disorders thought to involve neuropathic mechanisms. Intravenous administration of lidocaine is common but efficacy has also been reported for subcutaneous infusion. In advanced cancer patients, subcutaneous infusion is easy, advantageous, and accompanied by less discomfort. We report a case of severe and sustained hiccup caused by gastric cancer that was successfully treated with a continuous subcutaneous infusion of lidocaine (480 mg (24 ml)/day) without severe side effects.

Patient communication in hormone therapy.

PubMed

Schnare, S M

2001-01-01

Common regimens of HRT therapy are reviewed, including common routes of hormone administration. Inconsistent patterns of HRT use are discussed, including the reasons women most often give for discontinuing hormone therapies. Specific issues related to misperceptions and fears regarding HRT are clarified, and specific, focused patient education formats are discussed to address women's common concerns about HRT. Obstacles to HRT use are elucidated, with suggestions for clinicians about how to communicate more effectively with women: clinicians must focus on emotional and physical aspects of HRT choices and tailor therapies to the individual patient. Discussing frankly the very serious concerns of women regarding the association between lobular breast cancer and endometrial cancer is important; discussing and preparing women for possible side effects helps patients cope better if and when side effects occur. Finally, offering a wide variety of HRT therapies provides women with a broader choice if an initial regimen is unsuccessful.

Facing the challenges of new melanoma-targeted therapies: Treatment of severe fevers associated with dabrafenib/trametinib combination therapy.

PubMed

Lindsay, Julian N; Barras, Michael

2015-08-01

With the emergence of new oral therapies for metastatic melanoma to the market, as well as ongoing pre-marketing trials and special access schemes, it is important to keep up to date with the side effect profiles of these medications. A common side effect associated with the BRAF inhibitor dabrafenib is severe fever symptoms such as pyrexia and rigors/chills; however, treatment options are limited. We report a patient who was debilitated by severe pyrexia and rigors caused by dabrafenib used in combination with trametinib to treat metastatic melanoma, who was treated with low-dose steroids. To our knowledge, the use of prednisolone for the treatment and prevention of further dabrafenib-associated pyrexia is not published; however, it is a low risk and low cost option that was very effective in this case. © The Author(s) 2014.

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.

[Interaction of opioid analgesics at the level of biotransformation].

PubMed

Petri, H; Grandt, D

2016-12-01

Opioids are an important component of the drug treatment of patients with acute and chronic pain. They differ in effectiveness, side effect profile and the risk of interactions. In this article the pharmacokinetic mechanisms of drug-drug interactions at the level of biotransformation are described and the clinical consequences which can arise are discussed. The relation of the active components to the two isoenzymes CYP2D6 and CYP3A4 is of major importance for assessing the potential drug-drug interactions of opioid analgesics at the level of the cytochrome P450 enzyme.

[Diagnosis and therapy of gigantism].

PubMed

Sorgo, W; Teller, W M

1987-01-01

Some of the most important types of nonfamilial tall stature are discussed by stressing the clinical features, diagnostic aspects and therapeutic possibilities. The indications of treatment, the diagnostic procedures and steroid therapy of the familial type of tall stature, the predominant variant of tall stature, are presented in detail. The effects, side effects and contraindications of high dose steroid treatment are described. The important prerequisite for the evaluation of psychosomatic problems of tall stature is the understanding of the dynamics and variations of normal growth. This and the knowledge of methods concerning growth analyses continue to be the basis of an accurate diagnosis.

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.

[Customization of hormonal contraception].

PubMed

DE Leo, Vincenzo; Cianci, Antonio; DI Carlo, Costantino; Cappelli, Valentina; Fruzzetti, Franca

2018-02-01

In the last few years new oral contraceptives have been marketed showing a better safety profile for women. They are the result of important changes made to the old compounds. As far as the estrogenic component, with the aim of decreasing side effects, the dose of ethinyl estradiol has been reduced and synthetic estrogens have been replaced by natural estradiol, further improving the safety profile. Also the progestin component in the last years has been changed in terms of dose, endocrine and metabolic characteristics. Levonorgestrel is an androgenic progestin, but now there is the possibility of choosing progestins without androgenic effect (gestodene and desogestrel) or progestins with antiandrogenic effect (cyproterone acetate, dienogest, drospirenone, chlormadinone acetate), very useful in patients with hyperandrogenism. Some of these progestins, like Drospirenone, represented the real held contributing, because of its antimineralcorticoid action, to reduce an important side effect like fluid retention; moreover there is the possibility to choose products with high progestogen effect on endometrium (dienogest, nomegestrole acetate), resulting very effective in women with abnormal uterine bleedings. Also the regimens of administration have been changed, by shortening or eliminating the tablet-free period; in this way the women may avoid premenstrual symptoms. The oral is not the only route of administration, but today there are alternative routes like transdermal, transvaginal, intrauterine and subcutaneous, reducing gastro-intestinal interferences and possible mistakes in pill intake.

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.

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.

[How useful is physical therapy in old age?].

PubMed

Brenke, Rainer

2016-03-01

Physical therapy is the most important element of naturopathy. In old age conditions accumulate that can be readily treated with physical therapy. It is possible to save on simultaneous drug treatment, and the risk of side effects can be reduced. The prescription of physical therapy in old age should not be regarded as restrictive.

What Works May Hurt: Side Effects in Education

ERIC Educational Resources Information Center

Zhao, Yong

2017-01-01

Medical research is held as a field for education to emulate. Education researchers have been urged to adopt randomized controlled trials, a more "scientific" research method believed to have resulted in the advances in medicine. But a much more important lesson education needs to borrow from medicine has been ignored. That is the study…

Profiling primaquine metabolites in primary human hepatocytes by UPLC-QTOF-MS with 13c stable isotope labeling

USDA-ARS?s Scientific Manuscript database

Primaquine (PQ) is an important antimalarial agent because of its activity against exoerythrocytic forms of Plasmodium spp. However, hemolytic anemia is a dose-limiting side effect of primaquine therapy that limits its widespread use. The major plasma metabolite identified in humans and animals, car...

Student and Teacher Perception of Disciplinary Practices: Types, Reasons, Consequences and Alternatives

ERIC Educational Resources Information Center

Mumthas, N. S.; Munavvir, Jouhar; Abdul Gafoor, K.

2014-01-01

Inculcating self-discipline is important for systematic pursuit of learning, development of interest and potential in the child. Punishments involve employing a noxious or painful stimulus that generates a variety of problems and negative side effects to the child. Corporal punishments severely affect the human dignity of children. This study…

Understanding the side effects of classical biological control

Treesearch

Dean Pearson

2008-01-01

Classical biological control involves the use of imported natural enemies to suppress or control populations of the target pest species below an economically or ecologically relevant threshold. Biological control is a useful tool for mitigating the impacts of exotic invasive plants; however, its application is not without risk (see Carruthers and D’Antonio...

[Current guidelines for prevention and management of chemotherapy extravasation].

PubMed

Bahyrycz, Jan; Pityński, Kazimierz; Ludwin, Artur; Ludwin, Inga; Gawlik, Małgorzata

2012-01-01

Cytostatic drugs extravasation is the serious side effect of chemotherapy. It may lead to health-threatening complications as well as to impairment of cancer patients quality of life. Prevention, early diagnosis and appropriate treatment significantly reduce the consequences of extravasation. Training of medical staff and patients education have enormous importance on this point.

The ins and outs of caulking

Treesearch

Charles Carll

2006-01-01

Effective water management involves understanding the roles of siding, trim, fenestration units, flashing, and (where appropriate) caulk seals and how these entities interface with each other. Where caulk seals are used, their geometry and dimensions are important to joint performance, as is the care with which they are executed. In selection of caulking material,...

Is the treatment worse than the cure? Attitudes toward medications among persons with severe mental illness.

PubMed

Van Dongen, C J

1997-03-01

1. Patients' attitudes toward taking long-term psychotropic medications and factors that may influence drug attitudes are important factors in compliance. 2. Patients in this study had generally positive drug attitudes and perceived their medications as important in preventing relapse. 3. Attitudes toward psychotropic medications may be more positive than has been assumed by mental health professionals, as patients seem to realize that the advantages of medications outweight side effects.

Effects of 1,540-nm Fractional Nonablative Erbium and 2,940-nm Fractional Ablative Erbium on p53 Epidermal Expression After 3 months: A Split-Face Interventional Study.

PubMed

Borges, Juliano; Araújo, Luciana; de Oliveira, Rodrigo P B; Manela-Azulay, Monica

2018-04-16

Expression of p53 by keratinocytes may be important in the pathogenesis of skin cancer induced by ultraviolet light. We used side-by-side nonablative and ablative erbium fractional laser resurfacing to assess the effects on expression of p53 by facial keratinocytes. Ten female patients (age range, 50-63 years) with Fitzpatrick skin Types I-IV and clinical signs of photoaging underwent erbium fractional laser resurfacing (nonablative, 1,540-nm; ablative, 2,940-nm) on opposite sides of the face. Skin biopsies were obtained before treatment and 3 months after treatment for comparison with control biopsies of face and inner arm, quantifying p53 in immunostained tissue sections. Only ablative (2,940-nm) treatments produced a statistically significant reduction in p53 scoring after 3 months. The histologic appearance of skin after ablative resurfacing more closely resembled inner arm skin (rather than facial skin) of control subjects. Epidermal repopulation with p53-negative keratinocytes through ablative erbium fractional laser resurfacing may diminish the risk of eventual malignancy in photoaged skin.

What Are the Definitive Procedures and Instruments Used to Incorporate Chemotherapy Orientation and Preparation for Effective Team Membership, During Inservice and Preservice Training of Teachers and Administrators?

ERIC Educational Resources Information Center

Schwenn, John O.

An administrator discusses aspects of drug therapy with which special educators should be familiar. Briefly examined are administration form, factors affecting rate of absorption, dosage, interaction of one drug with another, drug tolerance, time factors, and side effects. The importance of a teacher's monitoring of the drugs is stressed, and…

Demonstration of hetero-gate-dielectric tunneling field-effect transistors (HG TFETs).

PubMed

Choi, Woo Young; Lee, Hyun Kook

2016-01-01

The steady scaling-down of semiconductor device for improving performance has been the most important issue among researchers. Recently, as low-power consumption becomes one of the most important requirements, there have been many researches about novel devices for low-power consumption. Though scaling supply voltage is the most effective way for low-power consumption, performance degradation is occurred for metal-oxide-semiconductor field-effect transistors (MOSFETs) when supply voltage is reduced because subthreshold swing (SS) of MOSFETs cannot be lower than 60 mV/dec. Thus, in this thesis, hetero-gate-dielectric tunneling field-effect transistors (HG TFETs) are investigated as one of the most promising alternatives to MOSFETs. By replacing source-side gate insulator with a high- k material, HG TFETs show higher on-current, suppressed ambipolar current and lower SS than conventional TFETs. Device design optimization through simulation was performed and fabrication based on simulation demonstrated that performance of HG TFETs were better than that of conventional TFETs. Especially, enlargement of gate insulator thickness while etching gate insulator at the source side was improved by introducing HF vapor etch process. In addition, the proposed HG TFETs showed higher performance than our previous results by changing structure of sidewall spacer by high- k etching process.

High-Temperature Nucleosynthesis Processes on the Proton-Rich Side of Stability: the Alpha-Rich Freezeout and the rp^2-Process

NASA Astrophysics Data System (ADS)

Meyer, Bradley S.

2001-10-01

Nucleosynthesis on the proton-rich side of stability has at least two intriguing aspects. First, the most abundant of the stable iron-group isotopes, such as ^48Ti, ^52Cr, and ^56,57Fe, are synthesized as proton-rich, radioactive parents in alpha-rich freezeouts from equilibrium. The production of these radioactive progenitors depends in large measure on reactions on the proton-rich side of stability. The second intriguing aspect is that explosive nucleosynthesis in a hydrogen-rich environment (namely, the rp-process) may be associated with exotic astrophysical settings, such as x-ray bursts, and may be responsible for production of some of the light p-process nuclei (for example, ^92,94Mo and ^96,98Ru). We have developed web-based tools to help nuclear physicists determine which nuclear reactions on the proton-rich side of stability govern the nucleosynthesis in these processes. For the alpha-rich freezeout, one may determine the effect of any one of 2,140 reactions on the yield of any isotope in the nuclear reaction network with the web calculator. As a relevant example, I will discuss the governing role of ^57Ni (n,p)^57Co in the synthesis of the important astronomical observable ^57Co. As for explosive, proton-rich burning, I will discuss the synthesis of p-process nuclei in the repetitive rp-process (the rp^2-process). Movies of the rp^2-process illustrate its important features and give some indications of the important nuclear reactions.

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

Impact direction effect on serious-to-fatal injuries among drivers in near-side collisions according to impact location: focus on thoracic injuries.

PubMed

Lai, Xinghua; Ma, Chunsheng; Hu, Jingwen; Zhou, Qing

2012-09-01

Occupant injury in real world vehicle accidents can be significantly affected by a set of crash characteristics, of which impact direction and impact location (or damage location) in general scale interval (e.g., frontal impact is frequently defined as general damage to vehicle frontal end with impact angle range of 11-1 o'clock) have been identified to associate with injury outcome. The effects of crash configuration in more specific scale of interval on the injury characteristics have not been adequately investigated. This paper presents a statistical analysis to investigate the combined effects of specific impact directions and impact locations on the serious-to-fatal injuries of driver occupants involved in near-side collisions using crash data from National Automotive Sampling System-Crashworthiness Data System (NASS-CDS) for the calendar years of 1995-2005. The screened injury dataset is categorized by three impact locations (side front, side center and side distributed) and two impact directions (oblique impact at 10 o'clock and pure lateral impact at 9 o'clock), resulting in six crash configurations in total. The weighted counts and the risks of different types of injuries in each subgroup are calculated, with which the relative risks along with 95% confidence intervals under oblique impacts versus lateral impacts in each impact location category are computed. Accordingly, the most frequent injury patterns, the risks and the coded-sources of serious thoracic injuries in different crash configurations are identified. The approach adopted in the present study provides new perspectives into occupant injury outcomes and associated mechanism. Results of the analyses reveal the importance of consideration of the crash configurations beyond the scope of existing side-impact regulatory tests and stress the necessity of vehicle crashworthiness and restraint system design in omni-direction to better protect occupants in real-world crash scenarios. Copyright © 2012 Elsevier Ltd. All rights reserved.

Role of chiral quantum Hall edge states in nuclear spin polarization.

PubMed

Yang, Kaifeng; Nagase, Katsumi; Hirayama, Yoshiro; Mishima, Tetsuya D; Santos, Michael B; Liu, Hongwu

2017-04-20

Resistively detected NMR (RDNMR) based on dynamic nuclear polarization (DNP) in a quantum Hall ferromagnet (QHF) is a highly sensitive method for the discovery of fascinating quantum Hall phases; however, the mechanism of this DNP and, in particular, the role of quantum Hall edge states in it are unclear. Here we demonstrate the important but previously unrecognized effect of chiral edge modes on the nuclear spin polarization. A side-by-side comparison of the RDNMR signals from Hall bar and Corbino disk configurations allows us to distinguish the contributions of bulk and edge states to DNP in QHF. The unidirectional current flow along chiral edge states makes the polarization robust to thermal fluctuations at high temperatures and makes it possible to observe a reciprocity principle of the RDNMR response. These findings help us better understand complex NMR responses in QHF, which has important implications for the development of RDNMR techniques.

Patient’s Knowledge and Perception Towards the use of Non-steroidal Anti-Inflammatory Drugs in Rheumatology Clinic Northern Malaysia

PubMed Central

Sulaiman, Wahinuddin; Seung, Ong Ping; Ismail, Rosli

2012-01-01

Objective In Rheumatology, non-steroidal anti-inflammatory drugs (NSAIDs) has been widely prescribed and used. However, despite their clinical benefits in the management of inflammatory and degenerative joint disease, NSAIDs have considerable side effects, mostly affecting the upper gastrointestinal system, which therefore, limit their use. This study was conducted to determine the patients’ knowledge and perception regarding the used of NSAIDS. Methods A total of 120 patients who attended the rheumatology clinic Hospital, Raja Permaisuri Bainun, Malaysia, and received NSAIDs more than 3 months were interviewed irrespective of their rheumatological conditions. Patient’s knowledge and perception on the side effects of NSAIDs were recorded. Result Fifty-four percent of the patients obtained information regarding the side effect of NSAIDs either from the rheumatologist, rheumatology staff nurse or other medical staffs (75.4%). The remaining 45.8% were naive of such knowledge. Fifteen percent obtained the information by surfing the internet and 9.2% from printed media. Twenty-four (24.2%) patients, experienced indigestion and/or stomach discomfort attributed to NSAIDs used. Two patients (1.7%) had hematemesis and malena once. Conclusion This study shows that half of the patients who attended the rheumatology clinic were unaware of the side effect of NSAIDs. Available data showed that most of the knowledgeable patients are more conscience and self-educated. This study also reveals the important roles of clinicians, trained staff nurses as well as the pharmacist in providing the guidance and knowledge of any medication taken by patients. PMID:23226825

Informing hot flash treatment decisions for breast cancer survivors: a systematic review of randomized trials comparing active interventions.

PubMed

Johns, Claire; Seav, Susan M; Dominick, Sally A; Gorman, Jessica R; Li, Hongying; Natarajan, Loki; Mao, Jun James; Irene Su, H

2016-04-01

Patient-centered decision making about hot flash treatments often incorporates a balance of efficacy and side effects in addition to patient preference. This systematic review examines randomized controlled trials (RCTs) comparing at least two non-hormonal hot flash treatments in breast cancer survivors. In July 2015, PubMed, SCOPUS, CINAHL, Cochrane, and Web of Science databases were searched for RCTs comparing active, non-hormonal hot flash treatments in female breast cancer survivors. Thirteen trials were included after identifying 906 potential studies. Four trials were dose comparison studies of pharmacologic treatments citalopram, venlafaxine, gabapentin, and paroxetine. Hot flash reduction did not differ by tamoxifen or aromatase inhibitor use. Citalopram 10, 20, and 30 mg daily had comparable outcomes. Venlafaxine 75 mg daily improved hot flashes without additional side effects from higher dosing. Gabapentin 900 mg daily improved hot flashes more than 300 mg. Paroxetine 10 mg daily had fewer side effects than 20 mg. Among four trials comparing different pharmacologic treatments, venlafaxine alleviated hot flash symptoms faster than clonidine; participants preferred venlafaxine over gabapentin. Five trials compared pharmacologic to non-pharmacologic treatments. Acupuncture had similar efficacy to venlafaxine and gabapentin but may have longer durability after completing treatment and fewer side effects. We could not perform a pooled meta-analysis because outcomes were not reported in comparable formats. Clinical trial data on non-hormonal hot flash treatments provide comparisons of hot flash efficacy and other patient important outcomes to guide clinical management. Clinicians can use the information to help patients select hot flash interventions.

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.

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

The side-effects to CPAP treatment inventory: the development and initial validation of a new tool for the measurement of side-effects to CPAP treatment.

PubMed

Broström, Anders; Arestedt, Kristofer Franzén; Nilsen, Per; Strömberg, Anna; Ulander, Martin; Svanborg, Eva

2010-12-01

Continuous positive airway pressure (CPAP) is the treatment of choice for obstructive sleep apnoea syndrome (OSAS), but side-effects are common. No validated self-rating scale measuring side-effects to CPAP treatment exists today. The aim was to develop the side-effects to CPAP treatment inventory (SECI), and investigate the validity and reliability of the instrument among patients with OSAS. SECI was developed on the basis of: (1) in-depth interviews with 23 patients; (2) examination of the scientific literature and (3) consensus agreement of a multi-professional expert panel. This yielded 15 different types of side-effects related to CPAP treatment. Each side-effect has three sub-questions (scales): perceived frequency (a) and magnitude (b) of the side-effect, as well as its perceived impact on CPAP use (c). A cross-sectional descriptive design was used. A total of 329 patients with OSAS with an average use of CPAP treatment for 39 months (2 weeks to 182 months) were recruited. Data were collected with SECI, and obtained from medical records (clinical variables and data related to CPAP treatment). Construct validity was confirmed with factor analysis (principal component analysis with orthogonal rotation). A logical two-factor solution, the device subscale and symptom subscale, emerged across all three scales. The symptom subscale describing physical and psychological side-effects and the device subscale described mask and device-related side-effects. Internal consistency reliability of the three scales was good (Cronbach's α = 0.74-0.86) and acceptable for the subscales (Cronbach's α = 0.62-0.86). The satisfactory measurement properties of this new instrument are promising and indicate that SECI can be used to measure side-effects to CPAP treatment. © 2010 European Sleep Research Society.

Sparse networks of directly coupled, polymorphic, and functional side chains in allosteric proteins.

PubMed

Soltan Ghoraie, Laleh; Burkowski, Forbes; Zhu, Mu

2015-03-01

Recent studies have highlighted the role of coupled side-chain fluctuations alone in the allosteric behavior of proteins. Moreover, examination of X-ray crystallography data has recently revealed new information about the prevalence of alternate side-chain conformations (conformational polymorphism), and attempts have been made to uncover the hidden alternate conformations from X-ray data. Hence, new computational approaches are required that consider the polymorphic nature of the side chains, and incorporate the effects of this phenomenon in the study of information transmission and functional interactions of residues in a molecule. These studies can provide a more accurate understanding of the allosteric behavior. In this article, we first present a novel approach to generate an ensemble of conformations and an efficient computational method to extract direct couplings of side chains in allosteric proteins, and provide sparse network representations of the couplings. We take the side-chain conformational polymorphism into account, and show that by studying the intrinsic dynamics of an inactive structure, we are able to construct a network of functionally crucial residues. Second, we show that the proposed method is capable of providing a magnified view of the coupled and conformationally polymorphic residues. This model reveals couplings between the alternate conformations of a coupled residue pair. To the best of our knowledge, this is the first computational method for extracting networks of side chains' alternate conformations. Such networks help in providing a detailed image of side-chain dynamics in functionally important and conformationally polymorphic sites, such as binding and/or allosteric sites. © 2014 Wiley Periodicals, Inc.

Lost in laterality: interpreting ''preferred side of the head during mobile phone use and risk of brain tumour'' associations.

PubMed

Schüz, Joachim

2009-08-01

Due to the highly localized exposure from mobile phones, the preferred side of the head during their use is important information when investigating a possible link with brain tumour risk, but at the same time, error and bias hamper the assessment of this information in case-control studies. Current studies provide evidence of reporting bias insofar as cases appear to over-report the side of the head where the tumour occurred as the one that they preferred in the past when using mobile phones. More refined methods of analysis among only cases or prospective studies with an assessment of the laterality of mobile phone use before the diagnosis of disease are needed to evaluate whether associations seen in some studies are entirely due to reporting bias or a mixture of reporting bias and a causal effect.

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.

Effects of planar and non-planar driver-side mirrors on age-related discomfort-glare responses

PubMed Central

Lockhart, Thurmon E.; Atsumi, Bunji; Ghosh, Arka; Mekaroonreung, Haruetai; Spaulding, Jeremy

2010-01-01

In this study, we evaluated subjective nighttime discomfort-glare responses on three different types of planar and non-planar driver-side mirrors on two age groups. Fifty-six individuals (28 young [18–35 years] and 28 old [65 years and over]) participated in this experiment. Subjective discomfort-glare rating scores on three different types of driver-side mirrors were assessed utilizing De Boer's rating scale in a controlled nighttime driving environment (laboratory ambient illuminant level—l lux with headlight turned off). Three driver-side mirrors included planar “flat mirror”: radius of curvature 242650.92 mm, reflectivity 0.60114, and surface reflectance 0.60568; “curved mirror”: radius of curvature 1433.3 mm, reflectivity 0.21652, and surface reflectance 0.58092; “blue mirror”: radius of curvature 1957.1 mm, reflectivity 0.25356, and surface reflectance 0.54585. The results indicated that with the same glare level (as measured by angle of incidence and illuminance in front of the eyes), older adults reported worse feelings of glare than their younger counterparts. Furthermore, the results indicated that both young and older adults reported worse feelings of glare for planar driver-side mirror than non-planar driver-side mirrors. These results suggest that older adults' criterion of discomfort-glare is more sensitive than their younger counterparts, and importantly, the non-planar driver-side mirrors can be beneficial in terms of reducing nighttime discomfort-glare for both the young and the elderly. PMID:20582252

[Questionnaire-based study on the key to the guidance to the patients with atopic dermatitis by pharmacist].

