Solvation thermodynamics of amino acid side chains on a short peptide backbone

NASA Astrophysics Data System (ADS)

Hajari, Timir; van der Vegt, Nico F. A.

2015-04-01

The hydration process of side chain analogue molecules differs from that of the actual amino acid side chains in peptides and proteins owing to the effects of the peptide backbone on the aqueous solvent environment. A recent molecular simulation study has provided evidence that all nonpolar side chains, attached to a short peptide backbone, are considerably less hydrophobic than the free side chain analogue molecules. In contrast to this, the hydrophilicity of the polar side chains is hardly affected by the backbone. To analyze the origin of these observations, we here present a molecular simulation study on temperature dependent solvation free energies of nonpolar and polar side chains attached to a short peptide backbone. The estimated solvation entropies and enthalpies of the various amino acid side chains are compared with existing side chain analogue data. The solvation entropies and enthalpies of the polar side chains are negative, but in absolute magnitude smaller compared with the corresponding analogue data. The observed differences are large; however, owing to a nearly perfect enthalpy-entropy compensation, the solvation free energies of polar side chains remain largely unaffected by the peptide backbone. We find that a similar compensation does not apply to the nonpolar side chains; while the backbone greatly reduces the unfavorable solvation entropies, the solvation enthalpies are either more favorable or only marginally affected. This results in a very small unfavorable free energy cost, or even free energy gain, of solvating the nonpolar side chains in strong contrast to solvation of small hydrophobic or nonpolar molecules in bulk water. The solvation free energies of nonpolar side chains have been furthermore decomposed into a repulsive cavity formation contribution and an attractive dispersion free energy contribution. We find that cavity formation next to the peptide backbone is entropically favored over formation of similar sized nonpolar side chain cavities in bulk water, in agreement with earlier work in the literature on analysis of cavity fluctuations at nonpolar molecular surfaces. The cavity and dispersion interaction contributions correlate quite well with the solvent accessible surface area of the nonpolar side chains attached to the backbone. This correlation however is weak for the overall solvation free energies owing to the fact that the cavity and dispersion free energy contributions are almost exactly cancelling each other.

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

Perspectives on prescribed fire in the south: does ethnicity matter?

Treesearch

Siew Hoon Lim; J.M. Bowker; Cassandra Y. Johnson; H. Ken Cordell

2009-01-01

Using a household survey and regression methods, we assessed preferences for prescribed fire in the southern United States. We found that the majority of the respondents favored the use of prescribed fire. However, we observed pronounced racial variation in opinions on prescribed fire and its side effects. African Americans and Hispanics were less supportive and were...

Optimal Drug Policy in Low-Income Neighborhoods

PubMed Central

Chang, Sheng-Wen; Coulson, N. Edward; Wang, Ping

2015-01-01

The control of drug activity currently favors supply-side policies: drug suppliers in the U.S. face a higher arrest rate and longer sentences than demanders. We construct a simple model of drug activity with search and entry frictions in labor and drug markets. Our calibration analysis suggests a strong “dealer replacement effect.” As a result, given a variety of community objectives, it is beneficial to lower supplier arrests and raise the demand arrest rate from current values. A 10% shift from supply-side to demand-side arrests can reduce the population of potential drug dealers by 22–25,000 and raise aggregate local income by $380–400 million, at 2002 prices. (JEL Classification: D60, J60, K42, H70) PMID:27616878

D-Side: A Facility and Workforce Planning Group Multi-criteria Decision Support System for Johnson Space Center

NASA Technical Reports Server (NTRS)

Tavana, Madjid

2005-01-01

"To understand and protect our home planet, to explore the universe and search for life, and to inspire the next generation of explorers" is NASA's mission. The Systems Management Office at Johnson Space Center (JSC) is searching for methods to effectively manage the Center's resources to meet NASA's mission. D-Side is a group multi-criteria decision support system (GMDSS) developed to support facility decisions at JSC. D-Side uses a series of sequential and structured processes to plot facilities in a three-dimensional (3-D) graph on the basis of each facility alignment with NASA's mission and goals, the extent to which other facilities are dependent on the facility, and the dollar value of capital investments that have been postponed at the facility relative to the facility replacement value. A similarity factor rank orders facilities based on their Euclidean distance from Ideal and Nadir points. These similarity factors are then used to allocate capital improvement resources across facilities. We also present a parallel model that can be used to support decisions concerning allocation of human resources investments across workforce units. Finally, we present results from a pilot study where 12 experienced facility managers from NASA used D-Side and the organization's current approach to rank order and allocate funds for capital improvement across 20 facilities. Users evaluated D-Side favorably in terms of ease of use, the quality of the decision-making process, decision quality, and overall value-added. Their evaluations of D-Side were significantly more favorable than their evaluations of the current approach. Keywords: NASA, Multi-Criteria Decision Making, Decision Support System, AHP, Euclidean Distance, 3-D Modeling, Facility Planning, Workforce Planning.

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.

Specific expectancies are associated with symptomatic outcomes and side effect burden in a trial of chamomile extract for generalized anxiety disorder.

PubMed

Keefe, John R; Amsterdam, Jay; Li, Qing S; Soeller, Irene; DeRubeis, Robert; Mao, Jun J

2017-01-01

Patient expectancies are hypothesized to contribute to the efficacy and side effects of psychiatric treatments, but little research has investigated this hypothesis in the context of psychopharmacological therapies for anxiety. We prospectively investigated whether expectancies predicted efficacy and adverse events in oral therapy for Generalized Anxiety Disorder (GAD), controlling for confounding patient characteristics correlating with outcomes. Expectancies regarding treatment efficacy and side effects were assessed at baseline of an eight week open-label phase of a trial of chamomile for Generalized Anxiety Disorder (GAD). The primary outcome was patient-reported GAD-7 scores, with clinical response and treatment-emergent side-effects as secondary outcomes. Expectancies were used to predict symptomatic and side-effect outcomes. Very few baseline patient characteristics predicted either type of expectancy. Controlling for a patient's predicted recovery based on their baseline characteristics, higher efficacy expectancies at baseline predicted greater change on the GAD-7 (adjusted β = -0.19, p = 0.011). Efficacy expectancies also predicted a higher likelihood of attaining clinical response (adjusted odds ratio = 1.69, p = 0.002). Patients with higher side effect expectancies reported more side effects (adjusted log expected count = 0.26, p = 0.038). Efficacy expectancies were unrelated to side effect reports (log expected count = -0.05, p = 0.680), and side effect expectancies were unrelated to treatment efficacy (β = 0.08, p = 0.306). Patients entering chamomile treatment for GAD with more favorable self-generated expectancies for the treatment experience greater improvement and fewer adverse events. Aligning patient expectancies with treatment selections may optimize outcomes. Trial Number NCT01072344 at ClinicalTrials.gov. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reorientation Motion and Preferential Interactions of a Peptide in Denaturants and Osmolyte.

PubMed

Jas, Gouri S; Rentchler, Eric C; Słowicka, Agnieszka M; Hermansen, John R; Johnson, Carey K; Middaugh, C Russell; Kuczera, Krzysztof

2016-03-31

Fluorescence anisotropy decay measurements and all atom molecular dynamics simulations are used to characterize the orientational motion and preferential interaction of a peptide, N-acetyl-tryptophan-amide (NATA) containing two peptide bonds, in aqueous, urea, guanidinium chloride (GdmCl), and proline solution. Anisotropy decay measurements as a function of temperature and concentration showed moderate slowing of reorientations in urea and GdmCl and very strong slowing in proline solution, relative to water. These effects deviate significantly from simple proportionality of peptide tumbling time to solvent viscosity, leading to the investigation of microscopic preferential interaction behavior through molecular dynamics simulations. Examination of the interactions of denaturants and osmolyte with the peptide backbone uncovers the presence of strongest interaction with urea, intermediate with proline, and weakest with GdmCl. In contrast, the strongest preferential solvation of the peptide side chain is by the nonpolar part of the proline zwitterion, followed by urea, and GdmCl. Interestingly, the local density of urea around the side chain is higher, but the GdmCl distribution is more organized. Thus, the computed preferential solvation of the side chain by the denaturants and osmolyte can account for the trend in reorientation rates. Analysis of water structure and its dynamics uncovered underlying differences between urea, GdmCl, and proline. Urea exerted the smallest perturbation of water behavior. GdmCl had a larger effect on water, slowing kinetics and stabilizing interactions. Proline had the largest overall interactions, exhibiting a strong stabilizing effect on both water-water and water-peptide hydrogen bonds. The results for this elementary peptide system demonstrate significant differences in microscopic behavior of the examined solvent environments. For the commonly used denaturants, urea tends to form disorganized local aggregates around the peptide groups and has little influence on water, while GdmCl only forms specific interactions with the side chain and tends to destabilize water structure. The protective osmolyte proline has the strongest and most specific interactions with the tryptophan side chain, and also stabilizes both water-water and water-peptide hydrogen bonds. Our results strongly suggest protein or peptide denaturation triggered by urea occurs by direct interaction, whereas GdmCl interacts favorably with side chains and destabilizes peptide-water hydrogen bonds. The stabilization of biopolymers by an osmolyte such as proline is governed by favorable preferential interaction with the side chains and stabilization of water.

Synthesis of uniformly distributed single- and double-sided zinc oxide (ZnO) nanocombs

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

Altintas Yildirim, Ozlem; Liu, Yuzi; Petford-Long, Amanda K.

Uniformly distributed single- and double-sided zinc oxide (ZnO) nanocomb structures have been prepared by a vapor-liquid-solid technique from a mixture of ZnO nanoparticles and graphene nanoplatelets. The ZnO seed nanoparticles were synthesized via a simple precipitation method. The structure of the ZnO nanocombs could easily be controlled by tuning the carrier-gas flow rate during growth. Higher flow rate resulted in the formation of uniformly-distributed single-sided comb structures with nanonail-shaped teeth, as a result of the self-catalysis effect of the catalytically active Zn-terminated polar (0001) surface. Lower gas flow rate was favorable for production of double-sided comb structures with the twomore » sets of teeth at an angle of similar to 110 degrees to each other along the comb ribbon, which was attributed to the formation of a bicrystal nanocomb ribbon. Lastly, the formation of such a double-sided structure with nanonail-shaped teeth has not previously been reported.« less

Synthesis of uniformly distributed single- and double-sided zinc oxide (ZnO) nanocombs

DOE PAGES

Altintas Yildirim, Ozlem; Liu, Yuzi; Petford-Long, Amanda K.

2015-08-21

Uniformly distributed single- and double-sided zinc oxide (ZnO) nanocomb structures have been prepared by a vapor-liquid-solid technique from a mixture of ZnO nanoparticles and graphene nanoplatelets. The ZnO seed nanoparticles were synthesized via a simple precipitation method. The structure of the ZnO nanocombs could easily be controlled by tuning the carrier-gas flow rate during growth. Higher flow rate resulted in the formation of uniformly-distributed single-sided comb structures with nanonail-shaped teeth, as a result of the self-catalysis effect of the catalytically active Zn-terminated polar (0001) surface. Lower gas flow rate was favorable for production of double-sided comb structures with the twomore » sets of teeth at an angle of similar to 110 degrees to each other along the comb ribbon, which was attributed to the formation of a bicrystal nanocomb ribbon. Lastly, the formation of such a double-sided structure with nanonail-shaped teeth has not previously been reported.« less

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.

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.

Improvement in Capsule Abort Performance Using Supersonic Aerodynamic Interaction by Fences

NASA Astrophysics Data System (ADS)

Koyama, Hiroto; Wang, Yunpeng; Ozawa, Hiroshi; Doi, Katsunori; Nakamura, Yoshiaki

The space transportation system will need advanced abort systems to secure crew against serious accidents. Here this study deals with the capsule-type space transportation systems with a Launch Abort System (LAS). This system is composed of a conic capsule as a Launch Abort Vehicle (LAV) and a cylindrical rocket as a Service Module (SM), and the capsule is moved away from the rocket by supersonic aerodynamic interactions in an emergency. We propose a method to improve the performance of the LAV by installing fences at the edges of surfaces on the rocket and capsule sides. Their effects were investigated by experimental measurements and numerical simulations. Experimental results show that the fences on the rocket and capsule surfaces increase the aerodynamic thrust force on the capsule by 70% in a certain clearance between the capsule and rocket. Computational results show the detailed flow fields where the centripetal flow near the surface on the rocket side is induced by the fence on the rocket side and the centrifugal flow near the surface on the capsule side is blocked by the fence on the capsule side. These results can confirm favorable effects of the fences on the performance of the LAS.

Southeast Asia Report

DTIC Science & Technology

1987-05-13

Paper Blasts Government Failure To Help Farmers (BAN MUANG, 17 Dec 86) .•••* Columnist on Favorable Trade, Intellectual Property Rights (BAN MUANG...responsibility and can block the entry of illegal workers into Malaysia. These workers usually are brought in by illegal syndicates , and the effort to...eradicate the activities of these syndicates will certainly be more effective if both sides of the border are carefully watched. With the achievement

Transient Three-Dimensional Analysis of Nozzle Side Load in Regeneratively Cooled Engines

NASA Technical Reports Server (NTRS)

Wang, Ten-See

2005-01-01

Three-dimensional numerical investigations on the start-up side load physics for a regeneratively cooled, high-aspect-ratio nozzle were performed. The objectives of this study are to identify the three-dimensional side load physics and to compute the associated aerodynamic side load using an anchored computational methodology. The computational methodology is based on an unstructured-grid, pressure-based computational fluid dynamics formulation, and a transient inlet condition based on an engine system simulation. Computations were performed for both the adiabatic and cooled walls in order to understand the effect of boundary conditions. Finite-rate chemistry was used throughout the study so that combustion effect is always included. The results show that three types of shock evolution are responsible for side loads: generation of combustion wave; transitions among free-shock separation, restricted-shock separation, and simultaneous free-shock and restricted shock separations; along with oscillation of shocks across the lip. Wall boundary conditions drastically affect the computed side load physics: the adiabatic nozzle prefers free-shock separation while the cooled nozzle favors restricted-shock separation, resulting in higher peak side load for the cooled nozzle than that of the adiabatic nozzle. By comparing the computed physics with those of test observations, it is concluded that cooled wall is a more realistic boundary condition, and the oscillation of the restricted-shock separation flow pattern across the lip along with its associated tangential shock motion are the dominant side load physics for a regeneratively cooled, high aspect-ratio rocket engine.

Density Functional Study of Stacking Structures and Electronic Behaviors of AnE-PV Copolymer.

PubMed

Dong, Chuan-Ding; Beenken, Wichard J D

2016-10-10

In this work, we report an in-depth investigation on the π-stacking and interdigitating structures of poly(p-anthracene-ethynylene)-alt-poly(p-phenylene-vinylene) copolymer with octyl and ethyl-hexyl side chains and the resulting electronic band structures using density functional theory calculations. We found that in the π-stacking direction, the preferred stacking structure, determined by the steric effect of the branched ethyl-hexyl side chains, is featured by the anthracene-ethynylene units stacking on the phenylene-vinylene units of the neighboring chains and vice versa. This stacking structure, combined with the interdigitating structure where the branched side chains of the laterally neighboring chains are isolated, defines the energetically favorable structure of the ordered copolymer phase, which provides a good compromise between light absorption and charge-carrier transport.

The effects of side-chain-induced disorder on the emission spectra and quantum yields of oligothiophene nano-aggregates. A combined experimental and MD-TDDFT study

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

Hong, Jiyun; Jeon, SuKyung; Kim, Janice J.

