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.

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.

Numerical investigations of shock wave interaction with laminar boundary layer on compressor profile

NASA Astrophysics Data System (ADS)

Piotrowicz, M.; Flaszyński, P.

2016-10-01

The investigation of shockwave boundary layer interaction on suction side of transonic compressor blade is one of main objectives of TFAST project (Transition Location Effect on Shock Wave Boundary Layer Interaction). In order to look more closely into the flow structure on suction side of a profile, a design of generic test section in linear transonic wind tunnel was proposed. The experimental and numerical results of flow structure on a suction side of the compressor profile investigations are presented. The numerical simulations are carried out for EARSM (Explicit Algebraic Reynolds Stress Model) turbulence model with transition model. The result are compared with oil flow visualisation, schlieren pictures, Pressure Sensitive Paint (PSP) and static pressure.

Real jet effects on dual jets in a crossflow

NASA Technical Reports Server (NTRS)

Schetz, J. A.

1984-01-01

A 6-ft by 6-ft wind tunnel section was modification to accommodate the 7-ft wide NASA dual-jet flate model in an effort to determine the effects of nonuniform and/or noncircular jet exhaust profiles on the pressure field induced on a nearby surface. Tests completed yield surface pressure measurements for a 90 deg circular injector producing exit profiles representative of turbofan nozzles (such as the TF-34 nozzle). The measurements were obtained for both tandem and side-by-side jet configurations, jet spacing of S/D =2, and velocity ratios of R=2.2 and 4.0. Control tests at the same mass flow rate but with uniform exit velocity profiles were also conducted, for comparison purposes. Plots for 90 deg injection and R=2.2 show that the effects of exit velocity profile nonuniformity are quite significant.

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

PubMed

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

2006-02-01

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

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.

Efficacy and side-effect profiles of lactulose, docusate sodium, and sennosides compared to PEG in opioid-induced constipation: a systematic review.

PubMed

Ruston, Teresa; Hunter, Kathleen; Cummings, Greta; Lazarescu, Adriana

2013-01-01

Opioid-induced constipation (OIC) is a side effect of opioid therapy that can affect quality of life, adherence to treatment, and morbidity and possibly mortality. To investigate whether docusate sodium, sennosides, and lactulose have equal efficacy and side effect profiles compared to PEG in the management of OIC in adults. A systematic review was undertaken. Randomized controlled trials of adults taking opioids for cancer or non-cancer pain were considered if they met inclusion criteria. Statistical pooling was not possible as no studies met inclusion criteria. Large, well-powered, randomized controlled trials are feasible. Standard definitions of OIC would assist with the execution of these studies and contribute to their internal and external validity. Further research is strongly encouraged.

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.

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single Enantiomer (+)-Mefloquine Compared with Racemic Mefloquine in Healthy Persons

PubMed Central

Tansley, Robert; Lotharius, Julie; Priestley, Anthony; Bull, Fiona; Duparc, Stephan; Möhrle, Jörg

2010-01-01

Racemic mefloquine is a highly effective antimalarial whose clinical utility has been compromised by its association with neuropsychiatric and gastrointestinal side effects. It is hypothesized that the cause of the side effects may reside in the (−) enantiomer. We sought to compare the safety, tolerability and pharmacokinetic profile of (+)-mefloquine with racemic mefloquine in a randomized, ascending-dose, double-blind, active and placebo-controlled, parallel cohort study in healthy male and female adult volunteers. Although differing in its manifestations, both study drugs displayed a substantially worse tolerability profile compared with placebo. The systemic clearance was slower for (−)-mefloquine than (+)-mefloquine. Thus, (+)-mefloquine has a different safety and tolerability profile compared with racemic mefloquine but its global safety profile is not superior and replacement of the currently used antimalarial drug with (+)-mefloquine is not warranted. PMID:21118921

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.

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

PubMed

Pelz, R; Banaschewski, T; Becker, K

2008-01-01

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

What Does Reflection from Cloud Sides Tell Us About Vertical Distribution of Cloud Droplet Sizes?

NASA Technical Reports Server (NTRS)

Marshak, Alexander; Martins, J. Vanderlei; Zubko, Victor; Kaufman, Yoram, J.

2005-01-01

Cloud development, the onset of precipitation and the effect of aerosol on clouds depend on the structure of the cloud profiles of droplet size and phase. Aircraft measurements of cloud profiles are limited in their temporal and spatial extent. Satellites were used to observe cloud tops not cloud profiles with vertical profiles of precipitation-sized droplets anticipated from Cloudsat. The recently proposed CLAIM-3D satellite mission (cloud aerosol interaction mission in 3D) suggests to measure profiles of cloud microphysical properties by retrieving them from the solar and infrared radiation reflected or emitted from cloud sides. Inversion of measurements from the cloud sides requires rigorous understanding of the 3-dimensional (3D) properties of clouds. Here we discuss the reflected sunlight from the cloud sides and top at two wavelengths: one nonabsorbing to solar radiation (0.67 micrometers) and one with liquid water efficient absorption of solar radiation (2.1 micrometers). In contrast to the plane-parallel approximation, a conventional approach to all current operational retrievals, 3D radiative transfer is used for interpreting the observed reflectances. General properties of the radiation reflected from the sides of an isolated cloud are discussed. As a proof of concept, the paper shows a few examples of radiation reflected from cloud fields generated by a simple stochastic cloud model with the prescribed vertically resolved microphysics. To retrieve the information about droplet sizes, we propose to use the probability density function of the droplet size distribution and its first two moments instead of the assumption about fixed values of the droplet effective radius. The retrieval algorithm is based on the Bayesian theorem that combines prior information about cloud structure and microphysics with radiative transfer calculations.

What does Reflection from Cloud Sides tell us about Vertical Distribution of Cloud Droplet Sizes?

NASA Technical Reports Server (NTRS)

Marshak, A.; Martins, J. V.; Zubko, V.; Kaufman, Y. J.

2006-01-01

Cloud development, the onset of precipitation and the effect of aerosol on clouds depend on the structure of the cloud profiles of droplet size and phase. Aircraft measurements of cloud profiles are limited in their temporal and spatial extent. Satellites were used to observe cloud tops not cloud profiles with vertical profiles of precipitation-sized droplets anticipated from CloudSat. The recently proposed CLAIM-3D satellite mission (cloud aerosol interaction mission in 3-D) suggests to measure profiles of cloud microphysical properties by retrieving them from the solar and infrared radiation reflected or emitted from cloud sides. Inversion of measurements from the cloud sides requires rigorous understanding of the 3-dimentional(3-D) properties of clouds. Here we discuss the reflected sunlight from the cloud sides and top at two wavelengths: one nonabsorbing to solar radiation (0.67 microns) and one with liquid water efficient absorption of solar radiation (2.1 microns). In contrast to the plane-parallel approximation, a conventional approach to all current operational retrievals, 3-D radiative transfer is used for interpreting the observed reflectances. General properties of the radiation reflected from the sides of an isolated cloud are discussed. As a proof of concept, the paper shows a few examples of radiation reflected from cloud fields generated by a simple stochastic cloud model with the prescribed vertically resolved microphysics. To retrieve the information about droplet sizes, we propose to use the probability density function of the droplet size distribution and its first two moments instead of the assumption about fixed values of the droplet effective radius. The retrieval algorithm is based on the Bayesian theorem that combines prior information about cloud structure and microphysics with radiative transfer calculations.

Details of Side Load Test Data and Analysis for a Truncated Ideal Contour Nozzle and a Parabolic Contour Nozzle

NASA Technical Reports Server (NTRS)

Ruf, Joseph H.; McDaniels, David M.; Brown, Andrew M.

2010-01-01

Two cold flow subscale nozzles were tested for side load characteristics during simulated nozzle start transients. The two test article contours were a truncated ideal and a parabolic. The current paper is an extension of a 2009 AIAA JPC paper on the test results for the same two nozzle test articles. The side load moments were measured with the strain tube approach in MSFC s Nozzle Test Facility. The processing techniques implemented to convert the strain gage signals into side load moment data are explained. Nozzle wall pressure profiles for separated nozzle flow at many NPRs are presented and discussed in detail. The effect of the test cell diffuser inlet on the parabolic nozzle s wall pressure profiles for separated flow is shown. The maximum measured side load moments for the two contours are compared. The truncated ideal contour s peak side load moment was 45% of that of the parabolic contour. The calculated side load moments, via mean-plus-three-standard-deviations at each nozzle pressure ratio, reproduced the characteristics and absolute values of measured maximums for both contours. The effect of facility vibration on the measured side load moments is quantified and the effect on uncertainty is calculated. The nozzle contour designs are discussed and the impact of a minor fabrication flaw in the nozzle contours is explained.

Sexual side effects associated with conventional and atypical antipsychotics.

PubMed

Compton, M T; Miller, A H

2001-01-01

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

Prophylactic Therapy for Hereditary Angioedema.

PubMed

Longhurst, Hilary; Zinser, Emily

2017-08-01

Long-term prophylaxis is needed in many patients with hereditary angioedema and poses many challenges. Attenuated androgens are effective in many but are limited by side effect profiles. There is less evidence for efficacy of tranexamic acid and progestagens; however, the small side effect profile makes tranexamic acid an option for prophylaxis in children and progestagens an option for women. C1 inhibitor is beneficial, but at present requires intravenous delivery and may need dose titration for maximum efficacy. Short-term prophylaxis should be considered for all procedures. New therapies are promising in overcoming many problems encountered with current options for long-term prophylaxis. Copyright © 2017 Elsevier Inc. All rights reserved.

A Comparison of Psychotropic Drug Side Effect Profiles in Adults Diagnosed with Intellectual Disabilities and Autism Spectrum Disorders

ERIC Educational Resources Information Center

Hess, Julie; Matson, Johnny; Neal, Daniene; Mahan, Sara; Fodstad, Jill; Bamburg, Jay; Holloway, Jodie

2010-01-01

Forty-eight adults diagnosed with intellectual disabilities and Autistic Disorder or Pervasive Developmental Disorder-Not Otherwise Specified were examined with regard to psychotropic medication side effects. Participants were divided into 4 groups: no psychotropic medication group (n = 9); atypical antipsychotic medication group (n = 13);…

Endovenous ablation of refluxing saphenous and perforating veins.

PubMed

Proebstle, Thomas; van den Bos, Renate

2017-05-01

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

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

[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.

Effects of electroconvulsive therapy and magnetic seizure therapy on acute memory retrieval.

PubMed

Polster, Julia D; Kayser, Sarah; Bewernick, Bettina H; Hurlemann, René; Schlaepfer, Thomas E

2015-03-01

Electroconvulsive therapy (ECT) is currently the most effective treatment for severe depression. However, it is frequently associated with negative cognitive side effects. Magnetic seizure therapy (MST) depicts an alternative, although experimental, convulsive treatment for major depression. Initial results suggest comparable antidepressant effects accompanied by a better side effect profile. However, no studies up to now have addressed acute retrieval disruption after MST in comparison to ECT. Therefore, we intended to broaden insight into the side effect profile of MST compared to ECT by examining the disruption of acute verbal memory processes after treatment. Twenty depressed patients were randomly assigned to either MST (10 patients) or ECT (10 patients) treatment. On 2 treatment days and 2 treatment-free days, the patients memorized words using a controlled learning paradigm derived from the Batchelder and Riefer storage retrieval model. Four hours after memorization, the patients were asked to retrieve words freely (delayed recall) and a second time with the help of an additional cue constructed out of a hypernymic category (cued recall). By comparing memory performance on treatment days to control days, treatment-induced memory disruption was evaluated. After ECT, delayed recall was disturbed, whereas after MST, it was not. However, this difference in performance was no longer apparent upon cue application (cued recall). This study demonstrates that ECT-induced acute memory disruption measured by delayed recall is absent after MST, confirming its superior side effect profile. We hope that confirming advantages of MST over ECT will improve therapy options for patients with severe depression.

Behavioral and Psychiatric Differences in Medication Side Effects in Adults with Severe Intellectual Disabilities

ERIC Educational Resources Information Center

Matson, Johnny L.; Fodstad, Jill C.; Rivet, Tessa T.; Rojahn, Johannes

2009-01-01

Participants were 109 adults with severe intellectual disabilities and long histories of psychotropic drug use. Side effect profiles were examined in the context of types of mental health disorders observed using the Diagnostic Assessment for the Severely Handicapped-Revised (DASH-II) and the Behavior Problems Inventory-Revised (BPI-01). The best…

Re-evaluating microglia expression profiles using RiboTag and cell isolation strategies.

PubMed

Haimon, Zhana; Volaski, Alon; Orthgiess, Johannes; Boura-Halfon, Sigalit; Varol, Diana; Shemer, Anat; Yona, Simon; Zuckerman, Binyamin; David, Eyal; Chappell-Maor, Louise; Bechmann, Ingo; Gericke, Martin; Ulitsky, Igor; Jung, Steffen

2018-06-01

Transcriptome profiling is widely used to infer functional states of specific cell types, as well as their responses to stimuli, to define contributions to physiology and pathophysiology. Focusing on microglia, the brain's macrophages, we report here a side-by-side comparison of classical cell-sorting-based transcriptome sequencing and the 'RiboTag' method, which avoids cell retrieval from tissue context and yields translatome sequencing information. Conventional whole-cell microglial transcriptomes were found to be significantly tainted by artifacts introduced by tissue dissociation, cargo contamination and transcripts sequestered from ribosomes. Conversely, our data highlight the added value of RiboTag profiling for assessing the lineage accuracy of Cre recombinase expression in transgenic mice. Collectively, this study indicates method-based biases, reveals observer effects and establishes RiboTag-based translatome profiling as a valuable complement to standard sorting-based profiling strategies.

[Functional selectivity of opioid receptors ligands].

PubMed

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

2010-01-01

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

Effect of asymmetrical street canyons on pedestrian thermal comfort in warm-humid climate of Cuba

NASA Astrophysics Data System (ADS)

Rodríguez-Algeciras, José; Tablada, Abel; Matzarakis, Andreas

2017-07-01

Walkability and livability in cities can be enhanced by creating comfortable environments in the streets. The profile of an urban street canyon has a substantial impact on outdoor thermal conditions at pedestrian level. This paper deals with the effect of asymmetrical street canyon profiles, common in the historical centre of Camagüey, Cuba, on outdoor thermal comfort. Temporal-spatial analyses are conducted using the Heliodon2 and the RayMan model, which enable the generation of accurate predictions about solar radiation and thermal conditions of urban spaces, respectively. On these models, urban settings are represented by asymmetrical street canyons with five different height-to-width ratios and four street axis orientations (N-S, NE-SW, E-W, SE-NW). Results are evaluated for daytime hours across the street canyon, by means of the physiologically equivalent temperature (PET index) which allows the evaluation of the bioclimatic conditions of outdoor environments. Our findings revealed that high profiles (façades) located on the east-facing side of N-S streets, on the southeast-facing side of NE-SW streets, on the south-facing side of E-W street, and on the southwest-facing side of SE-NW streets, are recommended to reduce the total number of hours under thermal stress. E-W street canyons are the most thermally stressed ones, with extreme PET values around 36 °C. Deviating from this orientation ameliorates the heat stress with reductions of up to 4 h in summer. For all analysed E-W orientations, only about one fifth of the street can be comfortable, especially for high aspect ratios (H/W > 3). Optimal subzones in the street are next to the north side of the E-W street, northwest side of the NE-SW street, and southwest side of the SE-NW street. Besides, when the highest profile is located on the east side of N-S streets, then the subzone next to the east-facing façade is recommendable for pedestrians. The proposed urban guidelines enable urban planners to create and renovate urban spaces which are more efficient in diminishing pedestrian thermal stress.

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.

Pharmacological profiling of zebrafish behavior using chemical and genetic classification of sleep-wake modifiers.

PubMed

Nishimura, Yuhei; Okabe, Shiko; Sasagawa, Shota; Murakami, Soichiro; Ashikawa, Yoshifumi; Yuge, Mizuki; Kawaguchi, Koki; Kawase, Reiko; Tanaka, Toshio

2015-01-01

Sleep-wake states are impaired in various neurological disorders. Impairment of sleep-wake states can be an early condition that exacerbates these disorders. Therefore, treating sleep-wake dysfunction may prevent or slow the development of these diseases. Although many gene products are likely to be involved in the sleep-wake disturbance, hypnotics and psychostimulants clinically used are limited in terms of their mode of action and are not without side effects. Therefore, there is a growing demand for developing new hypnotics and psychostimulants with high efficacy and few side effects. Toward this end, animal models are indispensable for use in genetic and chemical screens to identify sleep-wake modifiers. As a proof-of-concept study, we performed behavioral profiling of zebrafish treated with chemical and genetic sleep-wake modifiers. We were able to demonstrate that behavioral profiling of zebrafish treated with hypnotics or psychostimulants from 9 to 10 days post-fertilization was sufficient to identify drugs with specific modes of action. We were also able to identify behavioral endpoints distinguishing GABA-A modulators and hypocretin (hcrt) receptor antagonists and between sympathomimetic and non-sympathomimetic psychostimulants. This behavioral profiling can serve to identify genes related to sleep-wake disturbance associated with various neuropsychiatric diseases and novel therapeutic compounds for insomnia and excessive daytime sleep with fewer adverse side effects.

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

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.

Fluvoxamine versus other anti-depressive agents for depression

PubMed Central

Omori, Ichiro M; Watanabe, Norio; Nakagawa, Atsuo; Cipriani, Andrea; Barbui, Corrado; McGuire, Hugh; Churchill, Rachel; Furukawa, Toshi A

2014-01-01

Background Fluvoxamine, one of the oldest selective serotonin reuptake inhibitors (SSRIs), is prescribed to patients with major depression in many countries. Several studies have previously reviewed the efficacy and tolerability of fluvoxamine for the treatment of major depression. However, these reviews are now outdated. Objectives Our objective is to evaluate the effectiveness, tolerability and side effect profile of fluvoxamine for major depression in comparison with other anti-depressive agents, including tricyclics (TCAs), heterocyclics, other SSRIs, SNRIs, other newer agents and other conventional psychotropic drugs. Search methods We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register. Trial databases and ongoing trial registers in North America, Europe, Japan and Australia, were handsearched for randomised controlled trials. We checked reference lists of the articles included in the review, previous systematic reviews and major textbooks of affective disorder for published reports and citations of unpublished research. The date of last search was 31 August 2008. Selection criteria We included all randomised controlled trials, published in any language, that compared fluvoxamine with any other active antidepressants in the acute phase treatment of major depression. Data collection and analysis Two independent review authors inspected citations and abstracts, obtained papers, extracted data and assessed the risk of bias of included studies. We analysed dichotomous data using odds ratios (ORs) and continuous data using the standardised mean difference (SMD). A random effects model was used to combine studies. Main results A total of 54 randomised controlled trials (n = 5122) were included. No strong evidence was found to indicate that fluvoxamine was either superior or inferior to other antidepressants regarding response, remission and tolerability. However, differing side effect profiles were evident, especially with regard to gastrointestinal side effects of fluvoxamine when compared to other antidepressants. For example, fluvoxamine was generally associated with a higher incidence of vomiting/nausea (versus imipramine, OR 2.23, CI 1.59 to 3.14; versus clomipramine, OR 2.13, CI 1.06 to 4.27; versus amitriptyline, OR 2.86, CI 1.31 to 2.63). Authors’ conclusions We found no strong evidence that fluvoxamine was either superior or inferior to any other antidepressants in terms of efficacy and tolerability in the acute phase treatment of depression. However, differing side effect profiles were evident. Based on these findings, we conclude that clinicians should focus on practical or clinically relevant considerations, including these differences in side effect profiles. PMID:20238342

Do the emotional side-effects of hormonal contraceptives come from pharmacologic or psychological mechanisms?

PubMed

Robinson, Stephen A; Dowell, Matt; Pedulla, Dominic; McCauley, Larry

2004-01-01

Hormonal preparations have become one of the most popular methods used for controlling fertility. The literature over the last 40 years continues to reveal how their numerous side effects negatively impact many users and even society at large. Three large cohort trials were the first to demonstrate, on a grand scale, certain emotional and behavioral associations with contraceptive use. Current contraceptive use was associated with an increase rate in depression, divorce, tranquilizer use, sexual dysfunction, and suicide and other violent and accidental deaths. Despite the advent of more "user friendly" contraceptives, the discontinuation rate secondary to side effects has changed little through the years. While in rare cases hormonal preparations can be deadly to the user, there is substantial evidence that their negative effect issues more from their emotional and behavioral properties. This paper reviews the results of over seven studies which further characterize these prominent associations, particularly with hormonal contraception, in an attempt to demonstrate their association with the intrinsic pharmacologic properties of hormonal preparations. Hormonal contraceptive users, in contrast with non users, were found to have higher rates of depression, anxiety, fatigue, neurotic symptoms, sexual disturbances, compulsion, anger, and negative menstrual effects. The question of whether the association of these maladies is directly due to the effect of taking exogenous hormones versus the psychological impact of the contraceptive behavior itself had yet to be studied. Seven small randomized-controlled trials were found in a review of the literature which studied this hypothesis in a direct way. They do not support the origination of these side effects being from the pharmacological properties of hormones. No association was found between hormone levels and emotional functioning in females. Psychiatric evaluations among IUD and oral contraceptive pill (OCP) users reveal no significant differences. Women who were given an OCP placebo experienced a similar side effect profile of OCP users. Different hormonal concentrations and combinations made no significant difference in the side effect profile. A study of women who were given either "weak female hormones" or a placebo failed to duplicate the side effect profile found in all of the other studies where the hormones were labeled as contraceptives. The evidence suggests that most of the side effects of hormonal contraception are a result of a psychological response to the practice of contraception. More study is warranted to further understand this psychological phenomenon, especially now that an effective non-contraceptive method of fertility regulation and more reliable psychological instruments are available. Furthermore, it is reasonable to hypothesize, given the present data, that contraceptive activity itself is inherently damaging to women.

Sensorimotor dysfunction of grasping in schizophrenia: a side effect of antipsychotic treatment?

PubMed Central

Nowak, D A; Connemann, B J; Alan, M; Spitzer, M

2006-01-01

Background Antipsychotic treatment in schizophrenia is frequently associated with extrapyramidal side effects. Objective behavioural measures to evaluate the severity of extrapyramidal side effects in the clinical setting do not exist. Objectives This study was designed to investigate grasping movements in five drug naive and 13 medicated subjects with schizophrenia and to compare their performance with that of 18 healthy control subjects. Deficits of grip force performance were correlated with clinical scores of both parkinson‐like motor disability and psychiatric symptom severity Methods Participants performed vertical arm movements with a handheld instrumented object and caught a weight that was dropped into a handheld cup either expectedly from the opposite hand or unexpectedly from the experimenter's hand. The scaling of grip force and the temporospatial coupling between grip and load force profiles was analysed. The psychiatric symptom severity was assessed by the positive and negative symptom score of schizophrenia and the brief psychiatric rating scale. Extrapyramidal symptoms were assessed by the unified Parkinson's disease rating scale. Results Drug naive subjects with schizophrenia performed similar to healthy controls. In contrast, medicated subjects with schizophrenia exhibited excessive grip force scaling and impaired coupling between grip and load force profiles. These performance deficits were strongly correlated with the severity of both extrapyramidal side effects related to antipsychotic therapy and negative symptoms related to the underlying pathology. Conclusions These data provide preliminary evidence that deficits of sensorimotor performance in schizophrenia are, at least in part, related to the side effects of antipsychotic treatment. The investigation of grasping movements may provide a sensitive measure to objectively evaluate extrapyramidal side effects related to antipsychotic therapy. PMID:16614027

Analysis of temperature profile and electric field in natural rubber glove due to microwave heating: effects of waveguide position

NASA Astrophysics Data System (ADS)

Keangin, P.; Narumitbowonkul, U.; Rattanadecho, P.

2018-01-01

Natural rubber (NR) is the key raw material used in the manufacture of other products such as rubber band, tire and shoes. Recently, the NR is used in natural rubber glove ( NRG) manufacturing in the industrial and medical fields. This research aims to investigate the electromagnetic wave propagation and heat transfer in NRG due to heating with microwave energy within the microwave oven at a microwave frequency of 2.45 GHz. Three-dimensional model of NRG and microwave oven are considered in this work. The comparative effects of waveguide position on the electric field and temperature profile in NRG when subjected to microwave energy are discussed. The finite element method (FEM) is used to solve the transient Maxwell’s equation coupled with the transient heat transfer equation. The simulation results with computer programs are validated with experimental results. The placement of waveguides in three cases are left hand side of microwave oven, right hand side of microwave oven and left and right hand sides of microwave oven are investigated. The findings revealed that the placing the waveguide on the right side of the microwave oven gives the highest electric field and temperature profile. The values obtained provide an indication toward understanding the study of heat transfer in NRG during microwave heating in the industry.

Aripiprazole, A Drug that Displays Partial Agonism and Functional Selectivity.

PubMed

Tuplin, Erin W; Holahan, Matthew R

2017-11-14

The treatment of schizophrenia is challenging due to the wide range of symptoms (positive, negative, cognitive) associated with the disease. Typical antipsychotics that antagonize D2 receptors are effective in treating positive symptoms, but extrapyramidal side-effects (EPS) are a common occurrence. Atypical antipsychotics targeting 5-HT2A and D2 receptors are more effective at treating cognitive and negative symptoms compared to typical antipsychotics, but these drugs also result in side-effects such as metabolic syndromes. To identify evidence in the literature that elucidates the pharmacological profile of aripiprazole.s. We searched PubMed for peer reviewed articles on aripiprazole and its clinical efficacy, side-effects, pharmacology, and effects in animal models of schizophrenia symptoms. Aripiprazole is a newer atypical antipsychotic that displays a unique pharmacological profile, including partial D2 agonism and functionally selective properties. Aripiprazole is effective at treating the positive symptoms of schizophrenia and has the potential to treat negative and cognitive symptoms at least as well as other atypical antipsychotics. The drug has a favorable side-effect profile and has a low propensity to result in EPS or metabolic syndromes. Animal models of schizophrenia have been used to determine the efficacy of aripiprazole in symptom management. In these instances, aripiprazole resulted in the reversal of deficits in extinction, pre-pulse inhibition, and social withdrawal. Because aripiprazole requires a greater than 90% occupancy rate at D2 receptors to be clinically active and does not produce EPS, this suggests a functionally selective effect on intracellular signaling pathways. A combination of factors such as dopamine system stabilization via partial agonism, functional selectivity at D2 receptors, and serotonin-dopamine system interaction may contribute to the ability of aripiprazole to successfully manage schizophrenia symptoms. This review examines these mechanisms of action to further clarify the pharmacological actions of aripiprazole. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Adjuvant treatment or primary topical monotherapy for ocular surface squamous neoplasia: a systematic review.

PubMed

Viani, Gustavo Arruda; Fendi, Ligia Issa de

2017-01-01

In this systematic review, we evaluated studies involving adjuvant and primary topical treatment for ocular surface squamous neoplasia (OSSN). The findings were: (i) adjuvant 5-fluorouracil (5-FU) reduces the risk of relapse after surgical excision with mild side effects [level Ib, grade of recommendation (GR) A]. (ii) Primary topical mitomycin (MMC) produces a high rate of complete response, low recurrence rate, and mild side effects (level Ib, GR A). (iii) Primary chemotherapy versus adjuvant chemotherapy produce similar rates of recurrence, with no significant difference (level IIb, GR B). (iv) Adjuvant 5-FU versus MMC showed no significant differences, with mild side effects in both groups and a better toxicity profile for MMC (level III, GR C). (v) Primary topical 5-FU versus MMC versus interferon (IFN) showed similar rates of tumor recurrence, mild side effects for all drugs, and more severe side effects in the 5-FU arm, followed successively by MMC and IFN (level III, GR C).

Comparison of the discontinuation rates and side-effect profiles of pilocarpine and cevimeline for xerostomia in primary Sjögren's syndrome.

PubMed

Noaiseh, Ghaith; Baker, Joshua F; Vivino, Frederick B

2014-01-01

There are currently no head-to-head comparisons of sialagogues for Primary Sjögren's syndrome (pSS). We compared the tolerability and side effect profile of pilocarpine and cevimeline in patients with pSS and determined clinical, laboratory and pathological variables associated with therapeutic failure. We retrospectively reviewed the use of pilocarpine and cevimeline in 118 patients with pSS who fulfilled the 2002 American European Consensus Group criteria in a University-based setting. Clinical, laboratory and pathological baseline variables were collected. Failure of therapy was defined as the clinician or patient's decision to stop treatment either due to lack of efficacy or side effects. Cevimeline was associated with lower failure rates compared to pilocarpine among first-time users: 27% vs. 47% (p=0.02), and all users: 32% vs. 61% (p<0.001). Severe sweating was the most frequent side effect leading to cessation of therapy and occurred more frequently in pilocarpine (25%) than cevimeline (11%) users (p=0.02). Patients who previously failed one secretagogue were less likely to discontinue treatment with the other agent, 52% of first-time users vs. 27% of second-time users (p=0.004). Only ANA positivity was associated with failure: [59% vs. 38%] (p=0.03). pSS patients were more likely to continue cevimeline than pilocarpine long-term due to fewer reported side effects with cevimeline. Therapeutic failure of one secretagogue did not predict similar results with the other since second time users were more likely to continue long-term treatment.

Drug profile: transdermal rivastigmine patch in the treatment of Alzheimer disease.

PubMed

Emre, Murat; Bernabei, Roberto; Blesa, Rafael; Bullock, Roger; Cunha, Luis; Daniëls, Hugo; Dziadulewicz, Edward; Förstl, Hans; Frölich, Lutz; Gabryelewicz, Tomasz; Levin, Oleg; Lindesay, James; Martínez-Lage, Pablo; Monsch, Andreas; Tsolaki, Magda; van Laar, Teus

2010-08-01

Cholinesterase inhibitors constitute one of the mainstays of treatment of Alzheimer disease (AD). Gastrointestinal side effects, difficulty accessing therapeutic doses and poor patient compliance have been identified as barriers to effective treatment with these substances. The rivastigmine transdermal patch provides continuous delivery of drug through the skin into the bloodstream, avoiding the fluctuations in plasma concentration associated with oral administration. This pharmacokinetic profile is associated with reduced side effects, resulting in easier access to expected target doses. These benefits, along with other practical advantages of the transdermal patch, may contribute to enhanced patient compliance. Here, we present a review of the current literature on rivastigmine patch, and offer advice based on our own collective clinical experience. Rivastigmine patch provides an efficient option for managing patients with AD, to be considered among the first line therapies for the disease.

Tranexamic Acid in the Treatment of Melasma: A Review of the Literature.

PubMed

Perper, Marina; Eber, Ariel Eva; Fayne, Rachel; Verne, Sebastian Hugo; Magno, Robert James; Cervantes, Jessica; ALharbi, Mana; ALOmair, Ibrahim; Alfuraih, Abdulkarem; Nouri, Keyvan

2017-06-01

Melasma is a common acquired pigmentary disorder marked by irregular hyperpigmented macules or patches and most commonly occurs in women of darker skin color. It is a chronic often-relapsing condition that causes negative psychosocial effects in those affected. Current treatments such as hydroquinone, kojic acid, and retinoids, among others, demonstrate variable efficacy and side-effect profiles. We conducted a comprehensive literature review examining the use of tranexamic acid (TA), a well-known anti-fibrinolytic agent, in the treatment of melasma. TA delivered orally, topically, and through physical methods works via the inhibition of ultraviolet (UV)-induced plasmin activity in keratinocytes. Predefined search terms were entered into PubMed. Articles were then independently screened by two authors to include only those written in the English language and relating to human subjects with at least mild melasma. The search identified 28 articles, 15 of which met the criteria for full review. The review revealed that TA treatment for melasma is equally effective or more effective than other standard therapies and may induce fewer side effects. Our comprehensive review suggests that TA may be a promising treatment option for melasma because of its demonstrated effectiveness alone and in combination with other modalities as well as its limited side-effect profile.

How gender and boat-side affect shape characteristics of force-angle profiles in single sculling: Insights from functional data analysis.

PubMed

Warmenhoven, John; Cobley, Stephen; Draper, Conny; Harrison, Andrew; Bargary, Norma; Smith, Richard

2018-05-01

To examine whether gender or side of the boat influenced shape characteristics of the force-angle profile in on-water single sculling. Cross-sectional study design. Bivariate functional principal components analysis (bfPCA) was applied to force-angle data to identify the main modes of variance in curves of forty highly skilled male and female rowers (national and international level), rowing at 32 strokes per minute in a single scull boat. Separate discriminant function analyses for each side of the boat showed strong classification of rowers for gender. Force application close to (or closely around) the perpendicular oar position was demonstrated to be different between genders. A mixed ANOVA exploring gender, boat side and their interaction revealed that bow and stroke side forces were also statistically different from each other independently of gender. A main effect, independent of side of the boat, was also present for gender and no interaction was found between gender and boat side. Bow side forces seemingly acted as a driver of power and peak force production, while stroke side forces may have acted as a mediator of propulsive forces with an additional potential role in steering due to known asymmetrical offsets in boat rigging. Results demonstrate that propulsive force differences according to gender and boat-side are evident and must be acknowledged and accounted for before force-angle graphs are explored relative to performance measures. Copyright © 2017. Published by Elsevier Ltd.

Analytical model for thermal lensing and spherical aberration in diode side-pumped Nd:YAG laser rod having Gaussian pump profile

NASA Astrophysics Data System (ADS)

M, H. Moghtader Dindarlu; M Kavosh, Tehrani; H, Saghafifar; A, Maleki

2015-12-01

In this paper, according to the temperature and strain distribution obtained by considering the Gaussian pump profile and dependence of physical properties on temperature, we derive an analytical model for refractive index variations of the diode side-pumped Nd:YAG laser rod. Then we evaluate this model by numerical solution and our maximum relative errors are 5% and 10% for variations caused by thermo-optical and thermo-mechanical effects; respectively. Finally, we present an analytical model for calculating the focal length of the thermal lens and spherical aberration. This model is evaluated by experimental results.

An update of safety of clinically used atypical antipsychotics.

PubMed

Orsolini, L; Tomasetti, C; Valchera, A; Vecchiotti, R; Matarazzo, I; Vellante, F; Iasevoli, F; Buonaguro, E F; Fornaro, M; Fiengo, A L C; Martinotti, G; Mazza, M; Perna, G; Carano, A; De Bartolomeis, A; Di Giannantonio, M; De Berardis, D

2016-10-01

The atypical antipsychotic (APs) drugs have become the most widely used agents to treat a variety of psychoses because of their superiority with regard to safety and tolerability profile compared to conventional/'typical' APs. We aimed at providing a synthesis of most current evidence about the safety and tolerability profile of the most clinically used atypical APs so far marketed. Qualitative synthesis followed an electronic search made inquiring of the following databases: MEDLINE, Embase, PsycINFO and the Cochrane Library from inception until January 2016, combining free terms and MESH headings for the topics of psychiatric disorders and all atypical APs as following: ((safety OR adverse events OR side effects) AND (aripiprazole OR asenapine OR quetiapine OR olanzapine OR risperidone OR paliperidone OR ziprasidone OR lurasidone OR clozapine OR amisulpride OR iloperidone)). A critical issue in the treatment with atypical APs is represented by their metabolic side effect profile (e.g. weight gain, lipid and glycaemic imbalance, risk of diabetes mellitus and diabetic ketoacidosis) which may limit their use in particular clinical samples. Electrolyte imbalance, ECG abnormalities and cardiovascular adverse effects may recommend a careful baseline and periodic assessments.

Autistic spectrum disorder, epilepsy, and vagus nerve stimulation.

PubMed

Hull, Mariam Mettry; Madhavan, Deepak; Zaroff, Charles M

2015-08-01

In individuals with a comorbid autistic spectrum disorder and medically refractory epilepsy, vagus nerve stimulation may offer the potential of seizure control and a positive behavioral side effect profile. We aimed to examine the behavioral side effect profile using longitudinal and quantitative data and review the potential mechanisms behind behavioral changes. We present a case report of a 10-year-old boy with autistic spectrum disorder and epilepsy, who underwent vagus nerve stimulation subsequent to unsuccessful treatment with antiepileptic medication. Following vagus nerve stimulation implantation, initial, if temporary, improvement was observed in seizure control. Modest improvements were also observed in behavior and development, improvements which were observed independent of seizure control. Vagus nerve stimulation in autistic spectrum disorder is associated with modest behavioral improvement, with unidentified etiology, although several candidates for this improvement are evident.

Effects of inlet distortion on gas turbine combustion chamber exit temperature profiles

NASA Astrophysics Data System (ADS)

Maqsood, Omar Shahzada

Damage to a nozzle guide vane or blade, caused by non-uniform temperature distributions at the combustion chamber exit, is deleterious to turbine performance and can lead to expensive and time consuming overhaul and repair. A test rig was designed and constructed for the Allison 250-C20B combustion chamber to investigate the effects of inlet air distortion on the combustion chamber's exit temperature fields. The rig made use of the engine's diffuser tubes, combustion case, combustion liner, and first stage nozzle guide vane shield. Rig operating conditions simulated engine cruise conditions, matching the quasi-non-dimensional Mach number, equivalence ratio and Sauter mean diameter. The combustion chamber was tested with an even distribution of inlet air and a 4% difference in airflow at either side. An even distribution of inlet air to the combustion chamber did not create a uniform temperature profile and varying the inlet distribution of air exacerbated the profile's non-uniformity. The design of the combustion liner promoted the formation of an oval-shaped toroidal vortex inside the chamber, creating localized hot and cool sections separated by 90° that appeared in the exhaust. Uneven inlet air distributions skewed the oval vortex, increasing the temperature of the hot section nearest the side with the most mass flow rate and decreasing the temperature of the hot section on the opposite side. Keywords: Allison 250, Combustion, Dual-Entry, Exit Temperature Profile, Gas Turbine, Pattern Factor, Reverse Flow.

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.

Managing the side effects of multiple sclerosis therapy: pharmacotherapy options for patients.

PubMed

Rommer, Paulus S; Zettl, Uwe K

2018-04-01

Multiple sclerosis (MS) is an immune-mediated and neurodegenerative disease with an unpredictable outcome. Immune-modulatory treatment aims at decreasing long-term disability. With the increasing number of treatment options, it is essential to fully digest the possible side effects of the available therapeutics and to monitor patients is essential. Areas covered: All approved disease-modifying drugs (DMD) for MS are discussed in this review. Mode of action, adverse effects, reported risks for infections and malignancies, and pregnancy related issues are discussed in the review. The authors also provide suggestions for monitoring therapy. For all approved DMDs the pivotal studies have been included for possible side effects, as well as reports by health authorities. For this manuscript, PubMed was checked for reports on side effects for various drugs. Expert opinion: Treatment options in MS are manifold, each carrying different risks. The safety-risk profile for approved agents is favorable. Knowing and monitoring these possible side effects is essential to minimize risks associated with treatment. Presently, the long-term experience for some of these therapies is missing and this must be addressed.

Safety evaluation of lubiprostone in the treatment of constipation and irritable bowel syndrome.

PubMed

Chamberlain, Sherman M; Rao, Satish S C

2012-09-01

Lubiprostone is approved in the United States for the treatment of chronic idiopathic constipation and constipation predominant irritable bowel syndrome (IBS-C). Lubiprostone causes secretion of fluid and electrolytes in the small bowel, through the activation of chloride channels, and thereby induces laxation and improvement of bowel functions. It is generally considered to be safe and effective. Common side effects of lubiprostone include nausea, diarrhea, abdominal pain and bloating, and the rare side effect dyspnea. Likely mechanisms for these side effects may be related to lubiprostone's primary action on small bowel secretion and the associated intestinal distension, as well as smooth muscle contraction. This article reviews the pharmacokinetic and safety profile of lubiprostone, with particular relevance to the two FDA-approved dosages. Lubiprostone acts topically in the gut lumen and is almost completely metabolized in the gut lumen. Lubiprostone's M3 metabolite can be detected in low concentrations in the serum and may be responsible for some of its side effects. However, the exact mechanisms by which the side effects are produced are currently unknown.

A comparison of mesial molar root canal preparations using two engine-driven instruments and the balanced-force technique.

PubMed

Imura, N; Kato, A S; Novo, N F; Hata, G; Uemura, M; Toda, T

2001-10-01

The purpose of this study was to compare the effects of two engine-driven, nickel-titanium instrument systems with hand files in the final shape of slight and moderately curved canals. A total of 72 mesial roots of extracted human mandibular molars were divided into three groups: ProFile .04 taper, Pow-R rotary systems, and Flex-R hand-filing technique. The roots were mounted and cross-sectioned at two different horizontal levels using a modified Bramante technique. Pre- and postinstrumented cross-sectional roots were imaged, recorded, and computer analyzed. Results showed that, at the middle third, in almost all groups, there was a tendency of cutting more toward the mesial side with only one exception: Pow-R cut more to the distal side (danger zone) (p < 0.02). At the apical third, Flex-R (p < 0.03) and ProFile (0.001) transported to the mesial side (danger zone) when the curvature increased. When the three techniques were compared analyzing each side and considering the two groups of curvature, at the middle third in the moderately curved-canal group, Flex-R cut statistically more than Pow-R toward the lingual side. The other comparisons showed no statistically significant difference. When the techniques were compared in relation with the degree of curvature, in the apical third, ProFile .04 cut statistically more toward the mesial side in the moderately curved canal group than in the slightly curved canal group. The other comparisons showed no statistically significant difference. Canal preparation time was shorter with hand instrumentation (p < .05) in a few instances.

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

Spin Hall effect originated from fractal surface

NASA Astrophysics Data System (ADS)

Hajzadeh, I.; Mohseni, S. M.; Movahed, S. M. S.; Jafari, G. R.

2018-05-01

The spin Hall effect (SHE) has shown promising impact in the field of spintronics and magnonics from fundamental and practical points of view. This effect originates from several mechanisms of spin scatterers based on spin–orbit coupling (SOC) and also can be manipulated through the surface roughness. Here, the effect of correlated surface roughness on the SHE in metallic thin films with small SOC is investigated theoretically. Toward this, the self-affine fractal surface in the framework of the Born approximation is exploited. The surface roughness is described by the k-correlation model and is characterized by the roughness exponent H , the in-plane correlation length ξ and the rms roughness amplitude δ. It is found that the spin Hall angle in metallic thin film increases by two orders of magnitude when H decreases from H  =  1 to H  =  0. In addition, the source of SHE for surface roughness with Gaussian profile distribution function is found to be mainly the side jump scattering while that with a non-Gaussian profile suggests both of the side jump and skew scatterings are present. Our achievements address how details of the surface roughness profile can adjust the SHE in non-heavy metals.

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

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.

Color multiplexing method to capture front and side images with a capsule endoscope.

PubMed

Tseng, Yung-Chieh; Hsu, Hsun-Ching; Han, Pin; Tsai, Cheng-Mu

2015-10-01

This paper proposes a capsule endoscope (CE), based on color multiplexing, to simultaneously record front and side images. Only one lens associated with an X-cube prism is employed to catch the front and side view profiles in the CE. Three color filters and polarizers are placed on three sides of an X-cube prism. When objects locate at one of the X-cube's three sides, front and side view profiles of different colors will be caught through the proposed lens and recorded at the color image sensor. The proposed color multiplexing CE (CMCE) is designed with a field of view of up to 210 deg and a 180 lp/mm resolution under f-number 2.8 and overall length 13.323 mm. A ray-tracing simulation in the CMCE with the color multiplexing mechanism verifies that the CMCE not only records the front and side view profiles at the same time, but also has great image quality at a small size.

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

Numerical investigation on performance and sediment erosion of Francis runner with different guide vane profiles

NASA Astrophysics Data System (ADS)

Lama, R.; Dahal, D. R.; Gautam, S.; Acharya, N.; Neopane, H.; Thapa, B. S.

2018-06-01

Francis turbine are ideal turbines for Himalayan and Andes region where both low and high-altitude mountains are located. Turbines operating in such regions face operational and maintenance problems due to the sediment erosion. In order to reduce the erosion effects on these components the design of components for higher sediment handling is essence. This paper presents performance analysis of Francis runner and prediction of sediment erosion on the runner blades for different operating conditions with different guide vane profiles. The simulations were carried out for 11 guide vane opening angles using Tabakoff erosion model. At full load and best efficiency point the erosion was localized at pressure side of runner blades outlet due to higher relative velocity. On the other hand, at part load condition, erosion was observed at suction side of the blades. Application of asymmetric guide vane profile NACA 4412 showed higher efficiency for all operating conditions with minimum erosion on runner blades in compare to symmetric guide vane profile NACA 0012.

Switching long acting antipsychotic medications to aripiprazole long acting once-a-month: expert consensus by a panel of Italian and Spanish psychiatrists.

PubMed

Fagiolini, Andrea; Alfonsi, Emilia; Amodeo, Giovanni; Cenci, Mario; Di Lella, Michele; Farinella, Francesco; Ferraiuolo, Fabrizio; Fraguas, David; Loparco, Natale; Gutierrez-Rojas, Luis; Mignone, Maria Laura; Pataracchia, Giuseppe; Pillai, Gianluca; Russo, Felicia; Sanchez-Gistau, Vanessa; Spinogatti, Franco; Toscano, Marco; Villari, Vincenzo; De Filippis, Sergio

2016-01-01

Aripiprazole long acting once-monthly (AOM) is a long acting atypical antipsychotic with proven efficacy in schizophrenia and with a pharmacological and a side effect profile that is different from other antipsychotics. These and other characteristics make AOM a possible alternative in patients requiring a change in long acting antipsychotic treatment due to issues such as lack of efficacy or persistent side effects. Both clinical and pharmacological factors should be considered when switching antipsychotics, and specific guidelines for long acting antipsychotic switching that address all these factors are needed. A panel of Italian and Spanish experts in psychiatry met to discuss the strategies for the switch to AOM in patients with schizophrenia. Real life clinical experiences were shared and the clinical strategies to improve the likelihood of success were discussed. Due to its specific pharmacological and tolerability profile, AOM represents a suitable alternative for patients with schizophrenia requiring a switch to a new LAI treatment because of lack of efficacy or persistent side effects from another LAI. Possible strategies for the switch to AOM are presented in this expert consensus paper in an attempt to provide guidance throughout the entire switching process.

Loop Diuretics in the Treatment of Hypertension.

PubMed

Malha, Line; Mann, Samuel J

2016-04-01

Loop diuretics are not recommended in current hypertension guidelines largely due to the lack of outcome data. Nevertheless, they have been shown to lower blood pressure and to offer potential advantages over thiazide-type diuretics. Torsemide offers advantages of longer duration of action and once daily dosing (vs. furosemide and bumetanide) and more reliable bioavailability (vs. furosemide). Studies show that the previously employed high doses of thiazide-type diuretics lower BP more than furosemide. Loop diuretics appear to have a preferable side effect profile (less hyponatremia, hypokalemia, and possibly less glucose intolerance). Studies comparing efficacy and side effect profiles of loop diuretics with the lower, currently widely prescribed, thiazide doses are needed. Research is needed to fill gaps in knowledge and common misconceptions about loop diuretic use in hypertension and to determine their rightful place in the antihypertensive arsenal.

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.

Three-Dimensional Printing of Carbamazepine Sustained-Release Scaffold.

PubMed

Lim, Seng Han; Chia, Samuel Ming Yuan; Kang, Lifeng; Yap, Kevin Yi-Lwern

2016-07-01

Carbamazepine is the first-line anti-epileptic drug for focal seizures and generalized tonic-clonic seizures. Although sustained-release formulations exist, an initial burst of drug release is still present and this results in side effects. Zero-order release formulations reduce fluctuations in serum drug concentrations, thereby reducing side effects. Three-dimensional printing can potentially fabricate zero-order release formulations with complex geometries. 3D printed scaffolds with varying hole positions (side and top/bottom), number of holes (4, 8, and 12), and hole diameters (1, 1.5, and 2 mm) were designed. Dissolution tests and high performance liquid chromatography analysis were conducted. Good correlations in the linear release profiles of all carbamazepine-containing scaffolds with side holes (R(2) of at least 0.91) were observed. Increasing the hole diameters (1, 1.5, and 2 mm) resulted in increased rate of drug release in the scaffolds with 4 holes (0.0048, 0.0065, and 0.0074 mg/min) and 12 holes (0.0021, 0.0050, and 0.0092 mg/min), and the initial amount of carbamazepine released in the scaffolds with 8 holes (0.4348, 0.7246, and 1.0246 mg) and 12 holes (0.1995, 0.8598, and 1.4366 mg). The ultimate goal of this research is to improve the compliance of patients through a dosage form that provides a zero-order drug release profile for anti-epileptic drugs, so as to achieve therapeutic doses and minimize side effects. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Effectiveness of Nissen fundoplication versus anterior and posterior partial fundoplications for treatment of gastro-esophageal reflux disease: a systematic review protocol.

PubMed

Marshall-Webb, Matthew; Peters, Micah D J; Bright, Tim; Watson, David I

2018-05-01

The objective of this review is to determine the relative effectiveness of Nissen fundoplication compared to anterior and posterior partial fundoplication in controlling the symptoms of gastro-esophageal reflux disease and reducing their side effect profile in adults.The specific questions posed by this review are: what is the effectiveness of Nissen fundoplication in comparison to anterior partial fundoplication (90 degree, 120 degree and 180 degree) and posterior 270 degree fundoplication in terms of symptom control of gastro-esophageal reflux disease, and what are the side effects of these surgical interventions?

Quaternary sedimentary processes on the northwestern African continental margin - An integrated study using side-scan sonar, high-resolution profiling, and core data

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

Masson, D.G.; Huggett, Q.J.; Weaver, P.P.E.

1991-08-01

Side-scan sonar data, cores, and high-resolution profiles have been used to produce an integrated model of sedimentation for the continental margin west of the Canary Islands. Long-range side-scan sonar (GLORIA) data and a grid of 3.5-kHz profiles, covering some 200,000 km{sup 2} allow a regional appraisal of sedimentation. More detailed studies of selected areas have been undertaken using a new 30 kHz deep-towed side-scan sonar (TOBI) developed by the U.K. Institute of Oceanographic Sciences. Sediment cores have been used both to calibrate acoustic facies identified on sonographs and for detailed stratigraphic studies. The most recent significant sedimentation event in themore » area is to Saharan Sediment Slide, which carried material from the upper continental slope off West Africa to the edge of the Madeira Abyssal Plain, a distance of some 1000 km. The authors data shows the downslope evolution of the debris flow. Near the Canaries, it is a 20-m-thick deposit rafting coherent blocks of more than 1 km diameter; side-scan records show a strong flow-parallel fabric on a scale of tens of meters. On the lower slope, the debris flow thins to a few meters, the flow fabric disappears, and the rafted blocks decrease to meters in diameter. Side-scan data from the lower slope show that the Saharan Slide buries an older landscape of turbidity current channels, typically 1 km wide and 50 m deep. Evidence from the Madeiran Abyssal Plain indicates a history of large but infrequent turbidity currents, the emplacement of which is related to the effects of sea level changes on the northwest African margin.« less

Diuretics in primary hypertension - Reloaded.

PubMed

Mishra, Sundeep

Diuretics have long been cherished as drugs of choice for uncomplicated primary hypertension. Robust mortality and morbidity data is available for diuretics to back this strategy. Off-late the interest for diuretics has waned off perhaps due to availability of more effective drugs but more likely due to perceived lack of tolerance and side-effect profile of high-dose of diuretics required for mortality benefit. Low-dose diuretics particularly thiazide diuretics are safer but lack the mortality benefit shown by high-dose. However, indapamide and low dose chlorthalidone have fewer side-effects but continue to provide mortality benefit. Copyright © 2016. Published by Elsevier B.V.

Beta-blockers in the management of hypertension: focus on nebivolol.

PubMed

Wojciechowski, David; Papademetriou, Vasilios

2008-04-01

Hypertension is a major cardiovascular risk factor but most patients remain asymptomatic for many years. Successful therapy not only needs to be effective, it also needs to be well tolerated. beta-blockers are well established as effective antihypertensive agents. However, one major drawback to the currently available beta-blockers, particularly the noncardioselective beta-blockers, is their side-effect profile, including sexual dysfunction, fatigue, depression and metabolic abnormalities such as impaired glucose tolerance and lipid abnormalities. Nebivolol (Bystolic), a novel, highly cardioselective, third-generation beta-blocker that recently received approval by the US FDA for the treatment of hypertension in the USA, is effective in treating blood pressure and has a favorable side-effect profile. Studies conducted in Europe, where nebivolol has been available for some time for the treatment of hypertension, have shown that nebivolol achieves blood pressure reductions comparable to other beta-blockers but with fewer side effects. Additionally, nebivolol has demonstrated similar efficacy in blood pressure reduction when compared with calcium channel blockers and inhibitors of the renin-angiotensin system. When combined with hydrochlorothiazide there was an additive antihypertensive effect. Lastly, nebivolol exhibits a vasodilatory property that is related to its effect on nitric oxide, an intrinsic vasodilator produced in the vascular endothelium. Nebivolol enhances nitric oxide bioavailability. Studies have also demonstrated nebivolol's ability to function as an antioxidant and decrease markers of oxidative stress. These effects are believed to ultimately produce a modulation of the endothelial dysfunction typically seen in hypertension.

Haloperidol, risperidone, olanzapine and aripiprazole in the management of delirium: A comparison of efficacy, safety, and side effects.

PubMed

Boettger, Soenke; Jenewein, Josef; Breitbart, William

2015-08-01

The aim of this study was to compare the efficacy and side-effect profile of the typical antipsychotic haloperidol with that of the atypical antipsychotics risperidone, olanzapine, and aripiprazole in the management of delirium. The Memorial Delirium Assessment Scale (MDAS), the Karnofsky Performance Status (KPS) scale, and a side-effect rating were recorded at baseline (T1), after 2-3 days (T2), and after 4-7 days (T3). Some 21 cases were case-matched by age, preexisting dementia, and baseline MDAS scores, and subsequently analyzed. The baseline characteristics of the medication groups were not different: The mean age of the patients ranged from 64.0 to 69.6 years, dementia was present in between 23.8 and 28.6%, and baseline MDAS scores were 19.9 (haloperidol), 18.6 (risperidone), 19.4 (olanzapine), and 18.0 (aripiprazole). The doses of medication at T3 were 5.5 mg haloperidol, 1.3 mg risperidone, 7.1 mg olanzapine, and 18.3 mg aripiprazole. Over one week, the decline in MDAS scores between medications was equal, and no differences between individual MDAS scores existed at T2 or T3. After one week, the MDAS scores were 6.8 (haloperidol), 7.1 (risperidone), 11.7 (olanzapine), and 8.3 (aripiprazole). At T2, delirium resolution occurred in 42.9-52.4% of cases and at T3 in 61.9-85.7%; no differences in assessments between medications existed. Recorded side effects were extrapyramidal symptoms (EPSs) in haloperidol- and risperidone-managed patients (19 and 4.8%, respectively) and sedation with olanzapine (28.6%). Haloperidol, risperidone, aripiprazole, and olanzapine were equally effective in the management of delirium; however, they differed in terms of their side-effect profile. Extrapyramidal symptoms were most frequently recorded with haloperidol, and sedation occurred most frequently with olanzapine.

The macaque midbrain reticular formation sends side-specific feedback to the superior colliculus.

PubMed

Wang, Niping; Warren, Susan; May, Paul J

2010-04-01

The central mesencephalic reticular formation (cMRF) likely plays a role in gaze control, as cMRF neurons receive tectal input and provide a bilateral projection back to the superior colliculus (SC). We examined the important question of whether this feedback is excitatory or inhibitory. Biotinylated dextran amine (BDA) was injected into the cMRF of M. fascicularis monkeys to anterogradely label reticulotectal terminals and retrogradely label tectoreticular neurons. BDA labeled profiles in the ipsi- and contralateral intermediate gray layer (SGI) were examined electron microscopically. Postembedding GABA immunochemistry was used to identify putative inhibitory profiles. Nearly all (94.7%) of the ipsilateral BDA labeled terminals were GABA positive, but profiles postsynaptic to these labeled terminals were exclusively GABA negative. In addition, BDA labeled terminals were observed to contact BDA labeled dendrites, indicating the presence of a monosynaptic feedback loop connecting the cMRF and ipsilateral SC. In contrast, within the contralateral SGI, half of the BDA labeled terminals were GABA positive, while more than a third were GABA negative. All the postsynaptic profiles were GABA negative. These results indicate the cMRF provides inhibitory feedback to the ipsilateral side of the SC, but it has more complex effects on the contralateral side. The ipsilateral projection may help tune the "winner-take-all" mechanism that produces a unified saccade signal, while the contralateral projections may contribute to the coordination of activity between the two colliculi.

Complaints associated with the use of antiepileptic drugs: results from a community-based study.

PubMed

Carpay, J A; Aldenkamp, A P; van Donselaar, C A

2005-04-01

Few data exist with respect to the occurrence of chronic side effects due to antiepileptic drugs (AED) in routine clinical practice. To evaluate the prevalence of subjective complaints which patients with epilepsy regard as side effects of their AED treatment in a community-based population. Cross-sectional study. Subjects were identified through the database of AED-use in the pharmacies in a suburban area in The Netherlands. Respondents completed a brief questionnaire about their epilepsy, including a checklist with 30 complaints, which are common in AED users. We present data of 346 responding adults with treated epilepsy from a population of 107,000 adult inhabitants. Eighty percent was using monotherapy, with few patients taking new AEDs. Almost 60% of the patients reported complaints probably due to side effects in at least three domains. General CNS-related side effects were reported most often; memory problems (21.4% of the patients) and fatigue (20.3%) were dominant. Polytherapy was associated with more side effects than monotherapy. We identified differences in profiles of complaints between valproate, carbamazepine and phenytoin monotherapy. Complaints were not substantially associated with ongoing seizures or other treatment factors. The majority of patients taking AEDs for epilepsy think they have side effects form their drugs, even when seizures were in remission and when monotherapy was used. Our findings suggest a need to improve monitoring of complaints of side effects of AEDs and to explore the feasibility of interventions aimed at reduction of such complaints in everyday clinical practice.

A Study on Water Surface Profiles of Rivers with Constriction

NASA Astrophysics Data System (ADS)

Qian, Chaochao; Yamada, Tadashi

2013-04-01

Water surface profile of rivers with constrictions is precious in both classic hydraulics and river management practice. This study was conducted to clarify the essences of the water surface profiles. 3 cases of experiments and 1D numerical calculations with different discharges were made in the study and analysis solutions of the non-linear basic equation of surface profile in varied flow without considering friction were derived. The manning's number was kept in the same in each case by using crosspiece roughness. We found a new type of water surface profile of varied flow from the results of 1D numerical calculation and that of experiments and named it as Mc curve because of its mild condition with constriction segment. This kind of curves appears as a nature phenomenon ubiquitously. The process of water surface forming is dynamic and bore occurs at the upper side of constriction during increasing discharge before the surface profile formed. As a theoretical work, 3 analysis solutions were derived included 2 physical-meaning solutions in the study by using Man-Machine system. One of the derived physical-meaning solutions was confirmed that it is validity by comparing to the results of 1D numerical calculation and that of experiments. The solution represents a flow profile from under critical condition at the upper side to super critical condition at the down side of constriction segment. The other derived physical-meaning solution represents a flow profile from super critical condition at the upper side to under critical condition at the down side of constriction segment. These two kinds of flow profiles exist in the nature but no theoretical solution can express the phenomenon. We find the depth distribution only concerned with unit width discharge distribution and critical depth under a constant discharge from the derived solutions. Therefor, the profile can be gained simply and precisely by using the theoretical solutions instead of numerical calculation even in practice.

Treatment of resistant tattoos using a new generation Q-switched Nd:YAG laser: influence of beam profile and spot size on clearance success.

PubMed

Karsai, Syrus; Pfirrmann, Gudrun; Hammes, Stefan; Raulin, Christian

2008-02-01

Multiple treatments of resistant tattoos often result in fibrosis and visible textural changes that lessen response to subsequent treatments. The aim of this study is to evaluate the influence of beam profile and spot size on clearance rates and side effects in the setting of resistant tattoos. Thirty-six professional, black tattoos (32 patients) were treated unsuccessfully with a Q-switched Nd:YAG laser (MedLite C3, HoyaConBio Inc., Fremont, CA). Because of therapy resistance all tattoos were re-treated using a new generation Nd:YAG laser (MedLite C6, HoyaConBio Inc.). Maximum energy fluence (E (max)), mean energy fluence, mean spot size, level of clearance, side effects and beam profile (irradiance distribution) of both laser systems were assessed and evaluated in a retrospective study. All tattoos were previously treated with the C3 laser at 1,064 nm using a mean E(max) of 5.8+/-0.8 J/cm(2) (range 3.8-7.5 J/cm(2)) as compared with a mean E(max) of 6.4+/-1.6 J/cm(2) (range 3.2-9.0 J/cm(2)) during the C6 treatment course. Corresponding spot sizes were larger during C6 treatments as compared with C3 (5.0+/-0.9 and 3.6+/-0.2 mm, respectively). The C6 laser had a "flat top" and homogenous profile regardless of the spot size. For the C3 laser the beam shape was "Gaussian," and the homogeneity was reduced by numerous micro-spikes and micro-nadirs. After the C6 treatment course 33.3% of the tattoos showed clearance of grade 1 (0-25%), 16.7% of grade 2 (26-50%), 16.7% of grade 3 (51-75%), 30.5% of grade 4 (76-95%), 2.8% of grade 5 (96-100%). The total rate of side effects due to C6 treatment was 8.3% in all tattoos (hyperpigmentation 5.6%, hypopigmentation 2.7%, textural changes/scars 0%). This clinical study documents for the first time the impact of a 1,064-nm Nd:YAG laser with a more homogenous beam profile and a larger spot size on the management of resistant tattoos. Only a few treatment sessions were necessary to achieve an additional clearance with a low rate of side effects.

Convergence behavior that controls adaptive wind tunnel walls near the test section in the high angle of attack range

NASA Technical Reports Server (NTRS)

Ziemann, J.

1982-01-01

The NACA 0012 profile at Mach 0.5 was investigated in a wind tunnel with adaptive walls. It is found that adaptation of the flexible walls is possible in the high angle of attack range on both sides of maximum lift. Oil film photographs of the flow at the profile surface show three dimensional effects in the region of the corners between the profile and the sidewall. It is concluded that pure two dimensional separated flow is not possible.

Feasibility of high-resolution one-dimensional relaxation imaging at low magnetic field using a single-sided NMR scanner applied to articular cartilage

NASA Astrophysics Data System (ADS)

Rössler, Erik; Mattea, Carlos; Stapf, Siegfried

2015-02-01

Low field Nuclear Magnetic Resonance increases the contrast of the longitudinal relaxation rate in many biological tissues; one prominent example is hyaline articular cartilage. In order to take advantage of this increased contrast and to profile the depth-dependent variations, high resolution parameter measurements are carried out which can be of critical importance in an early diagnosis of cartilage diseases such as osteoarthritis. However, the maximum achievable spatial resolution of parameter profiles is limited by factors such as sensor geometry, sample curvature, and diffusion limitation. In this work, we report on high-resolution single-sided NMR scanner measurements with a commercial device, and quantify these limitations. The highest achievable spatial resolution on the used profiler, and the lateral dimension of the sensitive volume were determined. Since articular cartilage samples are usually bent, we also focus on averaging effects inside the horizontally aligned sensitive volume and their impact on the relaxation profiles. Taking these critical parameters into consideration, depth-dependent relaxation time profiles with the maximum achievable vertical resolution of 20 μm are discussed, and are correlated with diffusion coefficient profiles in hyaline articular cartilage in order to reconstruct T2 maps from the diffusion-weighted CPMG decays of apparent relaxation rates.

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

Novel Formulation Strategy to Improve the Feasibility of Amifostine Administration.

PubMed

Ranganathan, Kavitha; Simon, Eric; Lynn, Jeremy; Snider, Alicia; Zhang, Yu; Nelson, Noah; Donneys, Alexis; Rodriguez, Jose; Buchman, Lauren; Reyna, Dawn; Lipka, Elke; Buchman, Steven R

2018-03-19

Amifostine (AMF), a radioprotectant, is FDA-approved for intravenous administration in cancer patients receiving radiation therapy (XRT). Unfortunately, it remains clinically underutilized due to adverse side effects. The purpose of this study is to define the pharmacokinetic profile of an oral AMF formulation potentially capable of reducing side effects and increasing clinical feasibility. Calvarial osteoblasts were radiated under three conditions: no drug, AMF, and WR-1065 (active metabolite). Osteogenic potential of cells was measured using alkaline phosphatase staining. Next, rats were given AMF intravenously or directly into the jejunum, and pharmacokinetic profiles were evaluated. Finally, rats were given AMF orally or subcutaneously, and blood samples were analyzed for pharmacokinetics. WR-1065 preserved osteogenic potential of calvarial osteoblasts after XRT to a greater degree than AMF. Direct jejunal AMF administration incurred a systemic bioavailability of 61.5%. Subcutaneously administrated AMF yielded higher systemic levels, a more rapid peak exposure (0.438 vs. 0.875 h), and greater total systemic exposure of WR-1065 (116,756 vs. 16,874 ng*hr/ml) compared to orally administered AMF. Orally administered AMF achieves a similar systemic bioavailability and decreased peak plasma level of WR-1065 compared to intravenously administered AMF, suggesting oral AMF formulations maintain radioprotective efficacy without causing onerous side effects, and are clinically feasible.

NSAI activity study of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives.

PubMed

Darias, V; Abdallah, S S; Tello, M L; Delgado, L D; Vega, S

1994-12-01

A series of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives endowed with anti-inflammatory and related pharmacological properties were submitted to a more extensive study to know their exact pharmacological profile and their possible side effects. The studied compounds possess a remarkable analgesic activity, devoid of central effects. They also show an interesting anti-inflammatory profile evidenced by their effectiveness in different experimental models of inflammation. In addition, these compounds exhibit none or very little activity on CNS, scarce toxicity and low gastrointestinal aggressivity.

Swiftly moving focus points and forming shapes through the scattering media

NASA Astrophysics Data System (ADS)

Tran, Vinh; Sahoo, Sujit Kumar; Tang, Dongliang; Dang, Cuong

2018-02-01

Propagation of light through scattering media such as ground glass or biological tissue limits the quality and intensity of focusing point. Wave front shaping technique which uses spatial light modulator (SLM) devices to reshape the field profile of incoming light, is considered as one of the most effective and convenient methods. Advanced biomedical or manufacturing applications require drawing various contours or shapes quickly and precisely. However, creating each shape behind the scattering medium needs different phase profiles, which are time consuming to optimize or measure. Here, we demonstrate a technique to draw various shapes or contours behind the scattering medium by swiftly moving the focus point without any mechanical movements. Our technique relies on the existence of speckle correlation property in scattering media, also known as optical memory effect. In our procedure, we first modulate the phase-only SLM to create the focus point on the other side of scattering medium. Then, we digitally shift the preoptimized phase profile on the SLM and ramp it to tilt the beam accordingly. Now, the incoming beam with identical phase profile shines on the same scattering region at a tilted angle to regenerate the focus point at the desired position due to memory effect. Moreover, with linear combination of different field patterns, we can generate a single phase profile on SLM to produce two, three or more focus points simultaneously on the other side of a turbid medium. Our method could provide a useful tool for prominent applications such as opto-genetic excitation, minimally invasive laser surgery and other related fields.