PubMed

Kaneko, Sakae; Kakamu, Takeyasu; Matsuo, Hiroaki; Naora, Koji; Morita, Eishin

2014-11-01

Atopic dermatitis is a condition with a chronic or recurrent course that requires continued treatment, meaning that patients must be provided with instructions that fit their lifestyle. Surveys of doctors and patients have revealed the importance of instructions on how to apply topical medication. Here we conducted a survey of the instructions provided by pharmacists, who play an important role in educating patients on how to apply topical medication. Questionnaires were distributed to clinics and dispensing pharmacies in Shimane and Hiroshima prefectures. The questionnaire format comprised selecting each matter on which instructions are provided. A total of 548 questionnaires (response rate, 13.8%) were collected and analyzed. Concerning topical steroids, the most frequently instructed item was "Explanation of application site"(86%), followed by "Explanation of number and timing of applications"(68%). Only 45% chose "Instruction to apply a small amount to avoid side effects." For tacrolimus ointment, "Explanation of tingling sensation"(as a side effect) was the most frequently selected item (52%), and "Instruction by using a brochure"(27.3%) was more commonly selected for tacrolimus ointment than for steroids and emollients. "Demonstrate the application method by means of actual application" was selected by few respondents for any topical medication. Regarding what they wanted from doctors, many respondents wrote in the section for their own comments that they would like a clear description of the method of use and dose and indications of the amount to be applied. Failure included times when patients failed to apply medication correctly due to inadequate instructions and an insufficient explanation of side effects. Instructions vary among patients and professions, but good instructions lead to good results. Cross-tabulation showed that pharmacists who are aware of the guidelines of atopic dermatitis offer significantly more instructions in a range of areas, suggesting that the first important task is to spread awareness of these guidelines among them.

Preferred characteristics of vaginal microbicides in women with bacterial vaginosis.

PubMed

Cook, Robert L; Downs, Julie S; Marrazzo, Jeanne; Switzer, Galen E; Tanriover, Ozlem; Wiesenfeld, Harold; Murray, Pamela J; Hillier, Sharon L

2009-08-01

Vaginal microbicides have the potential to reduce HIV/STD acquisition when used consistently. Our objectives were to determine product attributes associated with willingness to use a vaginal microbicide and whether product preferences varied according to participant characteristics. Women (n = 408) with bacterial vaginosis (BV) were recruited as part of a randomized trial to prevent BV. Participants completed a survey interview that assessed demographic information, sexual history, and douching behavior. To assess microbicide preferences, women rated whether specific product attributes would make them more or less likely to use a vaginal microbicide. Principal components analyses revealed two major groupings for the product attribute items. We determined the relative importance of each group of product attributes and whether the importance of the different groupings varied among subgroups of women. The participants' mean age was 24 years (range 14-45), 64% were black, and 74% were unmarried. Overall, participants reported being most likely to use a vaginal product with protection properties (2.54), whereas they were nearly neutral regarding side effects (0.56). The individual product attributes, could prevent BV, could prevent vaginal odor (2.72), and could prevent vaginal itching and burning (2.61), were rated similarly or slightly higher than could reduce the risk of getting an STD (2.58) or could reduce the risk of getting HIV (2.44). In multivariate analyses, protection attributes were rated significantly higher among older women and marginally higher in women with a greater number of lifetime sexual partners. Younger women were most likely to report that side effects would affect their likelihood of using the product. Women with BV rated potential protection features of a vaginal microbicide higher than side effects. A product's personal hygiene aspects were rated equally or more important than the product's ability to prevent HIV/STD infections. Younger women may respond to different factors that influence product acceptability and adherence.

Intravenous pamidronate versus oral and intravenous clodronate in bone metastatic breast cancer: a randomized, open-label, non-inferiority Phase III trial.

PubMed

von Au, Alexandra; Milloth, Eva; Diel, Ingo; Stefanovic, Stefan; Hennigs, Andre; Wallwiener, Markus; Heil, Joerg; Golatta, Michael; Rom, Joachim; Sohn, Christof; Schneeweiss, Andreas; Schuetz, Florian; Domschke, Christoph

2016-01-01

Patients with metastasized breast cancer often suffer from discomfort caused by metastatic bone disease. Thus, osteoprotection is an important part of therapy in breast cancer metastasized to bone, and bisphosphonates (BPs) are a major therapeutic option. In this study, our objectives were to compare the side effects of oral versus intravenous BP treatment and to assess their clinical effectiveness. In this prospective randomized, open-label, non-inferiority trial, we enrolled breast cancer patients with at least one bone metastasis and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomly assigned to one of the three treatment groups: A, 60 mg pamidronate intravenously q3w; B-iv, 900 mg clodronate intravenously q3w; and B-o, 2,400 mg oral clodronate daily. Assessments were performed at baseline and every 3 months thereafter. Between 1995 and 1999, 321 patients with confirmed bone metastases from breast cancer were included in the study. At first follow-up, gastrointestinal (GI) tract side effects were most common, and adverse effects on the GI tract were more frequent in the oral treatment group (P=0.002 and P<0.001, respectively). There were no statistically significant differences among the treatment cohorts for other documented side effects (skin, serum electrolytes, urinary tract, immune system, and others). No significant differences in clinical effectiveness of BP treatment, as assessed by pain score, were detected among the groups; however, pathologic fractures were more effectively prevented by intravenous than oral BP administration (P=0.03). Noncompliance rates were similar among the study cohorts. We conclude that oral BP treatment is significantly associated with higher rates of adverse GI side effects. Additionally, our data indicate that intravenous BP administration is more effective than oral treatment in prevention of pathologic fractures; hence, oral administration should be considered with caution.

The design of a simulated in-line side-coupled 6 MV linear accelerator waveguide.

PubMed

St Aubin, Joel; Steciw, Stephen; Fallone, B G

2010-02-01

The design of a 3D in-line side-coupled 6 MV linac waveguide for medical use is given, and the effect of the side-coupling and port irises on the radio frequency (RF), beam dynamics, and dosimetric solutions is examined. This work was motivated by our research on a linac-MR hybrid system, where accurate electron trajectory information for a clinical medical waveguide in the presence of an external magnetic field was needed. For this work, the design of the linac waveguide was generated using the finite element method. The design outlined here incorporates the necessary geometric changes needed to incorporate a full-end accelerating cavity with a single-coupling iris, a waveguide-cavity coupling port iris that allows power transfer into the waveguide from the magnetron, as well as a method to control the RF field magnitude within the first half accelerating cavity into which the electrons from the gun are injected. With the full waveguide designed to resonate at 2998.5 +/- 0.1 MHz, a full 3D RF field solution was obtained. The accuracy of the 3D RF field solution was estimated through a comparison of important linac parameters (Q factor, shunt impedance, transit time factor, and resonant frequency) calculated for one accelerating cavity with the benchmarked program SUPERFISH. It was found that the maximum difference between the 3D solution and SUPERFISH was less than 0.03%. The eigenvalue solver, which determines the resonant frequencies of the 3D side-coupled waveguide simulation, was shown to be highly accurate through a comparison with lumped circuit theory. Two different waveguide geometries were examined, one incorporating a 0.5 mm first side cavity shift and another with a 1.5 mm first side cavity shift. The asymmetrically placed side-coupling irises and the port iris for both models were shown to introduce asymmetries in the RF field large enough to cause a peak shift and skewing (center of gravity minus peak shift) of an initially cylindrically uniform electron beam accelerating within the waveguide. The shifting and skewing of the electron beam were found to be greatest due to the effects of the side-coupling irises on the RF field. A further Monte Carlo study showed that this effect translated into a 1% asymmetry in a 40 x 40 cm2 field dose profile. A full 3D design for an in-line side-coupled 6 MV linear accelerator that emulates a common commercial waveguide has been given. The effect of the side coupling on the dose distribution has been shown to create a slight asymmetry, but overall does not affect the clinical applicability of the linac. The 3D in-line side-coupled linac model further provides a tool for the investigation of linac performance within an external magnetic field, which exists in an integrated linac-MR system.

The Importance of Non Struck Side Occupants in Side Collisions

PubMed Central

Frampton, R. J.; Brown, R.; Thomas, P.; Fay, P.

1998-01-01

In a representative sample of tow-away side collisions from the UK Midlands, one third of front seat occupants were alone, on the struck side of the car. The other two thirds were either a non struck side occupant alone or two occupants sitting together. Occupant restraint, especially in perpendicular side impacts, was a notable factor in determining injury outcome for belted non struck side occupants. With both front seats occupied, there was a reduction in AIS 2+ injury to belted non struck side occupants due to a reduction in chest and lower limb injuries. Struck side occupants sustained increased injury rates to the extremities when accompanied by a belted non struck side occupant but no notable increases in moderate to serious injury to the head, chest, abdomen or pelvis.

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.

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.

Effects of demand-side financing on utilisation, experiences and outcomes of maternity care in low- and middle-income countries: a systematic review

PubMed Central

2014-01-01

Background Demand-side financing, where funds for specific services are channelled through, or to, prospective users, is now employed in health and education sectors in many low- and middle-income countries. This systematic review aimed to critically examine the evidence on application of this approach to promote maternal health in these settings. Five modes were considered: unconditional cash transfers, conditional cash transfers, short-term payments to offset costs of accessing maternity services, vouchers for maternity services, and vouchers for merit goods. We sought to assess the effects of these interventions on utilisation of maternity services and on maternal health outcomes and infant health, the situation of underprivileged women and the healthcare system. Methods The protocol aimed for collection and synthesis of a broad range of evidence from quantitative, qualitative and economic studies. Nineteen health and social policy databases, seven unpublished research databases and 27 websites were searched; with additional searches of Indian journals and websites. Studies were included if they examined demand-side financing interventions to increase consumption of services or goods intended to impact on maternal health, and met relevant quality criteria. Quality assessment, data extraction and analysis used Joanna Briggs Institute standardised tools and software. Outcomes of interest included maternal and infant mortality and morbidity, service utilisation, factors required for successful implementation, recipient and provider experiences, ethical issues, and cost-effectiveness. Findings on Effectiveness, Feasibility, Appropriateness and Meaningfulness were presented by narrative synthesis. Results Thirty-three quantitative studies, 46 qualitative studies, and four economic studies from 17 countries met the inclusion criteria. Evidence on unconditional cash transfers was scanty. Other demand-side financing modes were found to increase utilisation of maternal healthcare in the index pregnancy or uptake of related merit goods. Evidence of effects on maternal and infant mortality and morbidity outcomes was insufficient. Important implementation aspects include targeting and eligibility criteria, monitoring, respectful treatment of beneficiaries, suitable incentives for providers, quality of care and affordable referral systems. Conclusions Demand-side financing schemes can increase utilisation of maternity services, but attention must be paid to supply-side conditions, the fine-grain of implementation and sustainability. Comparative studies and research on health impact and cost-effectiveness are required. PMID:24438560

Effects of demand-side financing on utilisation, experiences and outcomes of maternity care in low- and middle-income countries: a systematic review.

PubMed

Murray, Susan F; Hunter, Benjamin M; Bisht, Ramila; Ensor, Tim; Bick, Debra

2014-01-17

Demand-side financing, where funds for specific services are channelled through, or to, prospective users, is now employed in health and education sectors in many low- and middle-income countries. This systematic review aimed to critically examine the evidence on application of this approach to promote maternal health in these settings. Five modes were considered: unconditional cash transfers, conditional cash transfers, short-term payments to offset costs of accessing maternity services, vouchers for maternity services, and vouchers for merit goods. We sought to assess the effects of these interventions on utilisation of maternity services and on maternal health outcomes and infant health, the situation of underprivileged women and the healthcare system. The protocol aimed for collection and synthesis of a broad range of evidence from quantitative, qualitative and economic studies. Nineteen health and social policy databases, seven unpublished research databases and 27 websites were searched; with additional searches of Indian journals and websites. Studies were included if they examined demand-side financing interventions to increase consumption of services or goods intended to impact on maternal health, and met relevant quality criteria. Quality assessment, data extraction and analysis used Joanna Briggs Institute standardised tools and software. Outcomes of interest included maternal and infant mortality and morbidity, service utilisation, factors required for successful implementation, recipient and provider experiences, ethical issues, and cost-effectiveness. Findings on Effectiveness, Feasibility, Appropriateness and Meaningfulness were presented by narrative synthesis. Thirty-three quantitative studies, 46 qualitative studies, and four economic studies from 17 countries met the inclusion criteria. Evidence on unconditional cash transfers was scanty. Other demand-side financing modes were found to increase utilisation of maternal healthcare in the index pregnancy or uptake of related merit goods. Evidence of effects on maternal and infant mortality and morbidity outcomes was insufficient. Important implementation aspects include targeting and eligibility criteria, monitoring, respectful treatment of beneficiaries, suitable incentives for providers, quality of care and affordable referral systems. Demand-side financing schemes can increase utilisation of maternity services, but attention must be paid to supply-side conditions, the fine-grain of implementation and sustainability. Comparative studies and research on health impact and cost-effectiveness are required.

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.

Erythropoietin as an add-on treatment for cognitive side effects of electroconvulsive therapy: a study protocol for a randomized controlled trial.

PubMed

Schmidt, Lejla Sjanic; Petersen, Jeff Zarp; Vinberg, Maj; Hageman, Ida; Olsen, Niels Vidiendal; Kessing, Lars Vedel; Jørgensen, Martin Balslev; Miskowiak, Kamilla Woznica

2018-04-19

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, but its use is impeded by its cognitive side effects. Novel treatments that can counteract these side effects may therefore improve current treatment strategies for depression. The present randomized trial investigates (1) whether short-term add-on treatment with erythropoietin (EPO) can reduce the cognitive side -effects of ECT and (2) whether such effects are long-lasting. Further, structural and functional magnetic resonance imaging (MRI) will be used to explore the neural underpinnings of such beneficial effects of EPO. Finally, the trial examines whether potential protective effects of EPO on cognition are accompanied by changes in markers of oxidative stress, inflammation, and neuroplasticity. The trial has a double-blind, randomized, placebo-controlled, parallel group design. Patients with unipolar or bipolar disorder with current moderate to severe depression referred to ECT (N = 52) are randomized to receive four high-dose infusions of EPO (40,000 IU/ml) or placebo (saline). The first EPO/saline infusion is administered within 24 h before the first ECT. The following three infusions are administered at weekly intervals immediately after ECT sessions 1, 4, and 7. Cognition assessments are conducted at baseline, after the final EPO/saline infusion (3 days after eight ECT sessions), and at a 3 months follow-up after ECT treatment completion. The neuronal substrates for potential cognitive benefits of EPO are investigated with structural and functional MRI after the final EPO/saline infusion. The primary outcome is change from baseline to after EPO treatment (3 days after eight ECT sessions) in a cognitive composite score spanning attention, psychomotor speed, and executive functions. With a sample size of N = 52 (n = 26 per group), we have ≥ 80% power to detect a clinically relevant between-group difference in the primary outcome measure at an alpha level of 5% (two-sided test). Behavioral, mood, and blood-biomarker data will be analyzed using repeated measures analysis of covariance. Functional MRI data will be preprocessed and analyzed using the FMRIB Software Library. If EPO is found to reduce the cognitive side effects of ECT, this could have important implications for future treatment strategies for depression and for the scientific understanding of the neurobiological etiology of cognitive dysfunction in patients treated with ECT. ClinicalTrials.gov, NCT03339596 . Registered on 10 November 2017.

Comparative use of side and main channels by small-bodied fish in a large, unimpounded river

USGS Publications Warehouse

Reinhold, Ann Marie; Bramblett, Robert G.; Zale, Alexander V.; Roberts, David W.; Poole, Geoffrey C.

2016-01-01

Ecological theory and field studies suggest that lateral floodplain connectivity and habitat heterogeneity provided by side channels impart favourable habitat conditions for lotic fishes, especially fluvial fishes dependent on large patches of shallow, slow velocity habitats for some portion of their life cycle. However, anthropogenic modification of large, temperate floodplain rivers has led to extensive channel simplification and side-channel loss. Highly modified rivers consist of simplified channels in contracted, less dynamic floodplains.Most research examining the seasonal importance of side channels for fish assemblages in large rivers has been carried out in heavily modified rivers, where side-channel extents are substantially reduced from pre-settlement times, and has often overlooked small-bodied fishes. Inferences about the ecological importance of side channels for small-bodied fishes in large rivers can be ascertained only from investigations of large rivers with largely intact floodplains. The Yellowstone River, our study area, is a rare example of one such river.We targeted small-bodied fishes and compared their habitat use in side and main channels in two geomorphically distinct types of river bends during early and late snowmelt runoff, and autumn base flow. Species compositions of side and main channels differed throughout hydroperiods concurrent with the seasonal redistribution of the availability of shallow, slow current-velocity habitats. More species of fish used side channels than main channels during runoff. Additionally, catch rates of small fishes were generally greater in side channels than in main channels and quantitative assemblage compositions differed between channel types during runoff, but not during base flow. Presence of and access to diverse habitats facilitated the development and persistence of diverse fish assemblages in our study area.Physical dissimilarities between side and main channels may have differentially structured the side- and main-channel fish assemblages during runoff. Patches of shallow, slow current-velocity (SSCV) habitats in side channels were larger and had slightly slower water velocities than SSCV habitat patches in main channels during runoff, but not during base flow.Our findings establish a baseline importance of side channels to riverine fishes in a large, temperate river without heavy anthropogenic modification. Establishing this baseline contributes to basic fluvial ecology and provides empirical justification for restoration efforts that reconnect large rivers with their floodplains.

Norms inform mental state ascriptions: A rational explanation for the side-effect effect.

PubMed

Uttich, Kevin; Lombrozo, Tania

2010-07-01

Theory of mind, the capacity to understand and ascribe mental states, has traditionally been conceptualized as analogous to a scientific theory. However, recent work in philosophy and psychology has documented a "side-effect effect" suggesting that moral evaluations influence mental state ascriptions, and in particular whether a behavior is described as having been performed 'intentionally.' This evidence challenges the idea that theory of mind is analogous to scientific psychology in serving the function of predicting and explaining, rather than evaluating, behavior. In three experiments, we demonstrate that moral evaluations do inform ascriptions of intentional action, but that this relationship arises because behavior that conforms to norms (moral or otherwise) is less informative about underlying mental states than is behavior that violates norms. This analysis preserves the traditional understanding of theory of mind as a tool for predicting and explaining behavior, but also suggests the importance of normative considerations in social cognition. 2010 Elsevier B.V. All rights reserved.

You Can't Always Get What You Want: The Influence of Choice on Nocebo and Placebo Responding.

PubMed

Bartley, Hannah; Faasse, Kate; Horne, Rob; Petrie, Keith J

2016-06-01

Choice may be an important influence on the effectiveness and side effects of medical treatments. We investigated the impact of having a choice of medication compared to no choice on both nocebo and placebo responding. Sixty-one participants were randomly assigned to either choose between or be assigned to one of the two equivalent beta-blocker medications (actually placebos) for pre-examination anxiety. There was a greater nocebo response in the no choice group and an increased placebo response in the choice group. Participants in the no choice group attributed significantly more side effects to the tablet than the choice group (p = 0.045), particularly at the 24-h follow-up (p = 0.002). The choice group showed a stronger placebo response in heart rate than the non-choice group. Not being given a choice of medication increased the nocebo effect and reduced the placebo response to the treatment.

Herbal Medicine and Acupuncture for Breast Cancer Palliative Care and Adjuvant Therapy

PubMed Central

Liao, Guo-Shiou; Shyur, Lie-Fen

2013-01-01

Breast cancer is a life-threatening disease among women worldwide with annual rates of reported incidence and death increasing alarmingly. Chemotherapy is a recommended and effective treatment option for breast cancer; however, the narrow therapeutic indices and varied side effects of currently approved drugs present major hurdles in increasing its effectiveness. An increasing number of literature evidence indicate that complementary and alternative medicine (CAM) used in treatment-related symptom control and alleviation of side effects plays an important role in increasing survival rate and quality of life in breast cancer patients. This review focuses on the use of herbal medicines and acupuncture in palliative care and as adjuvants in the treatment of breast cancer. Herbal medicinal treatments, the correlation of clinical use with demonstrated in vitro and in vivo mechanisms of action, and the use of certain acupoints in acupuncture are summarized. The aim of this review is to facilitate an understanding of the current practice and usefulness of herbal medicine and acupuncture as adjuvants in breast cancer therapy. PMID:23840256

Antipsychotics and physical attractiveness.

PubMed

Seeman, Mary V

2011-10-01

Antipsychotics are effective in treating the symptoms of schizophrenia, but they may induce adverse effects, some of which-those that impact negatively on physical appearance-have not been sufficiently discussed in the psychiatric literature. Through a narrative review, to catalog antipsychotic side effects that interfere with physical attractiveness and to suggest ways of addressing them. PubMed databases were searched for information on the association between "antipsychotic side effects" and "attractiveness" using those two search phrases plus the following terms: "weight," "teeth," "skin," "hair," "eyes," "gait," "voice," "odor." Data from relevant qualitative and quantitative articles were considered, contextualized, and summarized. Antipsychotics, as a group, increase weight and may lead to dry mouth and bad breath, cataracts, hirsutism, acne, and voice changes; they may disturb symmetry of gait and heighten the risk for tics and spasms and incontinence, potentially undermining a person's attractiveness. Clinicians need to be aware of the impact of therapeutic drugs on appearance and how important this issue is to patients. Early in treatment, they need to plan preventive and therapeutic strategies.

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.

Sex-related functional asymmetry of the amygdala: preliminary evidence using a case-matched lesion approach.

PubMed

Tranel, Daniel; Bechara, Antoine

2009-06-01

We have reported previously that there appears to be an intriguing sex-related functional asymmetry of the prefrontal cortices, especially the ventromedial sector, in regard to social conduct, emotional processing, and decision-making, whereby the right-sided sector is important in men but not women and the left-sided sector is important in women but not men. The amygdala is another structure that has been widely implicated in emotion processing and social decision-making, and the question arises as to whether the amygdala, in a manner akin to what has been observed for the prefrontal cortex, might have sex-related functional asymmetry in regard to social and emotional functions. A preliminary test of this question was carried out in the current study, where we used a case-matched lesion approach and contrasted a pair of men cases and a pair of women cases, where in each pair one patient had left amygdala damage and the other had right amygdala damage. We investigated the domains of social conduct, emotional processing and personality, and decision-making. The results provide support for the notion that there is sex-related functional asymmetry of the amygdala in regard to these functions - in the male pair, the patient with right-sided amygdala damage was impaired in these functions, and the patient with left-sided amygdala damage was not, whereas in the female pair, the opposite pattern obtained, with the left-sided woman being impaired and the right-sided woman being unimpaired. These data provide preliminary support for the notion that sex-related functional asymmetry of the amygdala may entail functions such as social conduct, emotional processing, and decision-making, a finding that in turn could reflect (as either a cause or effect) differences in the manner in which men and women apprehend, process, and execute emotion-related information.

22 CFR 201.66 - Side payments.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Side payments. 201.66 Section 201.66 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT RULES AND PROCEDURES APPLICABLE TO COMMODITY TRANSACTIONS FINANCED BY USAID Price Provisions § 201.66 Side payments. Any payment which an importer makes to a...

22 CFR 201.66 - Side payments.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Side payments. 201.66 Section 201.66 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT RULES AND PROCEDURES APPLICABLE TO COMMODITY TRANSACTIONS FINANCED BY USAID Price Provisions § 201.66 Side payments. Any payment which an importer makes to a...

22 CFR 201.66 - Side payments.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Side payments. 201.66 Section 201.66 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT RULES AND PROCEDURES APPLICABLE TO COMMODITY TRANSACTIONS FINANCED BY USAID Price Provisions § 201.66 Side payments. Any payment which an importer makes to a...

22 CFR 201.66 - Side payments.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Side payments. 201.66 Section 201.66 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT RULES AND PROCEDURES APPLICABLE TO COMMODITY TRANSACTIONS FINANCED BY USAID Price Provisions § 201.66 Side payments. Any payment which an importer makes to a...