2014-07-24

Oligomeric thiophenes are commonly-used components in organic electronics and solar cells. These molecules stack and/or aggregate readily under the processing conditions used to form thin films for these applications, significantly altering their optical and charge-transport properties. To determine how these effects depend on the substitution pattern of the thiophene main chains, nano-aggregates of three sexi-thiophene (6T) oligomers having different alkyl substitution patterns were formed using solvent poisoning techniques and studied using steady-state and time-resolved emission spectroscopy. The results indicate the substantial role played by the side-chain substituents in determining the emissive properties of these species. Both the measured spectral changesmore » and their dependence on substitution are well modeled by combined quantum chemistry and molecular dynamics simulations. The simulations connect the side-chain-induced disorder, which determines the favorable chain packing configurations within the aggregates, with their measured electronic spectra.« less

Clinical courses after administration of oral corticosteroids in patients with severely cholestatic acute hepatitis A; three cases

PubMed Central

Yoon, Eileen L.; Kim, Seung Young; Kim, Jeong Han; Lee, Ju-Han; Lee, Young Sun; Lee, Hyun Jung; Jung, Sung Woo; Lee, Sang Woo; Choi, Jai Hyun

2010-01-01

Acute hepatitis A is currently outbreaking in Korea. Although prognosis of acute hepatitis A is generally favorable, a minority of patients are accompanied by fatal complications. Severe cholestasis is one of the important causes of prolonged hospitalization in patients with acute hepatitis A. In such cases, higher chances of additional complications and increased medical costs are inevitable. We report three cases of severely cholestatic hepatitis A, who showed favorable responses to oral corticosteroids. Thirty milligram of prednisolone was initiated and tapered according to the responses. Rapid improvement was observed in all cases without side effects. We suggest that corticosteroid administration can be useful in hepatitis A patients with severe cholestasis who do not show improvement by conservative managements. Clinical trial will be needed to evaluate effectiveness of corticosteroids in these patients. PMID:20924218

Single Sided Messaging v. 0.6.6

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

Curry, Matthew Leon; Farmer, Matthew Shane; Hassani, Amin

Single-Sided Messaging (SSM) is a portable, multitransport networking library that enables applications to leverage potential one-sided capabilities of underlying network transports. It also provides desirable semantics that services for highperformance, massively parallel computers can leverage, such as an explicit cancel operation for pending transmissions, as well as enhanced matching semantics favoring large numbers of buffers attached to a single match entry. This release supports TCP/IP, shared memory, and Infiniband.

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

PubMed

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

2017-01-01

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

[Clinical evaluation of open and close treatment in pediatric condylar fractures].

PubMed

Han, Jing; Li, Zhi; Zhou, Haihua; Yang, Rongtao; Xiong, Guizhong; Li, Zubing

2014-08-01

To evaluate the long-term clinical and radiographic outcomes of open and close treatment of condylar fractures of mandible in children. A total of 78 cases (105 mandibular condylar fractures) were included in this study. All patients (younger than 12 years at the time of injury were followed up for at least 3 years. According to the classification of the condylar fractures, open or close treatment was chosen. Clinical outcomes were classified as favorable or unfavorable depending on the mouth opening, pattern of mouth opening, occlusion, facial symmetry. Condylar remodeling was defined as complete, moderate, or poor based on the radiographic findings. Depending on the classification, 14 sides of type I, 48 sides of type II and 43 sides of type III were included in this study. Open treatment was chosen in 51 sides and close treatment was chosen in 54 sides. Most of the patients acquired satisfactory clinical outcomes. Better radiologic remodeling of the condylar process was found in the patients treated by open treatment. Favorable long-term clinical outcomes were obtained in both open and close treatment of mandibular condylar fractures. A better morphological remodeling of condylar process was found in patients with open treatment.

Infantile hemangioma: treatment with short course systemic corticosteroid therapy as an alternative for propranolol.

PubMed

Nieuwenhuis, Klaske; de Laat, Peter C J; Janmohamed, Sherief R; Madern, Gerard C; Oranje, Arnold P

2013-01-01

Infantile hemangiomas (IHs) are increasingly being treated with propranolol or other beta-blockers, but before this therapeutic option was available, oral glucocorticosteroids (GCSs) were the criterion standard treatment and are still the alternative modality in problematic cases. Nevertheless, there is no standard treatment protocol for the dose and duration of GCSs. Long-term treatment with GCSs is associated with unwanted side effects such as growth suppression, behavioral changes, and reflux. Twenty-one children with troublesome IHs were treated according to an algorithm with 3 mg/kg/day of oral prednisolone divided three times per day with varying duration and number of GCS courses. Two blinded investigators independently interpreted therapy results using the Hemangioma Activity Score (HAS). Side effects were determined according to reports in patient charts and parental questionnaires. The median duration of a short course of GCSs was 2 weeks (range 1-6 weeks). The number of courses was 2 (range 1-5). The median cumulative dose was 91 mg/kg. Growth stabilized in all patients, with a good response (>50% reduction in HAS) in 62% and a favorable response (30-50% reduction is HAS) in 23%. Twelve of the 21 children (57%) had minor side effects. Persistent side effects did not occur. Intermittent short course, systemic, high-dose GCS therapy is an effective and safe treatment modality for IH, with a substantially lower cumulative dose of GCSs compared to prolonged therapy and no major side effects. This treatment is an alternative in cases in which propranolol fails or is contraindicated. © 2012 Wiley Periodicals, Inc.

Effect of heat input on dissimilar welds of ultra high strength steel and duplex stainless steel: Microstructural and compositional analysis

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

Tasalloti, H., E-mail: hamed.tasalloti.kashani@stu

The effect of heat input on the microstructure and compositional heterogeneity of welds of direct-quenched ultra high strength steel (Optim 960 QC) and duplex stainless steel (UNS S32205) was studied. The dissimilar welds were made using GMAW with a fully austenitic filler wire. In addition to grain coarsening in the heat affected zone (HAZ) of the ferritic side, it was found that an increase in heat input correlatively increased the proportional volume of bainitic to martensitic phases. Coarse ferritic grains were observed in the duplex HAZ. Higher heat input, however, had a beneficial effect on the nucleation of austenite inmore » the HAZ. Heat input had a regulatory effect on grain growth within the austenitic weld and more favorable equiaxed austenite was obtained with higher heat input. On the ferritic side of the welds, macrosegregation in the form of a martensitic intermediate zone was observed for all the cooling rates studied. However, on the duplex side, macrosegregation in the fusion boundary was only noticed with higher cooling rates. Microstructural observations and compositional analysis suggest that higher heat input could be beneficial for the structural integrity of the weld despite higher heat input increasing the extent of adverse coarse grains in the HAZ, especially on the ferritic side. - Highlights: •The effect of heat input on dissimilar welds of UHSS and DSS was studied. •Transmutation of the microstructure was discussed in detail. •The influence of heat input on compositional heterogeneity of welds was described. •Higher heat input enhanced bainitic transformation on the ferritic side. •Macrosegregation was affected by the amount of heat input on the DSS side.« less

Inhibitory competition in figure-ground perception: context and convexity.

PubMed

Peterson, Mary A; Salvagio, Elizabeth

2008-12-15

Convexity has long been considered a potent cue as to which of two regions on opposite sides of an edge is the shaped figure. Experiment 1 shows that for a single edge, there is only a weak bias toward seeing the figure on the convex side. Experiments 1-3 show that the bias toward seeing the convex side as figure increases as the number of edges delimiting alternating convex and concave regions increases, provided that the concave regions are homogeneous in color. The results of Experiments 2 and 3 rule out a probability summation explanation for these context effects. Taken together, the results of Experiments 1-3 show that the homogeneity versus heterogeneity of the convex regions is irrelevant. Experiment 4 shows that homogeneity of alternating regions is not sufficient for context effects; a cue that favors the perception of the intervening regions as figures is necessary. Thus homogeneity alone does not alone operate as a background cue. We interpret our results within a model of figure-ground perception in which shape properties on opposite sides of an edge compete for representation and the competitive strength of weak competitors is further reduced when they are homogeneous.

Side-chain conformational space analysis (SCSA): A multi conformation-based QSAR approach for modeling and prediction of protein-peptide binding affinities

NASA Astrophysics Data System (ADS)

Zhou, Peng; Chen, Xiang; Shang, Zhicai

2009-03-01

In this article, the concept of multi conformation-based quantitative structure-activity relationship (MCB-QSAR) is proposed, and based upon that, we describe a new approach called the side-chain conformational space analysis (SCSA) to model and predict protein-peptide binding affinities. In SCSA, multi-conformations (rather than traditional single-conformation) have received much attention, and the statistical average information on multi-conformations of side chains is determined using self-consistent mean field theory based upon side chain rotamer library. Thereby, enthalpy contributions (including electrostatic, steric, hydrophobic interaction and hydrogen bond) and conformational entropy effects to the binding are investigated in terms of occurrence probability of residue rotamers. Then, SCSA was applied into the dataset of 419 HLA-A*0201 binding peptides, and nonbonding contributions of each position in peptide ligands are well determined. For the peptides, the hydrogen bond and electrostatic interactions of the two ends are essential to the binding specificity, van der Waals and hydrophobic interactions of all the positions ensure strong binding affinity, and the loss of conformational entropy at anchor positions partially counteracts other favorable nonbonding effects.

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.

TNF and cancer: the two sides of the coin.

PubMed

Mocellin, Simone; Nitti, Donato

2008-01-01

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

Taking side effects into account for HIV medication.

PubMed

Costanza, Vicente; Rivadeneira, Pablo S; Biafore, Federico L; D'Attellis, Carlos E

2010-09-01

A control-theoretic approach to the problem of designing "low-side-effects" therapies for HIV patients based on highly active drugs is substantiated here. The evolution of side effects during treatment is modeled by an extra differential equation coupled to the dynamics of virions, healthy T-cells, and infected ones. The new equation reflects the dependence of collateral damages on the amount of each dose administered to the patient and on the evolution of the viral load detected by periodical blood analysis. The cost objective accounts for recommended bounds on healthy cells and virions, and also penalizes the appearance of collateral morbidities caused by the medication. The optimization problem is solved by a hybrid dynamic programming scheme that adhere to discrete-time observation and control actions, but by maintaining the continuous-time setup for predicting states and side effects. The resulting optimal strategies employ less drugs than those prescribed by previous optimization studies, but maintaining high doses at the beginning and the end of each period of six months. If an inverse discount rate is applied to favor early actions, and under a mild penalization of the final viral load, then the optimal doses are found to be high at the beginning and decrease afterward, thus causing an apparent stabilization of the main variables. But in this case, the final viral load turns higher than acceptable.

Prediction of Relaminarization Effects on Turbine Blade Heat Transfer

NASA Technical Reports Server (NTRS)

Boyle, R. J.; Giel, P. W.

2001-01-01

An approach to predicting turbine blade heat transfer when turbulent flow relaminarizes due to strong favorable pressure gradients is described. Relaminarization is more likely to occur on the pressure side of a rotor blade. While stators also have strong favorable pressure gradients, the pressure surface is less likely to become turbulent at low to moderate Reynolds numbers. Accounting for the effects of relaminarization for blade heat transfer can substantially reduce the predicted rotor surface heat transfer. This in turn can lead to reduced rotor cooling requirements. Two-dimensional midspan Navier-Stokes analyses were done for each of eighteen test cases using eleven different turbulence models. Results showed that including relaminarization effects generally improved the agreement with experimental data. The results of this work indicate that relatively small changes in rotor shape can be utilized to extend the likelihood of relaminarization to high Reynolds numbers. Predictions showing how rotor blade heat transfer at a high Reynolds number can be reduced through relaminarization are given.

Side-chain-side-chain interactions and stability of the helical state

NASA Astrophysics Data System (ADS)

Zangi, Ronen

2014-01-01

Understanding the driving forces that lead to the stability of the secondary motifs found in proteins, namely α-helix and β-sheet, is a major goal in structural biology. The thermodynamic stability of these repetitive units is a result of a delicate balance between many factors, which in addition to the peptide chain involves also the solvent. Despite the fact that the backbones of all amino acids are the same (except of that of proline), there are large differences in the propensity of the different amino acids to promote the helical structure. In this paper, we investigate by explicit-solvent molecular dynamics simulations the role of the side chains (modeled as coarse-grained single sites) in stabilizing α helices in an aqueous solution. Our model systems include four (six-mer-nine-mer) peptide lengths in which the magnitude of the effective attraction between the side chains is systematically increased. We find that these interactions between the side chains can induce (for the nine-mer almost completely) a transition from a coil to a helical state. This transition is found to be characterized by three states in which the intermediate state is a partially folded α-helical conformation. In the absence of any interactions between the side chains the free energy change for helix formation has a small positive value indicating that favorable contributions from the side chains are necessary to stabilize the helical conformation. Thus, the helix-coil transition is controlled by the effective potentials between the side-chain residues and the magnitude of the required attraction per residue, which is on the order of the thermal energy, reduces with the length of the peptide. Surprisingly, the plots of the population of the helical state (or the change in the free energy for helix formation) as a function of the total effective interactions between the side chains in the helical state for all peptide lengths fall on the same curve.

Hepatitis C-related cryoglobulinemic neuropathy: potential role of oxcarbazepine for pain control.

PubMed

Moretti, Rita; Caruso, Paola; Dal Ben, Matteo; Gazzin, Silvia; Tiribelli, Claudio

2018-01-25

Peripheral neuropathy is one most common, limiting and invalidating neurological symptom in subjects with hepatitis C virus and mixed cryoglobulinemia. Notably, the medical therapy proposed to eradicate HCV, can frequently exacerbate the painful neuropathy. Therefore, neuropathy therapies are insufficient and inadequate, and comprise immunosuppressive drugs, such as steroid or cyclosporine, intravenous immunoglobulin or plasma exchange. These have shown variable success in case reports, with a presumably temporary effect, but with major side effects. We assessed the effects of oxcarbazepine treatment in 67 cases of cryoglobulinemia related neuropathy, who did not respond to either steroid or Gabapentin, or Pregabalin. Oxcarbazepine was chosen based on the promising preliminary results. Patients treated with Oxcarbazepine showed a rapid, discrete and persistent relief of polyneuropathic signs, without consistent side effects, and with a limited interaction with concomitant drugs. These data favor the use of oxcarbazepine as a useful tool in the management of neuropathic pain associated with Hepatitis-C cryoglobulin neuropathy.

Tripeptide inhibitors of dengue and West Nile virus NS2B-NS3 protease.

PubMed

Schüller, Andreas; Yin, Zheng; Brian Chia, C S; Doan, Danny N P; Kim, Hyeong-Kyu; Shang, Luqing; Loh, Teck Peng; Hill, Jeffery; Vasudevan, Subhash G

2011-10-01

A series of tripeptide aldehyde inhibitors were synthesized and their inhibitory effect against dengue virus type 2 (DENV2) and West Nile virus (WNV) NS3 protease was evaluated side by side with the aim to discover potent flaviviral protease inhibitors and to examine differences in specificity of the two proteases. The synthesized inhibitors feature a varied N-terminal cap group and side chain modifications of a P2-lysine residue. In general a much stronger inhibitory effect of the tripeptide inhibitors was observed toward WNV protease. The inhibitory concentrations against DENV2 protease were in the micromolar range while they were submicromolar against WNV. The data suggest that a P2-arginine shifts the specificity toward DENV2 protease while WNV protease favors a lysine in the P2 position. Peptides with an extended P2-lysine failed to inhibit DENV2 protease suggesting a size-constrained S2 pocket. Our results generally encourage the investigation of di- and tripeptide aldehydes as inhibitors of DENV and WNV protease. Copyright © 2011 Elsevier B.V. All rights reserved.

Visible light-induced crosslinking and physiological stabilization of diselenide-rich nanoparticles for redox-responsive drug release and combination chemotherapy.