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

PubMed Central

Solmi, Marco; Murru, Andrea; Pacchiarotti, Isabella; Undurraga, Juan; Veronese, Nicola; Fornaro, Michele; Stubbs, Brendon; Monaco, Francesco; Vieta, Eduard; Seeman, Mary V; Correll, Christoph U; Carvalho, André F

2017-01-01

Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed first. However, alongside with safety, efficacy should also be considered on a patient-tailored basis. PMID:28721057

Medical Cannabis Use Is Associated With Decreased Opiate Medication Use in a Retrospective Cross-Sectional Survey of Patients With Chronic Pain.

PubMed

Boehnke, Kevin F; Litinas, Evangelos; Clauw, Daniel J

2016-06-01

Opioids are commonly used to treat patients with chronic pain (CP), though there is little evidence that they are effective for long term CP treatment. Previous studies reported strong associations between passage of medical cannabis laws and decrease in opioid overdose statewide. Our aim was to examine whether using medical cannabis for CP changed individual patterns of opioid use. Using an online questionnaire, we conducted a cross-sectional retrospective survey of 244 medical cannabis patients with CP who patronized a medical cannabis dispensary in Michigan between November 2013 and February 2015. Data collected included demographic information, changes in opioid use, quality of life, medication classes used, and medication side effects before and after initiation of cannabis usage. Among study participants, medical cannabis use was associated with a 64% decrease in opioid use (n = 118), decreased number and side effects of medications, and an improved quality of life (45%). This study suggests that many CP patients are essentially substituting medical cannabis for opioids and other medications for CP treatment, and finding the benefit and side effect profile of cannabis to be greater than these other classes of medications. More research is needed to validate this finding. This article suggests that using medical cannabis for CP treatment may benefit some CP patients. The reported improvement in quality of life, better side effect profile, and decreased opioid use should be confirmed by rigorous, longitudinal studies that also assess how CP patients use medical cannabis for pain management. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Comparison of tolerability and adverse symptoms in oxcarbazepine and carbamazepine in the treatment of trigeminal neuralgia and neuralgiform headaches using the Liverpool Adverse Events Profile (AEP).

PubMed

Besi, E; Boniface, D R; Cregg, R; Zakrzewska, J M

2015-01-01

Adverse effects of drugs are poorly reported in the literature . The aim of this study was to examine the frequency of the adverse events of antiepileptic drugs (AEDs), in particular carbamazepine (CBZ) and oxcarbazepine (OXC) in patients with neuralgiform pain using the psychometrically tested Liverpool Adverse Events Profile (AEP) and provide clinicians with guidance as to when to change management. The study was conducted as a clinical prospective observational exploratory survey of 161 patients with idiopathic trigeminal neuralgia and its variants of whom 79 were on montherapy who attended a specialist clinic in a London teaching hospital over a period of 2 years. At each consultation they completed the AEP questionnaire which provides scores of 19-76 with toxic levels being considered as scores >45. The most common significant side effects were: tiredness 31.3 %, sleepiness 18.2 %, memory problems 22.7 %, disturbed sleep 14.1 %, difficulty concentrating and unsteadiness 11.6 %. Females reported significantly more side effects than males. Potential toxic dose for females is approximately 1200 mg of OXC and 800 mg of CBZ and1800mg of OXC and 1200 mg of CBZ for males. CBZ and OXC are associated with cognitive impairment. Pharmacokinetic and pharmacodynamic differences are likely to be the reason for gender differences in reporting side effects. Potentially, females need to be prescribed lower dosages in view of their tendency to reach toxic levels at lower dosages. Side effects associated with AED could be a major reason for changing drugs or to consider a referral for surgical management.

Effect of orlistat or metformin in overweight and obese polycystic ovary syndrome patients with insulin resistance.

PubMed

Song, Jinghua; Ruan, Xiangyan; Gu, Muqing; Wang, Lijuan; Wang, Husheng; Mueck, Alfred Otto

2018-05-01

The aim of this study was to evaluate the effect of orlistat or metformin combined with Diane-35 on anthropometric, hormonal and metabolic parameters in overweight and obese polycystic ovary syndrome (PCOS) patients with insulin resistance (fasting insulin > 10 mIU/L). A total of 240 PCOS women were randomly allocated to orlistat plus Diane-35(OD group), metformin plus Diane-35(MD group), orlistat plus metformin plus Diane-35(OMD group) or Diane-35 (D group). Body weight, BMI, waist and hip circumference, blood pressure, endocrine profile, lipid profile and insulin resistance were assessed at baseline and after 3 months. Significant reductions in waist and hip circumference, serum LH, total testosterone and uric acid were observed in all groups compared with baseline. TG and TC significantly decreased in the OD group. Homeostasis model assessment insulin resistance (HOMA-IR) index was reduced in the OD (p = .015), MD (p = .001) and OMD (p = .004) groups. Body weight, BMI, systolic BP and HDL-C significantly changed in the OD and OMD group compared with the D group (p < .05). Side effects were less with orlistat than metformin. This study demonstrated that orlistat is more effective in reducing weight and lipid profile than metformin. Besides, orlistat has mild side-effects and is better tolerated compared with metformin.

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.

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.

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

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

Chillara, Vamshi Krishna; Pantea, Cristian; Sinha, Dipen N.

Here, we numerically investigate the resonance and vibration characteristics of radial modes of laterally stiffened piezoelectric disc transducers. Lateral stiffening is modeled using a spring and vibration characteristics of the piezo-disc are investigated with increasing lateral stiffness. It is found that the resonant frequency response of the radial modes follows an asymptotic behavior approaching that of a clamped disc with increasing lateral stiffness. The radial mode vibration pattern of the discs is also found to be affected by lateral stiffness. While the vibration pattern of a free disc corresponds to a Bessel function, laterally stiffened discs show edge-effects where theymore » depart from the Bessel-like behavior. In addition, a fully clamped piezo-disc is found to have an extra side-lobe when compared to a free disc. Ultrasonic beam profiles generated from radial modes of laterally stiffened discs are numerically investigated. It is found that the free piezo-disc generates a Bessel beam that has multiple side-lobes. Increasing the lateral stiffness results in a significant reduction of side-lobes in the beam profile. This technique of generating a collimated beam with side-lobe reduction finds significant applications in imaging through concrete, drilling mud, and other highly attenuating materials.« less

The Economic Contribution of Canada's Colleges and Institutes. An Analysis of Investment Effectiveness and Economic Growth. Volume 2: Detailed Results by Gender and Entry Level of Education

ERIC Educational Resources Information Center

Robison, M. Henry; Christophersen, Kjell A.

2008-01-01

The purpose of this volume is to present the results of the economic impact analysis in detail by gender and entry level of education. On the data entry side, gender and entry level of education are important variables that help characterize the student body profile. This profile data links to national statistical databases which are already…

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.

Design of permanent magnet eddy current brake for a small scaled electromagnetic launch model

NASA Astrophysics Data System (ADS)

Zhou, Shigui; Yu, Haitao; Hu, Minqiang; Huang, Lei

2012-04-01

A variable pole-pitch double-sided permanent magnet (PM) linear eddy current brake (LECB) is proposed for a small scaled electromagnetic launch model. A two-dimensional (2D) analytical steady state model is presented for the double-sided PM-LECB, and the expression for the braking force is derived. Based on the analytical model, the material and eddy current skin effect of the conducting plate are analyzed. Moreover, a variable pole-pitch double-sided PM-LECB is proposed for the effective braking of the moving plate. In addition, the braking force is predicted by finite element (FE) analysis, and the simulated results are in good agreement with the analytical model. Finally, a prototype is presented to test the braking profile for validation of the proposed design.

Gait profile score and movement analysis profile in patients with Parkinson's disease during concurrent cognitive load

PubMed Central

Speciali, Danielli S.; Oliveira, Elaine M.; Cardoso, Jefferson R.; Correa, João C. F.; Baker, Richard; Lucareli, Paulo R. G.

2014-01-01

Background: Gait disorders are common in individuals with Parkinson's Disease (PD) and the concurrent performance of motor and cognitive tasks can have marked effects on gait. The Gait Profile Score (GPS) and the Movement Analysis Profile (MAP) were developed in order to summarize the data of kinematics and facilitate understanding of the results of gait analysis. Objective: To investigate the effectiveness of the GPS and MAP in the quantification of changes in gait during a concurrent cognitive load while walking in adults with and without PD. Method: Fourteen patients with idiopathic PD and nine healthy subjects participated in the study. All subjects performed single and dual walking tasks. The GPS/MAP was computed from three-dimensional gait analysis data. Results: Differences were found between tasks for GPS (P<0.05) and Gait Variable Score (GVS) (pelvic rotation, knee flexion-extension and ankle dorsiflexion-plantarflexion) (P<0.05) in the PD group. An interaction between task and group was observed for GPS (P<0.01) for the right side (Cohen's ¯d=0.99), left side (Cohen's ¯d=0.91), and overall (Cohen's ¯d=0.88). No interaction was observed only for hip internal-external rotation and foot internal-external progression GVS variables in the PD group. Conclusions: The results showed gait impairment during the dual task and suggest that GPS/MAP may be used to evaluate the effects of concurrent cognitive load while walking in patients with PD. PMID:25054382

Safety and side effects of cannabidiol, a Cannabis sativa constituent.

PubMed

Bergamaschi, Mateus Machado; Queiroz, Regina Helena Costa; Zuardi, Antonio Waldo; Crippa, José Alexandre S

2011-09-01

Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were "cannabinoids", "cannabidiol" and "side effects". Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions. Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans. Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals. However, further studies are needed to clarify these reported in vitro and in vivo side effects.

Intravitreal injection therapy in the treatment of noninfectious uveitis.

PubMed

Modorati, Giulio; Miserocchi, Elisabetta

2012-01-01

Uveitis is responsible for 5-20% of legal blindness in the United States and in Europe. In noninfectious uveitis, the most frequent uveitic complication that endangers sight is cystoid macular edema. Clinical characteristics, inflammation grading and visual acuity determine the choice of the correct therapy for each patient. We can utilize drugs either alone or in combination using different dosages and routes of administration. Intravitreal injection directly into the vitreous cavity leads to rapid therapeutic drug concentration in the retinal tissue and reduces systemic side effects. Intravitreally injected triamcinolone acetonide is the most powerful drug for the treatment of cystoid macular edema related to intraocular inflammation, but it also causes the most frequent and serious side effects. Due to the numerous side effects associated with the use of corticosteroids, there is a need to identify other anti-inflammatory agents with a better safety profile. Recent studies have demonstrated that intravitreal immunosuppressant injections of methotrexate or anti-VEGF agents may lead to fewer intraocular side effects, but also have a lower therapeutic activity for the reduction of macular edema. At present, intraocular anti-TNF-α drugs do not show promising results. As regards nonsteroidal anti-inflammatory drugs, further data are necessary to fully understand their efficacy and potential side effects. Copyright © 2012 S. Karger AG, Basel.

Complementary velocity and heat transfer measurements in a rotating turbine cooling passage

NASA Astrophysics Data System (ADS)

Bons, Jeffrey Peter

An experimental investigation was conducted on the internal flowfield of a simulated turbine blade cooling passage. The passage is of a square cross-section and was manufactured from quartz for optical accessibility. Velocity measurements were taken using Particle Image Velocimetry for both heated and non-heated cases. Thin film resistive heaters on the four passage walls allow heat to be added to the coolant flow without obstructing laser access. Under the same conditions, an infrared detector with associated optics collected wall temperature data for use in calculating local Nusselt number. The test section was operated with radial outward flow and at values of Reynolds number, Rotation number, and density ratio typical of applications. Velocity data for the non-heated case document the evolution of the Coriolis-induced double vortex. The vortex has the effect of increasing the leading side boundary layer thickness while decreasing the trailing side boundary layer thickness. Also, the streamwise component of the Coriolis acceleration creates a thinned side wall boundary layer. These data reveal an unsteady, turbulent flowfield in the cooling passage. Velocity data for the heated case show a strongly distorted streamwise profile indicative of a buoyancy effect on the leading side. The Coriolis vortex is the mechanism for the accumulation of stagnant flow on the leading side of the passage. Heat transfer data show a maximum factor of two difference in the Nusselt number from trailing side to leading side. An estimate of this heat transfer disparity based on the measured boundary layer edge velocity yields approximately the same factor of two. A momentum integral model was developed for data interpretation which accounts for Coriolis and buoyancy effects. Calculated streamwise profiles and secondary flows match the experimental data well. The model, the velocity data, and the heat transfer data combine to suggest the presence of separated flow on the leading wall starting at about five passage widths for the conditions studied. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.)

Evaluation of chemically diverse 5-HT₂c receptor agonists on behaviours motivated by food and nicotine and on side effect profiles.

PubMed

Higgins, G A; Silenieks, L B; Lau, W; de Lannoy, I A M; Lee, D K H; Izhakova, J; Coen, K; Le, A D; Fletcher, P J

2013-04-01

Selective 5-HT2C receptor agonists, such as lorcaserin, are being developed for the treatment of obesity. Studies suggest that they may also have therapeutic potential for addictive behaviours including nicotine dependence, although few drugs of this class have been evaluated. The primary aim was to evaluate the highly selective 5-HT2C agonist, CP-809101, against food-motivated (operant FR5 and progressive ratio schedules, palatability-induced feeding) and nicotine-motivated (intravenous self-administration, drug discrimination) behaviours in rats and to compare with equivalent findings for the structurally distinct 5-HT2C receptor agonists lorcaserin and Ro 60-0175. The secondary aims were to evaluate the side effect profiles of lorcaserin and CP-809101 and to determine the plasma levels of lorcaserin at a dose (1 mg/kg) that reduces both food and nicotine reinforcement for comparison to plasma concentrations reported in human trials. CP-809101 (0.3-3 mg/kg SC) reduced responding for both nicotine and food and blocked the discriminative stimulus properties of nicotine in a similar manner to lorcaserin and Ro 60-0175. Behaviours such as hypolocomotion, chewing and ptosis became evident following both CP-809101 and lorcaserin administration at higher doses. Plasma levels of lorcaserin were of similar range to those reported in obesity trials. These studies support the utility of 5-HT2C agonists as a therapeutic approach to treat nicotine dependence. Plasma exposure levels after acute lorcaserin treatment suggest that equivalent dosages could be used to evaluate these drugs in obesity and smoking cessation trials. Finally, there may be differences in the side effect profiles between lorcaserin and CP-809101, raising the possibility for tolerability differences amongst 5-HT2C agonists.

Pharmacogenetics and outcome with antipsychotic drugs.

PubMed

Pouget, Jennie G; Shams, Tahireh A; Tiwari, Arun K; Müller, Daniel J

2014-12-01

Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h(2)~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.

Pharmacogenetics and outcome with antipsychotic drugs

PubMed Central

Pouget, Jennie G.; Shams, Tahireh A.; Tiwari, Arun K.; Müller, Daniel J.

2014-01-01

Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h2~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future. PMID:25733959

Feasibility of high-resolution one-dimensional relaxation imaging at low magnetic field using a single-sided NMR scanner applied to articular cartilage.

PubMed

Rössler, Erik; Mattea, Carlos; Stapf, Siegfried

2015-02-01

Low field Nuclear Magnetic Resonance increases the contrast of the longitudinal relaxation rate in many biological tissues; one prominent example is hyaline articular cartilage. In order to take advantage of this increased contrast and to profile the depth-dependent variations, high resolution parameter measurements are carried out which can be of critical importance in an early diagnosis of cartilage diseases such as osteoarthritis. However, the maximum achievable spatial resolution of parameter profiles is limited by factors such as sensor geometry, sample curvature, and diffusion limitation. In this work, we report on high-resolution single-sided NMR scanner measurements with a commercial device, and quantify these limitations. The highest achievable spatial resolution on the used profiler, and the lateral dimension of the sensitive volume were determined. Since articular cartilage samples are usually bent, we also focus on averaging effects inside the horizontally aligned sensitive volume and their impact on the relaxation profiles. Taking these critical parameters into consideration, depth-dependent relaxation time profiles with the maximum achievable vertical resolution of 20 μm are discussed, and are correlated with diffusion coefficient profiles in hyaline articular cartilage in order to reconstruct T(2) maps from the diffusion-weighted CPMG decays of apparent relaxation rates. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

[Theoretical and practical considerations in rational polytherapy for epilepsy].

PubMed

Rajna, Péter

2011-11-30

Author analyses the consideration of rational polytherapy for epilepsy. Among the theoretical aspects he points the different effect of seizure inhibitory drugs on the epilepsy models but didn't find data enough for the basis of any successful combination. Combinations of compounds having different way of action are more promising. Rational polytherapy can serve also the epileptic patients' tailored therapy in the daily routine. There have already been some proved synergisms concerning drug interactions. Based on detailed analysis of side effects a possibility occurs for neutralization of side effects when anticonvulsants with side effects of opposite nature are combined. Considering both the side effect profiles and the different (somatic and psychic) habits of the patients we can create a special list of favourable combinations. Co-morbid states and their treatments play a significant role in the application of rational polytherapy. Combination of anticonvulsants of lower potential but without drug-interactions can be the choice in these cases. The non-epileptic indications of the anticonvulsants can also be utilized in polymorbid patients. Based on the theoretical and practical considerations the author defines the ten-step-cognitive-preparation-process in planning the optimal (poly)therapy. On speculative basis he suggests eight beneficial versions of seizure inhibitory rational polytherapy.

Managing side effects of JAK inhibitors for myelofibrosis in clinical practice.

PubMed

Saeed, Iram; McLornan, Donal; Harrison, Claire N

2017-07-01

Myelofibrosis (MF) is characterized by bone marrow fibrosis, abnormalities in peripheral counts, extramedullary hematopoiesis, splenomegaly and an increased risk of transformation to acute myeloid leukaemia. The disease course is often heterogeneous and management can range from observation alone through to allogeneic stem cell transplantation. As of 2017, the only approved medication for MF remains the JAK Inhibitor (JAKi), ruxolitinib (Novartis Pharmaceuticals, Basel, Switzerland; Incyte, Wilmington, Detroit, USA) although several others have reached advanced stages of clinical trials. Areas covered: In this review, we focus on the management of both common and uncommon side effects arising from the use of currently approved and clinical trial JAKi. Most of the discussion concerns ruxolitinib although we also cover both pacritinib (CTI BioPharma) and momelotinib (Gilead Sciences, Foster City, California) which have been in recent large, multinational phase III trials. The various approaches to management of JAKi-related side effects are discussed - with particular emphasis to anaemia, thrombocytopaenia and infection risk. Expert commentary: JAK inhibitors are effective in many individuals with MF and have revolutionized the current treatment paradigm. The side effect profile, in the most, is predictable and manageable with high degrees of clinical surveillance and dose modifications.

Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone, olanzapine, quetiapine, or haloperidol: the results of the EIRE study.

PubMed

Bobes, J; Garc A-Portilla, M P; Rejas, J; Hern Ndez, G; Garcia-Garcia, M; Rico-Villademoros, F; Porras, A

2003-01-01

Atypical antipsychotics seem to differ mainly in their tolerability profile. The aim of this cross-sectional study, the Estudio de Investigaci n de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea). We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method. We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%). Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment (< 12 weeks). However, data on longer-term treatment (> 12 weeks) are lacking. Our results suggest that none of the atypical antipsychotics that we studied significantly improved sexual dysfunction and other reproductive side-effects of the conventional antipsychotic, haloperidol, in stabilized patients during long-term treatment. Quetiapine appears to improve this profile during short-term treatment; however, longterm data, with larger samples, are required with this latter drug.

Buspirone versus methylphenidate in the treatment of attention deficit hyperactivity disorder: a double-blind and randomized trial.

PubMed

Davari-Ashtiani, Rozita; Shahrbabaki, Mahin Eslami; Razjouyan, Katayoon; Amini, Homayoun; Mazhabdar, Homa

2010-12-01

The efficacy and side effects of buspirone compared with methylphenidate (MPH) in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). A total of 34 children with ADHD as defined by DSM-IV-TR were randomized to buspirone or methylphenidate dosed on weight-adjusted basis at buspirone (0.5 mg/kg/day) and methylphenidate (0.3-1 mg/kg/day) for a 6-week double-blind clinical trial. The principle measures of outcome were the teacher and parent ADHD Rating Scale. The side effects were assessed by the special side effect checklist of each drug. In both groups, the scores of teacher and parent ADHD Rating Scale significantly declined on the 6th week as compared to baseline (p = 0.001). These effects were observed in the subscales too. No significant differences were observed between the two protocols on the total scores of parent and teacher ADHD Rating Scale, but methylphenidate was superior to buspirone in decreasing the symptoms of inattention. The side effects of buspirone were mild and rare in comparison with MPH. Buspirone has a favorable side-effects profile. It also has clinically and statistically significant impacts on improving the ADHD symptoms in children. These preliminary findings of the efficacy of buspirone in children with ADHD need large and cross-over studies.

Cycle control and side effects of a new combiphasic oral contraceptive regimen.

PubMed

Dieben, T O; op ten Berg, M T; Coelingh Bennink, H J

1994-07-01

In a multicentre study 882 women were treated during a total of 12,850 cycles with a new combiphasic contraceptive: CTR 24. The study period was 18 cycles. The combiphasic preparation CTR 24 contains 25 micrograms desogestrel (CAS 54024-22-5) plus 40 micrograms ethinylestradiol (CAS 57-63-6) daily for the first 7 days followed by the combination of 125 micrograms desogestrel and 30 micrograms ethinyl-estradiol daily for the subsequent 15 days. The bleeding patterns were analysed over pill cycles and a comparison was made between starters and switchers. The cycle control of the combination was very good. The side effect profile was favourable.

Laminar-turbulent transition tripped by step on transonic compressor profile

NASA Astrophysics Data System (ADS)

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

2018-02-01

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). 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. The two cases are investigated: without and with boundary layer tripping device. In the first case, boundary layer is laminar up to the shock wave, while in the second case the boundary layer is tripped by the step. Numerical results carried out by means of Fine/Turbo Numeca with Explicit Algebraic Reynolds Stress Model including transition modeling are compared with schlieren, Temperature Sensitive Paint and wake measurements. Boundary layer transition location is detected by Temperature Sensitive Paint.

Radial modes of laterally stiffened piezoelectric disc transducers for ultrasonic collimated beam generation

DOE PAGES

Chillara, Vamshi Krishna; Pantea, Cristian; Sinha, Dipen N.

2017-07-15

Here, we numerically investigate the resonance and vibration characteristics of radial modes of laterally stiffened piezoelectric disc transducers. Lateral stiffening is modeled using a spring and vibration characteristics of the piezo-disc are investigated with increasing lateral stiffness. It is found that the resonant frequency response of the radial modes follows an asymptotic behavior approaching that of a clamped disc with increasing lateral stiffness. The radial mode vibration pattern of the discs is also found to be affected by lateral stiffness. While the vibration pattern of a free disc corresponds to a Bessel function, laterally stiffened discs show edge-effects where theymore » depart from the Bessel-like behavior. In addition, a fully clamped piezo-disc is found to have an extra side-lobe when compared to a free disc. Ultrasonic beam profiles generated from radial modes of laterally stiffened discs are numerically investigated. It is found that the free piezo-disc generates a Bessel beam that has multiple side-lobes. Increasing the lateral stiffness results in a significant reduction of side-lobes in the beam profile. This technique of generating a collimated beam with side-lobe reduction finds significant applications in imaging through concrete, drilling mud, and other highly attenuating materials.« less

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

PubMed

Vitzthum, Virginia J; Ringheim, Karin

2005-03-01

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

An orthologous transcriptional signature differentiates responses towards closely related chemicals in Arabidopsis thaliana and brassica napus

EPA Science Inventory

Herbicides are structurally diverse chemicals that inhibit plant-specific targets, however their off-target and potentially differentiating side-effects are less well defined. In this study, genome-wide expression profiling based on Affymetrix AtH1 arrays was used to identify dis...

Ablative skin resurfacing.

PubMed

Agrawal, Nidhi; Smith, Greg; Heffelfinger, Ryan

2014-02-01

Ablative laser resurfacing has evolved as a safe and effective treatment for skin rejuvenation. Although traditional lasers were associated with significant thermal damage and lengthy recovery, advances in laser technology have improved safety profiles and reduced social downtime. CO2 lasers remain the gold standard of treatment, and fractional ablative devices capable of achieving remarkable clinical improvement with fewer side effects and shorter recovery times have made it a more practical option for patients. Although ablative resurfacing has become safer, careful patient selection and choice of suitable laser parameters are essential to minimize complications and optimize outcomes. This article describes the current modalities used in ablative laser skin resurfacing and examines their efficacy, indications, and possible side effects. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Study of high field side/low field side asymmetry in the electron temperature profile with electron cyclotron emission

NASA Astrophysics Data System (ADS)

Gugliada, V. R.; Austin, M. E.; Brookman, M. W.

2017-10-01

Electron cyclotron emission (ECE) provides high resolution measurements of electron temperature profiles (Te(R , t)) in tokamaks. Calibration accuracy of this data can be improved using a sawtooth averaging technique. This improved calibration will then be utilized to determine the symmetry of Te profiles by comparing low field side (LFS) and high field side (HFS) measurements. Although Te is considered constant on flux surfaces, cases have been observed in which there are pronounced asymmetries about the magnetic axis, particularly with increased pressure. Trends in LFS/HFS overlap are examined as functions of plasma pressure, MHD mode presence, heating techniques, and other discharge conditions. This research will provide information on the accuracy of the current two-dimensional mapping of flux surfaces in the tokamak. Findings can be used to generate higher quality EFITs and inform ECE calibration. Work supported in part by US DoE under the Science Undergraduate Laboratory Internship (SULI) program and under DE-FC02-04ER549698.

Active site specificity profiling of the matrix metalloproteinase family: Proteomic identification of 4300 cleavage sites by nine MMPs explored with structural and synthetic peptide cleavage analyses.

PubMed

Eckhard, Ulrich; Huesgen, Pitter F; Schilling, Oliver; Bellac, Caroline L; Butler, Georgina S; Cox, Jennifer H; Dufour, Antoine; Goebeler, Verena; Kappelhoff, Reinhild; Keller, Ulrich Auf dem; Klein, Theo; Lange, Philipp F; Marino, Giada; Morrison, Charlotte J; Prudova, Anna; Rodriguez, David; Starr, Amanda E; Wang, Yili; Overall, Christopher M

2016-01-01

Secreted and membrane tethered matrix metalloproteinases (MMPs) are key homeostatic proteases regulating the extracellular signaling and structural matrix environment of cells and tissues. For drug targeting of proteases, selectivity for individual molecules is highly desired and can be met by high yield active site specificity profiling. Using the high throughput Proteomic Identification of protease Cleavage Sites (PICS) method to simultaneously profile both the prime and non-prime sides of the cleavage sites of nine human MMPs, we identified more than 4300 cleavages from P6 to P6' in biologically diverse human peptide libraries. MMP specificity and kinetic efficiency were mainly guided by aliphatic and aromatic residues in P1' (with a ~32-93% preference for leucine depending on the MMP), and basic and small residues in P2' and P3', respectively. A wide differential preference for the hallmark P3 proline was found between MMPs ranging from 15 to 46%, yet when combined in the same peptide with the universally preferred P1' leucine, an unexpected negative cooperativity emerged. This was not observed in previous studies, probably due to the paucity of approaches that profile both the prime and non-prime sides together, and the masking of subsite cooperativity effects by global heat maps and iceLogos. These caveats make it critical to check for these biologically highly important effects by fixing all 20 amino acids one-by-one in the respective subsites and thorough assessing of the inferred specificity logo changes. Indeed an analysis of bona fide MEROPS physiological substrate cleavage data revealed that of the 37 natural substrates with either a P3-Pro or a P1'-Leu only 5 shared both features, confirming the PICS data. Upon probing with several new quenched-fluorescent peptides, rationally designed on our specificity data, the negative cooperativity was explained by reduced non-prime side flexibility constraining accommodation of the rigidifying P3 proline with leucine locked in S1'. Similar negative cooperativity between P3 proline and the novel preference for asparagine in P1 cements our conclusion that non-prime side flexibility greatly impacts MMP binding affinity and cleavage efficiency. Thus, unexpected sequence cooperativity consequences were revealed by PICS that uniquely encompasses both the non-prime and prime sides flanking the proteomic-pinpointed scissile bond. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Tapered microelectrode array system for dielectrophoretically filtration: fabrication, characterization, and simulation study

NASA Astrophysics Data System (ADS)

Buyong, Muhamad Ramdzan; Larki, Farhad; Takamura, Yuzuru; Majlis, Burhanuddin Yeop

2017-10-01

This paper presents the fabrication, characterization, and simulation of microelectrode arrays system with tapered profile having an aluminum surface for dielectrophoresis (DEP)-based manipulation of particles. The proposed structure demonstrates more effective electric field gradient compared with its counterpart with untapered profile. Therefore, according to the asymmetric distribution of the electric field in the active region of microelectrode, it produces more effective particle manipulation. The tapered aluminum microelectrode array (TAMA) fabrication process uses a state-of-the-art technique in the formation of the resist's taper profile. The performance of TAMA with various sidewall profile angles (5 deg to 90 deg) was analyzed through finite-element method numerical simulations to offer a better understanding of the origin of the sidewall profile effect. The ability of capturing and manipulating of the device was examined through modification of the Clausius-Mossotti factor and cross-over frequency (f). The fabricated system has been particularly implemented for filtration of particles with a desired diameter from a mixture of particles with three different diameters in an aqueous medium. The microelectrode system with tapered side wall profile offers a more efficient platform for particle manipulation and sensing applications compared with the conventional microelectrode systems.

Oblique incidence reflectometry: optical models and measurements using a side-viewing gradient index lens-based endoscopic imaging system

NASA Astrophysics Data System (ADS)

Wall, R. Andrew; Barton, Jennifer K.

2014-06-01

A side-viewing, 2.3-mm diameter oblique incidence reflectometry endoscope has been designed to obtain optical property measurements of turbid samples. Light from a single-mode fiber is relayed obliquely onto the tissue with a gradient index lens-based distal optics assembly and the resulting diffuse reflectance profile is imaged and collected with a 30,000 element, 0.72 mm clear aperture fiber bundle. Sampling the diffuse reflectance in two-dimensions allows for fitting of the reflected intensity profile to a well-known theoretical model, permitting the extraction of both absorption and reduced scattering coefficients of the tissue sample. Models and measurements of the endoscopic imaging system are presented in tissue phantoms and in vivo mouse colon, verifying the endoscope's capabilities to accurately measure effective attenuation coefficient and differentiate diseased from normal colon.

Anticonvulsant effects of structurally diverse GABA(B) positive allosteric modulators in the DBA/2J audiogenic seizure test: Comparison to baclofen and utility as a pharmacodynamic screening model.

PubMed

Brown, Jordan W; Moeller, Achim; Schmidt, Martin; Turner, Sean C; Nimmrich, Volker; Ma, Junli; Rueter, Lynne E; van der Kam, Elizabeth; Zhang, Min

2016-02-01

The GABA(B) receptor has been indicated as a promising target for multiple CNS-related disorders. Baclofen, a prototypical orthosteric agonist, is used clinically for the treatment of spastic movement disorders, but is associated with unwanted side-effects, such as sedation and motor impairment. Positive allosteric modulators (PAM), which bind to a topographically-distinct site apart from the orthosteric binding pocket, may provide an improved side-effect profile while maintaining baclofen-like efficacy. GABA, the major inhibitory neurotransmitter in the CNS, plays an important role in the etiology and treatment of seizure disorders. Baclofen is known to produce anticonvulsant effects in the DBA/2J mouse audiogenic seizure test (AGS), suggesting it may be a suitable assay for assessing pharmacodynamic effects. Little is known about the effects of GABA(B) PAMs, however. The studies presented here sought to investigate the AGS test as a pharmacodynamic (PD) screening model for GABA(B) PAMs by comparing the profile of structurally diverse PAMs to baclofen. GS39783, rac-BHFF, CMPPE, A-1295120 (N-(3-(4-(4-chloro-3-fluorobenzyl)-6-methoxy-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide), and A-1474713 (N-(3-(4-(4-chlorobenzyl)-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide) all produced robust, dose-dependent anticonvulsant effects; a similar profile was observed with baclofen. Pre-treatment with the GABA(B) antagonist SCH50911 completely blocked the anticonvulsant effects of baclofen and CMPPE in the AGS test, indicating such effects are likely mediated by the GABA(B) receptor. In addition to the standard anticonvulsant endpoint of the AGS test, video tracking software was employed to assess potential drug-induced motor side-effects during the acclimation period of the test. This analysis was sensitive to detecting drug-induced changes in total distance traveled, which was used to establish a therapeutic index (TI = hypoactivity/anticonvulsant effects). Calculated TIs for A-1295120, CMPPE, rac-BHFF, GS39783, and A-1474713 were 5.31x, 5.00x, 4.74x, 3.41x, and 1.83x, respectively, whereas baclofen was <1. The results presented here suggest the DBA/2J mouse AGS test is a potentially useful screening model for detecting PD effects of GABA(B) PAMs and can provide an initial read-out on target-related motor side-effects. Furthermore, an improved TI was observed for PAMs compared to baclofen, indicating the PAM approach may be a viable therapeutic alternative to baclofen. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preventive treatment of migraine.

PubMed

Silberstein, Steven D

2005-01-01

Migraine preventive therapy, even in the absence of a headache, is given in an attempt to reduce the frequency, duration, or severity of attacks. Circumstances that might warrant preventive treatment include disabling migraine attacks, the overuse of acute medications or failure of or contraindication to acute medications, troublesome side effects from medication, hemiplegic migraine, or very frequent headaches (more than 2 a week). The major medication groups for preventive treatment include anticonvulsants, antidepressants, b-adrenergic blockers, calcium channel antagonists, serotonin antagonists, neurotoxins, nonsteroidal anti-inflammatory drugs, and others. If preventive medication is indicated, the agent preferentially should be chosen from one of the first-line categories, based on the drug's side-effect profile and the patient's coexistent and comorbid conditions.

Side effects of beta-blocker treatments as related to the central nervous system.

PubMed

Dahlöf, C; Dimenäs, E

1990-04-01

During the last decade beta-adrenoceptor antagonists have become one of the first-line treatments for hypertension. Generally, they have been shown to be safe with a low frequency of serious side effects. However, minor subjective symptoms, usually considered to be CNS-related, have been reported for all beta-blockers used. Thus, all beta-blockers on the market seem to have a high benefit:risk ratio; independent of their physicochemical properties and pharmacodynamic profile, however, they seem to cause CNS-related side effects to about the same extent. These minor side effects, the mechanisms of which are unclear, consist of subtle effects on general well being, decreased initiative, a depressed frame of mind, and disturbed sleep. Generally, however, beta-blockers in therapeutic dosages do not affect the qualitative functions of the brain. The results so far available have been obtained primarily by using objective methods. Further comparison has now been initiated using documented subjective methods to investigate whether the objectively documented differences are of any clinical relevance to the patient's quality of life. Although it cannot be claimed with certainty, nonselective beta-blockers seem to cause CNS-related side effects to a greater extent than beta 1-selective blockers. Differences in the degree of hydrophilicity of the beta-blocker are apparently of no clinical relevance in this respect. Rather, the plasma concentration of the beta-blocking drug (degree of beta-blockade) seems to be the major determinant of whether or not CNS-related symptoms appear in susceptible patients.

A National Coordinating Center for Trauma Research

DTIC Science & Technology

2017-10-01

symptoms of acute stress disorder and depression to prevent syndromal PTSD and depression Related Research Presentations/Publications Posters Annual JHU...Site: Johns Hopkins University School of Medicine HRPO Assigned A-number: A-19299.2 Abstract: Background: Early, effective pain control for acute ...sparing drug for the treatment of acute post-traumatic pain • The side effect profile of ketamine when administered in sub-anesthetic doses • Whether

Caspofungin in the treatment of invasive fungal infections.

PubMed

Keady, Simon; Thacker, Meera

2006-02-01

Caspofungin is a member of a new class of antifungals called Echinocandins and is the first to have marketing authorisation in the United Kingdom. This article reviews the clinical efficacy, side effect profile, dosing and administration schedule of caspofungin. The article also discusses the warnings and precautions associated with the use of this drug. Caspofungin is an effective treatment option in the management of fungal infections.

Chromatography of Penicillins, Penicilloates, and Penicilloylamides on Dextran Gels

PubMed Central

Hyslop, Newton E.; Milligan, Richard J.

1974-01-01

The factors influencing the chromatographic behavior on dextran gels of penicillins and their derivatives were investigated by comparing elution profiles and partition coefficients (KD and KAV) of penicillins differing in side-chain structure and among penicillin derivatives of identical side-chain but different nuclear structure. Under the conditions of pH and ionic strength employed (pH 7.4, 0.145 M NaCl, 0.05 M PO4), side-chain adsorptive effects best explained the anomalous behavior of benzylpenicillin and of oxacillin and its chlorine-substituted analogues. Polar side-chain substituents, such as the amino group of ampicillin and the carboxyl group of carbenicillin, and cleavage of the β-lactam ring, exemplified by penicilloates and penicilloylamines, both appeared to interfere with side-chain-directed adsorption. The differential adsorption of penicillins and their derivatives to dextran gels is not only of theoretical interest relative to the mechanism of chromatography but of practical application to analytical and preparative procedures in penicillin chemistry. PMID:15825415

Male Batterer Profiles: Support for an Empirically Generated Typology

ERIC Educational Resources Information Center

Chiffriller, Sheila H.; Hennessy, James J.

2006-01-01

Domestic violence is an issue that affects different sides of society; numerous studies have shown that it is a problem that is increasing. This study used a discriminant analysis to identify those scales that might be more effective at predicting group membership among batterer types: pathological batterers, sexually violent batterers, generally…

[Use of methylphenidate in palliative patients with asthenia: a review].

PubMed

Saralegui, A; Palacio, P; Royo, P

2013-09-06

Asthenia (or fatigue) is one of the most common symptoms in palliative patients. Methylphenidate is currently being assessed for treating this condition. A review of related literature published to date was performed, revealing methylphenidate to be a safe drug which could decrease fatigue in palliative patients with a tolerable side-effects profile.

Tic Reduction with Risperidone Versus Pimozide in a Randomized, Double-Blind, Crossover Trial

ERIC Educational Resources Information Center

Gilbert, Donald L.; Batterson, J. Robert; Sethuraman, Gopalan; Sallee, Floyd R.

2004-01-01

Objective: To compare the tic suppression, electrocardiogram (ECG) changes, weight gain, and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders. Method: This was a randomized, double-blind, crossover (evaluable patient analysis) study. Nineteen children aged 7 to 17 years with Tourette's or chronic…

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...

Caregiver Survey of Pharmacotherapy to Treat Attention Deficit/Hyperactivity Disorder in Individuals with Williams Syndrome

ERIC Educational Resources Information Center

Martens, Marilee A.; Seyfer, Daisha L.; Andridge, Rebecca R.; Foster, Jessica E. A.; McClure, Kelsey E.; Coury, Daniel L.

2013-01-01

Williams syndrome (WS) is a genetic condition characterized by a unique neurocognitive and behavioral profile, including increased incidence of attention deficit/hyperactivity disorder (ADHD). The purpose of the present study was to examine the perceived helpfulness and side effects of medications used to treat ADHD (methylphenidate class,…

Efficacy and safety of novel antipsychotics: a critical review.

PubMed

Balestrieri, Matteo; Vampini, Claudio; Bellantuono, Cesario

2000-10-01

Efficacy and safety of novel antipsychotic (AP) drugs (amisulpride, olanzapine, quetiapine, ziprasidone and zotepine) have been reviewed. Data on their antipsychotic efficacy and side effects profile have been evaluated only on the basis of controlled trials so far published. Overall, all these drugs have shown an antipsychotic efficacy on positive symptoms of schizophrenia similar to that of the conventional AP drugs. On negative symptoms, all novel AP drugs, except quetiapine and ziprasidone, demonstrated a better efficacy than haloperidol. Long-term efficacy of these AP drugs in the maintenance treatment of schizophrenia needs to be explored by further, better-designed, epidemiological studies. The safety profile shows that the novel AP drugs are generally well-tolerated and induce significantly less acute extrapyramidal side effects in comparison with haloperidol. Some methodological flaws in the experimental design of the clinical trials analysed are discussed. Although these novel AP drugs have potential clinical advantages, a number of relevant questions still remain to be addressed, in order to establish the impact of these drugs in the overall treatment of schizophrenia. Copyright 2000 John Wiley & Sons, Ltd.

Identification of gene expression profiling associated with erlotinib-related skin toxicity in pancreatic adenocarcinoma patients

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

Caba, Octavio, E-mail: ocaba@ujaen.es

Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that showed activity against pancreatic ductal adenocarcinoma (PDAC). The drug's most frequently reported side effect as a result of EGFR inhibition is skin rash (SR), a symptom which has been associated with a better therapeutic response to the drug. Gene expression profiling can be used as a tool to predict which patients will develop this important cutaneous manifestation. The aim of the present study was to identify which genes may influence the appearance of SR in PDAC patients. The study included 34 PDAC patients treated with erlotinib: 21 patientsmore » developed any grade of SR, while 13 patients did not (controls). Before administering any chemotherapy regimen and the development of SR, we collected RNA from peripheral blood samples of all patients and studied the differential gene expression pattern using the Illumina microarray platform HumanHT-12 v4 Expression BeadChip. Seven genes (FAM46C, IFITM3, GMPR, DENND6B, SELENBP1, NOL10, and SIAH2), involved in different pathways including regulatory, migratory, and signalling processes, were downregulated in PDAC patients with SR. Our results suggest the existence of a gene expression profiling significantly correlated with erlotinib-induced SR in PDAC that could be used as prognostic indicator in this patients. - Highlights: • Skin rash (SR) is the most characteristic side effect of erlotinib in PDAC patients. • Erlotinib-induced SR has been associated with a better clinical outcome. • Gene expression profiling was used to determine who will develop this manifestation. • 7 genes involved in different pathways were downregulated in PDAC patients with SR. • Our profile correlated with erlotinib-induced SR in PDAC could be used for prognosis.« less

Creatine metabolism and safety profiles after six-week oral guanidinoacetic acid administration in healthy humans.

PubMed

Ostojic, Sergej M; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

2013-01-01

Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities.

Creatine Metabolism and Safety Profiles after Six-Week Oral Guanidinoacetic Acid Administration in Healthy Humans

PubMed Central

Ostojic, Sergej M.; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

2013-01-01

Objectives; Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Methods and Results; Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. Clinical trial registration: www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Conclusion; Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities. PMID:23329885

Pharmacokinetics, safety and tolerability of a novel tocopheryl phosphate mixture/oxycodone transdermal patch system: a Phase I study.

PubMed

Gavin, Paul D; Simon, Lee S; Schlagheck, Thomas; Smith, Alisha J; Shakib, Sepehr

2017-07-01

To characterize the pharmacokinetic profile and evaluate the safety and tolerability of a transdermal oxycodone patch containing tocopheryl phosphate mixture (TPM). Eleven healthy subjects received a single application of three TPM/oxycodone patches applied to the torso for 72 h. Oxycodone was detected 8.0 ± 2.7-h postpatch administration, reaching a mean maximum plasma concentration of 3.41 ± 1.34 ng/ml at 49.3 ± 21.2 h. The safety profile was consistent with the application method and known side-effect profile of oxycodone and naltrexone. No treatment-limiting skin irritation was observed. A 3-day application of the TPM/oxycodone patch demonstrated an acceptable safety profile and was well tolerated by healthy subjects, with limited dermal irritation following application.

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

PubMed

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

1990-01-01

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

Pharmacokinetic and pharmacodynamic profile of supratherapeutic oral doses of Δ9-THC in cannabis users

PubMed Central

Lile, Joshua A.; Kelly, Thomas H.; Charnigo, Richard J.; Stinchcomb, Audra L.; Hays, Lon R.

2013-01-01

Oral Δ9-tetrahydrocannabinol (Δ9-THC) has been evaluated as a medication for cannabis dependence, but repeated administration of acute oral doses up to 40 mg has not been effective at reducing drug-taking behavior. Larger doses might be necessary to affect cannabis use. The purpose of the present study was therefore to determine the physiological and behavioral effects of oral Δ9-THC at acute doses higher than those tested previously. The pharmacokinetic and pharmacodynamic profile of oral Δ9-THC, administered in ascending order in 15 mg increments across separate sessions, up to a maximum of 90 mg, was determined in seven cannabis users. Five subjects received all doses and two experienced untoward side effects at lower doses. Δ9-THC produced a constellation of effects consistent with previous clinical studies. Low cannabinoid concentrations were associated with significant effects on drug- sensitive measures, although progressively greater levels did not lead to proportionately larger drug effects. Considerable variability in Cmax and tmax was observed. Doses of oral Δ9-THC larger than those tested previously can be administered to individuals with a history of cannabis use, although given the pharmacokinetic variability of oral Δ9-THC and individual differences in sensitivity, individualized dose adjustment is needed to avoid side effects and maximize therapeutic response. PMID:23754596

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

PubMed

Morgan, Michael M; Christie, MacDonald J

2011-10-01

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

Spiral biasing adaptor for use in Si drift detectors and Si drift detector arrays

DOEpatents

Li, Zheng; Chen, Wei

2016-07-05

A drift detector array, preferably a silicon drift detector (SDD) array, that uses a low current biasing adaptor is disclosed. The biasing adaptor is customizable for any desired geometry of the drift detector single cell with minimum drift time of carriers. The biasing adaptor has spiral shaped ion-implants that generate the desired voltage profile. The biasing adaptor can be processed on the same wafer as the drift detector array and only one biasing adaptor chip/side is needed for one drift detector array to generate the voltage profiles on the front side and back side of the detector array.

Shoulder rotational profiles in young healthy elite female and male badminton players.

PubMed

Couppé, C; Thorborg, K; Hansen, M; Fahlström, M; Bjordal, J M; Nielsen, D; Baun, M; Storgaard, M; Magnusson, S P

2014-02-01

The aim of the present study was to profile shoulder passive range of motion (ROM) and isometric strength for external (ER) and internal (IR) rotation as part of a preseason screening in adolescent national badminton players. Passive external range of motion (EROM) and internal range of motion (IROM) were examined on the dominant and nondominant shoulder in 31 adolescent national badminton players (12 females and 19 males) with a standard goniometer. Muscle strength was examined with a hand-held dynamometer in ER and IR. Total range of motion (TROM = EROM+IROM) was lower on the dominant side compared with the nondominant side in both groups (P < 0.001). Males were generally stronger than females in all strength measurements except for IR on the dominant side (P < 0.01). In females, IR dominant side strength was greater compared with IR on the nondominant side (P < 0.05). TROM was reduced on the dominant side compared with the nondominant side in young elite badminton players, irrespective of gender. No rotational strength differences existed between the dominant and nondominant side in male players, but in female players a higher IR strength on the dominant side was not balanced by a higher ER strength. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[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.

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

NASA Technical Reports Server (NTRS)

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

2001-01-01

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

Structure of the ripple phase in lecithin bilayers.

PubMed Central

Sun, W J; Tristram-Nagle, S; Suter, R M; Nagle, J F

1996-01-01

The phases of the x-ray form factors are derived for the ripple (Pbeta') thermodynamic phase in the lecithin bilayer system. By combining these phases with experimental intensity data, the electron density map of the ripple phase of dimyristoyl-phosphatidylcholine is constructed. The phases are derived by fitting the intensity data to two-dimensional electron density models, which are created by convolving an asymmetric triangular ripple profile with a transbilayer electron density profile. The robustness of the model method is indicated by the result that many different models of the transbilayer profile yield essentially the same phases, except for the weaker, purely ripple (0,k) peaks. Even with this residual ambiguity, the ripple profile is well determined, resulting in 19 angstroms for the ripple amplitude and 10 degrees and 26 degrees for the slopes of the major and the minor sides, respectively. Estimates for the bilayer head-head spacings show that the major side of the ripple is consistent with gel-like structure, and the minor side appears to be thinner with lower electron density. Images Fig. 1 Fig. 2 PMID:8692934

Processing and attenuation of noise in deep seismic-reflection data from the Gulf of Maine

USGS Publications Warehouse

Hutchinson, D.R.; Lee, M.W.

1989-01-01

The U.S. Geological Survey deep crustal studies reflection profile across the Gulf of Maine off southeastern New England was affected by three sources of noise: side-scattered noise, multiples, and 20-Hz whale sounds. The special processing most effective in minimizing this noise consisted of a combination of frequency-wavenumber (F-K) filtering, predictive deconvolution, and spectral whitening, each applied in the shot domain (prestack). Application of the F-K filter to remove side-scatter noise in the poststack domain resulted in a much poorer quality profile. The prestack noise suppression processing techniques resulted in a reflection profile with good signal-to-noise ratios and reliable strong reflections, especially at depths equivalent to the lower crust (24-34 km). Certain geologic features, such as a buried rift basin and a crustal fault are resolved much better within the upper crust after this processing. Finite difference migration of these data using realistic velocities produced excellent results. Migration was essential to distinguish between abundant dipping and subhorizontal reflections in the lower crust as well as to show an essentially transparent upper mantle. ?? 1989 Kluwer Academic Publishers.

Efficacy and side-effects profile of the ethinylestradiol and etonogestrel contraceptive vaginal ring: a systematic review and meta-analysis.

PubMed

López-Picado, Amanda; Lapuente, Oihane; Lete, Iñaki

2017-04-01

To assess the efficacy and tolerability (side-effects profile), and compliance of the combined contraceptive vaginal ring (CCVR) compared with combined oral hormonal contraceptives (COC). The PubMed, Embase, POPLINE, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, ClinicalTrials.gov, Clinical Trials Registry Platform (ICTRP) and CINAHL databases were searched. Electronic databases were searched for randomised clinical trials comparing the CCVR with COC with a duration of at least 3 months between 01 December and 15 December 2015. The primary outcome was efficacy. The secondary outcomes were compliance, absence of withdrawal bleeding, breakthrough bleeding, nausea and headache. Heterogeneity was assessed using I 2 statistic and Cochran's Q statistic. Results were expressed as odds ratios (OR) with 95% confidence intervals (CIs) using random-effects models or fixed-effects models depending on the heterogeneity. 4368 records were identified, 2844 of which were removed after duplicates and 1524 records were screened. Of these, 1503 were excluded and 21 full text articles were assessed for eligibility. After removing another 7 articles, 14 records were finally included in the qualitative and quantitative analysis. The results show a trend to higher efficacy for the CCVR in preventing pregnancy (Peto OR: 0.52 [95% CI: 0.26-1.04]) and a significantly lower presence of nausea (Peto OR: 0.66 [95% CI: 0.46-0.93]). More cycles were compliant in the CCVR group (Peto OR: 1.22 [95% CI: 1.12-1.32]) and fewer women reported breakthrough bleeding (Peto OR: 0.68 [95% CI: 0.51-0.91]). Our findings demonstrate that the CCVR is as effective and tolerable as the COC but with a better bleeding profile.

Nanotechnological advances for cutaneous release of tretinoin: an approach to minimize side effects and improve therapeutic efficacy.

PubMed

Raminelli, Ana Claudia Pompeu; Romero, Valeria; Semreen, Mohammad H; Leonardi, Gislaine Ricci

2018-03-12

The clinical efficacy of the topical tretinoin is widely studied and has been well established for many therapeutic interventions, among some, photoaging, acne, and melasma. However, the side effects, mainly cutaneous irritation, erythema, xerosis and peeling, remain major obstacle to the patient compliance. Besides, the insight regarding the drug delivery profile is essential to understand the therapeutic action of the drug. Herein we highlight further advances and an update on tretinoin delivery systems such as liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, cyclodextrins, nanostructured polymers and other technological systems that reduce its side effects and improve the permeation profile to potentiate efficacy and drug safety on the skin. Pharmaceutical preparations were developed and evaluated for permeability in in vitro models using pig ear, snake, mouse and human skin, and potential for irritation was also verified using release systems for tretinoin and compared to available commercial formulations. Overall results indicated the composition, charge and size of the system influences the tretinoin delivery, modulating the type of release and its retention. Small unilamellar vesicles promoted greater cutaneous delivery of tretinoin. Negative charge, for both liposomes and niosomes, can improve pig skin hydration as well as the tretinoin retention. The quantity of solid lipids and the type of oil used in the composition of solid lipid nanoparticles and nanostructured lipid carriers affected percutaneous drug delivery. As evident from the literature, the tretinoin technological delivery systems consist an innovative and potential management for increasing the patient compliance presenting safety and efficacy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

Use of anti-epileptic drugs in a tertiary care hospital of Eastern India with emphasis on epilepsy due to neurocysticercosis.

PubMed

Sil, Amrita; Das, Kamalesh; Das, Nilay K; Chakraborty, Dibyendu; Mazumdar, Goutameswar; Tripathi, Santanu K

2012-01-01

Epilepsy is a chronic disease and neurocysticercosis is an important cause of secondary seizures. Its therapy is modified by a number of parameters and thus the pattern of anti-epileptic drugs used varies in different clinical settings. It was our objective to evaluate clinico-demographic and treatment profile of epilepsy patients attending neurology outpatient department, efficacy and side-effect profile of anti-epileptic drugs with special emphasis on epilepsy resulting from neurocysticercosis. This was a cross-sectional descriptive study of epilepsy patients over four months in neurology outpatient department. Clinico-biological data were obtained by interrogating patients and from recorded data using standard case-report form. 79 patients were studied with 54.43% having primary etiology, 40.51% having seizures secondary to neurocysticercosis. 81% had generalized tonic-clonic seizure, 17.7% partial and 1.3% myoclonic seizures. Phenytoin (86.08%), valproate (30.38%), clobazam (26.58%) and carbamazepine (10.13%) were used either alone or in combination, with no use of anthelmintics even in cases of neurocysticercosis. Control of seizure was obtained in 79.7% with significant decrease in seizure frequency from 2.92 to 0.51 (P < 0.0001). Weight loss, nausea, decreased appetite, increased sleep, drowsiness, tremors were found to be significantly associated (P < 0.05) with phenytoin use. Phenytoin is the primary antiepileptic in spite of its side effects; though addition of other anti-epileptic drugs (valproate, clobazam) was required for better seizure control. Cases of neurocysticercosis respond to anti-epileptic drugs without addition of anthelmintics. Side effects observed were mostly neurological in nature.

Epidural analgesia side effects, co-interventions, and care of women during childbirth: a systematic review.

PubMed

Mayberry, Linda J; Clemmens, Donna; De, Anindya

2002-05-01

The purpose of this article is to profile research findings targeting the intrapartum care implications of the most common side effects and co-interventions that go along with the use of epidural analgesia during labor. Randomized, controlled trials published in English from 1990 to 2000 that addressed each of the targeted side effects and 3 specified co-interventions were evaluated for inclusion in this report. Side effects such as pruritus, nausea, and hypotension during labor are common, but they are usually mild and necessitate treatment infrequently. However, even with the advent of newer low-dose epidurals, the extent of impaired motor ability remains variable across studies. The incidence of "walking" epidurals during labor is likely to be complicated by multiple factors, including individual patient desires, safety considerations, and hospital policies. In response to risks for a decrease in uterine contractions that could prolong labor, oxytocin augmentation is likely to be administered after epidural analgesia. The use of "delayed" pushing may be an effective way to minimize the risk for difficult deliveries. Upright positioning even when confined to bed may be advantageous and desirable to women; however, additional research to determine actual outcome benefits with epidurals is needed. Implications for further research linked to epidural analgesia also include informed consent, modification of caregiving procedures, and staffing/cost issues.

Emergency contraception: which is the best?

PubMed

Mittal, Suneeta

2016-12-01

Emergency contraception is a safe and effective method to prevent an unwanted pregnancy after an unprotected or inadequately protected sexual intercourse. Several methods for emergency contraception (EC) are currently registered in many countries for use in an emergency to prevent a pregnancy following an unprotected, possibly fertile intercourse or after a contraceptive accident like condom rupture. Different methods have varying modes of action, time frame of efficacy, dosage schedule and unwanted effects. Since several methods are available it is important to decide the best method. In this article the available literature on emergency contraception has been reviewed and an attempt has been made to discuss the need for emergency contraception and compare different options for emergency contraception in terms of their efficacy in pregnancy prevention, their safety profile and unwanted side effects. EC repeated use and initiating a regular method after EC use are also discussed. Emergency contraceptive methods include copper Intra-uterine devices (IUD) and different types of pills like estrogen progestin combination pill (Yuzpe Regimen), Progestin only pill (LNG), antiprogestin pill (Mifepristone), and progesterone modulator Uripristal Acetate (UPA). There is a marginal difference in the mechanism of action, efficacy including time frame and ability to protect from pregnancy with regular doses in obese women, drug interactions and side effects. These are discussed in detail. Copper IUD is the most effective emergency contraceptive with advantage of providing continued contraception. However, it cannot be used universally due to lack of infrastructure and a trained provider as well as not being suitable option for women at risk of sexually transmitted infections. Amongst different pills LNG is more effective with fewer side effects than Yuzpe regimen. LNG and UPA are comparable with similar efficacy and side effect profile. UPA has a wider window of efficacy, in LNG efficacy declines after 72 hours. UPA is more suitable for obese women. Mifepristone is effective but is registered as EC pill only in few countries and use is limited as it is also used as an abortion pill. Yuzpe regimen is the least effective of all contraceptive pills as EC, and works only till 72 hours of unprotected sex, but is useful in places where dedicated methods are not available, as it is easily accessible. Any combined pill can be used in this regimen except triphasic pill.

Usefulness of Corsair microcatheter to cross stent struts in bifurcation lesions.

PubMed

Fujimoto, Yoshihide; Iwata, Yo; Yamamoto, Masashi; Kobayashi, Yoshio

2014-01-01

Side branch compromise after stenting in bifurcation lesions is a matter of concern. It may happen that even low-profile balloon catheters do not cross stent struts after rewiring. The Corsair catheter is a hybrid catheter that has features of a microcatheter and a support catheter. The present study evaluated usefulness of the Corsair catheter to facilitate advancing a low-profile balloon catheter through stent struts in bifurcation lesions. After rewiring, low-profile balloon catheters failed to cross stent struts of 29 bifurcation lesions. The Corsair microcatheter successfully crossed stent struts in all lesions except one (97 %) where a stent was implanted to treat in-stent restenosis (stent-in-stent). Low-profile balloon catheters were able to advance into the side branch of all bifurcation lesions where the Corsair microcatheter crossed stent struts. In conclusion, the Corsair microcatheter may be utilized if low-profile balloon catheters are unable to cross stent struts in bifurcation lesions.

Cutaneous Side-effects of Immunomodulators in MS.

PubMed

Lebrun, C; Bertagna, M; Cohen, M

2011-09-01

Local skin reactions to subcutaneous injections of interferon beta (IFNB) or glatiramer acetate (GA) in multiple sclerosis (MS) are frequent, while severe cutaneous toxicity is rare. Both IFNB and GA are immunomodulatory drugs that have excellent safety profiles and are currently used for treatment of MS. They are administered by SC injection every other day for IFNB-1b, three times a week for IFNB-1a or daily for 20 mg for GA. The most common adverse effects, which occur in approximately 20-60% of patients, include pain, inflammation and induration at the injection sites. Another adverse effect is frank panniculitis followed by localized lipoatrophy at the injection sites, which has been described in half of the patients receiving GA injections but is also described with Subcutaneous IFNB-1b. No guidelines have yet been established for the treatment of skin reactions, which is a frequent point for discussion between neurologists and dermatologists. In addition, no treatment has been found for established lipoatrophy. The prevention and management of cutaneous side-effects include patient education, regular examination and manual palpation of all injection sites. Non-steroid antiinflammatory gels, local corticosteroids or endermology can help patients to resolve side-effects and to continue immunomodulatory treatment.

Structural evolution of self-ordered alumina tapered nanopores with 100 nm interpore distance

NASA Astrophysics Data System (ADS)

Li, Juan; Li, Congshan; Gao, Xuefeng

2011-10-01

We in-detail investigated the profile evolution processes of highly ordered alumina under the cyclic treatment of mild anodizing of aluminum foils in oxalic acid followed by etching in phosphoric acid. With the cyclic times increasing, the profiles of nanopores were gradually evolved into the parabola-like, trumpet-like and conical shape. Although the inserted etching itself nearly had no impact on the growth rate of the nanopores due to the rapid recovering of thinned barrier layer at the initial stage of next anodizing, overmuch etching could bring apparent side effects such as wall-breaking, thinning and taper-removing from the top down. The anodizing and etching kinetics and their synergetic effects in modulating different aspect ratios and open sizes of conical pores were studied systematically. These findings are helpful to tailor high-quality anodic alumina taper-pores with tunable profiles.

Retrieval method of aerosol extinction coefficient profile by an integral lidar system and case study

NASA Astrophysics Data System (ADS)

Shan, Huihui; Zhang, Hui; Liu, Junjian; Wang, Shenhao; Ma, Xiaomin; Zhang, Lianqing; Liu, Dong; Xie, Chenbo; Tao, Zongming

2018-02-01

Aerosol extinction coefficient profile is an essential parameter for atmospheric radiation model. But it is difficult to get the full aerosol extinction profile from the ground to the tropopause especially in near ground precisely using backscattering lidar. A combined measurement of side-scattering, backscattering and Raman-scattering lidar is proposed to retrieve the aerosol extinction coefficient profile from the surface to the tropopause which covered a dynamic range of 5 orders. The side-scattering technique solves the dead zone and the overlap problem caused by the traditional lidar in the near range. Using the Raman-scattering the aerosol lidar ratio (extinction to backscatter ratio) can be obtained. The cases studies in this paper show the proposed method is reasonable and feasible.

Experiments in dilution jet mixing

NASA Technical Reports Server (NTRS)

Holdeman, J. D.; Srinivasan, R.; Berenfeld, A.

1983-01-01

Experimental results are given on the mixing of a single row of jets with an isothermal mainstream in a straight duct, to include flow and geometric variations typical of combustion chambers in gas turbine engines. The principal conclusions reached from these experiments were: at constant momentum ratio, variations in density ratio have only a second-order effect on the profiles; a first-order approximation to the mixing of jets with a variable temperature mainstream can be obtained by superimposing the jets-in-an isothermal-crossflow and mainstream profiles; flow area convergence, especially injection-wall convergence, significantly improves the mixing; for opposed rows of jets, with the orifice centerlines in-line, the optimum ratio of orifice spacing to duct height is one half of the optimum value for single side injection at the same momentum ratio; and for opposed rows of jets, with the orifice centerlines staggered, the optimum ratio of orifice spacing to duct height is twice the optimum value for single side injection at the same momentum ratio.

Experimental study on the effects of fixed boundaries in channelized free surface dry granular flows

NASA Astrophysics Data System (ADS)

Sarno, Luca; Carleo, Luigi; Nicolina Papa, Maria

2017-04-01

The dynamics of granular mixtures, involved in geophysical flows like avalanches and debris flows, is far from being completely understood. Several features of their motion, such as rheological stratification, non-local and boundary effects, still represent open problems. Experimental investigations at laboratory scale are an important tool that can provide insights about the dynamics of gravity driven granular flows. The measuring techniques should be non-invasive in order to measure undisturbed flows. In this work we present an experimental campaign devoted to the measurement of the velocity profiles of free surface steady granular flows in an open channel. To achieve this goal the flows were recorded by two cameras and velocity profiles were obtained by image analysis. The employed granular medium consists of acetal-polymeric beads with a mean diameter of 3mm and an estimated internal friction angle of 27°. All the experiments have been performed in a 2m-long plexiglas flume with a rectangular cross-section and a slope angle of 30°. The upper part of the channel was used as a reservoir where the material was loaded before each run and then let flow down through an adjustable gate. Several mass flow rates were investigated. Three different basal surfaces were employed so as to observe slip and non-slip boundary conditions: a smooth Bakelite surface, a roughened surface, obtained by gluing a layer of grains on the bed surface and a sandpaper surface with characteristic length of the roughness equal to 425 µm. The flume is equipped with two high-speed cameras, one placed aside the channel and the other one perpendicular to the channel bed, as to get both side-wall and free surface velocity profiles. The particle image velocimetry open-source code, PIVlab, is employed for estimating the flow velocities. All the free surface velocity profiles show an approximately parabolic shape with a maximum at the cross-section midpoint and a minimum at the side-walls, due to the wall friction. Different kinds of side-wall velocity profiles are observed. As regards the smooth basal surface, a slip velocity at the bed is observed. The profiles are Bagnold-type near the free surface and become linear as the depth increases. On the glued-grain basal surface the flow velocity at the bed is null and all the velocity profiles show a rheological stratification with a lower exponential tail and an upper linear profile. Grain rolling is observed at the sandpaper bed, instead. With the increase of flow depths, the velocity profiles gradually shift from the ones observed on the smooth bed to the ones observed on the glued-grain bed. In order to further understand the constitutive behaviour of granular mixtures, it is useful to perform simultaneous measurements of flow velocity and volume fraction. In this perspective, a new series of experiments is actually undergoing for the measurement of the volume fraction.

Innate Immune Response and Off-Target Mis-splicing Are Common Morpholino-Induced Side Effects in Xenopus.

PubMed

Gentsch, George E; Spruce, Thomas; Monteiro, Rita S; Owens, Nick D L; Martin, Stephen R; Smith, James C

2018-03-12

Antisense morpholino oligomers (MOs) have been indispensable tools for developmental biologists to transiently knock down (KD) genes rather than to knock them out (KO). Here we report on the implications of genetic KO versus MO-mediated KD of the mesoderm-specifying Brachyury paralogs in the frog Xenopus tropicalis. While both KO and KD embryos fail to activate the same core gene regulatory network, resulting in virtually identical morphological defects, embryos injected with control or target MOs also show a systemic GC content-dependent immune response and many off-target splicing defects. Optimization of MO dosage and increasing incubation temperatures can mitigate, but not eliminate, these MO side effects, which are consistent with the high affinity measured between MO and off-target sequence in vitro. We conclude that while MOs can be useful to profile loss-of-function phenotypes at a molecular level, careful attention must be paid to their immunogenic and off-target side effects. Copyright © 2018 The Francis Crick Institute. Published by Elsevier Inc. All rights reserved.

Basic pharmacology of NMDA receptors.