22 CFR 201.66 - Side payments.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Side payments. 201.66 Section 201.66 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT RULES AND PROCEDURES APPLICABLE TO COMMODITY TRANSACTIONS FINANCED BY USAID Price Provisions § 201.66 Side payments. Any payment which an importer makes to a...

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.

Development of 5-Substituted N-Methylmorphinan-6-ones as Potent Opioid Analgesics with Improved Side-Effect Profile.

PubMed

Schmidhammer, Helmut; Spetea, Mariana

2012-01-01

One of the most important functions of the opioid system is the control of pain. Among the three main opioid receptor classes (μ, δ, κ), the μ (MOR) is the main type targeted for pharmacotherapy of pain. Opioid analgesics such as morphine, oxycodone and fentanyl are agonists at the MOR and are the mainstay for the treatment of moderate-to-severe pain. However, adverse effects related to opioid use are severe and often lead to early discontinuation and inadequate analgesia. The development of more effective and safer medications for the management of pain still remains a major direction in pharmaceutical research. Chemical approaches towards the identification of novel MOR analgesics with reduced side effects include structural modifications of 14-alkoxy-N-methylmorphinan-6-ones in key positions that are important for binding, selectivity, potency, and efficacy at opioid receptors. This paper describes a representative strategy to improve the therapeutic usefulness of opioid analgesics from the morphinan class of drugs by targeting position 5. The focus is on chemical and biological studies and structure-activity relationships of this series of ligands. We report on 14-alkoxymorphinan-6-ones having a methyl and benzyl group at position 5 as strong opioid antinociceptive agents with reduced propensity to cause undesired effects compared to morphine although interacting selectively with MORs.

Pain in children--are we accomplishing the optimal pain treatment?

PubMed

Lundeberg, Stefan

2015-01-01

Morphine, paracetamol and local anesthetics have for a long time been the foremost used analgesics in the pediatric patient by tradition but not always enough effective and associated with side effects. The purpose with this article is to propose alternative approaches in pain management, not always supported up by substantial scientific work but from a combination of science and clinical experience in the field. The scientific literature has been reviewed in parts regarding different aspects of pain assessment and analgesics used for treatment of diverse pain conditions with focus on procedural and acute pain. Clinical experience has been added to form the suggested improvements in accomplishing an improved pain management in pediatric patients. The aim with pain management in children should be a tailored analgesic medication with an individual acceptable pain level and optimal degree of mobilization with as little side effects as possible. Simple techniques of pain control are as effective as and complex techniques in pediatrics but the technique used is not of the highest importance in achieving a good pain management. Increased interest and improved education of the doctors prescribing analgesics is important in accomplishing a better pain management. The optimal treatment with analgesics is depending on the analysis of pain origin and analgesics used should be adjusted thereafter. A multimodal treatment regime is advocated for optimal analgesic effect. © 2014 John Wiley & Sons Ltd.

Structure-guided mutational analysis of the nucleotidyltransferase domain of Escherichia coli NAD+-dependent DNA ligase (LigA).

PubMed

Zhu, Hui; Shuman, Stewart

2005-04-01

NAD+-dependent DNA ligase (LigA) is essential for bacterial growth and a potential target for antimicrobial drug discovery. Here we queried the role of 14 conserved amino acids of Escherichia coli LigA by alanine scanning and thereby identified five new residues within the nucleotidyltransferase domain as being essential for LigA function in vitro and in vivo. Structure activity relationships were determined by conservative mutagenesis for the Glu-173, Arg-200, Arg-208, and Arg-277 side chains, as well as four other essential side chains that had been identified previously (Lys-115, Asp-117, Asp-285, and Lys-314). In addition, we identified Lys-290 as important for LigA activity. Reference to the structure of Enterococcus faecalis LigA allowed us to discriminate three classes of essential/important side chains that: (i) contact NAD+ directly (Lys-115, Glu-173, Lys-290, and Lys-314); (ii) comprise the interface between the NMN-binding domain (domain Ia) and the nucleotidyltransferase domain or comprise part of a nick-binding site on the surface of the nucleotidyltransferase domain (Arg-200 and Arg-208); or (iii) stabilize the active site fold of the nucleotidyltransferase domain (Arg-277). Analysis of mutational effects on the isolated ligase adenylylation and phosphodiester formation reactions revealed different functions for essential side chains at different steps of the DNA ligase pathway, consistent with the proposal that the active site is serially remodeled as the reaction proceeds.

Medium Effects on Freeze-Out of Light Clusters at NICA Energies

NASA Astrophysics Data System (ADS)

Röpke, G.; Blaschke, D.; Ivanov, Yu. B.; Karpenko, Iu.; Rogachevsky, O. V.; Wolter, H. H.

2018-05-01

We estimate the chemical freeze-out of light nuclear clusters for NICA energies of above 2 A GeV. On the one hand we use results from the low energy domain of about 35 A MeV, where medium effects have been shown to be important to explain experimental results. On the high energy side of LHC energies the statistical model without medium effects has provided results for the chemical freeze-out. The two approaches extrapolated to NICA energies show a discrepancy that can be attributed to medium effects and that for the deuteron/proton ratio amounts to a factor of about three. These findings underline the importance of a detailed investigation of light cluster production at NICA energies.

Classification of ictal and seizure-free HRV signals with focus on lateralization of epilepsy.

PubMed

Behbahani, Soroor; Dabanloo, Nader Jafarnia; Nasrabadi, Ali Motie; Dourado, Antonio

2016-01-01

Epileptic onsets often affect the autonomic function of the body during a seizure, whether it is in ictal, interictal or post-ictal periods. The different effects of localization and lateralization of seizures on heart rate variability (HRV) emphasize the importance of autonomic function changes in epileptic patients. On the other hand, the detection of seizures is of primary interests in evaluating the epileptic patients. In the current paper, we analyzed the HRV signal to develop a reliable offline seizure-detection algorithm to focus on the effects of lateralization on HRV. We assessed the HRV during 5-min segments of continuous electrocardiogram (ECG) recording with a total number of 170 seizures occurred in 16 patients, composed of 86 left-sided and 84 right-sided focus seizures. Relatively high and low-frequency components of the HRV were computed using spectral analysis. Poincaré parameters of each heart rate time series considered as non-linear features. We fed these features to the Support Vector Machines (SVMs) to find a robust classification method to classify epileptic and non-epileptic signals. Leave One Out Cross-Validation (LOOCV) approach was used to demonstrate the consistency of the classification results. Our obtained classification accuracy confirms that the proposed scheme has a potential in classifying HRV signals to epileptic and non-epileptic classes. The accuracy rates for right-sided and left-sided focus seizures were obtained as 86.74% and 79.41%, respectively. The main finding of our study is that the patients with right-sided focus epilepsy showed more reduction in parasympathetic activity and more increase in sympathetic activity. It can be a marker of impaired vagal activity associated with increased cardiovascular risk and arrhythmias. Our results suggest that lateralization of the seizure onset zone could exert different influences on heart rate changes. A right-sided seizure would cause an ictal tachycardia whereas a left-sided seizure would result in an ictal bradycardia.

[The concept of placebo and the effect of placebo].

PubMed

Göka, Erol

2002-01-01

The discussions about what placebo means and how its effect occurs go far back in the history of medicine. In general medicinal understanding, placebo means the subjective feeling of a positive effect in response to something that is used for curative intentions. In spite of difficulties in its definition and unknown content, its existence is generally accepted. What is discussed is its level of effectiveness in any disorder and medication. The placebo effect varies not only among diseases but also among regions and countries. Even the physicians' belief in a placebo increases its effect. Another interesting point about the placebo is its side effects. In many placebo controlled studies, the side effects of the placebo are found to be greater than those of real drugs. Different from other diseases, psychiatric disorders have strong connections with the placebo effect. The results of many studies support this idea. The increasing importance of placebos in psychiatry is really an interesting subject. For some people, the reason for this is hidden in the nature of psychiatric diseases. However, nonpharmacologic placebos such as "inspiration", "convincing", "confidence", and "belief" are believed to play a central role in psychiatry. In this article, placebo (the placebo effect) is defined, the implications of placebo in general medicine or psychiatry are discussed, and specific or nonspecific treatment methods are explained. The effects of a placebo on both the patient and the physician are emphasized. The significance of the placebo effect in psychiatry is also mentioned; and a new point of view, based upon the importance of symbolization and satisfaction is introduced in treatment and related action mechanisms.

Bulk electric system reliability evaluation incorporating wind power and demand side management

NASA Astrophysics Data System (ADS)

Huang, Dange

Electric power systems are experiencing dramatic changes with respect to structure, operation and regulation and are facing increasing pressure due to environmental and societal constraints. Bulk electric system reliability is an important consideration in power system planning, design and operation particularly in the new competitive environment. A wide range of methods have been developed to perform bulk electric system reliability evaluation. Theoretically, sequential Monte Carlo simulation can include all aspects and contingencies in a power system and can be used to produce an informative set of reliability indices. It has become a practical and viable tool for large system reliability assessment technique due to the development of computing power and is used in the studies described in this thesis. The well-being approach used in this research provides the opportunity to integrate an accepted deterministic criterion into a probabilistic framework. This research work includes the investigation of important factors that impact bulk electric system adequacy evaluation and security constrained adequacy assessment using the well-being analysis framework. Load forecast uncertainty is an important consideration in an electrical power system. This research includes load forecast uncertainty considerations in bulk electric system reliability assessment and the effects on system, load point and well-being indices and reliability index probability distributions are examined. There has been increasing worldwide interest in the utilization of wind power as a renewable energy source over the last two decades due to enhanced public awareness of the environment. Increasing penetration of wind power has significant impacts on power system reliability, and security analyses become more uncertain due to the unpredictable nature of wind power. The effects of wind power additions in generating and bulk electric system reliability assessment considering site wind speed correlations and the interactive effects of wind power and load forecast uncertainty on system reliability are examined. The concept of the security cost associated with operating in the marginal state in the well-being framework is incorporated in the economic analyses associated with system expansion planning including wind power and load forecast uncertainty. Overall reliability cost/worth analyses including security cost concepts are applied to select an optimal wind power injection strategy in a bulk electric system. The effects of the various demand side management measures on system reliability are illustrated using the system, load point, and well-being indices, and the reliability index probability distributions. The reliability effects of demand side management procedures in a bulk electric system including wind power and load forecast uncertainty considerations are also investigated. The system reliability effects due to specific demand side management programs are quantified and examined in terms of their reliability benefits.

Strong Poison Revisited

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

Prince, R.C.; Gailer, J.; Gunson, D.E.

2009-06-04

Selenium in the form of selenocysteine plays an essential role in a number of proteins, but its role in non-enzymatic biochemistry is also important. In this short review we discuss the interactions between inorganic selenium, arsenic and mercury under physiological conditions, especially in the presence of glutathione. This chemistry is obviously important in making the arsenic and mercury unavailable for more toxic interactions, but in the process it suggests that a side-effect of chronic arsenic and/or mercury exposure is likely to be functional selenium deficiency.

Central nervous system side effects associated with zolpidem treatment.

PubMed

Toner, L C; Tsambiras, B M; Catalano, G; Catalano, M C; Cooper, D S

2000-01-01

Zolpidem is one of the newer medications developed for the treatment of insomnia. It is an imidazopyridine agent that is an alternative to the typical sedative-hypnotic agents. Zolpidem use is gaining favor because of its efficacy and its side effect profile, which is milder and less problematic than that of the benzodiazepines and barbiturates used to treat insomnia. Still, side effects are not uncommon with zolpidem use. We report a series of cases in which the patients developed delirium, nightmares and hallucinations during treatment with zolpidem. We will review its pharmacology, discuss previous reports of central nervous system side effects, examine the impact of drug interactions with concurrent use of antidepressants, examine gender differences in susceptibility to side effects, and explore the significance of protein binding in producing side effects.

"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.

Energy Sustainability and the Green Campus.

ERIC Educational Resources Information Center

Simpson, Walter

2003-01-01

Discusses the importance of campus energy sustainability, explaining that both demand- and supply-side strategies are required. Suggests that on the demand side, an aggressive campus energy conservation program can reduce campus energy consumption by 30 percent or more. Asserts that addressing the supply side of the energy equation means shifting…

Are Student Groups Dysfunctional? Perspectives from Both Sides of the Classroom

ERIC Educational Resources Information Center

Chapman, Kenneth J.; Meuter, Matthew L.; Toy, Daniel; Wright, Lauren K.

2010-01-01

In today's business world, the ability to work efficiently and effectively in a team is mandatory to a business student's success. Many employers rank "ability to work with a group" as one of the most important attributes for hiring business school graduates. Although an abundance of research has investigated group processes and dynamics during…

Effects of General and Specific Cognitive Abilities on Reading Achievement in a Referred Sample

ERIC Educational Resources Information Center

Juarez, Betsy M.

2012-01-01

Psychoeducational assessment, and specifically cognitive testing, is important to the role of school psychologists; however, the utility of such testing has been called into question, and its future is unclear. Researchers are divided into two camps. One side grew disenchanted with cognitive testing after the failure of the discrepancy method to…

The Effects of Word-Learning Biases on Children's Concept of Angle

ERIC Educational Resources Information Center

Gibson, Dominic J.; Congdon, Eliza L.; Levine, Susan C.

2015-01-01

Despite evidence that young children are sensitive to differences in angle measure, older students frequently struggle to grasp this important mathematical concept. When making judgments about the size of angles, children often rely on erroneous dimensions such as the length of the angles' sides. The present study tested the possibility that…

THE RELATIVE IMPORTANCE OF NUTRIENT ENRICHMENT AND HERBIVORY ON MACROALGAL COMMUNITIES NEAR NORMAN'S POND CAY, EXUMAS CAYS, BAHAMAS: A "NATURAL" ENRICHMENT EXPERIMENT. (R830414)

EPA Science Inventory

The simultaneous effects of grazing and nutrient enrichment on macroalgal communities were experimentally investigated using plastic mesh enclosure/exclosure cages along a natural nutrient (DIN, SRP) gradient from the discharge of a tidal mangrove creek on the west side of Nor...

Expression of pleiotrophin, an important regulator of cell migration, is inhibited in intestinal epithelial cells by treatment with non-steroidal anti-inflammatory drugs

USDA-ARS?s Scientific Manuscript database

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs for the suppression of inflammation and pain. However, the analgesic properties of NSAIDs are also associated with significant negative side effects, most notably in the gastrointestinal (GI) tract. Increasingly, evi...

Rotator cuff strength in recurrent anterior shoulder instability.

PubMed

Edouard, Pascal; Degache, Francis; Beguin, Laurent; Samozino, Pierre; Gresta, Giorgio; Fayolle-Minon, Isabelle; Farizon, Frédéric; Calmels, Paul

2011-04-20

Although rotator-cuff muscle contraction plays an important role in stabilizing the glenohumeral joint, little is known about the role of these muscles in the pathophysiology of recurrent anterior instability. We intended to analyze the association between isokinetic internal rotator and external rotator muscle strength and glenohumeral joint instability in patients with recurrent anterior instability that was not previously treated surgically. We enrolled thirty-seven patients with unilateral recurrent anterior posttraumatic shoulder dislocation and eleven healthy nonathletic subjects in this controlled study. The association between internal rotator and external rotator strength and shoulder instability was analyzed by side-to-side comparisons and comparisons with a control group. Isokinetic internal rotator and external rotator strength was evaluated with a Con-Trex dynamometer, with the subject seated and the shoulder abducted 45° in the scapular plane. Tests were performed at 180°/s, 120°/s, and 60°/s in concentric mode for both sides. Peak torque normalized to body weight and external rotator to internal rotator ratio were calculated for each angular velocity. Clinical and isokinetic evaluation was done by the same rehabilitation physician. The association between shoulder instability and internal rotator and external rotator strength was associated with side-to-side differences (p < 0.05). Compared with a control group, strength values were lower on the pathological shoulder side of the patients with shoulder instability than on the healthy contralateral shoulder of control subjects at 180°/s and 120°/s (p < 0.05). The side-to-side differences were increased when the nondominant upper-extremity side was involved and were decreased when the dominant side was involved. There was no association between glenohumeral joint instability and external rotator to internal rotator ratio. Internal rotator and external rotator weakness was associated with recurrent anterior instability, and side-to-side differences depended on the side of hand dominance. Use of a control group may help in the analysis of the influence of constraints on shoulder strength. Further prospective studies are necessary to determine whether the weakness is a cause or an effect of the instability.

Primate translational vestibuloocular reflexes. IV. Changes after unilateral labyrinthectomy

NASA Technical Reports Server (NTRS)

Angelaki, D. E.; Newlands, S. D.; Dickman, J. D.

2000-01-01

The effects of unilateral labyrinthectomy on the properties of the translational vestibuloocular reflexes (trVORs) were investigated in rhesus monkeys trained to fixate near targets. Translational motion stimuli consisted of either steady-state lateral and fore-aft sinusoidal oscillations or short-lasting transient displacements. During small-amplitude, steady-state sinusoidal lateral oscillations, a small decrease in the horizontal trVOR sensitivity and its dependence on viewing distance was observed during the first week after labyrinthectomy. These deficits gradually recovered over time. In addition, the vertical response component increased, causing a tilt of the eye velocity vector toward the lesioned side. During large, transient lateral displacements, the deficits were larger and longer lasting. Responses after labyrinthectomy were asymmetric, with eye velocity during movements toward the side of the lesion being more compromised. The most profound effect of the lesions was observed during fore-aft motion. Whereas responses were kinematically appropriate for fixation away from the side of the lesion (e.g., to the left after right labyrinthectomy), horizontal responses were anticompensatory during fixation at targets located ipsilateral to the side of the lesion (e.g., for targets to the right after right labyrinthectomy). This deficit showed little recovery during the 3-mo post-labyrinthectomy testing period. These results suggest that inputs from both labyrinths are important for the proper function of the trVORs, although the details of how bilateral signals are processed and integrated remain unknown.

Radiolysis of N-acetyl amino acids as model compounds for radiation degradation of polypeptides

NASA Astrophysics Data System (ADS)

Wayne Garrett, R.; Hill, David J. T.; Ho, Sook-Ying; O'Donnell, James H.; O'Sullivan, Paul W.; Pomery, Peter J.

Radiation chemical yields of (i) the volatile radiolysis products and (ii) the trapped free radicals from the y-radiolysis of the N-acetyl derivatives of glycine, L-valine, L-phenylalanine and L-tyrosine in the polycrystalline state have been determined at room temperature (303 K). Carbon dioxide was found to be the major molecular product for all these compounds with G(CO 2) varying from 0.36 for N-acetyl-L-tyrosine to 8 for N-acetyl-L-valine. There was evidence for some scission of the N-C α bond, indicated by the production of acetamide and the corresponding aliphatic acid, but the determination reaction was found to be of much lesser importance than the decarboxylation reaction. A protective effect of the aromatic ring in N-acetyl-L-phenylalanine and in N-acetyl-L-tyrosine was indicated by the lower yields of volatile products for these compounds. The yields of trapped free radicals were found to vary with the nature of the amino acid side chain, increasing with chain length and chain branching. The radical yields were decreased by incorporation of an aromatic moiety in the side chain, this effect being greater for the tyrosyl side chain than for the phenyl side chain. The G(R·) values showed a good correlation with G(CO 2) indicating that a common reaction may be involved in radical production and carbon dioxide formation.

Extreme between-study homogeneity in meta-analyses could offer useful insights.

PubMed

Ioannidis, John P A; Trikalinos, Thomas A; Zintzaras, Elias

2006-10-01

Meta-analyses are routinely evaluated for the presence of large between-study heterogeneity. We examined whether it is also important to probe whether there is extreme between-study homogeneity. We used heterogeneity tests with left-sided statistical significance for inference and developed a Monte Carlo simulation test for testing extreme homogeneity in risk ratios across studies, using the empiric distribution of the summary risk ratio and heterogeneity statistic. A left-sided P=0.01 threshold was set for claiming extreme homogeneity to minimize type I error. Among 11,803 meta-analyses with binary contrasts from the Cochrane Library, 143 (1.21%) had left-sided P-value <0.01 for the asymptotic Q statistic and 1,004 (8.50%) had left-sided P-value <0.10. The frequency of extreme between-study homogeneity did not depend on the number of studies in the meta-analyses. We identified examples where extreme between-study homogeneity (left-sided P-value <0.01) could result from various possibilities beyond chance. These included inappropriate statistical inference (asymptotic vs. Monte Carlo), use of a specific effect metric, correlated data or stratification using strong predictors of outcome, and biases and potential fraud. Extreme between-study homogeneity may provide useful insights about a meta-analysis and its constituent studies.

Patient preferences for outcomes of depression treatment in Germany: a choice-based conjoint analysis study.

PubMed

Zimmermann, Thomas M; Clouth, Johannes; Elosge, Michael; Heurich, Matthias; Schneider, Edith; Wilhelm, Stefan; Wolfrath, Anette

2013-06-01

In general, treatment efficacy in depressed patients is evaluated mainly based on the core symptoms of depression. However, patients might consider different outcomes. This study used choice-based conjoint analysis (CBC) to evaluate patient preferences for depression treatment outcomes. Adult subjects from Germany, currently or previously on antidepressant treatment, were presented with 18 pairs of hypothetical treatment outcome scenarios, differing in eight attributes (2-3 factor levels each): depressed mood, loss of interest and enjoyment, loss of energy/fatigue, sleep disturbance, feelings of guilt, depression-related pain, treatment duration, side effects after 2 weeks. Attributes and factor levels were defined by literature review, expert consultations, and in-depth subject interviews. Data were analyzed using multinomial logit modeling; individual part-worth utilities were estimated using hierarchical Bayes routines. Two hundred twenty-seven subjects (89.4% currently treated with antidepressants, 30.0% with depression-related pain) completed the survey. They valued the relative importance of outcomes as follows: loss of energy/fatigue 18.5%, side effects after 2 weeks 14.2%, loss of interest and enjoyment 13.5%, depression-related pain 12.0%, sleep disturbance 12.0%, feelings of guilt 11.5%, treatment duration 9.9%, depressed mood 8.5%. Participants were not required to meet ICD-10 or DSM-IV criteria for depression and had heterogeneous disease severity. CBC analysis was able to reveal patient preferences for outcomes of depression treatment. Subjects valued the ability to cope with activities of everyday living highest. They considered being free of depression-related pain and side effects more important than being free of depressed mood. These findings should be considered when making treatment decisions. Copyright © 2012 Elsevier B.V. All rights reserved.

"I Did Not Want to Give Birth to a Child Who has HIV": Experiences Using PrEP During Pregnancy Among HIV-Uninfected Kenyan Women in HIV-Serodiscordant Couples.

PubMed

Pintye, Jillian; Beima-Sofie, Kristin M; Kimemia, Grace; Ngure, Kenneth; Trinidad, Susan Brown; Heffron, Renee A; Baeten, Jared M; Odoyo, Josephine; Mugo, Nelly; Bukusi, Elizabeth A; Kelley, Maureen C; John-Stewart, Grace C

2017-11-01

The perceptions, motivations, and beliefs of HIV-uninfected women about pre-exposure prophylaxis (PrEP) use during pregnancy can influence its uptake and adherence. This study elicited the views of HIV-uninfected women with personal experience taking PrEP during pregnancy. Qualitative interviews were conducted with HIV-uninfected women who had personal experience taking PrEP while pregnant. Semistructured interviews were conducted with 21 HIV-uninfected Kenyan women in HIV-serodiscordant couples enrolled in an open-label PrEP demonstration project who became pregnant while using PrEP and continued PrEP through their pregnancy. Interviews were audio-recorded and transcribed into English. A qualitative descriptive analysis was performed, using a constant comparison approach to identify key themes related to PrEP use in pregnancy. Desire to remain HIV uninfected and have an HIV-free infant were strong motivators influencing continued use of PrEP during pregnancy. Supporting HIV-infected partners and childbearing within an HIV-serodiscordant relationship were also motivators. Women had challenges distinguishing normal pregnancy symptoms from PrEP side effects and were concerned that observed side effects could be signs of danger for the infant related to PrEP exposure. Health care providers were important conduits of knowledge about PrEP, and continuity of PrEP providers throughout pregnancy facilitated adherence. HIV-uninfected women in HIV-serodiscordant couples were motivated to use PrEP during pregnancy to remain HIV uninfected and to have an HIV-free child but had concerns about side effects. Health care providers will be important for PrEP messaging and adherence support in this unique population.