PubMed

Zhai, Shaodong; Hu, Xianglong; Hu, Yongjun; Wu, Baoyan; Xing, Da

2017-03-01

Undesired physiological instability of nanocarriers and premature drug leakage during blood circulation result in compromised therapeutic efficacy and severe side effects, which have significantly impeded the development of nanomedicine. Facile crosslinking of drug-loaded nanocarriers while keeping the potency of site-specific degradation and drug release has emerged as a viable strategy to overcome these drawbacks. Additionally, combination therapy has already shown advantages in inhibiting advanced tumors and life extension than single drug therapy. Herein, three kinds of diselenide-rich polymers were fabricated with distinct hydrophobic side chains. The component effect was interrogated to screen out PEG-b-PBSe diblock copolymer due to its favorable self-assembly controllability and high drug loading of camptothecin (CPT) and doxorubicin (DOX) that had synergistic antitumor property. Facile visible light-induced diselenide metathesis and regeneration was employed to crosslink nanocarriers for the first time. The dual drug-loaded crosslinked micelles (CPT/DOX-CCM) were stable in physiological conditions with minimal drug leakage, possessing extended blood circulation, whereas hand-in-hand dual drug release was significantly accelerated in tumor's redox microenvironments. In vitro cytotoxicity evaluation and in vivo tumor suppression with low dosage drugs further demonstrated the favorable potency of the redox-responsive nanoplatform in tumor combination chemotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2017-01-01

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

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.

Stability of hydrogenated graphene: a first-principles study

DOE PAGES

Yi, Ding; Yang, Liu; Xie, Shijie; ...

2015-02-10

In order to explain the disagreement between present theoretical and experimental investigations on the stability of hydrogenated graphene, we have systematically studied hydrogenated graphene with different configurations from the consideration of single-side and double-side adsorption using first-principles calculations. Both binding energy and formation energy are calculated to characterize the stability of the system. It is found that single-side hydrogenated graphene is always unstable. However, for double-side hydrogenation, some configurations are stable due to the increased carbon–carbon sp 3 hybridization compared to single-side hydrogenation. Furthermore, it is found that the system is energetically favorable when an equal number of hydrogen atomsmore » are adsorbed on each side of the graphene.« less

Objectively discriminating the optical analogy of electromagnetically induced transparency from Autler-Townes splitting in a side coupled graphene-based waveguide system

NASA Astrophysics Data System (ADS)

Wei, Buzheng; Jian, Shuisheng

2017-11-01

A mid-infrared side coupled graphene nanotube waveguide system is proposed to investigate the origin discerning from electromagnetically induced transparency (EIT) to Autler-Townes splitting (ATS). The analytic transmission analysis seeks an evolution tendency of transmission spectrum from ATS to EIT, which is numerically verified by the simulation results. The origin of transparency is mainly attributed to ATS effect in the strong coupling regime while EIT is favored in the weak coupling condition. We plot the field distribution to help understand the underlying physics of the interference process. The high group index of 5000 indicates that a slow light effect is successfully observed and Fano resonance is presented by varying the Fermi energy of the dark mode. These ideas may provide potential views in filters, optical buffers, light storage and on chip metamaterials.

Study on Tritium Removal Performance by Gas Separation Membrane with Reflux Flow for Tritium Removal System of Fusion Reactor

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

Iwai, Yasunori; Yamanishi, Toshihiko; Hayashi, Takumi

2005-07-15

Addition of gas separation membrane process into the usual tritium removal process from an indoor atmosphere is attractive for a fusion plant, where a large amount of atmosphere should be processed. As a manner to improve the partial pressure difference between feed and permeated side, intended reflux of vapor and the hydrogen concentrated at permeated side is conceived to enlarge the partial pressure difference. Membrane separation with reflux flow has been proposed as an attractive process to enhance the recovery ratio of tritium component. Effect of reflux on the recovery ratio of tritium component was evaluated by numerical analysis. Themore » effect of reflux on separation performance becomes striking as the target species have higher permeability coefficients. Hence, the gas separation by membrane with reflux flow is favorable for tritium recovery.« less

Neuroreflexotherapy for nonspecific low back pain: a systematic review.

PubMed

Urrútia, Gerard; Burton, Kim; Morral, Antoni; Bonfill, Xavier; Zanoli, Gustavo

2005-03-15

Systematic review. To assess the effectiveness of neuroreflexotherapy (NRT) for low back pain (LBP). Few of the alternatives for the management of LBP have a firm base of evidence for their effectiveness. Recently, a new intervention known as NRT has been developed in Spain and has been reported to have favorable results. Searches were undertaken according to Cochrane Collaboration guidelines, and randomized controlled trials that evaluated NRT as treatment for patients with nonspecific LBP were included. A qualitative synthesis and an assessment of methodological quality were undertaken. Three randomized controlled trials were included, with 125 and 148 subjects in control and intervention groups, respectively. NRT was compared with sham in two trials and standard care in one. Individuals receiving active NRT showed significantly better outcomes for pain, mobility, disability, medication use, consumption of resources, and costs. No major side effects were reported by those receiving active NRT. NRT appears to be a safe and effective intervention for nonspecific LBP. This conclusion is limited to three trials conducted by a small number of experienced clinicians. Further trials in other settings are needed to determine whether these favorable results can be generalized.

Sports supplements: a modern case of caveat emptor.

PubMed

Pearce, P Z

2005-06-01

Performance is the combination of favorable genetics, proper training, and a sound approach to nutrition. Athletes attempting to gain a competitive edge often try artificial means of improving speed, strength, and endurance. Although some use oral or injectable medications, others turn to nutritional supplements. This article focuses on some of the most common methods athletes use to enhance performance. Reported dosages, representative studies, and potential side effects are reviewed, along with guidelines for evaluating supplements, and the claims of their manufacturers.

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.

Model Amphiphilic Block Copolymers with Tailored Molecular Weight and Composition in PDMS-Based Films to Limit Soft Biofouling

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

Wenning, Brandon M.; Martinelli, Elisa; Mieszkin, Sophie

A set of controlled surface composition films was produced utilizing amphiphilic block copolymers dispersed in a cross-linked poly(dimethylsiloxane) network. These block copolymers contained oligo(ethylene glycol) (PEGMA) and fluoroalkyl (AF6) side chains in selected ratios and molecular weights to control surface chemistry including antifouling and fouling-release performance. Such properties were assessed by carrying out assays using two algae, the green macroalga Ulva linza (favors attachment to polar surfaces) and the unicellular diatom Navicula incerta (favors attachment to nonpolar surfaces). All films performed well against U. linza and exhibited high removal of attached sporelings (young plants) under an applied shear stress, withmore » the lower molecular weight block copolymers being the best performing in the set. The composition ratios from 50:50 to 60:40 of the AF6/PEGMA side groups were shown to be more effective, with several films exhibiting spontaneous removal of the sporelings. The cells of N. incerta were also removed from several coating compositions. All films were characterized by surface techniques including captive bubble contact angle, atomic force microscopy, and near edge X-ray absorption fine structure spectroscopy to correlate surface chemistry and morphology with biological performance.« less

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.

Two lunar global asymmetries

NASA Technical Reports Server (NTRS)

Hartung, J. B.

1984-01-01

The Moon's center of mass is displaced from its center of figure about 2 km in a roughly earthward direction. Most maria are on the side of the Moon which faces the Earth. It is assumed that the Moon was initially spherically symmetric. The emplacement of mare basalts transfers mass which produces most of the observed center of mass displacement toward the Earth. The cause of the asymmetric distribution of lunar maria was examined. The Moon is in a spin orbit coupled relationship with the Earth and the effect of the Earth's gravity on the Moon is asymmetric. The earth-facing side of the Moon is a gravitational favored location for the extrusion of mare basalt magma in the same way that the topographically lower floor of a large impact basin is a gravitationally favored location. This asymmetric effect increases inversely with the fourth power of the Earth Moon distance. The history of the Earth-Moon system includes: formation of the Moon by accretion processes in a heliocentric orbit ner that of the Earth; a gravitational encounter with the Earth about 4 billion years ago resulting in capture of the Moon into a geocentric orbit and heating of the Moon through dissipation of energy related to tides raised during close approaches to the Earth(5) to produce mare basalt magma; and evolution of the Moon's orbit to its present position, slowly at first to accommodate more than 500 million years during which magmas were extruded.

Two lunar global asymmetries

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

Hartung, J.B.

1984-01-01

The Moon's center of mass is displaced from its center of figure about 2 km in a roughly earthward direction. Most maria are on the side of the Moon which faces the Earth. It is assumed that the Moon was initially spherically symmetric. The emplacement of mare basalts transfers mass which produces most of the observed center of mass displacement toward the Earth. The cause of the asymmetric distribution of lunar maria was examined. The Moon is in a spin orbit coupled relationship with the Earth and the effect of the Earth's gravity on the Moon is asymmetric. The earth-facingmore » side of the Moon is a gravitational favored location for the extrusion of mare basalt magma in the same way that the topographically lower floor of a large impact basin is a gravitationally favored location. This asymmetric effect increases inversely with the fourth power of the Earth Moon distance. The history of the Earth-Moon system includes: formation of the Moon by accretion processes in a heliocentric orbit near that of the Earth; a gravitational encounter with the Earth about 4 billion years ago resulting in capture of the Moon into a geocentric orbit and heating of the Moon through dissipation of energy related to tides raised during close approaches to the Earth(5) to produce mare basalt magma; and evolution of the Moon's orbit to its present position, slowly at first to accommodate more than 500 million years during which magmas were extruded.« less

Aromatic Side Chain Water-to-Lipid Transfer Free Energies Show a Depth Dependence across the Membrane Normal.

PubMed

McDonald, Sarah K; Fleming, Karen G

2016-06-29

Quantitating and understanding the physical forces responsible for the interactions of biomolecules are fundamental to the biological sciences. This is especially challenging for membrane proteins because they are embedded within cellular bilayers that provide a unique medium in which hydrophobic sequences must fold. Knowledge of the energetics of protein-lipid interactions is thus vital to understand cellular processes involving membrane proteins. Here we used a host-guest mutational strategy to calculate the Gibbs free energy changes of water-to-lipid transfer for the aromatic side chains Trp, Tyr, and Phe as a function of depth in the membrane. This work reveals an energetic gradient in the transfer free energies for Trp and Tyr, where transfer was most favorable to the membrane interfacial region and comparatively less favorable into the bilayer center. The transfer energetics follows the concentration gradient of polar atoms across the bilayer normal that naturally occurs in biological membranes. Additional measurements revealed nearest-neighbor coupling in the data set are influenced by a network of aromatic side chains in the host protein. Taken together, these results show that aromatic side chains contribute significantly to membrane protein stability through either aromatic-aromatic interactions or placement at the membrane interface.

To brake or to accelerate? Safety effects of combined speed and red light cameras.

PubMed

De Pauw, Ellen; Daniels, Stijn; Brijs, Tom; Hermans, Elke; Wets, Geert

2014-09-01

The present study evaluates the traffic safety effect of combined speed and red light cameras at 253 signalized intersections in Flanders, Belgium that were installed between 2002 and 2007. The adopted approach is a before-and-after study with control for the trend. The analyses showed a non-significant increase of 5% in the number of injury crashes. An almost significant decrease of 14% was found for the more severe crashes. The number of rear-end crashes turned out to have increased significantly (+44%), whereas a non-significant decrease (-6%) was found in the number of side crashes. The decrease for the severe crashes was mainly attributable to the effect on side crashes, for which a significant decrease of 24% was found. It is concluded that combined speed and red light cameras have a favorable effect on traffic safety, in particular on severe crashes. However, future research should examine the circumstances of rear-end crashes and how this increase can be managed. Copyright © 2014 National Safety Council and Elsevier Ltd. All rights reserved.

Prediction of Viking lander camera image quality

NASA Technical Reports Server (NTRS)

Huck, F. O.; Burcher, E. E.; Jobson, D. J.; Wall, S. D.

1976-01-01

Formulations are presented that permit prediction of image quality as a function of camera performance, surface radiance properties, and lighting and viewing geometry. Predictions made for a wide range of surface radiance properties reveal that image quality depends strongly on proper camera dynamic range command and on favorable lighting and viewing geometry. Proper camera dynamic range commands depend mostly on the surface albedo that will be encountered. Favorable lighting and viewing geometries depend mostly on lander orientation with respect to the diurnal sun path over the landing site, and tend to be independent of surface albedo and illumination scattering function. Side lighting with low sun elevation angles (10 to 30 deg) is generally favorable for imaging spatial details and slopes, whereas high sun elevation angles are favorable for measuring spectral reflectances.

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.

The Effect of Lateral-Directional Control Coupling on Pilot Control of an Airplane as Determined in Flight and in a Fixed-Base Flight Simulator

NASA Technical Reports Server (NTRS)

Vomaske, Richard F.; Sadoff, Melvin; Drinkwater, Fred J., III

1961-01-01

A flight and fixed-base simulator study was made of the effects of aileron-induced yaw on pilot opinion of aircraft lateral-directional controllability characteristics. A wide range of adverse and favorable aileron-induced yaw was investigated in flight at several levels of Dutch-roll damping. The flight results indicated that the optimum values of aileron- induced yaw differed only slightly from zero for Dutch-roll damping from satisfactory to marginally controllable levels. It was also shown that each range of values of aileron-induced yawing moment considered satisfactory, acceptable, or controllable increased with an increase in the Dutch- roll damping. The increase was most marked for marginally controllable configurations exhibiting favorable aileron-induced yaw. Comparison of fixed-base flight simulator results with flight results showed agreement, indicating that absence of kinesthetic motion cues did not markedly affect the pilots' evaluation of the type of control problem considered in this study. The results of the flight study were recast in terms of several parameters which were considered to have an important effect on pilot opinion of lateral-directional handling qualities, including the effects of control coupling. Results of brief tests with a three-axis side-arm controller indicated that for control coupling problems associated with highly favorable yaw and cross-control techniques, use of the three-axis controller resulted in a deterioration of control relative to results obtained with the conventional center stick and rudder pedals.

The Effects of Low-Dose Ketamine on Acute Pain in an Emergency Setting: A Systematic Review and Meta-Analysis.

PubMed

Lee, Eun Nam; Lee, Jae Hoon

2016-01-01

Currently ketamine is not used often as an analgesic in the emergency department (ED). Nonetheless, it can increase the efficiency of opioids and decrease their side effects. The purpose of this systematic review and meta-analysis was to evaluate whether low-dose ketamine in the ED provides better analgesia with fewer adverse effects. The PubMed, EMBASE, and Cochrane Library databases were searched by two reviewers independently (last search performed on January 2016). Data were also extracted independently. A total of 6 trials involving 438 patients were included in the current analysis. Our subgroup analysis of pain reduction indicates that the favorable effects of ketamine were similar or superior to those of placebo or opioids, although these effects were heterogeneous. However, low-dose ketamine was associated with a higher risk of neurological (relative risk [RR] = 2.17, 95% confidence interval [CI] = 1.37-3.42, P < 0.001) and psychological events (RR = 13.86, 95% CI = 4.85-39.58, P < 0.001). In contrast, the opioid group had a higher risk of major cardiopulmonary events (RR = 0.22, 95% CI = 0.05-1.01, P = 0.05). The efficiency of ketamine varies depending on the pain site, but low-dose ketamine may be a key agent for pain control in the ED, as it has no side effects. It may also help to reduce the side effects of opioids.

The Effects of Low-Dose Ketamine on Acute Pain in an Emergency Setting: A Systematic Review and Meta-Analysis

PubMed Central

2016-01-01

Objectives Currently ketamine is not used often as an analgesic in the emergency department (ED). Nonetheless, it can increase the efficiency of opioids and decrease their side effects. The purpose of this systematic review and meta-analysis was to evaluate whether low-dose ketamine in the ED provides better analgesia with fewer adverse effects. Methods The PubMed, EMBASE, and Cochrane Library databases were searched by two reviewers independently (last search performed on January 2016). Data were also extracted independently. Results A total of 6 trials involving 438 patients were included in the current analysis. Our subgroup analysis of pain reduction indicates that the favorable effects of ketamine were similar or superior to those of placebo or opioids, although these effects were heterogeneous. However, low-dose ketamine was associated with a higher risk of neurological (relative risk [RR] = 2.17, 95% confidence interval [CI] = 1.37–3.42, P < 0.001) and psychological events (RR = 13.86, 95% CI = 4.85–39.58, P < 0.001). In contrast, the opioid group had a higher risk of major cardiopulmonary events (RR = 0.22, 95% CI = 0.05–1.01, P = 0.05). Conclusions The efficiency of ketamine varies depending on the pain site, but low-dose ketamine may be a key agent for pain control in the ED, as it has no side effects. It may also help to reduce the side effects of opioids. PMID:27788221

Windward Cooling: An Overlooked Factor in the Calculation of Wind Chill.