PubMed

Gonda, Xenia

2012-01-01

NMDA receptors are ionotropic receptors mediating glutamatergic neurotransmission and play a role in several basic functions in the central nervous system, from regulating neurodevelopment and synaptic plasticity, learning and memory formation, cognitive processes, rhythm generation necessary for locomotor activity and breathing, and excitotoxicity. Due to their complex involvement in the above processes, NMDA receptors have been established to play a role in the etiopathology of several neuropsychiatric disorders such as ischaemia and traumatic brain injury, neurodegenerative disorders, pain syndromes, addiction, affective disorders and such neurodevelopmental disorders as autism or schizophrenia. NMDA receptors contain multiple types of subunits with distinct functional and pharmacological properties making the picture more complex. These receptors also offer multiple binding sites to be targeted with pharmacons, however, early broad-spectrum NMDA receptor antagonists had limited clinical use due to their intolerable adverse effect profile. The discovery of several types of subunit selective NMDA receptor antagonists may offer valuable therapeutic possibilities for several disorders, with improved clinical efficacy and decreased side effects. However, in spite of our increasing knowledge concerning the involvement of NMDA receptors in pathological processes, molecules with a selective action, tolerable side effect profile and good clinical efficacy are still only in clinical development in the majority of cases. Nevertheless, NMDA receptors offer a novel opportunity in the treatment of various neuropsychiatric conditions.

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

PubMed

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

2012-01-01

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

Tardive Dyskinesia and Intellectual Disability: An Examination of Demographics and Topography in Adults with Dual Diagnosis and Atypical Antipsychotic Use

ERIC Educational Resources Information Center

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

2010-01-01

Atypical antipsychotic medications are commonly used in large-scale residential care facilities for adults with developmental disabilities. While the benefits of this class of psychotropics are noted, debate exists whether the side effect profile of these medications outweigh their therapeutic benefit, especially in those who use them long-term.…

OnabotulinumtoxinA in the treatment of neurogenic bladder

PubMed Central

Gulamhusein, Aziz; Mangera, Altaf

2012-01-01

This review examines the evidence for use of onabotulinumtoxinA in the treatment of neurogenic lower urinary tract dysfunction. Since its first use in 1988 to treat detrusor sphincter dyssynergia, use of botulinum toxin has increased in this group of patients. We discuss the mechanism of action, patient selection, dosing, efficacy, and side effect profile of this now licensed treatment option. PMID:22977301

8. AFRD WAREHOUSE, EAST SIDE DETAIL SHOWS CONNECTION OF LEANTO ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. AFRD WAREHOUSE, EAST SIDE DETAIL SHOWS CONNECTION OF LEAN-TO TO WALL. FACING WEST. NOTE THE PROFILE OF THE METAL AWNING ON SOUTH SIDE. ELECTRICAL CONDUIT AND OTHER SERVICES PENETRATE WALL. POLE SECURED WITH TRIANGULAR BRACES AT CORNER IS COMMUNICATION POLE. - Minidoka Relocation Center Warehouse, 111 South Fir Street, Shoshone, Lincoln County, ID

Review of Post-Marketing Safety Data on Tapentadol, a Centrally Acting Analgesic.

PubMed

Stollenwerk, Ariane; Sohns, Melanie; Heisig, Fabian; Elling, Christian; von Zabern, Detlef

2018-01-01

Tapentadol is a centrally acting analgesic that has been available for the management of acute and chronic pain in routine clinical practice since 2009. This is the first integrated descriptive analysis of post-marketing safety data following the use of tapentadol in a broad range of pain conditions relating to the topics overall safety, dose administration above approved dosages, administration during pregnancy, serotonin syndrome, respiratory depression, and convulsion. The data analyzed pertain to spontaneous reports from healthcare and non-healthcare professionals and were put in the context of safety information known from interventional and non-interventional trials. The first years of routine clinical practice experience with tapentadol have confirmed the tolerability profile that emerged from the clinical trials. Moreover, the reporting of expected side effects such as respiratory depression and convulsion was low and no major risks were identified. The evaluation of available post-marketing data did not confirm the theoretical risk of serotonin syndrome nor did it reveal unexpected side effects with administration of higher than recommended doses. More than 8 years after its first introduction, the favorable overall safety profile of tapentadol in the treatment of various pain conditions is maintained in the general population. Grünenthal GmbH.

Keep-Left Behavior Induced by Asymmetrically Profiled Walls

NASA Astrophysics Data System (ADS)

Oliveira, C. L. N.; Vieira, A. P.; Helbing, D.; Andrade, J. S.; Herrmann, H. J.

2016-01-01

We show, computationally and analytically, that asymmetrically shaped walls can organize the flow of pedestrians driven in opposite directions through a corridor. Precisely, a two-lane ordered state emerges in which people always walk on the left-hand side (or right-hand side), controlled by the system's parameters. This effect depends on features of the channel geometry, such as the asymmetry of the profile and the channel width, as well as on the density and the drift velocity of pedestrians, and the intensity of noise. We investigate in detail the influence of these parameters on the flow and discover a crossover between ordered and disordered states. Our results show that an ordered state only appears within a limited range of drift velocities. Moreover, increasing noise may suppress such flow organization, but the flow is always sustained. This is in contrast with the "freezing by heating" phenomenon according to which pedestrians tend to clog in smooth channels for strong noise [Phys. Rev. Lett. 84, 1240 (2000)]. Therefore, the ratchetlike effect proposed here acts on the system not only to induce a "keep-left" behavior but also to prevent the freezing by heating clogging phenomenon. Besides pedestrian flow, this new phenomenon has other potential applications in microfluidics systems.

Thermostructural Behavior of a Hypersonic Aircraft Sandwich Panel Subjected to Heating on One Side

NASA Technical Reports Server (NTRS)

Ko, William L.

1997-01-01

Thermostructural analysis was performed on a heated titanium honeycomb-core sandwich panel. The sandwich panel was supported at its four edges with spar-like substructures that acted as heat sinks, which are generally not considered in the classical analysis. One side of the panel was heated to high temperature to simulate aerodynamic heating during hypersonic flight. Two types of surface heating were considered: (1) flat-temperature profile, which ignores the effect of edge heat sinks, and (2) dome-shaped-temperature profile, which approximates the actual surface temperature distribution associated with the existence of edge heat sinks. The finite-element method was used to calculate the deformation field and thermal stress distributions in the face sheets and core of the sandwich panel. The detailed thermal stress distributions in the sandwich panel are presented, and critical stress regions are identified. The study shows how the magnitudes of those critical stresses and their locations change with different heating and edge conditions. This technical report presents comprehensive, three-dimensional graphical displays of thermal stress distributions in every part of a titanium honeycomb-core sandwich panel subjected to hypersonic heating on one side. The plots offer quick visualization of the structural response of the panel and are very useful for hot structures designers to identify the critical stress regions.

What does reflection from cloud sides tell us about vertical distribution of cloud droplets?

NASA Technical Reports Server (NTRS)

Marshak, A.; Kaufman, Yoram; Martins, V.; Zubko, Victor

2006-01-01

In order to accurately measure the interaction of clouds with aerosols, we have to resolve the vertical distribution of cloud droplet sizes and determine the temperature of glaciation for clean and polluted clouds. Knowledge of the droplet vertical profile is also essential for understanding precipitation. So far, all existing satellites either measure cloud microphysics only at cloud top (e.g., MODIS) or give a vertical profile of precipitation sized droplets (e.g., Cloudsat). What if one measures cloud microphysical properties in the vertical by retrieving them from the solar and infrared radiation reflected or emitted from cloud sides? This was the idea behind CLAIM-3D (A 3D - cloud aerosol interaction mission) recently proposed by NASA GSFC. This presentation will focus on the interpretation of the radiation reflected from cloud sides. In contrast to plane-parallel approximation, a conventional approach to all current operational retrievals, 3D radiative transfer will be used for interpreting the observed reflectances. As a proof of concept, we will show a few examples of radiation reflected from cloud fields generated by a simple stochastic cloud model with prescribed microphysics. Instead of fixed values of the retrieved effective radii, the probability density functions of droplet size distributions will serve as possible retrievals.

Quantitative Profiling of Feruloylated Arabinoxylan Side-Chains from Graminaceous Cell Walls

PubMed Central

Schendel, Rachel R.; Meyer, Marleen R.; Bunzel, Mirko

2016-01-01

Graminaceous arabinoxylans are distinguished by decoration with feruloylated monosaccharidic and oligosaccharidic side-chains. Although it is hypothesized that structural complexity and abundance of these feruloylated arabinoxylan side-chains may contribute, among other factors, to resistance of plant cell walls to enzymatic degradation, quantitative profiling approaches for these structural units in plant cell wall materials have not been described yet. Here we report the development and application of a rapid and robust method enabling the quantitative comparison of feruloylated side-chain profiles in cell wall materials following mildly acidic hydrolysis, C18-solid phase extraction (SPE), reduction under aprotic conditions, and liquid chromatography with diode-array detection/mass spectrometry (LC-DAD/MS) separation and detection. The method was applied to the insoluble fiber/cell wall materials isolated from 12 whole grains: wild rice (Zizania aquatica L.), long-grain brown rice (Oryza sativa L.), rye (Secale cereale L.), kamut (Triticum turanicum Jakubz.), wheat (Triticum aestivum L.), spelt (Triticum spelta L.), intermediate wheatgrass (Thinopyrum intermedium), maize (Zea mays L.), popcorn (Zea mays L. var. everta), oat (Avena sativa L.) (dehulled), barley (Hordeum vulgare L.) (dehulled), and proso millet (Panicum miliaceum L.). Between 51 and 96% of the total esterified monomeric ferulates were represented in the quantified compounds captured in the feruloylated side-chain profiles, which confirms the significance of these structures to the global arabinoxylan structure in terms of quantity. The method provided new structural insights into cereal grain arabinoxylans, in particular, that the structural moiety α-l-galactopyranosyl-(1→2)-β-d-xylopyranosyl-(1→2)-5-O-trans-feruloyl-l-arabinofuranose (FAXG), which had previously only been described in maize, is ubiquitous to cereal grains. PMID:26834763

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.

[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.

Safety of vedolizumab in the treatment of Crohn's disease and ulcerative colitis.

PubMed

Hagan, Matilda; Cross, Raymond K

2015-01-01

Vedolizumab is the latest FDA-approved anti-integrin therapy for treatment of moderate-to-severe inflammatory bowel disease (IBD). The safety and efficacy of vedolizumab have been studied in short-term clinical trials. This paper reviews the safety profile of vedolizumab compared with other biologics. It also highlights the mechanism of action of the medication. We discuss the current position of vedolizumab in our current algorithm for IBD management and comment on future prospects of the drug. Vedolizumab appears to be a safe and effective option in the treatment of moderate-to-severe IBD in the short term. Long-term observational studies and post-marketing safety data are needed to ascertain the long-term efficacy and side effect profile.

Understanding of impurity poloidal distribution in the edge pedestal by modelling

NASA Astrophysics Data System (ADS)

Rozhansky, V.; Kaveeva, E.; Molchanov, P.; Veselova, I.; Voskoboynikov, S.; Coster, D.; Fable, E.; Puetterich, T.; Viezzer, E.; Kukushkin, A. S.; Kirk, A.; the ASDEX Upgrade Team

2015-07-01

Simulation of an H-mode ASDEX Upgrade shot with boron impurity was done with the B2SOLPS5.2 transport code. Simulation results were compared with the unique experimental data available for the chosen shot: radial density, electron and ion temperature profiles in the equatorial midplanes, radial electric field profile, radial profiles of the parallel velocity of impurities at the low-field side (LFS) and high-field side (HFS), radial density profiles of impurity ions at LHS and HFS. Simulation results reproduce all available experimental data simultaneously. In particular strong poloidal HFS-LFS asymmetry of B5+ ions was predicted in accordance with the experiment. The simulated HFS B5+ density inside the edge transport barrier is twice larger than that at LFS. This is consistent with the experimental observations where even larger impurity density asymmetry was observed. A similar effect was predicted in the simulation done for the MAST H-mode. Here the HFS density of He2+ is predicted to be 4 times larger than that at LHS. Such a large predicted asymmetry is connected with a larger ratio of HFS and LFS magnetic fields which is typical for spherical tokamaks. The HFS/LFS asymmetry was not measured in the experiment, however modelling qualitatively reproduces the observed change of sign of He+parallel velocity to the counter-current direction at LFS. The understanding of the asymmetry is based on neoclassical effects in plasma with strong gradients. It is demonstrated that simulation results obtained with account of sources of ionization, realistic geometry and turbulent transport are consistent with the simplified analytical approach. Difference from the standard neoclassical theory is emphasized.

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.

Neuroversion: using electroconvulsive therapy as a bridge to deep brain stimulation implantation.

PubMed

Williams, Nolan R; Sahlem, Greg; Pannu, Jaspreet; Takacs, Istvan; Short, Baron; Revuelta, Gonzalo; George, Mark S

2017-02-01

Parkinson's disease (PD) is a movement disorder with significant neuropsychiatric comorbidities. Electroconvulsive therapy (ECT) is effective in treating these neuropsychiatric symptoms; however, clinicians are reluctant to use ECT in patients with deep brain stimulation (DBS) implantations for fear of damaging the device, as well as potential cognitive side effects. Right unilateral ultra-brief pulse (RUL UBP) ECT has a more favorable cognitive side-effect profile yet has never been reported in PD patients with DBS implants. We present a case series of three patients with a history of PD that all presented with psychiatric decompensation immediately prior to planned DBS surgery. All three patients had DBS electrode(s) in place at the time and an acute course of ECT was utilized in a novel method to "bridge" these individuals to neurosurgery. The patients all experienced symptom resolution (psychosis and/or depression and/or anxiety) without apparent cognitive side effects. This case series not only illustrates that right unilateral ultra-brief pulse can be utilized in patients with DBS electrodes but also illustrates that this intervention can be utilized as a neuromodulatory "bridge", where nonoperative surgical candidates with unstable psychiatric symptoms can be converted to operative candidates in a manner similar to electrical cardioversion.

Curcuma longa L. as a therapeutic agent in intestinal motility disorders. 2: Safety profile in mouse.

PubMed

Micucci, Matteo; Aldini, Rita; Cevenini, Monica; Colliva, Carolina; Spinozzi, Silvia; Roda, Giulia; Montagnani, Marco; Camborata, Cecilia; Camarda, Luca; Chiarini, Alberto; Mazzella, Giuseppe; Budriesi, Roberta

2013-01-01

Curcuma extract exerts a myorelaxant effect on the mouse intestine. In view of a possible use of curcuma extract in motor functional disorders of the gastrointestinal tract, a safety profile study has been carried out in the mouse. Thirty mice were used to study the in vitro effect of curcuma on gallbladder, bladder, aorta and trachea smooth muscular layers and hearth inotropic and chronotropic activity. The myorelaxant effect on the intestine was also thoroughly investigated. Moreover, curcuma extract (200 mg/Kg/day) was orally administered to twenty mice over 28 days and serum liver and lipids parameters were evaluated. Serum, bile and liver bile acids qualitative and quantitative composition was were also studied. In the intestine, curcuma extract appeared as a not competitive inhibitor through cholinergic, histaminergic and serotoninergic receptors and showed spasmolytic effect on K(+) induced contraction at the level of L type calcium channels. No side effect was observed on bladder, aorta, trachea and heart when we used a dose that is effective on the intestine. An increase in gallbladder tone and contraction was observed. Serum liver and lipids parameters were normal, while a slight increase in serum and liver bile acids concentration and a decrease in bile were observed. Although these data are consistent with the safety of curcuma extract as far as its effect on the smooth muscular layers of different organs and on the heart, the mild cholestatic effect observed in absence of alteration of liver function tests must be further evaluated and the effective dose with minimal side effects considered.

Curcuma longa L. as a Therapeutic Agent in Intestinal Motility Disorders. 2: Safety Profile in Mouse

PubMed Central

Micucci, Matteo; Aldini, Rita; Cevenini, Monica; Colliva, Carolina; Spinozzi, Silvia; Roda, Giulia; Montagnani, Marco; Camborata, Cecilia; Camarda, Luca; Chiarini, Alberto; Mazzella, Giuseppe; Budriesi, Roberta

2013-01-01

Background Curcuma extract exerts a myorelaxant effect on the mouse intestine. In view of a possible use of curcuma extract in motor functional disorders of the gastrointestinal tract, a safety profile study has been carried out in the mouse. Methods Thirty mice were used to study the in vitro effect of curcuma on gallbladder, bladder, aorta and trachea smooth muscular layers and hearth inotropic and chronotropic activity. The myorelaxant effect on the intestine was also thoroughly investigated. Moreover, curcuma extract (200 mg/Kg/day) was orally administered to twenty mice over 28 days and serum liver and lipids parameters were evaluated. Serum, bile and liver bile acids qualitative and quantitative composition was were also studied. Results In the intestine, curcuma extract appeared as a not competitive inhibitor through cholinergic, histaminergic and serotoninergic receptors and showed spasmolytic effect on K+ induced contraction at the level of L type calcium channels. No side effect was observed on bladder, aorta, trachea and heart when we used a dose that is effective on the intestine. An increase in gallbladder tone and contraction was observed. Serum liver and lipids parameters were normal, while a slight increase in serum and liver bile acids concentration and a decrease in bile were observed. Conclusions Although these data are consistent with the safety of curcuma extract as far as its effect on the smooth muscular layers of different organs and on the heart, the mild cholestatic effect observed in absence of alteration of liver function tests must be further evaluated and the effective dose with minimal side effects considered. PMID:24260512

Systematic Review of the Side Effects Associated With Anti-HER2-Targeted Therapies Used in the Treatment of Breast Cancer, on Behalf of the EORTC Quality of Life Group.

PubMed

Sodergren, Samantha C; Copson, Ellen; White, Alice; Efficace, Fabio; Sprangers, Mirjam; Fitzsimmons, Deborah; Bottomley, Andrew; Johnson, Colin D

2016-06-01

Targeted therapies (TTs), notably trastuzumab, have improved outcomes for breast cancer characterised by overexpression of human epidermal growth factor receptors including HER2. Compared with chemotherapy treatments, TTs are more specific in their targets and are delivered over longer periods of time, thus presenting different side-effect profiles. The objective of this paper is to systematically review and describe the side effects associated with TTs used in the adjuvant and metastatic settings for HER2+ breast cancer. The MEDLINE, EMBASE, CINAHL, Web of Science and Cochrane Library databases were searched from January 2007 to March 2015 to identify clinical trials and prospective studies reporting toxicities associated with TTs (mainly trastuzumab and lapatinib) used without other therapies in the treatment of HER2-positive breast cancer. Two independent reviewers selected papers based on their titles and abstracts. All papers selected by either reviewer were included. A third reviewer extracted and tabulated the relevant data using a data extraction form. We identified 5478 papers, of which 299 were reviewed and 18 trials identified involving 6980 patients. A total of 66 side effects were identified, including 46 "patient-based" symptoms and 20 "medically defined" outcomes. Side effects were more common for patients treated with therapies other than trastuzumab or with dual-HER2 regimens and for patients with metastatic disease. Diarrhoea and skin rash were the most prevalent symptoms, experienced by 29 % and 22 % of patients overall, respectively. There were 119 (2 %) cardiac events reported, and these were not exclusive to trastuzumab-treated patients. The majority of side effects (n = 52) were experienced by 1 % or less of patients and were predominantly of grade 1/2 toxicity. This systematic review provides a detailed analysis of side effects of HER2+ therapies in a large number of patients included in trials, enabling an accurate estimate of prevalence and a complete understanding of the patients' experience. This will help clinicians and patients in treatment planning.

Novel device-based acne treatments: comparison of a 1450-nm diode laser and microneedling radiofrequency on mild-to-moderate acne vulgaris and seborrhoea in Korean patients through a 20-week prospective, randomized, split-face study.

PubMed

Kwon, H H; Park, H Y; Choi, S C; Bae, Y; Jung, J Y; Park, G-H

2018-04-01

While device-based acne treatments are widely applied for patients not tolerating conventional medications, related controlled studies have been still limited. Recently, non-ablative 1450-nm diode laser (DL) and fractional microneedling radiofrequency (FMR) have been effectively used for acne, in addition to well-recognized dermal remodelling effects. To compare the clinical course of acne treatment between DL and FMR. Twenty-five Korean patients with mild-to-moderate facial acne completed treatments with DL and FMR through a 20-week, randomized split-face study. One randomly assigned half side of each patient's face received DL and the other side by FMR. Treatments were scheduled to receive three consecutive sessions at 4-week intervals. Objective assessments including revised Leeds grades, lesion counts, sebum output measurements, and patients' subjective satisfaction were investigated. Both DL and FMR demonstrated steady improvement of acne and seborrhoea during treatment sessions. While results between two devices were similar during treatment sessions, FMR was superior to DL in the 12-week follow-up. Patients' subjective assessments for seborrhoea improvement were similar between two devices, while those for acne, skin texture, and acne scars were more satisfactory for FMR. For safety profile, no significant difference was observed between two regimens, while mild postinflammatory hyperpigmentation was observed only in DL side. Both DL and FMR demonstrated efficacies for acne and seborrhoea, with reasonable safety profile. FMR was more effective than DL for the long-term maintenance, and subjective assessments for texture and scar improvements. Therefore, a few sessions of these devices would be a viable option for acne treatments. © 2017 European Academy of Dermatology and Venereology.

Reproducibility of Automated Voice Range Profiles, a Systematic Literature Review.

PubMed

Printz, Trine; Rosenberg, Tine; Godballe, Christian; Dyrvig, Anne-Kirstine; Grøntved, Ågot Møller

2018-05-01

Reliable voice range profiles are of great importance when measuring effects and side effects from surgery affecting voice capacity. Automated recording systems are increasingly used, but the reproducibility of results is uncertain. Our objective was to identify and review the existing literature on test-retest accuracy of the automated voice range profile assessment. Systematic review. PubMed, Scopus, Cochrane Library, ComDisDome, Embase, and CINAHL (EBSCO). We conducted a systematic literature search of six databases from 1983 to 2016. The following keywords were used: phonetogram, voice range profile, and acoustic voice analysis. Inclusion criteria were automated recording procedure, healthy voices, and no intervention between test and retest. Test-retest values concerning fundamental frequency and voice intensity were reviewed. Of 483 abstracts, 231 full-text articles were read, resulting in six articles included in the final results. The studies found high reliability, but data are few and heterogeneous. The reviewed articles generally reported high reliability of the voice range profile, and thus clinical usefulness, but uncertainty remains because of low sample sizes and different procedures for selecting, collecting, and analyzing data. More data are needed, and clinical conclusions must be drawn with caution. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Targeting interleukin-6 for noninfectious uveitis

PubMed Central

Lin, Phoebe

2015-01-01

Interleukin-6 (IL-6) is a pleiotropic cytokine implicated in the pathogenesis of many immune-mediated disorders including several types of non-infectious uveitis. These uveitic conditions include Vogt-Koyanagi-Harada syndrome, uveitis associated with Behçet disease, and sarcoidosis. This review summarizes the role of IL-6 in immunity, highlighting its effect on Th17, Th1, and plasmablast differentiation. It reviews the downstream mediators activated in the process of IL-6 binding to its receptor complex. This review also summarizes the biologics targeting either IL-6 or the IL-6 receptor, including tocilizumab, sarilumab, sirukumab, olokizumab, clazakizumab, and siltuximab. The target, dosage, potential side effects, and potential uses of these biologics are summarized in this article based on the existing literature. In summary, anti-IL-6 therapy for non-infectious uveitis shows promise in terms of efficacy and side effect profile. PMID:26392750

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.

Gym and tonic: a profile of 100 male steroid users.

PubMed Central

Evans, N A

1997-01-01

OBJECTIVE: To identify unsupervised anabolic steroid regimens used by athletes. METHODS: 100 athletes attending four gymnasia were surveyed using an anonymous self administered questionnaire. RESULTS: Anabolic steroid doses ranged from 250 to 3200 mg per week and users combined different drugs to achieve these doses. Injectable and oral preparations were used in cycles lasting four to 12 weeks. Eighty six per cent of users admitted to the regular use of drugs other than steroids for various reasons, including additional anabolic effects, the minimisation of steroid related side effects, and withdrawal symptoms. Acne, striae, and gynaecomastia were the most commonly reported subjective side effects. CONCLUSIONS: Multiple steroids are combined in megadoses and self administered in a cyclical fashion. Polypharmacy is practised by over 80% of steroid users. Skeletal muscle hypertrophy along with acne, striae, and gynaecomastia are frequent physical signs associated with steroid use. Images Figure 2 PMID:9132214

Enhanced clinical outcome with manual massage following cryolipolysis treatment: a 4-month study of safety and efficacy.

PubMed

Boey, Gerald E; Wasilenchuk, Jennifer L

2014-01-01

Cryolipolysis procedures have been shown to safely and effectively reduce the thickness of fat in a treated region. This study was conducted to determine whether the addition of post-treatment manual massage would improve efficacy while maintaining the safety profile of the original cryolipolysis treatment protocol. The study population consisted of an efficacy group (n = 10) and a safety group (n = 7). Study subjects were treated on each side of the lower abdomen with a Cooling Intensity Factor of 42 (-72.9 mW/cm(2) ) for 60 minutes. One side of the abdomen was massaged post-treatment and the other side served as the control. Immediately post-treatment, the massage side was treated for 1 minute using a vigorous kneading motion followed by 1 minute of circular massage using the pads of the fingers. For the efficacy group, photos and ultrasound measurements were taken at baseline, 2 months, and 4 months post-treatment. For the safety group, histological analysis was completed at 0, 3, 8, 14, 30, 60, and 120 days post-treatment to examine the effects of massage on subcutaneous tissue over time. Post-treatment manual massage resulted in a consistent and discernible increase in efficacy over the non-massaged side. At 2 months post-treatment, mean fat layer reduction was 68% greater in the massage side than in the non-massage side as measured by ultrasound. By 4 months, mean fat layer reduction was 44% greater in the massage side. Histological results showed no evidence of necrosis or fibrosis resulting from the massage. Post-treatment manual massage is a safe and effective technique to enhance the clinical outcome from a cryolipolysis procedure. © 2013 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Focus on risperidone.

PubMed

Green, B

2000-01-01

Risperidone is a relatively new antipsychotic available world-wide since the early 1990s. It has been characterised as atypical, but shares some of the extrapyramidal side-effect profile of the earlier antipsychotics, when used at doses higher than those recommended by the manufacturer (4-6 mg/day). There is now adequate comparison with conventional antipsychotics to suggest its superiority, but a depot formulation is needed to complete the picture.

Seventh Symposium on Subtypes of Musccarinic Receptors.

DTIC Science & Technology

1997-01-01

promises fewer and less severe side effects because of its favourable receptor profile and pharmacokinetic properties (2, 3). This compound has been...6). Following median laparotomy electromagnetic flow probes were positioned on one or both renal arteries. A cannula was introduced into a femoral...equipment for thermodilution and electromagnetic flow measurement (IFD, Miuhlheim, Germany) was used. Respiratory rate was evaluated from the C0 2

Three-Dimensional Laminar Separation.

DTIC Science & Technology

1983-12-01

and are due to the power supply. ........................... 51 Fig. 26 The actual experimental points shown together with the smoothed profile on...Flow visualizations of the regions of interest are presented and compared with the calculated results. Streamwlse and cross flow velocity profiles ...the leeward side at the fourth .station . ............................................... 52 Fig. 27 The u-component velocity profile . Horizontal and

Familiar shapes attract attention in figure-ground displays.

PubMed

Nelson, Rolf A; Palmer, Stephen E

2007-04-01

We report five experiments that explore the effect of figure-ground factors on attention. We hypothesized that figural cues, such as familiar shape, would draw attention to the figural side in an attentional cuing task using bipartite figure-ground displays. The first two experiments used faces in profile as the familiar shape and found a perceptual advantage for targets presented on the meaningful side of the central contour in detection speed (Experiment 1) and discrimination accuracy (Experiment 2). The third experiment demonstrated the figural advantage in response time (RT) with nine other familiar shapes (including a sea horse, a guitar, a fir tree, etc.), but only when targets appeared in close proximity to the contour. A fourth experiment obtained a figural advantage in a discrimination task with the larger set of familiar shapes. The final experiment ruled out eye movements as a possible confounding factor by replicating the RT advantage for targets on the figural side of face displays when all trials containing eye movements were eliminated. The results are discussed in terms of ecological influences on attention, and are cast within the framework of Yantis and Jonides's hypothesis that attention is exogenously drawn to the onset of new perceptual objects. We argue that the figural side constitutes an "object" whereas the ground side does not, and that figural cues such as shape familiarity are effective in determining which areas represent objects.

A Gene Expression Profile of BRCAness that Predicts for Responsiveness to Platinum and PARP Inhibitors

DTIC Science & Technology

2011-08-01

tumors as BRCA-like (BL) or non-BRCA-like ( NBL ) corresponding to tumors predicted to have a BRCAness phenotype (BL tumors) or not ( NBL tumors). In...of six specimens with ATM knock down had the BL signature and six of six control specimens had the NBL signature (Fisher’s exact two sided p=0.002...control specimens had the NBL signature (Fisher’s exact two sided p=0.067). Figure 2. BRCAness profile distinguishes between BRCA1 knock down

Efficacy and tolerability of lumiracoxib, a highly selective cyclo-oxygenase-2 (COX2) inhibitor, in the management of pain and osteoarthritis

PubMed Central

Geusens, Piet; Lems, Willem

2008-01-01

Lumiracoxib is a COX2 inhibitor that is highly selective, is more effective than placebo on pain in osteoarthritis (OA), with similar analgesic and anti-inflammatory effects as non-selective NSAIDs and the selective COX2 inhibitor celecoxib, has a lower incidence of upper gastrointestinal (GI) side effects in patients not taking aspirin, and a similar incidence of cardiovascular (CV) side effects compared to naproxen or ibuprofen. In the context of earlier guidelines and taking into account the GI and CV safety results of the TARGET study, lumiracoxib had secured European Medicines Agency (EMEA) approval with as indication symptomatic treatment of OA as well as short-term management of acute pain associated with primary dysmenorrhea and following orthopedic or dental surgery. In the complex clinical context of efficiency and safety of selective and non-selective COX inhibitors, its prescription and use should be based on the risk and safety profile of the patient. In addition, there is further need for long-term GI and CV safety studies and general post-marketing safety on its use in daily practice. Meanwhile, at the time of submission of this manuscript, the EMEA has withdrawn lumiracoxib throughout Europe because of the risk of serious side effects affecting the liver. PMID:18728796

The efficacy of evolocumab in the management of hyperlipidemia: a systematic review

PubMed Central

AlHajri, Lamia; AlHadhrami, Asma; AlMheiri, Shama; AlMutawa, Yalwah; AlHashimi, Zainab

2017-01-01

Background: Hyperlipidemia or dyslipidemia has been a concern for a long time, with various guidelines emphasizing the importance of managing the lipid profile to prevent cardiac incidences. Although statins have been found to be highly effective, resistance and intolerability to side effects will continue to be a stumbling block for certain patients. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors tackle lipid profile via a novel mechanism and therefore provide an additional effective option for managing lipid profile. The overarching aim of this systematic review was to evaluate the efficacy of evolocumab among various populations with hypercholesterolemia. Methods: A comprehensive search was conducted in ProQuest Health & Medical Complete, Google Scholar, ScienceDirect, and PubMed to identify potential records; then titles, abstracts, and full texts were screened using the inclusion criteria to filter out irrelevant studies. Data extraction and quality assessment were undertaken using standardized tools and the results were narratively synthesized and presented in tables. Results: Eight studies were included in this systematic review after screening 1191 records. All studies demonstrated a statistically significant reduction in low-density lipoprotein cholesterol (LDL-C) values in the groups that received evolocumab compared with the comparator groups (p < 0.05). The decline in LDL-C levels from baseline in the majority of studies ranged from 40% to 80%, whether used alone or in combination with other agents. Also, high-density lipoprotein cholesterol, lipoprotein (a) and apolipoprotein B were improved with the use of evolocumab. Conclusions: This study helped to collate evidence from studies that tested the effectiveness of evolocumab in the management of hyperlipidemia. Evolocumab seems to be highly effective in reducing LDL-C and other lipid parameters. Hence, it provides an excellent alternative for patients with refractory disease or patients who develop intolerable side effects, therefore helping to overcome the stumbling block to achieving optimal lipid management. PMID:28488460

[Acetaminophen - A modern classic under suspicion].

PubMed

Buschmann, H; Heintze, K; Morgenstern, E

2011-12-15

Paracetamol is one of the most popular and widely used drugs for the treatment of pain and fever and provides safe and effective relief of these symptoms since decades. The mechanism of action is very complex and involves the inhibition of the peroxidase portion of the cyclooxygenase enzyme together with the modulation of the serotoninergic and cannabinoid system. Paracetamol is a safe drug, if used in accordance with the regulations and has demonstrated a superior side effect profile to many widely used NSAIDs.

Reducing secondary losses by blowing cold air in a turbine

NASA Technical Reports Server (NTRS)

Koschel, W.

1977-01-01

Local blowing on the profile suction side of the turbine guide wheel blades can be effective in preventing the propagation of secondary flows that is, the transport of casing and hub boundary layers by pressure gradients. Some preliminary results on how the blowing should be accomplished in order to influence the secondary flows in the desired manner are given. The effectiveness of blowing is demonstrated. Blowing is also seen to be more effective than using boundary layer slots as far as diminishing losses in the rim zones is concerned.

Paradoxical effect of dopamine medication on cognition in Parkinson's disease: relationship to side of motor onset.

PubMed

Hanna-Pladdy, Brenda; Pahwa, Rajesh; Lyons, Kelly E

2015-04-01

Parkinson's disease (PD) is characterized by asymmetric motor symptom onset attributed to greater degeneration of dopamine neurons contralateral to the affected side. However, whether motor asymmetries predict cognitive profiles in PD, and to what extent dopamine influences cognition remains controversial. This study evaluated cognitive variability in PD by measuring differential response to dopamine replacement therapy (DRT) based on hemispheric asymmetries. The influence of DRT on cognition was evaluated in mild PD patients (n = 36) with left or right motor onset symptoms. All subjects were evaluated on neuropsychological measures on and off DRT and compared to controls (n = 42). PD patients were impaired in executive, memory and motor domains irrespective of side of motor onset, although patients with left hemisphere deficit displayed greater cognitive impairment. Patients with right hemisphere deficit responded to DRT with significant improvement in sensorimotor deficits, and with corresponding improvement in attention and verbal memory functions. Conversely, patients with greater left hemisphere dopamine deficiency did not improve in attentional functions and declined in verbal memory recall following DRT. These findings support the presence of extensive mild cognitive deficits in early PD not fully explained by dopamine depletion alone. The paradoxical effects of levodopa on verbal memory were predicted by extent of fine motor impairment and sensorimotor response to levodopa, which reflects extent of dopamine depletion. The findings are discussed with respect to factors influencing variable cognitive profiles in early PD, including hemispheric asymmetries and differential response to levodopa based on dopamine levels predicting amelioration or overdosing.

The Effect of Different Repeated-High-Intensity-Effort Bouts on Subsequent Running, Skill Performance, and Neuromuscular Function.

PubMed

Johnston, Rich D; Gabbett, Tim J; Jenkins, David G; Speranza, Michael J

2016-04-01

To assess the impact of different repeated-high-intensity-effort (RHIE) bouts on player activity profiles, skill involvements, and neuromuscular fatigue during small-sided games. 22 semiprofessional rugby league players (age 24.0 ± 1.8 y, body mass 95.6 ± 7.4 kg). During 4 testing sessions, they performed RHIE bouts that each differed in the combination of contact and running efforts, followed by a 5-min off-side small-sided game before performing a second bout of RHIE activity and another 5-min small-sided game. Global positioning system microtechnology and video recordings provided information on activity profiles and skill involvements. A countermovement jump and a plyometric push-up assessed changes in lower- and upper-body neuromuscular function after each session. After running-dominant RHIE bouts, players maintained running intensities during both games. In the contact-dominant RHIE bouts, reductions in moderate-speed activity were observed from game 1 to game 2 (ES = -0.71 to -1.06). There was also moderately lower disposal efficiency across both games after contact-dominant RHIE activity compared with running-dominant activity (ES = 0.62-1.02). Greater reductions in lower-body fatigue occurred as RHIE bouts became more running dominant (ES = -0.01 to -1.36), whereas upper-body fatigue increased as RHIE bouts became more contact dominant (ES = -0.07 to -1.55). Physical contact causes reductions in running intensity and the quality of skill involvements during game-based activities. In addition, the neuromuscular fatigue experienced by players is specific to the activities performed.

[Proton pump inhibitor - side effects and complications of long-term proton pump inhibitor administration].

PubMed

Ueberschaer, Hendrik; Allescher, Hans-Dieter

2017-01-01

Proton Pump Inhibitors are among the most common drugs taken. The indication is for treatment of heartburn, reflux disease, prophylaxis and treatment of peptic ulcers, in combination with NSAIDs and steroids as well as H. pylori-eradication. PPI's are widely used, even with non-specific symptoms. This certainly has to do with good tolerability and a previously considered low side effect profile. At the moment, there is growing evidence that the long-term intake of PPI's may not be as safe as assumed. In addition to interactions with some drugs, including platelet aggregation inhibitors, recent studies have shown an increased risk of myocardial infarction, interstitial nephritis, chronic renal injury, infections, vitamin deficiencies and electrolyte shifts as well developing dementia. © Georg Thieme Verlag KG Stuttgart · New York.

[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.

Bilateral pneumothorax, surgical emphysema and pneumomediastinum in a young male patient following MDMA intake.

PubMed

Obiechina, Nonyelum Evangeline; Jayakumar, Ahrane; Khan, Yusra; Bass, James

2018-04-07

MDMA (3,4-methylenedioxymethamphetamine) or 'Ecstasy' is an illicit drug frequently used by young people at parties and 'raves'. It is readily available in spite of the fact that it is illegal. 1 It is perceived by a lot of young people as being 'harmless', but there have been a few high-profile deaths associated with its use. 2 Known side effects of MDMA include hyperthermia, rhabdomyolysis, coagulopathy and cardiac arrhythmias. 3 Rarer side effects include surgical emphysema and pneumomediastinum, which have been better described with cocaine abuse. 4-6 We present a case of bilateral pneumothorax, surgical emphysema and pneumomediastinum in a young man after taking ecstasy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Flow distribution in parallel microfluidic networks and its effect on concentration gradient

PubMed Central

Guermonprez, Cyprien; Michelin, Sébastien; Baroud, Charles N.

2015-01-01

The architecture of microfluidic networks can significantly impact the flow distribution within its different branches and thereby influence tracer transport within the network. In this paper, we study the flow rate distribution within a network of parallel microfluidic channels with a single input and single output, using a combination of theoretical modeling and microfluidic experiments. Within the ladder network, the flow rate distribution follows a U-shaped profile, with the highest flow rate occurring in the initial and final branches. The contrast with the central branches is controlled by a single dimensionless parameter, namely, the ratio of hydrodynamic resistance between the distribution channel and the side branches. This contrast in flow rates decreases when the resistance of the side branches increases relative to the resistance of the distribution channel. When the inlet flow is composed of two parallel streams, one of which transporting a diffusing species, a concentration variation is produced within the side branches of the network. The shape of this concentration gradient is fully determined by two dimensionless parameters: the ratio of resistances, which determines the flow rate distribution, and the Péclet number, which characterizes the relative speed of diffusion and advection. Depending on the values of these two control parameters, different distribution profiles can be obtained ranging from a flat profile to a step distribution of solute, with well-distributed gradients between these two limits. Our experimental results are in agreement with our numerical model predictions, based on a simplified 2D advection-diffusion problem. Finally, two possible applications of this work are presented: the first one combines the present design with self-digitization principle to encapsulate the controlled concentration in nanoliter chambers, while the second one extends the present design to create a continuous concentration gradient within an open flow chamber. PMID:26487905

Endocrine therapy for breast cancer prevention in high-risk women: clinical and economic considerations.

PubMed

Groom, Amy G; Younis, Tallal

2016-01-01

The global burden of breast cancer highlights the need for primary prevention strategies that demonstrate both favorable clinical benefit/risk profile and good value for money. Endocrine therapy with selective estrogen-receptor modulators (SERMs) or aromatase inhibitors (AIs) has been associated with a favorable clinical benefit/risk profile in the prevention of breast cancer in women at high risk of developing the disease. The available endocrine therapy strategies differ in terms of their relative reductions of breast cancer risk, potential side effects, and upfront drug acquisition costs, among others. This review highlights the clinical trials of SERMs and AIs for the primary prevention of breast cancer, and the cost-effectiveness /cost-utility studies that have examined their "value for money" in various health care jurisdictions.

Measurement of the main and critical parameters for optimal laser treatment of heart disease

NASA Astrophysics Data System (ADS)

Kabeya, FB; Abrahamse, H.; Karsten, AE

2017-10-01

Laser light is frequently used in the diagnosis and treatment of patients. As in traditional treatments such as medication, bypass surgery, and minimally invasive ways, laser treatment can also fail and present serious side effects. The true reason for laser treatment failure or the side effects thereof, remains unknown. From the literature review conducted, and experimental results generated we conclude that an optimal laser treatment for coronary artery disease (named heart disease) can be obtained if certain critical parameters are correctly measured and understood. These parameters include the laser power, the laser beam profile, the fluence rate, the treatment time, as well as the absorption and scattering coefficients of the target treatment tissue. Therefore, this paper proposes different, accurate methods for the measurement of these critical parameters to determine the optimal laser treatment of heart disease with a minimal risk of side effects. The results from the measurement of absorption and scattering properties can be used in a computer simulation package to predict the fluence rate. The computing technique is a program based on the random number (Monte Carlo) process and probability statistics to track the propagation of photons through a biological tissue.

Effects of feeding high protein or conventional canola meal on dry cured and conventionally cured bacon.

PubMed

Little, K L; Bohrer, B M; Stein, H H; Boler, D D

2015-05-01

Objectives were to compare belly, bacon processing, bacon slice, and sensory characteristics from pigs fed high protein canola meal (CM-HP) or conventional canola meal (CM-CV). Soybean meal was replaced with 0 (control), 33, 66, or 100% of both types of canola meal. Left side bellies from 70 carcasses were randomly assigned to conventional or dry cure treatment and matching right side bellies were assigned the opposite treatment. Secondary objectives were to test the existence of bilateral symmetry on fresh belly characteristics and fatty acid profiles of right and left side bellies originating from the same carcass. Bellies from pigs fed CM-HP were slightly lighter and thinner than bellies from pigs fed CM-CV, yet bacon processing, bacon slice, and sensory characteristics were unaffected by dietary treatment and did not differ from the control. Furthermore, testing the existence of bilateral symmetry on fresh belly characteristics revealed that bellies originating from the right side of the carcasses were slightly (P≤0.05) wider, thicker, heavier and firmer than bellies from the left side of the carcass. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Bulging Behavior of Thick-Walled 6063 Aluminum Alloy Tubes Under Double-Sided Pressures

NASA Astrophysics Data System (ADS)

Cui, Xiao-Lei; Wang, Xiao-Song; Yuan, Shi-Jian

2015-05-01

To make further exploration on the deformation behavior of tube under double-sided pressures, the thick-walled 6063 aluminum alloy tubes with an outer diameter of 65 mm and an average thickness of 7.86 mm have been used to be bulged under the combined action of internal and external pressures. In the experiment, two ends of the thick-walled tubes were fixed using the tooth and groove match. Three levels of external pressure (0 MPa, 40 MPa, and 80 MPa), in conjunction with the internal pressure, were applied on the tube outside and inside simultaneously. The effect of external pressure on the bulging behavior of the thick-walled tubes, such as the limiting expansion ratio, the bulging zone profile, and the thickness distribution, has been investigated. It is shown that the limiting expansion ratio, the bulging zone profile, and the thickness distribution in the homogeneous bulging area are all insensitive to the external pressure. However, the external pressure can make the thick-walled tube achieve a thinner wall at the fracture area. It reveals that the external pressure can only improve the fracture limit of the thick-walled 6063 tubes, but it has very little effect on their homogeneous bulging behavior. It might be because the external pressure can only increase the magnitude of the hydrostatic pressure for the tube but has no effect on the Lode parameter.

Light and laser treatment modalities for disseminated superficial actinic porokeratosis: a systematic review.

PubMed

Aird, Gregory A; Sitenga, Jenna L; Nguyen, Austin Huy; Vaudreuil, Adam; Huerter, Christopher J

2017-05-01

Treatment of disseminated superficial actinic porokeratosis (DSAP) is poorly standardized. The present review seeks to comprehensively discuss the potential for laser and light modalities in the treatment of DSAP. A systematic review of light and laser treatment modalities was conducted to include 26 cases of patients with DSAP. Systematic review resulted in 14 articles to be included. Photodynamic therapy (PDT) overall was the least successful treatment modality, with clinical improvement seen in a minority of patients (MAL-PDT: N = 9 patients, 33.3% showed improvement; ALA-PDT: N = 3 patients, 0% improvement; hypericin-PDT: N = 2 patients, 0% improvement) after numerous post-procedural side effects of hyperpigmentation, inflammation, erythema, and discomfort. Overall, in the available reports, PDT demonstrates poor outcomes with greater incidence of side effects. The response rates of DSAP lesions treated with lasers were as follows: (Q-switched ruby lasers: N = 2, 100%; CO 2 laser: N = 1, 100%; PDT and CO 2 combination therapy: N = 2, 0-50%; erbium and neodymium YAG lasers: N = 2, 100%; fractional 1927-nm thulium fiber lasers: N = 2, 100%; Grenz rays: N = 1, 100%; and fractional photothermolysis: N = 2, 100%). The side effects of laser therapy were minimal and included mild erythema, slight hyperpigmentation, and moderate edema. Laser therapy is a promising treatment option for DSAP with an excellent side effect profile. However, higher power studies are required to determine optimal guidelines for laser treatment of DSAP.

Pharmacodynamic and pharmacokinetic effects of MK-0343, a GABA(A) alpha2,3 subtype selective agonist, compared to lorazepam and placebo in healthy male volunteers.

PubMed

de Haas, S L; de Visser, S J; van der Post, J P; Schoemaker, R C; van Dyck, K; Murphy, M G; de Smet, M; Vessey, L K; Ramakrishnan, R; Xue, L; Cohen, A F; van Gerven, J M A

2008-01-01

The use of non-selective gamma-aminobutyric acid (GABA) enhancers, such as benzodiazepines in the treatment of anxiety disorders is still widespread but hampered by unfavourable side effects. some of these may be associated with binding properties to certain subtypes of the GABA(A) receptor that are unnecessary for therapeutic effects. MK-0343 was designed to be a less sedating anxiolytic, based on reduced efficacy at the alpha1 subtype and significant efficacy at alpha2 and alpha3 subtypes of the GABA(A) receptor. This paper is a double-blind, four-way cross-over (n = 12) study to investigate the effects of MK-0343 (0.25 and 0.75 mg) in comparison to placebo and an anxiolytic dose (2 mg) of the non-selective agonist lorazepam. Effects were measured by eye movements, body sway, Visual Analogue scales (VAS) and memory tests. Lorazepam impaired saccadic peak velocity (SPV), VAs alertness scores, postural stability and memory and increased saccadic latency and inaccuracy. MK-0343 0.75 mg was equipotent with lorazepam as indicated by SPV (-42.4 deg/s), saccadic latency (0.02 s) and VAS alertness scores (1.50 ln mm), while effects on memory and postural stability were smaller. MK-0343 0.25 mg only affected postural stability to a similar extent as MK-0343 0.75 mg. The effect profile of MK-0343 0.75 mg is different from the full agonist lorazepam, which could reflect the selective actions of this compound. Although less effect on VAS alertness was expected, diminished effects on memory and postural stability were present. Clinical studies in anxiety patients should show whether this dose of MK-0343 is therapeutically effective with a different side-effect profile.

Large-eddy simulation of a spatially-evolving turbulent mixing layer

NASA Astrophysics Data System (ADS)

Capuano, Francesco; Catalano, Pietro; Mastellone, Andrea

2015-11-01

Large-eddy simulations of a spatially-evolving turbulent mixing layer have been performed. The flow conditions correspond to those of a documented experimental campaign (Delville, Appl. Sci. Res. 1994). The flow evolves downstream of a splitter plate separating two fully turbulent boundary layers, with Reθ = 2900 on the high-speed side and Reθ = 1200 on the low-speed side. The computational domain starts at the trailing edge of the splitter plate, where experimental mean velocity profiles are prescribed; white-noise perturbations are superimposed to mimic turbulent fluctuations. The fully compressible Navier-Stokes equations are solved by means of a finite-volume method implemented into the in-house code SPARK-LES. The results are mainly checked in terms of the streamwise evolution of the vorticity thickness and averaged velocity profiles. The combined effects of inflow perturbations, numerical accuracy and subgrid-scale model are discussed. It is found that excessive levels of dissipation may damp inlet fluctuations and delay the virtual origin of the turbulent mixing layer. On the other hand, non-dissipative, high-resolution computations provide results that are in much better agreement with experimental data.

Bilastine: a new H1 -antihistamine with an optimal profile for updosing in urticaria.

PubMed

Church, M K; Labeaga, L

2017-09-01

This review set out to examine published papers detailing the efficacy of bilastine in skin models and urticaria to assess whether it meets the optimal profile for updosing in urticaria, that is, strong clinical efficacy and freedom from unwanted side effects, particularly sedation. Bilastine is a highly effective H 1 -antihistamine even when used at the basic dose of 20 mg daily. Its facilitated uptake after oral dosage gives it a rapid onset and long duration of action. In both wheal and flare studies and in urticaria updosing fourfold showed increased effectiveness. With respect to somnolence, bilastine is a substrate for P-glycoprotein, a membrane pump which prevents it crossing the blood-brain barrier. Consequently, bilastine is a practically 'non-sedating' H 1 -antihistamine. In conclusion, the excellent profile of bilastine in both efficacy and safety make it the ideal H 1 -antihistamine for updosing the daily dose fourfold in difficult-to-treat urticaria as recommended by the EAACI/GA 2 LEN/EDF/WAO guideline for the management of urticaria. © 2017 European Academy of Dermatology and Venereology.

Antinociceptive potency of a fluorinated cyclopeptide Dmt-c[D-Lys-Phe-p-CF3-Phe-Asp]NH2.

PubMed

Piekielna-Ciesielska, Justyna; Mollica, Adriano; Pieretti, Stefano; Fichna, Jakub; Szymaszkiewicz, Agata; Zielińska, Marta; Kordek, Radzisław; Janecka, Anna

2018-12-01

Opioid peptides and opiate drugs such as morphine, mediate their analgesic effects, but also undesired side effects, mostly through activation of the mu opioid receptor. However, delta- and kappa-opioid receptors can also contribute to the analgesic effects of opioids. Recent findings showed that simultaneous activation of multiple opioid receptors may result in additional analgesia with fewer side effects. Here, we evaluated the pharmacological profile of our formerly developed mixed mu/kappa-opioid receptor ligands, Dmt-c[D-Lys-Phe-Phe-Asp]NH 2 (C-36) and Dmt-c[D-Lys-Phe-p-CF 3 -Phe-Asp]NH 2 (F-81). The ability of these peptides to cross the blood-brain barrier was tested in the parallel artificial membrane permeability (PAMPA) assay. On the basis of the hot-plate test in mice after central and peripheral administration, analog F-81 was selected for the anti-nociceptive and anti-inflammatory activity assessment after peripheral administration.

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

PubMed Central

Morgan, Michael M; Christie, MacDonald J

2011-01-01

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

Role of natural herbs in the treatment of hypertension

PubMed Central

Tabassum, Nahida; Ahmad, Feroz

2011-01-01

Hypertension (HTN) is the medical term for high blood pressure. It is dangerous because it makes the heart work too hard and contributes to atherosclerosis (hardening of arteries), besides increasing the risk of heart disease and stroke. HTN can also lead to other conditions such as congestive heart failure, kidney disease, and blindness. Conventional antihypertensives are usually associated with many side effects. About 75 to 80% of the world population use herbal medicines, mainly in developing countries, for primary health care because of their better acceptability with human body and lesser side effects. In the last three decades, a lot of concerted efforts have been channeled into researching the local plants with hypotensive and antihypertensive therapeutic values. The hypotensive and antihypertensive effects of some of these medicinal plants have been validated and others disproved. However, ayurvedic knowledge needs to be coupled with modern medicine and more scientific research needs to be done to verify the effectiveness, and elucidate the safety profile of such herbal remedies for their antihypertensive potential. PMID:22096316

An Economic Evalution of Demand-side Energy Storage Systems by using a Multi-agent based Electricity Market

NASA Astrophysics Data System (ADS)

Furusawa, Ken; Sugihara, Hideharu; Tsuji, Kiichiro

Opened wholesale electric power market in April 2005, deregulation of electric power industry in Japan has faced a new competitive environment. In the new environment, Independent Power Producer (: IPP), Power Producer and Supplier (: PPS), Load Service Entity (: LSE) and electric utility can trade electric energy through both bilateral contracts and single-price auction at the electricity market. In general, the market clearing price (: MCP) is largely changed by amount of total load demand in the market. The influence may cause price spike, and consequently the volatility of MCP will make LSEs and their customers to face a risk of revenue and cost. DSM is attracted as a means of load leveling, and has effect on decreasing MCP at peak load period. Introducing Energy Storage systems (: ES) is one of DSM in order to change demand profile at customer-side. In case that customers decrease their own demand at jumped MCP, a bidding strategy of generating companies may be changed their strategy. As a result, MCP is changed through such complex mechanism. In this paper the authors evaluate MCP by multi-agent. It is considered that customer-side ES has an effect on MCP fluctuation. Through numerical examples, this paper evaluates the influence on MCP by controlling customer-side ES corresponding to variation of MCP.

Enhancing Electromagnetic Side-Channel Analysis in an Operational Environment

NASA Astrophysics Data System (ADS)

Montminy, David P.

Side-channel attacks exploit the unintentional emissions from cryptographic devices to determine the secret encryption key. This research identifies methods to make attacks demonstrated in an academic environment more operationally relevant. Algebraic cryptanalysis is used to reconcile redundant information extracted from side-channel attacks on the AES key schedule. A novel thresholding technique is used to select key byte guesses for a satisfiability solver resulting in a 97.5% success rate despite failing for 100% of attacks using standard methods. Two techniques are developed to compensate for differences in emissions from training and test devices dramatically improving the effectiveness of cross device template attacks. Mean and variance normalization improves same part number attack success rates from 65.1% to 100%, and increases the number of locations an attack can be performed by 226%. When normalization is combined with a novel technique to identify and filter signals in collected traces not related to the encryption operation, the number of traces required to perform a successful attack is reduced by 85.8% on average. Finally, software-defined radios are shown to be an effective low-cost method for collecting side-channel emissions in real-time, eliminating the need to modify or profile the target encryption device to gain precise timing information.

A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly

PubMed Central

Wongrakpanich, Supakanya; Wongrakpanich, Amaraporn; Melhado, Katie; Rangaswami, Janani

2018-01-01

NSAIDs, non-steroidal anti-inflammatory drugs, are one of the most commonly prescribed pain medications. It is a highly effective drug class for pain and inflammation; however, NSAIDs are known for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID induced nephrotoxicity. As our society ages, it is crucial to have comprehensive knowledge of this class of medication in the elderly population. Therefore, we reviewed the pharmacodynamics and pharmacokinetics, current guidelines for NSAIDs use, adverse effect profile, and drug interaction of NSAIDs and commonly used medications in the elderly. PMID:29392089

Impact of Substance Use Disorder on Presentation and Short-Term Course of Schizophrenia

PubMed Central

Chakraborty, Rudraprosad; Chatterjee, Arunima; Chaudhury, Suprakash

2014-01-01

The aim of the present study was to compare a cohort of schizophrenia patients with substance use disorder (SUD) with a similar cohort of schizophrenia patients without SUD with regard to sociodemographic variables, clinical variables, psychopathology, anxiety symptoms, depressive symptoms, treatment outcome, and side effect profile of drugs. A total of 143 consecutive inpatients with ICD-10 DCR diagnosis of schizophrenia were included after obtaining informed consent. Patients were evaluated by a semistructured data sheet and Maudsley Addiction Profile. They were then rated by Positive and Negative Symptoms Scale, Calgary Depression Scale, Hamilton Anxiety Rating Scale, and Brief Psychiatric Rating Scale at presentation, three weeks, and six weeks. At three weeks and six weeks, they were also evaluated by UKU Side Effect Rating Scale. Substance abuse was detected in 63.6% schizophrenia patients. Nicotine was the commonest substance followed by cannabis and alcohol. Substance users had longer untreated illness and more depressive symptoms at presentation and six-week follow-up. Dual diagnosis patients had difficulty in abstraction at three and six weeks but not at presentation. Schizophrenia patients with SUD had more depressive symptoms. SUD appeared to mask abstraction difficulties at presentation. Schizophrenia patients with SUD should be carefully assessed for presence of depression. PMID:24839596

mGluR antagonists and GABA agonists as novel pharmacological agents for the treatment of autism spectrum disorders.

PubMed

Oberman, Lindsay M

2012-12-01

The CDC currently estimates the prevalence of autism spectrum disorders (ASD) at 1 in 88 children. Though the exact etiology of ASD is unknown, recent studies implicate synaptic maturation and plasticity in the pathogenesis of ASD leading to an imbalance of excitation and inhibition, and specifically a disproportionately high level of excitation. Pharmacological agents that modulate excitation and inhibition are currently in clinical trials for treatment of ASD and show promising preliminary results. This paper reviews the literature implicating the role of glutamate and GABA pathways in the pathophysiology of ASD. It also provides a review of the current results from both animal models and human clinical trials of drugs aimed at normalizing the imbalance of excitation and inhibition through the use of metabotropic glutamate receptor (mGluR) antagonists and GABA agonists. Both mGluR antagonists and GABA agonists have promising preliminary data from animal model and small-scale Phase II human trials. They show significant efficacy in subpopulations and appear to have favorable side-effect profiles. Though preliminary data are extremely promising, results from ongoing larger, double-blind, placebo-controlled studies will give a more complete understanding of the efficacy and side-effect profile related to these drugs.

Reconciling Consumer and Utility Objectives in the Residential Solar PV Market

NASA Astrophysics Data System (ADS)

Arnold, Michael R.

Today's energy market is facing large-scale changes that will affect all market players. Near the top of that list is the rapid deployment of residential solar photovoltaic (PV) systems. Yet that growing trend will be influenced multiple competing interests between various stakeholders, namely the utility, consumers and technology provides. This study provides a series of analyses---utility-side, consumer-side, and combined analyses---to understand and evaluate the effect of increases in residential solar PV market penetration. Three urban regions have been selected as study locations---Chicago, Phoenix, Seattle---with simulated load data and solar insolation data at each locality. Various time-of-use pricing schedules are investigated, and the effect of net metering is evaluated to determine the optimal capacity of solar PV and battery storage in a typical residential home. The net residential load profile is scaled to assess system-wide technical and economic figures of merit for the utility with an emphasis on intraday load profiles, ramp rates and electricity sales with increasing solar PV penetration. The combined analysis evaluates the least-cost solar PV system for the consumer and models the associated system-wide effects on the electric grid. Utility revenue was found to drop by 1.2% for every percent PV penetration increase, net metering on a monthly or annual basis improved the cost-effectiveness of solar PV but not battery storage, the removal of net metering policy and usage of an improved the cost-effectiveness of battery storage and increases in solar PV penetration reduced the system load factor. As expected, Phoenix had the most favorable economic scenario for residential solar PV, primarily due to high solar insolation. The study location---solar insolation and load profile---was also found to affect the time of year at which the largest net negative system load was realized.

Quantum transport in graphene Hall bars: Effects of side gates

NASA Astrophysics Data System (ADS)

Petrović, M. D.; Peeters, F. M.

2017-05-01

Quantum electron transport in side-gated graphene Hall bars is investigated in the presence of quantizing external magnetic fields. The asymmetric potential of four side-gates distorts the otherwise flat bands of the relativistic Landau levels, and creates new propagating states in the Landau spectrum (i.e. snake states). The existence of these new states leads to an interesting modification of the bend and Hall resistances, with new quantizing plateaus appearing in close proximity of the Landau levels. The electron guiding in this system can be understood by studying the current density profiles of the incoming and outgoing modes. From the fact that guided electrons fully transmit without any backscattering (similarly to edge states), we are able to analytically predict the values of the quantized resistances, and they match the resistance data we obtain with our numerical (tight-binding) method. These insights in the electron guiding will be useful in predicting the resistances for other side-gate configurations, and possibly in other system geometries, as long as there is no backscattering of the guided states.

Significant treatment effect of add-on ketamine anesthesia in electroconvulsive therapy in depressive patients: A meta-analysis.

PubMed

Li, Dian-Jeng; Wang, Fu-Chiang; Chu, Che-Sheng; Chen, Tien-Yu; Tang, Chia-Hung; Yang, Wei-Cheng; Chow, Philip Chik-Keung; Wu, Ching-Kuan; Tseng, Ping-Tao; Lin, Pao-Yen

2017-01-01

Add-on ketamine anesthesia in electroconvulsive therapy (ECT) has been studied in depressive patients in several clinical trials with inconclusive findings. Two most recent meta-analyses reported insignificant findings with regards to the treatment effect of add-on ketamine anesthesia in ECT in depressive patients. The aim of this study is to update the current evidence and investigate the role of add-on ketamine anesthesia in ECT in depressive patients via a systematic review and meta-analysis. We performed a thorough literature search of the PubMed and ScienceDirect databases, and extracted all relevant clinical variables to compare the antidepressive outcomes between add-on ketamine anesthesia and other anesthetics in ECT. Total 16 articles with 346 patients receiving add-on ketamine anesthesia in ECT and 329 controls were recruited. We found that the antidepressive treatment effect of add-on ketamine anesthesia in ECT in depressive patients was significantly higher than that of other anesthetics (p<0.001). This significance persisted in both short-term (1-2 weeks) and moderate-term (3-4 weeks) treatment courses (all p<0.05). However, the side effect profiles and recovery time profiles were significantly worse in add-on ketamine anesthesia group than in control group. Our meta-analysis highlights the significantly higher antidepressive treatment effect of add-on ketamine in depressive patients receiving ECT compared to other anesthetics. However, clinicians need to take undesirable side effects into consideration when using add-on ketamine anesthesia in ECT in depressive patients. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Clinically Employed Opioid Analgesics Produce Antinociception via μ-δ Opioid Receptor Heteromers in Rhesus Monkeys

PubMed Central

2012-01-01

Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans. PMID:23019498

Clinically employed opioid analgesics produce antinociception via μ-δ opioid receptor heteromers in Rhesus monkeys.

PubMed

Yekkirala, Ajay S; Banks, Matthew L; Lunzer, Mary M; Negus, Stevens S; Rice, Kenner C; Portoghese, Philip S

2012-09-19

Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans.

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

PubMed

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

2014-12-01

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

Innovative design method of automobile profile based on Fourier descriptor

NASA Astrophysics Data System (ADS)

Gao, Shuyong; Fu, Chaoxing; Xia, Fan; Shen, Wei

2017-10-01

Aiming at the innovation of the contours of automobile side, this paper presents an innovative design method of vehicle side profile based on Fourier descriptor. The design flow of this design method is: pre-processing, coordinate extraction, standardization, discrete Fourier transform, simplified Fourier descriptor, exchange descriptor innovation, inverse Fourier transform to get the outline of innovative design. Innovative concepts of the innovative methods of gene exchange among species and the innovative methods of gene exchange among different species are presented, and the contours of the innovative design are obtained separately. A three-dimensional model of a car is obtained by referring to the profile curve which is obtained by exchanging xenogeneic genes. The feasibility of the method proposed in this paper is verified by various aspects.

New comparisons of ISR and RO data with the model IRI-Plas

NASA Astrophysics Data System (ADS)

Maltseva, Olga; Mozhaeva, Natalya; Zhbankov, Gennadii

2012-07-01

Space Weather events lead to strong changes in peak parameters of the ionosphere. These parameters, foF2 and hmF2, define the N(h)-profile, which is known to include bottom side and topside parts. Numerous studies have shown that adaptation of the IRI model to the experimental values of foF2 and hmF2 gave a good agreement between experimental and model N(h)-profiles of the bottom side ionosphere. This is not about the topside N(h)-profile. To improve the situation measurements of the total electron content TEC are involved. This work is devoted to the use of peak parameters with the TEC during Space Weather events for the evaluation of propagation conditions in both the bottom side and the topside ionosphere, based on the model IRI-Plas. To assess how well the model N(h)-profile matches the experimental one, the model IRI-Plas is tested according to the Incoherent Scatter Radars and the Radio Occultation measurements in various parts of the globe and at different levels of solar activity. The experimental N(h)-profiles are compared with profiles for the original model, the model adapted to the foF2 and hmF2, and for a model with full adaptation (including the TEC). The best fit is obtained in the European region, so the SW variations of peak parameters and N(h)-profiles are studied on the example of the European area. The IRI-Plas model allows to estimate the relative contributions of each region (bottom side BOT, topside TOP and plasmaspheric PL parts) in the value of the TEC. As the analysis of two W- and Wp-indexes (Gulyaeva, 2008; Gulyaeva and Stanislawska, 2008) is shown, TEC-storms occur in 2 times more likely than foF2-storms. This testifies that the variations of parts BOT, TOP and PL in the TEC are different. It determines different variations of N(h)-profiles. Results are given for several types of SW-events, in particular, for the strong positive and negative disturbances, when the variations of TEC and foF2 are of the same sign and the corresponding perturbation covers all regions of the ionosphere. Particular attention is paid to variations of peak parameters and N(h)-profiles during weak and moderate disturbances and bursts of TEC in long period of low activity, when the TEC and foF2 variations and variations of different parts of TEC are in the opposite phase.

Low dose mTHPC photodynamic therapy for cholangiocarcinoma

NASA Astrophysics Data System (ADS)

Stepp, Herbert; Kniebühler, Gesa; Pongratz, Thomas; Betz, Christian S.; Göke, Burkhard; Sroka, Ronald; Schirra, Jörg

2013-06-01

Objective: Demonstration of whether a low dose of mTHPC (temoporfin , Foscan) is sufficient to induce an efficient clinical response in palliative PDT of non-resectable cholangiocarcinoma (CC), while showing a low side effect profile as compared to the standard Photofrin PDT. Materials and Methods: 13 patients (14 treatment sessions) with non-resectable CC were treated with stenting and PDT (3 mg Foscan per treatment, 0.032-0.063 mg/kg body weight, 652 nm, 50 J/cm). Fluorescence measurements were performed with a single bare fiber for 5/13 patients prior to PDT at the tumor site to determine the fluorescence contrast. For another 7/13 patients, long-term fluorescence-kinetics were measured on the oral mucosa to determine the time of maximal relative fluorescence intensity. Results: Foscan fluorescence could clearly be identified spectroscopically as early as 20 hours after administration. It was not significantly different between lesion and normal tissue within the bile duct. Fluorescence kinetics assessed at the oral mucosa were highest at 72-96 hours after administration. The DLI was therefore extended from 20 hours to approx. 70 hours for the last 5 patients treated. The treatment effect was promising with a median survival of 11 months for the higher grade tumors (Bismuth types III and IV). Local side effects occurred in one patient (pancreatitis), systemic side effects were much reduced compared to prior experience with Photofrin. Conclusion: Combined stenting and photodynamic therapy (PDT) performed with a low dose of Foscan results in comparable survival times relative to standard Photofrin PDT, while lowering the risk of side effects significantly.