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

MedlinePlus

... 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 ...

[Radiation-induced bystander effect: the important part of ionizing radiation response. Potential clinical implications].

PubMed

Wideł, Maria; Przybyszewski, Waldemar; Rzeszowska-Wolny, Joanna

2009-08-18

It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the "bystander effect" or "radiation-induced bystander effect" (RIBE). This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy), but also after conventional irradiation (X-rays, gamma rays) at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not definitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effect may have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation field and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The bystander effect may be a potentially harmful or a useful event in radiotherapy. The elevation of damage to tumor cells not directly hit by radiation or the initiation of tumor cell differentiation may increase the therapeutic ratio. If, however, molecular species secreted by irradiated tumor cells in vivo damage neighboring normal cells (epithelial and endothelial cells, fibroblasts, or lymphocytes), the bystander effect would be harmful and could lead to increased side effects in normal tissue. This is especially important in modern radiotherapy, as 3D conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) are aimed at diminishing the radiation dose in normal tissues. Recent in vivo studies on animals indicate that bystander effects may appear in organs and tissues remote from the irradiated field and the extension of tissue damage seems to be tissue-type dependent. However, recent experimental results indicate that non-irradiated cells that are neighbors of irradiated cells may diminish radiation damage in the radiation-focused cells. Less is known about the bystander effect during fractionated irradiation. Thus the clinical implications of the bystander effect and its possible modification for radiotherapeutic usefulness is still under debate.

The effects of collision orientation and energy dependence in multinucleon transfer reactions

NASA Astrophysics Data System (ADS)

Li, Jingjing; Li, Cheng; Wen, Peiwei; Zhang, Feng-Shou

2018-05-01

Multinucleon transfer (MNT) reaction 136Xe+208Pb near Coulomb barrier energies are investigated within the dinuclear system (DNS) model. It is found that the collision orientation has an important influence on the mass distributions attributed to the depth of pocket in the driving potential. The calculation results of the isotopic production show that the energy dependence in neutron-deficient side is more sensitive than that in neutron-rich side. The production of the N = 126 isotones are calculated by GRAZING model, DNS+GEMINI model, and ImQMD+GEMINI model, respectively. It demonstrates that MNT reaction is a promising way to produce neutron-rich isotopes in the region of the neutron shell closure N = 126.

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

Not Available

The technical and economic studies were performed to examine the possible installation of a small, integral pressurized water reactor as an industrial energy source in the Duval Corporation's Frasch Process sulfur mining operation located in Culberson County, Texas. Since this is the first industrial application study attempted for this type of reactor, it has been a learning process on the nuclear plant side as well as the industrial side, particularly in the area of economic analysis. The importance of considering inflationary effects, the significance of plant financing form, and the annualized, after-tax cash flow and incremental rate-of-return methods of comparisonmore » in determing energy costs have all been recognized during the course of the study.« less

Single amino acid mutation in alpha-helical peptide affect second harmonic generation hyperpolarizability

NASA Astrophysics Data System (ADS)

Wei, Jing; Wang, Jin-Yun; Zhang, Min-Yi; Chai, Guo-Liang; Lin, Chen-Sheng; Cheng, Wen-Dan

2013-01-01

We investigate the effect of side chain on the first-order hyperpolarizability in α-helical polyalanine peptide with the 10th alanine mutation (Acetyl(ala)9X(ala)7NH2). Structures of various substituted peptides are optimized by ONIOM (DFT: AM1) scheme, and then linear and nonlinear optical properties are calculated by SOS//CIS/6-31G∗ method. The polarizability and first-order hyperpolarizability increase obviously only when 'X' represents phenylalanine, tyrosine and tryptophan. We also discuss the origin of nonlinear optical response and determine what caused the increase of first-order hyperpolarizability. Our results strongly suggest that side chains containing benzene, phenol and indole have important contributions to first-order hyperpolarizability.

A review of the efficacy and safety of oral antidiabetic drugs

PubMed Central

Stein, Stephanie Aleskow; Lamos, Elizabeth Mary; Davis, Stephen N

2014-01-01

Introduction Additional oral antidiabetic agents to metformin, sulfonylureas (SU) and thiazolidinediones (TZD) are approved for the treatment of type 2 diabetes. Areas covered The efficacy and safety of metformin, SUs, TZDs, dipeptidyl peptidase-IV (DPP-4) inhibitors, meglitinide analogs, α-glucosidase inhibitors (AGIs), bile-acid sequestrants (BAS) and bromocriptine will be reviewed. Expert opinion Several new oral agents have been approved for type 2 diabetes management in recent years. It is important to understand the efficacy and safety of these medications in addition to the older agents to best maximize oral drug therapy for diabetes. Of the recently introduced oral hypoglycemic/antihyperglycemic agents, the DPP-4 inhibitors are moderately efficacious compared with mainstay treatment with metformin with a low side-effect profile and have good efficacy in combination with other oral agents and insulin. They are a recommended alternative when metformin use is limited by gastrointestinal (GI) side effects or when SU treatment results in significant hypoglycemia or weight gain. Meglitinide analogs are limited by their frequent dosing, expense and hypoglycemia (repaglinide > nateglinide), while AGIs are also limited by their dosing schedule and GI side-effect profile. BAS and bromocriptine have the lowest efficacy with regard to HbA1c reduction, also are plagued by GI adverse reactions, but have a low risk of hypoglycemia. PMID:23241069

HIV and mental illness in Malawi and the neuropsychiatric sequelae of efavirenz.

PubMed

Drury, Andrew; Gleadow-Ware, Selena; Gilfillan, Sheila; Ahrens, Jen

2018-03-01

Little is published about mental disorders in Malawi, specifically in relation to Human Immunodeficiency Virus (HIV) and it's treatment. Efavirenz is a medication commonly used as part of triple therapy for HIV treatment. Indeed, in 2013, Malawi introduced 5A with Efavirenz as part of it's 1st line treatment for HIV. There exists some literature documenting known psychiatric side effects of Efavirenz, which include anxiety, mood changes, nightmares, psychosis and suicidal ideation. Little is known about what features are most common in the presentation and what factors in the patient and drug which may make this reaction more likely. The aim of this commentary is to review the association between HIV and psychiatric disorder, and consider the neuropsychiatric side-effects of Efavirenz. An evaluative literature review was completed by means of multiple electronic database search as well as an additional manual search to obtain published works identified through the electronic search. Search terms used were: Efavirenz, Acquired Immunodeficiency Syndrome, Africa, Antiretroviral Therapy, Developing Countries, Malawi, Mental Disorders, Public Health, and Psychiatry. This is an important area of study, as potentially large numbers of individuals with HIV are being placed on Efavirenz as first line treatment, yet 60% may experience some form of neuropsychiatric side effects.

Understanding the side effects of emission trading: implications for waste management.

PubMed

Braschel, Nina; Posch, Alfred; Pierer, Magdalena

2014-01-01

The trading of emission allowances is an important market instrument in climate policy. However, the inclusion of certain branches of industry in the trading system not only provides incentives for emission reduction, it also entails unwanted side effects. Thus, the objective of the present study is to identify such side effects-positive and negative-by examining the potential impact of waste management inclusion in the European Union Emissions Trading Scheme (EU ETS). Desk research was supplemented with qualitative and quantitative empirical analysis (based on expert interviews and a questionnaire) in order to analyse the related perceptions and expectations of actors and stakeholders. The impact of waste management inclusion in the EU ETS is analysed in terms of the following three areas: (i) costs and cost pass-through, (ii), competitiveness and market position, and (iii) carbon leakage. Concerning expectations in the area of costs, both the interviewed experts and the practitioners surveyed thought that costs were likely to increase or that they could be passed on to customers. However, experts and practitioners differed with respect to the possibility of carbon leakage. Clearly, increased knowledge of the possible impact arising from inclusion of the waste sector in the EU ETS would enable managers to become more proactive and to manage waste streams and treatment options more economically.

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: Memory Changes

MedlinePlus

... 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.

"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.

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"),…

Sided functions of an arginine-agmatine antiporter oriented in liposomes.

PubMed

Tsai, Ming-Feng; Fang, Yiling; Miller, Christopher

2012-02-28

The arginine-dependent extreme acid resistance system helps enteric bacteria survive the harsh gastric environment. At the center of this multiprotein system is an arginine-agmatine antiporter, AdiC. To maintain cytoplasmic pH, AdiC imports arginine and exports its decarboxylated product, agmatine, resulting in a net extrusion of one "virtual proton" in each turnover. The random orientation of AdiC in reconstituted liposomes throws up an obstacle to quantifying its transport mechanism. To overcome this problem, we introduced a mutation, S26C, near the substrate-binding site. This mutant exhibits substrate recognition and pH-dependent activity similar to those of the wild-type protein but loses function completely upon reaction with thiol reagents. The membrane-impermeant MTSES reagent can then be used as a cleanly sided inhibitor to silence those S26C-AdiC proteins whose extracellular portion projects from the external side of the liposome. Alternatively, the membrane-permeant MTSEA and membrane-impermeant reducing reagent, TCEP, can be used together to inhibit proteins in the opposite orientation. This approach allows steady-state kinetic analysis of AdiC in a sided fashion. Arginine and agmatine have similar Michaelis-Menten parameters for both sides of the protein, while the extracellular side selects arginine over argininamide, a mimic of the carboxylate-protonated form of arginine, more effectively than does the cytoplasmic side. Moreover, the two sides of AdiC have different pH sensitivities. AdiC activity increases to a plateau at pH 4 as the extracellular side is acidified, while the cytoplasmic side shows an optimal pH of 5.5, with further acidification inhibiting transport. This oriented system allows more precise analysis of AdiC-mediated substrate transport than has been previously available and permits comparison to the situation experienced by the bacterial membrane under acid stress.

Mechanisms of cardiac cell damage due to catecholamines: significance of drugs regulating central sympathetic outflow.

PubMed

Rupp, H; Dhalla, K S; Dhalla, N S

1994-01-01

A chronically increased rate of catecholamine release has various deleterious actions. Isoproterenol injections (80 mg/kg body weight) resulted in depressed Ca2+ transport in the sarcolemma (ATP-dependent Ca2+ uptake, Na(+)-dependent Ca2+ uptake) and sarcoplasmic reticulum (Ca2+ uptake) of rat heart. The formation of malondialdehyde owing to lipid peroxidation was increased. Pretreatment with vitamin E (10-25 mg/kg/day) strongly inhibited the membrane damage. The toxic effects of catecholamines arise most probably from their oxidation, and it is therefore important either to reduce the central sympathetic outflow or to prevent the oxidation. An inappropriately high sympathetic outflow is a typical feature of Western affluent societies, and is linked to psychosocial stress and hypercaloric nutrition. However, established pharmacologic interventions to reduce sympathetic outflow have proven not practicable because of marked side effects. Using radiotelemetry for monitoring cardiovascular parameters of spontaneously hypertensive rats treated with clonidine or moxonidine, we showed that clonidine, unlike moxonidine, resulted in rebound hypertension after drug withdrawal. Because the rebound blood pressure and the typical side effects of clonidine associated with low patient compliance are mainly mediated by alpha-adrenoceptors, it can be inferred that the I1-imidazoline agonist moxonidine does not exhibit the side effects commonly seen with clonidine and therefore represents a promising approach for reducing an inappropriately high central sympathetic outflow.

[Designing a tool to describe drug interactions and adverse events for learning and clinical routine].

PubMed

Auzéric, M; Bellemère, J; Conort, O; Roubille, R; Allenet, B; Bedouch, P; Rose, F-X; Juste, M; Charpiat, B

2009-11-01

Pharmacists play an important role in prescription analysis. They are involved in therapeutic drug monitoring, particularly for drugs with a narrow therapeutic index, prevention and management of drug interactions, and may be called in to identify side effects and adverse events related to drug therapy. For the polymedicated patient, the medical file, the list of prescribed drugs and the history of their administration may be insufficient to adequately assign the responsibility of a given adverse effect to one or more drugs. Graphical representations can sometimes be useful to describe and clarify a sequence of events. In addition, as part of their academic course, students have many occasions to hear about "side effects" and "drug interactions". However, in the academic setting, there are few opportunities to observe the evolution and the consequences of these events. In the course of their hospital training, these students are required to perform patient follow-up for pharmacotherapeutic or educational purposes and to comment case reports to physicians. The aim of this paper is to present a tool facilitating the graphic display of drug interaction consequences and side effects. This tool can be a useful aid for causality assessment. It structures the students' training course and helps them better understand the commentaries pharmacists provide for physicians. Further development of this tool should contribute to the prevention of adverse drug events.

[Local effects of transdermal treatment with rotigotine].

PubMed

Bermejo, Pedro Emilio; Zea, María Ascensión; Alba-Alcántara, Lucía; Ruiz-Huete, Cristina

2013-04-01

Rotigotine is the first transdermal non-ergolinic dopaminergic agonist used in the treatment of Parkinson's disease. It has several important advantages such as once-daily administration, absence of interactions with food, steady levels in plasma and continuous dopaminergic stimulation. Although its systemic side effects are similar to those seen in other dopaminergic agonists, rotigotine also has local side effects derived from the site of application. The aim of this paper is to review those local problems. A retrospective analysis was carried out in order to identify the first 165 patients treated with rotigotine. Patients with intracranial lesions, psychiatric pathology or dementia were excluded. Patients were evaluated before and at two, four and six months after beginning treatment with rotigotine. In all, 94 males and 71 females were identified, with an average age of 65.2 and an average rotigotine daily dose of 11.3 mg. Local side effects were present in 21 patients and they were usually mild. Two patients abandoned the treatment because of these local adverse events, presenting erythema and prurigo. Thirty patients complained about lack of adherence of the patch, specially when it was hot, and 36 about the formation of wrinkles in the patch. None of these problems was associated to motor fluctuations or other complications. Local complications of transdermal rotigotine are mild but frequent. We consider it is necessarily to take them into account to get a better treatment of patients suffering from Parkinson's disease.

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.

Characteristics of e-cigarette users and their perceptions of the benefits, harms and risks of e-cigarette use: survey results from a convenience sample in Ottawa, Canada.

PubMed

Volesky, K D; Maki, A; Scherf, C; Watson, L M; Cassol, E; Villeneuve, P J

2016-07-01

Although e-cigarette use ("vaping") is increasing in Canada, few attempts have been made to describe e-cigarette users ("vapers"). In this context, we conducted a study in Ottawa, Canada, to describe e-cigarette users' perceptions of the benefits, harms and risks of e-cigarettes. We also collected information on why, how and where they use e-cigarettes as well as information on side effects. A 24-item online survey was administered to individuals who purchased e-cigarettes or e-cigarette-related supplies at one of Ottawa's 17 e-cigarette shops. Descriptive analyses characterized respondents, and logistic regression models were fitted to evaluate the relationship between respondents' characteristics and their perception of e-cigarette harms. The mean age of the 242 respondents was 38.1 years (range: 16-70 years); 66% were male. Nearly all had smoked 100 or more cigarettes in their lifetime (97.9%). More than 80% indicated that quitting smoking was a very important reason for starting to use e-cigarettes and 60% indicated that they intend to stop using e-cigarettes at some point. About 40% reported experiencing some side effects within 2 hours of using e-cigarettes. Those who did not report experiencing any of the listed side effects had approximately 3.2 times higher odds of perceiving e-cigarettes as harmless than those who reported having side effects (odds ratio = 3.17; 95% confidence interval: 1.75-5.73). Our findings suggest that most e-cigarette users are using them to reduce or stop smoking cigarettes and perceive them as harmless. Due to our use of convenience sampling, the reader should be cautious in generalizing our findings to all Canadian e-cigarette users.

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.

Influence of Scattering on Ballistic Nanotransistor Design

NASA Technical Reports Server (NTRS)

Anantram, M. P.; Svizhenko, Alexei; Biegel, Bryan, A. (Technical Monitor)

2002-01-01

Importance of this work: (1) This is the first work to model electron-phonon scattering within a quantum mechanical approach to nanotransistors. The simulations use the non equilibrium Green's function method. (2) A simple equation which captures the importance of scattering as a function of the spatial location from source to drain is presented. This equation helps interpret the numerical simulations. (3) We show that the resistance per unit length in the source side is much larger than in the drain side. Thus making scattering in the source side of the device much more important than scattering in the drain side. Numerical estimates of ballisticity for 10nm channel length devices in the presence of of electron-phonon scattering are given. Based on these calculations, we propose that to achieve a larger on-current in nanotransistors, it is crucial to keep the highly doped source extension region extremely small, even if this is at the cost of making the highly doped drain extension region longer.

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 ...

Evaluation of salivary catalase, vitamin C, and alpha-amylase in smokers and non-smokers: a retrospective cohort study.

PubMed

Ahmadi-Motamayel, Fatemeh; Falsafi, Parisa; Goodarzi, Mohammad Taghi; Poorolajal, Jalal

2017-05-01

Saliva and its defence systems such as antioxidants and minerals are very important in the pathogenesis of different diseases. Cigarette smoking has many destructive effects. Oxidative stresses play an important role in the side effects of smoking. This study assessed the effect of cigarette smoking on salivary levels of catalase, vitamin C, and α-amylase. This retrospective cohort study was carried out in Hamadan, Iran, on 510 subjects; 259 subjects were smokers (the exposed group) and 251 were non-smokers (the unexposed group). Five microliters of unstimulated saliva was collected by spitting method. Catalase, vitamin C, and α-amylase salivary levels were determined by spectrophotometric assay. Data were analyzed with t-test using STATA 12. Vitamin C level in smokers was significantly lower than that in non-smokers. The salivary catalase levels were lower and α-amylase levels were higher in smokers, but the differences were not statistically significant (P = 0.416 and P = 0.265, respectively). Smokers were younger than non-smokers. Smoking resulted in a change in salivary antioxidant levels. Changes in antioxidant levels can influence the deleterious effects of smoking on oral mucosa; it might also indicate systemic changes and changes in the serum levels of oxidative agents. Further studies are necessary to understand the mechanisms and real effects of smoking, to determine the benefits of supplementary antioxidants for treatment and to reduce the dangerous side effects of smoking. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Selection of Server-Side Technologies for an E-Business Curriculum

ERIC Educational Resources Information Center

Sandvig, J. Christopher

2007-01-01

The rapid growth of e-business and e-commerce has made server-side programming an increasingly important topic in information systems (IS) and computer science (CS) curricula. This article presents an overview of the major features of several popular server-side programming technologies and discusses the factors that influence the selection of…

Cutaneous side effects of doxycycline: a pediatric case series.

PubMed

Bayhan, Gulsum Iclal; Akbayram, Sinan; Ozaydin Yavuz, Goknur; Oner, Ahmet Fayik

2017-06-01

Brucellosis is highly endemic in Turkey and doxycycline is commonly used for its treatment. The present study aimed at documenting the cutaneous side effects of doxycycline in pediatric brucellosis patients in Turkey. Pediatric patients with brucellosis that were treated between February 2014 and January 2016 were analyzed retrospectively, and those that developed doxycycline-related cutaneous side effects were identified. Demographic data, epidemiological history, physical examination findings, laboratory test results, anti-brucellosis treatment regimen, duration of follow up and outcome were recorded. Among the 189 brucellosis patients, 141 treated with doxycycline plus rifampicin. Seven patients (5%) (two female and five male) developed doxycycline-related cutaneous side effects. Mean duration of treatment before the onset of cutaneous side effects was 9.5 weeks. Doxycycline therapy was continued in five of these patients and was changed in two patients. In the patients that continued to receive doxycycline the cutaneous side effects gradually improved. Cutaneous side effects of doxycycline should always be a consideration, especially in regions in which brucellosis is endemic and doxycycline is commonly used to treat it.

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.

Gravel Bars Can Be Critical for Biodiversity Conservation: A Case Study on Scaly-Sided Merganser in South China

PubMed Central

Zeng, Qing; Shi, Linlu; Wen, Li; Chen, Junzhu; Duo, Hairui; Lei, Guangchun

2015-01-01

Gravel bars are characteristic components of river landscapes and are increasingly recognized as key sites for many waterbirds, though detailed studies on the ecological function of gravel bars for waterbirds are rare. In this study, we surveyed the endangered Scaly-sided Merganser Mergus squamatus along a 40 km river section of Yuan River, in Central China, for three consecutive winters. We derived the landscape metrics of river gravel bars from geo-rectified fine resolution (0.6 m) aerial image data. We then built habitat suitability models (Generalized Linear Models—GLMs) to study the effects of landscape metrics and human disturbance on Scaly-sided Merganser presence probability. We found that 1) the Scaly-sided Merganser tended to congregate at river segments with more gravel patches; 2) the Scaly-sided Merganser preferred areas with larger and more contiguous gravel patches; and 3) the number of houses along the river bank (a proxy for anthropogenic disturbance) had significantly negative impacts on the occurrence of the Scaly-sided Merganser. Our results suggest that gravel bars are vital to the Scaly-sided Merganser as shelters from disturbance, as well as sites for feeding and roosting. Therefore, maintaining the exposure of gravel bars in regulated rivers during the low water period in winter might be the key for the conservation of the endangered species. These findings have important implications for understanding behavioral evolution and distribution of the species and for delineating between habitats of different quality for conservation and management. PMID:25996671

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.

Effect of mandibular advancement device on sleep bruxism score and sleep quality.

PubMed

Solanki, Nehal; Singh, Balendra Pratap; Chand, Pooran; Siddharth, Ramashankar; Arya, Deeksha; Kumar, Lakshya; Tripathi, Suryakant; Jivanani, Hemant; Dubey, Abhishek

2017-01-01

The use of mandibular advancement devices (MADs) in the treatment of sleep bruxism is gaining widespread importance. However, the effects of MADs on sleep bruxism scores, sleep quality, and occlusal force are not clear. The purpose of this clinical study was to analyze the effect of MADs on sleep bruxism scores, sleep quality, and occlusal force. This uncontrolled before and after study enrolled 30 participants with sleep bruxism. Outcomes assessed were sleep quality, sleep bruxism scores (sleep bruxism bursts and sleep bruxism episodes/hour), and occlusal force before and after 15 and 30 days of using a MAD. Sleep bruxism scores were assessed by ambulatory polysomnography and sleep quality by using the Pittsburgh sleep quality index (PSQI). Occlusal force was recorded by using a digital gnathodynamometer in the first molar region on both sides. Statistical analysis was done by 1-factor repeated measures ANOVA (α=.05). Statistically significant reductions in sleep bruxism bursts/h, sleep bruxism episodes/h, and PSQI scores were found after 15 and 30 days of using a MAD (P<.001). Statistically significant reduction in occlusal force on both sides was found only after 15 days (P<.001) but not after 30 days of using a MAD (P=.292 on left side, and P=.575 on the right side). The study showed a short-term improvement in sleep bruxism scores, sleep quality, and reduction in occlusal force in sleep bruxism participants after using MADs. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Helicity of short E-R/K peptides.

PubMed

Sommese, Ruth F; Sivaramakrishnan, Sivaraj; Baldwin, Robert L; Spudich, James A

2010-10-01

Understanding the secondary structure of peptides is important in protein folding, enzyme function, and peptide-based drug design. Previous studies of synthetic Ala-based peptides (>12 a.a.) have demonstrated the role for charged side chain interactions involving Glu/Lys or Glu/Arg spaced three (i, i + 3) or four (i, i + 4) residues apart. The secondary structure of short peptides (<9 a.a.), however, has not been investigated. In this study, the effect of repetitive Glu/Lys or Glu/Arg side chain interactions, giving rise to E-R/K helices, on the helicity of short peptides was examined using circular dichroism. Short E-R/K-based peptides show significant helix content. Peptides containing one or more E-R interactions display greater helicity than those with similar E-K interactions. Significant helicity is achieved in Arg-based E-R/K peptides eight, six, and five amino acids long. In these short peptides, each additional i + 3 and i + 4 salt bridge has substantial contribution to fractional helix content. The E-R/K peptides exhibit a strongly linear melt curve indicative of noncooperative folding. The significant helicity of these short peptides with predictable dependence on number, position, and type of side chain interactions makes them an important consideration in peptide design.

Humic Acids as Therapeutic Compounds in Lead Intoxication.