NASA Astrophysics Data System (ADS)

Osczevski, Randall J.

2000-12-01

Wind chill equivalent temperatures calculated from a recent vertical cylinder model of wind chill are several degrees colder than those calculated from a facial cooling model. The latter was based on experiments with a heated model of a face in a wind tunnel. Wind chill has sometimes been modeled as the overall heat transfer from the surface of a cylinder in cross flow, but such models average the cooling over the whole surface and thus minimize the effect of local cooling on the upwind side, particularly at low wind speeds. In this paper, a vertical cylinder model of wind chill has been modified so that just the cooling of its windward side is considered. Wind chill equivalent temperatures calculated with this new model compare favorably with those calculated by the facial cooling model.

Physiological asymmetry in etiolated pea epicotyls: relation to patterns of auxin distribution and phototropic behavior

NASA Technical Reports Server (NTRS)

Kuhn, H.; Galston, A. W.

1992-01-01

Etiolated pea seedlings require transformation of Pr phytochrome to Pfr before they display optimal phototropic response to unilateral blue light. This study investigates the possible role of auxin transport in explaining these phenomena. Labeled [2-14C]IAA applied to the intact terminal buds of dark-grown and red light-treated pea seedlings was measured 210 min later on the shaded and illuminated sides of the epicotyl as a function of direction and duration of irradiation with blue light. Totally darkened epicotyls show an asymmetry in distribution of radioactivity in the upper growth zone of the epicotyl, in favor of the side under the concave part of the apical hook. Red light, which greatly potentiates curvature toward subsequent unilateral blue light, lowers this asymmetry. Blue light directed to the epicotyl of red-pretreated plants in a plane parallel to the hook and from the side bearing the convex portion of the hook induces positive phototropic curvature as well as a surplus of radioactivity on the illuminated side of the upper epicotyl and on the shaded side of the lower growth zone of the epicotyl. Light directed to the side bearing the concave part of the hook also causes an accumulation of counts in the upper part of the lighted side but produces neither curvature of the epicotyl nor accumulation of counts in the lower shaded side. Because of this built-in physiological asymmetry in the growth zone just below the apical hook, it is difficult to explain the effects of red and blue light on curvature in terms of patterns of auxin distribution alone.

Physiological asymmetry in etiolated pea epicotyls: relation to patterns of auxin distribution and phototropic behavior.

PubMed

Kuhn, H; Galston, A W

1992-01-01

Etiolated pea seedlings require transformation of Pr phytochrome to Pfr before they display optimal phototropic response to unilateral blue light. This study investigates the possible role of auxin transport in explaining these phenomena. Labeled [2-14C]IAA applied to the intact terminal buds of dark-grown and red light-treated pea seedlings was measured 210 min later on the shaded and illuminated sides of the epicotyl as a function of direction and duration of irradiation with blue light. Totally darkened epicotyls show an asymmetry in distribution of radioactivity in the upper growth zone of the epicotyl, in favor of the side under the concave part of the apical hook. Red light, which greatly potentiates curvature toward subsequent unilateral blue light, lowers this asymmetry. Blue light directed to the epicotyl of red-pretreated plants in a plane parallel to the hook and from the side bearing the convex portion of the hook induces positive phototropic curvature as well as a surplus of radioactivity on the illuminated side of the upper epicotyl and on the shaded side of the lower growth zone of the epicotyl. Light directed to the side bearing the concave part of the hook also causes an accumulation of counts in the upper part of the lighted side but produces neither curvature of the epicotyl nor accumulation of counts in the lower shaded side. Because of this built-in physiological asymmetry in the growth zone just below the apical hook, it is difficult to explain the effects of red and blue light on curvature in terms of patterns of auxin distribution alone.

Enthalpic Breakdown of Water Structure on Protein Active-Site Surfaces

PubMed Central

Haider, Kamran; Wickstrom, Lauren; Ramsey, Steven; Gilson, Michael K.; Kurtzman, Tom

2016-01-01

The principles underlying water reorganization around simple non-polar solutes are well understood and provide the framework for classical hydrophobic effect, whereby water molecules structure themselves around solutes so that they maintain favorable energetic contacts with both the solute and with other water molecules. However, for certain solute surface topographies, water molecules, due to their geometry and size, are unable to simultaneously maintain favorable energetic contacts with both the surface and neighboring water molecules. In this study, we analyze the solvation of ligand-binding sites for six structurally diverse proteins using hydration site analysis and measures of local water structure, in order to identify surfaces at which water molecules are unable to structure themselves in a way that maintains favorable enthalpy relative to bulk water. These surfaces are characterized by a high degree of enclosure, weak solute-water interactions, and surface constraints that induce unfavorable pair interactions between neighboring water molecules. Additionally, we find that the solvation of charged side-chains in an active site generally results in favorable enthalpy but can also lead to pair interactions between neighboring water molecules that are significantly unfavorable relative to bulk water. We find that frustrated local structure can occur not only in apolar and weakly polar pockets, where overall enthalpy tends to be unfavorable, but also in charged pockets, where overall water enthalpy tends to be favorable. The characterization of local water structure in these terms may prove useful for evaluating the displacement of water from diverse protein active-site environments. PMID:27169482

Self-Portraits: Smartphones Reveal a Side Bias in Non-Artists

PubMed Central

2013-01-01

According to surveys of art books and exhibitions, artists prefer poses showing the left side of the face when composing a portrait and the right side when composing a self-portrait. However, it is presently not known whether similar biases can be observed in individuals that lack formal artistic training. We collected self-portraits by naïve photographers who used the iPhone™ front camera, and confirmed a right side bias in this non-artist sample and even when biomechanical constraints would have favored the opposite. This result undermines explanations based on posing conventions due to artistic training or biomechanical factors, and is consistent with the hypothesis that side biases in portraiture and self-portraiture are caused by biologically- determined asymmetries in facial expressiveness. PMID:23405117

[Rare and severe complication of spinal anesthesia: bacterial meningitis (about a case and literature review)].

PubMed

Chouaib, Naoufal; Jidane, Said; Rafai, Mostafa; Belkouch, Ahmed; Zidouh, Saad; Belyamani, Lahcen

2017-01-01

Spinal anesthesia (SA) is the first locoregional anesthesia. It can cause side effects and carry risks that need to be avoided, prevented or treated early. We here report the case of a female patient operated under spinal anesthesia who had intense headache associated with nausea and vomiting evolving in the context of fever within a few days after surgeryLumbar puncture showed cloudy liquid revealing Gram + cocci on direct examination. This allowed the diagnosis of bacterial meningitis. Patient's evolution was favorable after antibiotic therapy.

"Job-Sharing" Storage of Hydrogen in Ru/Li₂O Nanocomposites.

PubMed

Fu, Lijun; Tang, Kun; Oh, Hyunchul; Manickam, Kandavel; Bräuniger, Thomas; Chandran, C Vinod; Menzel, Alexander; Hirscher, Michael; Samuelis, Dominik; Maier, Joachim

2015-06-10

A "job-sharing" hydrogen storage mechanism is proposed and experimentally investigated in Ru/Li2O nanocomposites in which H(+) is accommodated on the Li2O side, while H(-) or e(-) is stored on the side of Ru. Thermal desorption-mass spectroscopy results show that after loading with D2, Ru/Li2O exhibits an extra desorption peak, which is in contrast to Ru nanoparticles or ball-milled Li2O alone, indicating a synergistic hydrogen storage effect due to the presence of both phases. By varying the ratio of the two phases, it is shown that the effect increases monotonically with the area of the heterojunctions, indicating interface related hydrogen storage. X-ray diffraction, Fourier transform infrared spectroscopy, and nuclear magnetic resonance results show that a weak LiO···D bond is formed after loading in Ru/Li2O nanocomposites with D2. The storage-pressure curve seems to favor H(+)/H(-) over H(+)/e(-) mechanism.

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.

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2012-01-01

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

Combination Therapy with Cholinesterase Inhibitors and Memantine for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

PubMed Central

Kishi, Taro; Iwata, Nakao

2015-01-01

Background: We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer’s disease. Methods: We reviewed cognitive function, activities of daily living, behavioral disturbance, global assessment, discontinuation rate, and individual side effects. Results: Seven studies (total n=2182) were identified. Combination therapy significantly affected behavioral disturbance scores (standardized mean difference=−0.13), activity of daily living scores (standardized mean difference=−0.10), and global assessment scores (standardized mean difference=−0.15). In addition, cognitive function scores (standardized mean difference=−0.13, P=.06) exhibited favorable trends with combination therapy. The effects of combination therapy were more significant in the moderate-to-severe Alzheimer’s disease subgroup in terms of all efficacy outcome scores. The discontinuation rate was similar in both groups, and there were no significant differences in individual side effects. Conclusions: Combination therapy was beneficial for the treatment of moderate-to-severe Alzheimer’s disease in terms of cognition, behavioral disturbances, activities of daily living, and global assessment was well tolerated. PMID:25548104

Combination therapy with cholinesterase inhibitors and memantine for Alzheimer's disease: a systematic review and meta-analysis.

PubMed

Matsunaga, Shinji; Kishi, Taro; Iwata, Nakao

2014-12-28

We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer's disease. We reviewed cognitive function, activities of daily living, behavioral disturbance, global assessment, discontinuation rate, and individual side effects. Seven studies (total n=2182) were identified. Combination therapy significantly affected behavioral disturbance scores (standardized mean difference=-0.13), activity of daily living scores (standardized mean difference=-0.10), and global assessment scores (standardized mean difference=-0.15). In addition, cognitive function scores (standardized mean difference=-0.13, P=.06) exhibited favorable trends with combination therapy. The effects of combination therapy were more significant in the moderate-to-severe Alzheimer's disease subgroup in terms of all efficacy outcome scores. The discontinuation rate was similar in both groups, and there were no significant differences in individual side effects. Combination therapy was beneficial for the treatment of moderate-to-severe Alzheimer's disease in terms of cognition, behavioral disturbances, activities of daily living, and global assessment was well tolerated. © The Author 2015. Published by Oxford University Press on behalf of CINP.

The Use of Apatinib in Treating Nonsmall-Cell Lung Cancer: Case Report and Review of Literature.

PubMed

Ding, Lin; Li, Qing-Jian; You, Kai-Yun; Jiang, Zhi-Min; Yao, He-Rui

2016-05-01

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has been proved to be effective and safe in treating heavily pretreated patients with gastric cancer.The aim of the study was to explore the use of apatinib in treatment of nonsmall cell lung cancer and its side effects.We report 2 patients presented with advanced nonsmall-cell lung cancer, who received apatinib after failure in the first- or third-line chemotherapy. They are treated with apatinib in daily dose of 850 mg, 28 days per cycle.Favorable oncologic outcomes were achieved in the 2 cases after the treatment of apatinib. Patient I's progression-free-survival has increased to 4.6 months after palliative therapy of apatinib, whereas Patient II nearly 6 months. The common side effects of apatinib were hypertension and hand-foot syndrome; however, the toxicity of apatinib was controllable and tolerable.Apatinib may be an option for advanced nonsmall cell lung cancer after failure of chemotherapy or other targeted therapy. But that still warrants further investigation in the prospective study.

The Use of Apatinib in Treating Nonsmall-Cell Lung Cancer

PubMed Central

Ding, Lin; Li, Qing-Jian; You, Kai-Yun; Jiang, Zhi-Min; Yao, He-Rui

2016-01-01

Abstract Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has been proved to be effective and safe in treating heavily pretreated patients with gastric cancer. The aim of the study was to explore the use of apatinib in treatment of nonsmall cell lung cancer and its side effects. We report 2 patients presented with advanced nonsmall-cell lung cancer, who received apatinib after failure in the first- or third-line chemotherapy. They are treated with apatinib in daily dose of 850 mg, 28 days per cycle. Favorable oncologic outcomes were achieved in the 2 cases after the treatment of apatinib. Patient I's progression-free-survival has increased to 4.6 months after palliative therapy of apatinib, whereas Patient II nearly 6 months. The common side effects of apatinib were hypertension and hand-foot syndrome; however, the toxicity of apatinib was controllable and tolerable. Apatinib may be an option for advanced nonsmall cell lung cancer after failure of chemotherapy or other targeted therapy. But that still warrants further investigation in the prospective study. PMID:27196461

Morphological and behavioral evidence of Batesian mimicry in nestlings of a lowland Amazonian bird.

PubMed

Londoño, Gustavo A; García, Duván A; Sánchez Martínez, Manuel A

2015-01-01

Because predation is the main cause of avian nest failure, selection should favor strategies that reduce the probability of nest predation. We describe apparent Batesian mimicry in the morphology and behavior of a Laniocera hypopyrra nestling. On hatching, the nestling had a distinctive bright orange color and modified feathers all over its body, and 6 days after hatching, it started to move its head very slowly from side to side (in a "caterpillar" movement) when disturbed. These traits gave it a resemblance to a hairy, aposematic caterpillar. This species has a long nestling period for its size (20 days), perhaps due to slow provisioning rates (about one feeding per hour). We argue that the slow growth rate, combined with high nest predation, favors the evolution of antipredation mechanisms such as the unique morphological and behavioral characteristics of L. hypopyrra nestlings.

Bolus administration of steroid therapy is more favorable than the conventional use in preventing decrease of bone density and the increase of body fat percentage in patients with inflammatory bowel disease.

PubMed

Farkas, Klaudia; Bálint, Anita; Valkusz, Zsuzsanna; Szepes, Zoltán; Nagy, Ferenc; Szűcs, Mónika; Bor, Renáta; Wittmann, Tibor; Molnár, Tamás

2014-09-01

The effects of short course of corticosteroids on the metabolic processes and bone formation has not been well studied. Our aim was to compare the efficacy, the side effects and the bone and lipid metabolisms in IBD patients using bolus or conventional tapering of methylprednisolone for 12 weeks. Nineteen IBD patients received intravenous methylprednisolone of 1mg/kg for 5 days tapered by 4 mg per week. Patients were prospectively randomized in two groups. In "conventional" group (I) steroids were given daily. In "pulse" group (II) weekly doses of steroids were given on special days of the week. The body mass index (BMI) was measured before and after the corticosteroid therapy. Blood samples were collected to assess glucose level, electrolytes, cholesterol and triglyceride levels, inflammatory parameters, cortisol, osteocalcin and crosslaps values. Total body composition analysis was performed at the beginning and at the end of the steroid therapy. In Group I, BMI increased, total body bone density decreased significantly at the end of the steroid therapy. Body fat percent showed a tendency to be higher at the end of steroid therapy in Group I. Cholesterol level increased significantly in Group I patients. The decrease in serum cortisol level was more remarkable in Group I vs. Group II after steroid therapy. Less side-effect occurred in Group II vs. Group I. Our results suggest that bolus tapering of corticosteroids may have more favorable short term outcome than conventional tapering that may revolutionize steroid therapy in IBD. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Knowledge, attitudes and practices among parents and teachers about soil-transmitted helminthiasis control programs for school children in Guimaras, Philippines.

PubMed

Parikh, Divya Sinha; Totañes, Francis I G; Tuliao, Alex H; Ciro, Raezelle N T; Macatangay, Bernard J C; Belizario, Vicente Y

2013-09-01

We determined the attitudes toward and practices regarding soil-transmitted helminthes (STH) control among parents and school teachers to identify reasons behind attitudes and practices that do not promote STH control. Written knowledge, attitudes and practices surveys were distributed to parents (N = 531) and teachers (N = 105) of students at 11 elementary schools in Guimaras Province, the Philippines. The survey addressed attitudes about mass drug administration (MDA), knowledge about STH control, hygienic practices, and acceptability of distributing deworming tablets among teachers. More than 90% of parents and teachers held favorable attitudes towards MDA. Sixty-nine percent of parents and 75.5% of teachers believed stool exams were necessary before MDA. Thirty-seven percent of parents stated they would not allow teachers to administer deworming tablets and 91.5% of parents feared teachers would not detect side effects of the medication. Forty-eight percent of teachers felt they could safely give deworming tablets and 81.4% of teachers were afraid of managing the side effects of deworming tablets. Forty-seven point eight percent of parents and 42.2% of teachers stated defecation in the open occured in their community. Although attitudes toward STH control were largely favorable, misconceptions about the MDA strategy, lack of support for teachers giving deworming tablets, and the practice of open defecation still exist as barriers to STH control efforts. The next step to achieve effective STH control will be to clarify misconceptions in education campaigns, to train teachers about medication administration, campaign to improve sanitation and hygiene and begin targeted mass treatment in Guimaras, the Philippines.