Non-injection routes for allergen immunotherapy: focus on sublingual immunotherapy.

PubMed

Passalacqua, Giovanni; Guerra, Laura; Pasquali, Mercedes; Canonica, Giorgio Walter

2006-01-01

Allergen specific immunotherapy, together with drugs and allergen avoidance, is a cornerstone in the management of respiratory allergy. The non-injection or local routes were developed with the main goal of improving the safety and minimizing the risk of those side effects, which can accompany the injection route. The pure oral route and the bronchial route showed, in the clinical trials, only a marginal efficacy with not negligible side effects. Therefore, these routes are no longer recommended for clinical use. The nasal route proved effective and safe, but its efficacy is strictly limited to the nose. Moreover, the practical problems with administration have made the use of nasal immunotherapy progressively declining. The efficacy of the sublingual route is confirmed by numerous controlled trials, and a meta analysis (in allergic rhinitis). The safety profile, as derived from clinical trials and post marketing surveillance studies, is satisfactory, with mild gastrointestinal complaints being the more frequent side effect reported. Recent studies have also demonstrated that SLIT has a long-lasting effect and a preventive effect on the onset of new skin sensitizations, and interesting data on adherence and mechanisms of action have become recently available. Based on these experimental data, SLIT is now officially accepted as a viable alternative to the subcutaneous route in adults and children. Several points still need to be elucidated, including: mechanisms of action, optimal dosages, and indications in pediatric patients.

Synthesis and analgesic activity of some side-chain modified anpirtoline derivatives.

PubMed

Rádl, S; Hezky, P; Proska, J; Hejnová, L; Krejcí, I

2000-05-01

New derivatives of anpirtoline and deazaanpirtoline modified in the side chain have been synthesized. The series includes compounds 3 with side-chains containing piperidine or pyrrolidine rings, compounds 4 containing 8-azabicyclo[3.2.1]octane moiety, and compounds 5 having piperazine ring in their side-chains. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. Optimized structures (PM3-MOPAC, Alchemy 2000, Tripos Inc.) of the synthesized compounds 3-5 were compared with that of anpirtoline.

Measurement of velocities with an acoustic velocity meter, one side-looking and two upward-looking acoustic Doppler current profilers in the Chicago Sanitary and Ship Canal, Romeoville, Illinois

USGS Publications Warehouse

Oberg, Kevin A.; Duncker, James J.

1999-01-01

In 1998, a prototype 300 kHz, side-looking Acoustic Doppler Current Profiler (ADCP) was deployed in the Chicago Sanitary and Ship Canal (CSSC) at Romeoville, Illinois. Additionally, two upward-looking ADCP's were deployed in the same acoustic path as the side-looking ADCP and in the reach defined by the upstream and downstream acoustic velocity meter (AVM) paths. All three ADCP's were synchronized to the AVM clock at the gaging station so that data were sampled simultaneously. The three ADCP's were deployed for six weeks measuring flow velocities from 0.0 to 2.5 ft/s. Velocities measured by each ADCP were compared to AVM path velocities and to velocities measured by the other ADCP's.

ICT Solutions for Highly-Customized Water Demand Management Strategies

NASA Astrophysics Data System (ADS)

Giuliani, M.; Cominola, A.; Castelletti, A.; Fraternali, P.; Guardiola, J.; Barba, J.; Pulido-Velazquez, M.; Rizzoli, A. E.

2016-12-01

The recent deployment of smart metering networks is opening new opportunities for advancing the design of residential water demand management strategies (WDMS) relying on improved understanding of water consumers' behaviors. Recent applications showed that retrieving information on users' consumption behaviors, along with their explanatory and/or causal factors, is key to spot potential areas where targeting water saving efforts, and to design user-tailored WDMS. In this study, we explore the potential of ICT-based solutions in supporting the design and implementation of highly customized WDMS. On one side, the collection of consumption data at high spatial and temporal resolutions requires big data analytics and machine learning techniques to extract typical consumption features from the metered population of water users. On the other side, ICT solutions and gamifications can be used as effective means for facilitating both users' engagement and the collection of socio-psychographic users' information. This latter allows interpreting and improving the extracted profiles, ultimately supporting the customization of WDMS, such as awareness campaigns or personalized recommendations. Our approach is implemented in the SmartH2O platform and demonstrated in a pilot application in Valencia, Spain. Results show how the analysis of the smart metered consumption data, combined with the information retrieved from an ICT gamified web user portal, successfully identify the typical consumption profiles of the metered users and supports the design of alternative WDMS targeting the different users' profiles.

Metastatic pancreatic adenocarcinoma and renal cell carcinoma treated with gemcitabine and sunitinib malate. A case report.

PubMed

Bharthuar, Anubha; Pearce, Lori; Litwin, Alan; LeVea, Charles; Kuvshinoff, Boris; Iyer, Renuka

2009-09-04

Pancreatic adenocarcinoma and renal cell carcinoma are relatively frequent cancers that have been rarely reported as synchronous primary malignancies. When present simultaneously, they pose a therapeutic challenge given the many available targeted agents with reported efficacy in renal cell cancer and limited options for metastatic pancreatic cancer. We report the case of a 43-year-old Caucasian gentleman diagnosed simultaneously with metastatic pancreatic adenocarcinoma and localized renal cell carcinoma treated with combination chemotherapy, consisting of gemcitabine and sunitinib. Patient had a radiographic response and prolonged progression free survival of twenty six weeks; side effects were manageable and included grade 3 neutropenia and grade 2 hypertension. This encouraging response, safety profile and progression free survival response suggest that we should further examine this and other such regimens to improve clinical outcomes for maximum efficacy with minimal side-effects.

What is the role of sedating antidepressants, antipsychotics, and anticonvulsants in the management of insomnia?

PubMed

McCall, Catherine; McCall, W Vaughn

2012-10-01

Psychiatric medications such as antidepressants, antipsychotics, and anticonvulsants are commonly prescribed by physicians for the off-label use of improving sleep. Reasons for preferential prescription of these medications over FDA-approved insomnia drugs may include a desire to treat concurrent sleep problems and psychiatric illness with a single medication, and/or an attempt to avoid hypnotic drugs due to their publicized side effects. However, there have been few large studies demonstrating the efficacy and safety of most off-label medications prescribed to treat insomnia. In addition, many of these medications have significant known side effect profiles themselves. Here we review the pertinent research studies published in recent years on antidepressant, antipsychotic, and anticonvulsant medications frequently prescribed for sleep difficulties. Although there have been few large-scale studies for most of these medications, some may be appropriate in the treatment of sleep issues in specific well-defined populations.

Oral medications regarding their safety and efficacy in the management of patent ductus arteriosus

PubMed Central

Oncel, Mehmet Yekta; Erdeve, Omer

2016-01-01

Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants which is inversely related to birth weight and gestational age. Cyclooxygenase inhibitors such as indomethacin and ibuprofen which block the prostaglandin conversion from arachidonic acid are the most commonly used drugs for ductal closure. This review focuses on the safety and efficacy oral medications in the management of PDA in preterm infants. Ibuprofen seems to be the first choice due to its higher safety profile, as it is associated with fewer gastrointestinal and renal side effects when compared to indomethacin. PDA closure rates are better with oral than with intravenous ibuprofen probably due to the pharmacokinetic of the drug. However, these medications were reported to be associated with several adverse including transient renal failure, gastrointestinal bleeding and perforation, hyperbilirubinemia and platelet dysfunction. Paracetamol seems be an alternative to PDA therapy with lower adverse events and side effects. PMID:26862505

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

Effect of ambient temperature on the thermal profile of the human forearm, hand, and fingers

NASA Technical Reports Server (NTRS)

Montgomery, L. D.; Williams, B. A.

1976-01-01

Forearm, hand, and finger skin temperatures were measured on the right and left sides of seven resting men. The purpose was to determine the bilateral symmetry of these segmental temperature profiles at ambient temperatures from 10 to 45 C. Thermistors placed on the right and left forearms, hands, and index fingers were used to monitor the subjects until equilibration was reached at each ambient temperature. Additionally, thermal profiles of both hands were measured with copper-constantan thermocouples. During one experimental condition (23 C ambient), rectal, ear canal, and 24 skin temperatures were measured on each subject. Average body and average skin temperatures are given for each subject at the 23 C ambient condition. Detailed thermal profiles are also presented for the dorsal, ventral, and circumferential left forearm, hand, and finger skin temperatures at 23 C ambient. No significant differences were found between the mean skin temperatures of the right and left contralateral segments at any of the selected ambient temperatures.

Structure of micro-instabilities in tokamak plasmas: Stiff transport or plasma eruptions?

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

Dickinson, D., E-mail: dd502@york.ac.uk; EURATOM/CCFE Fusion Association, Culham Science Centre, Abingdon, Oxon OX14 3DB; Roach, C. M.

2014-01-15

Solutions to a model 2D eigenmode equation describing micro-instabilities in tokamak plasmas are presented that demonstrate a sensitivity of the mode structure and stability to plasma profiles. In narrow regions of parameter space, with special plasma profiles, a maximally unstable mode is found that balloons on the outboard side of the tokamak. This corresponds to the conventional picture of a ballooning mode. However, for most profiles, this mode cannot exist, and instead, a more stable mode is found that balloons closer to the top or bottom of the plasma. Good quantitative agreement with a 1D ballooning analysis is found, providedmore » the constraints associated with higher order profile effects, often neglected, are taken into account. A sudden transition from this general mode to the more unstable ballooning mode can occur for a critical flow shear, providing a candidate model for why some experiments observe small plasma eruptions (Edge Localised Modes, or ELMs) in place of large Type I ELMs.« less

[Infliximab therapy for Crohn's disease - a practical guideline: actualised consensus of the working group for chronic inflammatory bowel diseases of the Austrian Society for Gastroenterology and Hepatology].

PubMed

Reinisch, W; Dejaco, C; Feichtenschlager, T; Haas, T; Kaser, A; Miehsler, W; Novacek, G; Petritsch, W; Platzer, R; Tilg, H; Vogelsang, H; Knoflach, P

2011-04-01

Infliximab is a monoclonal antibody against tumor necrosis factor alpha (TNF-α), which is approved for the treatment of chronic inflammatory bowel disease (IBD) such as Crohn's disease (CD), fistulating Crohn's disease (FCD), ulcerative colitis (UC), and paediatric ulcerative colitis (PUC) from 6 years onwards. Besides its therapeutic efficacy, this antibody therapy is characterised by its side effects profile, which has been addressed in a seperate consensus statement by the Working Group for chronic inflammatory bowel diseases within the Austrian Society for Gastroenterology and Hepatology. Infliximab is an effective treatment option for the above-mentioned indications; however, use of this agent requires special knowledge to assess the benefit-risk profile for each patient individually. © Georg Thieme Verlag KG Stuttgart · New York.

Characterization of a piezo bendable X-ray mirror.

PubMed

Vannoni, Maurizio; Freijo Martín, Idoia; Siewert, Frank; Signorato, Riccardo; Yang, Fan; Sinn, Harald

2016-01-01

A full-scale piezo bendable mirror built as a prototype for an offset mirror at the European XFEL is characterized. The piezo ceramic elements are glued onto the mirror substrate, side-face on with respect to the reflecting surface. Using a nanometre optical component measuring machine and a large-aperture Fizeau interferometer, the mirror profile and influence functions were characterized, and further analysis was made to investigate the junction effect, hysteresis, twisting and reproducibility.

Seizures as a Potential Complication of Treatment With Simeprevir and Sofosbuvir.

PubMed

Syal, Gaurav; Heldenbrand, Seth D; Duarte-Rojo, Andres

2016-01-01

Newer direct-acting antiviral agents have revolutionized the medical management of chronic hepatitis C. In addition to being extremely efficacious, they report very mild adverse drug reactions from experience in clinical trials. However, because they are relatively new on the horizon, postmarketing surveillance studies refining the safety profile are not yet available. We present a case of seizures as a potential side effect of antiviral therapy with sofosbuvir and simeprevir.

Conference on Semi-Insulating III-V Materials (2nd), held 19-21 Apr 82, Evian (France),

DTIC Science & Technology

1983-02-28

Dist Special 19. KEY WORDS (Continue on reverse side If neceary mud Identity by block numb ) Semiconductor devices Field effect transitors Integrated...doped GaAs sub- 4 strates. The results showed no The catalog of defects includes statistically significant differ- vacancies, interstitials, anti...orientation also had high level profiles of GaAs active transconductance. In addition,the statistical scatter-uni-layers and their correlation to o m

UV resonance Raman finds peptide bond-Arg side chain electronic interactions.

PubMed

Sharma, Bhavya; Asher, Sanford A

2011-05-12

We measured the UV resonance Raman excitation profiles and Raman depolarization ratios of the arginine (Arg) vibrations of the amino acid monomer as well as Arg in the 21-residue predominantly alanine peptide AAAAA(AAARA)(3)A (AP) between 194 and 218 nm. Excitation within the π → π* peptide bond electronic transitions result in UVRR spectra dominated by amide peptide bond vibrations. The Raman cross sections and excitation profiles indicate that the Arg side chain electronic transitions mix with the AP peptide bond electronic transitions. The Arg Raman bands in AP exhibit Raman excitation profiles similar to those of the amide bands in AP which are conformation specific. These Arg excitation profiles distinctly differ from the Arg monomer. The Raman depolarization ratios of Arg in monomeric solution are quite simple with ρ = 0.33 indicating enhancement by a single electronic transition. In contrast, we see very complex depolarization ratios of Arg in AP that indicate that the Arg residues are resonance enhanced by multiple electronic transitions.

The effects of temperatures on the pebble flow in a pebble bed high temperature reactor

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

Sen, R. S.; Cogliati, J. J.; Gougar, H. D.

2012-07-01

The core of a pebble bed high temperature reactor (PBHTR) moves during operation, a feature which leads to better fuel economy (online refueling with no burnable poisons) and lower fuel stress. The pebbles are loaded at the top and trickle to the bottom of the core after which the burnup of each is measured. The pebbles that are not fully burned are recirculated through the core until the target burnup is achieved. The flow pattern of the pebbles through the core is of importance for core simulations because it couples the burnup distribution to the core temperature and power profiles,more » especially in cores with two or more radial burnup 'zones '. The pebble velocity profile is a strong function of the core geometry and the friction between the pebbles and the surrounding structures (other pebbles or graphite reflector blocks). The friction coefficient for graphite in a helium environment is inversely related to the temperature. The Thorium High Temperature Reactor (THTR) operated in Germany between 1983 and 1989. It featured a two-zone core, an inner core (IC) and outer core (OC), with different fuel mixtures loaded in each zone. The rate at which the IC was refueled relative to the OC in THTR was designed to be 0.56. During its operation, however, this ratio was measured to be 0.76, suggesting the pebbles in the inner core traveled faster than expected. It has been postulated that the positive feedback effect between inner core temperature, burnup, and pebble flow was underestimated in THTR. Because of the power shape, the center of the core in a typical cylindrical PBHTR operates at a higher temperature than the region next to the side reflector. The friction between pebbles in the IC is lower than that in the OC, perhaps causing a higher relative flow rate and lower average burnup, which in turn yield a higher local power density. Furthermore, the pebbles in the center region have higher velocities than the pebbles next to the side reflector due to the interaction between the pebbles and the immobile graphite reflector as well as the geometry of the discharge conus near the bottom of the core. In this paper, the coupling between the temperature profile and the pebble flow dynamics was analyzed by using PEBBED/THERMIX and PEBBLES codes by modeling the HTR-10 reactor in China. Two extreme and opposing velocity profiles are used as a starting point for the iterations. The PEBBED/THERMIX code is used to calculate the burnup, power and temperature profiles with one of the velocity profiles as input. The resulting temperature profile is then passed to PEBBLES code to calculate the updated pebble velocity profile taking the new temperature profile into account. If the aforementioned hypothesis is correct, the strong temperature effect upon the friction coefficients would cause the two cases to converge to different final velocity and temperature profiles. The results of this analysis indicates that a single zone pebble bed core is self-stabilizing in terms of the pebble velocity profile and the effect of the temperature profile on the pebble flow is insignificant. (authors)« less

In vivo systemic chlorogenic acid therapy under diabetic conditions: Wound healing effects and cytotoxicity/genotoxicity profile.

PubMed

Bagdas, Deniz; Etoz, Betul Cam; Gul, Zulfiye; Ziyanok, Sedef; Inan, Sevda; Turacozen, Ozge; Gul, Nihal Yasar; Topal, Ayse; Cinkilic, Nilufer; Tas, Sibel; Ozyigit, Musa Ozgur; Gurun, Mine Sibel

2015-07-01

Oxidative stress occurs following the impairment of pro-oxidant/antioxidant balance in chronic wounds and leads to harmful delays in healing progress. A fine balance between oxidative stress and endogenous antioxidant defense system may be beneficial for wound healing under redox control. This study tested the hypothesis that oxidative stress in wound area can be controlled with systemic antioxidant therapy and therefore wound healing can be accelerated. We used chlorogenic acid (CGA), a dietary antioxidant, in experimental diabetic wounds that are characterized by delayed healing. Additionally, we aimed to understand possible side effects of CGA on pivotal organs and bone marrow during therapy. Wounds were created on backs of streptozotocin-induced diabetic rats. CGA (50 mg/kg/day) was injected intraperitoneally. Animals were sacrificed on different days. Biochemical and histopathological examinations were performed. Side effects of chronic antioxidant treatment were tested. CGA accelerated wound healing, enhanced hydroxyproline content, decreased malondialdehyde/nitric oxide levels, elevated reduced-glutathione, and did not affect superoxide dismutase/catalase levels in wound bed. While CGA induced side effects such as cyto/genotoxicity, 15 days of treatment attenuated blood glucose levels. CGA decreased lipid peroxidation levels of main organs. This study provides a better understanding for antioxidant intake on diabetic wound repair and possible pro-oxidative effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Review of Indigo Naturalis as an Alternative Treatment for Nail Psoriasis.

PubMed

McDermott, Laura; Madan, Raman; Rupani, Reena; Siegel, Daniel

2016-03-01

Nail psoriasis is challenging to treat. The few currently available therapies are limited in efficacy, and often produce unfavorable side effects. A plant extract widely used in Traditional Chinese Medicine, indigo naturalis (Qing Dai), is presented in this review as an alternative topical treatment for skin and nail psoriasis. The purpose of this article is to present information on a viable alternative treatment with a favorable side effect profile for a difficult disease to treat. A PubMed search for the term "indigo naturalis" was performed, and literature from 2006 to the present relevant to indigo naturalis and treatment of psoriasis and nail psoriasis was reviewed. Indigo naturalis shares several therapeutic mechanisms with current psoriasis treatments, such as regulation of keratinocyte proliferation and differentiation, restoration of epidermal barrier function, and reduction of inflammatory processes. Clinically, it is well tolerated. Recent research of indigo naturalis suggests that it is a safe, inexpensive, and effective alternative topical treatment for skin and nail psoriasis.

[Vedolizumab (Entyvio®) for the treatment of inflammatory bowel diseases].

PubMed

Van Kemseke, C; Louis, E; Reenaers, C

2015-11-01

Anti-TNF agents are highly effective in treating inflammatory bowel diseases, but loss of response and side-effects leading to drug interruption are often reported. New molecules are needed to treat these patients. Vedolizumab is a fully humanized anti-body inhibiting the migration of circulating lymphocytes to the gut by binding the integrin α4β7. In ulcerative colitis, clinical response, remission and mucosal healing were observed at 6 weeks in 47%, 17% and 40% of the patients, respectively. The maintenance study demonstrated 42% and 52% of clinical remission and response at week 52. In Crohn's disease, clinical response and remission were respectively observed in 15% and 31% of the patients at 6 weeks. Clinical remission at week 52 was 39%. The time to clinical response was longer in patients who had failed anti-TNF. The safety profile is excellent with the same proportion of side-effects in the placebo and in the treated groups. The most frequently reported adverse events were pharyngitis and headaches.

Executive summary: the health and fitness benefits of regular participation in small-sided football games.

PubMed

Krustrup, P; Dvorak, J; Junge, A; Bangsbo, J

2010-04-01

The present special issue of Scandinavian Journal of Medicine & Science in Sports deals with health and fitness benefits of regular participation in small-sided football games. One review article and 13 original articles were the result of a 2-year multi-center study in Copenhagen and Zurich and include studies of different age groups analyzed from a physiological, medical, social and psychological perspective. The main groups investigated were middle-aged, former untrained, healthy men and women who were followed for up to 16 months. In addition, elderly, children and hypertensive patients were studied. A summary and interpretations of the main findings divided into an analysis of the physical demands during training of various groups and the effect of a period of training on performance, muscle adaptations and health profile follow. In addition, social and psychological effects on participation in recreational football are considered, the comparison of football training and endurance running is summarized and the effects of football practice on the elderly and children and youngsters are presented.

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

Thermocouple Boundary Layer Rake

NASA Technical Reports Server (NTRS)

Hwang, Danny P. (Inventor); Will, Herbert A. (Inventor); Fralick, Gustave C. (Inventor)

2002-01-01

Apparatus and method for providing a velocity flow profile near a reference surface. A measuring device utilizes a plurality of thermojunction pairs to provide the velocity flow profile in accordance with behavior of a gas relative to a constant thickness strut which stands vertically from the reference surface such that the span is normal to the surface, and the chord is parallel to the surface along the initial flow direction. Each thermojunction is carried on either side of a heater formed on a measuring surface in a constant thickness portion of a strut. Additionally, each thermojunction of a given pair is located at a predetermined height from the reference surface. Gas velocity data obtained from temperature differentials from one side of the heater to the other at each successive height is utilized to generate the velocity and turbulence level profiles.

Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea.

PubMed

Brierley, Daniel I; Samuels, James; Duncan, Marnie; Whalley, Benjamin J; Williams, Claire M

2016-01-01

Anticipatory nausea (AN) is a poorly controlled side effect experienced by chemotherapy patients. Currently, pharmacotherapy is restricted to benzodiazepine anxiolytics, which have limited efficacy, have significant sedative effects and induce dependency. The non-psychoactive phytocannabinoid, cannabidiolic acid (CBDA), has shown considerable efficacy in pre-clinical AN models, however determination of its neuromotor tolerability profile is crucial to justify clinical investigation. Provisional evidence for appetite-stimulating properties also requires detailed investigation. This study aims to assess the tolerability of CBDA in locomotor activity, motor coordination and muscular strength tests, and additionally for ability to modulate feeding behaviours. Male Lister Hooded rats administered CBDA (0.05-5 mg/kg; p.o.) were assessed in habituated open field (for locomotor activity), static beam and grip strength tests. A further study investigated whether these CBDA doses modulated normal feeding behaviour. Finally, evidence of anxiolytic-like effects in the habituated open field prompted testing of 5 mg/kg CBDA for anxiolytic-like activity in unhabituated open field, light/dark box and novelty-suppressed feeding (NSF) tests. CBDA had no adverse effects upon performance in any neuromotor tolerability test, however anxiolytic-like behaviour was observed in the habituated open field. Normal feeding behaviours were unaffected by any dose. CBDA (5 mg/kg) abolished the increased feeding latency in the NSF test induced by the 5-HT1AR antagonist, WAY-100,635, indicative of anxiolytic-like effects, but had no effect on anxiety-like behaviour in the novel open field or light/dark box. CBDA is very well tolerated and devoid of the sedative side effect profile of benzodiazepines, justifying its clinical investigation as a novel AN treatment.

Quantifying the effect of side branches in endothelial shear stress estimates

PubMed Central

Giannopoulos, Andreas A.; Chatzizisis, Yiannis S.; Maurovich-Horvat, Pal; Antoniadis, Antonios P.; Hoffmann, Udo; Steigner, Michael L.; Rybicki, Frank J.; Mitsouras, Dimitrios

2016-01-01

Background and aims Low and high endothelial shear stress (ESS) is associated with coronary atherosclerosis progression and high-risk plaque features. Coronary ESS is currently assessed via computational fluid dynamic (CFD) simulation in the lumen geometry determined from invasive imaging such as intravascular ultrasound and optical coherence tomography. This process typically omits side branches of the target vessel in the CFD model as invasive imaging of those vessels is not clinically-indicated. The purpose of this study was to determine the extent to which this simplification affects the determination of those regions of the coronary endothelium subjected to pathologic ESS. Methods We determined the diagnostic accuracy of ESS profiling without side branches to detect pathologic ESS in the major coronary arteries of 5 hearts imaged ex vivo with CT angiography. ESS of the three major coronary arteries was calculated both without (test model), and with (reference model) inclusion of all side branches >1.5 mm in diameter, using previously-validated CFD approaches. Diagnostic test characteristics (accuracy, sensitivity, specificity and negative and positive predictive value [NPV/PPV]) with respect to the reference model were assessed for both the entire length as well as only the proximal portion of each major coronary artery, where the majority of high-risk plaques occur. Results Using the model without side branches overall accuracy, sensitivity, specificity, NPV and PPV were 83.4%, 54.0%, 96%, 95.9% and 55.1%, respectively to detect low ESS, and 87.0%, 67.7%, 90.7%, 93.7% and 57.5%, respectively to detect high ESS. When considering only the proximal arteries, test characteristics differed for low and high ESS, with low sensitivity (67.7%) and high specificity (90.7%) to detect low ESS, and low sensitivity (44.7%) and high specificity (95.5%) to detect high ESS. Conclusions The exclusion of side branches in ESS vascular profiling studies greatly reduces the ability to detect regions of the major coronary arteries subjected to pathologic ESS. Single-conduit models can in general only be used to rule out pathologic ESS. PMID:27372207

Quantifying the effect of side branches in endothelial shear stress estimates.

PubMed

Giannopoulos, Andreas A; Chatzizisis, Yiannis S; Maurovich-Horvat, Pal; Antoniadis, Antonios P; Hoffmann, Udo; Steigner, Michael L; Rybicki, Frank J; Mitsouras, Dimitrios

2016-08-01

Low and high endothelial shear stress (ESS) is associated with coronary atherosclerosis progression and high-risk plaque features. Coronary ESS is currently assessed via computational fluid dynamic (CFD) simulation of coronary blood flow in the lumen geometry determined from invasive imaging such as intravascular ultrasound and optical coherence tomography. This process typically omits side branches of the target vessel in the CFD model as invasive imaging of those vessels is not usually clinically-indicated. The purpose of this study was to determine the extent to which this simplification affects the determination of those regions of the coronary endothelium subjected to pathologic ESS. We determined the diagnostic accuracy of ESS profiling without side branches to detect pathologic ESS in the major coronary arteries of 5 hearts imaged ex vivo with computed tomography angiography (CTA). ESS of the three major coronary arteries was calculated both without (test model), and with (reference model) inclusion of all side branches >1.5 mm in diameter, using previously-validated CFD approaches. Diagnostic test characteristics (accuracy, sensitivity, specificity and negative and positive predictive value [NPV/PPV]) with respect to the reference model were assessed for both the entire length as well as only the proximal portion of each major coronary artery, where the majority of high-risk plaques occur. Using the model without side branches overall accuracy, sensitivity, specificity, NPV and PPV were 83.4%, 54.0%, 96%, 95.9% and 55.1%, respectively to detect low ESS, and 87.0%, 67.7%, 90.7%, 93.7% and 57.5%, respectively to detect high ESS. When considering only the proximal arteries, test characteristics differed for low and high ESS, with low sensitivity (67.7%) and high specificity (90.7%) to detect low ESS, and low sensitivity (44.7%) and high specificity (95.5%) to detect high ESS. The exclusion of side branches in ESS vascular profiling studies greatly reduces the ability to detect regions of the major coronary arteries subjected to pathologic ESS. Single-conduit models can in general only be used to rule out pathologic ESS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Recent Advances in Fractional Laser Resurfacing: New Paradigm in Optimal Parameters and Post-Treatment Wound Care

PubMed Central

Hsiao, Francis C.; Bock, Gerald N.; Eisen, Daniel B.

2012-01-01

Background Laser plays an increasingly prominent role in skin rejuvenation. The advent of fractional photothermolysis revolutionizes its application. Microcolumns of skin are focally injured, leaving intervening normal skin to facilitate rapid wound healing and orderly tissue remodeling. The Problem Even with the popularity of fractional laser devices, we still have limited knowledge about the ideal treatment parameters and postlaser wound care. Basic/Clinical Science Advances Many clinicians believe that higher microbream energy in fractional laser devices results in better clinical outcome. Two recent studies argue against this assumption. One article demonstrates that lower fluence can induce comparable molecular changes with fewer side effects. Another study corroborates this by showing that lower-density settings produce similar clinical outcome in scar remodeling as higher-density ones, but with fewer side effects. To shed light on the optimal post-treatment wound care regimen from fractional ablative resurfacing, another paper shows that platelet-rich plasma (PRP) can reduce transepidermal water loss and skin color changes within 1 month after treatment. Clinical Care Relevance For fractional nonablative resurfacing, lower settings in fluence or density may produce similar dermal remodeling as higher settings and with a better side-effect profile. Moreover, autologous PRP appears to expedite wound healing after fractional ablative resurfacing. Conclusion Lower microbeam energy in fractional laser resurfacing produces similar molecular changes and clinical outcome with fewer side effects. The findings might portend a shift in the paradigm of treatment parameters. Autologous PRP can facilitate better wound healing, albeit modestly. Long-term follow-ups and larger studies are necessary to confirm these findings. PMID:24527307

Buprenorphine dose induction in non-opioid-tolerant pre-release prisoners.

PubMed

Vocci, Frank J; Schwartz, Robert P; Wilson, Monique E; Gordon, Michael S; Kinlock, Timothy W; Fitzgerald, Terrence T; O'Grady, Kevin E; Jaffe, Jerome H

2015-11-01

In a previously reported randomized controlled trial, formerly opioid-dependent prisoners were more likely to enter community drug abuse treatment when they were inducted in prison onto buprenorphine/naloxone (hereafter called buprenorphine) than when they received counseling without buprenorphine in prison (47.5% vs. 33.7%, p=0.012) (Gordon et al., 2014). In this communication we report on the results of the induction schedule and the adverse event profile seen in pre-release prisoners inducted onto buprenorphine. This paper examines the dose induction procedure, a comparison of the proposed versus actual doses given per week, and side effects reported for 104 adult participants who were randomized to buprenorphine treatment in prison. Self-reported side effects were analyzed using generalized estimated equations to determine changes over time in side effects. Study participants were inducted onto buprenorphine at a rate faster than the induction schedule. Of the 104 (72 males, 32 females) buprenorphine recipients, 64 (37 males, 27 females) remained on medication at release from prison. Nine participants (8.6%) discontinued buprenorphine because of unpleasant opioid side effects. There were no serious adverse events reported during the in-prison phase of the study. Constipation was the most frequent symptom reported (69 percent). Our findings suggest that buprenorphine administered to non-opioid-tolerant adults should be started at a lower, individualized dose than customarily used for adults actively using opioids, and that non-opioid-tolerant pre-release prisoners can be successfully inducted onto therapeutic doses prior to release. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A coarse-grained model of the effective interaction for charged amino acid residues and its application to formation of GCN4-pLI tetramer

NASA Astrophysics Data System (ADS)

Kawaguchi, Kazutomo; Nakagawa, Satoshi; Kurniawan, Isman; Kodama, Koichi; Arwansyah, Muhammad Saleh; Nagao, Hidemi

2018-03-01

We present a simple coarse-grained model of the effective interaction for charged amino acid residues, such as Glu and Lys, in a water solvent. The free-energy profile as a function of the distance between two charged amino acid side-chain analogues in an explicit water solvent is calculated with all-atom molecular dynamics simulation and thermodynamic integration method. The calculated free-energy profile is applied to the coarse-grained potential of the effective interaction between two amino acid residues. The Langevin dynamics simulations with our coarse-grained potential are performed for association of a small protein complex, GCN4-pLI tetramer. The tetramer conformation reproduced by our coarse-grained model is similar to the X-ray crystallographic structure. We show that the effective interaction between charged amino acid residues stabilises association and orientation of protein complex. We also investigate the association pathways of GCN4-pLI tetramer.

Component having cooling channel with hourglass cross section

DOEpatents

Campbell, Christian X; Lee, Ching-Pang

2015-04-28

A cooling channel (36, 36B, 63-66) cools inner surfaces (48, 50) of exterior walls (41, 43) of a component (20, 60). Interior side surfaces (52, 54) of the channel converge to a waist (W2), forming an hourglass shaped transverse profile (46). The inner surfaces (48, 50) may have fins (44) aligned with the coolant flow (22). The fins may have a transverse profile (56A, 56B) highest at mid-width of the inner surfaces (48, 50). Turbulators (92) may be provided on the side surfaces (52, 54) of the channel, and may urge the coolant flow toward the inner surfaces (48, 50). Each turbulator (92) may have a peak (97) that defines the waist of the cooling channel. Each turbulator may have a convex upstream side (93). These elements increase coolant flow in the corners (C) of the channel to more uniformly and efficiently cool the exterior walls (41, 43).

Single-sided magnetic resonance profiling in biological and materials science.

PubMed

Danieli, Ernesto; Blümich, Bernhard

2013-04-01

Single-sided NMR was inspired by the oil industry that strived to improve the performance of well-logging tools to measure the properties of fluids confined downhole. This unconventional way of implementing NMR, in which stray magnetic and radio frequency fields are used to recover information of arbitrarily large objects placed outside the magnet, motivated the development of handheld NMR sensors. These devices have moved the technique to different scientific disciplines. The current work gives a review of the most relevant magnets and methodologies developed to generate NMR information from spatially localized regions of samples placed in close proximity to the sensors. When carried out systematically, such measurements lead to 'single-sided depth profiles' or one-dimensional images. This paper presents recent and most relevant applications as well as future perspectives of this growing branch of MRI. Copyright © 2012 Elsevier Inc. All rights reserved.

On the stability analysis of sharply stratified shear flows

NASA Astrophysics Data System (ADS)

Churilov, Semyon

2018-05-01

When the stability of a sharply stratified shear flow is studied, the density profile is usually taken stepwise and a weak stratification between pycnoclines is neglected. As a consequence, in the instability domain of the flow two-sided neutral curves appear such that the waves corresponding to them are neutrally stable, whereas the neighboring waves on either side of the curve are unstable, in contrast with the classical result of Miles (J Fluid Mech 16:209-227, 1963) who proved that in stratified flows unstable oscillations can be only on one side of the neutral curve. In the paper, the contradiction is resolved and changes in the flow stability pattern under transition from a model stepwise to a continuous density profile are analyzed. On this basis, a simple self-consistent algorithm is proposed for studying the stability of sharply stratified shear flows with a continuous density variation and an arbitrary monotonic velocity profile without inflection points. Because our calculations and the algorithm are both based on the method of stability analysis (Churilov J Fluid Mech 539:25-55, 2005; ibid, 617, 301-326, 2008), which differs essentially from usually used, the paper starts with a brief review of the method and results obtained with it.

Improved performance of nanoscale junctionless tunnel field-effect transistor based on gate engineering approach

NASA Astrophysics Data System (ADS)

Molaei Imen Abadi, Rouzbeh; Sedigh Ziabari, Seyed Ali

2016-11-01

In this paper, a first qualitative study on the performance characteristics of dual-work function gate junctionless TFET (DWG-JLTFET) on the basis of energy band profile modulation is investigated. A dual-work function gate technique is used in a JLTFET in order to create a downward band bending on the source side similar to PNPN structure. Compared with the single-work function gate junctionless TFET (SWG-JLTFET), the numerical simulation results demonstrated that the DWG-JLTFET simultaneously optimizes the ON-state current, the OFF-state leakage current, and the threshold voltage and also improves average subthreshold slope. It is illustrated that if appropriate work functions are selected for the gate materials on the source side and the drain side, the JLTFET exhibits a considerably improved performance. Furthermore, the optimization design of the tunnel gate length ( L Tun) for the proposed DWG-JLTFET is studied. All the simulations are done in Silvaco TCAD for a channel length of 20 nm using the nonlocal band-to-band tunneling (BTBT) model.

Should Nitrous Oxide Be Used for Laboring Patients?

PubMed

Richardson, Michael G; Lopez, Brandon M; Baysinger, Curtis L

2017-03-01

Nitrous oxide, long used during labor in Europe, is gaining popularity in the United States. It offers many beneficial attributes, with few drawbacks. Cost, safety, and side effect profiles are favorable. Analgesic effectiveness is highly variable, yet maternal satisfaction is often high among the women who choose to use it. Despite being less effective in treating labor pain than neuraxial analgesic modalities, nitrous oxide serves the needs and preferences of a subset of laboring parturients. Nitrous oxide should, therefore, be considered for inclusion in the repertoire of modalities used to alleviate pain and facilitate effective coping during labor. Copyright © 2016 Elsevier Inc. All rights reserved.

Vamorolone, a dissociative steroidal compound, reduces pro-inflammatory cytokine expression in glioma cells and increases activity and survival in a murine model of cortical tumor.

PubMed

Wells, Elizabeth; Kambhampati, Madhuri; Damsker, Jesse M; Gordish-Dressman, Heather; Yadavilli, Sridevi; Becher, Oren J; Gittens, Jamila; Stampar, Mojca; Packer, Roger J; Nazarian, Javad

2017-02-07

Corticosteroids, such as dexamethasone, are routinely used as palliative care in neuro-oncology for their anti-inflammatory benefits, however many patients experience dose limiting side effects caused by glucocorticoid response element (GRE)-mediated transcription. The purpose of this study was to use a murine model to investigate a new steroid alternative, vamorolone, which promises to reduce side effects through dissociating GRE-mediated transcription and NF-κB -mediated anti-inflammatory actions. To compare vamorolone to dexamethasone in reducing pro-inflammatory signals in vitro, murine glioma cells were treated with dexamethasone, vamorolone or vehicle control. Changes in mRNA expression were assessed using the nanostring inflammatory platform. Furthermore, drug efficacy, post-treatment behavioral activity and side effects were assessed by treating two cohorts of brain tumor bearing mice with dexamethasone, vamorolone, or vehicle control. Our investigation showed that treatment with vamorolone resulted in a reduction of pro-inflammatory signals in tumor cells in vitro similar to treatment with dexamethasone. Treatment with vamorolone resulted in a better safety profile in comparison to dexamethasone treatment. Vamorolone- treated mice showed similar or better activity and survival when compared to dexamethasone-treated mice. Our data indicate vamorolone is a potential steroid-sparing alternative for treating patients with brain tumors.

A randomized comparison of side effects and patient convenience between Cyclogest suppositories and Endometrin tablets used for luteal phase support in IVF treatment.

PubMed

Ng, Ernest Hung Yu; Chan, Carina Chi Wai; Tang, Oi Shan; Ho, Pak Chung

2007-04-01

This study compared side effects and patient convenience of vaginal progesterone suppositories (Cyclogest) and vaginal progesterone tablets (Endometrin) used for luteal phase support in in vitro fertilization/embryo transfer (IVF/ET) cycles using pituitary downregulation. One hundred and thirty-two infertile patients were randomized on the day of ET by a computer-generated randomization list in sealed envelopes to receive either Cyclogest 400mg or Endometrin 100mg twice daily for 14 days. On days 6 and 16 after ET, they rated side effects and patient convenience into four grades: none, mild, moderate and severe by completing a questionnaire. No significant differences in perineal irritation were found on days 6 and 16 after ET between the two groups, although there was a trend of fewer patients with perineal irritation in the Endometrin group. Significantly more patients in the Endometrin group had difficulty of administration on day 6 after ET. There were no differences in the hormonal profile on day 6 after ET and IVF outcomes between the two groups. There was no difference in perineal irritation after the use of Cyclogest suppositories or Endometrin tablets for luteal phase support although more patients found administration of Endometrin tablets difficult.

DETERMINATION OF CENTRAL ENGINE POSITION AND ACCRETION DISK STRUCTURE IN NGC 4261 BY CORE SHIFT MEASUREMENTS

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

Haga, Takafumi; Doi, Akihiro; Murata, Yasuhiro

2015-07-01

We report multifrequency phase-referenced observations of the nearby radio galaxy NGC 4261, which has prominent two-sided jets, using the Very Long Baseline Array at 1.4–43 GHz. We measured radio core positions showing observing frequency dependences (known as “core shift”) in both approaching jets and counterjets. The limit of the core position as the frequency approaches infinity, which suggests a jet base, is separated by 82 ± 16 μas upstream in projection, corresponding to (310 ± 60)R{sub s} (R{sub s}: Schwarzschild radius) as a deprojected distance, from the 43 GHz core in the approaching jet. In addition, the innermost component atmore » the counterjet side appeared to approach the same position at infinity of the frequency, indicating that cores on both sides are approaching the same position, suggesting a spatial coincidence with the central engine. Applying a phase-referencing technique, we also obtained spectral index maps, which indicate that emission from the counterjet is affected by free–free absorption (FFA). The result of the core shift profile on the counterjet also requires FFA because the core positions at 5–15 GHz cannot be explained by a simple core shift model based on synchrotron self-absorption (SSA). Our result is apparently consistent with the SSA core shift with an additional disk-like absorber over the counterjet side. Core shift and opacity profiles at the counterjet side suggest a two-component accretion: a radiatively inefficient accretion flow at the inner region and a truncated thin disk in the outer region. We proposed a possible solution about density and temperature profiles in the outer disk on the basis of the radio observation.« less

Methylphenidate side effect profile is influenced by genetic variation in the attention-deficit/hyperactivity disorder-associated CES1 gene.

PubMed

Johnson, Katherine A; Barry, Edwina; Lambert, David; Fitzgerald, Michael; McNicholas, Fiona; Kirley, Aiveen; Gill, Michael; Bellgrove, Mark A; Hawi, Ziarih

2013-12-01

A naturalistic, prospective study of the influence of genetic variation on dose prescribed, clinical response, and side effects related to stimulant medication in 77 children with attention-deficit/hyperactivity disorder (ADHD) was undertaken. The influence of genetic variation of the CES1 gene coding for carboxylesterase 1A1 (CES1A1), the major enzyme responsible for the first-pass, stereoselective metabolism of methylphenidate, was investigated. Parent- and teacher-rated behavioral questionnaires were collected at baseline when the children were medication naïve, and again at 6 weeks while they were on medication. Medication dose, prescribed at the discretion of the treating clinician, and side effects, were recorded at week 6. Blood and saliva samples were collected for genotyping. Single nucleotide polymorphisms (SNPs) were selected in the coding, non-coding and the 3' flanking region of the CES1 gene. Genetic association between CES1 variants and ADHD was investigated in an expanded sample of 265 Irish ADHD families. Analyses were conducted using analysis of covariance (ANCOVA) and logistic regression models. None of the CES1 gene variants were associated with the dose of methylphenidate provided or the clinical response recorded at the 6 week time point. An association between two CES1 SNP markers and the occurrence of sadness as a side effect of short-acting methylphenidate was found. The two associated CES1 markers were in linkage disequilibrium and were significantly associated with ADHD in a larger sample of ADHD trios. The associated CES1 markers were also in linkage disequilibrium with two SNP markers of the noradrenaline transporter gene (SLC6A2). This study found an association between two CES1 SNP markers and the occurrence of sadness as a side effect of short-acting methylphenidate. These markers were in linkage disequilibrium together and with two SNP markers of the noradrenaline transporter gene.

Gene expression analysis using a highly sensitive DNA microarray for colorectal cancer screening.

PubMed

Koga, Yoshikatsu; Yamazaki, Nobuyoshi; Takizawa, Satoko; Kawauchi, Junpei; Nomura, Osamu; Yamamoto, Seiichiro; Saito, Norio; Kakugawa, Yasuo; Otake, Yosuke; Matsumoto, Minori; Matsumura, Yasuhiro

2014-01-01

Half of all patients with small, right-sided, non-metastatic colorectal cancer (CRC) have negative results for the fecal occult blood test (FOBT). In the present study, the usefulness of CRC screening with a highly sensitive DNA microarray was evaluated in comparison with that by FOBT using fecal samples. A total of 53 patients with CRC and 61 healthy controls were divided into "training" and "validation sets". For the gene profiling, total RNA extracted from 0.5 g of feces was hybridized to a highly sensitive DNA chip. The expressions of 43 genes were significantly higher in the patients with CRC than in healthy controls (p<0.05). In the training set, the sensitivity and specificity of the DNA chip assay using six genes were 85.4% and 85.2%, respectively. On the other hand, in the validation set, the sensitivity and specificity of the DNA chip assay were 85.2% and 85.7%, respectively. The sensitivities of the DNA chip assay were higher than those of FOBT in cases of the small, right-sided, early-CRC, tumor invading up to the muscularis propria (i.e. surface tumor) subgroups. In particular, the sensitivities of the DNA chip assay in the surface tumor and early-CRC subgroups were significantly higher than those of FOBT (p=0.023 and 0.019, respectively.). Gene profiling assay using a highly sensitive DNA chip was more effective than FOBT at detecting patients with small, right-sided, surface tumor, and early-stage CRC.

Characterisation of the pharmacological profile of desoxymethyltestosterone (Madol), a steroid misused for doping.

PubMed

Diel, P; Friedel, A; Geyer, H; Kamber, M; Laudenbach-Leschowsky, U; Schänzer, W; Thevis, M; Vollmer, G; Zierau, O

2007-02-28

Desoxymethyltestosterone (DMT), also known as Madol, is a steroid recently identified to be misused as a doping agent. Since, the knowledge of functions of this substance is rather limited, it was our aim to characterise the pharmacological profile of DMT and to identify potential adverse side effects. DMT was synthesised, its purity was confirmed and its biological activity was tested. The potency of Madol (DMT) to transactivate androgen receptor (AR) dependent reporter gene expression was two times lower as compared to dihydrotestosterone (DHT). Receptor binding tests demonstrate that DMT binds with high selectivity to the AR, binding to the progesterone receptor (PR) was low. In vivo experiments in orchiectomised rats demonstrated that treatment with DMT resulted only in a stimulation of the weight of the levator ani muscle; the prostate and seminal vesicle weights remained unaffected. Like testosterone, administration of DMT resulted in a stimulation of IGF-1 and myostatin mRNA expression in the gastrocnemius muscle. In the prostate proliferation was stimulated by TP (testosteronepropionate), but remained unaffected by DMT. Remarkably, treatment with DMT, in contrast to TP, resulted in a significant increase of the heart weight. In the liver, DMT slightly stimulates the expression of the tyrosine aminotransferase gene (TAT). Our results demonstrate that DMT is a potent AR agonist with an anabolic activity. Besides the levator ani weight, DMT also modulates the gene expression in the musculus gastrocnemius. The observed stimulation of TAT expression in the liver and the significant increase of the heart weight after DMT treatment can be taken as an indication for side effects. Summarizing these data it is obvious that DMT is a powerful anabolic steroid with selective androgen receptor modulators (SARM) like properties and some indications for toxic side effects. Therefore, there is a need for a strict control of a possible misuse.

Treatment of Acute Vocal Fold Injury With Platelet-Rich Plasma.

PubMed

Cobden, Serap Bulut; Oztürk, Kayhan; Duman, Selcuk; Esen, Hasan; Aktan, Tahsin Murad; Avunduk, Mustafa Cihat; Elsurer, Cagdas

2016-11-01

Platelet-rich plasma (PRP) is a reliable and has low side-effect profile and has beneficial effects on wound healing. Its investigatory effects on wound-healing process were shown on various tissues. The aim of the present study was to evaluate effectiveness of PRP application on scar tissue of acute vocal fold injury. Twenty-four Wistar rats were used in the study. The entire layer of the lamina propria down to the thyroarytenoid muscle of 10 subjects was unilaterally injured by with a microscissor. Gelfoam-absorbed PRP was applied on the injured area for 10 minutes. Control group consisted of rats unilaterally injured using a microscissor, and gelfoam with normal saline was applied on the injured area. Following sacrifice, the larynxes were carefully dissected and removed for histopathologic examination. After excised larynx experiments, serial sections were prepared from vocal fold. Hematoxylin eosin and immunohistochemical staining were done for epithelial growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR1), and vascular endothelial growth factor (VEGF) staining for histopathologic examinations. There was not a significant difference between the two groups for lymphocyte. Although collagen and VEGF were higher in the study group, there was not a significant difference between the groups (P > 0.05). There was a significant difference between control and study groups for EGFR and FGFR1(P < 0.05). PRP has beneficial effects on wound healing. PRP accelerates epithelization of injured rat vocal folds by inducing EGFR secretion. PRP is an autogenous, reliable, low side-effect profile, easily harvested material. PRP may be useful to prevent scar formation. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Validation of a questionnaire to monitor symptoms in HIV-infected patients during hepatitis C treatment.

PubMed

Cachay, Edward R; Ballard, Craig; Colwell, Bradford; Torriani, Francesca; Hicks, Charles; Mathews, Wm Christopher

2017-09-20

Clinicians are incorporating patient-reported outcomes in the management of HIV-infected persons co-infected with hepatitis C virus (HCV), but there are no validated inventories to monitor symptoms of patients during HCV therapy. Five-year retrospective cohort analysis of persons living with HIV (PLWH) treated for HCV. The HCV symptom-inventory (HCV-SI) was administered before, during, and after HCV treatment. Discriminant validity was assessed, separately, in mixed model linear regression of HCV-SI T-scores on treatment regimens (pegylated-interferon and ribavirin; pegylated-interferon, ribavirin, and telaprevir; and interferon-free antivirals); and side effect-related premature treatment discontinuation (SE-DC). From the 103 patients who completed the HCV-SI, 7% were female, 26% non-white, 32% cirrhotics and 91% had undetectable HIV viral loads. Most had genotype 1 (83%) and were HCV treatment-naïve (78%). We treated 19% of patients with pegylated-interferon and ribavirin, 22% with pegylated-interferon, ribavirin, and telaprevir and 59% received interferon-free antivirals. Overall, 77% achieved a sustained virologic response, and 6% discontinued HCV treatment due to side effects. In the treatment discrimination model, compared to the no treatment period, HCV-SI scores were significantly (p < 0.01) lower for interferon-free antivirals and higher for interferon-containing regimens. In the SE-DC model, the total HCV-SI, somatic and neuropsychiatric scores significantly predicted those patients who prematurely discontinued HCV treatment (P < 0.05). The HCV-SI effectively differentiated among treatment regimens known to vary by side effect profiles and between patients with and without treatment discontinuation due to side effects. The HCV-SI may have value as a patient-reported outcome instrument predicting the risk of HCV treatment discontinuation.

Comparison of efficacy and side-effect profile of oral PUVA vs. oral PUVA sol in the treatment of vitiligo: a 36-week prospective study.

PubMed

Singh, S; Khandpur, S; Sharma, V K; Ramam, M

2013-11-01

Both Oral PUVA and PUVA sol have been successfully used in vitiligo treatment. However, there is paucity of studies comparing the two therapies, especially under subtropical conditions of abundant sunlight where PUVA sol is more feasible. To compare the efficacy and side effects of oral PUVA versus oral PUVA sol therapy in generalized vitiligo. Comparative prospective clinical trial conducted on consecutive patients of generalized vitiligo. Response to treatment was assessed using change in Lund & Browder (L & B) score for assessment of reduction in body surface area of involvement, patient global assessment (PGA) of improvement in vitiligo, investigator's global assessment (IGA) of extent of repigmentation, and quality of life (QOL) assessment using Tjioe et al questionnaire. Thirty five patients were recruited- 18 in PUVA and 17 in PUVA sol group. Mean percentage change in L & B score at 36 weeks was 46.4% in PUVA and 26.1% in PUVA sol group (P = 0.06), mean PGA score in PUVA was 4.58 ± 2.23 and in PUVA sol group was 6 ± 2.08 (P = 0.13), mean IGA score was 3.08 ± 1.68 in PUVA and 1.79 ± 0.57 in PUVA sol group (P = 0.11). QOL scores were significantly higher in PUVA group as compared to the PUVA sol group (P = 0.04). Side effects were comparable in two groups except for phototoxic side effects which were significantly more in PUVA group. PUVA is more efficacious than PUVA sol and also provides greater psychological benefit in treatment of generalized vitiligo but is associated with more phototoxic adverse effects. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Endomorphin-2 analogs with C-terminal esterification produce potent systemic antinociception with reduced tolerance and gastrointestinal side effects.

PubMed

Wang, Chang-Lin; Qiu, Ting-Ting; Yang, Dai-Jun; Yuan, Bi-Yu; Han, Feng-Tong; Li, Li; Gu, Ning

2017-04-01

C-terminal esterification of opioid peptides may change their opioid activities due to the modified physicochemical properties. In the present study, the pharmacological activities of C-terminal esterified endomorphin-2 (EM-2) analogs 1-3 were characterized by in vitro metabolic stability and octanol/buffer distribution assays. Also, the antinociceptive profiles in the radiant heat paw withdrawal test and related side effects of these analogs were determined. Our results showed that all three analogs significantly increased the metabolic stability and lipophilicity. Moreover, analogs 1-3 displayed potent antinociceptive activities after intracerebroventricular (i.c.v.) administration. Analogs 1 and 3 exhibited about 2-fold higher antinociception than EM-2, and differential opioid mechanisms were involved. In addition, EM-2 at 50 μmol/kg failed to produce any significant antinociceptive activity after subcutaneous (s.c.) administration, whereas equimolar dose of analogs 1-3 produced significant analgesic effects. Analog 3 showed the highest antinociceptive activity after systemic administration, which was consistent with its in vitro stability and lipophilicity. We further evaluated the antinociceptive tolerance of analogs 1-3. In acute tolerance test, analogs 1-3 shifted the dose-response curves rightward by only 1.4-3.2 fold as determined by tolerance ratio, whereas EM-2 by 5.6-fold, demonstrating reduced antinociceptive tolerance. Also, analogs 1 and 2 decreased chronic antinociceptive tolerance by central and peripheral administration of drugs. In particular, analogs 3 displayed insignificant chronic antinociceptive tolerance. Furthermore, analogs 1-3 were less prone to induce gastrointestinal side effects at analgesic doses. The present investigation gave the evidence that C-terminal esterified modifications of EM-2 will facilitate the development of novel opioid analgesics with reduced side effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Overview of ASDEX Upgrade results

DOE PAGES

Aguiam, D.

2017-06-28

Here, the ASDEX Upgrade (AUG) programme is directed towards physics input to critical elements of the ITER design and the preparation of ITER operation, as well as addressing physics issues for a future DEMO design. Since 2015, AUG is equipped with a new pair of 3-strap ICRF antennas, which were designed for a reduction of tungsten release during ICRF operation. As predicted, a factor two reduction on the ICRF-induced W plasma content could be achieved by the reduction of the sheath voltage at the antenna limiters via the compensation of the image currents of the central and side straps in the antenna frame. There are two main operational scenario lines in AUG. Experiments with low collisionality, which comprise current drive, ELM mitigation/suppression and fast ion physics, are mainly done with freshly boronized walls to reduce the tungsten influx at these high edge temperature conditions. Full ELM suppression and non-inductive operation up to a plasma current ofmore » $${{I}_{\\text{p}}}=0.8$$ MA could be obtained at low plasma density. Plasma exhaust is studied under conditions of high neutral divertor pressure and separatrix electron density, where a fresh boronization is not required. Substantial progress could be achieved for the understanding of the confinement degradation by strong D puffing and the improvement with nitrogen or carbon seeding. Inward/outward shifts of the electron density profile relative to the temperature profile effect the edge stability via the pressure profile changes and lead to improved/decreased pedestal performance. Seeding and D gas puffing are found to effect the core fueling via changes in a region of high density on the high field side (HFSHD).« less

Anxiety profile in morphine-dependent and withdrawn rats: effect of voluntary exercise.

PubMed

Miladi-Gorji, Hossein; Rashidy-Pour, Ali; Fathollahi, Yaghoub

2012-01-18

Withdrawal from chronic opiates is associated with an increase in anxiogenic-like behaviours, but the anxiety profile in the morphine-dependent animals is not clear. Thus, one of the aims of the present study was to examine whether morphine-dependent rats would increase the expression of anxiogenic-like behaviours in novel and stressful conditions. Additionally, recent studies have shown that voluntary exercise can reduce anxiety levels in rodents. Therefore, another aim of this study was to examine the effect of voluntary exercise on the anxiety profile in both morphine-dependent animals and animals experiencing withdrawal. Rats were injected with bi-daily doses (10 mg/kg, at 12 h intervals) of morphine over a period of 10 days in which they were also allowed voluntary exercise. Following these injections, anxiety-like behaviours were tested in the elevated plus-maze (EPM) model and the light/dark (L/D) box. We found reductions in time spent in, and entries into, the EPM open arms and reductions in time spent in the lit side of the L/D box for both sedentary morphine-dependent and withdrawn rats as compared to the sedentary control groups. The exercising morphine-dependent and withdrawn rats exhibited an increase in EPM open arm time and entries and L/D box lit side time as compared with the sedentary control groups. We conclude that voluntary exercise decreases the severity of the anxiogenic-like behaviours in both morphine-dependent and withdrawn rats. Thus, voluntary exercise could be a potential natural method to ameliorate some of the deleterious behavioural consequences of opiate abuse. Copyright © 2011 Elsevier Inc. All rights reserved.

Significance of including field non-uniformities such as the heel effect and beam scatter in the determination of the skin dose distribution during interventional fluoroscopic procedures

NASA Astrophysics Data System (ADS)

Rana, Vijay; Gill, Kamaljit; Rudin, Stephen; Bednarek, Daniel R.

2012-03-01

The current version of the real-time skin-dose-tracking system (DTS) we have developed assumes the exposure is contained within the collimated beam and is uniform except for inverse-square variation. This study investigates the significance of factors that contribute to beam non-uniformity such as the heel effect and backscatter from the patient to areas of the skin inside and outside the collimated beam. Dose-calibrated Gafchromic film (XR-RV3, ISP) was placed in the beam in the plane of the patient table at a position 15 cm tube-side of isocenter on a Toshiba Infinix C-Arm system. Separate exposures were made with the film in contact with a block of 20-cm solid water providing backscatter and with the film suspended in air without backscatter, both with and without the table in the beam. The film was scanned to obtain dose profiles and comparison of the profiles for the various conditions allowed a determination of field non-uniformity and backscatter contribution. With the solid-water phantom and with the collimator opened completely for the 20-cm mode, the dose profile decreased by about 40% on the anode side of the field. Backscatter falloff at the beam edge was about 10% from the center and extra-beam backscatter decreased slowly with distance from the field, being about 3% of the beam maximum at 6 cm from the edge. Determination of the magnitude of these factors will allow them to be included in the skin-dose-distribution calculation and should provide a more accurate determination of peak-skin dose for the DTS.

Long-term Safety and Efficacy of Low-dose Azathioprine and Allopurinol Cotherapy in Inflammatory Bowel Disease: A Large Observational Study.

PubMed

Pavlidis, Polychronis; Stamoulos, Panagiotis; Abdulrehman, Answar; Kerr, Patrick; Bull, Claire; Duley, John; Ansari, Azhar

2016-07-01

Low-dose azathioprine with allopurinol (LDAA) has been proposed as a potent therapy in inflammatory bowel disease (IBD) with the benefit of overcoming side effects regularly associated with thiopurine monotherapy and poor responses. Concerns regarding safety remain, while a layer of complexity has been added by the trend toward treatment directed by red cell thioguanine nucleotide (TGN) profiling. We report on the clinical efficacy and safety of LDAA use in IBD undirected by metabolite profiling. Observational study of clinical practice from a single IBD center. Patient outcomes were defined clinically based on established activity scores and corticosteroid withdrawal. Red cell TGN was monitored only for suspected nonadherence. Overall, 113/164 (69%) patients with Crohn's disease and 83/136 (61%) patients with ulcerative/unclassified colitis had a clinical response by the end of follow-up (median 19 months), while 85 (52%) patients with Crohn's disease and 74 (54%) patients with ulcerative/unclassified colitis were in clinical remission. Clinical response was seen in 45/57 (79%) patients with Crohn's disease and 34/53 (64%) patients with ulcerative/unclassified colitis who were thiopurine naive, had active IBD, and received LDAA as the first line immunomodulator, while in 35 (61%) and 28 (53%), respectively, remission was achieved. LDAA was stopped in 20/300 (7%) patients because of side effects, all of which resolved on drug cessation. This is the largest cohort supporting the favorable safety profile and high efficacy of LDAA in IBD. It presents 2 advances in therapy: prescribing LDAA for thiopurine-naive patients, and bypassing TGN monitoring in favor of clinical monitoring (blood counts, etc.), which will make it more accessible for clinics without access to TGN assays.

Bottom side profiles for two close stations at the southern crest of the EIA: Differences and comparison with IRI-2012 and NeQuick2 for low and high solar activity

NASA Astrophysics Data System (ADS)

Perna, L.; Venkatesh, K.; Pillat, V. G.; Pezzopane, M.; Fagundes, P. R.; Ezquer, R. G.; Cabrera, M. A.

2018-01-01

Bottom side electron density profiles for two stations at the southern crest of the Equatorial Ionization Anomaly (EIA), São José dos Campos (23.1°S, 314.5°E, dip latitude 19.8°S; Brazil) and Tucumán (26.9°S, 294.6°E, dip latitude 14.0°S; Argentina), located at similar latitude and separated by only 20° in longitude, have been compared during equinoctial, winter and summer months under low (year 2008, minimum of the solar cycle 23/24) and high solar activity (years 2013-2014, maximum of the solar cycle 24) conditions. An analysis of parameters describing the bottom side part of the electron density profile, namely the peak electron density NmF2, the height hmF2 at which it is reached, the thickness parameter B0 and the shape parameter B1, is carried out. Further, a comparison of bottom side profiles and F-layer parameters with the corresponding outputs of IRI-2012 and NeQuick2 models is also reported. The variations of NmF2 at both stations reveal the absence of semi-annual anomaly for low solar activity (LSA), evidencing the anomalous activity of the last solar minimum, while those related to hmF2 show an uplift of the ionosphere for high solar activity (HSA). As expected, the EIA is particularly visible at both stations during equinox for HSA, when its strength is at maximum in the South American sector. Despite the similar latitude of the two stations upon the southern crest of the EIA, the anomaly effect is more pronounced at Tucumán than at São José dos Campos. The differences encountered between these very close stations suggest that in this sector relevant longitudinal-dependent variations could occur, with the longitudinal gradient of the Equatorial Electrojet that plays a key role to explain such differences together with the 5.8° separation in dip latitude between the two ionosondes. Furthermore at Tucumán, the daily peak value of NmF2 around 21:00 LT during equinox for HSA is in temporal coincidence with an impulsive enhancement of hmF2, showing a kind of "elastic rebound" under the action of the EIA. IRI-2012 and NeQuick2 bottom side profiles show significant deviations from ionosonde observations. In particular, both models provide a clear underestimation of the EIA strength at both stations, with more pronounced differences for Tucumán. Large discrepancies are obtained for the parameter hmF2 for HSA during daytime at São José dos Campos, where clear underestimations made by both models are observed. The shape parameter B0 is quite well described by the IRI-2012 model, with very good agreement in particular during equinox for both stations for both LSA and HSA. On the contrary, the two models show poor agreements with ionosonde data concerning the shape parameter B1.

Viscous-Inviscid Interactions over Transonic Tangentially Blown Airfoils.

DTIC Science & Technology

1982-04-01

analysis, computational fluid dynamics, asymptotic analysis. 20. RSTRACT fContinue on reverse side if neceseery and Identify by block number) A viscous...development of boundary layer and wall jet velocity profiles over airfoil. Profiles for upper surface shown in upper part of figure; lower surface values in...lower part of figure .......................... 33 6. Streanwise development of velocity profiles in wake for M = 0.75, a = 1, CJ = 0.055

Neuromodulation of chronic headaches: position statement from the European Headache Federation

PubMed Central

2013-01-01

The medical treatment of patients with chronic primary headache syndromes (chronic migraine, chronic tension-type headache, chronic cluster headache, hemicrania continua) is challenging as serious side effects frequently complicate the course of medical treatment and some patients may be even medically intractable. When a definitive lack of responsiveness to conservative treatments is ascertained and medication overuse headache is excluded, neuromodulation options can be considered in selected cases. Here, the various invasive and non-invasive approaches, such as hypothalamic deep brain stimulation, occipital nerve stimulation, stimulation of sphenopalatine ganglion, cervical spinal cord stimulation, vagus nerve stimulation, transcranial direct current stimulation, repetitive transcranial magnetic stimulation, and transcutaneous electrical nerve stimulation are extensively published although proper RCT-based evidence is limited. The European Headache Federation herewith provides a consensus statement on the clinical use of neuromodulation in headache, based on theoretical background, clinical data, and side effect of each method. This international consensus further gives recommendations for future studies on these new approaches. In spite of a growing field of stimulation devices in headaches treatment, further controlled studies to validate, strengthen and disseminate the use of neurostimulation are clearly warranted. Consequently, until these data are available any neurostimulation device should only be used in patients with medically intractable syndromes from tertiary headache centers either as part of a valid study or have shown to be effective in such controlled studies with an acceptable side effect profile. PMID:24144382

Toxicity and efficiency study of plant extracts-based bleaching agents.

PubMed

Baldea, Ioana; Olteanu, Diana Elena; Filip, Adriana Gabriela; Cenariu, Mihai; Dudea, Diana; Tofan, Alina; Alb, Camelia; Moldovan, Marioara

2017-05-01

Tooth bleaching is one of the most required dental esthetic treatments. However, it can generate side effects like oral irritation, enamel alteration, tooth sensitivity, especially caused by hydrogen peroxide, the main bleaching component of the commercial products. Therefore, development of new tooth bleaching agents, based on natural products, with comparable esthetic results and lower side effects is needed. The aim of this study was to evaluate the biological effects and bleaching efficacy of four experimental bleaching agents, derived from fruit juices, against the commercially available Opalescence (Ultradent, USA). Organic acid composition of the gels was characterized by HPLC. Bleaching efficiency was tested by spectrophotometry on composite restorative materials. Biological testing was done in vitro, on human fibroblasts. Cells were exposed to dilutions of the bleaching gel-conditioned medium. Viability was measured by MTS, apoptosis by FACS-AnnexinV FITC/Propidium iodide, NF-kB activation by western blot, malondyaldehide, and superoxide dismutase activity by spectrophotometry. All gels exhibited physical stability and dental bleaching capabilities. Experimental gels induced significantly better viability and apoptosis rates, lower lipid peroxidation, and increased antioxidant defense, compared to Opalescence. The studied experimental gel formulations exhibited a good safety profile in vitro, as well as bleaching efficiency on restorative composite materials. These data open new possibilities for the use of new natural products in dental bleaching treatments that can insure significant esthetic results and lower side effects.