PubMed

Krempaská, Klára; Vaško, Ladislav; Vašková, Janka

2016-01-01

The toxicity of lead and its compounds is well known, causing anemia by inhibiting the synthesis of porphyrins. The neurotoxic effects, particularly in the young, alter the structure of cell membranes and DNA. Chronic exposure to lead has adverse effects on the body by disrupting the mechanisms of energy production and tissue damage, in particular in its links with thiol groups and competition for binding sites with zinc. This review is therefore a description of the mechanism of lead toxicity as well as of possible interventions for the detoxification of the body. Part of the clinical intervention is the provision of chelates that form insoluble complexes with lead and eliminate the load in tissues. Most of these chelating agents have a number of side effects. It is therefore not surprising that active compounds with distinctive antioxidant and chelating properties are being sought after. The possibility of administering lower amounts, and the corresponding decrease in side effects, would be important for clinical practice. Both prospective studies and our initial studies on humic acids have highlighted positive effects based on their antioxidant and chelating properties.

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.

Attitudes toward Infection Prophylaxis in Pediatric Oncology: A Qualitative Approach

PubMed Central

Diorio, Caroline; Tomlinson, Deborah; Boydell, Katherine M.; Regier, Dean A.; Ethier, Marie-Chantal; Alli, Amanda; Alexander, Sarah; Gassas, Adam; Taylor, Jonathan; Kellow, Charis; Mills, Denise; Sung, Lillian

2012-01-01

Background The risks and benefits of infection prophylaxis are uncertain in children with cancer and thus, preferences should be considered in decision making. The purpose of this report was to describe the attitudes of parents, children and healthcare professionals to infection prophylaxis in pediatric oncology. Methods The study was completed in three phases: 1) An initial qualitative pilot to identify the main attributes influencing the decision to use infection prophylaxis, which were then incorporated into a discrete choice experiment; 2) A think aloud during the discrete choice experiment in which preferences for infection prophylaxis were elicited quantitatively; and 3) In-depth follow up interviews. Interviews were recorded verbatim and analyzed using an iterative, thematic analysis. Final themes were selected using a consensus approach. Results A total of 35 parents, 22 children and 28 healthcare professionals participated. All three groups suggested that the most important factor influencing their decision making was the effect of prophylaxis on reducing the chance of death. Themes of importance to the three groups included antimicrobial resistance, side effects of medications, the financial impact of outpatient prophylaxis and the route and schedule of administration. Conclusion Effect of prophylaxis on risk of death was a key factor in decision making. Other identified factors were antimicrobial resistance, side effects of medication, financial impact and administration details. Better understanding of factors driving decision making for infection prophylaxis will help facilitate future implementation of prophylactic regiments. PMID:23112849

Attitudes toward infection prophylaxis in pediatric oncology: a qualitative approach.

PubMed

Diorio, Caroline; Tomlinson, Deborah; Boydell, Katherine M; Regier, Dean A; Ethier, Marie-Chantal; Alli, Amanda; Alexander, Sarah; Gassas, Adam; Taylor, Jonathan; Kellow, Charis; Mills, Denise; Sung, Lillian

2012-01-01

The risks and benefits of infection prophylaxis are uncertain in children with cancer and thus, preferences should be considered in decision making. The purpose of this report was to describe the attitudes of parents, children and healthcare professionals to infection prophylaxis in pediatric oncology. THE STUDY WAS COMPLETED IN THREE PHASES: 1) An initial qualitative pilot to identify the main attributes influencing the decision to use infection prophylaxis, which were then incorporated into a discrete choice experiment; 2) A think aloud during the discrete choice experiment in which preferences for infection prophylaxis were elicited quantitatively; and 3) In-depth follow up interviews. Interviews were recorded verbatim and analyzed using an iterative, thematic analysis. Final themes were selected using a consensus approach. A total of 35 parents, 22 children and 28 healthcare professionals participated. All three groups suggested that the most important factor influencing their decision making was the effect of prophylaxis on reducing the chance of death. Themes of importance to the three groups included antimicrobial resistance, side effects of medications, the financial impact of outpatient prophylaxis and the route and schedule of administration. Effect of prophylaxis on risk of death was a key factor in decision making. Other identified factors were antimicrobial resistance, side effects of medication, financial impact and administration details. Better understanding of factors driving decision making for infection prophylaxis will help facilitate future implementation of prophylactic regiments.

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

Aerodynamics of sports balls

NASA Astrophysics Data System (ADS)

Mehta, R. D.

Research data on the aerodynamic behavior of baseballs and cricket and golf balls are summarized. Cricket balls and baseballs are roughly the same size and mass but have different stitch patterns. Both are thrown to follow paths that avoid a batter's swing, paths that can curve if aerodynamic forces on the balls' surfaces are asymmetric. Smoke tracer wind tunnel tests and pressure taps have revealed that the unbalanced side forces are induced by tripping the boundary layer on the seam side and producing turbulence. More particularly, the greater pressures are perpendicular to the seam plane and only appear when the balls travel at velocities high enough so that the roughness length matches the seam heigh. The side forces, once tripped, will increase with spin velocity up to a cut-off point. The enhanced lift coefficient is produced by the Magnus effect. The more complex stitching on a baseball permits greater variations in the flight path curve and, in the case of a knuckleball, the unsteady flow effects. For golf balls, the dimples trip the boundary layer and the high spin rate produces a lift coefficient maximum of 0.5, compared to a baseball's maximum of 0.3. Thus, a golf ball travels far enough for gravitational forces to become important.

Aerodynamics of sports balls

NASA Technical Reports Server (NTRS)

Mehta, R. D.

1985-01-01

Research data on the aerodynamic behavior of baseballs and cricket and golf balls are summarized. Cricket balls and baseballs are roughly the same size and mass but have different stitch patterns. Both are thrown to follow paths that avoid a batter's swing, paths that can curve if aerodynamic forces on the balls' surfaces are asymmetric. Smoke tracer wind tunnel tests and pressure taps have revealed that the unbalanced side forces are induced by tripping the boundary layer on the seam side and producing turbulence. More particularly, the greater pressures are perpendicular to the seam plane and only appear when the balls travel at velocities high enough so that the roughness length matches the seam heigh. The side forces, once tripped, will increase with spin velocity up to a cut-off point. The enhanced lift coefficient is produced by the Magnus effect. The more complex stitching on a baseball permits greater variations in the flight path curve and, in the case of a knuckleball, the unsteady flow effects. For golf balls, the dimples trip the boundary layer and the high spin rate produces a lift coefficient maximum of 0.5, compared to a baseball's maximum of 0.3. Thus, a golf ball travels far enough for gravitational forces to become important.

On the Connection Between Flap Side-Edge Noise and Tip Vortex Dynamics

NASA Technical Reports Server (NTRS)

Casalino, D.; Hazir, A.; Fares, E.; Duda, B.; Khorrami, M. R.

2015-01-01

The goal of the present work is to investigate how the dynamics of the vortical flow about the flap side edge of an aircraft determine the acoustic radiation. A validated lattice- Boltzmann CFD solution of the unsteady flow about a detailed business jet configuration in approach conditions is used for the present analysis. Evidence of the connection between the noise generated by several segments of the inboard flap tip and the aerodynamic forces acting on the same segments is given, proving that the noise generation mechanism has a spatially coherent and acoustically compact character on the scale of the flap chord, and that the edge-scattering effects are of secondary importance. Subsequently, evidence of the connection between the kinematics of the tip vortex system and the aerodynamic force is provided. The kinematics of the dual vortex system are investigated via a core detection technique. Emphasis is placed on the mutual induction effects between the two main vortices rolling up from the pressure and suction sides of the flap edge. A simple heuristic formula that relates the far-field noise spectrum and the cross-spectrum of the unsteady vortical positions is developed.

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.

Salient concerns in using analgesia for cancer pain among outpatients: A cluster analysis study.

PubMed

Meghani, Salimah H; Knafl, George J

2017-02-10

To identify unique clusters of patients based on their concerns in using analgesia for cancer pain and predictors of the cluster membership. This was a 3-mo prospective observational study ( n = 207). Patients were included if they were adults (≥ 18 years), diagnosed with solid tumors or multiple myelomas, and had at least one prescription of around-the-clock pain medication for cancer or cancer-treatment-related pain. Patients were recruited from two outpatient medical oncology clinics within a large health system in Philadelphia. A choice-based conjoint (CBC) analysis experiment was used to elicit analgesic treatment preferences (utilities). Patients employed trade-offs based on five analgesic attributes (percent relief from analgesics, type of analgesic, type of side-effects, severity of side-effects, out of pocket cost). Patients were clustered based on CBC utilities using novel adaptive statistical methods. Multiple logistic regression was used to identify predictors of cluster membership. The analyses found 4 unique clusters: Most patients made trade-offs based on the expectation of pain relief (cluster 1, 41%). For a subset, the main underlying concern was type of analgesic prescribed, i.e ., opioid vs non-opioid (cluster 2, 11%) and type of analgesic side effects (cluster 4, 21%), respectively. About one in four made trade-offs based on multiple concerns simultaneously including pain relief, type of side effects, and severity of side effects (cluster 3, 28%). In multivariable analysis, to identify predictors of cluster membership, clinical and socioeconomic factors (education, health literacy, income, social support) rather than analgesic attitudes and beliefs were found important; only the belief, i.e ., pain medications can mask changes in health or keep you from knowing what is going on in your body was found significant in predicting two of the four clusters [cluster 1 (-); cluster 4 (+)]. Most patients appear to be driven by a single salient concern in using analgesia for cancer pain. Addressing these concerns, perhaps through real time clinical assessments, may improve patients' analgesic adherence patterns and cancer pain outcomes.

In Vivo Analysis of the Role of Metabotropic Glutamate Receptors in the Afferent Regulation of Chick Cochlear Nucleus Neurons

PubMed Central

Carzoli, Kathryn L.; Hyson, Richard L.

2010-01-01

Cochlea removal results in the death of approximately 20-30% of neurons in the chick nucleus magnocellularis (NM). One early event in NM neuronal degradation is the disruption of their ribosomes. This can be visualized in the first few hours following cochlea removal using Y10B, an antibody that recognizes ribosomal RNA. Previous studies using a brain slice preparation suggest that maintenance of ribosomal integrity in NM neurons requires metabotropic glutamate receptor (mGluR) activation. Isolating the brain slice in vitro, however, may eliminate other potential sources of trophic support and only allows for evaluation of the early changes that occur in NM neurons following deafferentation. Consequently, it is not known if mGluR activation is truly required for the maintenance of NM neurons in the intact system. The current experiments evaluated the importance of mGluRs in vivo. The effects of short-term receptor blockade were assessed through Y10B labeling and the effects of long-term blockade were assessed through stereological counting of NM neurons in Nissl-stained tissue. mGluR antagonists or vehicle were administered intracerebroventricularly following unilateral cochlea removal. Vehicle-treated subjects replicated the previously reported effects of cochlea removal, showing lighter Y10B-labeling and fewer Nissl-stained NM neurons on the deafened side of the brain. Blockade of mGluRs prevented the rapid activity-dependent difference in Y10B labeling, and in some cases, had the reverse effect, yielding lighter labeling of NM neurons on the intact side of the brain. Similarly, mGluR blockade over longer survival periods resulted in a reduction in number of cells on both intact and deafferented sides of the brain, and in some cases, yielded a reverse effect of fewer neurons on the intact side versus deafened side. These data are consistent with in vitro findings and suggest that mGluR activation plays a vital role in the afferent maintenance of NM neurons. PMID:21059385

In vivo analysis of the role of metabotropic glutamate receptors in the afferent regulation of chick cochlear nucleus neurons.

PubMed

Carzoli, Kathryn L; Hyson, Richard L

2011-02-01

Cochlea removal results in the death of approximately 20-30% of neurons in the chick nucleus magnocellularis (NM). One early event in NM neuronal degradation is the disruption of their ribosomes. This can be visualized in the first few hours following cochlea removal using Y10B, an antibody that recognizes ribosomal RNA. Previous studies using a brain slice preparation suggest that maintenance of ribosomal integrity in NM neurons requires metabotropic glutamate receptor (mGluR) activation. Isolating the brain slice in vitro, however, may eliminate other potential sources of trophic support and only allows for evaluation of the early changes that occur in NM neurons following deafferentation. Consequently, it is not known if mGluR activation is truly required for the maintenance of NM neurons in the intact system. The current experiments evaluated the importance of mGluRs in vivo. The effects of short-term receptor blockade were assessed through Y10B labeling and the effects of long-term blockade were assessed through stereological counting of NM neurons in Nissl-stained tissue. mGluR antagonists or vehicle were administered intracerebroventricularly following unilateral cochlea removal. Vehicle-treated subjects replicated the previously reported effects of cochlea removal, showing lighter Y10B labeling and fewer Nissl-stained NM neurons on the deafened side of the brain. Blockade of mGluRs prevented the rapid activity-dependent difference in Y10B labeling, and in some cases, had the reverse effect, yielding lighter labeling of NM neurons on the intact side of the brain. Similarly, mGluR blockade over longer survival periods resulted in a reduction in number of cells on both intact and deafferented sides of the brain, and in some cases, yielded a reverse effect of fewer neurons on the intact side versus deafened side. These data are consistent with in vitro findings and suggest that mGluR activation plays a vital role in the afferent maintenance of NM neurons. Copyright © 2010 Elsevier B.V. All rights reserved.

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.

Combining doxorubicin-nanobubbles and shockwaves for anaplastic thyroid cancer treatment: preclinical study in a xenograft mouse model.

PubMed

Marano, Francesca; Frairia, Roberto; Rinella, Letizia; Argenziano, Monica; Bussolati, Benedetta; Grange, Cristina; Mastrocola, Raffaella; Castellano, Isabella; Berta, Laura; Cavalli, Roberta; Catalano, Maria Graziella

2017-06-01

Anaplastic thyroid cancer is one of the most lethal diseases, and a curative therapy does not exist. Doxorubicin, the only drug approved for anaplastic thyroid cancer treatment, has a very low response rate and causes numerous side effects among which cardiotoxicity is the most prominent. Thus, doxorubicin delivery to the tumor site could be an import goal aimed to improve the drug efficacy and to reduce its systemic side effects. We recently reported that, in human anaplastic thyroid cancer cell lines, combining doxorubicin-loaded nanobubbles with extracorporeal shock waves, acoustic waves used in lithotripsy and orthopedics without side effects, increased the intracellular drug content and in vitro cytotoxicity. In the present study, we tested the efficacy of this treatment on a human anaplastic thyroid cancer xenograft mouse model. After 21 days, the combined treatment determined the greatest drug accumulation in tumors with consequent reduction of tumor volume and weight, and an extension of the tumor doubling time. Mechanistically, the treatment induced tumor apoptosis and decreased cell proliferation. Finally, although doxorubicin caused the increase of fibrosis markers and oxidative stress in animal hearts, loading doxorubicin into nanobubbles avoided these effects preventing heart damage. The improvement of doxorubicin anti-tumor effects together with the prevention of heart damage suggests that the combination of doxorubicin-loaded nanobubbles with extracorporeal shock waves might be a promising drug delivery system for anaplastic thyroid cancer treatment. © 2017 Society for Endocrinology.

Sodium channel slow inactivation as a therapeutic target for myotonia congenita

PubMed Central

Novak, Kevin R; Norman, Jennifer; Mitchell, Jacob R; Pinter, Martin J; Rich, Mark M

2014-01-01

Objective Patients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the chloride channel in skeletal muscle, which causes spontaneous firing of muscle action potentials (myotonia), producing muscle stiffness. In patients, muscle stiffness lessens with exercise, a change known as the warm-up phenomenon. Our goal was to identify the mechanism underlying warm up and to use this information to guide development of novel therapy. Methods To determine the mechanism underlying warm-up, we used a recently discovered drug to eliminate muscle contraction, thus allowing prolonged intracellular recording from individual muscle fibers during induction of warm-up in a mouse model of myotonia congenita. Results Changes in action potentials suggested slow inactivation of sodium channels as an important contributor to warm-up. These data suggested enhancing slow inactivation of sodium channels might offer effective therapy for myotonia. Lacosamide and ranolazine enhance slow inactivation of sodium channels and are FDA-approved for other uses in patients. We compared the efficacy of both drugs to mexiletine, a sodium channel blocker currently used to treat myotonia. In vitro studies suggested both lacosamide and ranolazine were superior to mexiletine. However, in vivo studies in a mouse model of myotonia congenita suggested side effects could limit the efficacy of lacosamide. Ranolazine produced fewer side effects and was as effective as mexiletine at a dose that produced none of mexiletine’s hypoexcitability side effects. Interpretation We conclude ranolazine has excellent therapeutic potential for treatment of patients with myotonia congenita. PMID:25515836

Comparison of investigation methods of heat injury in grapevine (Vitis) and assessment to heat tolerance in different cultivars and species.

PubMed

Xu, Hongguo; Liu, Guojie; Liu, Guotian; Yan, Bofang; Duan, Wei; Wang, Lijun; Li, Shaohua

2014-06-05

In the context of global climate change, heat stress is becoming an increasingly important constraint on grapevine growth and berry quality. There is a need to breed new grape cultivars with heat tolerance and to design effective physiological defenses against heat stress. The investigation of heat injury to plants or tissues under high temperature is an important step in achieving these goals. At present, evaluation methods for heat injury include the gas exchange parameters of photosynthesis, membrane thermostability, chlorophyll content etc.; however, these methods have obvious disadvantages, such as insensitivity, inconvenience and delayed information. An effective and convenient method for investigating the heat injury of grapevine must be developed. In this study, an investigation protocol for a critical temperature (47°C) and heat treatment time (40 min) was developed in detached grape leaves. Based on the results, we found that the OJIP test was superior to measuring electrolyte leakage or photosynthetic O₂ evolution for investigating the heat injury of three cultivars of grapevine. Heat tolerance of 47 grape species and cultivars was evaluated through investigating heat injury using the OJIP test. Moreover, the electron transport chain (donor side, acceptor side and reaction center) of PSII in photosynthesis was further investigated. The OJIP test was a rapid, sensitive and convenient method for investigating heat injury in grapevine. An analysis of PSII function using this method indicated that the acceptor side was less sensitive to heat than was the donor side or the reaction center in grape leaves. Among the 47 taxa evaluated (cultivars, hybrids, and wild species), heat tolerance varied largely in each genotype group: most wild species and hybrids between V. labrusca and V. vinifera had relatively strong heat tolerance, but most cultivars from V. vinifera had relatively weak heat tolerance.

Comparison of investigation methods of heat injury in grapevine (Vitis) and assessment to heat tolerance in different cultivars and species

PubMed Central

2014-01-01

Background In the context of global climate change, heat stress is becoming an increasingly important constraint on grapevine growth and berry quality. There is a need to breed new grape cultivars with heat tolerance and to design effective physiological defenses against heat stress. The investigation of heat injury to plants or tissues under high temperature is an important step in achieving these goals. At present, evaluation methods for heat injury include the gas exchange parameters of photosynthesis, membrane thermostability, chlorophyll content etc.; however, these methods have obvious disadvantages, such as insensitivity, inconvenience and delayed information. An effective and convenient method for investigating the heat injury of grapevine must be developed. Results In this study, an investigation protocol for a critical temperature (47°C) and heat treatment time (40 min) was developed in detached grape leaves. Based on the results, we found that the OJIP test was superior to measuring electrolyte leakage or photosynthetic O2 evolution for investigating the heat injury of three cultivars of grapevine. Heat tolerance of 47 grape species and cultivars was evaluated through investigating heat injury using the OJIP test. Moreover, the electron transport chain (donor side, acceptor side and reaction center) of PSII in photosynthesis was further investigated. Conclusions The OJIP test was a rapid, sensitive and convenient method for investigating heat injury in grapevine. An analysis of PSII function using this method indicated that the acceptor side was less sensitive to heat than was the donor side or the reaction center in grape leaves. Among the 47 taxa evaluated (cultivars, hybrids, and wild species), heat tolerance varied largely in each genotype group: most wild species and hybrids between V. labrusca and V. vinifera had relatively strong heat tolerance, but most cultivars from V. vinifera had relatively weak heat tolerance. PMID:24898786

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.

Wettability, Polarity, and Water Absorption of Holm Oak Leaves: Effect of Leaf Side and Age1[OPEN

PubMed Central

Fernández, Victoria; Sancho-Knapik, Domingo; Guzmán, Paula; Peguero-Pina, José Javier; Gil, Luis; Karabourniotis, George; Khayet, Mohamed; Fasseas, Costas; Heredia-Guerrero, José Alejandro; Heredia, Antonio; Gil-Pelegrín, Eustaquio

2014-01-01

Plant trichomes play important protective functions and may have a major influence on leaf surface wettability. With the aim of gaining insight into trichome structure, composition, and function in relation to water-plant surface interactions, we analyzed the adaxial and abaxial leaf surface of holm oak (Quercus ilex) as a model. By measuring the leaf water potential 24 h after the deposition of water drops onto abaxial and adaxial surfaces, evidence for water penetration through the upper leaf side was gained in young and mature leaves. The structure and chemical composition of the abaxial (always present) and adaxial (occurring only in young leaves) trichomes were analyzed by various microscopic and analytical procedures. The adaxial surfaces were wettable and had a high degree of water drop adhesion in contrast to the highly unwettable and water-repellent abaxial holm oak leaf sides. The surface free energy and solubility parameter decreased with leaf age, with higher values determined for the adaxial sides. All holm oak leaf trichomes were covered with a cuticle. The abaxial trichomes were composed of 8% soluble waxes, 49% cutin, and 43% polysaccharides. For the adaxial side, it is concluded that trichomes and the scars after trichome shedding contribute to water uptake, while the abaxial leaf side is highly hydrophobic due to its high degree of pubescence and different trichome structure, composition, and density. Results are interpreted in terms of water-plant surface interactions, plant surface physical chemistry, and plant ecophysiology. PMID:24913938

Students Today, Teachers Tomorrow? Identifying Constraints on the Provision of Education. Policy Research Working Paper 5674

ERIC Educational Resources Information Center

Andrabi, Tahir; Das, Jishnu; Khwaja, Asim Ijaz

2011-01-01

With an estimated 115 million children not attending primary school in the developing world, increasing access to education is critical. Resource constraints limit the effectiveness of demand-based subsidies. This paper focuses on the importance of a supply-side factor--the availability of low-cost teachers--and the resulting ability of the market…

Children's Literature-Comparatively Reading. Thinking about the Pink Bits: A Consideration of the Influence of English Children's Literature.

ERIC Educational Resources Information Center

Webb, Jean

This paper examines the state of children's literature by tracing some of the side effects of nineteenth-century English children's literature. During their early histories, the British colonies, including America, were economically unable to produce their own children's books. Reading materials were imported from the home country, and, likewise,…

Is Life in a One-Parent Family Damaging to Children? A Look at Both Sides.

ERIC Educational Resources Information Center

Doering, William G.

The increasing divorce rate, along with other circumstances resulting in one-parent families, makes the study of the effects of living in a one-parent situation for children of crucial importance. Children of divorced parents have been characterized as having lower I.Q. scores, more behavior problems, and academic handicaps than children from…

Self-management of older adolescents with inflammatory bowel disease: a pilot study of behavior and knowledge as prelude to transition.

PubMed

Fishman, Laurie N; Barendse, Renée M; Hait, Elizabeth; Burdick, Cynthia; Arnold, Janis

2010-12-01

Patients gradually assume responsibility for self-management. This study sought to determine whether adolescents with inflammatory bowel disease (IBD) have developed key skills of self-management prior to the age at which many transfer to adult care. Adolescents aged 16 to 18 years old in the Children's Hospital Boston IBD database (94 total) received a mailed survey assessing knowledge and confidence of their own health information and behaviors. Respondents (43%) could name medication and dose with confidence but had very poor knowledge of important side effects. Most patients deferred responsibility mostly or completely to parents for scheduling appointments (85%), requesting refills (75%), or contacting provider between visits (74%). Older adolescents with IBD have good recall of medications but not of side effects. Parents remain responsible for the majority of tasks related to clinic visits and the acquisition of medications.

Print Advertisements for Alzheimer’s Disease Drugs: Informational and Transformational Features

PubMed Central

Gooblar, Jonathan; Carpenter, Brian D.