Effects of ridge cracking and interface sliding on morphological symmetry breaking in straight-sided blisters

NASA Astrophysics Data System (ADS)

Li, Shi-Chen; Yu, Sen-Jiang; He, Linghui; Ni, Yong

2018-03-01

Complex surface patterns generated by nonlinear buckling originate from various symmetry-breaking instabilities. Identifying possible key factors that regulate the instability modes is critical to reveal the mechanism of the surface pattern selection. In this paper, how another two factors (ridge cracking and interface sliding) including Poisson's ratio influence the morphological symmetry breaking in straight-sided blisters are systematically studied. Morphology diagrams from stability analysis show that ridge cracking and low Poisson's ratio promote symmetric instability mode and favor bubble-like blisters while interface sliding and high Poisson's ratio facilitate antisymmetric instability mode and result in telephone cord buckles. The analytical predictions are evidenced by experimental observations on annealed silicon nitride films on glass substrates and confirmed by nonlinear numerical simulations. This study explains how and why the rarely observed bubble-like blisters in accompany with ridge crack can appear in brittle thin films in comparison with the ubiquitously observed telephone cord buckles that usually form as the development of an antisymmetric instability mode when straight-sided blisters undergo the super-critical isotropic compression.

Separation characteristics of generic stores from lee side of an inclined flat plate at Mach 6

NASA Technical Reports Server (NTRS)

Wilcox, Floyd J., Jr.

1995-01-01

An experimental investigation was conducted to determine the aerodynamic characteristics of a store as it was separated from the lee side of a flat plate inclined at 15 deg to the free-stream flow at Mach 6. Two store models were tested: a cone cylinder and a roof delta. Force and moment data were obtained for both stores as they were moved in 0.5-in. increments away from the flat plate lee-side separated flow region into the free-stream flow while the store angle of attack was held constant at either 0 deg or 15 deg. The results indicate that both stores had adverse separation characteristics (i.e., negative normal force and pitching moment) at an angle of attack of 0 deg, and the cone cylinder had favorable separation characteristics (i.e., positive normal force and pitching moment) at an angle of attack of 15 deg. At an angle of attack of 15 deg, the separation characteristics of the roof delta are indeterminate at small separation distances and favorable at greater separation distances. These characteristics are the result of the local flow inclination relative to the stores as they traversed through the flat plate lee-side flow field. In addition to plotted data, force and moment data are tabulated and schlieren photographs of the stores and flat plate are presented.

Intrathecal clonidine and bupivacaine have synergistic analgesia for acute thermally or inflammatory-induced pain in rats.

PubMed

Nishiyama, Tomoki; Hanaoka, Kazuo

2004-04-01

We investigated the interaction between spinally administered bupivacaine and clonidine using an animal model of acute and inflammatory pain. Rats implanted with lumbar intrathecal catheters were injected intrathecally with saline (control), bupivacaine (1 to 100 microg), or clonidine (0.1 to 3 microg) and tested for their responses to thermal stimulation to the tail (tail flick test) and subcutaneous formalin injection into the hindpaw (formalin test). The effects of the combination of bupivacaine and clonidine on both stimuli were tested by isobolographic analysis. General behavior and motor function were examined as side effects. The 50% effective doses of bupivacaine and clonidine were significantly smaller when combined compared with each single drug in both the tail flick test (2.82 and 0.11 microg versus 7.1 and 0.29 microg, respectively) and phase 1 (0.24 and 0.009 microg versus 5.7 and 0.15 microg) and phase 2 (0.31 and 0.012 microg versus 3.2 and 0.16 microg) of the formalin test. Side effects were decreased by the combination. These results suggest a favorable combination of intrathecal bupivacaine and clonidine in the management of acute and inflammatory pain. The analgesic interaction between intrathecally administered bupivacaine and clonidine was examined during acute thermal and inflammatory-induced pain in rats. The analgesia produced by the combination of these two drugs was synergistic in both acute thermal and inflammatory induced pain, with a decrease in behavioral side effects.

Lactoferrin or ferrous salts for iron deficiency anemia in pregnancy: A meta-analysis of randomized trials.

PubMed

Abu Hashim, Hatem; Foda, Osama; Ghayaty, Essam

2017-12-01

This systematic review and meta-analysis aimed to evaluate the efficacy of daily oral bovine lactoferrin versus daily oral ferrous iron preparations for treatment of iron deficiency anemia (IDA) during pregnancy. Searches were conducted on PubMed, ScienceDirect, ClinicalTrials.gov and CENTRAL databases from inception to February 2017 and the bibliographies of retrieved articles were screened. The PRISMA Statement was followed. Published English language randomized trials comparing lactoferrin with oral ferrous iron preparations in pregnant women with iron deficiency anemia were included. Quasi-randomized, non- randomized or studies including other known cause of anemia, gestational or pre-existent maternal diseases were excluded. Accordingly, 4 eligible trials (600 women) were analyzed. Primary outcome was change in hemoglobin level at 4 weeks of treatment. Secondary outcomes were; change in serum ferritin and iron, rates of gastrointestinal side effects, preterm birth, low birthweight, neonatal death and mean birthweight. Quality assessment was performed by the Cochrane risk of bias tool. Odds ratio and mean difference were used to integrate dichotomous and continuous outcomes respectively. Pooled estimates for change in hemoglobin levels at four weeks favored daily oral lactoferrin over daily oral ferrous sulphate (mean difference 0.77; 95% confidence interval [CI] 0.04-1.55; P=0.04, 4 trials, 600 women). However, after subgroup analysis (degree of anemia), no significant difference in hemoglobin levels were found between both groups in mild anemia (mean difference 0.80; 95% CI -0.21 to 1.82, 3 trials, 372 women), but a significant increase favoring lactoferrin was reported in moderate anemia (mean difference 0.68; 95% CI 0.53-0.83; P<0.00001, one trial, 228 women). Significantly less gastrointestinal side effects were reported with lactoferrin treatment. No significant differences existed with regard to other outcomes. In conclusion, for pregnant women with IDA, daily oral bovine lactoferrin is just as good as ferrous sulfate in improving hematological parameters with fewer gastrointestinal side effects. Thereby, lactoferrin should be the iron replacement agent of choice for treatment of IDA in pregnancy. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Trivalent ions modification for high-silica mordenite: A first principles study

NASA Astrophysics Data System (ADS)

Chen, Fayun; Zhang, Laijun; Feng, Gang; Wang, Xuewen; Zhang, Rongbin; Liu, Jianwen

2018-03-01

Using periodic DFT-D3-U methods, the present work give a mechanistic insight into the high silica B-, Al-, Ga- and Fe-MOR with H, Li, Na, and K as charge balance ions. The acid properties of the zeolite were probed via NH3 and pyridine adsorption. It is found that the charge balance ions influence the location of the trivalent ions, the cell volumes, as well as the synthesis difficulty of the zeolites. The energy differences for B, Al, Ga and Fe in different T sites are small for the H-form zeolites, while large for the Na- and K-form zeolites. For H-form MOR, the proton of the sbnd OH group prefers to bond to O(7) and O(3) and pointing to the 12MR for trivalent ions in T1 sites. The proton bonds to O(3), O(2), O(2) and O(5), respectively, for B, Al, Ga and Fe in T2 site of MOR, with the sbnd OH group pointing to intersection of 12MR and the side-pocket, except for the B-MOR that sbnd OH group pointing to the 12MR. For trivalent ions located in T3 and T4 sites, the protons prefers to bond to O(1) and O(2), respectively, with the sbnd OH group pointing to the intersection of 8MR and side-pocket as well as the intersection of 12MR and side-pocket. All incorporated B, Al, Ga, and Fe framework ions are tetra-coordinated, except the B atoms are tri-coordinated. The NH4-form MOR has smaller cell volume than the other form MOR. Na and K are energetically more favored charge balance ions than Li and NH3 for MOR zeolites synthesis, and the H-form zeolite is the most difficult to be synthesized directly. The strength of the Brønsted acidity follows the order: HBMOR < HFeMOR ≈ HGaMOR < HAlMOR, vs. the Lewis acidity order: HBMOR < HAlMOR < HFeMOR ≈ HGaMOR. NH3 could be adsorbed inside all kinds of channels, and especially favors in the small 8MR vs. pyridine could only be adsorbed in the main channel of MOR due to the steric effect. It indicates that the acid sites in the side pocket and the small 8-membered ring and the side pocket could not be effectively determined just by the pyridine adsorption experiments. In comparison, the NH3 adsorption experiments could detect all kinds of Brønsted sites of the MOR zeolites.

Changing environments and alternative perspectives in evaluating the cost-effectiveness of new antipsychotic drugs.

PubMed

Rosenheck, Robert; Doyle, Jefferson; Leslie, Douglas; Fontana, Alan

2003-01-01

This article examines the ways in which changes in the treatment environment and in measurement perspectives can affect the evaluation of cost-effectiveness of new medications. In three studies we reexamined data from a clinical trial of haloperidol and clozapine conducted from 1993 to 1996. The results of the studies are as follows: Study 1 found that clozapine treatment was associated with significantly reduced inpatient costs, and increased outpatient costs, suggesting that as systems use less inpatient care and more outpatient care, more effective medications may increase, rather than decrease, costs in sicker patients. Study 2 found that while provider assessments and standard measures favored clozapine over haloperidol, patient responses showed little evidence of a clinical advantage for clozapine and a less favorable side-effect profile. Study 3 found that while annual drug costs in the published trial were estimated to be dollars 4,545 for a full year of clozapine treatment, atypical antipsychotic costs in 2000 were estimated to range from dollars 1,254 to dollars 3,016 in the Department of Veterans Affairs system, and from dollars 2,221 to dollars 8,147 in the private sector. In conclusion, cost-effectiveness, as evaluated in studies like CATIE, will increasingly need to be tied to service system contingencies, environments, and evaluation perspectives.

Synthesis of waterborne polyurethane containing alkoxysilane side groups and the properties of the hybrid coating films

NASA Astrophysics Data System (ADS)

Li, Qi; Guo, Longhai; Qiu, Teng; Xiao, Weidong; Du, Dianxing; Li, Xiaoyu

2016-07-01

A series of waterborne polyurethane (WPU) containing alkoxysilane side groups were synthesized by using the dihydroxy functionalized alkoxysilane. The diol with trimethoxysilane groups at the side chains was synthesized via Michael addition between 3-(methacryloxypropyl)trimethoxysilane (MAPTS) and diethanolamine (DEA). The silane diol was applied as the chain extender for the NCO-endcapped prepolymer of isophorone diisocyanate, polycarbonate diol, 2,2-bis(hydroxymethyl) butyric acid and 1,4-butanediol. The products with the silane content varied from 1.2 to 16.5 wt% were dispersed in water after neutralization. The effect of the silane diol on the particle size and morphology of the WPU dispersion was studied by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. X-ray photoelectron spectroscopy (XPS) characterization was carried out on the coating film of the WPU, revealing that the long flexible side chain is favorable for the silane components to emigrate toward the film surface and crosslink during the film formation process. As a result, both the surface contact angle to water and water adsorption of the WPU coating films increased with the silane content. Furthermore, the mechanical properties including the modulus and tensile strength of the films were also improved by the incorporation of silane diol.

National markets for organic waste-derived fertilizers and soil amendments

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

Logan, T.J.; Pierzynski, G.M.; Pepperman, R.E.

1995-12-31

The last decade has seen enormous growth in the U.S. in the recycling of organic waste materials like sewage sludge, manures, yard waste, solid waste and various industrial wastes. This has been prompted by real or perceived shortages of landfill capacity, state and federal regulations favoring beneficial use of organic wastes, and public support for recycling. Use of fertilizers and soil amendments derived from these wastes has been stimulated by favorable supply-side economics, a shift to organic/sustainable agriculture, and water quality concerns that favor slow-release nutrient sources. This paper summarizes the properties and beneficial use attributes of the various wastesmore » and their derived products, markets for these materials, and constraints/strategies for market penetration.« less

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.

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.

Sunitinib-induced nephrotic syndrome in association with drug response in a patient with Xp11.2 translocation renal cell carcinoma.

PubMed

Liu, Yao-Chung; Chang, Peter Mu-Hsin; Liu, Chun-Yu; Yang, Chih-Yu; Chen, Ming-Han; Pan, Chin-Chen; Chen, Ming-Huang

2011-11-01

We report the case of a patient with metastatic renal cell carcinoma with Xp11.2 translocation/transcription factor E3 (TFE3) gene fusion who had presented with sunitinib-induced nephrotic syndrome in association with favorable and durable treatment response. The nephrotic syndrome was managed successfully by discontinuing sunitinib and symptomatic treatment. The 27-year-old female patient presenting with right upper abdominal pain was diagnosed with Xp11.2 translocation renal cell carcinoma on the right side with multiple pulmonary and hepatic metastases. She underwent radical nephrectomy and took a daily dose of 37.5 mg sunitinib. Partial response to sunitinib was achieved and maintained for 5 months, but when nephrotic syndrome occurred, drug intake was discontinued. The nephrotic syndrome gradually resolved around 2 months after discontinuation of sunitinib and medical management. Our case highlighted the favorable response of a particular non-clear cell type renal cell carcinoma to sunitinib and the specific toxicity associated with the antiangiogenic effect of sunitinib.

Effect of Increasing Doses of Saw Palmetto on Lower Urinary Tract Symptoms: A Randomized Trial

PubMed Central

Barry, Michael J.; Meleth, Sreelatha; Lee, Jeannette Y.; Kreder, Karl J.; Avins, Andrew L.; Nickel, J. Curtis; Roehrborn, Claus G.; Crawford, E. David; Foster, Harris E.; Kaplan, Steven A.; McCullough, Andrew; Andriole, Gerald L.; Naslund, Michael J.; Williams, O. Dale; Kusek, John W.; Meyers, Catherine M.; Betz, Joseph M.; Cantor, Alan; McVary, Kevin T.

2012-01-01

Context Saw palmetto fruit extracts are widely used for treating lower urinary tract symptoms attributed to benign prostatic hyperplasia. However, recent clinical trials have questioned their efficacy, at least at standard doses (320 mg daily). Objective To determine the effect of a saw palmetto extract at up to three times the standard dose on lower urinary tract symptoms attributed to benign prostatic hyperplasia. Design Multicenter placebo-controlled randomized trial conducted from June, 2008 through October, 2010. Setting Eleven North American clinical sites. Participants Were men at least 45 years old, with a peak urinary flow rate ≥ 4 ml/sec, an AUA Symptom Index (AUASI) score ≥ 8 and ≤ 24, and no exclusions. Interventions One, two, and then three 320 mg daily doses of saw palmetto extract or placebo, with dose increases at 24 and 48 weeks. Main Outcome Measures Primary outcome was the difference in AUASI score from baseline to 72 weeks. Secondary outcomes were measures of urinary bother; nocturia; uroflow; postvoid residual; prostate-specific antigen; participants’ global assessments; and indices of sexual function, continence, sleep quality, and prostatitis symptoms. Results From baseline to 72 weeks, mean AUASI scores decreased from 14.4 to 12.2 points with saw palmetto and from 14.7 to 11.7 points with placebo. The group mean difference in AUASI score change from baseline to 72 weeks between the saw palmetto and placebo groups was 0.79 points favoring placebo (bound of the 95% confidence interval most favorable to saw palmetto was 1.77 points, one-sided P=0.91). Saw palmetto was no more effective than placebo for any secondary outcome. No attributable side effects were identified. Conclusions Increasing doses of a saw palmetto fruit extract did not reduce lower urinary tract symptoms more than placebo. (CAMUS study number NCT00603304 http://www.ClinicalTrials.gov) PMID:21954478

Formulary review of therapeutic alternatives for atopic dermatitis: focus on pimecrolimus.