Modelling of directional solidification of BSO

NASA Astrophysics Data System (ADS)

Lin, Chenting; Motakef, Shahryar

1993-03-01

A thermo-fluid model for vertical Bridgman growth of bismuth silicon oxide (BSO) as model material for semi-transparent, low thermal conductivity oxides is developed. Internal radiative heat transfer, together with convective and conductive heat transfer are considered in this model. Due to the strong internal thermal radiation within the grown crystal, the growth interface is highly convex into the melt, instead of being concave as is the case for opaque materials with the thermal conductivity of the melt larger than that of the solid. Reduction of the growth interface non-planarity through variations in the growth configuration is investigated. A furnace temperature profile consisting of a steep gradient on the melt side and shallow gradient on the solid side of the charge is found to be the most effective approach.

Synthesis and evaluation of 4-substituted piperidines and piperazines as balanced affinity μ opioid receptor (MOR) agonist/δ opioid receptor (DOR) antagonist ligands.

PubMed

Bender, Aaron M; Clark, Mary J; Agius, Michael P; Traynor, John R; Mosberg, Henry I

2014-01-15

In this letter, we describe a series of 4-substituted piperidine and piperazine compounds based on tetrahydroquinoline 1, a compound that shows balanced, low nanomolar binding affinity for the mu opioid receptor (MOR) and the delta opioid receptor (DOR). We have shown that by changing the length and flexibility profile of the side chain in this position, binding affinity is improved at both receptors by a significant degree. Furthermore, several of the compounds described herein display good efficacy at MOR, while simultaneously displaying DOR antagonism. The MOR agonist/DOR antagonist has shown promise in the reduction of negative side effects displayed by selective MOR agonists, namely the development of dependence and tolerance. Copyright © 2013 Elsevier Ltd. All rights reserved.

Development & experimental validation of a SINDA/FLUINT thermal/fluid/electrical model of a multi-tube AMTEC cell

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

Hendricks, T.J.; Borkowski, C.A.; Huang, C.

1998-01-01

AMTEC (Alkali Metal Thermal-to-Electric Conversion) cell development has received increased attention and funding in the space power community because of several desirable performance characteristics compared to current radioisotope thermoelectric generation and solar photovoltaic (PV) power generation. AMTEC cell development is critically dependent upon the ability to predict thermal, fluid dynamic and electrical performance of an AMTEC cell which has many complex thermal, fluid dynamic and electrical processes and interactions occurring simultaneously. Development of predictive capability is critical to understanding the complex processes and interactions within the AMTEC cell, and thereby creating the ability to design high-performance, cost-effective AMTEC cells. Amore » flexible, sophisticated thermal/fluid/electrical model of an operating AMTEC cell has been developed using the SINDA/FLUINT analysis software. This model can accurately simulate AMTEC cell performance at any hot side and cold side temperature combination desired, for any voltage and current conditions, and for a broad range of cell design parameters involving the cell dimensions, current collector and electrode design, electrode performance parameters, and cell wall and thermal shield emissivity. The model simulates the thermal radiation network within the AMTEC cell using RadCAD thermal radiation analysis; hot side, cold side and cell wall conductive and radiative coupling; BASE (Beta Alumina Solid Electrode) tube electrochemistry, including electrode over-potentials; the fluid dynamics of the low-pressure sodium vapor flow to the condenser and liquid sodium flow in the wick; sodium condensation at the condenser; and high-temperature sodium evaporation in the wick. The model predicts the temperature profiles within the AMTEC cell walls, the BASE tube temperature profiles, the sodium temperature profile in the artery return, temperature profiles in the evaporator, thermal energy flows throughout the AMTEC cell, all sodium pressure drops from hot BASE tubes to the condenser, the current, voltage, and power output from the cell, and the cell efficiency. This AMTEC cell model is so powerful and flexible that it is used in radioisotope AMTEC power system design, solar AMTEC power system design, and combustion-driven power system design on several projects at Advanced Modular Power Systems, Inc. (AMPS). The model has been successfully validated against actual cell experimental data and its performance predictions agree very well with experimental data on PX-5B cells and other test cells at AMPS. {copyright} {ital 1998 American Institute of Physics.}« less

Adverse Effects of the Common Treatments for Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

PubMed Central

Domecq, Juan Pablo; Prutsky, Gabriela; Mullan, Rebecca J.; Sundaresh, Vishnu; Wang, Amy T.; Erwin, Patricia J.; Welt, Corrine; Ehrmann, David; Montori, Victor M.

2013-01-01

Context: Polycystic ovary syndrome (PCOS) is common among women of childbearing age and the available pharmacological therapies have different side-effect profiles. Objective: We summarized the evidence about the side effects of oral contraceptive pills, metformin, and anti-androgens in women with PCOS. Data Source: Sources included Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL from inception through April 2011. Study Selection: We included comparative observational studies enrolling women with PCOS who received the agents of choice for at least 6 months and reported adverse effects. Data Extraction: Using a standardized, piloted, and Web-based data extraction form and working in duplicate, we abstracted data from each study and performed meta-analysis when possible. Data Synthesis: We found 22 eligible studies of which 20 were randomized. No study reported severe side effects (eg, lactic acidosis, thromboembolic episodes, liver toxicity, cancer incidence, or pregnancy loss). Meta-analysis demonstrated no significant change in weight in oral contraceptive pills or flutamide users. Indirect evidence from populations without PCOS demonstrated no increased risk of lactic acidosis with metformin, only case reports of liver toxicity with flutamide (no comparative evidence), and increased relative risk difference of venous thromboembolism with oral contraceptive pills but very low absolute risk. Evidence on mortality, cardiovascular mortality, and cancer was inconclusive. Conclusions: Drugs commonly used to treat PCOS appear to be associated with very low risk of severe adverse effects although data are extrapolated from other populations. PMID:24092830

Adverse effects of the common treatments for polycystic ovary syndrome: a systematic review and meta-analysis.

PubMed

Domecq, Juan Pablo; Prutsky, Gabriela; Mullan, Rebecca J; Sundaresh, Vishnu; Wang, Amy T; Erwin, Patricia J; Welt, Corrine; Ehrmann, David; Montori, Victor M; Murad, Mohammad Hassan

2013-12-01

Polycystic ovary syndrome (PCOS) is common among women of childbearing age and the available pharmacological therapies have different side-effect profiles. We summarized the evidence about the side effects of oral contraceptive pills, metformin, and anti-androgens in women with PCOS. Sources included Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL from inception through April 2011. We included comparative observational studies enrolling women with PCOS who received the agents of choice for at least 6 months and reported adverse effects. Using a standardized, piloted, and Web-based data extraction form and working in duplicate, we abstracted data from each study and performed meta-analysis when possible. We found 22 eligible studies of which 20 were randomized. No study reported severe side effects (eg, lactic acidosis, thromboembolic episodes, liver toxicity, cancer incidence, or pregnancy loss). Meta-analysis demonstrated no significant change in weight in oral contraceptive pills or flutamide users. Indirect evidence from populations without PCOS demonstrated no increased risk of lactic acidosis with metformin, only case reports of liver toxicity with flutamide (no comparative evidence), and increased relative risk difference of venous thromboembolism with oral contraceptive pills but very low absolute risk. Evidence on mortality, cardiovascular mortality, and cancer was inconclusive. Drugs commonly used to treat PCOS appear to be associated with very low risk of severe adverse effects although data are extrapolated from other populations.

Cyclooxygenase-2 inhibitors: promise or peril?

PubMed Central

Mengle-Gaw, Laurel J; Schwartz, Benjamin D

2002-01-01

The discovery of two isoforms of the cyclooxygenase enzyme, COX-1 and COX-2, and the development of COX-2-specific inhibitors as anti-inflammatories and analgesics have offered great promise that the therapeutic benefits of NSAIDs could be optimized through inhibition of COX-2, while minimizing their adverse side effect profile associated with inhibition of COX-1. While COX-2 specific inhibitors have proven to be efficacious in a variety of inflammatory conditions, exposure of large numbers of patients to these drugs in postmarketing studies have uncovered potential safety concerns that raise questions about the benefit/risk ratio of COX-2-specific NSAIDs compared to conventional NSAIDs. This article reviews the efficacy and safety profiles of COX-2-specific inhibitors, comparing them with conventional NSDAIDs. PMID:12467519

Laser treatment of primary axillary hyperhidrosis: a review of the literature.

PubMed

Cervantes, Jessica; Perper, Marina; Eber, Ariel E; Fertig, Raymond M; Tsatalis, John P; Nouri, Keyvan

2018-04-01

Hyperhidrosis o`ccurs when the body produces sweat beyond what is essential to maintain thermal homeostasis. The condition tends to occur in areas marked by high-eccrine density such as the axillae, palms, and soles and less commonly in the craniofacial area. The current standard of care is topical aluminum chloride hexahydrate antiperspirant (10-20%), but other treatments such as anticholinergics, clonidine, propranolol, antiadrenergics, injections with attenuated botulinum toxin, microwave technology, and surgery have been therapeutically implicated as well. Yet, many of these treatments have limited efficacy, systemic side effects, and may be linked with significant surgical morbidity, creating need for the development of new and effective therapies for controlling excessive sweating. In this literature review, we examined the use of lasers, particularly the Neodynium:Yttrium-Aluminum-Garnet (Nd:YAG) and diode lasers, in treating hyperhidrosis. Due to its demonstrated effectiveness and limited side effect profile, our review suggests that Nd:YAG laser may be a promising treatment modality for hyperhidrosis. Nevertheless, additional large, randomized controlled trials are necessary to confirm the safety and efficacy of this treatment option.

Comparison of Experimental Data and Computations Fluid Dynamics Analysis for a Three Dimensional Linear Plug Nozzle

NASA Technical Reports Server (NTRS)

Ruf, J. H.; Hagemann, G.; Immich, H.

2003-01-01

A three dimensional linear plug nozzle of area ratio 12.79 was designed by EADS Space Transportation (former Astrium Space Infrastructure). The nozzle was tested within the German National Technology Program 'LION' in a cold air wind tunnel by TU Dresden. The experimental hardware and test conditions are described. Experimental data was obtained for the nozzle without plug side wall fences at a nozzle pressure ratio of 116 and then with plug side wall fences at NPR 110. Schlieren images were recorded and axial profiles of plug wall static pressures were measured at several spanwise locations and on the plug base. Detailed CFD analysis was performed for these nozzle configurations at NPR 116 by NASA MSFC. The CFD exhibits good agreement with the experimental data. A detailed comparison of the CFD results and the experimental plug wall pressure data are given. Comparisons are made for both the without and with plug side wall fence configurations. Numerical results for density gradient are compared to experimental Schlieren images. Experimental nozzle thrust efficiencies are calculated based on the CFD results. The CFD results are used to illustrate the plug nozzle fluid dynamics. The effect of the plug side wall is emphasized.

Acoustic Measurements of Rectangular Nozzles with Bevel

NASA Technical Reports Server (NTRS)

Bridges, James E.

2012-01-01

A series of convergent rectangular nozzles of aspect ratios 2:1, 4:1, and 8:1 were constructed with uniform exit velocity profiles. Additional nozzles were constructed that extended the wide lip on one side of these nozzles to form beveled nozzles. Far-field acoustic measurements were made and analyzed, and the results presented. The impact of aspect ratio on jet noise was similar to that of enhanced mixing devices: reduction in aft, peak frequency noise with an increase in broadside, high frequency noise. Azimuthally, it was found that rectangular jets produced more noise directed away from their wide sides than from their narrow sides. The azimuthal dependence decreased at aft angles where noise decreased. The effect of temperature, keeping acoustic Mach number constant, was minimal. Since most installations would have the observer on the wide size of the nozzle, the increased high frequency noise has a deleterious impact on the observer. Extending one wide side of the rectangular nozzle, evocative of an aft deck in an installed propulsion system, increased the noise of the jet with increasing length. The impact of both aspect ratio and bevel length were relatively well behaved, allowing a simple bilinear model to be constructed relative to a simple round jet.

Assessment of IRI-2016 profile parameters over Indian low latitude station

NASA Astrophysics Data System (ADS)

Patel, Nilesh C.; Karia, Sheetal P.; Pathak, Kamlesh N.

2018-05-01

The present study reports the assessment of the bottom-side profile thickness (B0), shape (B1) and F2-peak height (hmF2) parameters IRI-2016 model over the Indian region by using digisonde observations. The digisonde data from a low latitude station Ahmedabad, (located at the crest of the northern equatorial anomaly) during three months June-2012, July-2012 and December-2012 are considered for this study. Simultaneous comparison is made on the performance of three different options `Gul-1987', `Bil-2000' and the `ABT-2009' for the bottom-side profile, three different options`AMTB2013 (AMT)', `SHU-2015 (SHU)', and `BSE-1979 (BSE)' for the hmF2 estimation in the latest available IRI-2016 to that obtained from digisonde measurements. Further, the diurnal characteristics of the B0 and B1 from digisonde measurements are also compared with those from the IRI-2016 model using the three different options.

Safety profile of bilastine: 2nd generation H1-antihistamines.

PubMed

Scaglione, F

2012-12-01

Bilastine is a new H1 antagonist with no sedative side effects, no cardiotoxic effects, and no hepatic metabolism. In addition, bilastine has proved to be effective for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Pharmacological studies have shown that bilastine is highly selective for the H1 receptor in both in vivo and in vitro studies, and with no apparent affinity for other receptors. The absorption of bilastine is fast, linear and dose-proportional; it appears to be safe and well tolerated at all doses levels in healthy population. Multiple administration of bilastine has confirmed the linearity of the kinetic parameters. The distribution in the brain is undetectable. The safety profile in terms of adverse effects is very similar to placebo in all Phase I, II and III clinical trials. Bilastine (20 mg), unlike cetirizine, does not increase alcohol effects on the CNS. Bilastine 20 mg does not increase the CNS depressant effect of lorazepam. Bilastine 20 mg is similar to placebo in the driving test. Therefore, it meets the current criteria for medication used in the treatment of allergic rhinitis and urticaria.

Violence between Therapy-Seeking Veterans and Their Partners: Prevalence and Characteristics of Nonviolent, Mutually Violent, and One-Sided Violent Couples

ERIC Educational Resources Information Center

Teten, Andra L.; Sherman, Michelle D.; Han, Xiaotong

2009-01-01

Among male veterans and their female partners seeking therapy for relationship issues, three violence profiles were identified based on self-reports of physical violence: nonviolent, in which neither partner reported perpetrating physical violence (44%); one-sided violent, in which one partner reported perpetrating violence (30%); and mutually…

Ocular Hypotensive Response in Nonhuman Primates of (8R)-1-[(2S)-2-Aminopropyl]-8,9-dihydro-7H-pyrano[2,3-g]indazol-8-ol a Selective 5-HT2 Receptor Agonist.

PubMed

May, Jesse A; Sharif, Najam A; McLaughlin, Marsha A; Chen, Hwang-Hsing; Severns, Bryon S; Kelly, Curtis R; Holt, William F; Young, Richard; Glennon, Richard A; Hellberg, Mark R; Dean, Thomas R

2015-11-25

Recently, it has been reported that 5-HT2 receptor agonists effectively reduce intraocular pressure (IOP) in a nonhuman primate model of glaucoma. Although 1-[(2S)-2-aminopropyl]indazol-6-ol (AL-34662) was shown to have good efficacy in this nonhuman primate model of ocular hypertension as well as a desirable physicochemical and permeability profile, subsequently identified cardiovascular side effects in multiple species precluded further clinical evaluation of this compound. Herein, we report selected structural modifications that resulted in the identification of (8R)-1-[(2S)-2-aminopropyl]-8,9-dihydro-7H-pyrano[2,3-g]indazol-8-ol (13), which displayed an acceptable profile to support advancement for further preclinical evaluation as a candidate for proof-of-concept studies in humans.

Effect-directed analysis of cold-pressed hemp, flax and canola seed oils by planar chromatography linked with (bio)assays and mass spectrometry.

PubMed

Teh, Sue-Siang; Morlock, Gertrud E

2015-11-15

Cold-pressed hemp, flax and canola seed oils are healthy oils for human consumption as these are rich in polyunsaturated fatty acids and bioactive phytochemicals. However, bioactive information on the food intake side is mainly focused on target analysis. For more comprehensive information with regard to effects, single bioactive compounds present in the seed oil extracts were detected by effect-directed assays, like bioassays or an enzymatic assay, directly linked with chromatography and further characterized by mass spectrometry. This effect-directed analysis is a streamlined method for the analysis of bioactive compounds in the seed oil extracts. All effective compounds with regard to the five assays or bioassays applied were detected in the samples, meaning also bioactive breakdown products caused during oil processing, residues or contaminants, aside the naturally present bioactive phytochemicals. The investigated cold-pressed oils contained compounds that exert antioxidative, antimicrobial, acetylcholinesterase inhibitory and estrogenic activities. This effect-directed analysis can be recommended for bioactivity profiling of food to obtain profound effect-directed information on the food intake side. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-01-01

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

Study of the kinematic and load sharing properties of wormgearing with non-symmetric tooth profiles

NASA Technical Reports Server (NTRS)

Sun, D. C.; Yuan, Qin

1995-01-01

The geometry of non-symmetric tooth profiles, i.e. tooth profiles with different pressure angles on the two sides of the tooth, is studied. A feasible non-symmetric tooth profile for application in helicopter transmissions is laid out as the best compromise among several conflicting factors. The non-symmetric tooth profile is then compared with the symmetric tooth profile studied previously. Based on the detailed comparisons it is concluded that the use of the non-symmetric tooth profile would severely limit the face width of the worm, consequently reduce the number of meshing teeth and cause much higher normal load on the individual gear teeth.

Centrifuge training program with "push-pull" elements.

PubMed

Mikuliszyn, Romuald; Zebrowski, Mariusz; Kowalczuk, Krzysztof

2005-05-01

Pilots of fighter aircraft are often exposed to maneuvers that produce negative acceleration (-Gz) immediately followed by positive acceleration (+Gz). This sequence has been found to reduce tolerance to +Gz, a phenomenon known as the "push-pull" effect. We devised a centrifuge training program to demonstrate this phenomenon to pilots. The centrifuge of the Military Institute of Aviation Medicine in Warsaw, Poland, was modified in 1996 to allow active positioning of the gondola during rotation. Head-down position of -6 degrees to -40 degrees were used to produce relative -Gz (r-Gz) in a range down to 0.2. As a side effect, this produces Gy acceleration between -1.3 Gy and -1.6 Gy. Pilots completed normal centrifuge training, including a relaxed, gradual-onset run and three rapid-onset runs. They were then exposed to a profile that included a series of push-pull exposures where r-Gz was followed by +Gz with stepwise increases in the latter from +2.5 to +5 Gz. The final profile was a simulated aerial combat maneuver with push-pull elements. The trainees expressed surprise at the push-pull effect, which forced them to begin an anti-G straining maneuver at lower levels than normal. They complained about the presence of the Gy, which rarely occurs in aircraft. This type of profile appears useful for training pilots about the push-pull phenomenon. After collection of additional data, the profiles may be refined.

A Healthy Balance of Plasma Cholesterol by a Novel Annurca Apple-Based Nutraceutical Formulation: Results of a Randomized Trial.

PubMed

Tenore, Gian Carlo; Caruso, Domenico; Buonomo, Giuseppe; D'Avino, Maria; Campiglia, Pietro; Marinelli, Luciana; Novellino, Ettore

2017-03-01

Cardiovascular diseases are nowadays preferential targets of preventive medicine through a straightforward therapy on lipid profile. However, statins, the first-line lipid-lowering drug therapy, specifically act on low-density lipoprotein cholesterol (LDL-C), having a modest effect on plasma high-density lipoprotein cholesterol (HDL-C) concentrations. Today, a number of novel HDL-targeted therapies are emerging, along with unexpected side effects. Thus, novel and possibly safe substances, able to correct impaired lipid profile in humans, are still in great demand. Herein, based on encouraging clinical data, we formulated a nutraceutical product (AppleMetS ® , AMS), based on a polyphenolic extract from Annurca apple, and demonstrated that two capsules a day of AMS, after one month, have a LDL-C lowering outcome equivalent to 40 mg of simvastatin or 10 mg of atorvastatin. Nevertheless, different from statin-based therapy, AMS exerted a notable effect on HDL (+49.2%). Based on the trial results, we can assert that AMS formulation could effectively integrate the current therapeutic arsenal to correct impaired lipid profile in humans. Specifically, AMS may be considered a complementary and/or alternative safe substance suitable for the treatment of mildly hypercholesterolemic subjects who do not present occurrence of atheromatous plaques yet.

Effect of Olanzapine on Clinical and Polysomnography Profiles in Patients with Schizophrenia

PubMed Central

Sarkar, Sukanto; Nizamie, S. Haque

2018-01-01

Acute and short-term administration of olanzapine has a favorable effect on sleep in schizophrenia patients. This study aimed to clarify the effect of olanzapine on polysomnographic profiles of schizophrenia patients during the acute phase of illness after controlling for previous drug exposure. Twenty-five drug-naïve or drug-free schizophrenia patients were assessed at baseline and after six weeks of olanzapine treatment on Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), and Udvalg for Kliniske Undersogelser (UKU) side-effect rating scale and a whole-night polysomnography; fifteen patients completed the study. There was a significant reduction in all psychopathological variables with maximum reduction in PANSS total, BPRS total, and PANSS positive scores. A significant increase in total sleep time (TST), sleep efficiency (SE), nonrapid eye movement (NREM) stage 1 duration, stage 3 duration, stage 4 duration, and stage 4 percentage of TST, number of rapid eye movement (REM) periods, REM duration, and REM percentage of TST was observed. REM latency at baseline inversely predicted the reduction in BPRS total and PANSS total and positive scores. In summary, short-term treatment with olanzapine produced significant improvement in clinical and polysomnography profiles of patients with schizophrenia with shorter REM latency predicting a good clinical response. PMID:29675276

A Healthy Balance of Plasma Cholesterol by a Novel Annurca Apple-Based Nutraceutical Formulation: Results of a Randomized Trial

PubMed Central

Tenore, Gian Carlo; Caruso, Domenico; Buonomo, Giuseppe; D'Avino, Maria; Campiglia, Pietro; Marinelli, Luciana

2017-01-01

Abstract Cardiovascular diseases are nowadays preferential targets of preventive medicine through a straightforward therapy on lipid profile. However, statins, the first-line lipid-lowering drug therapy, specifically act on low-density lipoprotein cholesterol (LDL-C), having a modest effect on plasma high-density lipoprotein cholesterol (HDL-C) concentrations. Today, a number of novel HDL-targeted therapies are emerging, along with unexpected side effects. Thus, novel and possibly safe substances, able to correct impaired lipid profile in humans, are still in great demand. Herein, based on encouraging clinical data, we formulated a nutraceutical product (AppleMetS®, AMS), based on a polyphenolic extract from Annurca apple, and demonstrated that two capsules a day of AMS, after one month, have a LDL-C lowering outcome equivalent to 40 mg of simvastatin or 10 mg of atorvastatin. Nevertheless, different from statin-based therapy, AMS exerted a notable effect on HDL (+49.2%). Based on the trial results, we can assert that AMS formulation could effectively integrate the current therapeutic arsenal to correct impaired lipid profile in humans. Specifically, AMS may be considered a complementary and/or alternative safe substance suitable for the treatment of mildly hypercholesterolemic subjects who do not present occurrence of atheromatous plaques yet. PMID:28296588

Geochemistry of Red Mountain Creek, Colorado, under low-flow conditions, August 2002

USGS Publications Warehouse

Runkel, Robert L.; Kimball, Briant A.; Walton-Day, Katherine; Verplanck, Philip L.

2005-01-01

Red Mountain Creek, an acid mine drainage stream in southwestern Colorado, was the subject of a synoptic study conducted in August 2002. During the synoptic study, a solution containing lithium chloride was injected continuously to allow for the calculation of streamflow using the tracer-dilution method. Synoptic water-quality samples were collected from 48 stream sites and 29 inflow locations along a 5.4-kilometer study reach. Data from the study provide profiles of pH, concentration, and mass load with a high degree of spatial resolution. Despite the presence of 10 circumneutral inflows, pH remained below 3.4 at all stream sites. Concentration profiles indicate that dissolved concentrations of aluminum, cadmium, copper, lead, and zinc exceed chronic aquatic-life standards established by the State of Colorado along the entire study reach. Comparison of total recoverable and dissolved concentrations suggests that most constituents were transported conservatively. Exceptions to this pattern include arsenic, iron, molybdenum, and vanadium, four constituents that were subject to precipitation and(or) sorption reactions as the addition of a circumneutral tributary resulted in a slight increase in instream pH. Evaluation of data from the 29 inflow locations indicates a sharp contrast between the east and west sides of the watershed; inflows from the east side have high constituent concentrations and acidic pH, whereas inflows from the west side have lower concentrations and generally higher pH. Loading profiles, the product of streamflow and concentration, are used to rank potential sources of metals and acidity within the watershed. Four sources account for 83, 72, 70, 69, 64, and 61 percent of the aluminum, iron, arsenic, zinc, copper, and cadmium loading within the study reach, respectively. All four sources appear to be the result of surface inflows that have been affected by mining activities. The relatively small number of major sources and the fact that they are attributable to surface inflows are two factors that may facilitate effective remediation.

Effect of Stepwise Doping on Lifetime and Efficiency of Blue and White Phosphorescent Organic Light Emitting Diodes.

PubMed

Lee, Song Eun; Lee, Ho Won; Lee, Seok Jae; Koo, Ja-ryong; Lee, Dong Hyung; Yang, Hyung Jin; Kim, Hye Jeong; Yoon, Seung Soo; Kim, Young Kwan

2015-02-01

We investigated a light emission mechanism of blue phosphorescent organic light emitting diodes (PHOLEDs), using a stepwise doping profile of 2, 8, and 14 wt.% within the emitting layer (EML). We fabricated several blue PHOLEDs with phosphorescent blue emitter iridium(III) bis[(4,6-difluorophenyl)-pyridinato-N,C2]picolinate doped in N,N'-dicarbazolyl-3,5-benzene as a p-type host material. A blue PHOLED with the highest doping concentration as part of the EML close to an electron transporting layer showed a maximum luminous efficiency of 20.74 cd/A, and a maximum external quantum efficiency of 10.52%. This can be explained by effective electron injection through a highly doped EML side. Additionally, a white OLED based on the doping profile was fabricated with two thin red EMLs within a blue EML maintaining a thickness of 30 nm for the entire EML. Keywords: Blue Phosphorescent Organic Light Emitting Diodes, Stepwise Doping Structure, Charge Trapping Effect.

St. John's wort: a new alternative for depression?

PubMed

Josey, E S; Tackett, R L

1999-03-01

The primary purpose of this article is to review the existing literature concerning the therapeutic uses, adverse effects, and possible drug interactions of St. John's wort (Hypericum perforatum) as compared to other antidepressant medications. Reference material was obtained through database searches with time restrictions of 1985 to the present. Studies selected were those written in the English language which compared the role of St. John's wort, tricyclic antidepressants, monoamine oxidase inhibitors, and serotonin-selective reuptake inhibitors in the treatment of depression. Other studies were selected based on their evaluation of the safety and efficacy of St. John's wort as an antidepressant for a minimum of four weeks. A review of existing literature recognized nine clinical trials that reported the efficacy of St. John's wort as compared to placebo and to other antidepressant medications. Of these nine, four controlled studies were chosen based upon their large patient populations and their consistency in brand and dosage of St. John's wort used. These four studies demonstrated that St. John's wort was as effective as other antidepressant medications and more effective than placebo, as the clinical symptoms of depression greatly decreased upon administration of H. perforatum. The side-effect profile of H. perforatum at this time appears to be superior to any current U.S.-approved antidepressant medication. From the existing literature, St. John's wort appears to be a safe and effective alternative in the treatment of depression. Tricylic antidepressants and monoamine oxidase inhibitors can produce serious cardiac side-effects, such as tachycardia and postural hypotension, and many unwanted anticholinergic side-effects, including dry mouth and constipation. St. John's wort has proven to be free of any cardiac, as well as anticholinergic, side-effects normally seen with antidepressant medications. Based upon limited studies, St. John's wort appears to be an acceptable alternative to traditional antidepressant therapy, although trials on a larger scale are warranted in this area. Hypericum is available to the lay public as an over-the-counter preparation and may be misused if not fully understood.

Role of preemptive tapentadol in reduction of postoperative analgesic requirements after laparoscopic cholecystectomy

PubMed Central

Yadav, Ghanshyam; Jain, Gaurav; Samprathi, Abhishek; Baghel, Annavi; Singh, Dinesh Kumar

2016-01-01

Background and Aims: Poorly managed acute postoperative pain may result in prolonged morbidity. Various pharmacotherapies have targeted this, but research on an ideal preemptive analgesic continues, taking into account drug-related side effects. Considering the better tolerability profile of tapentadol, we assessed its role as a preemptive analgesic in the reduction of postoperative analgesic requirements, after laparoscopic cholecystectomy. Material and Methods: In a prospective-double-blinded fashion, sixty patients posted for above surgery, were randomized to receive tablet tapentadol 75 mg (Group A) or starch tablets (Group B) orally, an hour before induction of general anesthesia. Perioperative analgesic requirement, time to first analgesia, pain, and sedation score were compared for first 24 h during the postoperative period and analyzed by one-way analysis of variance test. A P < 0.05 was considered significant. Results: Sixty patients were analyzed. The perioperative analgesic requirement was significantly lower in Group A. Verbal numerical score was significantly lower in Group A at the time point, immediately after shifting the patient to the postanesthesia care unit. Ramsay sedation scores were similar between the groups. No major side effects were observed except for nausea and vomiting in 26 cases (10 in Group A, 16 in Group B). Conclusion: Single preemptive oral dose of tapentadol (75 mg) is effective in reducing perioperative analgesic requirements and acute postoperative pain, without added side effects. It could be an appropriate preemptive analgesic, subjected to future trials concentrating upon its dose-response effects. PMID:28096581

Paclitaxel Nano-Delivery Systems: A Comprehensive Review

PubMed Central

Ma, Ping; Mumper, Russell J.

2013-01-01

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

[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.

Emergency contraception review: evidence-based recommendations for clinicians

PubMed Central

Cleland, Kelly; Raymond, Elizabeth G.; Westley, Elizabeth; Trussell, James

2014-01-01

Several options for emergency contraception are available in the United States. This article describes each method, including efficacy, mode of action, safety, side effect profile and availability. The most effective emergency contraceptive is the copper IUD, followed by ulipristal acetate and levonorgestrel pills. Levonorgestrel is available for sale without restrictions, while ulipristal acetate is available with prescription only, and the copper IUD must be inserted by a clinician. Although EC pills have not been shown to reduce pregnancy or abortion rates at the population level, they are an important option for individual women seeking to prevent pregnancy after sex. PMID:25254919

New antibiotics for healthcare-associated pneumonia.

PubMed

Neuner, Elizabeth A; Ritchie, David J; Micek, Scott T

2009-02-01

Current antibiotics available for the treatment of healthcare-associated pneumonia (HCAP) may result in clinical failure due to resistance development, side effect intolerance, or poor pharmacokinetic-pharmacodynamic profiles. New agents active against common HCAP pathogens are needed. The mechanism of action, spectrum of activity, pharmacokinetics, adverse effects, and clinical efficacy of seven new agents in clinical development or recently approved with either methicillin-resistant Staphylococcus aureus (MRSA) or pseudomonal activity are reviewed. They include doripenem, a new antipseudomonal carbapenem; ceftobiprole and ceftaroline, two anti-MRSA cephalosporins; iclaprim, a selective dihydrofolate reductase antagonist; and three glycopeptides, dalbavancin, telavancin, and oritavancin.

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.

Comparison of the effects of the GABAB receptor positive modulator BHF177 and the GABAB receptor agonist baclofen on anxiety-like behavior, learning, and memory in mice

PubMed Central

Li, Xia; Risbrough, Victoria B.; Cates-Gatto, Chelsea; Kaczanowska, Katarzyna; Finn, M. G.; Roberts, Amanda J; Markou, Athina

2013-01-01

γ-Aminobutyric acid B (GABAB) receptor activation is a potential therapeutic approach for the treatment of drug addiction, pain, anxiety, and depression. However, full agonists of this receptor induce side-effects, such as sedation, muscle relaxation, tolerance, and cognitive disruption. Positive allosteric modulators (PAMs) of the GABAB receptor may have similar therapeutic effects as agonists with superior side-effect profiles. The present study behaviorally characterized N-([1R,2R,4S]-bicyclo[2.2.1]hept-2-yl)-2-methyl-5-(4-[trifluoromethyl]phenyl)-4-pyrimidinamine (BHF177), a GABAB receptor PAM, in mouse models of anxiety-like behavior, learning and memory. In addition, the effects of BHF177 were compared with the agonist baclofen. Unlike the anxiolytic chlordiazepoxide, baclofen (0.5, 1.5, and 2.5 mg/kg, intraperitoneally) and BHF177 (10, 20, and 40 mg/kg, orally) had no effect on anxiety-like behavior in the elevated plus maze, light/dark box, or the Vogel conflict test. Baclofen increased punished drinking in the Vogel conflict test, however this effect may be attributable to analgesic actions of baclofen. At the highest dose tested (2.5 mg/kg), baclofen-treated mice exhibited sedation-like effects (i.e., reduced locomotor activity) across many of the tests, whereas BHF177-treated mice exhibited no sedation-like effects. BHF177 exhibited pro-convulsion properties only in mice, but not in rats, indicating that this effect may be species-specific. At doses that were not sedative or pro-convulsant, baclofen and BHF177 had no selective effects on fear memory retrieval in contextual and cued fear conditioning or spatial learning and memory in the Barnes maze. These data suggest that BHF177 has little sedative activity, no anxiolytic-like profile, and minimal impairment of learning and memory in mice. PMID:23376712

Preventing Terrorism in the Long Term: The Disutility of Racial Profiling in Preventing Crime and the Counterproductive Nature of Ethnic and Religious Profiling in Counterterrorism Policing

DTIC Science & Technology

2009-12-01

enforcement officers, many of whom are now or have been active participants in CT-operations, use in identifying suspicious behavior and building...provide benefits that are greater than the costs of using profiling as part of an overall counterterrorism strategy. 2 A. IMPORTANCE: TAKING SIDES ON...that the benefits of ethnic and religious profiling are trumped by the social costs and consequences of its use . More specifically, the ethnic and

Risk factors for non-adherence to antidepressant treatment in patients with mood disorders.

PubMed

De las Cuevas, Carlos; Peñate, Wenceslao; Sanz, Emilio J

2014-01-01

Adherence to antidepressant therapy by patients with depressive disorders is essential not only to achieve a positive patient outcome but also to prevent a relapse. The aim of this study was to identify potential modelling factors influencing adherence to antidepressant treatment by patients with mood disorders in the community mental health care setting A total of 160 consecutive psychiatric outpatients attending two Community Mental Health Centres on Tenerife Island between September 2011 and May 2012 were asked to participate in the study; of these, 145 accepted. The Morisky self-report scale was used to assess adherence. The potential predictors examined included socio-demographic, clinical and therapeutic variables. The Clinical Global Impression-Severity and -Improvement scales and the Beck Depression Inventory were used for clinical assessment. Drug treatment side-effects were assessed using the "Self-report Antidepressant Side-Effect Checklist." All participants were also asked to complete the "Drug Attitude Inventory" (DAI), "Beliefs about Medicine Questionnaire" (BMQ), and "Leeds Attitude towards concordance Scale". Discriminant analyses were performed to predict non-adherence. There was no clear correlation between adherence and the socio-demographic variables examined, but adherence was related to a positive attitude of the patients towards his/her treatment (DAI) and low scores in the BMQ-Harm and -Concern subscales. Non-adherence was also related to an increasing severity of depression and to the presence and severity of side-effects. Among our study cohort, the profiles of adherent patients to antidepressant treatment were more closely associated with each patient's attitudes and beliefs than to objective socio-demographic variables. The severity of depression played a relevant role in adherence, but whether this role is direct or an interaction with several concurrent factors is not yet clear. Side-effects were also closely related to adherence, as conditioned by frequent polypharmacy.

RASopathic Skin Eruptions during Vemurafenib Therapy

PubMed Central

Rinderknecht, Jeannine D.; Goldinger, Simone M.; Rozati, Sima; Kamarashev, Jivko; Kerl, Katrin; French, Lars E.

2013-01-01

Purpose Vemurafenib is a potent inhibitor of V600 mutant BRAF with significant impact on progression-free and overall survival in advanced melanoma. Cutaneous side effects are frequent. This single-center observational study investigates clinical and histological features of these class-specific cutaneous adverse reactions. Patients and Methods Patients were all treated with Vemurafenib 960 mg b.i.d. within local ethic committees approved clinical trials. All skin reactions were collected and documented prospectively. Cutaneous reactions were classified by reaction pattern as phototoxic and inflammatory, hair and nail changes, keratinocytic proliferations and melanocytic disorders. Results Vemurafenib was well tolerated, only in two patients the dose had to be reduced to 720 mg due to arthralgia. 26/28 patients (93%) experienced cutaneous side effects. Observed side effects included UVA dependent photosensitivity (n = 16), maculopapular exanthema (n = 14), pruritus (n = 8), folliculitis (n = 5), burning feet (n = 3), hair thinning (mild alopecia) (n = 8), curly hair (n = 2) and nail changes (n = 2). Keratosis pilaris and acanthopapilloma were common skin reactions (n = 12/n = 13), as well as plantar hyperkeratosis (n = 4), keratoacanthoma (n = 5) and invasive squamous cell carcinoma (n = 4). One patient developed a second primary melanoma after more than 4 months of therapy (BRAF and RAS wild type). Conclusion Vemurafenib has a broad and peculiar cutaneous side effect profile involving epidermis and adnexa overlapping with the cutaneous manifestations of genetic diseases characterized by activating germ line mutations of RAS (RASopathy). They must be distinguished from allergic drug reaction. Regular skin examination and management by experienced dermatologists as well as continuous prophylactic photo protection including an UVA optimized sun screen is mandatory. PMID:23516541

Menopausal Symptom Relief and Side Effects Experienced by Women Using Bioidentical Hormone Replacement Therapy and Synthetic Conjugated Equine Estrogen and/or Progestin Hormone Replacement Therapy, Part 1.

PubMed

Deleruyelle, Laura J

2016-01-01

The use of compounded bioidentical hormone replacement therapy by menopausal women has become a popular alternative to traditional synthetic conjugated equine estrogen and progestin hormone replacement therapy due to safety concerns raised by recent studies. However, due to the lack of randomized, large-scale trials to evaluate the efficacy and side-effect profile of compounded bioidentical hormone replacement therapy many healthcare providers are reluctant to prescribe such therapy. The purpose of this study was to compare women's menopausal symptom relief and side effects experienced when using compounded bioidentical hormone replacement therapy and traditional hormone replacement therapy. A descriptive comparative design was used. Inferential and descriptive statistical procedures including a paired difference t -test, two-sample t -test, and f tests (percentage, mean, standard deviation, frequency) were run on the Statistical Package for the Social Sciences. The framework used to guide this study was Lenz and Pugh's Theory of Unpleasant Symptoms. Surveys were distributed once to a convenient sample of women aged 35 and older when they dropped off or picked up their prescriptions at a pharmacy. Of the 216 surveys distributed, 70 were returned from those women taking compounded bioidentical hormone replacement therapy and 53 from traditional hormone replacement therapy. The survey contained 15 questions pertaining to age, duration of hormone replacement therapy, type and formulation of hormone replacement therapy, reasons for initiating hormone replacement therapy, symptoms before and one month after hormone replacement therapy, and side effects related to hormone replacement therapy. The results of this study will be summarized in forthcoming articles in this series. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Diuretics in heart failure: practical considerations.

PubMed

Basraon, Jagroop; Deedwani, Prakash C

2012-09-01

This review discusses the role of diuretics in heart failure by focusing on different classifications and mechanisms of action. Pharmacodynamic and pharmacokinetic properties of diuretics are elucidated. The predominant discussion highlights the use of loop diuretics, which are the most commonly used drugs in heart failure. Different methods of using this therapy in different settings along with a comprehensive review of the side-effect profile are highlighted. Special situations necessitating adjustment and the phenomenon of diuretic resistance are explained. Copyright © 2012. Published by Elsevier Inc.

Low-molecular-weight heparins: differential characterization/physical characterization.

PubMed

Guerrini, Marco; Bisio, Antonella

2012-01-01

Low-molecular-weight heparins (LMWHs), derived from unfractionated heparin (UFH) through different depolymerization processes, have advantages with respect to the parent heparin in terms of pharmacokinetics, convenience of administration, and reduced side effects. Each LMWH can be considered as an independent drug with its own activity profile, placing significance on their biophysical characterization, which will also enable a better understanding of their structure-function relationship. Several chemical and physical methods, some involving sample modification, are now available and are reviewed.

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

Fenalti, Gustavo; Zatsepin, Nadia A.; Betti, Cecilia

Bi-functional μ- and δ- opioid receptor (OR) ligands are potential therapeutic alternatives to alkaloid opiate analgesics with diminished side effects. We solved the structure of human δ-OR bound to the bi-functional δ-OR antagonist and μ-OR agonist tetrapeptide H-Dmt-Tic-Phe-Phe-NH 2 (DIPP-NH 2) by serial femtosecond crystallography, revealing a cis-peptide bond between H-Dmt and Tic. In summary, the observed receptor-peptide interactions are critical to understand the pharmacological profiles of opioid peptides, and to develop improved analgesics.

The PLATO trial: do you believe in magic?

PubMed

Serebruany, Victor L; Atar, Dan

2010-04-01

The PLATO trial revealed a remarkable advantage of ticagrelor over clopidogrel in ACS patients. Unless the regulatory authorities discover serious flaws with the study, which is unlikely, the drug may substantially change the present landscape of oral antiplatelet therapy, especially in high-risk patients. Despite a somewhat unfavourable safety profile, ticagrelor has a lot of room to compensate for these well-defined side effects based on a documented absolute mortality reduction, solid prevention of MI, and convincing pattern of benefit growing over time.

Sedimentary processes on the Mekong subaqueous delta: Clay mineral and geochemical analysis

NASA Astrophysics Data System (ADS)

Xue, Zuo; Paul Liu, J.; DeMaster, Dave; Leithold, Elana L.; Wan, Shiming; Ge, Qian; Nguyen, Van Lap; Ta, Thi Kim Oanh

2014-01-01

Sedimentary processes on the inner Mekong Shelf were investigated by examining the characteristics of sediments sampled in gravity cores at 15 locations, including grain size, clay mineralogy, sediment accumulation rates, and the elemental and stable carbon isotopic composition of organic matter (atomic C/N ratios and δ13C). Deltaic deposits exhibit contrasting characteristics along different sides of the delta plain (South China Sea, SCS hereafter, to the east and Gulf of Thailand, GOT hereafter, to the west) as well as on and off the subaqueous deltaic system. On one hand, cores recovered from the subaqueous delta in the SCS/GOT are consisted of poorly/well sorted sediments with similar/different clay mineral assemblage with/from Mekong sediments. Excess 210Pb profiles, supported by 14C chronologies, indicate either "non-steady" (SCS side) or "rapid accumulation" (GOT side) processes on the subaqueous delta. The δ13C and C/N ratio indicate a mixture of terrestrial and marine-sourced organic matter in the deltaic sediment. On the other hand, cores recovered from areas with no deltaic deposits or seaward of the subaqueous delta show excess 210Pb profiles indicating "steady-state" accumulation with a greater proportion of marine-sourced organic matter. Core analysis's relevance with local depositional environment and previous acoustic profiling are discussed.

Using UAVSAR to Estimate Creep Along the Superstition Hills Fault, Southern California

NASA Astrophysics Data System (ADS)

Donnellan, A.; Parker, J. W.; Pierce, M.; Wang, J.

2012-12-01

UAVSAR data were first acquired over the Salton Trough region, just north of the Mexican border in October 2009. Second passes of data were acquired on 12 and 13 April 2010, about one week following the 5 April 2010 M 7.2 El Mayor - Cucapah earthquake. The earthquake resulted in creep on several faults north of the main rupture, including the Yuha, Imperial, and Superstition Hills faults. The UAVSAR platform acquires data about every six meters in swaths about 15 km wide. Tropospheric effects and residual aircraft motion contribute to error in the estimation of surface deformation in the Repeat Pass Interferometry products. The Superstition Hills fault shows clearly in the associated radar interferogram; however, error in the data product makes it difficult to infer deformation from long profiles that cross the fault. Using the QuakeSim InSAR Profile tool we extracted line of site profiles on either side of the fault delineated in the interferogram. We were able to remove much of the correlated error by differencing profiles 250 m on either side of the fault. The result shows right-lateral creep of 1.5±.4 mm along the northern 7 km of the fault in the interferogram. The amount of creep abruptly changes to 8.4±.4 mm of right lateral creep along at least 9 km of the fault covered in the image to the south. The transition occurs within less than 100 m along the fault. We also extracted 2 km long line of site profiles perpendicular to this section of the fault. Averaging these profiles shows a step across the fault of 14.9±.3 mm with greater creep on the order of 20 mm on the northern two profiles and lower creep of about 10 mm on the southern two profiles. Nearby GPS stations P503 and P493 are consistent with this result. They also confirm that the creep event occurred at the time of the El Mayor - Cucapah earthquake. By removing regional deformation resulting from the main rupture we were able to invert for the depth of creep from the surface. Results indicate that the slip occurred from the surface to 10-20 km, not shallowly, as previously suggested.

Pressure- and buoyancy-driven thermal convection in a rectangular enclosure

NASA Technical Reports Server (NTRS)

Spradley, L. W.; Churchill, S. W.

1975-01-01

Results are presented for unsteady laminar thermal convection in compressible fluids at various reduced levels of gravity in a rectangular enclosure which is heated on one side and cooled on the opposite side. The results were obtained by solving numerically the equations of conservation for a viscous, compressible, heat-conducting, ideal gas in the presence of a gravitational body force. The formulation differs from the Boussinesq simplification in that the effects of variable density are completely retained. A conservative, explicit, time-dependent, finite-difference technique was used and good agreement was found for the limited cases where direct comparison with previous investigations was possible. The solutions show that the thermally induced motion is acoustic in nature at low levels of gravity and that the unsteady-state rate of heat transfer is thereby greatly enhanced relative to pure conduction. The nonlinear variable density profile skews the streamlines towards the cooler walls but is shown to have little effect on the steady-state isotherms.

Predicting NonInertial Effects with Algebraic Stress Models which Account for Dissipation Rate Anisotropies

NASA Technical Reports Server (NTRS)

Jongen, T.; Machiels, L.; Gatski, T. B.

1997-01-01

Three types of turbulence models which account for rotational effects in noninertial frames of reference are evaluated for the case of incompressible, fully developed rotating turbulent channel flow. The different types of models are a Coriolis-modified eddy-viscosity model, a realizable algebraic stress model, and an algebraic stress model which accounts for dissipation rate anisotropies. A direct numerical simulation of a rotating channel flow is used for the turbulent model validation. This simulation differs from previous studies in that significantly higher rotation numbers are investigated. Flows at these higher rotation numbers are characterized by a relaminarization on the cyclonic or suction side of the channel, and a linear velocity profile on the anticyclonic or pressure side of the channel. The predictive performance of the three types of models are examined in detail, and formulation deficiencies are identified which cause poor predictive performance for some of the models. Criteria are identified which allow for accurate prediction of such flows by algebraic stress models and their corresponding Reynolds stress formulations.

Effects of internal structure on equilibrium of field-reversed configuration plasma sustained by rotating magnetic field

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

Yambe, Kiyoyuki; Inomoto, Michiaki; Okada, Shigefumi

The effects of an internal structure on the equilibrium of a field-reversed configuration (FRC) plasma sustained by rotating magnetic field is investigated by using detailed electrostatic probe measurements in the FRC Injection Experiment apparatus [S. Okada, et al., Nucl. Fusion. 45, 1094 (2005)]. An internal structure installed axially on the geometrical axis, which simulates Ohmic transformer or external toroidal field coils on the FRC device, brings about substantial changes in plasma density profile. The internal structure generates steep density-gradients not only on the inner side but on the outer side of the torus. The radial electric field is observed tomore » sustain the ion thermal pressure-gradient in the FRC without the internal structure; however, the radial electric field is not sufficient to sustain the increased ion thermal pressure-gradient in the FRC with the internal structure. Spontaneously driven azimuthal ion flow will be accountable for the imbalance of the radial pressure which is modified by the internal structure.« less

Minireview: Challenges and Opportunities in Development of PPAR Agonists

PubMed Central

Bortolini, Michele; Tadayyon, Moh; Bopst, Martin

2014-01-01

The clinical impact of the fibrate and thiazolidinedione drugs on dyslipidemia and diabetes is driven mainly through activation of two transcription factors, peroxisome proliferator-activated receptors (PPAR)-α and PPAR-γ. However, substantial differences exist in the therapeutic and side-effect profiles of specific drugs. This has been attributed primarily to the complexity of drug-target complexes that involve many coregulatory proteins in the context of specific target gene promoters. Recent data have revealed that some PPAR ligands interact with other non-PPAR targets. Here we review concepts used to develop new agents that preferentially modulate transcriptional complex assembly, target more than one PPAR receptor simultaneously, or act as partial agonists. We highlight newly described on-target mechanisms of PPAR regulation including phosphorylation and nongenomic regulation. We briefly describe the recently discovered non-PPAR protein targets of thiazolidinediones, mitoNEET, and mTOT. Finally, we summarize the contributions of on- and off-target actions to select therapeutic and side effects of PPAR ligands including insulin sensitivity, cardiovascular actions, inflammation, and carcinogenicity. PMID:25148456

Early and Late Onset Side Effects of Photodynamic Therapy

PubMed Central

Borgia, Francesco; Giuffrida, Roberta; Caradonna, Emanuela; Guarneri, Fabrizio; Cannavò, Serafinella P.

2018-01-01

Photodynamic Therapy (PDT) is a non-invasive treatment successfully used for neoplastic, inflammatory and infectious skin diseases. One of its strengths is represented by the high safety profile, even in elderly and/or immuno-depressed subjects. PDT, however, may induce early and late onset side effects. Erythema, pain, burns, edema, itching, desquamation, and pustular formation, often in association with each other, are frequently observed in course of exposure to the light source and in the hours/days immediately after the therapy. In particular, pain is a clinically relevant short-term complication that also reduces long-term patient satisfaction. Rare complications are urticaria, contact dermatitis at the site of application of the photosensitizer, and erosive pustular dermatosis. Debated is the relationship between PDT and carcinogenesis: the eruptive appearance of squamous cell carcinoma (SCC) in previously treated areas has been correlated to a condition of local and/or systemic immunosuppression or to the selection of PDT-resistant SCC. Here we review the literature, with particular emphasis to the pathogenic hypotheses underlying these observations. PMID:29382133

Adverse events associated with apremilast use and withdrawal for psoriasis in a real-world setting.

PubMed

Lee, Erica B; Amin, Mina; Egeberg, Alexander; Wu, Jashin J

2018-05-06

Apremilast, a phosphodiesterase-4 inhibitor, is an oral therapy for treatment of psoriasis. Its safety profile is favorable, with side effects including diarrhea, nausea, vomiting, depression, and weight decrease, primarily based on clinical trial data. However, limited research exists on the side effect frequency and subsequent adverse events (AEs) in real-world practice. This retrospective chart review included patients who presented to the dermatology clinic at Kaiser Permanente Los Angeles Medical Center and were treated with apremilast at any time between January 1, 2015 and January 11, 2018. Patients were not included if they did not have at least one follow-up by clinic visit, telephone, or email correspondence after being prescribed apremilast. A total of 77 patients were included. AEs and withdrawal due to AEs were assessed throughout the treatment period from each patient's respective medical record. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Conformational Changes of Bovine Serum Albumin Induced by Adsorption on Different Clay Surfaces: FTIR Analysis.

PubMed

Servagent-Noinville; Revault; Quiquampoix; Baron

2000-01-15

Interactions between proteins and clays perturb biological activity in ecosystems, particularly soil extracellular enzyme activity. The pH dependence of hydrophobic, hydrophilic, and electrostatic interactions on the adsorption of bovine serum albumin (BSA) is studied. BSA secondary structures and hydration are revealed from computation of the Amide I and II FTIR absorption profiles. The influence of ionization of Asp, Glu, and His side chains on the adsorption processes is deduced from correlation between p(2)H dependent carboxylic/carboxylate ratio and Amide band profiles. We quantify p(2)H dependent internal and external structural unfolding for BSA adsorbed on montmorillonite, which is an electronegative phyllosilicate. Adsorption on talc, a hydrophobic surface, is less denaturing. The results emphasize the importance of electrostatic interactions in both adsorption processes. In the first case, charged side chains directly influence BSA adsorption that generate the structural transition. In the second case, the forces that attract hydrophobic side chains toward the protein-clay interface are large enough to distort peripheral amphiphilic helical domains. The resulting local unfolding displaces enough internal ionized side chains to prevent them from establishing salt bridges as for BSA native structure in solution. On montmorillonite, a particular feature is a higher protonation of the Asp and Glu side chains of the adsorbed BSA than in solution, which decreases coulombic repulsion. Copyright 2000 Academic Press.

β-Arrestins: Regulatory Role and Therapeutic Potential in Opioid and Cannabinoid Receptor-Mediated Analgesia

PubMed Central

Bohn, Laura M.

2016-01-01

Pain is a complex disorder with neurochemical and psychological components contributing to the severity, the persistence, and the difficulty in adequately treating the condition. Opioid and cannabinoids are two classes of analgesics that have been used to treat pain for centuries and are arguably the oldest of “pharmacological” interventions used by man. Unfortunately, they also produce several adverse side effects that can complicate pain management. Opioids and cannabinoids act at G protein-coupled receptors (GPCRs), and much of their effects are mediated by the mu-opioid receptor (MOR) and cannabinoid CB1 receptor (CB1R), respectively. These receptors couple to intracellular second messengers and regulatory proteins to impart their biological effects. In this chapter, we review the role of the intracellular regulatory proteins, β-arrestins, in modulating MOR and CB1R and how they influence the analgesic and side-effect profiles of opioid and cannabinoid drugs in vivo. This review of the literature suggests that the development of opioid and cannabinoid agonists that bias MOR and CB1R toward G protein signaling cascades and away from β-arrestin interactions may provide a novel mechanism by which to produce analgesia with less severe adverse effects. PMID:24292843

Separating Drought Effects from Roof Artifacts on Ecosystem Processes in a Grassland Drought Experiment

PubMed Central

Vogel, Anja; Fester, Thomas; Eisenhauer, Nico; Scherer-Lorenzen, Michael; Schmid, Bernhard; Weisser, Wolfgang W.; Weigelt, Alexandra

2013-01-01

1 Given the predictions of increased drought probabilities under various climate change scenarios, there have been numerous experimental field studies simulating drought using transparent roofs in different ecosystems and regions. Such roofs may, however, have unknown side effects, called artifacts, on the measured variables potentially confounding the experimental results. A roofed control allows the quantification of potential artifacts, which is lacking in most experiments. 2 We conducted a drought experiment in experimental grasslands to study artifacts of transparent roofs and the resulting effects of artifacts on ecosystems relative to drought on three response variables (aboveground biomass, litter decomposition and plant metabolite profiles). We established three drought treatments, using (1) transparent roofs to exclude rainfall, (2) an unroofed control treatment receiving natural rainfall and (3) a roofed control, nested in the drought treatment but with rain water reapplied according to ambient conditions. 3 Roofs had a slight impact on air (+0.14°C during night) and soil temperatures (−0.45°C on warm days, +0.25°C on cold nights), while photosynthetically active radiation was decreased significantly (−16%). Aboveground plant community biomass was reduced in the drought treatment (−41%), but there was no significant difference between the roofed and unroofed control, i.e., there were no measurable roof artifact effects. 4 Compared to the unroofed control, litter decomposition was decreased significantly both in the drought treatment (−26%) and in the roofed control treatment (−18%), suggesting artifact effects of the transparent roofs. Moreover, aboveground metabolite profiles in the model plant species Medicago x varia were different from the unroofed control in both the drought and roofed control treatments, and roof artifact effects were of comparable magnitude as drought effects. 5 Our results stress the need for roofed control treatments when using transparent roofs for studying drought effects, because roofs can cause significant side effects. PMID:23936480

Velocity measurements in the near field of a diesel fuel injector by ultrafast imagery

NASA Astrophysics Data System (ADS)

Sedarsky, David; Idlahcen, Saïd; Rozé, Claude; Blaisot, Jean-Bernard

2013-02-01

This paper examines the velocity profile of fuel issuing from a high-pressure single-orifice diesel injector. Velocities of liquid structures were determined from time-resolved ultrafast shadow images, formed by an amplified two-pulse laser source coupled to a double-frame camera. A statistical analysis of the data over many injection events was undertaken to map velocities related to spray formation near the nozzle outlet as a function of time after start of injection. These results reveal a strong asymmetry in the liquid profile of the test injector, with distinct fast and slow regions on opposite sides of the orifice. Differences of ˜100 m/s can be observed between the `fast' and `slow' sides of the jet, resulting in different atomization conditions across the spray. On average, droplets are dispersed at a greater distance from the nozzle on the `fast' side of the flow, and distinct macrostructure can be observed under the asymmetric velocity conditions. The changes in structural velocity and atomization behavior resemble flow structures which are often observed in the presence of string cavitation produced under controlled conditions in scaled, transparent test nozzles. These observations suggest that widely used common-rail supply configurations and modern injectors can potentially generate asymmetric interior flows which strongly influence diesel spray morphology. The velocimetry measurements presented in this work represent an effective and relatively straightforward approach to identify deviant flow behavior in real diesel sprays, providing new spatially resolved information on fluid structure and flow characteristics within the shear layers on the jet periphery.

Comparison of safety and immunogenicity of purified chick embryo cell vaccine using Zagreb and Essen regimens in patients with category II exposure in China.

PubMed

Hu, Quan; Liu, Man-Qing; Zhu, Zheng-Gang; Zhu, Ze-Rong; Lu, Sha

2014-01-01

The aim was to compare the safety and immunogenicity of purified chick embryo cell vaccine (PCECV) with Zagreb 2-1-1 and Essen 1-1-1-1-1 regimens in patients with WHO category II exposure in China. Side effects including systemic and local symptoms were recorded for all patients during vaccination with purified chick embryo cell vaccine (PCECV) under Zagreb 2-1-1 or Essen 1-1-1-1-1 regimens, and the rabies neutralization antibody titers in patients' serum at days 0, 7, 14, 45, 365 post-immunization were measured to determine the immunogenicity. Fever and pain were the most common events for systemic and local symptoms respectively, and most side effects (86.78%, 105/121) occurred after the first dose of vaccination. Safety analysis showed differences in side effects in<5-year-old patients between Zagreb and Essen regimens, especially after the first dose of vaccination (P = 0.043). Immunogenicity analysis indicated that Zagreb can achieve higher neutralization antibody titers and a greater seroconversion rate in a shorter time but had less persistence than Essen. When compared with the Essen regimen, the Zagreb regimen had a different immunogenicity in all study subjects, and different safety profile in young children, and a further study with a larger population and longer surveillance is warranted.

Tumor regression achieved by encapsulating a moderately soluble drug into a polymeric thermogel

PubMed Central

Ci, Tianyuan; Chen, Liang; Yu, Lin; Ding, Jiandong

2014-01-01

For cancer chemotherapy, a tumor regression without any surgical resection and severe side effects is greatly preferred to merely slowing down the growth of tumors. Here, we report a formulation composed of irinotecan (IRN) and poly(D,L-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA). IRN is a clinically used antitumor drug with active and inactive chemical forms in equilibrium, and the major form at physiological conditions is inactive but still has side effects. The aqueous solution of the PLGA-PEG-PLGA is a sol at room temperature and physically gels at body temperature, forming a thermogel. We successfully mixed this moderately soluble drug into the amphiphilic copolymer aqueous solution for the first time. The mixture was subcutaneously injected into nude mice with xenografted SW620 human colon tumors. Excellent in vivo antitumor efficacy was observed in the group that received the IRN-loaded thermogel. The tumor was significantly regressed after being treated with the IRN/thermogel, and the side effects (blood toxicity and body weight decrease) were very mild. These results might be attributed to the ideal sustained release profile and period of release of the drug from the thermogel and to the significant enhancement of the fraction of the active form of the drug by the thermogel. PMID:24980734

Network Biomarkers of Bladder Cancer Based on a Genome-Wide Genetic and Epigenetic Network Derived from Next-Generation Sequencing Data.

PubMed

Li, Cheng-Wei; Chen, Bor-Sen

2016-01-01

Epigenetic and microRNA (miRNA) regulation are associated with carcinogenesis and the development of cancer. By using the available omics data, including those from next-generation sequencing (NGS), genome-wide methylation profiling, candidate integrated genetic and epigenetic network (IGEN) analysis, and drug response genome-wide microarray analysis, we constructed an IGEN system based on three coupling regression models that characterize protein-protein interaction networks (PPINs), gene regulatory networks (GRNs), miRNA regulatory networks (MRNs), and epigenetic regulatory networks (ERNs). By applying system identification method and principal genome-wide network projection (PGNP) to IGEN analysis, we identified the core network biomarkers to investigate bladder carcinogenic mechanisms and design multiple drug combinations for treating bladder cancer with minimal side-effects. The progression of DNA repair and cell proliferation in stage 1 bladder cancer ultimately results not only in the derepression of miR-200a and miR-200b but also in the regulation of the TNF pathway to metastasis-related genes or proteins, cell proliferation, and DNA repair in stage 4 bladder cancer. We designed a multiple drug combination comprising gefitinib, estradiol, yohimbine, and fulvestrant for treating stage 1 bladder cancer with minimal side-effects, and another multiple drug combination comprising gefitinib, estradiol, chlorpromazine, and LY294002 for treating stage 4 bladder cancer with minimal side-effects.

Tumor regression achieved by encapsulating a moderately soluble drug into a polymeric thermogel

NASA Astrophysics Data System (ADS)

Ci, Tianyuan; Chen, Liang; Yu, Lin; Ding, Jiandong

2014-07-01

For cancer chemotherapy, a tumor regression without any surgical resection and severe side effects is greatly preferred to merely slowing down the growth of tumors. Here, we report a formulation composed of irinotecan (IRN) and poly(D,L-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA). IRN is a clinically used antitumor drug with active and inactive chemical forms in equilibrium, and the major form at physiological conditions is inactive but still has side effects. The aqueous solution of the PLGA-PEG-PLGA is a sol at room temperature and physically gels at body temperature, forming a thermogel. We successfully mixed this moderately soluble drug into the amphiphilic copolymer aqueous solution for the first time. The mixture was subcutaneously injected into nude mice with xenografted SW620 human colon tumors. Excellent in vivo antitumor efficacy was observed in the group that received the IRN-loaded thermogel. The tumor was significantly regressed after being treated with the IRN/thermogel, and the side effects (blood toxicity and body weight decrease) were very mild. These results might be attributed to the ideal sustained release profile and period of release of the drug from the thermogel and to the significant enhancement of the fraction of the active form of the drug by the thermogel.

A Strategy Combining Higher Energy C-Trap Dissociation with Neutral Loss- and Product Ion-Based MSn Acquisition for Global Profiling and Structure Annotation of Fatty Acids Conjugates

NASA Astrophysics Data System (ADS)

Bi, Qi-rui; Hou, Jin-jun; Yang, Min; Shen, Yao; Qi, Peng; Feng, Rui-hong; Dai, Zhuo; Yan, Bing-peng; Wang, Jian-wei; Shi, Xiao-jian; Wu, Wan-ying; Guo, De-an

2017-03-01

Fatty acids conjugates (FACs) are ubiquitous but found in trace amounts in the natural world. They are composed of multiple unknown substructures and side chains. Thus, FACs are difficult to be analyzed by traditional mass spectrometric methods. In this study, an integrated strategy was developed to global profiling and targeted structure annotation of FACs in complex matrix by LTQ Orbitrap. Dicarboxylic acid conjugated bufotoxins (DACBs) in Venenum bufonis (VB) were used as model compounds. The new strategy (abbreviated as HPNA) combined higher-energy C-trap dissociation (HCD) with product ion- (PI), neutral loss- (NL) based MSn (n ≥ 3) acquisition in both positive-ion mode and negative-ion mode. Several advantages are presented. First, various side chains were found under HCD in negative-ion mode, which included both known and unknown side chains. Second, DACBs with multiple side chains were simultaneously detected in one run. Compared with traditional quadrupole-based mass method, it greatly increased analysis throughput. Third, the fragment ions of side chain and steroids substructure could be obtained by PI- and NL-based MSn acquisition, respectively, which greatly increased the accuracy of the structure annotation of DACBs. In all, 78 DACBs have been discovered, of which 68 were new compounds; 25 types of substructure formulas and seven dicarboxylic acid side chains were found, especially five new side chains, including two saturated dicarboxylic acids [(azelaic acid (C9) and sebacic acid (C10)] and three unsaturated dicarboxylic acids (u-C8, u-C9, and u-C10). All these results greatly enriched the structures of DACBs in VB.

[The assessment of oral NSAID use in patients with rheumatoid arthritis in Hungary--a cross sectional non interventional study].

PubMed

Inotai, András; Rojkovich, Bernadette; Mészáros, Agnes

2010-01-01

Continuous NSAID (nonsteroidal anti-inflammatory drug) therapy is associated with gastrointestinal (GI) and cardiovascular (CV) side effects. In this paper, the oral NSAID use of 143 patients with rheumatoid arthritis was assessed focusing on safety and farmacoeconomic aspects in a cross sectional non interventional study. The most widely used NSAIDs were meloxicam (n = 55, 38.5%) and diclofenac (n = 30, 21%). We found that coxibs were overused (n = 13, 9.1%) compared with the average total coxib consumption in Hungary. According to our results, drugs associated with GI friend side effect profile (meloxicam, celecoxib, etoricoxib) were much preferred in patients with previous GI events, than in patients with low GI risk. The previous occurrence of GI events were significantly higher (p = 0.019) in patients currently treated with safer NSAIDs, probably because of the so-called 'indication bias'. No statistically significant difference in patient's quality of life could be proved between NSAID drug groups. The uses of NSAIDs were considered to be rational concerning CV and GI risk as well as cost-effectiveness.

BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology.

PubMed

Wilson, E N; Do Carmo, S; Iulita, M F; Hall, H; Ducatenzeiler, A; Marks, A R; Allard, S; Jia, D T; Windheim, J; Cuello, A C

2017-08-01

Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer's disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology. This formulation allows microdose lithium delivery to the brain in the absence of negative side effects. We found that NP03 rescued key initiating components of AD pathology, including inactivating GSK-3β, reducing BACE1 expression and activity, and reducing amyloid levels. Notably, NP03 rescued memory loss, impaired CRTC1 promoter binding of synaptic plasticity genes and hippocampal neurogenesis. These results raise the possibility that NP03 be of therapeutic value in the early or preclinical stages of AD.