2014-01-01

Purpose We examined print advertisements for Alzheimer’s disease drugs published in journals and magazines between January 2008 and February 2012, using an informational versus transformational theoretical framework to identify objective and persuasive features. Methods In 29 unique advertisements, we used qualitative methods to code and interpret identifying information, charts, benefit and side effect language, and persuasive appeals embedded in graphics and narratives. Results Most elements contained a mixture of informational and transformational features. Charts were used infrequently, but when they did appear the accompanying text often exaggerated the data. Benefit statements covered an array of symptoms, drug properties, and caregiver issues. Side effect statements often used positive persuasive appeals. Graphics and narrative features emphasized positive emotions and outcomes. Implications We found subtle and sophisticated attempts both to educate and to persuade readers. It is important for consumers and prescribing physicians to read print advertisements critically so that they can make informed treatment choices. PMID:23687184

Medication adherence to oral iron therapy in patients with iron deficiency anemia

PubMed Central

Gereklioglu, Cigdem; Asma, Suheyl; Korur, Asli; Erdogan, Ferit; Kut, Altug

2016-01-01

Objective: This study aimed at investigating the factors affecting medication adherence in patients who use oral iron therapy due to iron deficiency anemia. Methods: A total of 96 female patients in fertile age with mean age of 30±10.1 years (range 18-53) who were admitted to Family Medicine Clinic between 01 January and 31 March 2015 and who had received iron therapy within the recent three years were enrolled in the study. Data were collected through a questionnaire form. Results: Of the patients, 39 (40,6%) were detected not to use the medication regularly or during the recommended period. A statistically significant relationship was found between non-adherence to therapy and gastrointestinal side effects and weight gain (p<0.05). Conclusion: Medication adherence is deficient in patients with iron deficiency anemia. The most important reason for this seems gastrointestinal side effects, in addition to weight gain under treatment. PMID:27375698

Lattice density functional theory investigation of pore shape effects. I. Adsorption in single nonperiodic pores.

PubMed

Malanoski, A P; van Swol, Frank

2002-10-01

A fully explicit in three dimensions lattice density functional theory is used to investigate adsorption in single nonperiodic pores. The effect of varying pore shape from the slits and cylinders that are normally simulated was our primary interest. A secondary concern was the results for pores with very large diameters. The shapes investigated were square pores with or without surface roughness, cylinders, right triangle pores, and trapezoidal pores. It was found that pores with very similar shape factors gave similar results but that the introduction of acute angled corners or very large side ratio lengths in rectangular pores gave results that were significantly different. Further, a rectangular pore going towards the limit of infinite side ratio does not approach the results of a slit pore. In all of these cases, the importance of features that are present for only a small portion of the pore is demonstrated.

Elicitation of cognitions related to HIV risk behaviors in persons with mental illnesses: implications for prevention.

PubMed

Tennille, Julie; Solomon, Phyllis; Fishbein, Martin; Blank, Michael

2009-01-01

An important step in research using the Theory of Reasoned Action and Theory of Planned Behavior (TRA/TPB) is conducting an elicitation process to identify topic and population specific cognitions. This study explored HIV risk behaviors in persons with mental illnesses and introduces findings from focus groups conducted during the development phase of an HIV primary and secondary prevention intervention study. Researchers held four focus groups with persons with mental illnesses focused on HIV risks and condom use. Participants discussed sexual side effects of psychotropic medications as a potential cause of both medication non-adherence and HIV risk behaviors. The intersection of these two issues is specific to this population. We conclude with the recommendation that HIV primary and secondary prevention intervention for persons with mental illnesses must incorporate the promotion of healthy sexuality, including attention to sexual side effects of psychotropic medications.

Medication adherence to oral iron therapy in patients with iron deficiency anemia.

PubMed

Gereklioglu, Cigdem; Asma, Suheyl; Korur, Asli; Erdogan, Ferit; Kut, Altug

2016-01-01

This study aimed at investigating the factors affecting medication adherence in patients who use oral iron therapy due to iron deficiency anemia. A total of 96 female patients in fertile age with mean age of 30±10.1 years (range 18-53) who were admitted to Family Medicine Clinic between 01 January and 31 March 2015 and who had received iron therapy within the recent three years were enrolled in the study. Data were collected through a questionnaire form. Of the patients, 39 (40,6%) were detected not to use the medication regularly or during the recommended period. A statistically significant relationship was found between non-adherence to therapy and gastrointestinal side effects and weight gain (p<0.05). Medication adherence is deficient in patients with iron deficiency anemia. The most important reason for this seems gastrointestinal side effects, in addition to weight gain under treatment.

Health-Related Quality of Life, Depression, Anxiety, and Self-Image in Acute Lymphocytic Leukemia Survivors.

PubMed

Baytan, Birol; Aşut, Çiğdem; Çırpan Kantarcıoğlu, Arzu; Sezgin Evim, Melike; Güneş, Adalet Meral

2016-12-01

With increasing survival rates in childhood acute lymphocytic leukemia (ALL), the long-term side effects of treatment have become important. Our aim was to investigate health-related quality of life, depression, anxiety, and self-image among ALL survivors. Fifty patients diagnosed with ALL and their siblings were enrolled. The Kovacs Children's Depression Inventory, State-Trait Anxiety Inventory, Offer Self-Image Questionnaire, and Pediatric Quality of Life InventoryTM were used for collecting data. ANOVA tests were used to determine if there were any significant differences between groups. ALL survivors had higher depression, more anxiety symptoms, lower quality of life, and more negative self-image when compared to their siblings. Continuous diagnostic and interventional mental health services might be necessary for possible emotional side effects of treatment during and after the treatment. Rehabilitation and follow-up programs should be implemented for children during and after treatment for ALL.

Print advertisements for Alzheimer's disease drugs: informational and transformational features.

PubMed

Gooblar, Jonathan; Carpenter, Brian D

2013-06-01

We examined print advertisements for Alzheimer's disease drugs published in journals and magazines between January 2008 and February 2012, using an informational versus transformational theoretical framework to identify objective and persuasive features. In 29 unique advertisements, we used qualitative methods to code and interpret identifying information, charts, benefit and side effect language, and persuasive appeals embedded in graphics and narratives. Most elements contained a mixture of informational and transformational features. Charts were used infrequently, but when they did appear the accompanying text often exaggerated the data. Benefit statements covered an array of symptoms, drug properties, and caregiver issues. Side effect statements often used positive persuasive appeals. Graphics and narrative features emphasized positive emotions and outcomes. We found subtle and sophisticated attempts both to educate and to persuade readers. It is important for consumers and prescribing physicians to read print advertisements critically so that they can make informed treatment choices.

Modern contraceptive use among women in the Asuogyaman district of Ghana: is reliability more important than health concerns?

PubMed

Teye, Joseph Kofi

2013-06-01

This study examines the socio-demographic determinants of modern contraceptive use among women in the Asuogyaman district of Ghana. The results reveal that although 97% of the survey respondents knew of at least one modern method of contraception, only 16% of them were using modern contraceptives. Statistical tests show that level of education, place of residence, and work status significantly influence modern contraceptive use among women in the study area. Fear of side effects, desire for more children, and partner's disapproval were the main barriers to modern contraceptive use in the study area. The use of traditional methods of contraception was very high because of the perception that they are safer. Based on these findings, it has been suggested that in addition to making family planning services available and accessible, health workers must address attitudinal factors such as fear of side effects and high fertility preferences.

Tinidazole versus Metronidazole for the Treatment of Bacterial Vaginosis

PubMed Central

SCHWEBKE, Jane R.; DESMOND, Renee A.

2010-01-01

Objective To compare the efficacy of two different doses of tinidazole with metronidazole for treatment of bacterial vaginosis and compare side effects of the drugs. Study design Women were randomized to metronidazole 500 mg BID, tinidazole 500 mg BID, or tinidazole 1 gm BID all for 7 days. Follow-up visits were conducted at day 14 and day 28. Results 593 women were enrolled. There were no significant differences between the treatment arms. Overall cure rates were 76.8% at 14 days and 64.5% at one month. Women who admitted to engaging in sexual intercourse during the study were significantly more likely to have BV at follow-up. There were no significant differences in adverse events across treatment arms. Conclusions There were no differences in cure rates between metronidazole and either of the tinidazole dosing regimens studied. In addition, there were no important differences in the side effect profiles of metronidazole and tinidazole. PMID:21167471

Changes in values of cholesterol and tryglicerides after weight loss during treatment with aripiprazole in a patient with schizophrenia - Case report.

PubMed

Uzun, Suzana; Kozumplik, Oliver; Sedić, Biserka

2010-06-01

Metabolic syndrome can contribute to significant morbidity and premature mortality and should be accounted for in the treatment of mental disorders. Patients with schizophrenia are at risk of undetected somatic comorbidity. Patients with schizophrenia have metabolically unfavorable body composition, comprising abdominal obesity, high fat percentage and low muscle mass, leading to increased risk of metabolic and cardiovascular diseases. Smoking, poor diet, reduced physical activity and alcohol or drug abuse are prevalent in people with schizophrenia and contribute to the overall cardiovascular disease risk. Side effects of antipsychotics may cause diagnostic problems in deciding regarding the origin of particular symptoms (somatic illness vs. side effects) during treatment of psychotic disorders. Bearing in mind frequent comorbidity between of psychotic and somatic disorders, early recognition of such comorbidity is important, as well as the selection of antipsychotics. The aim of this article is to report a case of changes in values of cholesterol and tryglicerides after weight loss, during treatment with aripiprazole in a patient with schizophrenia. This case report emphasizes the importance of regular monitoring of values of cholesterol and tryglicerides during treatment with antipsychotics.

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 ...

A ruthenium(II) complex inhibits tumor growth in vivo with fewer side-effects compared with cisplatin.

PubMed

Wang, Jin-Quan; Zhang, Ping-Yu; Ji, Liang-Nian; Chao, Hui

2015-05-01

The antitumor activity of a ruthenium(II) polypyridyl complex, Δ-[Ru(bpy)2(HPIP)](ClO4)2 (Δ-Ru1, where bpy=2,2'-bipyridine, HPIP=2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline), was evaluated. The in vivo experiments showed that Δ-Ru1 inhibited the growth of a human cervical carcinoma cell line (HeLa) xenotransplanted into nude mice with efficiency similar to that of cisplatin. Histopathology examination of the tumors from treated xenograft models was consistent with apoptosis in tumor cells. Importantly, in striking contrast with cisplatin, Δ-Ru1 did not cause any detectable side effects on the kidney, liver, peripheral neuronal system, or the hematological system at the pharmacologically effective dose. The preclinical studies reported here provide support for the clinical use of Δ-Ru1 as an exciting new drug candidate with lower toxicity than cisplatin, endowed with proapoptotic properties. Copyright © 2015 Elsevier Inc. All rights reserved.

Breaking the barrier: the Health Belief Model and patient perceptions regarding contraception.

PubMed

Brown, Wendy; Ottney, Anne; Nguyen, Sammie

2011-05-01

The study was conducted to determine the discrepancy between unintended pregnancies and use of contraception is attributed to imperfect use, misconceptions and an inability to adjust therapy to lifestyle. A survey administered at a Federal clinic incorporated the Health Belief Model to determine patient's emphasis in pregnancy prevention. Analysis focused on comparing participant demographics to reasons for contraceptive selection. Ease of use ranked the most important for contraception as patient's education levels increased (p=.001). As household income increased, emphasis on potential side effects became less (p=.02). Patients with private insurance ranked ease of use most frequently (p=.01). Males emphasized effectiveness and menstrual suppression more than females (p=.04 and .008). A positive correlation between perceived benefit regarding ease of use as educational level increased and perceived barriers due to side effects as income level decreased immerged. Special counseling by practitioners to improve patient's self-efficacy, ultimately enhancing contraceptive adherence, are warranted. Copyright © 2011 Elsevier Inc. All rights reserved.

A Comet Engulfs Mars: MAVEN Observations of Comet Siding Spring's Influence on the Martian Magnetosphere

NASA Technical Reports Server (NTRS)

Espley, Jared R.; Dibraccio, Gina A.; Connerney, John E. P.; Brain, David; Gruesbeck, Jacob; Soobiah, Yasir; Halekas, Jasper S.; Combi, Michael; Luhmann, Janet; Ma, Yingjuan

2015-01-01

The nucleus of comet C/2013 A1 (Siding Spring) passed within 141,000?km of Mars on 19 October 2014. Thus, the cometary coma and the plasma it produces washed over Mars for several hours producing significant effects in the Martian magnetosphere and upper atmosphere. We present observations from Mars Atmosphere and Volatile EvolutioN's (MAVEN's) particles and field's instruments that show the Martian magnetosphere was severely distorted during the comet's passage. We note four specific major effects: (1) a variable induced magnetospheric boundary, (2) a strong rotation of the magnetic field as the comet approached, (3) severely distorted and disordered ionospheric magnetic fields during the comet's closest approach, and (4) unusually strong magnetosheath turbulence lasting hours after the comet left. We argue that the comet produced effects comparable to that of a large solar storm (in terms of incident energy) and that our results are therefore important for future studies of atmospheric escape, MAVEN's primary science objective.

Overview of clinical use and side effect profile of valsartan in Chinese hypertensive patients

PubMed Central

Huang, Qi-Fang; Li, Yan; Wang, Ji-Guang

2014-01-01

We reviewed the Chinese and English literature for the efficacy and safety data of valsartan monotherapy or combination therapy in Chinese hypertensive patients. According to the data of ten randomized controlled trials, valsartan monotherapy was as efficacious as another angiotensin receptor blocker or other classes of antihypertensive drugs, excepting the slightly inferior diastolic blood pressure-lowering effect in comparison with calcium channel blockers. According to the data of six randomized controlled trials, valsartan combination, with hydrochlorothiazide, amlodipine, or nifedipine gastrointestinal therapeutic system, was more efficacious than monotherapy of valsartan, amlodipine, or nifedipine gastrointestinal therapeutic system. According to these trials, valsartan had an acceptable tolerability, regardless of whether it was used as monotherapy or in combination therapy. Nonetheless, several rare side effects have been reported, indicating that it should still be used with caution. This is of particular importance given that there are millions of hypertensive patients, worldwide, currently exposed to the drug. PMID:24403822

Parameter study for child injury mitigation in near-side impacts through FE simulations.

PubMed

Andersson, Marianne; Pipkorn, Bengt; Lövsund, Per

2012-01-01

The objective of this study is to investigate the effects of crash-related car parameters on head and chest injury measures for 3- and 12-year-old children in near-side impacts. The evaluation was made using a model of a complete passenger car that was impacted laterally by a barrier. The car model was validated in 2 crash conditions: the Insurance Institute for Highway Safety (IIHS) and the US New Car Assessment Program (NCAP) side impact tests. The Small Side Impact Dummy (SID-IIs) and the human body model 3 (HBM3) (Total HUman Model for Safety [THUMS] 3-year-old) finite element models were used for the parametric investigation (HBM3 on a booster). The car parameters were as follows: vehicle mass, side impact structure stiffness, a head air bag, a thorax-pelvis air bag, and a seat belt with pretensioner. The studied dependent variables were as follows: resultant head linear acceleration, resultant head rotational acceleration, chest viscous criterion, rib deflection, and relative velocity at head impact. The chest measurements were only considered for the SID-IIs. The head air bag had the greatest effect on the head measurements for both of the occupant models. On average, it reduced the peak head linear acceleration by 54 g for the HBM3 and 78 g for the SID-IIs. The seat belt had the second greatest effect on the head measurements; the peak head linear accelerations were reduced on average by 39 g (HBM3) and 44 g (SID-IIs). The high stiffness side structure increased the SID-IIs' head acceleration, whereas it had marginal effect on the HBM3. The vehicle mass had a marginal effect on SID-IIs' head accelerations, whereas the lower vehicle mass caused 18 g higher head acceleration for HBM3 and the greatest rotational acceleration. The thorax-pelvis air bag, vehicle mass, and seat belt pretensioner affected the chest measurements the most. The presence of a thorax-pelvis air bag, high vehicle mass, and a seat belt pretensioner all reduced the chest viscous criterion (VC) and peak rib deflection in the SID-IIs. The head and thorax-pelvis air bags have the potential to reduce injury measurements for both the SID-IIs and the HBM3, provided that the air bag properties are designed to consider these occupant sizes also. The seat belt pretensioner is also effective, provided that the lateral translation of the torso is managed by other features. The importance of lateral movement management is greater the smaller the occupant is. Light vehicles require interior restraint systems of higher performance than heavy vehicles do to achieve the same level of injury measures for a given side structure. Copyright © 2012 Taylor & Francis Group, LLC

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.

Use of lipid-lowering medicinal herbs during pregnancy: A systematic review on safety and dosage

PubMed Central

Rouhi-Boroujeni, Hojjat; Heidarian, Esfandiar; Rouhi-Boroujeni, Hamid; Khoddami, Minasadat; Gharipour, Mojgan; Rafieian-Kopaei, Mahmoud

2017-01-01

BACKGROUND Hyperlipidemia is one of the important diseases in pregnancy that causes fetal abnormalities during pregnancy and after the birth. Unfortunately, the usual anti-fat drugs are associated with high morbidity in fetus and due to people's inclination towards taking herbs, it is required to identify side effects of medicinal herbs in pregnancy. The aim of this study was to present hypolipidemic herbs that would not any complications for mother and fetus. METHODS In this review article, the major electronic databases such as EBSCO, Central Register of Controlled Trials (CENTRAL), China Network Knowledge Infrastructure (CNKI), Cochrane, Google scholar, MEDLINE, SciVerse, Scopus, and Web of Science were searched using the key words “herbal” and “hyperlipidemia”, “herbal” and “pregnancy” matched by MeSH from their respective inceptions till September, 2016. Total of 1723 publications (145 review articles, 855 original research articles, and 723 abstracts) about the effect of herbals on hyperlipidemia and 682 publications (200 abstracts, 423 original research articles, and 59 review articles) about the effect of herbals in pregnancy were retrieved. At the end, a list of medicinal plants effective on hyperlipidemia alongside their effects on pregnancy was developed. Finally, the plants effective on hyperlipidemia and safe during pregnancy were determined and their dosage, complications, mechanism of action, and side effects were reported. RESULTS A total of 110 effective herbs on hyperlipidemia were identified and complications of 95 plants in pregnancy were studied. At last, among the 55 selected plants effective on hyperlipidemia and examined for pregnancy, we reported 12 herbs with their dosage and special considerations that can be used to treat hyperlipidemia during pregnancy. CONCLUSION Some medicinal plants can be used to treat hyperlipidemia during pregnancy without any significant side effects both on mother or fetus. PMID:29147122

[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.

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.

Radiation Protection Methods for the Interventionalist’s Hands: Use of an Extension Tube

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

Dixon, Shaheen, E-mail: shaheen7noorani@gmail.com; Schick, Daniel, E-mail: Daniel.Schick@health.qld.gov.au; Harper, John, E-mail: John-Harper@health.qld.gov.au

2015-04-15

PurposeCumulative radiation exposure to the hands during certain interventional procedures may be high. It is important to decrease the amount of radiation to the operator due to the possibility of deterministic effects. We performed a pilot study to demonstrate a significant decrease in operator dose when using extension tubing (ET) in combination with shielding and collimation during a simulated percutaneous transhepatic cholangiogram (PTC) procedure.MethodsA whole body, anthropomorphic phantom was used to simulate the patient. A Unfors-Xi Survey detector (to measure scatter) supported by a retort stand and trolley was placed in various positions to simulate the position of hands andmore » eyes/thyroid of an interventionalist. Radiation dose was measured simulating left and right-sided PTC punctures with and without a lead shield, and with and without ET.ResultsRegarding the radiation dose to the hands; the use of an ET reduces dose by 54 % in right-sided PTC punctures without a shield and by 91 % if used in combination with a shield. For left-sided PTC punctures, ET reduces hand dose by 75 %. The use of collimation decreases hand dose by approximately 60 %. The use of shielding reduces dose to the eyes/thyroid by 98 %.ConclusionsThe dose to the hands can be significantly reduced with the appropriate use of a shield, ET, and tight collimation. The use of a shield is paramount to reduce dose to the eyes/thyroid. It is important for interventionalists to adhere to radiation protective practice considering the potential deterministic effects during a lifelong career.« less

Using a multidimensional unfolding approach to assess multiple sclerosis patient preferences for disease-modifying therapy: a pilot study

PubMed Central

Sempere, Angel Perez; Vera-Lopez, Vanesa; Gimenez-Martinez, Juana; Ruiz-Beato, Elena; Cuervo, Jesús; Maurino, Jorge

2017-01-01

Purpose Multidimensional unfolding is a multivariate method to assess preferences using a small sample size, a geometric model locating individuals and alternatives as points in a joint space. The objective was to evaluate relapsing–remitting multiple sclerosis (RRMS) patient preferences toward key disease-modifying therapy (DMT) attributes using multidimensional unfolding. Patients and methods A cross-sectional pilot study in RRMS patients was conducted. Drug attributes included relapse prevention, disease progression prevention, side-effect risk and route and schedule of administration. Assessment of preferences was performed through a five-card game. Patients were asked to value attributes from 1 (most preferred) to 5 (least preferred). Results A total of 37 patients were included; the mean age was 38.6 years, and 78.4% were female. Disease progression prevention was the most important factor (51.4%), followed by relapse prevention (40.5%). The frequency of administration had the lowest preference rating for 56.8% of patients. Finally, 19.6% valued the side-effect risk attribute as having low/very low importance. Conclusion Patients’ perspective for DMT attributes may provide valuable information to facilitate shared decision-making. Efficacy attributes were the most important drug characteristics for RRMS patients. Multidimensional unfolding seems to be a feasible approach to assess preferences in multiple sclerosis patients. Further elicitation studies using multidimensional unfolding with other stated choice methods are necessary to confirm these findings. PMID:28615928

Ten Important Tips in Treating a Patient with Lumbar Disc Herniation

PubMed Central

Hejrati, Hamid; Ariamanesh, Shahrara

2016-01-01

Lumbar disc herniation is a common spinal disorder that usually responds favorably to conservative treatment. In a small percentage of the patients, surgical decompression is necessary. Even though lumbar discectomy constitutes the most common and easiest spine surgery globally, adverse or even catastrophic events can occur. Appropriate patient selection and effective neural decompression constitute the most important points for better surgical outcomes and avoidance of unpleasant complications. Other important tips include timely performance of magnetic resonance imaging, correct interpretation of scan data, preoperative detection of underlying instability, exclusion of non-discogenic sciatica, determination of the main cause of clinical pathology, avoidance of the wrong side or level, and being sure that the more detailed procedure does not necessarily mean the more effective procedure. PMID:27790328

Cochlear implant effectiveness in postlingual single-sided deaf individuals: what's the point?

PubMed

Finke, Mareike; Bönitz, Hanna; Lyxell, Björn; Illg, Angelika

2017-06-01

By extending the indication criteria for cochlear implants (CI), the population of CI candidates increased in age, as well as range and type of hearing loss. This qualitative study identified factors that contributed to seek CI treatment in single-sided deaf individuals and gained insights how single-sided deafness (SSD) and hearing with a CI affect their lives. An open-ended questionnaire and a standardised inventory (IOI-HA) were used. Qualitative data reflecting the reasons to seek CI treatment and the individual experiences after CI switch-on were collected. A total of 19 postlingually deafened single-sided deaf CI users. Participants use their CI daily and stated that their life satisfaction increased since CI activation. The analysis of the qualitative data revealed four core categories: sound localisation, tinnitus and noise sensitivity, fear to lose the second ear and quality of life. Our results show how strongly and diversely quality of hearing and quality of life is affected by acquired SSD and improved after CI activation. Our data suggest that the fear of hearing loss (HL) on the normal hearing (NH) ear is an important but so far neglected reason to seek treatment with a CI in individuals with postlingual SSD.

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.

Ocular side-effects associated with imatinib mesylate (Gleevec).

PubMed

Fraunfelder, Frederick W; Solomon, Jonathan; Druker, Brian J; Esmaeli, Bita; Kuyl, Jennifer

2003-08-01

This retrospective case series describes ocular side-effects associated with imatinib mesylate (Gleevec) and the clinical characteristics of these adverse reactions. A chart review of 104 patients on imatinib mesylate therapy from Oregon Health & Science University's Cancer Center were studied with regard to ocular side-effects. In addition, spontaneous reports from the Food and Drug Administration, the World Health Organization, and the National Registry of Drug-Induced Ocular Side-Effects databases were reviewed, including a Medline literature search. Seventy-three (70%) of the patients at OHSU developed periorbital edema and 19 patients (18%) developed epiphora after receiving imatinib mesylate. Average dose was 407.5+/-60 mg. Periorbital edema occurred an average of 68+/-48 days after initiation of therapy. WHO classification of side-effects is as follows: certain: periorbital edema; probable: epiphora; possible: extraocular muscle palsy, ptosis, blepharoconjunctivitis; unlikely: glaucoma, papilledema, retinal hemorrhage, photosensitivity, abnormal vision, and increased intraocular pressure. Periorbital edema and epiphora are the two most common ocular side-effects related to imatinib mesylate therapy. Clinical characteristics of imatinib mesylate induced periorbital edema are described. Management of ocular side-effects is conservative except in very rare cases of visually significant periorbital edema.