PubMed

Weinberg, Jeffrey M

2005-01-01

Atopic dermatitis (AD), often called eczema, is characterized by intense pruritus, erythema, dry skin, and inflammation. The condition is chronic and relapsing, and often occurs in patients with a family history of the atopic triad (asthma, allergic rhinitis, and AD). Use of topical steroids has been the mainstay of medical treatment for AD. Steroid-free treatments for AD, with a more favorable safety profile, have become available within the past 2 years. Tacrolimus ointment, a topical immunomodulator, became available in early 2001 and is indicated for moderate-to-severe AD. A similar but highly skinselective cytokine inhibitor, pimecrolimus cream 1%, became available in March 2002. Pimecrolimus is indicated for mild-to-moderate AD. The objective of this article is to review the key characteristics that differentiate pimecrolimus from steroids and tacrolimus in the treatment of AD. Using secondary resources, the clinical aspects and conventional treatment strategies for AD are reviewed as are the pivotal clinical studies with pimecrolimus and literature on quality of life and economic burden of disease for AD patients and families. Pimecrolimus is an effective, steroid-sparing therapy for mild-tomoderate AD. Early treatment prevents flares, the agent works quickly to reduce signs and symptoms of more advanced AD, and it is safe and appropriate for intermittent long-term therapy. Pimecrolimus has fewer side effects than topical steroids and a better side-effect profile than tacrolimus. It can also be used as a first-line therapy. In studies with patients aged 2 to 17 years, it has been shown to be particularly effective in improving eczema of the face and neck, and its use may improve quality of life for many patients, especially children. A single-strength dose (1%) is safe and medically beneficial for pediatric, adolescent, and adult patients. The direct drug cost of pimecrolimus compares favorably with tacrolimus, but it is significantly more expensive than generic topical steroid creams.

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.

Capping Parallel β-Sheets of Acetyl(Ala)6NH2 with an Acetyl(Ala)5ProNH2 Can Arrest the Growth of the Sheet, Suggesting a Potential for Curtailing Amyloid Growth. An ONIOM and Density Functional Theory Study

PubMed Central

2015-01-01

We present ONIOM calculations using B3LYP/d95(d,p) as the high level and AM1 as the medium level on parallel β-sheets containing four strands of Ac-AAAAAA-NH2 capped with either Ac-AAPAAA-NH2 or Ac-AAAPAA-NH2. Because Pro can form H-bonds from only one side of the peptide linkage (that containing the C=O H-bond acceptor), only one of the two Pro-containing strands can favorably add to the sheet on each side. Surprisingly, when the sheet is capped with AAPAAA-NH2 at one edge, the interaction between the cap and sheet is slightly more stabilizing than that of another all Ala strand. Breaking down the interaction enthalpies into H-bonding and distortion energies shows the favorable interaction to be due to lower distortion energies in both the strand and the four-stranded sheet. Because another strand would be inhibited for attachment to the other side of the capping (Pro-containing) strand, we suggest the possible use of Pro residues in peptides designed to arrest the growth of many amyloids. PMID:24422496

Nature versus nurture in determining athletic ability.

PubMed

Brutsaert, Tom D; Parra, Esteban J

2009-01-01

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

Duloxetine, an antidepressant with analgesic properties – a preliminary analysis

PubMed Central

Onuţu, Adela Hilda

2015-01-01

Serotonin and norepinephrine reuptake inhibitors are second-line antidepressants largely used because of their good tolerance and their reduced side effects. Two of these drugs, duloxetine and venlafaxine, are used also in chronic pain management. In this review we present recent data regarding duloxetine’s effects on the central nervous system, linked to acute pain management, and their efficiency in reducing postoperative chronic pain. The drug’s efficacy results from its modulating effect on the descending inhibitory pain pathways and the inhibition of the nociceptive input. There are already several studies in favor of the analgesic properties of duloxetine. However, further and larger randomized studies are necessary in order to clarify duloxetine efficiency in acute postoperative settings, and thereafter on persistent chronic postoperative pain. PMID:28913467

Refractory Cardiogenic Shock During Tramadol Poisoning: A Case Report.

PubMed

Belin, Nicolas; Clairet, Anne-Laure; Chocron, Sidney; Capellier, Gilles; Piton, Gaël

2017-04-01

Tramadol is a weak opioid analgesic indicated for the treatment of moderate to severe pain. Tramadol intoxication can be lethal, and this drug is frequently involved in voluntary overdose. Classically, tramadol intoxication is associated with neurological and respiratory side effects. In contrast, cardiac effects are poorly documented in the literature. We report a case of severe tramadol intoxication, with plasma concentration 20 times the toxic threshold, complicated by refractory cardiogenic shock, successfully treated by extra corporeal life support (ECLS) with a favorable cardiac outcome and ECLS weaning at day 10. Seizure, clonus, and nonreactive mydriasis were present during 4 days, and complete awakening was delayed to day 15. Poisoning caused by high doses of tramadol can lead to refractory cardiogenic shock, and ECLS can be considered as effective rescue therapy in this context.

E-Learning in Medical Education in India.

PubMed

Dhir, Shashi Kant; Verma, Devender; Batta, Meenal; Mishra, Devendra

2017-10-15

E-learning, or learning and teaching facilitated and supported through the application of technology, is presently being used widely in all fields of education, and also being utilized extensively in medical education. This narrative review aims to introduce the concept of e-learning, and discuss its need and scope in medical education in India. Experience shows that students and faculty are mostly in favor of adopting e-learning side-by-side with traditional learning, and the advantages far outweigh the likely discomfort associated with adoption of this new method.

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

Promoting ethical and objective practice in the medicolegal arena of disability evaluation.

PubMed

Martelli, M F; Zasler, N D; Johnson-Greene, D

2001-08-01

As providers of medical information and testimony, clinicians have ultimate responsibility for ethical conduct as it relates to this information. The authors offer the following recommendations for enhancing ethical relationships between expert clinicians and the courts. 1. Avoid or resist attorney efforts at enticement into joining the attorney-client team. Such compromises of scientific boundaries and ethical principles exist on a continuum ranging from standard attorney-client advocacy at the beginning of the expert consultation phase (e.g., promotional information at the forefront of retaining an expert, with either provision of selective or incomplete records or less than enthusiastic efforts to produce all records) and extending to completion of evaluation, when requests for changes in reports and documentation might be made. 2. Respect role boundaries and do not mix conflicting roles. Remember that the treating doctor possesses a bond with the patient but does not as a rule obtain complete preinjury and postinjury information in the context of assessing causality and apportionment. In contrast, the expert witness must conduct a thorough and multifaceted case analysis sans the physician-patient relationship in order to facilitate objectivity and allow optimum diagnostic formulations. Finally, the trial consultant's function in this adversarial process is to assist with critically scrutinizing and attacking positions of experts for the opposing side. These roles all represent inherently different interests, and mixing them can only reduce objectivity. 3. Insist on adequate time for thorough record review, evaluation, and report generation. Also insist on sufficient time and preparation for deposition and court appearances. 4. Work at building a reputation for general objectivity, reliance on multiple data sources, reaching opinions only after reviewing complete information from both sides, and completing the evaluation. 5. Spend a good amount of time actually treating the patient population being examined or being offered testimony about. This treatment should be current and should be of a similar frequency to treating practitioner specialists. Be able to discuss relevant research and scientific methodology issues competently and without notes. 6. Arrive at opinions only after reviewing all of the evidence from both sides of the adversarial fence, employing multiple data sources, completing the evaluation, and interpreting data within the full context of comprehensive historical, behavioral observation, and contextual information. Being otherwise favorable to retaining attorney interests suggests endorsement of "opinion prostitute," "scientific perjurer," or "hired gun" status. The only way a practitioner can reduce the likelihood of facing an "opinion prostitute" on the opposing side in future cases is to insist on establishing and maintaining a reputation for scientific objectivity. 7. Balance cases from plaintiff and defense attorneys. Predilection for one side or the other suggests bias and sets up predisposition to nonobjectivity. For example, a preponderance of plaintiff work suggests an overdiagnosis or uncritical sympathy bias, whereas a ratio that favors hiring by the defense suggests an underdiagnosis or skepticism bias. Perhaps Brodsky's suggested cut-off ratio of .8 for favorability findings would represent an initial cutoff for defense versus plaintiff ratio. That is, experts should do at least 20% work for the opposite side of the current case being represented. Further, it might be a reasonable expectation that data on these ratios be collected as an important method for ensuring objective opinions. 8. Ensure against excessive favorability to the side of the retaining attorney or firm. Objectivity demands that scientific opinions not be influenced by the position of the legal advocate. Importantly, Brodsky recommends using a ratio of .8 as a cut-off for detecting excessive bias. That is, practitioners should possess prerequisite objectivity to disagree with the referring attorney at least 20% of the time. We suggest that a more useful cut-off would be .75, where experts are expected to generate findings that do not support the referring attorney's position at least 25% of the time. 9. Never arrive at opinions that are inconsistent with plaintiff records, examination data, test data, behavioral presentation, and so forth, especially when such opinions are favorable to the side of the retaining attorney firm. Instead, use the following recommendations. (ABSTRACT TRUNCATED)

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

PubMed

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

2011-05-09

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

Pramipexole in the treatment of Parkinson's disease: new developments.

PubMed

Möller, J Carsten; Oertel, Wolfgang H

2005-09-01

The nonergot dopamine agonist pramipexole is an efficient and safe drug for the treatment of Parkinson's disease. Clinicians may favor pramipexole over other dopamine agonists because of its suggested higher tolerability with respect to peripheral dopaminergic side effects. Importantly, nonergot dopamine agonists such as pramipexole may not cause restrictive valvular heart disease and may therefore represent the first choice in patients with valvular lesions under treatment with ergot dopamine agonists. However, particular caution has to be exercised in younger Parkinson's disease patients with a shorter disease duration regarding the occurrence of sudden onset of sleep. In light of cost-effectiveness and quality-of-life issues, its final significance for the initial treatment of patients with early Parkinson's disease remains to be determined.

Antibiotic Extraction as a Recent Biocontrol Method for Aspergillus Niger andAspergillus Flavus Fungi in Ancient Egyptian mural paintings

NASA Astrophysics Data System (ADS)

Hemdan, R. Elmitwalli; Fatma, Helmi M.; Rizk, Mohammed A.; Hagrassy, Abeer F.

Biodeterioration of mural paintings by Aspergillus niger and Aspergillus flavus Fungi has been proved in different mural paintings in Egypt nowadays. Several researches have studied the effect of fungi on mural paintings, the mechanism of interaction and methods of control. But none of these researches gives us the solution without causing a side effect. In this paper, for the first time, a recent treatment by antibiotic "6 penthyl α pyrone phenol" was applied as a successful technique for elimination of Aspergillus niger and Aspergillus flavus. On the other hand, it is favorable for cleaning Surfaces of Murals executed by tembera technique from the fungi metabolism which caused a black pigments on surfaces.

Substituent effects that control conjugated oligomer conformation through non-covalent interactions

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

Sharber, Seth A.; Baral, Rom Nath; Frausto, Fanny

Although understanding the conformations and arrangements of conjugated materials as solids is key to their prospective applications, predictive power over these structural factors remains elusive. In this work, substituent effects tune non-covalent interactions between side-chain fluorinated benzyl esters and main-chain terminal arenes, in turn controlling the conformations and interchromophore aggregation of three-ring phenylene-ethynylenes (PEs). Cofacial fluoroarene–arene (ArF–ArH) interactions cause twisting in the PE backbone, interrupting intramolecular conjugation as well as blocking chromophore aggregation, both of which prevent the typically observed bathochromic shift observed upon transitioning PEs from solution to solid. This work highlights two structural factors that determine whether themore » ArF–ArH interactions, and the resulting twisted, unaggregated chromophores, occur in these solids: (i) the electron-releasing characteristic of substituents on ArH, with more electron-releasing character favoring ArF–ArH interactions, and (ii) the fluorination pattern of the ArF ring, with 2,3,4,5,6-pentafluorophenyl favoring ArF–ArH interactions over 2,4,6-trifluorophenyl. Furthermore, these trends indicate that considerations of electrostatic complementarity, whether through a polar-π or substituent–substituent mechanism, can serve as an effective design principle in controlling the interaction strengths, and therefore the optoelectronic properties, of these molecules as solids.« less

Substituent effects that control conjugated oligomer conformation through non-covalent interactions

DOE PAGES

Sharber, Seth A.; Baral, Rom Nath; Frausto, Fanny; ...

2017-03-31

Although understanding the conformations and arrangements of conjugated materials as solids is key to their prospective applications, predictive power over these structural factors remains elusive. In this work, substituent effects tune non-covalent interactions between side-chain fluorinated benzyl esters and main-chain terminal arenes, in turn controlling the conformations and interchromophore aggregation of three-ring phenylene-ethynylenes (PEs). Cofacial fluoroarene–arene (ArF–ArH) interactions cause twisting in the PE backbone, interrupting intramolecular conjugation as well as blocking chromophore aggregation, both of which prevent the typically observed bathochromic shift observed upon transitioning PEs from solution to solid. This work highlights two structural factors that determine whether themore » ArF–ArH interactions, and the resulting twisted, unaggregated chromophores, occur in these solids: (i) the electron-releasing characteristic of substituents on ArH, with more electron-releasing character favoring ArF–ArH interactions, and (ii) the fluorination pattern of the ArF ring, with 2,3,4,5,6-pentafluorophenyl favoring ArF–ArH interactions over 2,4,6-trifluorophenyl. Furthermore, these trends indicate that considerations of electrostatic complementarity, whether through a polar-π or substituent–substituent mechanism, can serve as an effective design principle in controlling the interaction strengths, and therefore the optoelectronic properties, of these molecules as solids.« less

Anidulafungin (Eli Lilly & Co).

PubMed

Hawser, S

1999-12-01

The pentyloxyterphenyl side chain derivative of echinocandin B, anidulafungin, is a 1,3-alpha-glucan synthesis inhibitor undergoing phase II clinical trials by Versicor and Eli Lilly, in various formulations, for the potential treatment of fungal and protozoal infections. Eli Lilly has retained options to the oral formulation of the compound, but development, clinical registration and marketing rights were licensed to Versicor in June 1999. The primary target of this compound is Candida, but Eli Lilly also intends to develop the drug for Aspergillus infections. No activity has been shown against Cryptococcus. The oral activity of anidulafungin is compromised by a low bioavailability, a decreased absorption when taken with food, and gastrointestinal side effects at higher doses. The development of a phosphorylated prodrug, LY-307853, which is converted in the body to anidulafungin by tissue and serum phosphatases, was discontinued in favor of an oral formulation, which uses anidulafungin directly. In February 1999, Deutsche Bank predicted sales of $100 million in 2001, rising to $300 million in 2003.

Women's preferences regarding infant or maternal antiretroviral prophylaxis for prevention of mother-to-child transmission of HIV during breastfeeding and their views on Option B+ in Dar es Salaam, Tanzania.