Growth of Malignant Non-CNS Tumors Alters Brain Metabolome

PubMed Central

Kovalchuk, Anna; Nersisyan, Lilit; Mandal, Rupasri; Wishart, David; Mancini, Maria; Sidransky, David; Kolb, Bryan; Kovalchuk, Olga

2018-01-01

Cancer survivors experience numerous treatment side effects that negatively affect their quality of life. Cognitive side effects are especially insidious, as they affect memory, cognition, and learning. Neurocognitive deficits occur prior to cancer treatment, arising even before cancer diagnosis, and we refer to them as “tumor brain.” Metabolomics is a new area of research that focuses on metabolome profiles and provides important mechanistic insights into various human diseases, including cancer, neurodegenerative diseases, and aging. Many neurological diseases and conditions affect metabolic processes in the brain. However, the tumor brain metabolome has never been analyzed. In our study we used direct flow injection/mass spectrometry (DI-MS) analysis to establish the effects of the growth of lung cancer, pancreatic cancer, and sarcoma on the brain metabolome of TumorGraft™ mice. We found that the growth of malignant non-CNS tumors impacted metabolic processes in the brain, affecting protein biosynthesis, and amino acid and sphingolipid metabolism. The observed metabolic changes were similar to those reported for neurodegenerative diseases and brain aging, and may have potential mechanistic value for future analysis of the tumor brain phenomenon. PMID:29515623

Amorfrutins are potent antidiabetic dietary natural products

PubMed Central

Weidner, Christopher; de Groot, Jens C.; Prasad, Aman; Freiwald, Anja; Quedenau, Claudia; Kliem, Magdalena; Witzke, Annabell; Kodelja, Vitam; Han, Chung-Ting; Giegold, Sascha; Baumann, Matthias; Klebl, Bert; Siems, Karsten; Müller-Kuhrt, Lutz; Schürmann, Annette; Schüler, Rita; Pfeiffer, Andreas F. H.; Schroeder, Frank C.; Büssow, Konrad; Sauer, Sascha

2012-01-01

Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease. PMID:22509006

BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology

PubMed Central

Wilson, E N; Do Carmo, S; Iulita, M F; Hall, H; Ducatenzeiler, A; Marks, A R; Allard, S; Jia, D T; Windheim, J; Cuello, A C

2017-01-01

Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer’s disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology. This formulation allows microdose lithium delivery to the brain in the absence of negative side effects. We found that NP03 rescued key initiating components of AD pathology, including inactivating GSK-3β, reducing BACE1 expression and activity, and reducing amyloid levels. Notably, NP03 rescued memory loss, impaired CRTC1 promoter binding of synaptic plasticity genes and hippocampal neurogenesis. These results raise the possibility that NP03 be of therapeutic value in the early or preclinical stages of AD. PMID:28763060

Dual-opioid therapy: changing the paradigm. Introduction.

PubMed

Nicholson, Bruce D

2012-03-01

Morphine sulfate and oxycodone hydrochloride are commonly used for pain management because of their pharmacologic profile, pharmacokinetics, and analgesic potency. However, opioids are associated with a significant adverse event (AE) burden that limits their use in both the acute and the chronic pain settings. Co-administration of opioids demonstrated synergistic analgesia and reduced side effects. Thus, dual-opioid therapy has the potential to enhance the positive analgesic benefits of opioids, while limiting the burden of opioid-related AEs. This symposium proceedings was based on presentations at the 13th World Congress on Pain in August 2010. This program will review the rationale for dual-opioid therapy based on preclinical findings and data from clinical studies showing the efficacy and tolerability profile of a dual-opioid formulation when used to treat acute postoperative pain. Wiley Periodicals, Inc.

A Tapered Aluminium Microelectrode Array for Improvement of Dielectrophoresis-Based Particle Manipulation

PubMed Central

Buyong, Muhamad Ramdzan; Larki, Farhad; Faiz, Mohd Syafiq; Hamzah, Azrul Azlan; Yunas, Jumrail; Majlis, Burhanuddin Yeop

2015-01-01

In this work, the dielectrophoretic force (FDEP) response of Aluminium Microelectrode Arrays with tapered profile is investigated through experimental measurements and numerical simulations. A standard CMOS processing technique with a step for the formation of a tapered profile resist is implemented in the fabrication of Tapered Aluminium Microelectrode Arrays (TAMA). The FDEP is investigated through analysis of the Clausius-Mossotti factor (CMF) and cross-over frequency (fxo). The performance of TAMA with various side wall angles is compared to that of microelectrodes with a straight cut sidewall profile over a wide range of frequencies through FEM numerical simulations. Additionally, electric field measurement (EFM) is performed through scanning probe microscopy (SPM) in order to obtain the region of force focus in both platforms. Results showed that the tapered profile microelectrodes with angles between 60° and 70° produce the highest electric field gradient on the particles. Also, the region of the strongest electric field in TAMA is located at the bottom and top edge of microelectrode while the strongest electric field in microelectrodes with straight cut profile is found at the top corner of the microelectrode. The latter property of microelectrodes improves the probability of capturing/repelling the particles at the microelectrode’s side wall. PMID:25970255

A tapered aluminium microelectrode array for improvement of dielectrophoresis-based particle manipulation.

PubMed

Buyong, Muhamad Ramdzan; Larki, Farhad; Faiz, Mohd Syafiq; Hamzah, Azrul Azlan; Yunas, Jumrail; Majlis, Burhanuddin Yeop

2015-05-11

In this work, the dielectrophoretic force (F(DEP)) response of Aluminium Microelectrode Arrays with tapered profile is investigated through experimental measurements and numerical simulations. A standard CMOS processing technique with a step for the formation of a tapered profile resist is implemented in the fabrication of Tapered Aluminium Microelectrode Arrays (TAMA). The F(DEP) is investigated through analysis of the Clausius-Mossotti factor (CMF) and cross-over frequency (f(xo)). The performance of TAMA with various side wall angles is compared to that of microelectrodes with a straight cut sidewall profile over a wide range of frequencies through FEM numerical simulations. Additionally, electric field measurement (EFM) is performed through scanning probe microscopy (SPM) in order to obtain the region of force focus in both platforms. Results showed that the tapered profile microelectrodes with angles between 60° and 70° produce the highest electric field gradient on the particles. Also, the region of the strongest electric field in TAMA is located at the bottom and top edge of microelectrode while the strongest electric field in microelectrodes with straight cut profile is found at the top corner of the microelectrode. The latter property of microelectrodes improves the probability of capturing/repelling the particles at the microelectrode's side wall.

Issues related to sex differences in antipsychotic treatment.

PubMed

Crawford, Mitchell B; DeLisi, Lynn E

2016-05-01

The effectiveness, side-effect profiles, and numerous other characteristics of antipsychotic medications have been extensively studied. However, the majority of publications do not address the many potential sex differences in efficacy and doses of medications, as well as other sex-specific considerations. Of studies that exist, some suggest that female patients respond to lower doses of antipsychotic medications than males and that side-effect profiles vary between the sexes. However, the majority of preclinical trials use only male laboratory animals, and human clinical trials consist of too few women to analyze their response as a separate group. Although changes in hormone production occurring at multiple stages throughout a women's life (such as during pregnancy, breast feeding, menopause, and postmenopausal) are presented as too complex to deal with in clinical trials, they could instead be embraced as clinical dilemmas that require additional study and consideration. We suggest that a focus should be made to reanalyze data from existing major treatment trials of antipsychotics to determine what medications specifically provide the most efficacy for female patients and at what dose range. In addition, new prospective studies are needed to specifically address appropriate adjustments in psychopharmacologic treatment for female patients during pregnancy, and when postmenopausal. More studies of the effects of antipsychotics on male and female fetuses in utero and during breast feeding are also needed to better manage women with schizophrenia and their offspring on a long-term basis in the community. There is currently too little known about sex differences in neuropharmacology. With the new USA National Institutes of Health policy to include sex in all new proposals, the time has come to close this gap in knowledge.

Effects of 6-week sling-based training of the external-rotator muscles on the shoulder profile in elite female high school handball players.

PubMed

Genevois, Cyril; Berthier, Philippe; Guidou, Vincent; Muller, Franck; Thiebault, Boris; Rogowski, Isabelle

2014-11-01

In women's handball, the large numbers of throws and passes make the shoulder region vulnerable to overuse injuries. Repetitive throwing motions generate imbalance between shoulder internal- and external-rotator muscles. It has not yet been established whether sling-based training can improve shoulder external-rotator muscle strength. This study investigated the effectiveness of a 6-wk strengthening program in improving shoulder functional profile in elite female high school handball players. Crossover study. National elite handball training center. 25 elite female high school handball players. The program, completed twice per week for 6 wk, included sling-based strengthening exercises using a suspension trainer for external rotation with scapular retraction and scapular retraction alone. Maximal shoulder external- and internal-rotation strength, shoulder external- and internal-rotation range of motion (ROM), and maximal throwing velocity were assessed preintervention and postintervention for dominant and nondominant sides. After sling training, external- and internal-rotation strength increased significantly for both sides (P ≤ .001, and P = .004, respectively), with the result that there was no significant change in external- and internal-rotation strength ratios for either the dominant or the nondominant shoulder. No significant differences were observed for external-rotation ROM, while internal-rotation ROM decreased moderately, in particular in the dominant shoulder (P = .005). Maximal throwing velocity remained constant for the dominant arm, whereas a significant increase was found for the nondominant arm (P = .017). This 6-wk strengthening program was effective in improving shoulder external-rotator muscle strength but resulted in a decrease in the ROM in shoulder internal rotation, while throwing velocity remained stable. Adding a stretching program to this type of sling-based training program might help avoid potential detrimental effects on shoulder ROM.

Dual-gate operation and carrier transport in SiGe p–n junction nanowires

DOE PAGES

Delker, Collin James; Yoo, Jink Young; Bussmann, Ezra; ...

2017-10-23

Here, we investigate carrier transport in silicon–germanium nanowires with an axial p–n junction doping profile by fabricating these wires into transistors that feature separate top gates over each doping segment. By independently biasing each gate, carrier concentrations in the n- and p-side of the wire can be modulated. For these devices, which were fabricated with nickel source–drain electrical contacts, holes are the dominant charge carrier, with more favorable hole injection occurring on the p-side contact. Channel current exhibits greater sensitivity to the n-side gate, and in the reverse biased source–drain configuration, current is limited by the nickel/n-side Schottky contact.

Dual-gate operation and carrier transport in SiGe p-n junction nanowires

NASA Astrophysics Data System (ADS)

Delker, C. J.; Yoo, J. Y.; Bussmann, E.; Swartzentruber, B. S.; Harris, C. T.

2017-11-01

We investigate carrier transport in silicon-germanium nanowires with an axial p-n junction doping profile by fabricating these wires into transistors that feature separate top gates over each doping segment. By independently biasing each gate, carrier concentrations in the n- and p-side of the wire can be modulated. For these devices, which were fabricated with nickel source-drain electrical contacts, holes are the dominant charge carrier, with more favorable hole injection occurring on the p-side contact. Channel current exhibits greater sensitivity to the n-side gate, and in the reverse biased source-drain configuration, current is limited by the nickel/n-side Schottky contact.

Dual-gate operation and carrier transport in SiGe p–n junction nanowires

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

Delker, Collin James; Yoo, Jink Young; Bussmann, Ezra

Here, we investigate carrier transport in silicon–germanium nanowires with an axial p–n junction doping profile by fabricating these wires into transistors that feature separate top gates over each doping segment. By independently biasing each gate, carrier concentrations in the n- and p-side of the wire can be modulated. For these devices, which were fabricated with nickel source–drain electrical contacts, holes are the dominant charge carrier, with more favorable hole injection occurring on the p-side contact. Channel current exhibits greater sensitivity to the n-side gate, and in the reverse biased source–drain configuration, current is limited by the nickel/n-side Schottky contact.

Metabolic syndrome and atypical antipsychotics: Possibility of prediction and control.

PubMed

Franch Pato, Clara M; Molina Rodríguez, Vicente; Franch Valverde, Juan I

Schizophrenia and other psychotic disorders are associated with high morbidity and mortality, due to inherent health factors, genetic factors, and factors related to psychopharmacological treatment. Antipsychotics, like other drugs, have side-effects that can substantially affect the physical health of patients, with substantive differences in the side-effect profile and in the patients in which these side-effects occur. To understand and identify these risk groups could help to prevent the occurrence of the undesired effects. A prospective study, with 24 months follow-up, was conducted in order to analyse the physical health of severe mental patients under maintenance treatment with atypical antipsychotics, as well as to determine any predictive parameters at anthropometric and/or analytical level for good/bad outcome of metabolic syndrome in these patients. There were no significant changes in the physical and biochemical parameters individually analysed throughout the different visits. The baseline abdominal circumference (lambda Wilks P=.013) and baseline HDL-cholesterol levels (lambda Wilks P=.000) were the parameters that seem to be more relevant above the rest of the metabolic syndrome constituents diagnosis criteria as predictors in the long-term. In the search for predictive factors of metabolic syndrome, HDL-cholesterol and abdominal circumference at the time of inclusion were selected, as such that the worst the baseline results were, the higher probability of long-term improvement. Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

Discovery, clinical development, and therapeutic uses of bisphosphonates.

PubMed

Licata, Angelo A

2005-04-01

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

Evidence for retrograde lithospheric subduction on Venus

NASA Technical Reports Server (NTRS)

Sandwell, David T.; Schubert, Gerald

1992-01-01

Though there is no plate tectonics per se on Venus, recent Magellan radar images and topographic profiles of the planet suggest the occurrence of the plate tectonic processes of lithospheric subduction and back-arc spreading. The perimeters of several large coronae (e.g., Latona, Artemis, and Eithinoha) resemble Earth subduction zones in both their planform and topographic profile. The planform of arcuate structures in Eastern Aphrodite were compared with subduction zones of the East Indies. The venusian structures have radii of curvature that are similar to those of terrestrial subduction zones. Moreover, the topography of the venusian ridge/trench structures is highly asymmetric with a ridge on the concave side and a trough on the convex side; Earth subduction zones generally display the same asymmetry.

Decomposition of superimposed ground reaction forces into left and right force profiles

NASA Technical Reports Server (NTRS)

Davis, B. L.; Cavanagh, P. R.

1993-01-01

The process of collecting ground reaction force data by mounting a forceplate beneath a treadmill belt has the advantage that numerous walking trials can be analyzed without the problem of subjects 'targeting' their footsteps. However, a potential problem is that the measured forces represent a summation of bilateral force profiles during the double support phase of walking. To address this issue, an algorithm is described for decomposing superimposed ground reaction force data into individual left and right profiles. It is based on an examination of the side-to-side oscillations of the measured center of pressure (CoP). Whenever the measured CoP exceeds a certain threshold, it is assumed that the person is being supported by a single limb, and the measured GRF data reflect the forces under that limb. Conversely, when the measured CoP indicates that both feet are on the treadmill, it is assumed that the location of the individual CoP under each foot is given by wL2 and wR2. These quantities reflect the greatest excursion of the measured CoP towards the left and right sides of the forceplate, respectively. With this assumption, individual GRF profiles can be calculated by means of solving two simultaneous equations--one describing the equilibrium of forces in the vertical direction, and one describing the equilibrium of moments about an antero-posterior axis of the forceplate. The algorithm describing this procedure is simple enough to be implemented on a spreadsheet and yields estimates for average force, impulse, peak force and stance time that are typically within 3% of the true values.

[Therapeutic potential of Hibiscus sabdariffa: a review of the scientific evidence].

PubMed

Guardiola, Soledad; Mach, Núria

2014-05-01

Infusion of Hibiscus sabdariffa (H. sabdariffa) is a very popular drink in many parts of the world. Its phytochemical composition is associated to antioxidant, hypotensive, and antiatherosclerotic effects. However, the molecular mechanisms involved in these processes are not well known. The aim of this review was to report the scientific evidence supporting that regular use of H. sabdariffa decreases oxidative stress, atherosclerosis, lipid profile, and blood pressure. A search of recent publications was made in the following specialized electronic databases: Elsevier Journal, SciELO, FSTA, Science Direct, Springer Link, and NCBI. Results of research conducted in clinical trials in humans and in animal models and cell cultures were recorded. Keywords used included Hibiscus sabdariffa, oxidative stress, polyphenols, hypertension, atherosclerosis, and lipid profile. Results of the different articles suggested a possible therapeutic effect of H. sabdariffa extracts on oxidative stress, lipid profile, hypertension, and atherosclerosis thanks to its composition rich in phenolic compounds. Anthocyanins significantly decrease LDL oxidation, inhibit adipogenesis by regulating adipogenic signaling pathways and transcription factors, and modulate gene expression of certain microRNAs. No adverse events or side effects were reported. Further more homogeneous, placebo-controlled studies in humans are needed to state that H. sabdariffa has therapeutic efficacy in humans. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

UDE-based control of variable-speed wind turbine systems

NASA Astrophysics Data System (ADS)

Ren, Beibei; Wang, Yeqin; Zhong, Qing-Chang

2017-01-01

In this paper, the control of a PMSG (permanent magnet synchronous generator)-based variable-speed wind turbine system with a back-to-back converter is considered. The uncertainty and disturbance estimator (UDE)-based control approach is applied to the regulation of the DC-link voltage and the control of the RSC (rotor-side converter) and the GSC (grid-side converter). For the rotor-side controller, the UDE-based vector control is developed for the RSC with PMSG control to facilitate the application of the MPPT (maximum power point tracking) algorithm for the maximum wind energy capture. For the grid-side controller, the UDE-based vector control is developed to control the GSC with the power reference generated by a UDE-based DC-link voltage controller. Compared with the conventional vector control, the UDE-based vector control can achieve reliable current decoupling control with fast response. Moreover, the UDE-based DC-link voltage regulation can achieve stable DC-link voltage under model uncertainties and external disturbances, e.g. wind speed variations. The effectiveness of the proposed UDE-based control approach is demonstrated through extensive simulation studies in the presence of coupled dynamics, model uncertainties and external disturbances under varying wind speeds. The UDE-based control is able to generate more energy, e.g. by 5% for the wind profile tested.

Making scents: improvement of olfactory profile after botulinum toxin-A treatment in healthy individuals.

PubMed

Heckmann, Marc; Kütt, Sandra; Dittmar, Sabine; Hamm, Henning

2007-01-01

The axilla is particularly associated with body odor and putative pheromone production in humans. Although botulinum toxin type A (BT-A) is injected increasingly into the axillary skin to stop excessive sweating, its potential to control body odor is largely unexplored. The objective was to measure the impact of BT-A on human axillary odor in an objective and reproducible fashion. This study was a randomized, double-blind, placebo-controlled trial with 51 healthy volunteers receiving 50 U of BOTOX (Allergan, Inc.) in one axilla and placebo in the other. Odor quality was assessed by treated subjects (questionnaire) as well as by independent raters who were exposed to blinded T-shirt samples. No major side effects occurred, and no subject withdrew from the study for medical reasons. Samples from the BT-A-treated side smelled less intense (p<.001) and better (p<.001) according to self-assessments. Likewise, independent raters found the BT-A-treated samples to smell less intense and better (p<.001). They preferred "to work together with the respective person" and found the odor "more erotic" (p<.001). Side-by-side comparison of odor samples (T-shirt sniff test) by independent raters showed that axillary odor in healthy individuals is significantly more appealing after BT-A injection.

The local and referred pain from myofascial trigger points in the temporalis muscle contributes to pain profile in chronic tension-type headache.

PubMed

Fernández-de-Las-Peñas, César; Ge, Hong-You; Arendt-Nielsen, Lars; Cuadrado, Maria Luz; Pareja, Juan A

2007-01-01

To assess the local and referred pain areas and pain characteristics evoked from temporalis muscle trigger points (TrPs) in chronic tension-type headache (CTTH). Thirty CTTH patients and 30 age and sex-matched controls were studied. A headache diary was kept for 4 weeks to substantiate the diagnosis and record the pain history. Both temporalis muscles were examined for the presence of myofascial TrPs in a blinded fashion. The local and referred pain intensities, referred pain pattern, and pressure pain threshold were recorded. Referred pain was evoked in 87% and 54% on the dominant and nondominant sides in CTTH patients, which was significantly higher (P<0.001) than in controls (10% vs. 17%, respectively). Referred pain spread to the temple ipsilateral to the stimulated muscle in both patients and controls, with additional referral behind the eyes in most patients, but none in controls. CTTH patients reported a higher local [visual analog scale (VAS): 5.6+/-1.2 right side, 5.3+/-1.4 left side] and referred pain (VAS: 4.7+/-2 right side, 3.5+/-2.8 left side) intensity than healthy controls (VAS: 0.8+/-0.7 right side, 0.7+/-0.7 left side for local pain; and 0.3+/-0.2 right side, 0.4+/-0.3 left side for referred pain) in both temporalis muscles (both, P<0.001). The local and referred pain areas were larger in patients than in controls (P<0.001). Twenty-three out of 30 CTTH patients (77%) had active TrPs in the temporalis muscle leading to their usual headache (17 patients on the right side; 12 on the left side, whereas 6 with bilateral active TrPs). CTTH patients with active TrPs in either right or left temporalis muscle showed longer headache duration than those with latent TrPs (P=0.004). CTTH patients showed significantly (P<0.001) lower pressure pain threshold (1.1+/-0.2 right side, 1.2+/-0.3 left side) as compared with controls (2.5+/-0.5 right side, 2.6+/-0.4 left side). In CTTH patients, the evoked local and referred pain from active TrPs in the temporalis muscle and its sensory characteristics shared similar patterns as their habitual headache pain. Local and referred pain from active TrPs in the temporalis muscles may constitute one of the sources contributing to the pain profile of CTTH.

Profiles of dyadic adjustment for advanced prostate cancer to inform couple-based intervention.

PubMed

Elliott, Kate-Ellen J; Scott, Jennifer L; Monsour, Michael; Nuwayhid, Fadi

2015-01-01

The purpose of the study is to describe from a relational perspective, partners' psychological adjustment, coping and support needs for advanced prostate cancer. A mixed methods design was adopted, employing triangulation of qualitative and quantitative data, to produce dyadic profiles of adjustment for six couples recruited from the urology clinics of local hospitals in Tasmania, Australia. Dyads completed a video-taped communication task, semi-structured interview and standardised self-report questionnaires. Themes identified were associated with the dyadic challenges of the disease experience (e.g. relationship intimacy, disease progression and carer burden). Couples with poor psychological adjustment profiles had both clinical and global locus of distress, treatment side-effects, carer burden and poor general health. Resilient couples demonstrated relationship closeness and adaptive cognitive and behavioural coping strategies. The themes informed the adaption of an effective program for couples coping with women's cancers (CanCOPE, to create a program for couples facing advanced prostate cancer (ProCOPE-Adv). Mixed method results inform the development of psychological therapy components for couples coping with advanced prostate cancer. The concomitance of co-morbid health problems may have implications for access and engagement for older adult populations in face-to-face intervention.

Numerical investigation of galloping instabilities in Z-shaped profiles.

PubMed

Gomez, Ignacio; Chavez, Miguel; Alonso, Gustavo; Valero, Eusebio

2014-01-01

Aeroelastic effects are relatively common in the design of modern civil constructions such as office blocks, airport terminal buildings, and factories. Typical flexible structures exposed to the action of wind are shading devices, normally slats or louvers. A typical cross-section for such elements is a Z-shaped profile, made out of a central web and two-side wings. Galloping instabilities are often determined in practice using the Glauert-Den Hartog criterion. This criterion relies on accurate predictions of the dependence of the aerodynamic force coefficients with the angle of attack. The results of a parametric analysis based on a numerical analysis and performed on different Z-shaped louvers to determine translational galloping instability regions are presented in this paper. These numerical analysis results have been validated with a parametric analysis of Z-shaped profiles based on static wind tunnel tests. In order to perform this validation, the DLR TAU Code, which is a standard code within the European aeronautical industry, has been used. This study highlights the focus on the numerical prediction of the effect of galloping, which is shown in a visible way, through stability maps. Comparisons between numerical and experimental data are presented with respect to various meshes and turbulence models.

Effects of turbulence intensity and gravity on transport of inertial particles across a shearless turbulence interface

NASA Astrophysics Data System (ADS)

Good, Garrett; Gerashchenko, Sergiy; Warhaft, Zellman

2010-11-01

Water droplets of sub-Kolmogorov size are sprayed into the turbulence side of a shearless turbulent-non-turbulent interface (TNI) as well as a turbulent-turbulent interface (TTI). An active grid is used to form the mixing layer and a splitter plate separates the droplet-non droplet interface near the origin. Particle concentration, size and velocity are determined by Phase Doppler Particle Analyzer, the velocity field by hot wires, and the droplet accelerations by particle tracking. As for a passive scalar, for the TTI, the concentration profiles are described by an error function. For the TNI, the concentration profiles fall off more rapidly than for the TTI due to the large-scale intermittency. The profile evolution and effects of initial conditions are discussed, as are the relative importance of the large and small scales in the transport process. It is shown that the concentration statistics are better described in terms of the Stokes number based on the large scales than the small, but some features of the mixing are determined by the small scales, and these will be discussed. Sponsored by the U.S. NSF.

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.

Electromyographic Patterns during Golf Swing: Activation Sequence Profiling and Prediction of Shot Effectiveness.

PubMed

Verikas, Antanas; Vaiciukynas, Evaldas; Gelzinis, Adas; Parker, James; Olsson, M Charlotte

2016-04-23

This study analyzes muscle activity, recorded in an eight-channel electromyographic (EMG) signal stream, during the golf swing using a 7-iron club and exploits information extracted from EMG dynamics to predict the success of the resulting shot. Muscles of the arm and shoulder on both the left and right sides, namely flexor carpi radialis, extensor digitorum communis, rhomboideus and trapezius, are considered for 15 golf players (∼5 shots each). The method using Gaussian filtering is outlined for EMG onset time estimation in each channel and activation sequence profiling. Shots of each player revealed a persistent pattern of muscle activation. Profiles were plotted and insights with respect to player effectiveness were provided. Inspection of EMG dynamics revealed a pair of highest peaks in each channel as the hallmark of golf swing, and a custom application of peak detection for automatic extraction of swing segment was introduced. Various EMG features, encompassing 22 feature sets, were constructed. Feature sets were used individually and also in decision-level fusion for the prediction of shot effectiveness. The prediction of the target attribute, such as club head speed or ball carry distance, was investigated using random forest as the learner in detection and regression tasks. Detection evaluates the personal effectiveness of a shot with respect to the player-specific average, whereas regression estimates the value of target attribute, using EMG features as predictors. Fusion after decision optimization provided the best results: the equal error rate in detection was 24.3% for the speed and 31.7% for the distance; the mean absolute percentage error in regression was 3.2% for the speed and 6.4% for the distance. Proposed EMG feature sets were found to be useful, especially when used in combination. Rankings of feature sets indicated statistics for muscle activity in both the left and right body sides, correlation-based analysis of EMG dynamics and features derived from the properties of two highest peaks as important predictors of personal shot effectiveness. Activation sequence profiles helped in analyzing muscle orchestration during golf shot, exposing a specific avalanche pattern, but data from more players are needed for stronger conclusions. Results demonstrate that information arising from an EMG signal stream is useful for predicting golf shot success, in terms of club head speed and ball carry distance, with acceptable accuracy. Surface EMG data, collected with a goal to automatically evaluate golf player's performance, enables wearable computing in the field of ambient intelligence and has potential to enhance exercising of a long carry distance drive.

Electromyographic Patterns during Golf Swing: Activation Sequence Profiling and Prediction of Shot Effectiveness

PubMed Central

Verikas, Antanas; Vaiciukynas, Evaldas; Gelzinis, Adas; Parker, James; Olsson, M. Charlotte

2016-01-01

This study analyzes muscle activity, recorded in an eight-channel electromyographic (EMG) signal stream, during the golf swing using a 7-iron club and exploits information extracted from EMG dynamics to predict the success of the resulting shot. Muscles of the arm and shoulder on both the left and right sides, namely flexor carpi radialis, extensor digitorum communis, rhomboideus and trapezius, are considered for 15 golf players (∼5 shots each). The method using Gaussian filtering is outlined for EMG onset time estimation in each channel and activation sequence profiling. Shots of each player revealed a persistent pattern of muscle activation. Profiles were plotted and insights with respect to player effectiveness were provided. Inspection of EMG dynamics revealed a pair of highest peaks in each channel as the hallmark of golf swing, and a custom application of peak detection for automatic extraction of swing segment was introduced. Various EMG features, encompassing 22 feature sets, were constructed. Feature sets were used individually and also in decision-level fusion for the prediction of shot effectiveness. The prediction of the target attribute, such as club head speed or ball carry distance, was investigated using random forest as the learner in detection and regression tasks. Detection evaluates the personal effectiveness of a shot with respect to the player-specific average, whereas regression estimates the value of target attribute, using EMG features as predictors. Fusion after decision optimization provided the best results: the equal error rate in detection was 24.3% for the speed and 31.7% for the distance; the mean absolute percentage error in regression was 3.2% for the speed and 6.4% for the distance. Proposed EMG feature sets were found to be useful, especially when used in combination. Rankings of feature sets indicated statistics for muscle activity in both the left and right body sides, correlation-based analysis of EMG dynamics and features derived from the properties of two highest peaks as important predictors of personal shot effectiveness. Activation sequence profiles helped in analyzing muscle orchestration during golf shot, exposing a specific avalanche pattern, but data from more players are needed for stronger conclusions. Results demonstrate that information arising from an EMG signal stream is useful for predicting golf shot success, in terms of club head speed and ball carry distance, with acceptable accuracy. Surface EMG data, collected with a goal to automatically evaluate golf player’s performance, enables wearable computing in the field of ambient intelligence and has potential to enhance exercising of a long carry distance drive. PMID:27120604

Focus on ulcerative colitis: stable gastric pentadecapeptide BPC 157.

PubMed

Sikiric, P; Seiwerth, S; Rucman, R; Turkovic, B; Rokotov, D S; Brcic, L; Sever, M; Klicek, R; Radic, B; Drmic, D; Ilic, S; Kolenc, D; Stambolija, V; Zoricic, Z; Vrcic, H; Sebecic, B

2012-01-01

Stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419) may be the new drug stable in human gastric juice, effective both in the upper and lower GI tract, and free of side effects. BPC 157, in addition to an antiulcer effect efficient in therapy of inflammatory bowel disease (IBD) (PL 14736) so far only tested in clinical phase II, has a very safe profile, and exhibited a particular wound healing effect. It also has shown to interact with the NO-system, providing endothelium protection and angiogenic effect, even in severely impaired conditions (i.e., it stimulated expression of early growth response 1 gene responsible for cytokine and growth factor generation and early extracellular matrix (collagen) formation (but also its repressor nerve growth factor 1-A binding protein-2)), important to counteract severe complications of advanced and poorly controlled IBD. Hopefully, the lessons from animal studies, particularly advanced intestinal anastomosis healing, reversed short bowel syndrome and fistula healing indicate BPC 157's high significance in further IBD therapy. Also, this supportive evidence (i.e., no toxic effect, limit test negative, LD1 not achieved, no side effect in trials) may counteract the problems commonly exercised in the use of peptidergic agents, particularly those used on a long-term basis.

Initial study of transdermal oxybutynin for treating hyperhidrosis.

PubMed

Millán-Cayetano, José Francisco; Del Boz, Javier; Toledo-Pastrana, Tomas; Nieto-Guindo, Miriam; García-Montero, Pablo; de Troya-Martín, Magdalena

2017-06-01

Oral oxybutynin for treating hyperhidrosis is effective and safe. Its side-effects are mild but frequent so we consider whether transdermal oxybutynin (considered to have a better side-effect profile) could be an alternative for treating hyperhidrosis. During 2015, a prospective study was conducted. Epidemiological variables, effectiveness (using the Hyperhidrosis Disease Severity Scale) and tolerance to transdermal oxybutynin were compiled concerning two different groups (patients previously treated or untreated with oral oxybutynin), at baseline, and at 3 and 12 months. Seven previously treated and six previously untreated patients were included. Five patients in the first group discontinued the treatment within 3 months. Of the two remaining patients, one reported ineffectiveness and the other obtained an excellent response but discontinued due to local irritation. Among the untreated patients, two showed no response and four experienced improvement (three with "partial response" and one with "excellent response"). All patients discontinued treatment within 12 months. No major adverse effects were observed. The absence of active metabolites after transdermal oxybutynin could result in less effectiveness than oral oxybutynin, although it is usually well tolerated. In conclusion, transdermal oxybutynin could have low effectiveness for the treatment of hyperhidrosis in patients following intolerance to oral oxybutynin but could provide good results in patients who have never tried systemic drugs. © 2017 Japanese Dermatological Association.

Comparison between neurostimulation techniques repetitive transcranial magnetic stimulation vs electroconvulsive therapy for the treatment of resistant depression: patient preference and cost-effectiveness.

PubMed

Magnezi, Racheli; Aminov, Emanuel; Shmuel, Dikla; Dreifuss, Merav; Dannon, Pinhas

2016-01-01

Major depressive disorder (MDD) is a common disorder, widely distributed in the population, and is often associated with severe symptoms and functional impairment. It has been estimated that 30% of MDD patients do not benefit adequately from therapeutic interventions, including pharmacotherapy and psychotherapy. Treatment-resistant depression (TRD) is generally defined as a failure to achieve remission, despite therapeutic interventions. The most effective treatment alternatives for TRD are hospitalization, electroconvulsive therapy (ECT), and transcranial magnetic stimulation (TMS). Here we compared the clinical effectiveness of ECT and TMS, including success rates, patient responses, side-effect profiles, and financial worthiness. We found that ECT (P<0.0001) was more effective than TMS (P<0.012) (not statistically significant in group effect) in TRD patients. However, ECT patients reported a higher percentage of side effects (P<0.01) and the TMS treatment scored better in terms of patient preference. The cost benefit of ECT was higher than that of TMS (US$2075 vs US$814). Patient's preferences for treatment could be more intense in the TMS, if the TMS is included in the Health Maintenance Organization's service list. We propose that both of these treatment options should be available in psychiatric wards, thus expanding the therapeutic toolkit for TRD.

A randomized study comparing the side effects and hormonal status of triptorelin and leuprorelin following conservative laparoscopic surgery for ovarian endometriosis in Chinese women.

PubMed

Li, Zheng; Zhang, Hong Yuan; Zhu, Ying Jun; Hu, Yuan Jing; Qu, Peng Peng

2014-12-01

Different gonadotropin-releasing-hormone agonist (GnRH-a) formulations with different potency and associated side effects, therefore, different compliance and persistence of therapy. This study was to evaluate the difference of hormonal profile and side effects due to hypoestrogenic status after treatment of leuprorelin and triptorelin in Chinese women with ovarian endometrioma after conservative surgical treatment. A total of 302 women underwent laparoscopic excision of ovarian endometriomas with rASRM III and IV were enrolled in the study.Subjects were randomized into two groups with use of a random table. Twenty two patients dropped out during the study. Thus 142 patients had three doses of i.m. leuprorelin (group A) and 138 patients had three doses of i.m. triptorelin(group B) at 4 weeks intervals after surgical treatment. Menopausal symptoms were evalutaed using a questionnaire and serum sex hormonal levels were also measured during the follow-up. At week 4 after the treatment, most of the patients in leuprorelin group have no obvious side effects. After 9 weeks, bone pain, hot flashes and sweating, and irregular bleeding were the main side effects and showed no difference between the groups. Anxiety, depression, vaginal dryness, headache, and acne rates were all significantly higher in triptorelin group than in leuprorelin group. A significant difference in FSH (p=0.003), LH (p=0.026) and E2 (p=0.002) levels between the groups were observed after 21 days of the GnRHa treatment. The FSH (p=0.021) and E2 (p=0.033) levels remained higher in the leuprorelin group than the triptorelin group after six weeks of treatment, but the difference of LH(p=0.917) level was no longer discernible. Leuprorelin in down-regulating the pituitary-ovarian function was more moderate, and the hormonal levels decrease progressively and gradually, therefore, with lower rate of menopausal symptoms. Leuprorelin acetate maybe better tolerated than triptorelin. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Biochemical profiling in silico--predicting substrate specificities of large enzyme families.

PubMed

Tyagi, Sadhna; Pleiss, Juergen

2006-06-25

A general high-throughput method for in silico biochemical profiling of enzyme families has been developed based on covalent docking of potential substrates into the binding sites of target enzymes. The method has been tested by systematically docking transition state--analogous intermediates of 12 substrates into the binding sites of 20 alpha/beta hydrolases from 15 homologous families. To evaluate the effect of side chain orientations to the docking results, 137 crystal structures were included in the analysis. A good substrate must fulfil two criteria: it must bind in a productive geometry with four hydrogen bonds between the substrate and the catalytic histidine and the oxyanion hole, and a high affinity of the enzyme-substrate complex as predicted by a high docking score. The modelling results in general reproduce experimental data on substrate specificity and stereoselectivity: the differences in substrate specificity of cholinesterases toward acetyl- and butyrylcholine, the changes of activity of lipases and esterases upon the size of the acid moieties, activity of lipases and esterases toward tertiary alcohols, and the stereopreference of lipases and esterases toward chiral secondary alcohols. Rigidity of the docking procedure was the major reason for false positive and false negative predictions, as the geometry of the complex and docking score may sensitively depend on the orientation of individual side chains. Therefore, appropriate structures have to be identified. In silico biochemical profiling provides a time efficient and cost saving protocol for virtual screening to identify the potential substrates of the members of large enzyme family from a library of molecules.

In Search of Police Investigative Thinking Styles: An Exploratory Study of Detectives in Norway and Singapore

ERIC Educational Resources Information Center

Dean, Geoff; Fahsing, Ivar Andre; Gottschalk, Petter

2007-01-01

In this paper, we argue that more research attention needs to be devoted to profile how investigators think when attempting to solve crimes and dismantle terrorist networks. Since 9/11, there is much activity focused on profiling criminals and terrorists but little on the other side of the investigative equation the detectives/investigators…

The topical treatment of psoriasis.

PubMed

van de Kerkhof, P C M; Vissers, W H P M

2003-01-01

According to the patients, improvement of efficacy, long-term safety and improvement of compliance are needed. The topical treatment has been innovated during the last decade. Most important are the introduction of two new classes of treatments: topical vitamin D(3) analogues and the retinoid tazarotene. To what extent, however, have we achieved developments which are in line with the needs as expressed by the patients? Improved efficacy has been realized by successful combinations of topical treatments. In particular, the combinations of dithranol, vitamin D(3) and tazarotene with a topical corticosteroid proved to be very effective with a reduced profile of side-effects. The efficacy of vitamin D(3) analogues and tazarotene is such that the efficacy of a potent corticosteroid (betamethasone-17-valerate) is approached; calcipotriol even showed an efficacy which is at least as good as this corticosteroid. The long-term safety of new compounds has been evaluated for at least 12 months in large studies. Remarkably for corticosteroids such information is available for only 12 weeks. However, intermittent applications of a topical corticosteroid in combination with another topical treatment provide an effective and safe long-term control of psoriasis. Compliance is a conditio sine qua non for an effective topical treatment. Important progress has been made to increase compliance. Short-contact dithranol has been popularized as an ambulatory treatment which is a highly effective approach as a care instruction programme. Formulations which are better from a cosmetical point of view have been developed for various topical treatments. Reduction of the frequency of applications proved to be possible for most treatments. Once daily applications for corticosteroids, vitamin D(3) analogues and retinoids have been developed, and intermittent applications, a few times per week, are possible for corticosteroids, which proved to be very effective with a reduced profile of side-effects, and are also developed for dithranol. Copyright 2003 S. Karger AG, Basel

A comparative safety review between GLP-1 receptor agonists and SGLT2 inhibitors for diabetes treatment.

PubMed

Consoli, Agostino; Formoso, Gloria; Baldassarre, Maria Pompea Antonia; Febo, Fabrizio

2018-03-01

Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile. Area Covered: adverse events and the safety concerns most often emerged in trials with GLP-1RA namely, exenatide long acting release (LAR), dulaglutide, liraglutide, semaglutide, lixisenatide or SGLT2i, namely empagliflozin, dapagliflozin, canagliflozin and SGLT2i with an attempt at comparing the safety profiles of molecules of these two classes. Expert opinion: GLP-1RA and SGLT2i, although each associated with different specific side effects, share a 'similar' safety profile and are both drugs relatively easy to handle. The potentially complementary mechanisms of action, the cardio and nephroprotective effects demonstrated by molecules of both classes, make these drugs potentially useful even in add on to each other.

Novel biotherapies are needed in youth mental health.

PubMed

Amminger, G Paul; Berger, Maximus; Rice, Simon M; Davey, Christopher G; Schäfer, Miriam R; McGorry, Patrick D

2017-04-01

Adverse effects and lack of efficacy in a significant number of patients limit pharmaceutical interventions in youth psychiatry. This is exemplified by the fact that no medication is currently approved for the treatment of non-OCD anxiety disorders or major depressive disorder in young people younger than 18 years of age in Australia. Here, emerging biological therapies for youth with mental health problems are discussed. There is an urgent need for more research into biological interventions with acceptable risk-benefit balances. Omega-3 fatty acids, cannabidiol and N-acetylcysteine are currently being evaluated. If initial findings are confirmed, they may offer alternatives with more benign side-effect profiles than existing treatments.

Corticosteroids in Myositis and Scleroderma.

PubMed

Postolova, Anna; Chen, Jennifer K; Chung, Lorinda

2016-02-01

Idiopathic inflammatory myopathies (IIMs) involve inflammation of the muscles and are classified by the patterns of presentation and immunohistopathologic features on skin and muscle biopsy into 4 categories: dermatomyositis, polymyositis, inclusion body myositis, and immune-mediated necrotizing myopathy. Systemic corticosteroid (CS) treatment is the standard of care for IIM with muscle and organ involvement. The extracutaneous features of systemic sclerosis are frequently treated with CS; however, high doses have been associated with scleroderma renal crisis in high-risk patients. Although CS can be effective first-line agents, their significant side effect profile encourages concomitant treatment with other immunosuppressive medications to enable timely tapering. Published by Elsevier Inc.

Evidence-Based Pharmacologic Treatment of Pediatric Bipolar Disorder.

PubMed

Findling, Robert L

2016-01-01

Pharmacotherapy is an important component of treatment for children and adolescents with bipolar disorder. The body of evidence supporting safe and effective treatments in this population is growing. Available data provide information on the risks and benefits of pharmacologic agents used for acute manic, mixed, and depressive episodes as well as for maintenance treatment. Lithium, anticonvulsants, and antipsychotics comprise the armamentarium for treating pediatric bipolar disorder. When selecting treatment, clinicians must consider the efficacy and side effect profile of potential pharmacotherapies, as well as the patient's history, including the presence of comorbidities, in order to develop a treatment plan that will ensure optimal outcomes. © Copyright 2016 Physicians Postgraduate Press, Inc.

Shoulder strength imbalances as injury risk in handball.

PubMed

Edouard, P; Degache, F; Oullion, R; Plessis, J-Y; Gleizes-Cervera, S; Calmels, P

2013-07-01

This study was conducted to analyze whether internal (IR) and external (ER) rotator shoulder muscles weakness and/or imbalance collected through a preseason assessment could be predictors of subsequent shoulder injury during a season in handball players. In preseason, 16 female elite handball players (HPG) and 14 healthy female nonathletes (CG) underwent isokinetic IR and ER strength test with use of a Con-Trex® dynamometer in a seated position with 45° shoulder abduction in scapular plane, at 60, 120 and 240°/s in concentric and at 60°/s in eccentric, for both sides. An imbalanced muscular strength profile was determined using -statistically selected cut-offs from CG values. For HPG, all newly incurred shoulder injuries were reported during the season. There were significant differences between HPG and CG only for dominant eccentric IR strength, ER/IR ratio at 240°/s and for IRecc/ERcon ratio. In HPG, IR and ER strength was higher, and ER/IR ratios lower for dominant than for nondominant side. The relative risk was 2.57 (95%CI: 1.60-3.54; P<0.05) if handball players had an imbalanced muscular strength profile. In youth female handball players IR and ER muscle strength increases on the dominant side without ER/IR imbalances; and higher injury risk was associated with imbalanced muscular strength profile. © Georg Thieme Verlag KG Stuttgart · New York.

Influence of a Simple Heat Loss Profile on a Pure Diffusion Flame

NASA Technical Reports Server (NTRS)

Ray, Anjan; Wichman, Indrek S.

1996-01-01

The presence of soot on the fuel side of a diffusion flame results in significant radiative heat losses. The influence of a fuel side heat loss zone on a pure diffusion flame established between a fuel and an oxidizer wall is investigated by assuming a hypothetical sech(sup 2) heat loss profile. The intensity and width of the loss zone are parametrically varied. The loss zone is placed at different distances from the Burke-Schumann flame location. The migration of the temperature and reactivity peaks are examined for a variety of situations. For certain cases the reaction zone breaks through the loss zone and relocates itself on the fuel side of the loss zone. In all cases the temperature and reactivity peaks move toward the fuel side with increased heat losses. The flame structure reveals that the primary balance for the energy equation is between the reaction term and the diffusion term. Extinction plots are generated for a variety of situations. The heat transfer from the flame to the walls and the radiative fraction is also investigated, and an analytical correlation formula, derived in a previous study, is shown to produce excellent predictions of our numerical results when an O(l) numerical multiplicative constant is employed.

The behavioral profile of spice and synthetic cannabinoids in humans.

PubMed

Müller, Helge H; Kornhuber, Johannes; Sperling, Wolfgang

2016-09-01

The use of synthetic cannabinoids (spice) is increasing. The number of descriptions of (new) clinical side effects is also increasing. We screened relevant publications for articles about spice with a focus on the clinical manifestations of the use of this drug. Spice creates diffuse psychiatric and somatic effects that are only partially similar to those of natural cannabinoids. Most of the observed effects are related to sympathomimetic-cardiac effects and neuropsychiatric manifestations. Clinical treatment is primarily based on intensive apparative and laboratory monitoring and supportive therapy. Because the exact active ingredients of spice are often difficult to determine with standard specific toxicology testing, the assessment and analysis of consumed substances by specialized laboratories is recommended. Copyright © 2015 Elsevier Inc. All rights reserved.

Geometric Corrections for Topographic Distortion from Side Scan Sonar Data Obtained by ANKOU System

NASA Astrophysics Data System (ADS)

Yamamoto, Fujio; Kato, Yukihiro; Ogasawara, Shohei

The ANKOU is a newly developed, full ocean depth, long-range vector side scan sonar system. The system provides real time vector side scan sonar data to produce backscattering images and bathymetric maps for seafloor swaths up to 10 km on either side of ship's centerline. Complete geometric corrections are made using towfish attitude and cross-track distortions known as foreshortening and layover caused by violation of the flat bottom assumption. Foreshortening and layover refers to pixels which have been placed at an incorrect cross-track distance. Our correction of this topographic distortion is accomplished by interpolating a bathymetric profile and ANKOU phase data. We applied these processing techniques to ANKOU backscattering data obtained from off Boso Peninsula, and confirmed their efficiency and utility for making geometric corrections of side scan sonar data.

Looking on the bright side: The story of AA Doradus as revealed by its cool companion

NASA Astrophysics Data System (ADS)

Vučković, M.; Østensen, R. H.; Németh, P.; Bloemen, S.; Pápics, P. I.

2016-02-01

The effects of irradiation on the secondary stars of close binary systems are crucial for reliably determining the system parameters and for understanding the close binary evolution. They affect the stellar structure of the irradiated star and are reflected in the appearance of characteristic features in the spectroscopic and photometric data of these systems. We aim to study the light that originates from the irradiated side of the low-mass component of a close binary eclipsing system, which comprises a hot subdwarf primary and a low mass companion, to precisely interpret their high precision photometric and spectroscopic data, and accurately determine their system and surface parameters. We reanalyse the archival high-resolution time-resolved VLT/UVES spectra of AA Dor system, where irradiation features have already been detected. After removing the predominant contribution of the hot subdwarf primary, the residual spectra reveal more than 100 emission lines from the heated side of the secondary, which show maximum intensity close to the phases around the secondary eclipse. We analyse the residual spectrum to model the irradiation of the low-mass secondary. We perform a detailed analysis of 22 narrow emission lines of the irradiated secondary, mainly of O II, with a few significant C II lines. Their phase profiles constrain the emission region of the heated side to a radius ≥95% of the radius of the secondary, while the shape of their velocity profiles reveals two distinct asymmetry features, one at the quadrature and the other at the secondary eclipse. In addition, we identify weaker emission signatures originating from more than 70 lines, including lines from He I, N II, Si III, Ca II, and Mg II. From the emission lines of the heated side of the secondary star, we determine the radial velocity semi-amplitude of the centre-of-light and correct it to the centre-of-mass of the secondary which, in turn, gives accurate masses of both components of the AA Dor system. The resulting masses M1 = 0.46 ± 0.01 M⊙ and M2 = 0.079 ± 0.002 M⊙ are in perfect accordance with those of a canonical hot subdwarf primary and a low mass that is just at the substellar limit for the companion. We also compute a first generation atmosphere model of the low mass secondary, which includes irradiation effects and matches the observed spectrum well. We find an indication of an extended atmosphere of the irradiated secondary star. Based on observations collected at the European Southern Observatory, Chile. Program ID: 066.D-1800.

Raman-Scattering Line Profiles of the Symbiotic Star AG Peg

NASA Astrophysics Data System (ADS)

Lee, Seong-Jae; Hyung, Siek

2017-06-01

The high dispersion Hα and Hβ line profiles of the Symbiotic star AG Peg consist of top double Gaussian and bottom components. We investigated the formation of the broad wings with Raman scattering mechanism. Adopting the same physical parameters from the photo-ionization study of Kim and Hyung (2008) for the white dwarf and the ionized gas shell, Monte Carlo simulations were carried out for a rotating accretion disk geometry of non-symmetrical latitude angles from -7° < θ < +7° to -16° < θ < +16°. The smaller latitude angle of the disk corresponds to the approaching side of the disk responsible for weak blue Gaussian profile, while the wider latitude angle corresponds to the other side of the disk responsible for the strong red Gaussian profile. We confirmed that the shell has the high gas density ˜ 109.85 cm-3 in the ionized zone of AG Peg derived in the previous photo-ionization model study. The simulation with various HI shell column densities (characterized by a thickness ΔD × gas number density nH) shows that the HI gas shell with a column density Hhi ≈ 3 - 5 × 1019 cm-2 fits the observed line profiles well. The estimated rotation speed of the accretion disk shell is in the range of 44 - 55 kms-1. We conclude that the kinematically incoherent structure involving the outflowing gas from the giant star caused an asymmetry of the disk and double Gaussian profiles found in AG Peg.

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.

Exploration of a Doxorubicin-Polymer Conjugate in Lipid-Polymer Hybrid Nanoparticle Drug Delivery

NASA Astrophysics Data System (ADS)

Lough, Emily

Nanoparticle (NP) drug delivery is a major focus in the research community because of its potential to use existing drugs in safer and more effective ways. Chemotherapy encapsulation in NPs shields the drug from the rest of the body while it is within the NP, with less systemic exposure leading to fewer off-target effects of the drug. However, passive loading of drugs into NPs is a suboptimal method, often leading to burst release upon administration. This work explores the impact of incorporating the drug-polymer conjugate doxorubicin-poly (lactic-co-glycolic) acid (Dox-PLGA) into a lipid-polymer hybrid nanoparticle (LPN). The primary difference in using a drug-polymer conjugate for NP drug delivery is the drug's release kinetics. Dox-PLGA LPNs showed a more sustained and prolonged release profile over 28 days compared to LPNs with passively loaded, unconjugated doxorubicin. This sustained release translates to cytotoxicity; when systemic circulation was simulated using dialysis, Dox-PLGA LPNs retained their cytotoxicity at a higher level than the passively loaded LPNs. The in vivo implication of preserving cytotoxic potency through a slower release profile is that the majority of Dox delivered via Dox-PLGA LPNs will be kept within the LPN until it reaches the tumor. This will result in fewer systemic side effects and more effective treatments given the higher drug concentration at the tumor site. An intriguing clinical application of this drug delivery approach lies in using Dox-PLGA LPNs to cross the blood-brain barrier (BBB). The incorporation of Dox-PLGA is hypothesized to have a protective effect on the BBB as its slow release profile will prevent drug from harming the BBB. Using induced pluripotent stem cells differentiated to human brain microvascular endothelial cells that comprise the BBB, the Dox-PLGA LPNs were shown to be less destructive to the BBB than their passively loaded counterparts. Dox-PLGA LPNs showed superior cytotoxicity against plated tumor cells than the passively loaded Dox LPNs after passing through an in vitro transwell BBB model. Dox-PLGA LPNs and drug-polymer conjugates are exciting alternatives to passively loaded NPs and show strong clinical promise of a treatment that is more potent with fewer side effects and less frequent administration.

Plasma metabolic profiling analysis of nephrotoxicity induced by acyclovir using metabonomics coupled with multivariate data analysis.

PubMed

Zhang, Xiuxiu; Li, Yubo; Zhou, Huifang; Fan, Simiao; Zhang, Zhenzhu; Wang, Lei; Zhang, Yanjun

2014-08-01

Acyclovir (ACV) is an antiviral agent. However, its use is limited by adverse side effect, particularly by its nephrotoxicity. Metabonomics technology can provide essential information on the metabolic profiles of biofluids and organs upon drug administration. Therefore, in this study, mass spectrometry-based metabonomics coupled with multivariate data analysis was used to identify the plasma metabolites and metabolic pathways related to nephrotoxicity caused by intraperitoneal injection of low (50mg/kg) and high (100mg/kg) doses of acyclovir. Sixteen biomarkers were identified by metabonomics and nephrotoxicity results revealed the dose-dependent effect of acyclovir on kidney tissues. The present study showed that the top four metabolic pathways interrupted by acyclovir included the metabolisms of arachidonic acid, tryptophan, arginine and proline, and glycerophospholipid. This research proves the established metabonomic approach can provide information on changes in metabolites and metabolic pathways, which can be applied to in-depth research on the mechanism of acyclovir-induced kidney injury. Copyright © 2014 Elsevier B.V. All rights reserved.

Clinical experience with trimegestone as a new progestin in HRT.

PubMed

Grubb, Gary; Spielmann, Daniele; Pickar, James; Constantine, Ginger

2003-11-01

Trimegestone (TMG) is a novel, 19-norpregnane progestin, which demonstrates endometrial selectivity with a reduced progestin-related side effect profile when compared to several other currently marketed progestins. TMG has been studied in combination with 17beta-estradiol (17beta-E2) and conjugated equine estrogens (CEE). TMG-containing HRT agents were effective in relieving vasomotor symptoms and providing protection from endometrial hyperplasia with < or =1% hyperplasia. In clinical trials with sequential regimens, TMG provided predictable withdrawal bleeding associated with a low incidence of irregular and prolonged bleeding. Clinical studies of continuous combined regimens of estrogen/TMG combinations demonstrated high levels of amenorrhea. Both 17beta-E2 and CEE/TMG combinations have shown improved bone mineral density and quality-of-life assessments. Both continuous combined and sequential regimens of 17beta-E2/TMG and CEE/TMG have a favorable clinical profile. TMG provides an important new option for the treatment of postmenopausal symptoms and the prevention of osteoporosis.

Topical capsaicin for pain in osteoarthritis: A literature review.

PubMed

Guedes, Vânia; Castro, João Paulo; Brito, Iva

Osteoarthritis is the most common joint disorder worldwide. The predominant symptom, pain, is usually treated with acetaminophen or oral non-steroidal anti-inflammatory drugs, although they are associated with a significant risk of side effects. Topical capsaicin may represent an effective and safe alternative. The aim of this review is to examine the evidence for the efficacy and safety profile of topical capsaicin in the management of pain caused by osteoarthritis. Databases were searched for articles published between 2004 and 2016, in Portuguese, English or Spanish, using the search terms "capsaicin" and "osteoarthritis". When compared to placebo, it was found that topical capsaicin has a good safety profile and efficacy in reducing osteoarthritis pain of the hand, knee, hip or shoulder. However, the studies have significant limitations, the most important the difficulty of blinding. It is attributed to this review the strength of recommendation B. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

A Novel Counter Sheet-flow Sandwich Cell Culture Device for Mammalian Cell Growth in Space

NASA Astrophysics Data System (ADS)

Sun, Shujin; Gao, Yuxin; Shu, Nanjiang; Tang, Zemei; Tao, Zulai; Long, Mian

2008-08-01

Cell culture and growth in space is crucial to understand the cellular responses under microgravity. The effects of microgravity were coupled with such environment restrictions as medium perfusion, in which the underlying mechanism has been poorly understood. In the present work, a customer-made counter sheet-flow sandwich cell culture device was developed upon a biomechanical concept from fish gill breathing. The sandwich culture unit consists of two side chambers where the medium flow is counter-directional, a central chamber where the cells are cultured, and two porous polycarbonate membranes between side and central chambers. Flow dynamics analysis revealed the symmetrical velocity profile and uniform low shear rate distribution of flowing medium inside the central culture chamber, which promotes sufficient mass transport and nutrient supply for mammalian cell growth. An on-orbit experiment performed on a recovery satellite was used to validate the availability of the device.

An Approach with Hybrid Segmental Mechanics.

PubMed

Mishra, Harsh Ashok; Maurya, Raj Kumar

2016-06-01

Present case report provides an insight into the hybrid segmental mechanics with treatment of 13-year-old male, considering the side effects of sole continuous arch wire sliding mechanics. Patient was diagnosed as a case of skeletal class I jaw relationship, low mandibular plane angle, class II molar relation on right and class I molar relation on left side, anterior cross bite, crowding of 12mm in upper, 5mm in lower arch. He also had proclined upper and lower anteriors by 2mm, convex profile and incompetent lips. Total treatment duration was 20 months, during which segmental canine retraction was performed with TMA (Titanium, Molybdenum, Aluminum) 'T' loop retraction spring followed by consolidation of spaces with continuous arch mechanics. Most of the treatment objectives were met with good intraoral and facial results within reasonable framework of time. This approach used traditional twin brackets, which offered the versatility to use continuous arch-wire mechanics, segmental mechanics and hybrid sectional mechanics.

Structural basis for bifunctional peptide recognition at human δ-opioid receptor

DOE PAGES

Fenalti, Gustavo; Zatsepin, Nadia A.; Betti, Cecilia; ...

2015-02-16

Bi-functional μ- and δ- opioid receptor (OR) ligands are potential therapeutic alternatives to alkaloid opiate analgesics with diminished side effects. We solved the structure of human δ-OR bound to the bi-functional δ-OR antagonist and μ-OR agonist tetrapeptide H-Dmt-Tic-Phe-Phe-NH 2 (DIPP-NH 2) by serial femtosecond crystallography, revealing a cis-peptide bond between H-Dmt and Tic. In summary, the observed receptor-peptide interactions are critical to understand the pharmacological profiles of opioid peptides, and to develop improved analgesics.

Managing residual limb hyperhidrosis in wounded warriors.

PubMed

Pace, Sarah; Kentosh, Joshua

2016-06-01

Residual limb dermatologic problems are a common concern among young active traumatic amputee patients who strive to maintain an active lifestyle. Hyperhidrosis of residual limbs is a recognized inciting factor that often contributes to residual limb dermatoses and is driven by the design of the prosthetic liner covering the residual limb. Treatment of hyperhidrosis in this population presents a unique challenge. Several accepted treatments of hyperhidrosis can offer some relief but have been limited by lack of results or side-effect profiles. Microwave thermal ablation has presented an enticing potential for residual limb hyperhidrosis.

Switching antipsychotic medications.

PubMed

Weiden, P J; Aquila, R; Dalheim, L; Standard, J M

1997-01-01

Compared with conventional antipsychotics, the so-called "atypical" antipsychotics promise improved side effect profiles and better control of the symptoms of schizophrenia. Therefore, most patients currently taking conventional antipsychotics could potentially benefit from a switch to an atypical antipsychotic. Often, the key issue in deciding whether to switch is the presence of countervailing factors that mitigate against the change. This paper discusses the indications and contraindications for switching antipsychotics, plus issues that require consideration before a switch is made. Also, the advantages and disadvantages of various switching techniques are discussed, with a particular focus on the newer antipsychotic olanzapine.

Prescription of medroxyprogesterone acetate to a patient with pedophilia, resulting in Cushing's syndrome and adrenal insufficiency.

PubMed

Krueger, Richard B; Hembree, Wylie; Hill, Michael

2006-04-01

This article provides a case report of a patient with pedophilia who was treated over a 4-year period with medroxyprogesterone acetate (MPA) at a dose of 300 mg/day and as a consequence developed Cushing's Syndrome and adrenal insufficiency, for which he was treated and from which he recovered. He also reported a hypersexual reaction to his own past cessation of MPA. Gonadotropin-releasing hormone agonists, which have a more benign side-effect profile than MPA, are suggested as an alternative to MPA.

Impulsive and Compulsive Behaviours in Parkinson's disease

PubMed Central

Averbeck, BB; O’Sullivan, SS; Djamshidian, A

2014-01-01

Impulsive compulsive behaviours (ICBs) in Parkinson’s disease (PD) are a common and devastating side effect of dopamine replacement therapy. In this review we describe the phenomenology, prevalence and risk factors of these patients. Results of behavioural studies assessing the neuropsychological profile emphasize that the ICBs, which are behavioural addictions, are not hedonically motivated. Rather, other factors such as the inability to cope with uncertainty may be triggering ICBs. New insights from functional imaging studies, strengthening the incentive salience hypothesis are discussed and therapeutic guidelines for the management of ICBs in PD are given. PMID:24313567

Evaluations of dielectric property and drug release profile of 5-FU patches based on plasma charged electrets

NASA Astrophysics Data System (ADS)

Wang, YUAN; Hejuan, LIANG; Ping, HUANG; Xiaoqiang, AN; Jian, JIANG; Lili, CUI

2018-05-01

In the present study, the electret 5-fluorouracil patch was developed, the effective surface potential, piezoelectric coefficient d 33, open-circuit thermally stimulated discharge (TSD) current spectra and shear adhesion of the patch were measured. The drug release profile of the patch was determined by using high performance liquid chromatography method. A stable potential difference which was positively dependent on the surface potential of the electret was generated on two sides of the patch. The measurements of d 33 coefficient, TSD current spectra and adhesion performance showed that the electrostatic field of the electret could cause polarization and cohesive strength decreasing of the matrix molecules, change the distribution and interaction of the drug molecules in patch, therefore to increase the release of drug from the transdermal patch.

Linear nozzle with tailored gas plumes

DOEpatents

Leon, David D.; Kozarek, Robert L.; Mansour, Adel; Chigier, Norman

2001-01-01

There is claimed a method for depositing fluid material from a linear nozzle in a substantially uniform manner across and along a surface. The method includes directing gaseous medium through said nozzle to provide a gaseous stream at the nozzle exit that entrains fluid material supplied to the nozzle, said gaseous stream being provided with a velocity profile across the nozzle width that compensates for the gaseous medium's tendency to assume an axisymmetric configuration after leaving the nozzle and before reaching the surface. There is also claimed a nozzle divided into respective side-by-side zones, or preferably chambers, through which a gaseous stream can be delivered in various velocity profiles across the width of said nozzle to compensate for the tendency of this gaseous medium to assume an axisymmetric configuration.

Linear nozzle with tailored gas plumes and method

DOEpatents

Leon, David D.; Kozarek, Robert L.; Mansour, Adel; Chigier, Norman

1999-01-01

There is claimed a method for depositing fluid material from a linear nozzle in a substantially uniform manner across and along a surface. The method includes directing gaseous medium through said nozzle to provide a gaseous stream at the nozzle exit that entrains fluid material supplied to the nozzle, said gaseous stream being provided with a velocity profile across the nozzle width that compensates for the gaseous medium's tendency to assume an axisymmetric configuration after leaving the nozzle and before reaching the surface. There is also claimed a nozzle divided into respective side-by-side zones, or preferably chambers, through which a gaseous stream can be delivered in various velocity profiles across the width of said nozzle to compensate for the tendency of this gaseous medium to assume an axisymmetric configuration.

Modular synthesis and in vitro and in vivo antimalarial assessment of C-10 pyrrole mannich base derivatives of artemisinin.

PubMed

Pacorel, Bénédicte; Leung, Suet C; Stachulski, Andrew V; Davies, Jill; Vivas, Livia; Lander, Hollie; Ward, Stephen A; Kaiser, Marcel; Brun, Reto; O'Neill, Paul M

2010-01-28

In two steps from dihydroartemisinin, a small array of 16 semisynthetic C-10 pyrrole Mannich artemisinin derivatives (7a-p) have been prepared in moderate to excellent yield. In vitro analysis against both chloroquine sensitive and resistant strains has demonstrated that these analogues have nanomolar antimalarial activity, with several compounds being more than 3 times more potent than the natural product artemisinin. In addition to a potent antimalarial profile, these molecules also have very high in vitro therapeutic indices. Analysis of the optimal Mannich side chain substitution for in vitro and in vivo activity reveals that the morpholine and N-methylpiperazine Mannich side chains provide analogues with the best activity profiles, both in vitro and in vivo in the Peter's 4 day test.

Linear nozzle with tailored gas plumes

DOEpatents

Kozarek, Robert L.; Straub, William D.; Fischer, Joern E.; Leon, David D.

2003-01-01

There is claimed a method for depositing fluid material from a linear nozzle in a substantially uniform manner across and along a surface. The method includes directing gaseous medium through said nozzle to provide a gaseous stream at the nozzle exit that entrains fluid material supplied to the nozzle, said gaseous stream being provided with a velocity profile across the nozzle width that compensates for the gaseous medium's tendency to assume an axisymmetric configuration after leaving the nozzle and before reaching the surface. There is also claimed a nozzle divided into respective side-by-side zones, or preferably chambers, through which a gaseous stream can be delivered in various velocity profiles across the width of said nozzle to compensate for the tendency of this gaseous medium to assume an axisymmetric configuration.

The effect of deformation after backarc spreading between the rear arc and current volcanic front in Shikoku Basin obtained by seismic reflection survey

NASA Astrophysics Data System (ADS)

Yamashita, M.; Takahashi, N.; Nakanishi, A.; Kodaira, S.; Tamura, Y.

2012-12-01

Detailed crustal structure information of a back-arc basin must be obtained to elucidate the mechanism of its opening. Especially, the Shikoku Basin, which occupies the northern part of the Philippine Sea Plate between the Kyushu-Palau Ridge and the Izu-Bonin (Ogasawara) Arc, is an important area to understand the evolution of the back-arc basins as a part of the growth process of the Philippine Sea. Especially, the crustal structure oft the east side of Shikoku Basin is complicated by colliding to the Izu Peninsula Japan Agency for Marine-Earth Science and Technology has been carried out many multi-channel seismic reflection surveys since 2004 in Izu-Bonin region. Kodaira et al. (2008) reported the results of a refraction seismic survey along a north-south profile within paleoarc in the rear arc (i.e., the Nishi-shichito ridge) about 150 km west of current volcanic front. According to their results, the variation relationship of crustal thickness between the rear arc and volcanic front is suggested the evidence of rifting from current volcanic arc. There is the en-echelon arrangement is located in the eastern side of Shikoku Basin from current arc to rear arc, and it is known to activate after ceased spreading at 15 Ma (Okino et al., 1994) of Shikoku Basin by geologic sampling of Ishizuka et al. (2003). Our MCS results are also recognized the recent lateral fault zone is located in east side of Shikoku Basin. We carried out high density grid multi-channel seismic reflection (MCS) survey using tuned airgun in order to obtain the relationship between the lateral faults and en-echelon arrangement in KR08-04 cruise. We identified the deformation of sediments in Shikoku Basin after activity of Kanbun seamount at 8 Ma in MCS profile. It is estimated to activate a part of the eastern side of Shikoku Basin after construction of en-echelon arrangement and termination of Shikoku Basin spreading. Based on analyses of magnetic and gravity anomalies, Yamazaki and Yuasa (1998) proposed that the Miocene rifting had occurred at the western half of the northern Izu-Bonin Arc during the Middle Miocene, immediately after spreading ended in the Shikoku Basin. In this study, we compare about this hypothesis from the characteristics of MCS profiles. In 2012, we also carried out the new MCS survey around the Zenisu ridge. From the primary onboard result, many crustal reflectors are identified around the Zenisu ridge. We will report the new MCS result in northeast side of Shikoku Basin.