Understanding Statin Use in America and Gaps in Patient Education (USAGE): an internet-based survey of 10,138 current and former statin users.

PubMed

Cohen, Jerome D; Brinton, Eliot A; Ito, Matthew K; Jacobson, Terry A

2012-01-01

Statins substantially reduce the risk of cardiovascular disease and are generally well-tolerated. Despite this, many patients discontinue therapy. A better understanding of the characteristics of current and former statin users may be helpful for formulating strategies to improve long-term adherence. The Understanding Statin Use in America and Gaps in Education (USAGE) survey assessed the attitudes, beliefs, practices, and behavior of current and former statin users. Individuals 18 years or older who reported a history of high cholesterol and current or former statin use were identified within a registered consumer panel cohort in the United States and invited to participate in an Internet survey. Of the 10,138 respondents, 8918 (88%) were current statin users and 1220 (12%) were former users. Participants (mean age 61 years) were predominantly white (92%), female (61%), of middle income (median $44,504/yr), and had health insurance (93%). Among current users, 95% took a statin alone, and 70% had not missed a dose in the past month. Although ∼70% reported that their physicians had explained the importance of cholesterol levels for their heart health former users were less satisfied with the discussions (65% vs. 83%, P < .05). Muscle-related side effects were reported by 60% and 25% of former and current users, respectively (P < .05). Nearly half of all respondents switched statins at least once. The primary reason for switching by current users was cost (32%) and the primary reason for discontinuation was side effects (62%). This survey provides important insights into behavior and attitudes among current and former statin users and the results suggest that more effective dialogue between healthcare providers and patients may increase persistence of statin use, particularly when the patient has concerns about side effects and drug costs. Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Possible immunosuppressive effects of drug exposure and environmental and nutritional effects on infection and vaccination.

PubMed

Huemer, H P

2015-01-01

A variety of drugs which are not primarily considered to be immunosuppressive agents have been described to modulate the humoral and cellular immune response in humans or animals. Thereby they may have an influence on the effectiveness and possible side effects of vaccines. This mini review lists some of the different substance classes and also some of endogeneous, infectious, nutritional, and environmental influences with suspected capability to interfere with immunizations. Studies in most cases focused on substances with known immunosuppressive functions, but there is growing evidence for immunomodulatory effects also of commonly used drugs with wide distribution. In particular combinations of those antiproliferative and antiphlogistic side effects of different substance classes have not been studied in detail but may substantially interfere with the development of a functional humoral and cellular immune response. The drugs of importance include antipyretics, anticoagulants, tranquilizers, and substances influencing lipid metabolism but also commonly used drugs of abuse like alcohol or cannabinoids. Additional substances of environmental, nutritional, or microbiological origin may also play a role but their combinatory/synergistic effects have been disregarded so far due to the lack of systematic data and the complex study designs necessary to elucidate those complex epidemiologic questions.

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.

Patterns of fish assemblage structure and habitat use among main- and side-channel environments in the lower Kootenai River, Idaho

USGS Publications Warehouse

Watkins, Carson J.; Stevens, Bryan S.; Quist, Michael C.; Shepard, Bradley B.; Ireland, Susan C.

2015-01-01

The lower Kootenai River, Idaho, was sampled during the summers of 2012 and 2013 to evaluate its fish assemblage structure at seven sites within main- and side-channel habitats where large-scale habitat rehabilitation was undertaken. Understanding the current patterns of fish assemblage structure and their relationships with habitat is important for evaluating the effects of past and future rehabilitation projects on the river. Species-specific habitat associations were modeled, and the variables that best explained the occurrence and relative abundance of fish were identified in order to guide future habitat rehabilitation so that it benefits native species. The results indicated that the side-channel habitats supported higher species richness than the main-channel habitats and that nonnative fishes were closely associated with newly rehabilitated habitats. This research provides valuable insight on the current fish assemblages in the Kootenai River and the assemblage-level responses that may occur as a result of future rehabilitation activities.

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.

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

The inhibitory effects of a rhamnogalacturonan I (RG-I) domain from ginseng pectin on galectin-3 and its structure-activity relationship.

PubMed

Gao, Xiaoge; Zhi, Yuan; Sun, Lin; Peng, Xiaoxia; Zhang, Tao; Xue, Huiting; Tai, Guihua; Zhou, Yifa

2013-11-22

Pectin has been shown to inhibit the actions of galectin-3, a β-galactoside-binding protein associated with cancer progression. The structural features of pectin involved in this activity remain unclear. We investigated the effects of different ginseng pectins on galectin-3 action. The rhamnogalacturonan I-rich pectin fragment, RG-I-4, potently inhibited galectin-3-mediated hemagglutination, cancer cell adhesion and homotypic aggregation, and binding of galectin-3 to T-cells. RG-I-4 specifically bound to the carbohydrate recognition domain of galectin-3 with a dissociation constant of 22.2 nm, which was determined by surface plasmon resonance analysis. The structure-activity relationship of RG-I-4 was investigated by modifying the structure through various enzymatic and chemical methods followed by activity tests. The results showed that (a) galactan side chains were essential to the activity of RG-I-4, whereas arabinan side chains positively or negatively regulated the activity depending on their location within the RG-I-4 molecule. (b) The activity of galactan chain was proportional to its length up to 4 Gal residues and largely unchanged thereafter. (c) The majority of galactan side chains in RG-I-4 were short with low activities. (d) The high activity of RG-I-4 resulted from the cooperative action of these side chains. (e) The backbone of the molecule was very important to RG-I-4 activity, possibly by maintaining a structural conformation of the whole molecule. (f) The isolated backbone could bind galectin-3, which was insensitive to lactose treatment. The novel discovery that the side chains and backbone play distinct roles in regulating RG-I-4 activity is valuable for producing highly active pectin-based galectin-3 inhibitors.

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.

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.

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.

[Drug-induced gynecomastia].

PubMed

Schirren, U; Hinz, B; Schirren, C

1986-01-01

Concerning four own observations by men in the age of 41-69 years it has been reported about the drug-induced gynecomastia. It can be demonstrated that the spironolactone induced gynecomastia disappeared after stopping this drug. The knowledge of such side effects is the condition for a pre-information of the patient at the beginning of therapy. The mode of action of spironolactone is discussed. It is referred about the important role of the disturbance of the relation androgen: estrogens under spironolactone as well as the peripheral antiandrogen effect of this substance.

Bradykinesia induced by frequency-specific pallidal stimulation in patients with cervical and segmental dystonia.

PubMed

Huebl, Julius; Brücke, Christof; Schneider, Gerd-Helge; Blahak, Christian; Krauss, Joachim K; Kühn, Andrea A

2015-07-01

Pallidal deep brain stimulation (DBS) is an effective treatment for patients with primary dystonia leading to a substantial reduction of symptom severity. However, stimulation induced side effects such as bradykinesia have also been reported recently. The influence of stimulation parameters on such side effects have not yet been systemically assessed in these patients. Here we tested the effect of stimulation frequency and duration of stimulation period on hand motor function in 22 patients with primary cervical and segmental dystonia using an unimanual tapping task. Patients performed the task at 4 different stimulation frequencies (0 Hz = OFF stimulation, 20, 50 and ≥130 Hz = high frequency stimulation) after either an SHORT (5 min, N = 16) or a LONG (60 min, N = 6) stimulation period (i.e. changing of DBS-frequency). The change of overall mobility under HFS compared to the preoperative state was assessed with a 5-point Likert-scale. Tapping performance was analysed using a repeated measures ANOVA with the main factor 'FREQUENCY'. Tapping performance at HFS and changes in general mobility were correlated using Spearman's Rho. We found a frequency specific modulation of hand motor function: HFS led to deterioration and 20 Hz stimulation to improvement of tapping rate. The effects were predominant in the 'LONG' group suggesting a significant contribution of stimulation duration. This is important to consider during DBS-programming and evaluation of potential side effects. Furthermore, the impairment in hand motor function under HFS was mirrored by the patients' observation of a deterioration of general mobility. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rauwolfia in the Treatment of Hypertension.

PubMed

Lobay, Douglas

2015-06-01

Rauwolfia serpentina is a safe and effective treatment for hypertension. The plant was used by many physicians throughout India in the 1940s and then was used throughout the world in the 1950s, including in the United States and Canada. It fell out of popularity when adverse side effects, including depression and cancer, became associated with it. This author reviews the scientific literature with regard to the use of Rauwolfia and the treatment of hypertension. The author reviews the plant's botany, chemistry, and pharmacology and provides a researched and documented method of action for the active ingredients. With special emphasis on the plant's role in treating high blood pressure, the author looks at medical uses of the plant, critically examining its adverse side effects, toxicology, and carcinogenicity. The author refutes the association between the plant and carcinogenicity and discusses the importance of correct dosing and of screening patients to minimize the occurrence of depression. He concludes with the recommendation of use of low dose Rauwolfia (LDR) for suitable patients with hypertension. The plant provides clinicians with a safe and effective adjunct to pharmaceuticals in the treatment of high blood pressure.

Experiments in free shear flows: Status and needs for the future

NASA Technical Reports Server (NTRS)

Kline, S. J.; Coles, D. E.; Eggers, J. M.; Harsha, P. T.

1973-01-01

Experiments in free turbulent flows are recommended with the primary concern placed on classical flows in order to augment understanding and for model building. Five classes of experiments dealing with classical free turbulent flows are outlined and proposed as being of particular significance for the near future. These classes include the following: (1) Experiments clarifying the effect of density variation owing to use of different gases, with and without the additional effect of density variation due to high Mach number or other effects; (2) experiments clarifying the role and importance of various parameters which determine the behavior of the near field as well as the condictions under which any of these parameters can be neglected; (3) experiments determining the cumulative effect of initial conditions in terms of distance to fully established flow; (4) experiments for cases where two layers of distinctly different initial turbulence structure flow side by side at the same mean speed; and (5) experiment using contemporary experimental techniques to study structure in free turbulent shear flows in order to compliment and support contemporary work on boundary layers.

Effective Utilization of Oral Hypoglycemic Agents to Achieve Individualized HbA1c Targets in Patients with Type 2 Diabetes Mellitus.

PubMed

Bannister, Margaret; Berlanga, Jenny

2016-09-01

Type 2 diabetes is a progressive condition that may require the combination of three oral treatments to achieve optimal glycemic management to prevent microvascular and macrovascular complications whilst minimizing the risk of acute complications and side effects or adverse reactions to treatments. With the widening availability of treatment options and increasing importance of individualized treatment pathways, including personalized HbA1c targets, this article will explore the mode of action of currently available oral treatments, factors to consider when individualizing HbA1c targets, the relevance of estimated glomerular filtration rate assessment, and the importance of reviewing the clinical impact of all treatment decisions.

Interaction Enthalpy of Side Chain and Backbone Amides in Polyglutamine Solution Monomers and Fibrils.

PubMed

Punihaole, David; Jakubek, Ryan S; Workman, Riley J; Asher, Sanford A

2018-04-19

We determined an empirical correlation that relates the amide I vibrational band frequencies of the glutamine (Q) side chain to the strength of hydrogen bonding, van der Waals, and Lewis acid-base interactions of its primary amide carbonyl. We used this correlation to determine the Q side chain carbonyl interaction enthalpy (Δ H int ) in monomeric and amyloid-like fibril conformations of D 2 Q 10 K 2 (Q10). We independently verified these Δ H int values through molecular dynamics simulations that showed excellent agreement with experiments. We found that side chain-side chain and side chain-peptide backbone interactions in fibrils and monomers are more enthalpically favorable than are Q side chain-water interactions. Q10 fibrils also showed a more favorable Δ H int for side chain-side chain interactions compared to backbone-backbone interactions. This work experimentally demonstrates that interamide side chain interactions are important in the formation and stabilization of polyQ fibrils.

Cerebral Arterial Occlusion Did Not Promote the Prevalence of Cerebral Amyloid Angiopathy.

PubMed

Honda, Kazuhiro

2016-08-01

An impairment of amyloid-β (Aβ) clearance has been suggested in Alzheimer's disease. Perivascular drainage along cerebrovascular vessels is considered an important amyloid clearance pathway. This study examined the effect of reduced arterial pulsation that could cause an impairment in cerebral amyloid drainage on the prevalence of cortical microbleeds (CMBs), a surrogate marker for cerebral amyloid angiopathy (CAA). Patients who lost depiction of either side of the carotid artery or the middle cerebral artery on magnetic resonance angiography were studied. Those who showed acute cerebral infarction or a previous cortical cerebral infarction were excluded. The number of CMBs was counted on the occluded and non-occluded sides of the brain in each subject. The number of subjects who showed more CMBs on the occluded side of the brain was compared with the number of subjects who showed more CMBs on the non-occluded side of the brain. Twenty-eight patients were studied. The extent of lacunar infarction and white matter lesions was not different, irrespective of the occluded vessels or the distribution of CMBs. The prevalence of CMBs was not different between the occluded and non-occluded sides of the brain. In this cross-sectional study, reduction of arterial pulsation was not associated with a higher prevalence of CAA. Therefore, reduced arterial pulsation alone may not be enough to promote CAA.

Mouse interleukin-2 structure-function studies: substitutions in the first alpha-helix can specifically inactivate p70 receptor binding and mutations in the fifth alpha-helix can specifically inactivate p55 receptor binding.

PubMed Central

Zurawski, S M; Zurawski, G

1989-01-01

The function of two alpha-helical regions of mouse interleukin-2 were analyzed by saturation substitution analysis. The functional parts of the first alpha-helix (A) was defined as residues 31-39 by the observation that proline substitutions within this region inactivate the protein. Four residues within alpha-helix A, Leu31, Asp34, Leu35 and Leu38, were found to be crucial for biological activity. Structural modeling suggested that these four residues are clustered on one face of alpha-helix A. Residues 31 and 35 had to remain hydrophobic for the molecule to be functional. At residue 38 there was a preference for hydrophobic side chain residues, while at residue 34 some small side chain residues as well as acidic or amide side chain residues were functionally acceptable. Inactivating changes at residue 34 had no effect upon the ability of the protein to interact with the p55 receptor. Disruption of the fifth alpha-helix (E), which had little effect upon biological activity, resulted in an inability of the protein to interact with the p55 receptor. Mutagenesis of the alpha-helix E region demonstrated that alpha-helicity and the nature of the side chain residues in this region were unimportant for biological activity. The region immediately proximal to alpha-helix E was important only for the single intramolecular disulfide linkage. PMID:2583124

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.

Compensation Effect in Electrical Conduction Process: Effect of Substituent Group

NASA Astrophysics Data System (ADS)

Mitra, Bani; Misra, T. N.

1987-05-01

The semiconductive properties of Vitamin A acid (Retinoic Acid), a long chain conjugated polyene, were studied as a function of the adsorption of different vapours. A compensation effect was observed in the electrical conduction process; unlike that in Vitamin A alcohol and Vitamin A acetate the compensation temperature was observed on the lower side of the experimental temperature (T0≈285 K). It is concluded that the terminal \\diagdown\\diagupC=0 group conjugated to the polyene chain plays an important role in the manifestation of the compensation effect. Various conduction parameters have been evaluated.

Reduction of Flap Side Edge Noise - the Blowing Flap

NASA Technical Reports Server (NTRS)

Hutcheson, Florence V.; Brooks, THomas F.

2005-01-01

A technique to reduce the noise radiating from a wing-flap side edge is being developed. As an airplane wing with an extended flap is exposed to a subsonic airflow, air is blown outward through thin rectangular chord-wise slots at various locations along the side edges and side surface of the flap to weaken and push away the vortices that originate in that region of the flap and are responsible for important noise emissions. Air is blown through the slots at up to twice the local flow velocity. The blowing is done using one or multiple slots, where a slot is located along the top, bottom or side surface of the flap along the side edge, or also along the intersection of the bottom (or top) and side surfaces.

Spin-bowling in cricket re-visited: model trajectories for various spin-vector angles

NASA Astrophysics Data System (ADS)

Robinson, Garry; Robinson, Ian

2016-08-01

In this paper we investigate, via the calculation of model trajectories appropriate to slow bowling in cricket, the effects on the flight path of the ball before pitching due to changes in the angle of the spin-vector. This was accomplished by allowing the spin-vector to vary in three ways. Firstly, from off-spin, where the spin-vector points horizontally and directly down the pitch, to top-spin where it points horizontally towards the off-side of the pitch. Secondly, from off-spin to side-spin where, for side-spin, the spin-vector points vertically upwards. Thirdly, where the spin-vector points horizontally and at 45° to the pitch (in the general direction of ‘point’, as viewed by the bowler), and is varied towards the vertical, while maintaining the 45° angle in the horizontal plane. It is found that, as is well known, top-spin causes the ball to dip in flight, side-spin causes the ball to move side-ways in flight and, perhaps most importantly, off-spin can cause the ball to drift to the off-side of the pitch late in its flight as it begins to fall. At a more subtle level it is found that, if the total spin is kept constant and a small amount of top-spin is added to the ball at the expense of some off-spin, there is little change in the side-ways drift. However, a considerable reduction in the length at which the ball pitches occurs, ˜25 cm, an amount that batsmen can ignore at their peril. On the other hand, a small amount of side-spin introduced to a top-spin delivery does not alter the point of pitching significantly, but produces a considerable amount of side-ways drift, ˜10 cm or more. For pure side-spin the side-ways drift is up to ˜30 cm. When a side-spin component is added to the spin of a ball bowled with a mixture of off-spin and top-spin in equal proportions, significant movement occurs in both the side-ways direction and in the point of pitching, of the order of a few tens of centimetres.

Patients' Values in Clinical Decision-Making.

PubMed

Faggion, Clovis Mariano; Pachur, Thorsten; Giannakopoulos, Nikolaos Nikitas

2017-09-01

Shared decision-making involves the participation of patient and dental practitioner. Well-informed decision-making requires that both parties understand important concepts that may influence the decision. This fourth article in a series of 4 aims to discuss the importance of patients' values when a clinical decision is made. We report on how to incorporate important concepts for well-informed, shared decision-making. Here, we present patient values as an important issue, in addition to previously established topics such as the risk of bias of a study, cost-effectiveness of treatment approaches, and a comparison of therapeutic benefit with potential side effects. We provide 2 clinical examples and suggestions for a decision tree, based on the available evidence. The information reported in this article may improve the relationship between patient and dental practitioner, resulting in more well-informed clinical decisions. Copyright © 2017 Elsevier Inc. All rights reserved.

Predicting drug side-effect profiles: a chemical fragment-based approach

PubMed Central

2011-01-01

Background Drug side-effects, or adverse drug reactions, have become a major public health concern. It is one of the main causes of failure in the process of drug development, and of drug withdrawal once they have reached the market. Therefore, in silico prediction of potential side-effects early in the drug discovery process, before reaching the clinical stages, is of great interest to improve this long and expensive process and to provide new efficient and safe therapies for patients. Results In the present work, we propose a new method to predict potential side-effects of drug candidate molecules based on their chemical structures, applicable on large molecular databanks. A unique feature of the proposed method is its ability to extract correlated sets of chemical substructures (or chemical fragments) and side-effects. This is made possible using sparse canonical correlation analysis (SCCA). In the results, we show the usefulness of the proposed method by predicting 1385 side-effects in the SIDER database from the chemical structures of 888 approved drugs. These predictions are performed with simultaneous extraction of correlated ensembles formed by a set of chemical substructures shared by drugs that are likely to have a set of side-effects. We also conduct a comprehensive side-effect prediction for many uncharacterized drug molecules stored in DrugBank, and were able to confirm interesting predictions using independent source of information. Conclusions The proposed method is expected to be useful in various stages of the drug development process. PMID:21586169

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.

Four measures of transportation's economic importance

DOT National Transportation Integrated Search

2000-04-01

As a commodity, transportation has a supply side and a demand side. Unlike many other commodities, however, transportation's supply and demand overlap extensively. A significant portion of transportation : is provided by consumers for their own use. ...

The Effect of One Session Low Level Laser Therapy of Extracted Follicular Units on the Outcome of Hair Transplantation.

PubMed

Tabaie, Seyed Mehdi; Berenji Ardestani, Hoda; Azizjalali, Mir Hadi

2016-01-01

Photobiostimulation with low level laser (LLL) has been used in medicine for a long time and its effects have been shown in many diseases. Some studies have evaluated the effect of LLL on androgenic alopecia. One of the most important limitations of the use of LLL in the treatment of alopecia is the requirement for multiple sessions, which is hardly accepted by patients. This study was conducted to evaluate the effect of the irradiation of extracted follicular hair units by LLL on the outcome of hair transplantation. We enrolled 10 patients with androgenic alopecia and after screening tests for infections and other diseases, we extracted hair follicular units. The hair units were divided in two groups. One group was irradiated by LLL 20 minutes before transplantation (660 nm, 80 Hz, 100 mW) and the other one was used as control. The containing plates were labeled as A and B and sent to the operation room. The surgeon was unaware of the therapy assigned to the plates and transplanted them randomly on the right or left side of the head. One hundred follicular units on each sides of the scalp were transplanted symmetrically. The follicles on both sides were evaluated at 3 and 6 months of transplantation for hair growth rate by another physician, blinded to the treatment assigned to each side. Ten patient with androgenic alopecia and mean (SD) age of 31.5 (6.6) years (range 25-45 years) completed the study. All patients had 100% hair growth at 3 and 6 months follow-up except one who had hair growth of 20% at three months of transplantation, which changed to 100% at sixth months. There was no significant difference between the groups regarding hair growth (P > 0.8). One session of LLL irradiation has no significant effect on the outcome of transplanted hair follicles. Studies with larger sample size are needed to draw a definite conclusion.

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

An analysis of the gastro-intestinal side-effects of non-steroidal anti-inflammatory drugs, with particular reference to comparative studies in man and laboratory species.

PubMed

Rainsford, K D

1982-01-01

A critical analysis has been performed of reports published on the incidence of gastro-intestinal (GI) side-effects found in arthritic patients being treated with non-steroid anti-inflammatory (NSAI) drugs. The results show the following: 1. The incidence of GI ulceration (as revealed by gastroscopy) and haemorrhage in arthritic patients taking NSAI drugs may be higher than suspected from clinical trial data. 2. Incidence of all GI side-effects (including ulceration and haemorrhage) may be lower with some of the new NSAI drugs than with traditional drugs (e.g. aspirin, indomethacin and phenylbutazone). 3. Arthritic patients may be more susceptible to the ulcerogenic actions of NSAI drugs. Experiments with animals, together with evidence from clinical studies, indicate that stress factors and the presence of decreased mucosal resistance in the diseased state may contribute to the enhanced susceptibility of the GI tract towards the ulcerogenicity of NSAI drugs. 4. Comparison of data on gastroscopic observations in man with the author's data on the effects of NSAI drugs in stress-sensitized rats shows the latter technique appears to be a useful means of predicting the ulcerogenic potential of NSAI drugs in man. The comparison has also been used to predict the ulcerogenicity of drug - alcohol combinations; alcohol being a common ulcerogen consumed by many patients. Some NSAI drugs with low ulcerogenic activity (i.e. azapropazone, benoxaprofen and fenclofenac) in the stressed-rat assay show little or no interaction with alcohol. These studies using laboratory animals show the importance of employing conditions to mimic environmental factors (e.g. stress and alcohol consumption) which might predispose individuals to ulcerogenic or other side-effects of NSAI drugs. From these studies it appears possible to construct 'predictive profiles' of the relative ulcerogenicity of NSAI drugs which may be applicable to the clinical situation in man.