PubMed

Ngarina, Matilda; Tarimo, Edith A M; Naburi, Helga; Kilewo, Charles; Mwanyika-Sando, Mary; Chalamilla, Guerino; Biberfeld, Gunnel; Ekstrom, Anna Mia

2014-01-01

The WHO 2010 guidelines for prevention of mother-to-child transmission (PMTCT) of HIV recommended prophylactic antiretroviral treatment (ART) either for infants (Option A) or mothers (Option B) during breastfeeding for pregnant women with a CD4 count of >350 cell/µL in low-income countries. In 2012, WHO proposed that all HIV-infected pregnant women should receive triple ART for life (B+) irrespective of CD4 count. Tanzania has recently switched from Option A to B+, with a few centers practicing B. However, more information on the real-life feasibility of these options is needed. This qualitative study explored women's preferences for Option A vs B and their views on Option B+ in Dar es Salaam, Tanzania. We conducted four focus group discussions with a total of 27 pregnant women with unknown HIV status, attending reproductive and child health clinics, and 31 in-depth interviews among HIV-infected pregnant and post-delivery women, 17 of whom were also asked about B+. Most participants were in favor of Option B compared to A. The main reasons for choosing Option B were: HIV-associated stigma, fear of drug side-effects on infants and difficult logistics for postnatal drug adherence. Some of the women asked about B+ favored it as they agreed that they would eventually need ART for their own survival. Some were against B+ anticipating loss of motivation after protecting the child, fearing drug side-effects and not feeling ready to embark on lifelong medication. Some were undecided. Option B was preferred. Since Tanzania has recently adopted Option B+, women with CD4 counts of >350 cell/µL should be counseled about the possibility to "opt-out" from ART after cessation of breastfeeding. Drug safety and benefits, economic concerns and available resources for laboratory monitoring and evaluation should be addressed during B+ implementation to enhance long-term feasibility and effectiveness.

Promethazine and its use as a treatment for space motion sickness

NASA Technical Reports Server (NTRS)

Bagian, James P.; Beck, Bradley G.

1993-01-01

Until Mar. 1989, no effective treatment--either prophylactic or symptomatic--for space motion sickness (SMS) had been discovered. Since Mar. 1989, intramuscular (IM) promethazine (PMZ) has been used in the treatment of SMS with extremely favorably results reported by the crew. A retrospective study was undertaken to quantify the efficacy of IM PMZ since its institution and the incidence of its major anticipated side-effect drowsiness and sedation. The results from a standardized crew medical debriefing conducted immediately after landing and follow-up interviews with the crews were used in establishing the efficacy and incidence of side effects from treatment. Only crews from the first 44 Shuttle flights on their first mission were considered. For a total of 132 crewmembers, 96 exhibited symptoms of SMS; and, of these, 20 were treated with IM PMZ. Ninety percent of those receiving IM PMZ 25-50mg received nearly immediate (less than 2 hours) relief of symptoms and 75 percent required no further treatment through the first 2 days of spaceflight. Those not receiving this treatment did not have any near-term resolution of their symptoms, and 50 percent were still ill through the second day of flight. This represents a significant difference at the p = 0.46 level. In stark contrast to the 60 percent to 73 percent incidence of sedation or drowsiness reported in individuals treated with PMZ in terrestrial environment at the doses used here, less than 5 percent reported these symptoms during spaceflight. IM PMZ is an effective therapy for SMS and is associated with minimal incidence of sedation or drowsiness. This combination of efficacy that is absent of significant side effects represents a substantial improvement in the operational situation of crewmembers afflicted with SMS. Studies to understand the mechanisms underlying these observations will be undertaken in the future.

Chronic cannabinoid CB2 activation reverses paclitaxel neuropathy without tolerance or CB1-dependent withdrawal

PubMed Central

Deng, Liting; Guindon, Josée; Cornett, Benjamin L.; Makriyannis, Alexandros; Mackie, Ken; Hohmann, Andrea G.

2014-01-01

Background Mixed cannabinoid CB1/CB2 agonists such as Δ9-tetrahydrocannabinol (Δ9-THC) can produce tolerance, physical withdrawal, and unwanted CB1-mediated central nervous system side effects. Whether repeated systemic administration of a CB2-preferring agonist engages CB1 receptors or produces CB1-mediated side effects is unknown. Methods We evaluated anti-allodynic efficacy, possible tolerance, and cannabimimetic side effects of repeated dosing with a CB2-preferring agonist AM1710 in a model of chemotherapy-induced neuropathy produced by paclitaxel using CB1KO, CB2KO, and WT mice. Comparisons were made with the prototypic classical cannabinoid Δ9-THC. We also explored the site and possible mechanism of action of AM1710. Results Paclitaxel-induced mechanical and cold allodynia developed equivalently in CB1KO, CB2KO, and WT mice. Both AM1710 and Δ9-THC suppressed established paclitaxel-induced allodynia in WT mice. Unlike Δ9-THC, chronic AM1710 did not engage CB1 activity or produce antinociceptive tolerance, CB1-mediated cannabinoid withdrawal, hypothermia, or motor dysfunction. Anti-allodynic efficacy of systemic AM1710 was absent in CB2KO mice or WT mice receiving the CB2 antagonist AM630, administered either systemically or intrathecally. Intrathecal AM1710 also attenuated paclitaxel-induced allodynia in WT but not CB2KO mice, implicating a possible role for spinal CB2 receptors in AM1710 anti-allodynic efficacy. Finally, both acute and chronic treatment with AM1710 decreased mRNA levels of tumor necrosis factor alpha and monocyte chemoattractant protein-1 in lumbar spinal cord of paclitaxel-treated WT mice. Conclusions Our results highlight the potential of prolonged use of CB2 agonists for managing chemotherapy-induced allodynia with a favorable therapeutic ratio marked by sustained efficacy and absence of tolerance, physical withdrawal, or CB1-mediated side effects. PMID:24853387

Politics and Evaluation: More than Methodology

ERIC Educational Resources Information Center

Datta, Lois-ellin

2011-01-01

In the 1960s, evaluation thrived in the sunshine of political support for our work. We also experienced the dark side of the force of politics: efforts to introduce partisan biases favorable to special interests. In response to politics as contamination, at least two families of stances developed: populist and public interest. The populist stances…

Moral Rudders and Superintendent Values

ERIC Educational Resources Information Center

Kidder, Rushworth M.

2008-01-01

The core challenge is this--a difficult ethical decision, where values are in play and both sides have powerful moral arguments in their favor. One case presented in this article outlines a dilemma faced by one teacher who became a superintendent herself. The case exploded dramatically in a midsize metropolitan school district, where a principal…

Using Both Sides of the Brain: Experiences that Integrate Art and Talk Therapy Through Scribble Drawings

ERIC Educational Resources Information Center

McNamee, Carole M.

2004-01-01

Neuroscience researchers identify a cerebral cortex with two functioning hemispheres: a left hemisphere associated with language and speech and a right hemisphere associated with visual-motor activities. Additionally, neuroscientists argue that contemporary lifestyles favor the verbal, logical left brain and often ignore the truths that present in…

Holographic Solar Photon Thrusters

NASA Technical Reports Server (NTRS)

Johnson, Les; Matloff, Greg

2006-01-01

A document discusses a proposal to incorporate holographic optical elements into solar photon thrusters (SPTs). First suggested in 1990, SPTs would be systems of multiple reflective, emissive, and absorptive surfaces (solar sails) that would be attached to spacecraft orbiting the Earth to derive small propulsive forces from radiation pressures. An SPT according to the proposal would include, among other things, a main sail. One side of the sail would be highly emissive and would normally face away from the Earth. The other side would be reflective and would be covered by white-light holographic images that would alternately become reflective, transmissive, and absorptive with small changes in the viewing angle. When the spacecraft was at a favorable orbital position, the main sail would be oriented to reflect sunlight in a direction to maximize the solar thrust; when not in a favorable position, the main sail would be oriented to present a substantially absorptive/emissive aspect to minimize the solar drag. By turning the main sail slightly to alternate between the reflective and absorptive/ emissive extremes, one could achieve nearly a doubling or halving of the radiational momentum transfer and, hence, of the solar thrust.

Treatment hurts: Lay theories of graded exposure in the treatment of four anxiety disorders

PubMed Central

Furnham, Adrian; Wilson, Emma; Chapman, Amy; Persuad, Raj

2013-01-01

Objective This paper concerned the perceived suffering/side effects caused by various well-known treatments for personal problems. It looked at whether people understood whether potentially painful treatments that confront negative aversive affect were effective or not. Method In total, 106 participants completed a long questionnaire assessing the ‘psychological pain’ ratings of 30 psychotherapy treatments, varying in fear exposure, for four relatively common anxiety disorders: social phobia, agoraphobia, post-traumatic stress disorder, and obsessive compulsive disorder. Results Factor analytic results revealed four clear factors underlying lay efficacy beliefs of psychotherapy interventions, varying in fear exposure: talking therapies, fear confrontation, fear avoidance, and alternative therapies. Talking therapies were rated the most effective across all disorders, but also the most painful. Fear avoidance therapies were rated the least effective and, along with alternative medicine, the least painful. Treatments involving fear exposure were rated the most painful. Regression analysis revealed talking therapies to be rated more efficacious by younger subjects than older subjects. Conclusion Most people seem able to differentiate between the efficacies of interventions for different anxiety disorders and hold consensually held optimistic conceptions about the usefulness of psychotherapy treatments and counseling that involve fear exposure, despite knowledge of the psychophysical side effects that these therapies often entail. They favored talking cures over others, but that may have been due to misleading items in the questionnaire. PMID:26405431

A nano-disperse ferritin-core mimetic that efficiently corrects anemia without luminal iron redox activity

PubMed Central

Powell, Jonathan J.; Bruggraber, Sylvaine F.A.; Faria, Nuno; Poots, Lynsey K.; Hondow, Nicole; Pennycook, Timothy J.; Latunde-Dada, Gladys O.; Simpson, Robert J.; Brown, Andy P.; Pereira, Dora I.A.

2014-01-01

The 2-5 nm Fe(III) oxo-hydroxide core of ferritin is less ordered and readily bioavailable compared to its pure synthetic analogue, ferrihydrite. We report the facile synthesis of tartrate-modified, nano-disperse ferrihydrite of small primary particle size, but with enlarged or strained lattice structure (~ 2.7 Å for the main Bragg peak versus 2.6 Å for synthetic ferrihydrite). Analysis indicated that co-precipitation conditions can be achieved for tartrate inclusion into the developing ferrihydrite particles, retarding both growth and crystallization and favoring stabilization of the cross-linked polymeric structure. In murine models, gastrointestinal uptake was independent of luminal Fe(III) reduction to Fe(II) and, yet, absorption was equivalent to that of ferrous sulphate, efficiently correcting the induced anemia. This process may model dietary Fe(III) absorption and potentially provide a side effect-free form of cheap supplemental iron. From the Clinical Editor Small size tartrate-modified, nano-disperse ferrihydrite was used for efficient gastrointestinal delivery of soluble Fe(III) without the risk for free radical generation in murine models. This method may provide a potentially side effect-free form iron supplementation. PMID:24394211

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.

Role of Gabapentin in Managing Mucositis Pain in Patients Undergoing Radiation Therapy to the Head and Neck.

PubMed

Milazzo-Kiedaisch, Carol Ann; Itano, Joanne; Dutta, Pinaki R

2016-12-01

Oral mucositis (OM) is a painful and debilitating side effect that affects 80%-100% of patients undergoing radiation therapy for head and neck cancer. This dose-limiting side effect may potentially lead to pain, dehydration, malnutrition, infection, and treatment breaks. Treatment breaks can lead to decreased disease control and suboptimal patient outcomes. No primary prevention exists for OM, and management is focused on pain control. Compelling evidence exists that OM pain has somatic and neuropathic components. This article reviews the existing literature on the use of gabapentin (Neurontin®) as a co-analgesic in treating the neuropathic pain in OM. A literature search was performed using CINAHL® and PubMed with the search terms gabapentin and oral mucositis. The selected articles were briefly screened for relevance, and three were included in this review. No systematic reviews exist on the role of gabapentin for neuropathic pain in radiation-induced OM. Two retrospective studies concluded that gabapentin reduced escalation of opioid doses and unplanned treatment breaks. One retrospective study demonstrated favorable swallowing outcomes. Pain and OM are nursing-sensitive outcomes that can be significantly affected by evidence-based nursing interventions.

Differential Learning as a Key Training Approach to Improve Creative and Tactical Behavior in Soccer.

PubMed

Santos, Sara; Coutinho, Diogo; Gonçalves, Bruno; Schöllhorn, Wolfgang; Sampaio, Jaime; Leite, Nuno

2018-03-01

The aim of this study was to identify the effects of a differential-learning program, embedded in small-sided games, on the creative and tactical behavior of youth soccer players. Forty players from under-13 (U13) and under-15 (U15) were allocated into control and experimental groups and were tested using a randomized pretest to posttest design using small-sided games situations. The experimental group participated in a 5-month differential-learning program embodied in small-sided games situations, while the control group participated in a typical small-sided games training program. In-game creativity was assessed through notational analyses of the creative components, and the players' positional data were used to compute tactical-derived variables. The findings suggested that differential learning facilitated the development of creative components, mainly concerning attempts (U13, small; U15, small), versatility (U13, moderate; U15, small), and originality (U13, unclear; U15, small) of players' actions. Likewise, the differential-learning approach provided a decrease in fails during the game in both experimental groups (moderate). Moreover, differential learning seemed to favor regularity in pitch-positioning behavior for the distance between players' dyads (U13, small; U15, small), the distance to the team target (U13, moderate; U15, small), and the distance to the opponent target (U13, moderate; U15, small). The differential-learning program stressed creative and positional behavior in both age groups with a distinct magnitude of effects, with the U13 players demonstrating higher improvements over the U15 players. Overall, these findings confirmed that the technical variability promoted by differential learning nurtures regularity of positioning behavior.

Reducing pain from palatal needle stick by topical anesthetics: a comparative study between two lidocaine/prilocaine substances.

PubMed

Al-Melh, Manal Abu; Andersson, Lars

2008-01-01

The aims of this study were to compare the topical anesthetic effect of two different preparations of lidocaine/prilocaine, cream versus thermosetting gel, on the reduction of pain from needle stick in the palate. The study also compared the subjects' preferences with regard to the substances. Two preparations of 2.5% lidocaine/2.5% prilocaine topical anesthetic agents were applied on the palatal mucosa in the canine region bilaterally and blindly to forty subjects. In the same visit, the cream (EMLA) was applied on one side and the thermosetting gel (Oraqix) on the other side, simultaneously. After that, a needle stick was given on each side using a 27-gauge needle inserted to bone contact through the palatal mucosa every second minute during a ten-minute period. Immediately after the needle stick, the subjects started recording their findings using a verbal scale, a visual analogue scale, and a questionnaire form. Significant differences were set at p < 0.05. Both substances reduced or eliminated pain from needle stick in the palate. Significant differences in pain reduction were observed between the two substances. EMLA reduced pain significantly better than Oraqix. With regard to comfort, taste, anesthetic effect, personal preference, and recommendation, the majority of the subjects favored the EMLA cream to the thermosetting gel. No adverse effects were reported by the subjects. Although both topical anesthetic agents are similar in content, the cream seemed to be preferred by the patients and reduced pain from needle stick in the palate significantly better than the thermosetting gel.

Late-onset granulomatous prostatitis following intravesical bacille Calmette-Guerin therapy: case report.

PubMed

Castillo Cádiz, Octavio; Villasenín Parrado, Lorena; Borgna Christie, Vincenzo; Gallegos Méndez, Iván; Martínez Corta, Virginia

2016-06-20

Bacille Calmette-Guerin intravesical treatment is the most effective treatment for reducing the recurrence of non-muscle-invasive urothelial carcinomas. This treatment can sometimes have side effects and serious complications. Granulomatous prostatitis is a common histological finding but it rarely has a clinical presentation. We report a case of a 75-year-old, type 2 diabetic, male patient who was diagnosed with urothelial in situ carcinoma, for which he began treatment with Bacille Calmette-Guerin instillations. Five years later the patient presented nocturia, pollakiuria, severe urgency, and intense and recurrent perineal pain associated with marked elevation of prostatic specific antigen. A prostatic biopsy was performed that showed a moderate to severe granulomatous prostatitis related to bacille Calmette-Guerin. The patient received full antituberculosis combination drugs with a favorable clinical response.

Ten Important Tips in Treating a Patient with Lumbar Disc Herniation

PubMed Central

Hejrati, Hamid; Ariamanesh, Shahrara

2016-01-01

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

Treatment of tardive dyskinesia with tetrabenazine or valbenazine: a systematic review.