Transient bedrock channel evolution across a precipitation gradient: A case study from Kohala, Hawaii.

NASA Astrophysics Data System (ADS)

Gasparini, N. M.; Han, J.; Johnson, J. P.; Menking, J. A.

2011-12-01

This study uses observations from the Kohala Peninsula, on the Big Island of Hawaii, and numerical modeling, to explore how precipitation gradients may affect fluvial bedrock incision and channel morphology. Orographic precipitation patterns result in over 4 m/yr of rainfall on the wet side of the peninsula and less than 0.5 m/yr on the dry side. These precipitation patterns likely strongly contribute to the observed channel morphology. Further, the region is subsiding, leading to prolonged transient channel evolution. We explore changes in a number of channel morphologic parameters with watershed averaged precipitation rate. We use PRISM precipitation data and data from isohyets developed from historic rain gauge data. Not surprisingly, valley depth, measured from a 10 meter DEM, increases with spatially averaged precipitation rate. We also find that channel profile form varies with precipitation rate, with drier channels exhibiting a straight to slightly concave channel form and wetter channels exhibiting a convex to concave channel form. The precipitation value at which this transition in channel profile form occurs depends on the precipitation data-set used, highlighting the need for more accurate measurements of precipitation in settings with extreme precipitation patterns similar to our study area. The downstream pattern in precipitation is likely significant in the development of the convex-concave profile form. Numerical modeling results support that precipitation patterns such as those observed on the wet-side of the Kohala Peninsula may contribute to the convex-concave profile form. However, we emphasize that while precipitation patterns may contribute to the channel form, these channel features are transient and not expected to be sustained in steady-state landscapes. We also emphasize that it is fluvial discharge, as driven by precipitation, rather than precipitation alone, that drives the processes shaping the channel form. Because fluvial discharge is integrative, relatively extreme precipitation gradients are required to produce anomalous channel profile forms.

A Balloon Sounding Technique for Measuring SO2 Plumes

NASA Technical Reports Server (NTRS)

Morris, Gary A.; Komhyr, Walter D.; Hirokawa, Jun; Lefer, Barry; Krotkov, Nicholay; Ngan, Fong

2010-01-01

This paper reports on the development of a new technique for inexpensive measurements of SO2 profiles using a modified dual-ozonesonde instrument payload. The presence of SO2 interferes with the standard electrochemical cell (ECC) ozonesonde measurement, resulting in -1 molecule of O3 reported for each molecule of SO2 present (provided [O3] > [SO2]). In laboratory tests, an SO2 filter made with Cr03 placed on the inlet side of the sonde removes nearly 100% of the SO2 present for concentrations up to 60 ppbv and remained effective after exposure to 2.8 X 10(exp 16) molecules of SO2 [equivalent to a column approximately 150 DU (1 DU = 2.69 X 10(exp 20) molecules m(exp -2))]. Flying two ECC instruments on the same payload with one filtered and the other unfiltered yields SO2 profiles, inferred by subtraction. Laboratory tests and field experience suggest an SO2 detection limit of approximately 3 pbb with profiles valid from the surface to the ozonopause [i.e., approximately (8-10 km)]. Two example profiles demonstrate the success of this technique for both volcanic and industrial plumes.

Computer Recognition of Facial Profiles

DTIC Science & Technology

1974-08-01

facial recognition 20. ABSTRACT (Continue on reverse side It necessary and Identify by block number) A system for the recognition of human faces from...21 2.6 Classification Algorithms ........... ... 32 III FACIAL RECOGNITION AND AUTOMATIC TRAINING . . . 37 3.1 Facial Profile Recognition...provide a fair test of the classification system. The work of Goldstein, Harmon, and Lesk [81 indicates, however, that for facial recognition , a ten class

Influence of pelvic floor muscle contraction on the profile of vaginal closure pressure in continent and stress urinary incontinent women.

PubMed

Shishido, Keiichi; Peng, Qiyu; Jones, Ruth; Omata, Sadao; Constantinou, Christos E

2008-05-01

We characterized the vaginal pressure profile as a representation of closure forces along the length and circumference of the vaginal wall. Vaginal pressure profile data were used to test the hypothesis that the strength of pelvic floor muscle contractions differs significantly between continent women and women with stress urinary incontinence. Vaginal pressure profile recordings were made in 23 continent subjects and in 10 patients with stress urinary incontinence. The recordings characterized closure forces along the entire length of the vagina and identified differences among the anterior, posterior, left and right sides of the vaginal wall. Using a novel, directionally sensitive vaginal probe we made vaginal pressure profile measurements with the women at rest and during pelvic floor muscle contraction while supine. The nature of the vaginal pressure profile was characterized in terms of force distribution in the anterior and posterior vaginal walls, which was significantly greater than that on the left and right sides. The continent group had significant greater maximum pressure than the stress urinary incontinence group on the posterior side at rest (mean +/- SE 3.4 +/- 0.3 vs 2.01 +/- 0.36 N/cm(2)) and during pelvic floor muscle contraction (4.18 +/- 0.26 vs 2.25 +/- 0.41 N/cm(2)). The activity pressure difference between the posterior and anterior vaginal walls in the continent group was significantly increased when the pelvic floor muscles contracted vs that at rest (3.29 +/- 0.21 vs 2.45 +/- 0.26 N/cm(2)). However, the change observed in the stress urinary incontinence group was not significant (1.85 +/- 0.38 vs 1.35 +/- 0.27 N/cm(2)). The results demonstrate that the voluntary pelvic floor muscles impose significant closure forces along the vaginal wall of continent women but not in women with stress urinary incontinence. The implication of these findings is that extrinsic urethral closure pressure is insufficiently augmented by pelvic floor muscle contraction in women with stress urinary incontinence.

β-adrenergic-stimulated macrophages: Comprehensive localization in the M1–M2 spectrum

PubMed Central

Lamkin, Donald M.; Ho, Hsin-Yun; Ong, Tiffany H.; Kawanishi, Carly K.; Stoffers, Victoria L.; Ahlawat, Nivedita; Ma, Jeffrey C.Y.; Arevalo, Jesusa M. G.; Cole, Steve W.; Sloan, Erica K.

2016-01-01

β-adrenergic signaling can regulate macrophage involvement in several diseases and often produces anti-inflammatory properties in macrophages, which are similar to M2 properties in a dichotomous M1 vs. M2 macrophage taxonomy. However, it is not clear that β-adrenergic-stimulated macrophages may be classified strictly as M2. In this in vitro study, we utilized recently published criteria and transcriptome-wide bioinformatics methods to map the relative polarity of murine β-adrenergic-stimulated macrophages within a wider M1–M2 spectrum. Results show that β-adrenergic-stimulated macrophages did not fit entirely into any one predefined category of the M1–M2 spectrum but did express genes that are representative of some M2 side categories. Moreover, transcript origin analysis of genome-wide transcriptional profiles located β-adrenergic-stimulated macrophages firmly on the M2 side of the M1–M2 spectrum and found active suppression of M1 side gene transcripts. The signal transduction pathways involved were mapped through blocking experiments and bioinformatics analysis of transcription factor binding motifs. M2-promoting effects were mediated specifically through β2-adrenergic receptors and were associated with CREB, C/EBPβ, and ATF transcription factor pathways but not with established M1–M2 STAT pathways. Thus, β-adrenergic-signaling induces a macrophage transcriptome that locates on the M2 side of the M1–M2 spectrum but likely accomplishes this effect through a signaling pathway that is atypical for M2-spectrum macrophages. PMID:27485040

β-Adrenergic-stimulated macrophages: Comprehensive localization in the M1-M2 spectrum.

PubMed

Lamkin, Donald M; Ho, Hsin-Yun; Ong, Tiffany H; Kawanishi, Carly K; Stoffers, Victoria L; Ahlawat, Nivedita; Ma, Jeffrey C Y; Arevalo, Jesusa M G; Cole, Steve W; Sloan, Erica K

2016-10-01

β-Adrenergic signaling can regulate macrophage involvement in several diseases and often produces anti-inflammatory properties in macrophages, which are similar to M2 properties in a dichotomous M1 vs. M2 macrophage taxonomy. However, it is not clear that β-adrenergic-stimulated macrophages may be classified strictly as M2. In this in vitro study, we utilized recently published criteria and transcriptome-wide bioinformatics methods to map the relative polarity of murine β-adrenergic-stimulated macrophages within a wider M1-M2 spectrum. Results show that β-adrenergic-stimulated macrophages did not fit entirely into any one pre-defined category of the M1-M2 spectrum but did express genes that are representative of some M2 side categories. Moreover, transcript origin analysis of genome-wide transcriptional profiles located β-adrenergic-stimulated macrophages firmly on the M2 side of the M1-M2 spectrum and found active suppression of M1 side gene transcripts. The signal transduction pathways involved were mapped through blocking experiments and bioinformatics analysis of transcription factor binding motifs. M2-promoting effects were mediated specifically through β2-adrenergic receptors and were associated with CREB, C/EBPβ, and ATF transcription factor pathways but not with established M1-M2 STAT pathways. Thus, β-adrenergic-signaling induces a macrophage transcriptome that locates on the M2 side of the M1-M2 spectrum but likely accomplishes this effect through a signaling pathway that is atypical for M2-spectrum macrophages. Copyright © 2016 Elsevier Inc. All rights reserved.

Mental Fatigue: Impairment of Technical Performance in Small-Sided Soccer Games.

PubMed

Badin, Oliver O; Smith, Mitchell R; Conte, Daniele; Coutts, Aaron J

2016-11-01

To assess the effects of mental fatigue on physical and technical performance in small-sided soccer games. Twenty soccer players (age 17.8 ± 1.0 y, height 179 ± 5 cm, body mass 72.4 ± 6.8 kg, playing experience 8.3 ± 1.4 y) from an Australian National Premier League soccer club volunteered to participate in this randomized crossover investigation. Participants played 15-min 5-vs-5 small-sided games (SSGs) without goalkeepers on 2 occasions separated by 1 wk. Before the SSG, 1 team watched a 30-min emotionally neutral documentary (control), while the other performed 30 min of a computer-based Stroop task (mental fatigue). Subjective ratings of mental and physical fatigue were recorded before and after treatment and after the SSG. Motivation was assessed before treatment and SSG; mental effort was assessed after treatment and SSG. Player activity profiles and heart rate (HR) were measured throughout the SSG, whereas ratings of perceived exertion (RPEs) were recorded before the SSG and immediately after each half. Video recordings of the SSG allowed for notational analysis of technical variables. Subjective ratings of mental fatigue and effort were higher after the Stroop task, whereas motivation for the upcoming SSG was similar between conditions. HR during the SSG was possibly higher in the control condition, whereas RPE was likely higher in the mental-fatigue condition. Mental fatigue had an unclear effect on most physical-performance variables but impaired most technical-performance variables. Mental fatigue impairs technical but not physical performance in small-sided soccer games.

The use of antidepressant drugs in dermatology.

PubMed

Gupta, M A; Guptat, A K

2001-11-01

This paper provides an updated review of the use of antidepressant drugs in dermatology. Some of the psychiatric disorders that are usually comorbid with dermatological disorders and respond to antidepressants include major depressive disorder, obsessive compulsive disorder, body dysmorphic disorder, social phobia and post-traumatic stress disorder usually secondary to trauma and abuse during early life. Cutaneous symptoms may be the feature of a primary psychiatric disorder, e.g. cutaneous body image problems, dermatitis artefacta, neurotic excoriations and trichotillomania, or psychiatric syndromes may be comorbid with a primary dermatological disorder such as the association of major depressive disorder or social phobia with psoriasis and obsessive compulsive disorder with acne excoriee. Some of the salient pharmacological properties of the tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitor (SSRI) antidepressants are reviewed. The review indicates that the SSRI antidepressants are potentially beneficial in the management of all the major psychiatric syndromes that are encountered in dermatological disorders. The generally more favourable side-effect profile of the SSRIs, such as lower cardiotoxicity in contrast to the TCAs, has made them the first-line agents for the treatment of depression. Furthermore, some of the pharmacological properties of the antidepressant agents that are not related to their antidepressant activity, such as the histamine H1 blocking effect of TCAs, such as doxepin, amitriptyline and trimipramine, are of benefit in dermatological conditions such as urticaria and pruritus. This paper reviews the general guidelines for use of antidepressants and salient drug-drug interactions resulting mainly from the inhibition of the cytochrome P450 (CYP) 2D6 and 3A3/4 isoenzymes by some of the SSRI antidepressants. Before prescribing an antidepressant agent, the specific guidelines, side-effect profile, drug-drug interactions and most current indications should always be obtained.

Outcomes of fractional CO2 laser application in aesthetic surgery: a retrospective review.

PubMed

Neaman, Keith C; Baca, Marissa E; Piazza, Rocco C; VanderWoude, Douglas L; Renucci, John D

2010-01-01

Despite the effectiveness of ablative CO(2) laser resurfacing for facial rejuvenation, its application has been limited owing to an undesirable side-effect profile, including prolonged hyperemia and potential pigmentary changes. However, newer fractional CO(2) laser technology has reduced the recovery time and led to decreases in postprocedural hypo- and hyperpigmentation. The authors investigate the application and outcomes of ablative fractional technology in a private cosmetic surgery practice. In this retrospective cohort study, the charts of patients who received fractional CO(2) laser resurfacing between March 2007 and May 2008 were reviewed. Data regarding patient demographics, pretreatment regimens, detailed operative data, and posttreatment findings were obtained. The length of hyperemia (less than five weeks, five to eight weeks, and more than eight weeks), complication rates, and revision rates were analyzed. A satisfaction survey was also sent to all patients. Throughout the 19-month study period, 97 patients received 101 treatments with an average follow-up of 4.5 months. Full-face laser resurfacing was performed in 81.1% of patients, with 64.3% receiving their treatment under local anesthesia without sedation. Length of hyperemia was less than five weeks in 93%, five to eight weeks in 5.9%, and more than eight weeks in 0.9% of patients. Hyperpigmentation (9.9%), milia (6.9%), acne breakout (5.9%), and transient ectropion (0.9%) were less common. Patient satisfaction surveys revealed that a majority of patients were satisfied with their results. New fractional CO(2) laser skin resurfacing is associated with shorter periods of hyperemia, resulting in shorter recovery time in comparison with older ablative technology. The side-effect profile is minor and infrequent. This new technology provides significant clinical improvement with high patient satisfaction.

Some Novel Mannich Bases of 5-(3,4-Dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one and Their Anti-Inflammatory Activity.

PubMed

Koksal, Meric; Ozkan-Dagliyan, Irem; Ozyazici, Tugce; Kadioglu, Beril; Sipahi, Hande; Bozkurt, Ayhan; Bilge, Suleyman S

2017-09-01

Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for the treatment of rheumatic arthritis, pain, and many different types of inflammatory disorders, cause serious gastrointestinal (GI) side effects. The free carboxylic acid group existing on their chemical structure is correlated with GI toxicity related with all routine NSAIDs. Replacing this functional group with the 1,3,4-oxadiazole bioisostere is a generally used strategy to obtain an anti-inflammatory agent devoid of GI side effects. In the present work, a novel group of 5-(3,4-dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one Mannich bases were synthesized and characterized on the basis of IR, 1 H NMR, and elemental analysis results. The target compounds were first tested for cytotoxicity to determine a non-toxic concentration for anti-inflammatory screening. Anti-inflammatory effects of the compounds were evaluated by in vitro lipopolysaccharide (LPS)-induced NO production and in vivo carrageenan footpad edema with ulcerogenic profile. In LPS-induced RAW 264.7 macrophages, most of the compounds showed inhibitory activity on nitrite production while compounds 5a, 5h, and 5j exhibited the best profiles by suppressing the NO production. To evaluate the in vivo anti-inflammatory potency of the compounds, the inflammatory response was quantified by increment in paw size in the carrageenan footpad edema assay. The anti-inflammatory data scoring showed that compounds 5a-d, 5g, and 5j, at the dose of 100 mg/kg, exhibited anti-inflammatory activity, which for compound 5g was comparable to that of the reference drug indomethacin with 53.9% and 55.5% inhibition in 60 and 120 min, respectively. © 2017 Deutsche Pharmazeutische Gesellschaft.

Somatoform symptoms and treatment nonadherence in depressed family medicine outpatients.

PubMed

Keeley, R; Smith, M; Miller, J

2000-01-01

To examine whether somatoform symptoms, specifically symptoms of conversion, somatization, and hypochondriasis, are associated with side-effect reporting and treatment nonadherence in depressed family medicine outpatients, and to measure whether symptoms improve with pharmacotherapy. Inception cohort study with 14-week follow-up. Inner-city family medicine residency clinic. Thirty-nine consecutive adults with major depressive disorder were asked to participate, and 30 consented. Antidepressants for 14 weeks. The Personality Assessment Inventory (PAI) was administered before treatment. The PAI is a self-reported inventory compatible with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, designed to measure a broad range of personality characteristics. After 14 weeks, the side-effect incidence and treatment nonadherence rates were determined, and 12 patients were readministered the PAI. Depressed family medicine patients demonstrated trends toward elevated Somatic Complaints scale and conversion subscale scores and a lower Suicidal Ideation scale score relative to those of a standardized depressed psychiatric patient profile. Conversion and hypochondriacal symptoms were associated with side-effect reporting and treatment nonadherence. Somatization and hypochondriacal symptoms improved clinically and statistically during treatment for depression. Somatoform distress is a complex, common, and understudied phenomenon in primary care that can adversely affect the treatment of depression. Somatoform symptoms of conversion and hypochondriasis, but not somatization, were found to be risk factors for treatment nonadherence. Somatization and hypochondriacal symptoms may represent personality states that improve with pharmacotherapy, and conversion symptoms may be a personality trait resistant to medical treatment for depression.

Safety, tolerability, and efficacy of metformin extended-release oral antidiabetic therapy in patients with type 2 diabetes: An observational trial in Asia

PubMed Central

Kim, Chul-Hee; Han, Kyung-Ah; Oh, Han-Jin; Tan, Kevin Eng-Kiat; Sothiratnam, Radhakrishna; Tjokroprawiro, Askandar; Klein, Marcus

2012-01-01

Background The aim of the present prospective observational study was to assess the tolerability and antihyperglycemic efficacy of metformin extended-release (MXR) in the routine treatment of patients with type 2 diabetes mellitus (T2DM) from six Asian countries. Methods Data from 3556 patients treated with once-daily MXR for 12 weeks, or until discontinuation, were analyzed. Results Treatment with MXR was well tolerated, with 97.4% of patients completing 12 weeks of treatment. Only 3.3% of patients experienced one or more gastrointestinal (GI) side-effects and only 0.7% of patients discontinued for this reason (primary endpoint). The incidence of GI side-effects and related discontinuations appeared to be considerably lower during short-term MXR therapy than during previous treatment (mean 2.71 years’ duration), most commonly with immediate-release metformin. A 12-week course of MXR therapy also reduced HbA1c and fasting glucose levels from baseline. Conclusions The present study provides new insights into the incidence of GI side-effects with MXR in Asian patients with T2DM and on the tolerability of MXR in non-Caucasian populations. Specifically, these data indicate that once-daily MXR not only improves measures of glycemic control in Asian patients with T2DM, but also has a favorable GI tolerability profile that may help promote enhanced adherence to oral antidiabetic therapy. PMID:22742083

Spatial distribution of fluorescent light emitted from neon and nitrogen excited by low energy electron beams

NASA Astrophysics Data System (ADS)

Morozov, A.; Krücken, R.; Ulrich, A.; Wieser, J.

2006-11-01

Side-view intensity profiles of fluorescent light were measured for neon and nitrogen excited with 12keV electron beams at gas pressures from 250to1400hPa. The intensity profiles were compared with theoretical profiles calculated using the CASINO program which performs Monte Carlo simulations of electron scattering. It was assumed that the spatial distribution of fluorescent intensity is directly proportional to the spatial distribution of energy loss by primary electrons. The comparison shows good correlation of experimental data and the results of numeric simulations.

Effectiveness and tolerance of anti-inflammatory drugs' add-on therapy in major mental disorders: a systematic qualitative review.

PubMed

Fond, G; Hamdani, N; Kapczinski, F; Boukouaci, W; Drancourt, N; Dargel, A; Oliveira, J; Le Guen, E; Marlinge, E; Tamouza, R; Leboyer, M

2014-03-01

To provide a systematic review of the literature regarding the efficacy of anti-inflammatory drugs in three major mental disorders [major depressive disorder (MDD), schizophrenia and bipolar disorders]. Four databases were explored, without any year or language restrictions. The baseline search paradigm was limited to open-labelled clinical and randomized controlled trials (RCTs). Four major classes of anti-inflammatory drugs were identified, namely polyunsaturated fatty acids (PUFAs), cyclooxygenase (COX) inhibitors, anti-TNFalpha and minocycline. Effectiveness and benefit/risk ratio of each class in MDD, bipolar disorders and schizophrenia was detailed when data were available. Several meta-analyses indicated effectiveness of PUFAs in MDD with a good tolerance profile. One meta-analysis indicated that COX-2 specific inhibitors showed effectiveness in schizophrenia. Anti-TNFalpha showed important effectiveness in resistant MDD with blood inflammatory abnormalities. Minocycline showed effectiveness in schizophrenia. Polyunsaturated fatty acids seem to have the best benefit/risk ratio profile but proved their effectiveness only in MDD. A number of anti-inflammatory drugs are available as adjunct treatment for treatment-resistant patients with MDD, schizophrenia and bipolar disorder. If used with caution regarding their possible side-effects, they may be reasonable therapeutic alternatives for resistant symptomatology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Attenuation of neurodegenerative phenotypes in Alzheimer-like presenilin 1/presenilin 2 conditional double knockout mice by EUK1001, a promising derivative of xanomeline.

PubMed

Wang, Dong; Yang, Liguo; Su, Jingjing; Niu, Yan; Lei, Xiaoping; Xiong, Juan; Cao, Xiaohua; Hu, Yinghe; Mei, Bing; Hu, Jin-Feng

2011-07-01

The M1/M4-preferring muscarinic agonist xanomeline was found to have some benefit in the treatment of the memory impairment of Alzheimer's disease (AD), but side effects precluded further development. EUK1001, a fluorinated derivative of xanomeline, because of greater affinity for M1 muscarinic receptors, is likely to have a significantly better side effect profile than xanomeline. We have now studied the effects of 3-month chronic administration of EUK1001 and xanomeline (0.5mg/kg/day) in AD-like presenilin 1/presenilin 2 conditional double knockout (PS cDKO) mice. Only EUK1001 was found to significantly ameliorate the deficit in recognition memory. Histological analysis demonstrated partial attenuation of the brain atrophy in EUK1001-treated PS cDKO mice and minimal effect in the xanomeline-treated mice. Both compounds effectively suppressed the elevation of brain tau phosphorylation in the PS cDKO mice, but neither inhibited the increased inflammatory responses. These results indicate that EUK1001 showed superiority to xanomeline with regard to attenuation of several AD-like neurodegenerative phenotypes in PS cDKO mice. These results suggest further investigation of the development of EUK1001 for the treatment of AD is indicated. Copyright © 2011 Elsevier Inc. All rights reserved.

A Profile of Glenohumeral Internal and External Rotation Motion in the Uninjured High School Baseball Pitcher, Part I: Motion

PubMed Central

Hurd, Wendy J.; Kaplan, Kevin M.; ElAttrache, Neal S.; Jobe, Frank W.; Morrey, Bernard F.; Kaufman, Kenton R.

2011-01-01

Context: The magnitude of motion that is normal for the throwing shoulder in uninjured baseball pitchers has not been established. Chronologic factors contributing to adaptations in motion present in the thrower's shoulder also have not been established. Objectives: To develop a normative profile of glenohumeral rotation motion in uninjured high school baseball pitchers and to evaluate the effect of chronologic characteristics on the development of adaptations in shoulder rotation motion. Design: Cohort study. Setting: Baseball playing field. Patients or Other Participants: A total of 210 uninjured male high school baseball pitchers (age = 16±1.1 years, height = 1.8 + 0.1 m, mass = 77.5±11.2 kg, pitching experience = 6±2.3 years). Intervention(s): Using standard goniometric techniques, we measured passive rotational glenohumeral range of motion bilaterally with participants in the supine position. Main Outcome Measure(s): Paired t tests were performed to identify differences in motion between limbs for the group. Analysis of variance and post hoc Tukey tests were conducted to identify differences in motion by age. Linear regressions were performed to determine the influence of chronologic factors on limb motion. Results: Rotation motion characteristics for the population were established. We found no difference between sides for external rotation (ER) at 0° of abduction (t209 = 0.658, P = .51), but we found side-to-side differences in ER (t209 = −13.012, P<.001) and internal rotation (t209 = 15.304, P<.001) at 90° of abduction. Age at the time of testing was a significant negative predictor of ER motion for the dominant shoulder (R2 = 0.019, P = .049) because less ER motion occurred at the dominant shoulder with advancing age. We found no differences in rotation motion in the dominant shoulder across ages (F4,205 range, 0.451–1.730, P>.05). Conclusions: This range-of-motion profile might be used to assist with the interpretation of normal and atypical shoulder rotation motion in this population. Chronologic characteristics of athletes had no influence on range-of-motion adaptations in the thrower's shoulder. PMID:21669098

Adeno-Associated Virus Type 2 Wild-Type and Vector-Mediated Genomic Integration Profiles of Human Diploid Fibroblasts Analyzed by Third-Generation PacBio DNA Sequencing

PubMed Central

Hüser, Daniela; Gogol-Döring, Andreas; Chen, Wei

2014-01-01

ABSTRACT Genome-wide analysis of adeno-associated virus (AAV) type 2 integration in HeLa cells has shown that wild-type AAV integrates at numerous genomic sites, including AAVS1 on chromosome 19q13.42. Multiple GAGY/C repeats, resembling consensus AAV Rep-binding sites are preferred, whereas rep-deficient AAV vectors (rAAV) regularly show a random integration profile. This study is the first study to analyze wild-type AAV integration in diploid human fibroblasts. Applying high-throughput third-generation PacBio-based DNA sequencing, integration profiles of wild-type AAV and rAAV are compared side by side. Bioinformatic analysis reveals that both wild-type AAV and rAAV prefer open chromatin regions. Although genomic features of AAV integration largely reproduce previous findings, the pattern of integration hot spots differs from that described in HeLa cells before. DNase-Seq data for human fibroblasts and for HeLa cells reveal variant chromatin accessibility at preferred AAV integration hot spots that correlates with variant hot spot preferences. DNase-Seq patterns of these sites in human tissues, including liver, muscle, heart, brain, skin, and embryonic stem cells further underline variant chromatin accessibility. In summary, AAV integration is dependent on cell-type-specific, variant chromatin accessibility leading to random integration profiles for rAAV, whereas wild-type AAV integration sites cluster near GAGY/C repeats. IMPORTANCE Adeno-associated virus type 2 (AAV) is assumed to establish latency by chromosomal integration of its DNA. This is the first genome-wide analysis of wild-type AAV2 integration in diploid human cells and the first to compare wild-type to recombinant AAV vector integration side by side under identical experimental conditions. Major determinants of wild-type AAV integration represent open chromatin regions with accessible consensus AAV Rep-binding sites. The variant chromatin accessibility of different human tissues or cell types will have impact on vector targeting to be considered during gene therapy. PMID:25031342

Suitability of the adenosine antagonist istradefylline for the treatment of Parkinson's disease: pharmacokinetic and clinical considerations.

PubMed

Müller, Thomas

2013-08-01

Recent experimental and clinical research has shown that A2A adenosine receptor antagonism can bring about an improvement in the motor behavior of patients with Parkinson's disease. Istradefylline , a xanthine derivative, has the longest half-life of all the currently available A2A adenosine receptor antagonists; it can successfully permeate through the blood-brain barrier and has a high human A2A adenosine receptor affinity. In this article, the author discusses the potential role of A2A adenosine receptor antagonists in the treatment of Parkinson's disease through the evaluation of istradefylline. Specifically, the article reviews the clinical and pharmacokinetic information available to elucidate its therapeutic potential. A2A adenosine receptor antagonists are efficacious in combination with l-dopa. l-dopa has a complex pharmacokinetic behavior and causes long-term behavioral and metabolic side effects. Future research on A2A adenosine receptor antagonism should consider compounds like istradefylline as l-dopa and/or dopamine agonist-sparing treatment alternatives, since their clinical handling, safety and side-effect profile are superior to l-dopa and/or dopamine agonists. The current focus to demonstrate a specific dyskinesia-ameliorating efficacy of A2A adenosine receptor antagonism in clinical trials is risky, since the presentation of dyskinesia varies on a day-to-day basis and is considerably influenced by peripheral l-dopa metabolism. The demonstration of an antidyskinetic effect may convince authorities, but this is far less relevant in clinical practice as patients generally better tolerate dyskinesia than other phenomena and dopaminergic side effects.

Double-Track Electrochemical Green Approach for Simultaneous Dissolution Profiling of Naproxen Sodium and Diphenhydramine Hydrochloride.

PubMed

Shehata, Mostafa A; Fawaz, Esraa M; El-Rahman, Mohamed K Abd; Abdel-Moety, Ezzat M

2017-11-30

Acquisition of the dissolution profiles of more than single active ingredient in a multi-analyte pharmaceutical formulation is a mandatory manufacturing practice that is dominated by utilization of the off-line separation-based chromatographic methods. This contribution adopts a new "Double-Track" approach with the ultimate goal of advancing the in-line potentiometric sensors to their most effective applicability for simultaneous acquisition of the dissolution profiles of two active ingredients in a binary pharmaceutical formulation. The unique abilities of these sensors for real-time measurements is the key driver for adoption of "green analytical chemistry" (GAC) principles aiming to expand the application of eco-friendly analytical methods With the aim of performing a side-by-side comparison, this work investigates the degree of adherence of ISEs to the 12 principles of GAC in multicomponent dissolution profiling with respect to the HPLC. For the proof of concept, a binary mixture of naproxen sodium (NAPR) and diphenhydramine hydrochloride (DIPH) marketed as Aleve pm ® tablets was selected as a model for which dissolution profiles were attained by two techniques. The first "Double-Track" in-line strategy depends on dipping two highly integrated membrane sensors for continuous monitoring of the dissolution of each active pharmaceutical ingredient (API) by tracing the e.m.f change over the time scale. For the determination of NAPR, sensor I was developed using tridodecyl methyl ammonium chloride as an anion exchanger, while sensor II was developed for the determination of DIPH using potassium tetrakis (4-chlorophenyl) borate as a cation exchanger. The second off-line strategy utilizes a separation-based HPLC method via off-line tracking the increase of peak area by UV detection at 220nm over time using a mobile phase of acetonitrile: water (90:10) pH 3. The advantages of the newly introduced "Double-Track" approach regarding GAC principles are highlighted, and the merits of these benign real-time analyzers (ISEs) that can deliver equivalent analytical results as HPLC while significantly reducing solvent consumption/waste generation are described. Copyright © 2017 Elsevier B.V. All rights reserved.

Transient thermal analysis during friction stir welding between AA2014-T6 and pure copper

NASA Astrophysics Data System (ADS)

Gadhavi, A. R.; Ghetiya, N. D.; Patel, K. M.

2018-04-01

AA2xxx-Cu alloys showed larger applications in the defence sectors and in aerospace industries due to high strength to weight ratio and toughness. FSW in a butt joint configuration was carried out between AA2014-T6 and pure Copper placing AA2014 on AS and Cu on RS. Temperature profiles were observed by inserting K-type thermocouples in the mid-thickness at various locations of the plate. A sharp decrease in temperature profiles was observed on Copper side due to its higher thermal conductivity. A thermal numerical model was prepared in ANSYS to compare the simulated temperature profiles with the experimental temperature profiles and both the temperature profiles were found to be in good agreement.

Medical Systemic Therapies for Hepatocellular Carcinoma: Clinical Perspectives and Safety Profile.

PubMed

Facciorusso, Antonio; Antonino, Matteo; Del Prete, Valentina; Amoruso, Annabianca; Neve, Viviana; Barone, Michele

2015-01-01

A multidisciplinary approach based on clinical expertise and knowledge of molecular processes involved in hepatocarcinogenesis is needed for the proper management of hepatocellular carcinoma (HCC) patients. Such information must be considered in the context of pathobiology of the underlying liver disease. New drugs targeting specific molecular steps in pathways involved in HCC growth and development bear the promise to radically modify the pharmacological therapies currently in use in hepatooncology. Sorafenib was the first drug approved in the setting of advanced HCC, but although it produces some improvement in survival, the responses are not durable. In addition, there are significant side effects. Other angiogenesis inhibitors are in development to treat HCC both in the first-line setting and after progression following sorafenib failure; among them, tivantinib, an inhibitor of cMET receptor, showed interesting results in a recent phase-II study. Additional agents currently studied for the treatment of HCC patients are briefly examined in this review. Aim of this paper is to discuss the state of the art in the management of advanced HCC patients, with a particular interest for the description of their side effects.

Validation of accelerated ageing of Thales rotary Stirling cryocoolers for the estimation of MTTF

NASA Astrophysics Data System (ADS)

Seguineau, C.,; Cauquil, J.-M.; Martin, J.-Y.; Benschop, T.

2016-05-01

The cooled IR detectors are used in a wide range of applications. Most of the time, the cryocoolers are one of the components dimensioning the lifetime of the system. The current market needs tend to reliability figures higher than 15,000hrs in "standard conditions". Field returns are hardly useable mostly because of the uncertain environmental conditions of use, or the differences in user profiles. A previous paper explains how Thales Cryogenics has developed an approach based on accelerated ageing and statistical analysis [1]. The aim of the current paper is to compare results obtained on accelerated ageing on one side, and on the other side, specific field returns where the conditions of use are well known. The comparison between prediction and effective failure rate is discussed. Moreover, a specific focus is done on how some new applications of cryocoolers (continuous operation at a specific temperature) can increase the MTTF. Some assumptions are also exposed on how the failure modes, effects and criticality analysis evolves for continuous operation at a specific temperature and compared to experimental data.

Synthesis and evaluation of aryl-naloxamide opiate analgesics targeting truncated exon 11-associated μ opioid receptor (MOR-1) splice variants.

PubMed

Majumdar, Susruta; Subrath, Joan; Le Rouzic, Valerie; Polikar, Lisa; Burgman, Maxim; Nagakura, Kuni; Ocampo, Julie; Haselton, Nathan; Pasternak, Anna R; Grinnell, Steven; Pan, Ying-Xian; Pasternak, Gavril W

2012-07-26

3-Iodobenzoylnaltrexamide 1 (IBNtxA) is a potent analgesic acting through a novel receptor target that lack many side-effects of traditional opiates composed, in part, of exon 11-associated truncated six transmembrane domain MOR-1 (6TM/E11) splice variants. To better understand the SAR of this drug target, a number of 4,5-epoxymorphinan analogues were synthesized. Results show the importance of a free 3-phenolic group, a phenyl ring at the 6 position, an iodine at the 3'or 4' position of the phenyl ring, and an N-allyl or c-propylmethyl group to maintain high 6TM/E11 affinity and activity. 3-Iodobenzoylnaloxamide 15 (IBNalA) with a N-allyl group displayed lower δ opioid receptor affinity than its naltrexamine analogue, was 10-fold more potent an analgesic than morphine, elicited no respiratory depression or physical dependence, and only limited inhibition of gastrointestinal transit. Thus, the aryl-naloxamide scaffold can generate a potent analgesic acting through the 6TM/E11 sites with advantageous side-effect profile and greater selectivity.

Advanced Analgesic Drug Delivery and Nanobiotechnology.

PubMed

Stoicea, Nicoleta; Fiorda-Diaz, Juan; Joseph, Nicholas; Shabsigh, Muhammad; Arias-Morales, Carlos; Gonzalez-Zacarias, Alicia A; Mavarez-Martinez, Ana; Marjoribanks, Stephen; Bergese, Sergio D

2017-07-01

Transdermal administration of analgesic medications offers several benefits over alternative routes of administration, including a decreased systemic drug load with fewer side effects, and avoidance of drug degradation by the gastrointestinal tract. Transdermal administration also offers a convenient mode of drug administration over an extended period of time, particularly desirable in pain medicine. A transdermal administration route may also offer increased safety for drugs with a narrow therapeutic window. The primary barrier to transdermal drug absorption is the skin itself. Transdermal nanotechnology offers a novel method of achieving enhanced dermal penetration with an extended delivery profile for analgesic drugs, due to their small size and relatively large surface area. Several materials have been used to enhance drug duration and transdermal penetration. The application of nanotechnology in transdermal delivery of analgesics has raised new questions regarding safety and ethical issues. The small molecular size of nanoparticles enables drug delivery to previously inaccessible body sites. To ensure safety, the interaction of nanoparticles with the human body requires further investigation on an individual drug basis, since different formulations have unique properties and side effects.

Comparison of Two brands of Methylphenidate (Stimdate(®) vs. Ritalin(®)) in Children and Adolescents with Attention Deficit Hyperactivity Disorder: A Double-Blind, Randomized Clinical Trial.

PubMed

Khodadust, Naser; Jalali, Amir-Hossein; Ahmadzad-Asl, Masoud; Khademolreza, Noushin; Shirazi, Elham

2012-01-01

To compare the effectiveness and safety of the methylphenidate produced in Iran (Stimdate®) with its original brand (Ritalin®) in children with Attention deficit hyperactivity disorder (ADHD). In this double-blinded randomized clinical trial, 30 patients with ADHD who were 6 to 16 years old, were divided into two groups: 15 in Stimdate® and 15 in Ritalin® group. The two groups were compared for side effects profile, Conner's Parent's Rating Scale-Persion version (CPRS-R), Child Symptom Inventory-4 (CSI-4), Clinical Global Impressions (CGI), and Children's Global Assessment Scale (CGAS), at baseline and at the 4(th) and 6(th) weeks. The subjects showed significant decreases in the CPRS-Rand CSI-4 scores and significant increase of CGAS scores during the follow-up, but there were no significant difference between Stimdate® and Ritalin® group, regarding the pattern of changes observed. The mean therapeutic dose and the number of side effects were not significantly different between the two studied groups. Both Stimdate® and Ritalin® had comparable clinical efficacy and safety in children with ADHD.

Administration of ketamine for unipolar and bipolar depression.

PubMed

Kraus, Christoph; Rabl, Ulrich; Vanicek, Thomas; Carlberg, Laura; Popovic, Ana; Spies, Marie; Bartova, Lucie; Gryglewski, Gregor; Papageorgiou, Konstantinos; Lanzenberger, Rupert; Willeit, Matthäus; Winkler, Dietmar; Rybakowski, Janusz K; Kasper, Siegfried

2017-03-01

Clinical trials demonstrated that ketamine exhibits rapid antidepressant efficacy when administered in subanaesthetic dosages. We reviewed currently available literature investigating efficacy, response rates and safety profile. Twelve studies investigating unipolar, seven on bipolar depression were included after search in medline, scopus and web of science. Randomized, placebo-controlled or open-label trials reported antidepressant response rates after 24 h on primary outcome measures at 61%. The average reduction of Hamilton Depression Rating Scale (HAM-D) was 10.9 points, Beck Depression Inventory (BDI) 15.7 points and Montgomery-Asberg Depression Rating Scale (MADRS) 20.8 points. Ketamine was always superior to placebo. Most common side effects were dizziness, blurred vision, restlessness, nausea/vomiting and headache, which were all reversible. Relapse rates ranged between 60% and 92%. To provide best practice-based information to patients, a consent-form for application and modification in local language is included. Ketamine constitutes a novel, rapid and efficacious treatment option for patients suffering from treatment resistant depression and exhibits rapid and significant anti-suicidal effects. New administration routes might serve as alternative to intravenous regimes for potential usage in outpatient settings. However, long-term side effects are not known and short duration of antidepressant response need ways to prolong ketamine's efficacy.

Dexmedetomidine: a novel sedative-analgesic agent

PubMed Central

2001-01-01

Since the first report of clonidine, an α2-adrenoceptor agonist, the indications for this class of drugs have continued to expand. In December 1999, dexmedetomidine was approved as the most recent agent in this group and was introduced into clinical practice as a short-term sedative (<24 hours). α2-Adrenoceptor agonists have several beneficial actions during the perioperative period. They decrease sympathetic tone, with attenuation of the neuroendocrine and hemodynamic responses to anesthesia and surgery; reduce anesthetic and opioid requirements; and cause sedation and analgesia. They allow psychomotoric function to be preserved while letting the patient rest comfortably. With this combination of effects, α2-adrenoceptor agonists may offer benefits in the prophylaxis and adjuvant treatment of perioperative myocardial ischemia. Furthermore, their role in pain management and regional anesthesia is expanding. Side effects consist of mild to moderate cardiovascular depression, with slight decreases in blood pressure and heart rate. The development of new, more selective α2-adrenoceptor agonists with improved side effect profiles may provide a new concept for the administration of perioperative anesthesia and analgesia. This review aims to give background information to improve understanding of the properties and applications of the novel α2-adrenoceptor agonist, dexmedetomidine. PMID:16369581

Long-Pulsed 532-Nm Neodymium-Doped Yttrium Aluminium Garnet Laser for Treatment of Facial Plane Warts in 160 Yemeni Patients.

PubMed

Alshami, Mohammad Ali; Mohana, Mona Jameel; Alshami, Ahlam Mohammad

2016-11-01

Warts in general and plane warts in particular pose a therapeutic challenge for dermatologists. Many treatment modalities exist, with variable success rates, side effect profiles, and precautions. The long-pulsed 532-nm neodymium-doped yttrium aluminium garnet (LP Nd:YAG) laser has not been previously used for this indication. This study was conducted to assess the efficacy and safety of the LP Nd:YAG laser for treating facial plane warts. A total of 160 Yemeni patients (62 women, 98 men; age range, 5-55 years) were exposed to 1 laser treatment session with the following parameters: wavelength, 532 nm; pulse duration, 20 millisecond; spot size, 2 to 3 mm; and fluence, 25 J/cm. The end point was graying or whitening of the lesion. Color photographs were taken before and immediately after treatment and at follow-up visits 1, 4, and 16 weeks after the laser session. An overall clearance rate of 92% after only one session was achieved, with minimal and transient side effects. The LP Nd:YAG laser is safe and effective for treating facial plane warts, with a success rate of 92% after only one session.

Pharmacotherapy for schizophrenia in postmenopausal women.

PubMed

González-Rodríguez, Alexandre; Seeman, Mary V

2018-06-01

Reduced estrogen levels at menopause mean a loss of the neuroprotection that is conferred, from puberty until menopause, on women with schizophrenia. The postmenopausal stage of schizophrenia requires therapeutic attention because women with this diagnosis almost invariably experience increased symptoms and increased side effects at this time. So far, few targeted therapies have been successfully developed. Areas covered: This non-systematic, narrative review is based on the relevant published literature indexed in PubMed. A digital search was combined with a manual check of references from studies in the field of gender differences, menopause and schizophrenia. Aside from the inclusion of a few early classic papers, the review focuses on 21st century basic, psychopharmacologic, and clinical literature on the treatment of women with schizophrenia after menopause. Expert opinion: Beyond a relatively low dose threshold, all antipsychotic medications have adverse effects, which become more prominent for women at the time of menopause. Estrogen modulators may not help all symptoms of schizophrenia but are, nevertheless, relatively safe and, when used as adjuncts, help to keep antipsychotic doses low, thus reducing the side effect burden. The field is currently moving towards precision medicine and individual genetic profiles will help to determine the efficacy of available treatments in the future.

Augmentin duo™ in the treatment of childhood blepharokeratoconjunctivitis.

PubMed

Cehajic-Kapetanovic, Jasmina; Kwartz, Jeff

2010-01-01

To report the use of Augmentin Duo 400/57 (GlaxoSmithKline, Middlesex, UK) in the treatment of childhood blepharokeratoconjunctivitis (BKC). This is a retrospective interventional case series. The case notes of 7 consecutive patients treated with Augmentin Duo 400/57 for BKC during 18 months were reviewed. Diagnostic criteria for BKC were blepharitis including recurrent chalazia and meibomian gland dysfunction, eyelid margin telangiectasia and facial rosacea, recurrent episodes of chronic red eye, photophobia, watering, punctate superficial keratopathy, corneal neovascularization, and corneal ulcers. Seven children (age range: 6 to 14 years) were diagnosed as having BKC. All children received systemic Augmentin Duo 400/57 and showed considerable improvement within the first month of therapy. Six children had no recurrences during a mean follow-up of 6 months. No patients experienced any side effects from this treatment. Augmentin Duo 400/57 has not previously been reported in the treatment of BKC in children. In this case series, Augmentin Duo 400/57 proved to be at least as effective as current treatments with systemic erythromycin or doxycycline with the advantage of a twice-daily dosage and a superior side-effect profile. Copyright 2010, SLACK Incorporated.

Paracetamol in Patent Ductus Arteriosus Treatment: Efficacious and Safe?

PubMed Central

Bardanzellu, Flaminia; Neroni, Paola; Fanos, Vassilios

2017-01-01

In preterm infants, failure or delay in spontaneous closure of Ductus Arteriosus (DA), resulting in the condition of Patent Ductus Arteriosus (PDA), represents a significant issue. A prolonged situation of PDA can be associated with several short- and long-term complications. Despite years of researches and clinical experience on PDA management, unresolved questions about the treatment and heterogeneity of clinical practices in different centers still remain, in particular regarding timing and modality of intervention. Nowadays, the most reasonable strategy seems to be reserving the treatment only to hemodynamically significant PDA. The first-line therapy is medical, and ibuprofen, related to several side effects especially in terms of nephrotoxicity, is the drug of choice. Administration of oral or intravenous paracetamol (acetaminophen) recently gained attention, appearing effective as traditional nonsteroidal anti-inflammatory drugs (NSAIDs) in PDA closure, with lower toxicity. The results of the studies analyzed in this review mostly support paracetamol efficacy in ductal closure, with inconstant low and transient elevation of liver enzymes as reported side effect. However, more studies are needed to confirm if this therapy shows a real safety profile and to evaluate its long-term outcomes, before considering paracetamol as first-choice drug in PDA treatment. PMID:28828381

The combined oral contraceptive pill containing drospirenone and ethinyl estradiol plus levomefolate calcium.

PubMed

Rapkin, Rachel B; Creinin, Mitchell D

2011-10-01

Neural tube defects are the second most common congenital anomaly in the United States, although their incidence may be decreased by periconception folic acid supplementation. A new oral contraceptive containing drospirenone and ethinyl estradiol plus levomefolate calcium was formulated to decrease the risk of neural tube defects in pregnancies conceived while taking or shortly after discontinuing this pill. Because of its novelty, very few studies have been performed to evaluate the efficacy, side effects and safety related to contraception, premenstrual dysphoric disorder and acne; therefore, literature evaluating similar contraceptives without levomefolate is reviewed. Additionally, we review studies evaluating the addition of levomefolate calcium to oral contraceptives containing 3 mg drospirenone and either 20 or 30 μg ethinyl estradiol. To date, no study has been performed to evaluate the effect this new oral contraceptive has on reducing the incidence of neural tube defects. This new pill has similar contraceptive efficacy, side effect, safety and benefits profile to other drospirenone-containing contraceptives. While also approved to prevent neural tube defects, no studies validate this claim and physician time is better spent counseling women, regardless of contraceptive choice, on the importance of folic acid supplementation during the child-bearing years.

The pulsation-rotation interaction: Greatest hits and the B-side

NASA Astrophysics Data System (ADS)

Townsend, Rich

2014-02-01

It has long been known that rotation can have an appreciable impact on stellar pulsation - by modifying the usual p and g modes found in the non-rotating case, and by introducing new classes of modes. However, it's only relatively recently that advances in numerical simulations and complementary theoretical treatments have enabled us to model these phenomena in any great detail. In this talk I'll review highlights in this area (the `Greatest Hits'), before considering the flip side (or the `B-side', for those of us old enough to remember vinyl records) of the pulsation-rotation interaction: how pulsation can itself influence internal rotation profiles.

Pharmacodynamic effects of pilocarpine eye drop enhanced by decreasing its volume of instillation.

PubMed

Lal, A; Kataria, V; Rajpal, A; Khanna, N

1995-07-01

Previous studies have proved that as the volume of the drug solution instilled into the eye is decreased, the fraction of the dose absorbed into the ocular tissue is increased and the adverse drug reactions lowered. The present study investigated the acute effects of different drop volumes (10 microliters, 20 microliters, 40 microliters, and 80 microliters) of pilocarpine nitrate (2%) on pupil diameter, heart rate, and adverse reaction profile, in 12 healthy human volunteers. The drop volumes of 10 microliters and 20 microliters produced more miosis and less side effects than 40 microliters and 80 microliters drop volumes. This may be due to more penetration of the drug into the ocular tissue and less drainage into the nasolacrimal system.

Adalimumab for the treatment of uveitis.

PubMed

LaMattina, Kara C; Goldstein, Debra A

2017-03-01

Adalimumab, an inhibitor of tumor necrosis factor-alpha (TNFα), is the only systemic non-corticosteroid agent which has been approved by the US Food and Drug Administration (FDA) for the treatment of non-infectious uveitis. Areas covered: The aim of this review is to summarize the research which demonstrated the effectiveness of adalimumab in the treatment of intraocular inflammation and helped to establish its side effect profile, ultimately leading to its FDA approval. Expert commentary: Adalimumab is a useful second-line agent in the treatment of non-infectious uveitis. While it is only approved in the United States for use in intermediate, posterior, and panuveitis in adults, I find it to be effective in off-label treatment of pediatric uveitis and scleritis as well.

1. Historic American Buildings Survey Aubrey P. Janion, Photographer August ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. Historic American Buildings Survey Aubrey P. Janion, Photographer August 1959 Courtesy of New Hampshire Profiles magazine FRONT OR NORTHWEST SIDE - Wheeler House, Orford Street, Orford, Grafton County, NH

Examining the clinical course of genotype 1 chronic hepatitis C patients treated with the cosmos regimen: including patients with advanced liver disease and East Asian ancestry

PubMed Central

Roytman, Marina; Ramkissoon, Resham; Wu, Christina; Hong, Leena; Trujillo, Ruby; Huddleston, Leslie; Poerzgen, Peter; Seto, Todd; Wong, Linda; Tsai, Naoky

2017-01-01

Background/objectives The COSMOS study was a phase 2a clinical trial that showed high cure rates of genotype 1 chronic hepatitis C (CHC) and a favorable side effect profile using a 12-week regimen of simeprevir + sofosbuvir (SIM + SOF). Given the small number of patients treated with the SIM + SOF regimen in the COSMOS trial, there is uncertainty regarding the efficacy and safety of this combination therapy. We now report our experience with the COSMOS regimen in the multiethnic population of Hawaii, including patients of East Asian ancestry and with decompensated cirrhosis. Methods This study is a retrospective review of 138 patients treated with a fixed dose regimen of SIM 150 mg and SOF 400 mg daily at a single referral center. We collected data on demographics, side effects, laboratory studies and sustained virological response (SVR). Statistical analysis was performed with Stata v8.2 software. Results Baseline characteristics of the 138 patients initiated with SIM + SOF therapy were: 68.8 % cirrhotic (22.1 % of those Child-Pugh Class B), 37 % Asian, 11.6 % Pacific Islander, 63 % male, mean age 61.3 ± 7.8 years, mean BMI 27.8 ± 6.1 kg/m2, 26.8 % diabetic, 63.8 % genotype 1a, 44.9 % previously treatment experienced. A total of 100 % of patients that completed therapy (n = 137) had undetectable viral loads at end of treatment (EOT). Twelve patients relapsed post-treatment resulting in an overall 12 week SVR (SVR12) rate of 89.1 %. 95 % of decompensated cirrhotic patients achieved SVR12, compared to 85.3 % of compensated cirrhotic patients and 93 % of non-cirrhotic patients. 92 % of Asian patients achieved SVR12 compared to 87.5 % in non-Asian patients. There were no statistically significant differences in SVR12 between treatment naive and treatment experienced patients (86.8 vs 91.9 %). 87.5 % of post-transplant patients achieved SVR12. The main side effects were headache 16.2 %, fatigue 24.2 %, pruritis 14.1 %; none were >grade 2 in severity. There were no differences in side effect profiles of patients with decompensated cirrhosis. Pruritis only was statistically significant between Asians and non-Asians (22 vs 5.7 %). Trends toward improvement in platelet counts and total bilirubin were noted at 12-weeks post treatment, while improvement in albumin in cirrhotic patients reached statistical significance (3.77–4.01 mg/dL, p = 0.0108). Conclusions The 12-week fixed dose course of SIM + SOF was well tolerated in a multiethnic population of primarily cirrhotic patients, including those with decompensated disease. This real world trial achieved SVR12 rates comparable to the COSMOS data. Higher incidence of adverse side effects was not observed with an exception of higher rate of pruritis in Asians. The increase in albumin in cirrhotic patients was statistically significant and suggested early improvement in synthetic function following viral eradication. Higher BMI (≥30 kg/m2) was the only factor that correlated with post-treatment relapse by multivariate analysis. PMID:27026431

Tension Amplification in Molecular Brushes in Solutions and on Substrates

PubMed Central

Panyukov, Sergey; Zhulina, Ekaterina B.; Sheiko, Sergei S.; Randall, Greg C.; Brock, James; Rubinstein, Michael

2009-01-01

Molecular bottle-brushes are highly branched macromolecules with side chains densely grafted to a long polymer backbone. The brush-like architecture allows focusing of the side-chain tension to the backbone and its amplification from the picoNewton to nanoNewton range. The backbone tension depends on the overall molecular conformation and the surrounding environment. Here we study the relation between the tension and conformation of the molecular brushes in solutions, melts, and on substrates. In solutions, we find that the backbone tension in dense brushes with side chains attached to every backbone monomer is on the order of f0N3/8 in athermal solvents, f0N1/3 in θ-solvents, and f0 in poor solvents and melts, where N is the degree of polymerization of side chains, f0≃ kBT/b is the maximum tension in side chains, b is the Kuhn length, kB is Boltzmann constant, and T is absolute temperature. Depending on the side chain length and solvent quality, molecular brushes in solutions develop tension on the order of 10–100 picoNewtons, which is sufficient to break hydrogen bonds. Significant amplification of tension occurs upon adsorption of brushes onto a substrate. On a strongly attractive substrate, maximum tension in the brush backbone is ~ f0N, reaching values on the order of several nanoNewtons which exceed the strength of a typical covalent bond. At low grafting density and high spreading parameter the cross-sectional profile of adsorbed molecular brush is approximately rectangular with thicknes ~bA/S, where A is the Hamaker constant and S is the spreading parameter. At a very high spreading parameter (S > A), the brush thickness saturates at monolayer ~ b. At a low spreading parameter, the cross-sectional profile of adsorbed molecular brush has triangular tent-like shape. In the cross-over between these two opposite cases, covering a wide range of parameter space, the adsorbed molecular brush consists of two layers. Side chains in the lower layer gain surface energy due to the direct interaction with the substrate, while the second layer spreads on the top of the first layer. Scaling theory predicts that this second layer has a triangular cross-section with width R ~ N3/5 and height h ~ N2/5. Using self-consistent field theory we calculate the cap profile y (x) = h (1 − x2/R2)2, where x is the transverse distance from the backbone. The predicted cap shape is in excellent agreement with both computer simulation and experiment. PMID:19673133

Current Approaches and New Developments in the Pharmacological Management of Tourette Syndrome.

PubMed

Quezada, Julio; Coffman, Keith A

2018-01-01

Tourette syndrome (TS) is a neurodevelopmental disorder of unknown etiology characterized by spontaneous, involuntary movements and vocalizations called tics. Once thought to be rare, TS affects 0.3-1% of the population. Tics can cause physical discomfort, emotional distress, social difficulties, and can interfere with education and desired activities. The pharmacologic treatment of TS is particularly challenging, as currently the genetics, neurophysiology, and neuropathology of this disorder are still largely unknown. However, clinical experience gained from treating TS has helped us better understand its pathogenesis and, as a result, derive treatment options. The strongest data exist for the antipsychotic agents, both typical and atypical, although their use is often limited in children and adolescents due to their side-effect profiles. There are agents in a variety of other pharmacologic categories that have evidence for the treatment of TS and whose side-effect profiles are more tolerable than the antipsychotics; these include clonidine, guanfacine, baclofen, topiramate, botulinum toxin A, tetrabenazine, and deutetrabenazine. A number of new agents are being developed and tested as potential treatments for TS. These include valbenazine, delta-9-tetrahydrocannabidiol, and ecopipam. Additionally, there are agents with insufficient data for efficacy, as well as agents that have been shown to be ineffective. Those without sufficient data for efficacy include clonazepam, ningdong granule, 5-ling granule, omega-3 fatty acids, and n-acetylcysteine. The agents that have been shown to be ineffective include pramipexole and metoclopramide. We will review all of the established pharmacologic treatments, and discuss those presently in development.

Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks.

PubMed

Ilfeld, Brian M; Viscusi, Eugene R; Hadzic, Admir; Minkowitz, Harold S; Morren, Michael D; Lookabaugh, Janice; Joshi, Girish P

2015-01-01

Liposome bupivacaine (Exparel) is a multivesicular liposomal formulation of bupivacaine currently approved in the United States for single-dose administration into the surgical site to provide postsurgical analgesia. This retrospective analysis examined safety data from clinical trials involving the off-label use of this formulation in peripheral nerve blocks. Data from 6 controlled (phases I-III) studies were compiled involving single-injection ankle, femoral nerve, and intercostal nerve blocks (2 each). Adverse events (AEs) were monitored for 1 to 30 days after study drug administration. Of 575 subjects, 335 received liposome bupivacaine (2-310 mg), 33 received bupivacaine HCl (75-125 mg), and 207 received normal saline (placebo). Overall, 76% of subjects receiving liposome bupivacaine experienced 1 or more AEs compared with 61% receiving bupivacaine HCl and 76% receiving placebo. The most frequently reported AEs among subjects receiving liposome bupivacaine were nausea, pyrexia, pruritus, constipation, and vomiting. The most common treatment-related AE was hypesthesia among subjects treated with liposome bupivacaine or bupivacaine HCl. Incidence of nervous system AEs for liposome bupivacaine, bupivacaine HCl, and placebo was 21%, 27%, and 21%, respectively. Similarly, incidence of cardiac AEs was 9%, 0%, and 12%, respectively. At least 1 serious AE occurred in 8% of subjects receiving liposome bupivacaine compared with 10% of those receiving placebo (none assessed by investigators as related to study medication). Liposome bupivacaine has a similar safety and side effect profile to bupivacaine HCl and normal saline, suggesting that most of the more common AEs are related to either opioid rescue or the surgical procedure itself.

MAO-inhibitors in Parkinson's Disease

PubMed Central

Laux, Gerd

2011-01-01

Monoamine oxidase inhibitors (MAO-I) belong to the earliest drugs tried in Parkinson's disease (PD). They have been used with or without levodopa (L-DOPA). Non-selective MAO-I due to their side-effect/adverse reaction profile, like tranylcypromine have limited use in the treatment of depression in PD, while selective, reversible MAO-A inhibitors are recommended due to their easier clinical handling. For the treatment of akinesia and motor fluctuations selective irreversible MAO-B inhibitors selegiline and rasagiline are recommended. They are safe and well tolerated at the recommended daily doses. Their main differences are related to (1) metabolism, (2) interaction with CYP-enzymes and (3) quantitative properties at the molecular biological/genetic level. Rasagiline is more potent in clinical practise and has a hypothesis driven more favourable side effect/adverse reaction profile due to its metabolism to aminoindan. Both selegiline and rasagiline have a neuroprotective and neurorestaurative potential. A head-to head clinical trial would be of utmost interest from both the clinical outcome and a hypothesis-driven point of view. Selegiline is available as tablet and melting tablet for PD and as transdermal selegiline for depression, while rasagiline is marketed as tablet for PD. In general, the clinical use of MAO-I nowadays is underestimated. There should be more efforts to evaluate their clinical potency as antidepressants and antidementive drugs in addition to the final proof of their disease-modifying potential. In line with this are recent innovative developments of MAO-I plus inhibition of acetylcholine esterase for Alzheimer's disease as well as combined MAO-I and iron chelation for PD. PMID:22110357

Personalized medicine could transform healthcare

PubMed Central

Mathur, Sunil; Sutton, Joseph

2017-01-01

Personalized medicine (PM) is about tailoring a treatment as individualized as the disease. The approach relies on identifying genetic, epigenomic, and clinical information that allows the breakthroughs in our understanding of how a person's unique genomic portfolio makes them vulnerable to certain diseases. PM approach is a complete extension of traditional approach (One-Size-Fits-All) to increasing our ability to predict which medical treatments will be safe and effective for individual patient, and which ones will not be, based on the patient's unique genetic profile. Implementation of PM has the potential to reduce financial and time expenditure, and increase quality of life and life extension of patients. Knowledge of PM facilitates earlier disease detection via enhanced use of existing biomarkers and detection of early genomic and epigenomic events in disease development, particularly carcinogenesis. The PM approach predominantly focuses on preventative medicine and favours taking pro-active actions rather than just reactive. This approach delays or prevents the need to apply more severe treatments which are usually less tolerated and with increased quality of life and financial considerations. Increasing healthcare costs have placed additional pressure on government funded healthcare systems globally, especially regarding end of life care. PM may increase the effectiveness of existing treatments and negate the inherent problems associated with non-PM approaches. PM is a young but rapidly expanding field of healthcare where a physician can select a treatment based on a patient's genetic profile that may not only minimize harmful side effects and guarantee a more successful result, but can be less cost effective compared with a ‘trial-and-error’ approach to disease treatment. The less efficient non-PM (‘trial-and-error’) approach, which can lead to drug toxicity, severe side effects, reactive treatment and misdiagnosis continue to contribute to increasing healthcare costs. Increased patient stratification will allow for the enhanced application of PM and pro-active treatment regimens, resulting in reduced costs and quality of life enhancement. PMID:28685051

The use of electroconvulsive therapy in the elderly: a study from the psychiatric unit of a north Indian teaching hospital.

PubMed

Jain, Gaurav; Kumar, Vineet; Chakrabarti, Subho; Grover, Sandeep

2008-06-01

There are very little data on elderly patients receiving electroconvulsive therapy (ECT) in India. This study was a preliminary attempt at characterizing the clinical and demographic profile of elderly subjects (>or=60 years) who received ECT in the psychiatric department of a teaching hospital in north India. A retrospective case-note review was carried out to identify patients 60 years or older who had received ECT over an 8-year period at the Postgraduate Institute of Medical Education and Research, Chandigarh, India. Several details about their demographic and clinical profile, indications for ECT, response patterns, and adverse effects were extracted. Over the 8 years, 373 patients received ECT, of which 56 (15%) were 60 years or older. Complete records were available for only 50 of these patients. The majority (96%) had depression. The index depressive episode for which ECT was used was severe in 91.6% of the subjects, and 68% had not responded to adequate psychotropic treatment before ECT. Comorbid medical illnesses were present in 66% of cases and were associated with significantly higher risk of cognitive side effects. However, side effects were usually mild; there were no serious untoward events caused by ECT. About 80% to 90% showed some response to treatment. Those who had received inadequate antidepressant treatment before ECT were significantly more likely to respond to ECT. Elderly with depression constitute a substantial proportion of those receiving ECT in India. Use of ECT in this population seemed to be mainly restricted to those who were very severely ill and poorly responsive to medications. Electroconvulsive therapy seemed to be a safe and effective treatment in such situations. However, particular care may be required in the subgroup with comorbid physical problems that may be more vulnerable to cognitive adverse effects.

Diversity of Bradyrhizobium strains nodulating Lupinus micranthus on both sides of the Western Mediterranean: Algeria and Spain.

PubMed

Bourebaba, Yasmina; Durán, David; Boulila, Farida; Ahnia, Hadjira; Boulila, Abdelghani; Temprano, Francisco; Palacios, José M; Imperial, Juan; Ruiz-Argüeso, Tomás; Rey, Luis

2016-06-01

Lupinus micranthus is a lupine distributed in the Mediterranean basin whose nitrogen fixing symbiosis has not been described in detail. In this study, 101 slow-growing nodule isolates were obtained from L. micranthus thriving in soils on both sides of the Western Mediterranean. The diversity of the isolates, 60 from Algeria and 41 from Spain, was addressed by multilocus sequence analysis of housekeeping genes (16S rRNA, atpD, glnII and recA) and one symbiotic gene (nodC). Using genomic fingerprints from BOX elements, 37 different profiles were obtained (22 from Algeria and 15 from Spain). Phylogenetic analysis based on 16S rRNA and concatenated atpD, glnII and recA sequences of a representative isolate of each BOX profile displayed a homogeneous distribution of profiles in six different phylogenetic clusters. All isolates were taxonomically ascribed to the genus Bradyrhizobium. Three clusters comprising 24, 6, and 4 isolates, respectively, accounted for most of the profiles. The largest cluster was close to the Bradyrhizobium canariense lineage, while the other two were related to B. cytisi/B. rifense. The three remaining clusters included only one isolate each, and were close to B. canariense, B. japonicum and B. elkanii species, respectively. In contrast, phylogenetic clustering of BOX profiles based on nodC sequences yielded only two phylogenetic groups. One of them included all the profiles except one, and belonged to symbiovar genistearum. The remaining profile, constituted by a strain related to B. elkanii, was not related to any well-defined symbiotic lineage, and may constitute both a new symbiovar and a new genospecies. Copyright © 2016 Elsevier GmbH. All rights reserved.