Japan Report

DTIC Science & Technology

1985-03-18

increased profitability, productivity and more effective management ." Members of the British side also called for an increase in Japan’s defense...copyright transfer, or rental permission is called technology trade. According to the Statistic Bureau of the Management and Coordina- tion Agency...1- 8.8 -Swizerland 6.3 5.6 Others 13.1 Source: Statistics Bureau of the Management and Coordination Agency China. 66.2% of Japan’s imported

Positioning hospitals for improved access to capital.

PubMed

Ponton, Kevin T; Sandrick, Karen M

2002-11-01

Hospitals need to actively position themselves in the next 18 to 24 months to ensure continued access to financing. Hospitals need to shift their focus from investment income to operations. Hospitals should recognize the importance of balance-sheet liquidity to institutional investors. Not-for-profit hospitals should focus on both sides of the balance sheet. Healthcare executives need to develop effective leadership and investor-relations skills.

Drug induced neutropaenia--a trigger for necrotising fasciitis?

PubMed

Foulkes, Rhiannon; Hoare, David; Somasekar, Krishnamurthy

2011-08-04

The authors present a case of necrotising fasciitis of the peristomal area, in a patient who had undergone a previous ileostomy for ulcerative colitis. This was associated with neutropaenia, secondary to carbimazole, which had been commenced a few weeks previously for thyrotoxicosis. The authors therefore, stress the importance of monitoring patients closely for possible side effects and complications, while they are on immunosuppressive medication.

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.

Life after prostate cancer treatment: a mixed methods study of the experiences of men with sexual dysfunction and their partners.

PubMed

Albaugh, Jeffrey A; Sufrin, Nat; Lapin, Brittany R; Petkewicz, Jacqueline; Tenfelde, Sandi

2017-06-15

Prostate cancer is the most common non-skin cancer in men and sexual dysfunction is the most frequently reported long-term side effect of prostate cancer surgery or radiation. The aim of this study was to examine the experiences of men with sexual dysfunction and their partners following prostate cancer treatment. Men with sexual dysfunction from either surgical removal or radiation therapy 1-5 years after treatment were interviewed, as well as their partners. A mixed method design was used to determine the lived experience of men with sexual dysfunction. Open-ended questions guided the interviews. Twenty seven men completed the study with a mean age of 61 years (SD = 8.0; range = 44-77 years). Nine partners also participated. The majority of men (92.6%) had surgery. The average time from treatment to the interview was 23.5 months (SD = 11.7). Themes were frustration with sexual dysfunction, importance of support and understanding from others, depression and anxiety related to sexual dysfunction, importance of intimacy with partner, factors that impact treatment satisfaction, and education and comprehensive information about sex. Prostate cancer survivors and partners need accurate information about sexual side effects before during and after treatment. Men and partners required individualized help and guidance to manage sexual dysfunction. Support and understanding from partners, family, and others was also identified as an important aspect of healing and adjustment after prostate cancer treatment. Prostate cancer education/support groups played a key role in helping men and partners gain advocacy, education, and support. Psychological problems such as depression and anxiety need to be identified and addressed in men after prostate cancer treatment. Men and partners need assistance in understanding and navigating their way through intimacy to move forward with connectedness in their relationship. Satisfaction with treatment and with providers is dependent on patient education and understanding of all aspects of prostate cancer treatment including sexual side effects and incontinence.

Bilateral increase in expression and concentration of tachykinin in a unilateral rabbit muscle overuse model that leads to myositis

PubMed Central

2013-01-01

Background Tachykinins can have pro-inflammatory as well as healing effects during tissue reorganization and inflammation. Recent studies report an up-regulation in the expression of the substance P (SP)-preferred receptor, the neurokinin-1 receptor, in marked muscle inflammation (myositis). There is, however, only very little information on the expression patterns and levels of tachykinins in this situation. Methods The tachykinin system was analyzed using a rabbit experimental model of muscle overuse, whereby unilateral muscle exercise in combination with electrical stimulation led to muscle derangement and myositis in the triceps surae muscle (experimental length 1–6 weeks). Evaluations were made for both parts of the muscle (soleus and gastrocnemius muscles) in experimental and non-experimental (contralateral) sides. Morphologic evaluation, immunohistochemistry, in situ hybridization and enzyme immunoassay (EIA) analyses were applied. Results Myositis and muscle derangement occurred focally not only in the experimental side but also in the non-experimental side. In the inflammatory areas (focal myositis areas), there were frequent nerve fibers showing tachykinin-like immunoreactivity and which were parts of nerve fascicles and which were freely dispersed in the tissue. Cells in the inflammatory infiltrates showed tachykinin-like immunoreactivity and tachykinin mRNA expression. Specific immunoreactivity and mRNA expression were noted in blood vessel walls of both sides, especially in focally affected areas. With increasing experimental length, we observed an increase in the degree of immunoreactivity in the vessel walls. The EIA analyses showed that the concentration of tachykinin in the tissue on both sides increased in a time-dependent manner. There was a statistical correlation in the concentration of tachykinin and the level of tachykinin immunoreactivity in the blood vessel walls between experimental and non-experimental sides. Conclusions The observations show an up-regulation of the tachykinin system bilaterally during muscle derangement/myositis in response to pronounced unilateral muscle overuse. This up-regulation occurred in inflammatory areas and was related not only to increased tachykinin innervation but also to tachykinin expression in blood vessel walls and inflammatory cells. Importantly, the tachykinin system appears to be an important factor not only ipsilaterally but also contralaterally in these processes. PMID:23587295

Bilateral increase in expression and concentration of tachykinin in a unilateral rabbit muscle overuse model that leads to myositis.

PubMed

Song, Yafeng; Stål, Per S; Yu, Ji-Guo; Forsgren, Sture

2013-04-12

Tachykinins can have pro-inflammatory as well as healing effects during tissue reorganization and inflammation. Recent studies report an up-regulation in the expression of the substance P (SP)-preferred receptor, the neurokinin-1 receptor, in marked muscle inflammation (myositis). There is, however, only very little information on the expression patterns and levels of tachykinins in this situation. The tachykinin system was analyzed using a rabbit experimental model of muscle overuse, whereby unilateral muscle exercise in combination with electrical stimulation led to muscle derangement and myositis in the triceps surae muscle (experimental length 1-6 weeks). Evaluations were made for both parts of the muscle (soleus and gastrocnemius muscles) in experimental and non-experimental (contralateral) sides. Morphologic evaluation, immunohistochemistry, in situ hybridization and enzyme immunoassay (EIA) analyses were applied. Myositis and muscle derangement occurred focally not only in the experimental side but also in the non-experimental side. In the inflammatory areas (focal myositis areas), there were frequent nerve fibers showing tachykinin-like immunoreactivity and which were parts of nerve fascicles and which were freely dispersed in the tissue. Cells in the inflammatory infiltrates showed tachykinin-like immunoreactivity and tachykinin mRNA expression. Specific immunoreactivity and mRNA expression were noted in blood vessel walls of both sides, especially in focally affected areas. With increasing experimental length, we observed an increase in the degree of immunoreactivity in the vessel walls. The EIA analyses showed that the concentration of tachykinin in the tissue on both sides increased in a time-dependent manner. There was a statistical correlation in the concentration of tachykinin and the level of tachykinin immunoreactivity in the blood vessel walls between experimental and non-experimental sides. The observations show an up-regulation of the tachykinin system bilaterally during muscle derangement/myositis in response to pronounced unilateral muscle overuse. This up-regulation occurred in inflammatory areas and was related not only to increased tachykinin innervation but also to tachykinin expression in blood vessel walls and inflammatory cells. Importantly, the tachykinin system appears to be an important factor not only ipsilaterally but also contralaterally in these processes.

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.

Psychiatric side effects of antihypertensive drugs other than reserpine.

PubMed

Paykel, E S; Fleminger, R; Watson, J P

1982-02-01

The psychiatric side effects of the major antihypertensive drugs other than reserpine are reviewed, including centrally acting drugs such as methyldopa and clonidine, peripheral adrenergic drugs such as guanethidine, beta-adrenoceptor blockers such as propranolol, and diuretics. Problems with differential diagnosis and with the interpretation of case reports make assessment of psychiatric side effects difficult. Sedation and sleep disturbances are the most common side effects, occurring with methyldopa, clonidine, and propranolol. Only methyldopa is clearly associated with depression. Other reported effects are toxic confusional states and psychotic reactions. These are rare, however, and no clear patterns of development have been recognized.

The PsyLOG mobile application: development of a tool for the assessment and monitoring of side effects of psychotropic medication.

PubMed

Kuzman, Martina Rojnic; Andlauer, Olivier; Burmeister, Kai; Dvoracek, Boris; Lencer, Rebekka; Koelkebeck, Katja; Nawka, Alexander; Riese, Florian

2017-06-01

Mobile health interventions are regarded as affordable and accessible tools that can enhance standard psychiatric care. As part of the mHealth Psycho-Educational Intervention Versus Antipsychotic-Induced Side Effects (mPIVAS) project (www.psylog.eu), we developed the mobile application "PsyLOG" based on mobile "smartphone" technology to monitor antipsychotic-induced side effects. The aim of this paper is to describe the rationale and development of the PsyLOG and its clinical use. The PsyLOG application runs on smartphones with Android operating system. The application is currently available in seven languages (Croatian, Czech, English, French, German, Japanese and Serbian). It consists of several categories: "My Drug Effects", "My Life Styles", "My Charts", "My Medication", "My Strategies", "My Supporters", "Settings" and "About". The main category "My Drug Effects" includes a list of 30 side effects with the possibility to add three additional side effects. Side effects are each accompanied by an appropriate description and the possibility to rate its severity on a visual analogue scale from 0-100%. The PsyLOG application is intended to enhance the link between patients and mental health professionals, serving as a tool that more objectively monitors side-effects over certain periods of time. To the best of our knowledge, no such applications have so far been developed for patients taking antipsychotic medication or for their therapists.

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…

Fat grafting to the nose: personal experience with 36 patients.

PubMed

Monreal, Juan

2011-10-01

Clinicians are facing an increasing trend toward nonsurgical nose reshaping using synthetic injectables, mainly for patients who refuse standard rhinoplasties. Autologous fat grafting is a safer and convenient alternative to permanent or semipermanent injectables due to better results as well as fewer and milder side effects. The author reports his experience with fat grafting to the nose using his personal technique for 36 consecutive patients. The experience covers primary treatments of noses not treated by surgery, treatment of post rhinoplasty deformities, and combination fat grafting and rhinoplasties. The technique used by the author for fat grafting to the nose does not differ significantly from that used for other body or face areas. It is based in the atraumatic extraction of fat fragments using a multi-orifice cannula and injection of these fragments using 1.4- to 1.6-mm cannulas or needles. In combining rhinoplasties with fat grafting, fat grafts are used in the same location instead of a prosthesis or cartilage grafts. The initial analysis of postoperative results showed a good to high level of patient satisfaction, particularly in primary cases, with virtually no complications or severe side effects. Some easily corrected side effects probably were learning curve dependent. Autologous fat grafting is an effective and reliable technique for aesthetic and reconstructive nose reshaping for patients who refuse surgical treatments. Although optimal results can be achieved with this technique, they are not comparable with those obtained by surgical rhinoplasties, and this is an important issue to discuss with the prospective patient.

The Clinical Practice of Assessing Cognitive Function in Adults Receiving Electroconvulsive Therapy: Whom Are We Missing?

PubMed

Obbels, Jasmien; Vanbrabant, Koen; Bouckaert, Filip; Verwijk, Esmée; Sienaert, Pascal

2016-06-01

Cognition can be affected by electroconvulsive therapy (ECT). Good clinical practice includes neuropsychological assessment, although this is seldom a part of routine clinical practice. It looks like a substantial part of patients fail to complete cognitive assessments. This constitutes a problem in the generalizability of published clinical research on cognitive side effects. Most studies of ECT-related cognitive adverse effects do not discuss this important issue of so-called cognitive test nonparticipants. Recent findings suggest that cognitive test nonparticipants are more severely ill, and probably more vulnerable to cognitive side effects. To examine the feasibility of a neuropsychological test battery in daily clinical practice, in an adult population referred for ECT. We reviewed the clinical records of 84 patients referred for ECT. Demographic and clinical characteristics of those patients who were able to complete our routine cognitive testing at baseline are compared with those who could not complete the assessment. From 84 ECT patients, 60 (71%) completed a pre-ECT cognitive assessment, whereas 24 (29%) did not. Patients with a unipolar depression, with psychotic symptoms, who started their treatment with a bitemporal electrode placement were more likely to be test noncompleters than test completers. Patients with a unipolar depression, with psychotic features, who are treated with a bitemporal electrode placement, have a higher likelihood of not completing a pre-ECT cognitive assessment. These patients probably represent a subgroup more vulnerable to cognitive side effects.

Vaccine hesitancy and trust. Ethical aspects of risk communication.

PubMed

Nihlén Fahlquist, Jessica

2018-03-01

This paper analyses vaccination policy from an ethical perspective, against the background of the growing hesitancy towards e.g. the measles vaccine. The paper is normative and analyses ethical aspects of risk communication in the context of vaccination. It is argued that ethical analysis of risk communication should be done at the level of the message, the procedure and the effects. The paper takes examples from the Swedish context, linking the current lack of trust in experts to the 2009 vaccination policy and communication promoting the H1N1 vaccine Pandemrix. During the Swedish H1N1 vaccination policy in 2009, the message was that the vaccine is safe. However, a group of adolescents developed narcolepsy as a side effect of the vaccine. Taking this into account, it becomes clear that the government should communicate risks and benefits responsibly and take responsibility for individuals affected negatively by populational health interventions. To communicate respectfully entails not treating vaccine sceptics as ill-informed or less educated, but instead taking the concerns of the vaccine hesitant, who potentially could change their minds, as a starting-point of a respectful discussion. There will inevitably be individuals who suffer from side effects of justifiable population-based health promotion activities. However, the public should be able to trust the message and count on the government to take responsibility for individuals affected by side effects. This is important for normative reasons, but is additionally likely to contribute to restored and maintained trust.

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.

Bone morphogenetic proteins: a powerful osteoinductive compound with non-negligible side effects and limitations.

PubMed

Oryan, Ahmad; Alidadi, Soodeh; Moshiri, Ali; Bigham-Sadegh, Amin

2014-01-01

Healing and regeneration of large bone defects leading to non-unions is a great concern in orthopedic surgery. Since auto- and allografts have limitations, bone tissue engineering and regenerative medicine (TERM) has attempted to solve this issue. In TERM, healing promotive factors are necessary to regulate the several important events during healing. An ideal treatment strategy should provide osteoconduction, osteoinduction, osteogenesis, and osteointegration of the graft or biomaterials within the healing bone. Since many materials have osteoconductive properties, only a few biomaterials have osteoinductive properties which are important for osteogenesis and osteointegration. Bone morphogenetic proteins (BMPs) are potent inductors of the osteogenic and angiogenic activities during bone repair. The BMPs can regulate the production and activity of some growth factors which are necessary for the osteogenesis. Since the introduction of BMP, it has added a valuable tool to the surgeon's possibilities and is most commonly used in bone defects. Despite significant evidences suggesting their potential benefit on bone healing, there are some evidences showing their side effects such as ectopic bone formation, osteolysis and problems related to cost effectiveness. Bone tissue engineering may create a local environment, using the delivery systems, which enables BMPs to carry out their activities and to lower cost and complication rate associated with BMPs. This review represented the most important concepts and evidences regarding the role of BMPs on bone healing and regeneration from basic to clinical application. The major advantages and disadvantages of such biologic compounds together with the BMPs substitutes are also discussed. © 2014 International Union of Biochemistry and Molecular Biology.

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.

[Effectiveness and safety of oxcarbazepine in chronic neuropathic pain: a study of 40 cases].

PubMed

Fenollosa-Vázquez, P; Canós-Verdecho, M A; Núñez-Cornejo, C; Pallarés-Delgado, J

Neuropathic pain (NP) often fails to respond to the commonly established analgesic treatment. This fact, together with the existence of side effects, has led to the need to evaluate the analgesic effectiveness of antiepileptic drugs, which, as in the case of oxcarbazepine (OXC), are a valid alternative. The aim of this study was to evaluate the effectiveness and safety of OXC in patients suffering from chronic NP. We conducted a prospective, open study involving a series of 40 patients diagnosed with a long history of NP, which was previously resistant to different kinds of treatment with anticonvulsants, non-steroidal anti-inflammatory (NSAI) drugs, opiates and adjuncts. Patients were treated with OXC and they were evaluated in both the basal (prior to treatment) and final visits (after treatment) by means of the visual analogue scale (VAS), SF-McGill questionnaire and the Lattinen test. The patient's general impression of the result was also obtained. The statistical analysis was performed by calculating the "effect size", by computing Cohen's d. Treatment with OXC diminishes different symptomatic variations of this pain, but especially so in the case of lancinating discharges (d = 0.87, important effect) and burning pain (d = 0.60, moderate-important effect), although the allodynia (d = 0.48, moderate effect) also improved with treatment. In the opinion of the patients themselves, response to treatment was good or very good in 50% of cases. The chief side effects observed were dizziness, drowsiness and abdominal upsets. OXC can be seen as a therapeutic alternative to be taken very much into account in patients with NP having different aetiologies; it has a good benefit-risk ratio and is a form of treatment that is well accepted by patients.

Effects of surgical side and site on psychological symptoms following epilepsy surgery in adults.

PubMed

Prayson, Brigid E; Floden, Darlene P; Ferguson, Lisa; Kim, Kevin H; Jehi, Lara; Busch, Robyn M

2017-03-01

This retrospective study examined the potential role of side and site of surgery in psychological symptom change after epilepsy surgery and determined the base rate of psychological change at the individual level. Two-hundred twenty-eight adults completed the Personality Assessment Inventory (PAI) before and after temporal (TLR; n=190) or frontal lobe resection (FLR; n=38). Repeated measures ANOVAs with bootstrapping examined differences in psychological outcome as a function of surgical site separately in patients who underwent left- versus right-sided resections. Individual's PAI score changes were then used to determine the prevalence of clinically meaningful postoperative symptom change. Following left-sided resections, there were significant group-by-time interactions on Somatic Complaints, Anxiety, and Anxiety Related Disorders. There was also a trend in this direction on the Depression scale. TLR patients endorsed greater preoperative symptoms than FLR patients on all of these scales, except the Somatic Complaints scale. After surgery, TLR patients reported symptom improvement on all four scales, while scores of FLR patients remained relatively stable over time. Endorsement of Mania-related symptoms increased in both TLR and FLR groups from pre-to post-surgical testing. Following right-sided resections, both groups endorsed symptom improvements on Somatic Complaints, Anxiety, and Depression scales following surgery. In addition, the TLR group endorsed more Mania-related symptoms than the FLR group regardless of time. Patterns of meaningful change in individual patients were generally consistent with group findings, with the most frequent improvements observed following TLR. However, there were a small subset of patients who reported symptom exacerbation after surgery. Our results suggest that surgical lateralization and localization are important factors in postoperative psychological outcome and highlight the importance of considering psychological change at the individual patient level. Further research is needed to identify potential risk factors for symptom exacerbation to aid in preoperative counseling and identify those patients most in need of postoperative psychological surveillance. Copyright © 2016 Elsevier Inc. All rights reserved.

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…

Management of Side Effects of Novel Therapies for Multiple Myeloma: Consensus Statements Developed by the International Myeloma Foundation’s Nurse Leadership Board

PubMed Central

Bertolotti, Page; Bilotti, Elizabeth; Colson, Kathleen; Curran, Kathleen; Doss, Deborah; Faiman, Beth; Gavino, Maria; Jenkins, Bonnie; Lilleby, Kathy; Love, Ginger; Mangan, Patricia A.; McCullagh, Emily; Miceli, Teresa; Miller, Kena; Rogers, Kathryn; Rome, Sandra; Sandifer, Stacey; Smith, Lisa C.; Tariman, Joseph D.; Westphal, Jeanne

2014-01-01

Nurses play an essential role in managing the care of patients with multiple myeloma, who require education and support to receive and adhere to optimal therapy. The International Myeloma Foundation created a Nurse Leadership Board comprised of oncology nurses from leading cancer centers and community practices. An assessment survey identified the need for specific recommendations for managing key side effects of novel antimyeloma agents. Myelosuppression, thromboembolic events, peripheral neuropathy, steroid toxicities, and gastrointestinal side effects were selected for the first consensus statements. The board developed recommendations for healthcare providers in any medical setting, including grading of side-effect toxicity and strategies for managing the side effects in general, with specific recommendations pertaining to the novel agents. PMID:18490252

Comprehensive prediction of drug-protein interactions and side effects for the human proteome

PubMed Central

Zhou, Hongyi; Gao, Mu; Skolnick, Jeffrey

2015-01-01

Identifying unexpected drug-protein interactions is crucial for drug repurposing. We develop a comprehensive proteome scale approach that predicts human protein targets and side effects of drugs. For drug-protein interaction prediction, FINDSITEcomb, whose average precision is ~30% and recall ~27%, is employed. For side effect prediction, a new method is developed with a precision of ~57% and a recall of ~24%. Our predictions show that drugs are quite promiscuous, with the average (median) number of human targets per drug of 329 (38), while a given protein interacts with 57 drugs. The result implies that drug side effects are inevitable and existing drugs may be useful for repurposing, with only ~1,000 human proteins likely causing serious side effects. A killing index derived from serious side effects has a strong correlation with FDA approved drugs being withdrawn. Therefore, it provides a pre-filter for new drug development. The methodology is free to the academic community on the DR. PRODIS (DRugome, PROteome, and DISeasome) webserver at http://cssb.biology.gatech.edu/dr.prodis/. DR. PRODIS provides protein targets of drugs, drugs for a given protein target, associated diseases and side effects of drugs, as well as an interface for the virtual target screening of new compounds. PMID:26057345

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.

Neuroprotective and Cognitive Enhancement Potentials of Baicalin: A Review.

PubMed

Sowndhararajan, Kandhasamy; Deepa, Ponnuvel; Kim, Minju; Park, Se Jin; Kim, Songmun

2018-06-11

Neurodegenerative diseases are a heterogeneous group of disorders that are characterized by the gradual loss of neurons. The development of effective neuroprotective agents to prevent and control neurodegenerative diseases is specifically important. Recently, there has been an increasing interest in selecting flavonoid compounds as potential neuroprotective agents, owing to their high effectiveness with low side effects. Baicalin is one of the important flavonoid compounds, which is mainly isolated from the root of Scutellaria baicalensis Georgi (an important Chinese medicinal herb). In recent years, a number of studies have shown that baicalin has a potent neuroprotective effect in various in vitro and in vivo models of neuronal injury. In particular, baicalin effectively prevents neurodegenerative diseases through various pharmacological mechanisms, including antioxidative stress, anti-excitotoxicity, anti-apoptotic, anti-inflammatory, stimulating neurogenesis, promoting the expression of neuronal protective factors, etc. This review mainly focuses on the neuroprotective and cognitive enhancement effects of baicalin. The aim of the present review is to compile all information in relation to the neuroprotective and cognitive enhancement effects of baicalin and its molecular mechanisms of action in various in vitro and in vivo experimental models.

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

Biomarkers of Cytotoxic, Genotoxic and Apoptotic Effects in Cyprinus carpio Exposed to Complex Mixture of Contaminants from Hospital Effluents.

PubMed

Olvera-Néstor, Corina G; Morales-Avila, Enrique; Gómez-Olivan, Leobardo M; Galár-Martínez, Marcela; García-Medina, Sandra; Neri-Cruz, Nadia

2016-03-01

Hospital wastewater is an important source of emerging contaminants. Recent studies emphasize the importance of assessing the effects of mixtures of contaminants rather than environmental risk of their individual components, as well as the determination of intrinsic toxicity of wastewater. Mixtures of pollutants has possible interactions that have notable environmental side effects. The aim of this study is an attempt to characterize biomarkers in Cyprinus carpio related to the exposure to a complex mixture of contaminants found in hospital wastewater. Results of a particular hospital effluent show the presence of traces of heavy metals, high chlorine concentration and emerging contaminants such as non-steroidal anti-inflammatory drugs. The LC50 was of 5.49 % at 96 h. The cytotoxic, genotoxic and apoptotic biomarkers increase when fishes were exposed to wastewater (1/10 CL50) from hospital wastewater. This study emphasizes the importance of identifying and quantifying the effects of contaminants as pharmaceuticals, disinfectants and surfactants in order to design and implement an ecotoxicological plan.