Calculating Nozzle Side Loads using Acceleration Measurements of Test-Based Models

NASA Technical Reports Server (NTRS)

Brown, Andrew M.; Ruf, Joe

2007-01-01

As part of a NASA/MSFC research program to evaluate the effect of different nozzle contours on the well-known but poorly characterized "side load" phenomena, we attempt to back out the net force on a sub-scale nozzle during cold-flow testing using acceleration measurements. Because modeling the test facility dynamics is problematic, new techniques for creating a "pseudo-model" of the facility and nozzle directly from modal test results are applied. Extensive verification procedures were undertaken, resulting in a loading scale factor necessary for agreement between test and model based frequency response functions. Side loads are then obtained by applying a wide-band random load onto the system model, obtaining nozzle response PSD's, and iterating both the amplitude and frequency of the input until a good comparison of the response with the measured response PSD for a specific time point is obtained. The final calculated loading can be used to compare different nozzle profiles for assessment during rocket engine nozzle development and as a basis for accurate design of the nozzle and engine structure to withstand these loads. The techniques applied within this procedure have extensive applicability to timely and accurate characterization of all test fixtures used for modal test.A viewgraph presentation on a model-test based pseudo-model used to calculate side loads on rocket engine nozzles is included. The topics include: 1) Side Loads in Rocket Nozzles; 2) Present Side Loads Research at NASA/MSFC; 3) Structural Dynamic Model Generation; 4) Pseudo-Model Generation; 5) Implementation; 6) Calibration of Pseudo-Model Response; 7) Pseudo-Model Response Verification; 8) Inverse Force Determination; 9) Results; and 10) Recent Work.

National survey of adherence, efficacy, and side effects of methylphenidate in children with attention-deficit/hyperactivity disorder in Taiwan.

PubMed

Gau, Susan Shur-Fen; Chen, Shin-Jaw; Chou, Wen-Jiun; Cheng, Helen; Tang, Ching-Shu; Chang, Hsueh-Ling; Tzang, Ruu-Fen; Wu, Yu-Yu; Huang, Ya-Fen; Chou, Miao-Chun; Liang, Hsin-Yi; Hsu, Ya-Chen; Lu, Hui-Hua; Huang, Yu-Shu

2008-01-01

To identify the determinants of adherence to immediate-release (IR) methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder (ADHD); to examine the impact of adherence on ADHD-related symptoms; and to compare the efficacy, adherence, and side effects of IR methylphenidate and osmotic release oral system (OROS) methylphenidate. This national survey, involving 12 hospitals, consisted of 2 phases of assessment. Treatment adherence in 240 (39.5%) of the 607 children aged 5 to 16 years with a clinical diagnosis of DSM-IV ADHD enrolled in the study was poor (defined as missing >or= 1 dose of ADHD medication a day and on 2 days or more during school days). Children with poor adherence at phase 1 were able to switch to OROS methylphenidate, while adherents remained on the IR variant. We reassessed 124 poor adherents who switched to OROS methylphenidate. The global ADHD severity, parent-child interaction, classroom behavior, academic performance, and side effects of the child subjects were evaluated by investigators. Parents completed the rating scales about the ADHD-related symptoms. The study began in April 2005 and was completed in February 2006. Determinants for poor adherence included older age, later onset of ADHD, family history of ADHD, higher paternal education level, and multi-dose administration. Mental retardation and treatment at medical centers were inversely related to poor adherence. Overall, poor adherence was associated with more severe ADHD-related symptoms by comparison to good adherence. Similar side effect profile, superior adherence, and improved efficacy were demonstrated in intra-individual comparison of the OROS and IR methylphenidate forms. Given that poor adherence to medication may be an important reason for suboptimal outcome in ADHD treatment, physicians should ensure adherence with therapy before adjusting dosage or switching medication. clinicaltrials.gov Identifier NCT00460720.

The Immersive Virtual Reality Experience: A Typology of Users Revealed Through Multiple Correspondence Analysis Combined with Cluster Analysis Technique.

PubMed

Rosa, Pedro J; Morais, Diogo; Gamito, Pedro; Oliveira, Jorge; Saraiva, Tomaz

2016-03-01

Immersive virtual reality is thought to be advantageous by leading to higher levels of presence. However, and despite users getting actively involved in immersive three-dimensional virtual environments that incorporate sound and motion, there are individual factors, such as age, video game knowledge, and the predisposition to immersion, that may be associated with the quality of virtual reality experience. Moreover, one particular concern for users engaged in immersive virtual reality environments (VREs) is the possibility of side effects, such as cybersickness. The literature suggests that at least 60% of virtual reality users report having felt symptoms of cybersickness, which reduces the quality of the virtual reality experience. The aim of this study was thus to profile the right user to be involved in a VRE through head-mounted display. To examine which user characteristics are associated with the most effective virtual reality experience (lower cybersickness), a multiple correspondence analysis combined with cluster analysis technique was performed. Results revealed three distinct profiles, showing that the PC gamer profile is more associated with higher levels of virtual reality effectiveness, that is, higher predisposition to be immersed and reduced cybersickness symptoms in the VRE than console gamer and nongamer. These findings can be a useful orientation in clinical practice and future research as they help identify which users are more predisposed to benefit from immersive VREs.

An update on the safety of nutraceuticals and effects on lipid parameters.

PubMed

Cicero, Arrigo F G; Colletti, Alessandro

2018-03-01

Cardiovascular diseases (CVDs) are the leading cause of mortality and disability in developed countries, whereas a large portion of patients in primary prevention have uncontrolled level of CVD risk factors. Dietary supplementation with bioactive natural compounds with demonstrated lipid-lowering effects is currently supported by the international guidelines for CVD prevention and some international expert panels. Areas covered: This review provides insights on issues concerning the tolerability and safety of the most commonly used nutraceuticals with demonstrated lipid-lowering effect in humans. They will be then divided into three main categories according to their mechanism of action (cholesterol synthesis inhibitors, intestinal cholesterol absorption inhibitors, and LDL-C excretion stimulants) and their pharmacological profile will be discussed. Expert opinion: A growing body of preclinical, epidemiological and clinical evidence has defined the tolerability and safety profile of the most commonly used lipid-lowering nutraceuticals. In the most part of cases, the side effects are mild and reversible. However, detailed knowledge of specific health risks and pharmacological interactions for each individual compound is needed for the management of frail patients, such as children, elderly, patients with liver or renal failure, and patients consuming numerous drugs.

[New direct-acting antiviral agents for the treatment of chronic hepatitis C in 2014].

PubMed

Cornberg, M; Höner zu Siederdissen, C; Maasoumy, B; Manns, M P

2014-04-01

The development of direct-acting antiviral agents (DAA) against the hepatitis C virus (HCV) has seen enormous progress in recent years. In 2011, the first protease inhibitors boceprevir (BOC) and telaprevir (TLV) were approved, which still need to be combined with pegylated interferon α (PEG-IFN α) and ribavirin (RBV) and are used only in patients with genotype 1. With sofosbuvir (SOF) and simeprevir (SMV), two new DAA are available. More DAA are in clinical development. Which changes in the treatment of chronic hepatitis C infection can be expected with the approval of the new DAA in 2014? Relevant phase IIb and phase III studies for the approval in 2014 were considered for drugs approved by the FDA or EMA at the editorial deadline. For patients with genotype 1, the combination of SOF, SMV or faldaprevir with PEG-IFN α and RBV was successfully evaluated in phase III studies. In contrast to previous treatment with PEG-IFN α, RBV and telaprevir (TLV) or boceprevir (BOC), therapy can be shortened in most cases with a significantly improved side-effect profile. Cure rates above 80 % are possible. Data are also available for an interferon-free therapy with either SOF and RBV or SOF and SMV in GT-1 patients. SVR rates exceeding 60 % and up to 90 % are possible. However, treatment experience with these combinations is low and an unrestricted interferon-free therapy for genotype 1 should not be expected before 2015. For patients with genotypes 2 and 3, valid data for interferon-free therapies are available. The combination of SOF and RBV for 12 weeks in genotype 2 and 24 weeks for genotype 3 is effective and shows equal or superior cure rates with fewer side effects than the PEG-IFN α/RBV therapy. For patients with genotype 1, the duration of therapy can be further reduced with better side effect profile. In certain situations, therapy without PEG-IFN α is possible and should be considered. For patients with genotypes 2 and 3, an interferon-free therapy will be standard of care in 2014.

9 CFR 91.20 - General construction.

Code of Federal Regulations, 2011 CFR

2011-01-01

... adjacent to the ship's sides which have steel casing, frames, stays or similar fittings, the carrier shall... accessible to animals. A combination of wood and steel pipe or other steel profile construction may be...

9 CFR 91.20 - General construction.

Code of Federal Regulations, 2010 CFR

2010-01-01

... adjacent to the ship's sides which have steel casing, frames, stays or similar fittings, the carrier shall... accessible to animals. A combination of wood and steel pipe or other steel profile construction may be...

Links between ocean properties, ice cover, and plankton dynamics on interannual time scales in the Canadian Arctic Archipelago

NASA Astrophysics Data System (ADS)

Hamilton, James M.; Collins, Kate; Prinsenberg, Simon J.

2013-10-01

A decade of instrumented mooring data from Barrow Strait in the eastern Canadian Arctic Archipelago reveals connections between sea ice, water characteristics, and zooplankton dynamics on interannual time scales. On the North side of the Strait, the timing of breakup is positively related to the timing of freezeup in the previous year and negatively related to spring water temperature. This suggests that an early freezeup insulates the ocean from a cold autumn atmosphere, allowing heat to be retained until spring when it contributes to early sea ice erosion. There is also a very strong negative association between the timing of freezeup and late summer salinity, suggesting that monitoring of salinity in real time could be used to predict freezeup. A zooplankton biomass index derived from acoustic Doppler current profiler echo intensity data is used to demonstrate that on the North side there are also strong connections between early summer water temperature and the start, length, and productivity of the zooplankton growth season. On the South side of the Strait where currents are stronger, the relationships seen on the North side were not observed. But here integrated zooplankton biomass index and measured currents are used to identify interannual variability in the zooplankton biomass being delivered downstream into Lancaster Sound. Also on the South side, two yearlong records of daily fluorescence profiles reveal a large difference in the phytoplankton biomass being delivered downstream between years and demonstrate a strong relationship between the timing of the spring phytoplankton bloom and that of breakup.

A novel orvinol analog, BU08028, as a safe opioid analgesic without abuse liability in primates.

PubMed

Ding, Huiping; Czoty, Paul W; Kiguchi, Norikazu; Cami-Kobeci, Gerta; Sukhtankar, Devki D; Nader, Michael A; Husbands, Stephen M; Ko, Mei-Chuan

2016-09-13

Despite the critical need, no previous research has substantiated safe opioid analgesics without abuse liability in primates. Recent advances in medicinal chemistry have led to the development of ligands with mixed mu opioid peptide (MOP)/nociceptin-orphanin FQ peptide (NOP) receptor agonist activity to achieve this objective. BU08028 is a novel orvinol analog that displays a similar binding profile to buprenorphine with improved affinity and efficacy at NOP receptors. The aim of this preclinical study was to establish the functional profile of BU08028 in monkeys using clinically used MOP receptor agonists for side-by-side comparisons in various well-honed behavioral and physiological assays. Systemic BU08028 (0.001-0.01 mg/kg) produced potent long-lasting (i.e., >24 h) antinociceptive and antiallodynic effects, which were blocked by MOP or NOP receptor antagonists. More importantly, the reinforcing strength of BU08028 was significantly lower than that of cocaine, remifentanil, or buprenorphine in monkeys responding under a progressive-ratio schedule of drug self-administration. Unlike MOP receptor agonists, BU08028 at antinociceptive doses and ∼10- to 30-fold higher doses did not cause respiratory depression or cardiovascular adverse events as measured by telemetry devices. After repeated administration, the monkeys developed acute physical dependence on morphine, as manifested by precipitated withdrawal signs, such as increased respiratory rate, heart rate, and blood pressure. In contrast, monkeys did not show physical dependence on BU08028. These in vivo findings in primates not only document the efficacy and tolerability profile of bifunctional MOP/NOP receptor agonists, but also provide a means of translating such ligands into therapies as safe and potentially abuse-free opioid analgesics.

Simulation of a circular phased array for a portable ultrasonic polar scan

NASA Astrophysics Data System (ADS)

Daemen, Jannes; Kersemans, Mathias; Martens, Arvid; Verboven, Erik; Delrue, Steven; Van Paepegem, Wim; Degrieck, Joris; Van Den Abeele, Koen

2018-04-01

The development of new composite materials, often anisotropic in nature, requires intricate approaches to characterize these materials and to detect internal defects. The Ultrasonic Polar Scan (UPS) is able to achieve both goals. During an UPS experiment, a material spot is insonified at several angles Ψ(θ,ϕ), after which the reflected or transmitted signal is recorded. While excellent results have been obtained using an in-house developed 5-axis scanner, UPS measurements with the current set-up are too lengthy and cumbersome for in-situ industrial application. Therefore, we propose to replace the complex mechanical steering of the transducers by a hemispherical phased array consisting of small PZT elements. This allows to create a compact and portable setup without compromising the current data quality. By successively activating a specific set of elements of the array and choosing appropriate inter-element time delays, the beam can be electronically steered from any angle to a fixed position on the targeted sample. Consequently, UPS reflection measurements can be performed at this position from a wide range of angles in a timeframe of seconds. Additionally, by using apodization windows, it is possible to efficiently reduce the intensity of unwanted side lobes and to create a phase profile which closely resembles that of a bounded plane wave, leading to an easier interpretation of the recorded data. The appropriate time delays and apodization parameters can be found though a multi-objective inverse problem in which both the phase profile and the side lobe reduction are optimized. This approach enables the creation of an effective beam profile to be used during UPS experiments for the characterization and inspection of composite materials. Our simulation approach is a crucial step towards a next-generation UPS device for industrial applications and in-field measurements.

Current sheet Formation in a Conical Theta Pinch Faraday Accelerator with Radio-Frequency Assisted Discharge

NASA Technical Reports Server (NTRS)

Hallock, Ashley K.; Choueiri, Edgar Y.; Polzin, Kurt A.

2007-01-01

The inductive formation of current sheets in a conical theta pinch FARAD (Faraday Accelerator with Radio-frequency Assisted Discharge) thruster is investigated experimentally with time-integrated photography. The goal is to help in understanding the mechanisms and conditions controlling the strength and extent of the current sheet, which are two indices important for FARAD as a propulsion concept. The profiles of these two indices along the inside walls of the conical acceleration coil are assumed to be related to the profiles of the strength and extent of the luminosity pattern derived from photographs of the discharge. The variations of these profiles as a function of uniform back-fill neutral pressure (with no background magnetic field and all parameters held constant) provided the first clues on the nature and qualitative dependencies of current sheet formation. It was found that there is an optimal pressure for which both indices reach a maximum and that the rate of change in these indices with pressure differs on either side of this optimal pressure. This allowed the inference that current sheet formation follows a Townsend-like breakdown mechanism modified by the existence of a finite pressure-dependent radio-frequency-generated electron density background. The observation that the effective location of the luminosity pattern favors the exit-half of the conical coil is explained as the result of the tendency of the inductive discharge circuit to operate near its minimal self-inductance. Movement of the peak in the luminosity pattern towards the upstream side of the cone with increasing pressure is believed to result from the need of the circuit to compensate for the increase in background plasma resistivity due to increasing pressure.

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.

Efficacy and bleeding profile of a combined oral contraceptive containing oestradiol valerate/dienogest: a pooled analysis of three studies conducted in North America and Europe.

PubMed

Nelson, Anita; Parke, Susanne; Makalova, Dagmar; Serrani, Marco; Palacios, Santiago; Mellinger, Uwe

2013-08-01

To summarise all clinical data on the contraceptive efficacy and bleeding profile associated with an oestradiol valerate (E2V) and dienogest (DNG) [E2V/DNG] combined oral contraceptive (COC) derived from Phase III trials. Pooled analysis of three large-scale multicentre trials conducted in healthy women who received oral E2V/DNG for 7 to 28 cycles (28-day cycles). A total of 2266 women were included in this analysis. Overall, 19 pregnancies occurred over 13 cycles during 880,950 days of relevant exposure (Pearl Index [PI] of 0.79; upper limit of the two-sided 95% confidence interval [CI]: 1.23). Ten pregnancies attributed to method failure came about during 871,091 days of relevant exposure (adjusted PI of 0.42; upper limit of the two-sided 95% CI: 0.77). In women aged 18 to 35 years (n = 1687), the corresponding PI and adjusted PI were 1.01 (upper limit of the two-sided 95% CI: 1.59) and 0.51 (upper limit of the two-sided 95% CI: 0.97), respectively. In the first 13 cycles of treatment, 76 to 81% of women experienced scheduled withdrawal bleeding, and 13 to 23% experienced intracyclic bleeding. E2V/DNG provides reliable contraceptive efficacy in women aged 18 to 50 years.

A Meta-analysis of the Effectiveness of Albendazole Compared with Metronidazole as Treatments for Infections with Giardia duodenalis

PubMed Central

Solaymani-Mohammadi, Shahram; Genkinger, Jeanine M.; Loffredo, Christopher A.; Singer, Steven M.

2010-01-01

Background Metronidazole is the most commonly used drug for the treatment of giardiasis in humans. In spite of its therapeutic efficacy for giardiasis, low patient compliance, especially in children, side effects, and the emergence of metronidazole-resistant strains may restrict its use. Albendazole has been used to treat Giardia duodenalis infections in recent years. However, efficacy studies in vivo and in vitro have produced diverse results as to its effectiveness. A moderately benign side effect profile, combined with established efficacy against many helminths, renders it promising for treatment of giardiasis in humans. Methodology and Principal Findings We performed a search in the PubMed, Scopus, EMBASE, the ISI Web of Science, LILIACS, and Cochrane Controlled Trials Register for trials published before February 2010 as well as in references of relevant research and review articles. Eight randomized clinical trials (including 900 patients) comparing the effectiveness of albendazole with that of metronidazole were included in meta-analysis. After extracting and validating the data, the pooled risk ratio (RR) was calculated using an inverse-variance random-effects model. Albendazole was found to be equally as effective as metronidazole in the treatment of giardiasis in humans (RR 0.97; 95% CI, 0.93, 1.01). In addition, safety analysis suggested that patients treated with albendazole had a lower risk of adverse effects compared with those who received metronidazole (RR 0.36; 95% CI, 0.10, 1.34), but limitations of the sample size precluded a definite conclusion. Conclusions/Significance The effectiveness of albendazole, when given as a single dose of 400 mg/day for 5 days, was comparable to that of metronidazole. Patients treated with albendazole tended to have fewer side effects compared with those who took metronidazole. Given the safety, effectiveness, and low costs of albendazole, this drug could be potentially used as an alternative and/or a replacement for the existing metronidazole therapy protocols in the treatment of giardiasis in humans. PMID:20485492

Psychosis during pregnancy: treatment considerations.

PubMed

Pinkofsky, H B

1997-09-01

The onset of psychosis during pregnancy presents several difficult management decisions and a careful risk-benefit analysis is required. Withholding antipsychotic treatment may produce more risks than benefits. Studies on neuroleptic teratogenicity are contradictory. Most of the commonly used neuroleptics exhibit a pregnancy risk of category C. Neuroleptic use during pregnancy may be associated with adverse effects in the pre- and postnatal period. These concerns include compromising uterine blood flow, post-partum neonatal sedation, and extrapyramidal signs expressed in the neonate. Each neuroleptic exhibits a unique pharmacokinetic profile. The antipsychotic properties and side effects considered most significant include sedation, half-life, hypotension, and apparent hydrophilicity. In this case study a decision to select molindone was based on these parameters.

Big enough for an aromatase inhibitor? How adiposity affects male fertility.

PubMed

Stephens, Sahar M; Polotsky, Alex J

2013-07-01

Obesity is a pandemic and is associated with multiple medical problems including subfertility. Male obesity has been associated with altered semen parameters and reproductive hormonal levels, including a reduced testosterone:estradiol (T:E₂) ratio. Treatment methods employed for obesity-related male subfertility include gonadotropin administration, weight loss, and aromatase inhibitors. Letrozole is a highly effective nonsteroidal aromatase inhibitor that has been used to treat male subfertility in several case series with promising results. Adequately designed randomized controlled studies are needed to produce evidence-based data on the role of aromatase inhibitors in male subfertility management and evaluate the side-effect profile. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Effects of positive ion implantation into antireflection coating of silicon solar cells

NASA Technical Reports Server (NTRS)

Middleton, A. E.; Harpster, J. W.; Collis, W. J.; Kim, C. K.

1971-01-01

The state of technological development of Si solar cells for highest obtained efficiency and radiation resistance is summarized. The various theoretical analyses of Si solar cells are reviewed. It is shown that factors controlling blue response are carrier diffusion length, surface recombination, impurity concentration profile in surface region, high level of surface impurity concentration (degeneracy), reflection coefficient of oxide, and absorption coefficient of Si. The theory of ion implantation of charge into the oxide antireflection coating is developed and side effects are discussed. The experimental investigations were directed at determining whether the blue response of Si solar cells could be improved by phosphorus ion charges introduced into the oxide antireflection coating.

Wigner Transport Simulation of Resonant Tunneling Diodes with Auxiliary Quantum Wells

NASA Astrophysics Data System (ADS)

Lee, Joon-Ho; Shin, Mincheol; Byun, Seok-Joo; Kim, Wangki

2018-03-01

Resonant-tunneling diodes (RTDs) with auxiliary quantum wells ( e.g., emitter prewell, subwell, and collector postwell) are studied using a Wigner transport equation (WTE) discretized by a thirdorder upwind differential scheme. A flat-band potential profile is used for the WTE simulation. Our calculations revealed functions of the auxiliary wells as follows: The prewell increases the current density ( J) and the peak voltage ( V p ) while decreasing the peak-to-valley current ratio (PVCR), and the postwell decreases J while increasing the PVCR. The subwell affects J and PVCR, but its main effect is to decrease V p . When multiple auxiliary wells are used, each auxiliary well contributes independently to the transport without producing side effects.

The behavior of surface tension on steady-state rotating fluids in the low gravity environments

NASA Technical Reports Server (NTRS)

Hung, R. J.; Leslie, Fred W.

1987-01-01

The effect of surface tension on steady-state rotating fluids in a low gravity environment is studied. All the values of the physical parameters used in these calculations, except in the low gravity environments, are based on the measurements carried out by Leslie (1985) in the low gravity environment of a free-falling aircraft. The profile of the interface of two fluids is derived from Laplace's equation relating the pressure drop across an interface to the radii of curvature which has been applied to a low gravity rotating bubble that contacts the container boundary. The interface shape depends on the ratio of gravity to surface tension forces, the ratio of centrifugal to surface tension forces, the contact radius of the interface to the boundary, and the contact angle. The shape of the bubble is symmetric about its equator in a zero-gravity environment. This symmetry disappears and gradually shifts to parabolic profiles as the gravity environment becomes non-zero. The location of the maximum radius of the bubble moves upward from the center of the depth toward the top boundary of the cylinder as gravity increases. The contact radius of interface to the boundary r0 at the top side of cylinder increases and r0 at the bottom side of the cylinder decreases as the gravity environment increases from zero to 1 g.

Does Emotional Intelligence have a “Dark” Side? A Review of the Literature

PubMed Central

Davis, Sarah K.; Nichols, Rachel

2016-01-01

Emotional intelligence (EI) was once touted as the panacea for a satisfying and successful life. Consequently, there has been much emphasis on developing interventions to promote this personal resource in applied settings. Despite this, a growing body of research has begun to identify particular contexts when EI does not appear helpful and may even be deleterious to a person, or those they have contact with, suggesting a “dark” side to the construct. This paper provides a review of emergent literature to examine when, why and how trait and ability EI may contribute to negative intrapersonal (psychological ill-health; stress reactivity) and interpersonal outcomes (emotional manipulation; antisocial behavior). Negative effects were found to operate across multiple contexts (health, academic, occupational) however these were often indirect, suggesting that outcomes depend on pre-existing qualities of the person. Literature also points to the possibility of “optimal” levels of EI—both within and across EI constructs. Uneven profiles of self-perceptions (trait facets) or actual emotional skills contribute to poorer outcomes, particularly emotional awareness, and management. Moreover, individuals who possess high levels of skill but have lower self-perceptions of their abilities fare worse that those with more balanced profiles. Future research must now improve methodological and statistical practices to better capture EI in context and the negative corollary associated with high levels. PMID:27625627

¹H NMR-based metabolic profiling of naproxen-induced toxicity in rats.

PubMed

Jung, Jeeyoun; Park, Minhwa; Park, Hye Jin; Shim, Sun Bo; Cho, Yang Ha; Kim, Jinho; Lee, Ho-Sub; Ryu, Do Hyun; Choi, Donwoong; Hwang, Geum-Sook

2011-01-15

The dose-dependent perturbations in urinary metabolite concentrations caused by naproxen toxicity were investigated using ¹H NMR spectroscopy coupled with multivariate statistical analysis. Histopathologic evaluation of naproxen-induced acute gastrointestinal damage in rats demonstrated a significant dose-dependent effect. Furthermore, principal component analysis (PCA) of ¹H NMR from rat urine revealed a dose-dependent metabolic shift between the vehicle-treated control rats and rats treated with low-dose (10 mg/kg body weight), moderate-dose (50 mg/kg), and high-dose (100 mg/kg) naproxen, coinciding with their gastric damage scores after naproxen administration. The resultant metabolic profiles demonstrate that the naproxen-induced gastric damage exhibited energy metabolism perturbations that elevated their urinary levels of citrate, cis-aconitate, creatine, and creatine phosphate. In addition, naproxen administration decreased choline level and increased betaine level, indicating that it depleted the main protective constituent of the gastric mucosa. Moreover, naproxen stimulated the decomposition of tryptophan into kynurenate, which inhibits fibroblast growth factor-1 and delays ulcer healing. These findings demonstrate that ¹H NMR-based urinary metabolic profiling can facilitate noninvasive and rapid diagnosis of drug side effects and is suitable for elucidating possible biological pathways perturbed by drug toxicity. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The progestational and androgenic properties of medroxyprogesterone acetate: gene regulatory overlap with dihydrotestosterone in breast cancer cells

PubMed Central

Ghatge, Radhika P; Jacobsen, Britta M; Schittone, Stephanie A; Horwitz, Kathryn B

2005-01-01

Introduction Medroxyprogesterone acetate (MPA), the major progestin used for oral contraception and hormone replacement therapy, has been implicated in increased breast cancer risk. Is this risk due to its progestational or androgenic properties? To address this, we assessed the transcriptional effects of MPA as compared with those of progesterone and dihydrotestosterone (DHT) in human breast cancer cells. Method A new progesterone receptor-negative, androgen receptor-positive human breast cancer cell line, designated Y-AR, was engineered and characterized. Transcription assays using a synthetic promoter/reporter construct, as well as endogenous gene expression profiling comparing progesterone, MPA and DHT, were performed in cells either lacking or containing progesterone receptor and/or androgen receptor. Results In progesterone receptor-positive cells, MPA was found to be an effective progestin through both progesterone receptor isoforms in transient transcription assays. Interestingly, DHT signaled through progesterone receptor type B. Expression profiling of endogenous progesterone receptor-regulated genes comparing progesterone and MPA suggested that although MPA may be a somewhat more potent progestin than progesterone, it is qualitatively similar to progesterone. To address effects of MPA through androgen receptor, expression profiling was performed comparing progesterone, MPA and DHT using Y-AR cells. These studies showed extensive gene regulatory overlap between DHT and MPA through androgen receptor and none with progesterone. Interestingly, there was no difference between pharmacological MPA and physiological MPA, suggesting that high-dose therapeutic MPA may be superfluous. Conclusion Our comparison of the gene regulatory profiles of MPA and progesterone suggests that, for physiologic hormone replacement therapy, the actions of MPA do not mimic those of endogenous progesterone alone. Clinically, the complex pharmacology of MPA not only influences its side-effect profile; but it is also possible that the increased breast cancer risk and/or the therapeutic efficacy of MPA in cancer treatment is in part mediated by androgen receptor. PMID:16457685

Pharmacodynamics of combined estrogen-progestin oral contraceptives: 1. Effects on metabolism.

PubMed

Bastianelli, Carlo; Farris, Manuela; Rosato, Elena; Brosens, Ivo; Benagiano, Giuseppe

2017-03-01

The risk-benefit profile of any pharmacologic agent must be evaluated against risks connected with the events to be avoided. This is especially true in the case of hormonal contraception, not intended to combat a disease. Over the six decades during which their use has progressively expanded, the risk-benefit profile of combined oral contraceptives (COC) has substantially changed, with new combinations, dosages and mode of administration appearing on the market. Area covered: In a series of articles, recent information on the complex issue of COC risks and benefits will be reviewed in the hope of providing an updated picture. The present article reviews metabolic changes occurring during use of modern combinations of estrogens (ethinyl estradiol, estradiol, estradiol valerate and estetrol) and new progestins (desogestrel, gestodene, dienogest, drospirenone, nomegestrol acetate), often compared to classic compounds, such as levonorgestrel. Three categories of metabolic effects in healthy women are detailed: on carbohydrates, lipid and bone mineral content. Expert commentary: Overall, the picture is reassuring: the new generations of progestins are basically devoid of androgenic, estrogenic or glucocorticoid related side-effects. This should result in an improved safety profile, although past history teaches us that that large comparative and surveillance studies are required before firm conclusions can be drawn. At any rate, available evidence indicates that metabolic effects of third and fourth generation progestins, especially when they are combined with natural estrogens, are minimal and, if used in healthy women, should not cause concern.

Empirically Supported Use of Psychiatric Medications in Adolescents and Adults with IBD.

PubMed

Thorkelson, Gregory; Bielefeldt, Klaus; Szigethy, Eva

2016-06-01

The use of psychotropic medications, particularly antidepressants, is common in patients with inflammatory bowel disease (IBD) in spite of a lack of their robust efficacy in this population. This review provides an overview of the use trends of different classes of antidepressant and anti-anxiety medication and their effects on mood, nervous system function, gastrointestinal physiology and immunity drawing from the literature available in the general population, other medical conditions, and when available, patients with IBD. It also covers the evidence base for the actions, efficacy, and potential complications of antidepressants organized by different classes. We conducted a PubMed search of articles relating the different drug classes probed to the terms above in different populations of interest. All types of articles were accepted including case reports and series, open and randomized trials, reviews, and expert opinion. We also examined the reference lists of the publications found. Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are the most commonly prescribed agents for anxiety and depression in patients with IBD, though their efficacy for these conditions in the general population are mild to moderate at best. SSRIs are generally well tolerated, though at higher doses, they, like most antidepressant classes, can be associated with activation, serotonergic syndrome, and increased suicidal ideation. TCAs have many more serious side effects but have some shown efficacy for functional GI symptoms. A newer class, the serotonin noradrenergic reuptake inhibitors (SNRIs), can be effective for refractory depression, anxiety and chronic pain syndromes with a side effect profile similar to both SSRIs and more mild manifestations of TCAs. Mirtazapine has moderate efficacy for depression if sedation and weight gain side effects are tolerated and some small support for use in nausea and vomiting. Bupropion targets dopamine and noradrenaline reuptake and has moderate efficacy for depression, and some small support for use in fatigue and smoking cessation. Buspirone has an indication for generalized anxiety disorder though studies show only a minimal benefit. It has some growing evidence for use in functional dyspepsia. Most of these agents have physiological effects on the brain, immune system, and gastrointestinal tract (with the exception of bupropion) hence their therapeutic and side effects manifested in these systems. Antidepressant medications are frequently prescribed for depression, anxiety disorders, and chronic pain syndromes, but overall support for their efficacy is modest at best. Psychological interventions have growing support for having much more robust effects without the side effects of antidepressants and should be considered first-line treatment or at least an adjunct to psychotropic medications for these conditions.

Monitoring and Management of Toxicities of Novel B Cell Signaling Agents.

PubMed

Rhodes, Joanna; Mato, Anthony; Sharman, Jeff P

2018-04-11

B cell signaling agents, including ibrutinib, idelalisib, and the BCL-2 inhibitor venetoclax have become an integral part of therapy for patients with non-Hodgkin's lymphomas. The toxicity profiles of these medications is distinct from chemoimmunotherapy. Here, we will review the mechanism of action of these drugs, their efficacy, and toxicity management. Ibrutinib use is associated with increased risk of atrial fibrillation and bleeding which can be managed using dose interruptions and modifications. Patients on idelalisib require close clinical and frequent laboratory monitoring, particularly of liver function tests to ensure there are no serious adverse events. Monitoring for infections is important in patients on both idelalisib and ibrutinib. Venetoclax requires close clinical and laboratory monitoring to prevent significant tumor lysis. Targeted B cell receptor therapies each have unique side effect profiles which require careful clinical monitoring. As we continue to use these therapies, optimal management strategies will continue to be elucidated.

Numerical simulation of transient temperature profiles for canned apple puree in semi-rigid aluminum based packaging during pasteurization.

PubMed

Shafiekhani, Soraya; Zamindar, Nafiseh; Hojatoleslami, Mohammad; Toghraie, Davood

2016-06-01

Pasteurization of canned apple puree was simulated for a 3-D geometry in a semi-rigid aluminum based container which was heated from all sides at 378 K. The computational fluid dynamics code Ansys Fluent 14.0 was used and the governing equations for energy, momentum, and continuity were computed using a finite volume method. The food model was assumed to have temperature-dependent properties. To validate the simulation, the apple puree was pasteurized in a water cascading retort. The effect of the mesh structures was studied for the temperature profiles during thermal processing. The experimental temperature in the slowest heating zone in the container was compared with the temperature predicted by the model and the difference was not significant. The study also investigated the impact of head space (water-vapor) on heat transfer.

Flows and Stratification of an Enclosure Containing Both Localised and Vertically Distributed Sources of Buoyancy

NASA Astrophysics Data System (ADS)

Partridge, Jamie; Linden, Paul

2013-11-01

We examine the flows and stratification established in a naturally ventilated enclosure containing both a localised and vertically distributed source of buoyancy. The enclosure is ventilated through upper and lower openings which connect the space to an external ambient. Small scale laboratory experiments were carried out with water as the working medium and buoyancy being driven directly by temperature differences. A point source plume gave localised heating while the distributed source was driven by a controllable heater mat located in the side wall of the enclosure. The transient temperatures, as well as steady state temperature profiles, were recorded and are reported here. The temperature profiles inside the enclosure were found to be dependent on the effective opening area A*, a combination of the upper and lower openings, and the ratio of buoyancy fluxes from the distributed and localised source Ψ =Bw/Bp . Industrial CASE award with ARUP.

Complex permittivity measurements during high temperature recycling of space shuttle antenna window and dielectric heat shield materials

NASA Technical Reports Server (NTRS)

Bassett, H. L.; Bomar, S. H., Jr.

1973-01-01

The research performed and the data obtained on candidate space shuttle antenna window and heat shield materials are presented. The measurement technique employs a free-space focused beam microwave bridge for obtaining RF transmission data, and a device which rotates a sample holder which is heated on one side by natural gas-air flames. The surface temperature of each sample is monitored by IR pyrometry; embedded and rear surface thermocouples are also used in obtaining temperature data. The surface of the sample undergoing test is subjected to approximately the same temperature/time profile that occurs at a proposed antenna position on the space shuttle as it re-enters. The samples are cycled through ten of these temperature profiles to determine the recycling effects. Very little change was noted in the materials due to the recycling.

Streaked x-ray backlighting with twin-slit imager for study of density profile and trajectory of low-density foam target filled with deuterium liquid

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

Shiraga, H.; Mahigashi, N.; Yamada, T.

2008-10-15

Low-density plastic foam filled with liquid deuterium is one of the candidates for inertial fusion target. Density profile and trajectory of 527 nm laser-irradiated planer foam-deuterium target in the acceleration phase were observed with streaked side-on x-ray backlighting. An x-ray imager employing twin slits coupled to an x-ray streak camera was used to simultaneously observe three images of the target: self-emission from the target, x-ray backlighter profile, and the backlit target. The experimentally obtained density profile and trajectory were in good agreement with predictions by one-dimensional hydrodynamic simulation code ILESTA-1D.

Primary intestinal lymphangiectasia in children: is octreotide an effective and safe option in the treatment?

PubMed

Sari, Sinan; Baris, Zeren; Dalgic, Buket

2010-10-01

Octreotide has been suggested as a medical treatment option in refractory cases of primary intestinal lymphangiectasia (IL). There are few data about the long-term effect and safety of octreotide for IL in the literature. In the present article we analyzed pediatric cases of primary IL with long-term octreotide treatment and discussed its safety profile. Between 1999 and 2008, 13 children were diagnosed in our clinic as having IL. Six patients with primary IL were followed up, receiving octreotide therapy. The clinical data of the patients and duration of therapy, dose, and side effects of octreotide were evaluated. Octreotide, 15 to 20 μg per body weight 2 times daily subcutaneously, was given to all of the patients. Duration of the octreotide treatment changed between 3 and 37 months. Stool frequency decreased in all of the patients after starting octreotide treatment. Serum albumin could be maintained at normal levels in 3 patients. The requirement of albumin infusions decreased in all of the patients. Acute pancreatitis was observed as a side effect of octreotide in 1 patient. Octreotide may help to maintain serum albumin levels, improve clinical findings, and decrease the requirement of albumin infusions in refractory cases of primary IL.

Glucocorticoid (dexamethasone)-induced metabolome changes in healthy males suggest prediction of response and side effects.

PubMed

Bordag, Natalie; Klie, Sebastian; Jürchott, Kathrin; Vierheller, Janine; Schiewe, Hajo; Albrecht, Valerie; Tonn, Jörg-Christian; Schwartz, Christoph; Schichor, Christian; Selbig, Joachim

2015-11-03

Glucocorticoids are indispensable anti-inflammatory and decongestant drugs with high prevalence of use at (~)0.9% of the adult population. Better holistic insights into glucocorticoid-induced changes are crucial for effective use as concurrent medication and management of adverse effects. The profiles of 214 metabolites from plasma of 20 male healthy volunteers were recorded prior to and after ingestion of a single dose of 4 mg dexamethasone (+20 mg pantoprazole). Samples were drawn at three predefined time points per day: seven untreated (day 1 midday - day 3 midday) and four treated (day 3 evening - day 4 evening) per volunteer. Statistical analysis revealed tremendous impact of dexamethasone on the metabolome with 150 of 214 metabolites being significantly deregulated on at least one time point after treatment (ANOVA, Benjamini-Hochberg corrected, q < 0.05). Inter-person variability was high and remained uninfluenced by treatment. The clearly visible circadian rhythm prior to treatment was almost completely suppressed and deregulated by dexamethasone. The results draw a holistic picture of the severe metabolic deregulation induced by single-dose, short-term glucocorticoid application. The observed metabolic changes suggest a potential for early detection of severe side effects, raising hope for personalized early countermeasures increasing quality of life and reducing health care costs.

Acupuncture for chronic prostatitis: A systematic review and meta-analysis protocol.

PubMed

Peng, Tianzhong; Cheng, Ying; Jin, Yuhao; Xu, Na; Guo, Taipin

2018-04-01

Chronic prostatitis (CP) is a prevalent genitourinary condition. Considering its safety profile, acupuncture can be an option treating CP symptoms. The aim of this review is to undertake a systematic review to estimate the effectiveness and safety of acupuncture on CP. We will search all randomized controlled trials for CP in August 2018 in the databases of MEDLINE, Cochrane Library, Web of Science, EMBASE, Springer, WHO International Clinical Trials Registry Platform (ICTRP), China National Knowledge Infrastructure (CNKI), Wan fang, Chinese Biomedical Literature Database (CBM), PsycInfo, Chinese Scientific Journal Database (VIP), and other available resources. Languages are limited as English and Chinese. Search terms used are will "acupuncture," and "chronic prostatitis," "non-bacterial prostatitis," "abacterial prostatitis." And duplicates will be screened. The primary outcomes consisted of improvement rate and pain relief evaluated by The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) index. Secondary outcomes include the recurrence rate and side effects, such as pneumothorax, discomforts, and infection. This study will demonstrate an evidence-based review of acupuncture for chronic prostatitis. The study will provide clear evidence to assess the effectiveness and side effects of acupuncture for chronic prostatitis. There is no requirement of ethical approval and it will be in print or disseminated by electronic copies. CRD42018088834.

Autobiographical Memory and ECT: Don’t Throw Out the Baby

PubMed Central

Sackeim, Harold A.

2014-01-01

Retrograde amnesia for autobiographical information is the most critical side effect of ECT. Much, if not most, modern research demonstrating long-term autobiographical amnesia following ECT has used either the Columbia University Autobiographical Memory Interview (CUAMI) or the short form of this scale (CUAMI-SF). Semkovska and McLoughlin claimed that studies using these instruments should be dismissed and the findings ignored due to a lack of normative data, as well as concerns about the reliability and validity of these instruments. In this commentary, the development and use of these scales is reviewed. It is shown that Semkovska and McLoughlin’s critique is factually incorrect, as normative data were simultaneously collected in virtually all studies using these instruments. Furthermore, there is substantial evidence supporting the reliability and validity of these scales. Indeed, these instruments are the only neuropsychological tests repeatedly shown to covary with patient self-evaluations of ECT’s effects on memory, and have repeatedly demonstrated long-term differences in the magnitude of amnesia as a function of ECT technique. Findings with the CUAMI and CUAMI-SF provide key evidence regarding ECT’s cognitive side effect profile. It is inaccurate and inadvisable to continue to deny that ECT can exert long-term adverse effects in this domain. PMID:24755727

Magnetic Seizure Therapy for Unipolar and Bipolar Depression: A Systematic Review

PubMed Central

Cretaz, Eric; Brunoni, André R.

2015-01-01

Objective. Magnetic seizure therapy (MST) is a novel, experimental therapeutic intervention, which combines therapeutic aspects of electroconvulsive therapy (ECT) and transcranial magnetic stimulation, in order to achieve the efficacy of the former with the safety of the latter. MST might prove to be a valuable tool in the treatment of mood disorders, such as major depressive disorder (MDD) and bipolar disorder. Our aim is to review current literature on MST. Methods. OVID and MEDLINE databases were used to systematically search for clinical studies on MST. The terms “magnetic seizure therapy,” “depression,” and “bipolar” were employed. Results. Out of 74 studies, 8 met eligibility criteria. There was considerable variability in the methods employed and samples sizes were small, limiting the generalization of the results. All studies focused on depressive episodes, but few included patients with bipolar disorder. The studies found reported significant antidepressant effects, with remission rates ranging from 30% to 40%. No significant cognitive side effects related to MST were found, with a better cognitive profile when compared to ECT. Conclusion. MST was effective in reducing depressive symptoms in mood disorders, with generally less side effects than ECT. No study focused on comparing MST to ECT on bipolar depression specifically. PMID:26075100

Efficacy and toxicity profile of carfilzomib based regimens for treatment of multiple myeloma: A systematic review.

PubMed

Mushtaq, Adeela; Kapoor, Vikas; Latif, Azka; Iftikhar, Ahmad; Zahid, Umar; McBride, Ali; Abraham, Ivo; Riaz, Irbaz Bin; Anwer, Faiz

2018-05-01

Standard induction therapy for multiple myeloma is three-drug combination based on following classes of drugs: proteasome inhibitors, immunomodulators and steroids. Despite its notable efficacy, bortezomib has side effects like peripheral neuropathy (PNP) with reported incidence of grade ≥3 PNP between 2%-23% Schlafer et al., 2017. Carfilzomib (CFZ) has high selectivity and minimal off-target adverse effects including lower rates of PNP. CFZ is already approved for treatment of relapsed and refractory multiple myeloma (RRMM) as single agent as well as in combination with lenalidomide and/or dexamethasone. Extensive literature search identified a total of 1839 articles. Twenty-six articles (n = 5980) met the inclusion criteria, 15 in newly diagnosed multiple myeloma (NDMM) and 11 in RRMM group. CFZ demonstrates comparable or even better efficacy to bortezomib with much favorable AE profile. Deep, rapid and sustainable response using KRd with safer toxicity profile supports extension of KRd therapy to frontline therapy for all risk categories of MM. High incidence of grade ≥3 HTN underscores the importance of serial BP monitoring. In RRMM, CFZ has documented efficacy with standard 20-27mg/m2 dose. Further large-scale trials are needed to study benefit-to-risk profile of 20-56 and 20-70 mg/m2 dose of CFZ vs standard 20-27 mg/m2 dose in NDMM and RRMM. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of transverse magnetic fields on a simulated in-line 6 MV linac

NASA Astrophysics Data System (ADS)

St. Aubin, J.; Steciw, S.; Fallone, B. G.

2010-08-01

The effects of a transverse magnetic field on an in-line side-coupled 6 MV linear accelerator are given. The results are directly applicable to a linac-MR system used for real-time image guided adaptive radiotherapy. Our previously designed end-to-end linac simulation incorporated the results from the axisymmetric 2D electron gun program EGN2w. However, since the magnetic fields being investigated are non-axisymmetric in nature for the work presented here, the electron gun simulation was performed using OPERA-3d/SCALA. The simulation results from OPERA-3d/SCALA showed excellent agreement with previous results. Upon the addition of external magnetic fields to our fully 3D linac simulation, it was found that a transverse magnetic field of 6 G resulted in a 45 ± 1% beam loss, and by 14 G, no electrons were incident on the target. Transverse magnetic fields on the linac simulation produced a highly asymmetric focal spot at the target, which translated into a 13% profile asymmetry at 6 G. Upon translating the focal spot with respect to the target coordinates, profile symmetry was regained at the expense of a lateral shift in the dose profiles. It was found that all points in the penumbra failed a 1%/1 mm acceptance criterion for fields between 4 and 6 G. However, it was also found that the lateral profile shifts were corrected by adjusting the jaw positions asymmetrically.

One-dimensional scanning of moisture in heated porous building materials with NMR.

PubMed

van der Heijden, G H A; Huinink, H P; Pel, L; Kopinga, K

2011-02-01

In this paper we present a new dedicated NMR setup which is capable of measuring one-dimensional moisture profiles in heated porous materials. The setup, which is placed in the bore of a 1.5 T whole-body scanner, is capable of reaching temperatures up to 500 °C. Moisture and temperature profiles can be measured quasi simultaneously with a typical time resolution of 2-5 min. A methodology is introduced for correcting temperature effects on NMR measurements at these elevated temperatures. The corrections are based on the Curie law for paramagnetism and the observed temperature dependence of the relaxation mechanisms occurring in porous materials. Both these corrections are used to obtain a moisture content profile from the raw NMR signal profile. To illustrate the methodology, a one-sided heating experiment of concrete with a moisture content in equilibrium with 97% RH is presented. This kind of heating experiment is of particular interest in the research on fire spalling of concrete, since it directly reveals the moisture and heat transport occurring inside the concrete. The obtained moisture profiles reveal a moisture peak building up behind the boiling front, resulting in a saturated layer. To our knowledge the direct proof of the formation of a moisture peak and subsequent moisture clogging has not been reported before. Copyright © 2010 Elsevier Inc. All rights reserved.

Measurements of Electron Temperature and Density Profiles of Plasmas Produced by Nike KrF Laser for Laser Plasma Instability (LPI) Research

NASA Astrophysics Data System (ADS)

Oh, Jaechul; Weaver, J. L.; Obenschain, S. P.; Schmitt, A. J.; Kehne, D. M.; Karasik, M.; Chan, L.-Y.; Serlin, V.; Phillips, L.

2012-10-01

ExperimentsfootnotetextJ. Oh, et al, GO5.4, APS DPP (2010).^,footnotetextJ. L. Weaver, et al, GO5.3, APS DPP (2010). using Nike KrF laser observed LPI signatures from CH plasmas at the laser intensities above ˜1x10^15 W/cm^2. Knowing spatial profiles of temperature (Te) and density (ne) in the underdense coronal region (0 < n < nc/4) of the plasma is essential to understanding the LPI observation. However, numerical simulation was the only way to access the profiles for the previous experiments. In the current Nike LPI experiment, a side-on grid imaging refractometer (GIR)footnotetextR. S. Craxton, et al, Phys. Fluids B 5, 4419 (1993). is being deployed for measuring the underdense plasma profiles. The GIR will resolve Te and ne in space taking a 2D snapshot of probe laser (λ= 263 nm, δt = 10 psec) beamlets (50μm spacing) refracted by the plasma at a selected time during the laser illumination. Time-resolved spectrometers with an absolute-intensity-calibrated photodiode array and a streak camera will simultaneously monitor light emission from the plasma in spectral ranges relevant to Raman (SRS) and two plasmon decay (TDP) instabilities. The experimental study of effects of the plasma profiles on the LPI initiation will be presented.

Testing the antidepressant properties of the peptide ARA290 in a human neuropsychological model of drug action.

PubMed

Cerit, Hilâl; Veer, Ilya M; Dahan, Albert; Niesters, Marieke; Harmer, Catherine J; Miskowiak, Kamilla W; Rombouts, Serge A R B; Van der Does, Willem

2015-12-01

Studies on the neural effects of Erythropoietin (EPO) indicate that EPO may have antidepressant effects. Due to its hematopoietic effects, EPO may cause serious side-effects with repeated administration if patients are not monitored extensively. ARA290 is an EPO-analog peptide without such hematopoietic side-effects but may have neurotrophic and antidepressant effects. The aim of this study was to investigate the possible antidepressant effects of ARA290 in a neuropsychological model of drug action. Healthy participants (N=36) received ARA290 (2mg) or placebo in a double-blind, randomized, parallel-group design. Neural and cognitive effects were assessed one week after administration. Primary outcome measures were the neural processing of fearful vs happy faces and the behavioral recognition of emotional facial expressions. ARA290-treated individuals displayed lower neural responses to happy faces in the fusiform gyrus. ARA290 tended to lower the recognition of happy and disgust facial expressions. Although ARA290 was not associated with a better memory for positive words, it was associated with faster categorization of positive vs negative words. Finally, ARA290 increased attention towards positive emotional pictures. No effects were observed on mood and affective symptoms. ARA290 may modulate some aspects of emotional processing, however, the direction and the strength of its effects do not unequivocally support an antidepressant-like profile for ARA290. Future studies may investigate the effects of different timing and dose. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Neuropsychological Effects of Neuromodulation Techniques for Treatment-Resistant Depression: A Review

PubMed Central

Moreines, Jared L.; McClintock, Shawn M.; Holtzheimer, Paul E.

2010-01-01

Electroconvulsive therapy (ECT) and ablative neurosurgical procedures are established interventions for treatment-resistant depression (TRD), but their use may be limited in part by neuropsychological adverse effects. Additional neuromodulation strategies are being developed that aim to match or exceed the efficacy of ECT/ablative surgery with a better neurocognitive side effect profile. In this review, we briefly discuss the neurocognitive effects of ECT and ablative neurosurgical procedures, then synthesize the available neurocognitive information for emerging neuromodulation therapies including repetitive transcranial magnetic stimulation, magnetic seizure therapy, transcranial direct current stimulation, vagus nerve stimulation, and deep brain stimulation. The available evidence suggests these procedures may be more cognitively benign relative to ECT or ablative neurosurgical procedures, though further research is clearly needed to fully evaluate the neurocognitive effects, both positive and negative, of these novel neuromodulation interventions. PMID:21255751

Metabonomic profiling in studying anti-osteoporosis effects of strontium fructose 1,6-diphosphate on estrogen deficiency-induced osteoporosis in rats by GC/TOF-MS.

PubMed

Ma, Bo; Li, Xiaotian; Zhang, Qi; Wu, Di; Wang, Guangji; A, Jiye; Sun, Jianguo; Li, Jing; Liu, Yinhui; Wang, Yonglu; Ying, Hanjie

2013-10-15

A novel strontium salt compound strontium fructose 1, 6-diphosphate (FDP-Sr) has been proved to have highly effective for bone loss via dual effects of stimulating bone formation and suppressing bone absorption. In the present study, metabolomic approach was used to identify and study potential biomarkers associated with the effect and safety of FDP-Sr. The metabolomic profiles of bone loss induced by estrogen deficiency in a rat model was described to attain a system-level map of the shift on the metabolic response in plasma using GC/TOF-MS, after FDP-Sr was orally administered at the dose of 110 mg/kg/day for the prevention and 220 mg/kg/day for the treatment. Meanwhile, bone turnover biomarkers and bone mineral density were investigated to identify the specific changes of potential anti-osteoporosis effects of FDP-Sr. The differences in metabolic profiles between osteoporosis rats and FDP-Sr treated rats were well observed by the partial least squares-discriminant analysis (PLS-DA) to the MS spectra. Some metabolites including homocysteine, arachidonic acid, alanine, and hydroxyproline, which significantly changed during osteoporosis progression could be effectively reversed after FDP-Sr therapy. Of course some metabolites such as uric acid, glyceric acid, octadecadienoic acid, docosahexaenoic acid, oleic acid, and hexadecanoic acid were not found to reverse significantly after FDP-Sr administration. These results delineated the FDP-Sr effects-related metabolic alterations in the bone loss rats, suggesting that metabonomic analysis could provide helpful information on the new potential biomarkers relating to the mechanism of anti-osteoporosis action and side effects of FDP-Sr against estrogen deficiency induced bone loss. © 2013 Elsevier B.V. All rights reserved.

The effect of chronic administration of sarizotan, 5-HT1A agonist/D3/D4 ligand, on haloperidol-induced repetitive jaw movements in rat model of tardive dyskinesia.

PubMed

Rosengarten, Helen; Bartoszyk, Gerd D; Quartermain, David; Lin, Yan

2006-03-01

Dyskinesia is the most troublesome side effect in long-term treatment of both Parkinson's disease (PD) and schizophrenia. The 5-HT1A agonist and D3/D4 ligand sarizotan [Bartoszyk, G.D., van Amsterdam, C., Greiner, H.E., Rautenberg, W., Russ, H., Seyfried, C.A., 2004. Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile. J. Neural Transm. 111, 113-126.] is in clinical development for the treatment of PD-associated dyskinesia. Because 5-HT1A agonists are known to counteract antipsychotic-induced motor side effects, sarizotan was investigated for its effects in two rat models of tardive dyskinesia (TD). The acute administration of sarizotan (0.17-13.5 mg/kg i.p.) reduced episodes of SKF 38393-induced repetitive jaw movements (RJM) in rats with a maximal effect at 1.5 mg/kg. In a chronic study, sarizotan (0.04-9 mg/kg/day), administered in the drinking water for 7 weeks during withdrawal from chronic haloperidol treatment (1.5 mg/kg/day), dose-dependently reversed haloperidol-induced RJM, significant at the doses of 1.5 and 9 mg/kg. Agonism at 5-HT1A receptors may be mediating the inhibitory effect of sarizotan on RJM in rat models of tardive dyskinesia.

Treatment of acne scars and wrinkles in asian patients using carbon-dioxide fractional laser resurfacing: its effects on skin biophysical profiles.

PubMed

Hwang, Young Ji; Lee, Yu Na; Lee, Yang Won; Choe, Yong Beom; Ahn, Kyu Joong

2013-11-01

Although ablative fractional resurfacing is known to be effective against photoaging and acne scars, studies on its efficacy, safety and changes in the skin characteristics of Asians are limited. The aim of this study is to assess the efficacy and safety of carbon dioxide fractional laser (CO2FL) in Koreans treated for wrinkles and acne scars, and to define the changes in skin characteristics during recovery period. We administered one session of CO2FL on 10 acne scar patients and 14 wrinkles patients with skin types IV and V. The surveillance of efficacy and side effects along with the measurement of biophysical properties was carried out before 1 day, 1 week, 1 month and 3 months after treatment. Using a non-invasive method, skin barrier damage, erythema and bronzing of skin during the recovery period were assessed, and all of the items eventually returned to the pre-treatment level. Skin elasticity was measured in the wrinkle group, and the statistically significant effect was sustained throughout the next three months. The outcome of treatment was found to be better than 'moderate improvement' in both the acne scar and wrinkle groups. Further, there were no serious side effects three months post-procedure. CO2 FL is thought to be an effective and safe method for treating moderate to severe acne scars and wrinkles in Asians.

BCL2 Inhibition by Venetoclax: Targeting the Achilles' Heel of the Acute Myeloid Leukemia Stem Cell?

PubMed

Pullarkat, Vinod A; Newman, Edward M

2016-10-01

Venetoclax is an oral drug with an excellent side-effect profile that has the potential to revolutionize acute myeloid leukemia (AML) therapy in two areas. Venetoclax-based combination therapies could be a bridge to hematopoietic cell transplant with curative intent for patients with refractory/relapsed AML, and venetoclax-based therapy could provide meaningful survival prolongation for older patients with AML who are not candidates for more aggressive therapies. Cancer Discov; 6(10); 1082-3. ©2016 AACR.See related article by Konopleva and colleagues, p. 1106. ©2016 American Association for Cancer Research.

Electron-cyclotron resonance preionization and heating in the Proto-cleo torsatron

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

Goes, L.C.S.

1986-01-01

ECR-breakdown and heating in a bifurcated torsatron topology are investigated with extraordinary mode injection from the high-field side (7.2 GHz/2 KW/10 ms). The breakdown characteristics are explained by stochastic heating enhanced by helical ripple effects. In the quasi-stationary regime (0.01 n/sub cr/ < n < 0.6 n/sub cr/), two-dimensional plasma profiles indicated heating inhomogeneities associated with RF power absorption near the UHR layer. The production of a suprathermal electron population, at the outer plasma edge, was indicated by nonthermal microwave emission and target SXR emission.

MMP Inhibitors: Past, present and future.

PubMed

Cathcart, Jillian M; Cao, Jian

2015-06-01

  Development of inhibitors of matrix metalloproteinases (MMPs) has been fraught with challenges. Early compounds largely failed due to poor selectivity and bioavailability. Dose-limiting side effects, off-target interactions, and improperly designed clinical trials significantly impeded clinical success. As information becomes available and technology evolves, tools to combat these obstacles have been developed. Improved methods for high throughput screening and drug design have led to identification of compounds exhibiting high potency, binding affinity, and favorable pharmacokinetic profiles. Current research into MMP inhibitors employs innovative approaches for drug delivery methods and allosteric inhibitors. Such innovation is key for development of clinically successful compounds.

Practice Parameter: Pharmacologic treatment of spasticity in children and adolescents with cerebral palsy (an evidence-based review)

PubMed Central

Delgado, M R.; Hirtz, D; Aisen, M; Ashwal, S; Fehlings, D L.; McLaughlin, J; Morrison, L A.; Shrader, M W.; Tilton, A; Vargus-Adams, J

2010-01-01

Objective: To evaluate published evidence of efficacy and safety of pharmacologic treatments for childhood spasticity due to cerebral palsy. Methods: A multidisciplinary panel systematically reviewed relevant literature from 1966 to July 2008. Results: For localized/segmental spasticity, botulinum toxin type A is established as an effective treatment to reduce spasticity in the upper and lower extremities. There is conflicting evidence regarding functional improvement. Botulinum toxin type A was found to be generally safe in children with cerebral palsy; however, the Food and Drug Administration is presently investigating isolated cases of generalized weakness resulting in poor outcomes. No studies that met criteria are available on the use of phenol, alcohol, or botulinum toxin type B injections. For generalized spasticity, diazepam is probably effective in reducing spasticity, but there are insufficient data on its effect on motor function and its side-effect profile. Tizanidine is possibly effective, but there are insufficient data on its effect on function and its side-effect profile. There were insufficient data on the use of dantrolene, oral baclofen, and intrathecal baclofen, and toxicity was frequently reported. Recommendations: For localized/segmental spasticity that warrants treatment, botulinum toxin type A should be offered as an effective and generally safe treatment (Level A). There are insufficient data to support or refute the use of phenol, alcohol, or botulinum toxin type B (Level U). For generalized spasticity that warrants treatment, diazepam should be considered for short-term treatment, with caution regarding toxicity (Level B), and tizanidine may be considered (Level C). There are insufficient data to support or refute use of dantrolene, oral baclofen, or continuous intrathecal baclofen (Level U). GLOSSARY AAN = American Academy of Neurology; AE = adverse event; AS = Ashworth scale; BoNT-A = botulinum toxin type A; BoNT-B = botulinum toxin type B; CP = cerebral palsy; FDA = Food and Drug Administration; GAS = Goal Attainment Scale; GMFM = Gross Motor Function Measure; ITB = intrathecal baclofen; MAS = Modified Ashworth scale; OT = occupational therapy; PT = physiotherapy; QUEST = Quality of Upper Extremity Skills Test; TS = Tardieu scale. PMID:20101040

Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy.

PubMed

Chen, Baibing; Choi, Hyunmi; Hirsch, Lawrence J; Katz, Austen; Legge, Alexander; Buchsbaum, Richard; Detyniecki, Kamil

2017-11-01

Psychiatric and behavioral side effects (PBSEs) are common, undesirable effects associated with antiepileptic drug (AED) use. The objective of the study was to compare the PBSE profiles of older and newer AEDs in a large specialty practice-based sample of patients diagnosed with epilepsy. As part of the Columbia and Yale AED Database Project, we reviewed patient records including demographics, medical history, AED use, and side effects for 4085 adult patients (age: 18 years) newly started on an AED regimen. Psychiatric and behavioral side effects were determined by patient or physician report in the medical record, which included depressive mood, psychosis, anxiety, suicidal thoughts, irritability, aggression, and tantrum. Significant non-AED predictors of PBSE rate were first determined from 83 variables using logistic regression. Predictors were then controlled for in the comparison analysis of the rate of PBSEs and intolerable PBSEs (PBSEs that led to dosage reduction or discontinuation) between 18 AEDs. Psychiatric and behavioral side effects occurred in 17.2% of patients and led to intolerability in 13.8% of patients. History of psychiatric condition(s), secondary generalized seizures, absence seizures, and intractable epilepsy were associated with increased incidence of PBSE. Levetiracetam (LEV) had the greatest PBSE rate (22.1%). This was statistically significant when compared with the aggregate of the other AEDs (P<0.001, OR=6.87). Levetiracetam was also significantly (P<0.001) associated with higher intolerability rate (17.7%), dose decreased rate (9.4%), and complete cessation rate (8.3%), when compared with the aggregate of the other AEDs. Zonisamide (ZNS) was also significantly associated with a higher rate of PBSE (9.7%) and IPBSE (7.9%, all P<0.001). On the other hand, carbamazepine (CBZ), clobazam (CLB), gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OXC), phenytoin (PHT), and valproate (VPA) were significantly associated with a decreased PBSE rates (P<0.001). Carbamazepine, GBP, LTG, PHT, and VPA were also associated with lower IPBSE rates when compared individually with the aggregate of other AEDs. All other AEDs were found to have intermediate rates that were not either increased or decreased compared with other AEDs. When each AED was compared to LTG, only CBZ had a significantly lower PBSE rate. The main limitations of this study were that the study design was retrospective and not blinded, and the AEDs were not randomly assigned to patients. Psychiatric and behavioral side effects occur more frequently in patients taking LEV and ZNS than any other AED and led to higher rates of intolerability. Lower PBSE rates were seen in patients taking CBZ, CLB, GBP, LTG, OXC, PHT, and VPA. Our findings may help facilitate the AED selection process. Copyright © 2017 Elsevier Inc. All rights reserved.

Randomised controlled trial of informal team sports for cardiorespiratory fitness and health benefit in Pacific adults.

PubMed

Biddle, Mark G; Vincent, Grace; McCambridge, Alana; Britton, Gabrielle; Dewes, Ofa; Elley, C Raina; Moyes, Simon A; Edge, Johann

2011-12-01

Rates of obesity, Type 2 diabetes and cardiovascular disease are high among Pacific people in New Zealand. Physical activity is recommended in the prevention and management of these conditions. Community-based, 'small-sided game' group activities may be an effective and culturally appropriate way to promote physical activity within Pacific communities. To assess the effectiveness of small-sided games-based exercise on fitness and health parameters among Pacific adults over four weeks. Twenty untrained (13 female) Pacific adults were randomised to intervention or control. Intervention participants were offered 45 minutes of small-sided games three times per week for four weeks. Control participants were offered one-month gym membership after the trial. Primary outcomes included cardiorespiratory fitness (VO₂peak) and leg strength (maximal concentric force of quadriceps at 60°/second) measured at baseline and four weeks. Secondary outcomes included glycaemia, lipid profile, blood pressure (BP), and inflammatory markers. Multivariable regression models were used to assess differences between groups, adjusting for baseline values, age and gender. At baseline, mean age was 34.8 years (SD 12.6), BMI 36.3 (6.7), systolic BP 127.7 mmHg (12.1), HbA1c 6.1% (1.9), VO₂peak 2.5 L/min (0.6) and leg strength 170.0 N.m (57.4). Sixteen participants completed the trial. Change in outcomes were greater in intervention than control participants in absolute VO₂peak (0.9 L/min (p=0.003)), leg strength (17.8 N.m (p=0.04)) and HDL (0.12 mmol/L (p=0.02)). There were no other significant differences. Small-sided games appear to be a promising means for improving the health and cardiorespiratory fitness and reducing the risk of diabetes and cardiovascular disease in Pacific adults.

Phenylalanine 445 within oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae influences C-Ring cyclization and deprotonation reactions.

PubMed

Wu, Tung-Kung; Liu, Yuan-Ting; Chiu, Feng-Hsuan; Chang, Cheng-Hsiang

2006-10-12

[reaction: see text] We describe the Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase Phe445 site-saturated mutants that generate truncated tricyclic and altered deprotonation product profiles. Among these mutants, only polar side-chain group substitutions genetically complemented yeast viability and produced spatially related product diversity, supporting the Johnson model that cation-pi interactions between a carbocationic intermediate and an enzyme can be replaced by an electrostatic or polar side chain to stabilize the cationic intermediate, but with product differentiation.

View looking aft along the starboard side of the midfuselage ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View looking aft along the starboard side of the mid-fuselage of the Orbiter Discovery. This view shows the wing profile as it intersects with the fuselage. Also note in the foreground the panels protecting the Reinforced Carbon-Carbon leading edge of the wing. This view was taken from the service platform in the Orbiter Processing Facility at Kennedy Space Center. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

Extended OLED operational lifetime through phosphorescent dopant profile management

DOEpatents

Forrest, Stephen R.; Zhang, Yifan

2017-05-30

This disclosure relates, at least in part, an organic light emitting device, which in some embodiments comprises an anode; a cathode; a first emissive layer disposed between the anode and the cathode, the first emissive layer comprising an electron transporting compound and a phosphorescent emissive dopant compound; and wherein the phosphorescent emissive dopant compound has a concentration gradient, in the emissive layer, which varies from the cathode side of the first emissive layer to the anode side of the emissive layer.

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

PubMed

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

2017-12-14

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

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.

Influence of Shockwave Profile on Ejection of Micron-Scale Material From Shocked Tin Surfaces

NASA Astrophysics Data System (ADS)

Zellner, Michael; Hammerberg, Jim; Hixson, Robert; Olson, Russel; Rigg, Paulo; Stevens, Gerald; Turley, William; Buttler, William

2008-03-01

This effort investigates the relation between shock-pulse shape and the amount of micron-scale fragments ejected (ejecta) upon shock release at the metal/vacuum interface of shocked Sn targets. Two shock-pulse shapes are considered: a supported shock created by impacting a Sn target with a sabot that was accelerated using a powder gun; and an unsupported or triangular-shaped Taylor shockwave, created by detonation of high explosive that was press-fit to the front-side of the Sn target. Ejecta production at the back-side or free-side of the Sn coupons were characterized through use of piezoelectric pins, Asay foil, optical shadowgraphy, and X-ray attenuation.