PubMed

Caroff, Stanley N; Aggarwal, Saurabh; Yonan, Charles

2018-02-01

Up to 30% of patients taking antipsychotics may develop tardive dyskinesia (TD). Recent evidence-based recommendations demonstrate an unmet need for effective TD management. This systematic review was designed to update the evidence for TD treatment, comparing two vesicular monoamine transporter 2 (VMAT2) inhibitors, tetrabenazine and valbenazine. Of 487 PubMed/Embase search results, 11 studies met the review criteria. Valbenazine efficacy was demonstrated in rigorously designed clinical trials that meet the guidelines for AAN Class I evidence. Due to differences in study designs and a lack of standardized and controlled trials with tetrabenazine, a formal meta-analysis comparing the agents was not possible. However, valbenazine appears to have fewer side effects and a more favorable once-daily dosing regimen for the treatment of TD.

Case report and review of esophageal lichen planus treated with fluticasone

PubMed Central

Ynson, Marie Lourdes; Forouhar, Faripour; Vaziri, Haleh

2013-01-01

Lichen planus is a fairly common chronic idiopathic disorder of the skin, nails and mucosal surfaces. Esophageal involvement of this disease on the other hand is rare and only about 50 cases have been reported in literature. Given its rarity, it can be difficult to diagnose and may be easily misdiagnosed as reflux esophagitis. Currently, there are no clear recommendations on the optimal management of this disease and little is known about the best treatment approach. Systemic steroids are usually the first line treatment and offer a favorable response. In this report, we would like to present a novel approach in the management of esophageal lichen planus in a middle-aged woman treated successfully with swallowed fluticasone propionate 220 mcg twice a day for 6 wk, as evidenced by objective clinical findings. Based on our review of related literature and experience in this patient, we feel that a trial of swallowed fluticasone may be a prudent approach in the management of these patients since it has a more favorable side effect profile than systemic treatment. PMID:23539434

Why square lattices are not seen on curved ionic membranes

NASA Astrophysics Data System (ADS)

Thomas, Creighton; Olvera de La Cruz, Monica

2013-03-01

Ionic crystalline membranes on curved surfaces are ubiquitous in nature, appearing for example on the membranes of halophilic organisms. Even when these membranes buckle into polyhedra with square or rectangular sides, the crystalline structure is seen to have hexagonal symmetry. Here, we theoretically and numerically investigate the effects of curvature on square lattices. Our model system consists of both positive and negative ions with a 1:1 charge ratio adsorbed onto the surface of a sphere. In flat space, the lowest-energy configuration of this system can be a square lattice. This bipartite arrangement is favored because there are two types of ions. It leads to a fundamentally different defect structure than what has been seen when triangular lattices are favored. We classify these defects and find that curvature disrupts long-range square symmetry in a crystal. Through numerical simulations, we see that small square regions are possible in some cases, but this phase coexists with other structures, limiting the scale of these square-lattice microstructures. Thus, at large length scales, curvature leads to triangular structures.

Patients' Preference for Integrating Homoeopathy Services within the Secondary Health Care Settings in India: The Part 3 (PPIH-3) Study.

PubMed

Manchanda, Rajkumar; Koley, Munmun; Saha, Subhranil; Sarkar, Debabrata; Mondal, Ramkumar; Thakur, Prosenjit; Biswas, Debjyoti; Rawat, Birendra Singh; Rajachandrasekar, Bhuvaneswari; Mittal, Renu

2016-05-23

Indian patients' preference for integrated homoeopathy services remains underresearched. Two earlier surveys revealed favorable attitude toward and satisfaction from integrated services. The objectives of this study were to examine knowledge, attitudes, and practice of homoeopathy and to evaluate preference toward its integration into secondary-level health care. A cross-sectional survey was conducted during May to October 2015 among 659 adult patients visiting randomly selected secondary-level conventional health care setups in Kolkata, Mumbai, Kottayam, and New Delhi (India) using a self-administered 24-item questionnaire in 4 local vernaculars (Bengali, Marathi, Malayalam, and Hindi). Knowledge and practice scores were compromised; attitude scores toward integration and legal regulation were high. Respondents were uncertain regarding side effects of homoeopathy and concurrent use and interactions with conventional medicines. A total of 82.40% (95% confidence interval = 79.23, 85.19) of the participants were in favor of integrating homoeopathy services. Preference was significantly higher in Delhi and lower in Kottayam. Probable strategic measures for further development of integrated models are discussed. © The Author(s) 2016.

Patients’ Preference for Integrating Homoeopathy Services within the Secondary Health Care Settings in India

PubMed Central

Manchanda, Rajkumar; Koley, Munmun; Saha, Subhranil; Sarkar, Debabrata; Mondal, Ramkumar; Thakur, Prosenjit; Biswas, Debjyoti; Rawat, Birendra Singh; Rajachandrasekar, Bhuvaneswari; Mittal, Renu

2016-01-01

Indian patients’ preference for integrated homoeopathy services remains underresearched. Two earlier surveys revealed favorable attitude toward and satisfaction from integrated services. The objectives of this study were to examine knowledge, attitudes, and practice of homoeopathy and to evaluate preference toward its integration into secondary-level health care. A cross-sectional survey was conducted during May to October 2015 among 659 adult patients visiting randomly selected secondary-level conventional health care setups in Kolkata, Mumbai, Kottayam, and New Delhi (India) using a self-administered 24-item questionnaire in 4 local vernaculars (Bengali, Marathi, Malayalam, and Hindi). Knowledge and practice scores were compromised; attitude scores toward integration and legal regulation were high. Respondents were uncertain regarding side effects of homoeopathy and concurrent use and interactions with conventional medicines. A total of 82.40% (95% confidence interval = 79.23, 85.19) of the participants were in favor of integrating homoeopathy services. Preference was significantly higher in Delhi and lower in Kottayam. Probable strategic measures for further development of integrated models are discussed. PMID:27215693

Asymmetric Alkyl Side-Chain Engineering of Naphthalene Diimide-Based n-Type Polymers for Efficient All-Polymer Solar Cells.

PubMed

Jia, Tao; Li, Zhenye; Ying, Lei; Jia, Jianchao; Fan, Baobing; Zhong, Wenkai; Pan, Feilong; He, Penghui; Chen, Junwu; Huang, Fei; Cao, Yong

2018-02-13

The design and synthesis of three n-type conjugated polymers based on a naphthalene diimide-thiophene skeleton are presented. The control polymer, PNDI-2HD, has two identical 2-hexyldecyl side chains, and the other polymers have different alkyl side chains; PNDI-EHDT has a 2-ethylhexyl and a 2-decyltetradecyl side chain, and PNDI-BOOD has a 2-butyloctyl and a 2-octyldodecyl side chain. These copolymers with different alkyl side chains exhibit higher melting and crystallization temperatures, and stronger aggregation in solution, than the control copolymer PNDI-2HD that has the same side chain. Polymer solar cells based on the electron-donating copolymer PTB7-Th and these novel copolymers exhibit nearly the same open-circuit voltage of 0.77 V. Devices based on the copolymer PNDI-BOOD with different side chains have a power-conversion efficiency of up to 6.89%, which is much higher than the 4.30% obtained with the symmetric PNDI-2HD. This improvement can be attributed to the improved charge-carrier mobility and the formation of favorable film morphology. These observations suggest that the molecular design strategy of incorporating different side chains can provide a new and promising approach to developing n-type conjugated polymers. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transparent bifacial dye-sensitized solar cells based on organic counter electrodes and iodine-free electrolyte

NASA Astrophysics Data System (ADS)

Ku, Zhiliang; Rong, Yaoguang; Han, Hongwei

2013-10-01

In this study, a novel bifacially active transparent dye-sensitized solar cell (DSSCs) assembled with a transparent poly(3,4-ethylenedioxythiophene) (PEDOT) counter electrode and a colorless iodine-free polymer gel (IFPG) electrolyte was developed. The IFPG electrolyte was prepared by employing an ionic liquid (1,2-dimethyl-3-propylinmidazolium iodide, DMPII) as the charge transfer intermediate and a polymer composite as the gelator without the addition of iodine, exhibiting high conductivity and non-absorption characters. PEDOT electrodes were prepared via a facile electro-polymerization method. By controlling the amount of polymerization charge capacity, we optimized the PEDOT electrodes with high transparency and a favorable activity for catalyzing the IFPG electrolyte. The bifacial DSSCs device fabricated by this kind of transparent PEDOT electrode and colorless IFPG electrolyte showed a power conversion efficiency (PCE) of 6.35% and 4.98% at 100 mW cm-2 AM1.5 illumination corresponding to front- and rear-side illumination. It is notable that the PCE under rear-side illumination approaches 80% that of front-side illumination. Moreover, the device shows excellent stability as confirmed by aging test. These promising results highlight the enormous potential of this transparent PEDOT CE and colorless IFPG electrolyte in scaling up and commercialization of low cost and effective bifacial DSSCs.

The psychopharmacology algorithm project at the Harvard South Shore Program: an algorithm for acute mania.

PubMed

Mohammad, Othman; Osser, David N

2014-01-01

This new algorithm for the pharmacotherapy of acute mania was developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. The authors conducted a literature search in PubMed and reviewed key studies, other algorithms and guidelines, and their references. Treatments were prioritized considering three main considerations: (1) effectiveness in treating the current episode, (2) preventing potential relapses to depression, and (3) minimizing side effects over the short and long term. The algorithm presupposes that clinicians have made an accurate diagnosis, decided how to manage contributing medical causes (including substance misuse), discontinued antidepressants, and considered the patient's childbearing potential. We propose different algorithms for mixed and nonmixed mania. Patients with mixed mania may be treated first with a second-generation antipsychotic, of which the first choice is quetiapine because of its greater efficacy for depressive symptoms and episodes in bipolar disorder. Valproate and then either lithium or carbamazepine may be added. For nonmixed mania, lithium is the first-line recommendation. A second-generation antipsychotic can be added. Again, quetiapine is favored, but if quetiapine is unacceptable, risperidone is the next choice. Olanzapine is not considered a first-line treatment due to its long-term side effects, but it could be second-line. If the patient, whether mixed or nonmixed, is still refractory to the above medications, then depending on what has already been tried, consider carbamazepine, haloperidol, olanzapine, risperidone, and valproate first tier; aripiprazole, asenapine, and ziprasidone second tier; and clozapine third tier (because of its weaker evidence base and greater side effects). Electroconvulsive therapy may be considered at any point in the algorithm if the patient has a history of positive response or is intolerant of medications.

Effectiveness of a motionless ultrasonic toothbrush in reducing plaque and gingival inflammation in patients with fixed orthodontic appliances.

PubMed

Saruttichart, Thayika; Chantarawaratit, Pintu-On; Leevailoj, Chalermpol; Thanyasrisung, Panida; Pitiphat, Waranuch; Matangkasombut, Oranart

2017-03-01

To compare the effectiveness of a motionless ultrasonic toothbrush to a manual toothbrush in reducing dental plaque, gingival inflammation, and mutans streptococci in patients with fixed orthodontic appliances. Twenty-five orthodontic patients were recruited to this crossover study. The patients were randomized into two groups starting with manual or motionless ultrasonic toothbrushes for 30 days. After a 30-day washout period, the patients switched to the other toothbrush type for 30 days. Plaque and gingival indices were evaluated by two calibrated-blinded examiners before and after each 30-day period of brushing. Salivary samples were also collected for quantification of mutans streptococci. On the bracket side, the motionless ultrasonic toothbrush showed a significantly higher mean plaque index bracket score after 30-day usage than baseline (P = .049), while the manual toothbrush group showed no difference between the before and after brushing periods (P = .10). The changes in plaque index bracket score were significantly more favorable in the manual toothbrush group than in the ultrasonic toothbrush group (P = .04). In contrast, no difference was observed on the nonbracket side. There was no significant difference in the changes of gingival index or the numbers of mutans streptococci between the two groups. Manual toothbrushing performed better than brushing with the motionless ultrasonic toothbrush in plaque removal on the bracket side in orthodontic patients. However, no difference was observed in terms of gingival status and the numbers of mutans streptococci.

Chorion Mesenchymal Stem Cells Show Superior Differentiation, Immunosuppressive, and Angiogenic Potentials in Comparison With Haploidentical Maternal Placental Cells

PubMed Central

González, Paz L.; Carvajal, Catalina; Cuenca, Jimena; Alcayaga-Miranda, Francisca; Figueroa, Fernando E.; Bartolucci, Jorge; Salazar-Aravena, Lorena

2015-01-01

Mesenchymal stem cells (MSCs) of placental origin have become increasingly translational owing to their abundance and accessibility. MSCs of different origin share several features but also present biological differences that might point to distinct clinical properties. Hence, mixing fetal and maternal cells from the same placenta can lead to contradicting results. We analyzed the biological characteristics of haploidentical MSCs isolated from fetal sources, including the umbilical cord (UC-MSCs) and chorion (Ch-MSCs), compared with maternal decidua MSCs (Dc-MSCs). All MSCs were analyzed for general stem cell properties. In addition, immunosuppressive capacity was assessed by the inhibition of T-cell proliferation, and angiogenic potential was evaluated in a Matrigel transplantation assay. The comparison between haploidentical MSCs displayed several distinct features, including (a) marked differences in the expression of CD56, (b) a higher proliferative capacity for Dc-MSCs and UC-MSCs than for Ch-MSCs, (c) a diversity of mesodermal differentiation potential in favor of fetal MSCs, (d) a higher capacity for Ch-MSCs to inhibit T-cell proliferation, and (e) superior angiogenic potential of Ch-MSCs evidenced by a higher capability to form tubular vessel-like structures and an enhanced release of hepatocyte growth factor and vascular endothelial growth factor under hypoxic conditions. Our results suggest that assessing the prevalence of fetomaternal contamination within placental MSCs is necessary to increase robustness and limit side effects in their clinical use. Finally, our work presents evidence positioning fetoplacental cells and notably Ch-MSCs in the forefront of the quest for cell types that are superior for applications in regenerative medicine. Significance This study analyzed the biological characteristics of mesenchymal stem cells (MSCs) isolated from fetal and maternal placental origins. The findings can be summarized as follows: (a) important differences were found in the expression of CD56, (b) a different mesodermal differentiation potential was found in favor of fetal MSCs, (c) a higher immunosuppressive capacity for chorion MSCs was noted, and (d) superior angiogenic potential of Ch-MSCs was observed. These results suggest that assessing the prevalence of fetomaternal contamination within placental MSCs is necessary to increase robustness and limit side effects in their clinical use. The evidence should allow clinicians to view fetoplacental cells, notably Ch-MSCs, favorably as candidates for use in regenerative medicine. PMID:26273064

Steroid hydroxylation by basidiomycete peroxygenases: a combined experimental and computational study.

PubMed

Babot, Esteban D; Del Río, José C; Cañellas, Marina; Sancho, Ferran; Lucas, Fátima; Guallar, Víctor; Kalum, Lisbeth; Lund, Henrik; Gröbe, Glenn; Scheibner, Katrin; Ullrich, René; Hofrichter, Martin; Martínez, Angel T; Gutiérrez, Ana

2015-06-15

The goal of this study is the selective oxyfunctionalization of steroids under mild and environmentally friendly conditions using fungal enzymes. With this purpose, peroxygenases from three basidiomycete species were tested for the hydroxylation of a variety of steroidal compounds, using H2O2 as the only cosubstrate. Two of them are wild-type enzymes from Agrocybe aegerita and Marasmius rotula, and the third one is a recombinant enzyme from Coprinopsis cinerea. The enzymatic reactions on free and esterified sterols, steroid hydrocarbons, and ketones were monitored by gas chromatography, and the products were identified by mass spectrometry. Hydroxylation at the side chain over the steroidal rings was preferred, with the 25-hydroxyderivatives predominating. Interestingly, antiviral and other biological activities of 25-hydroxycholesterol have been reported recently (M. Blanc et al., Immunity 38:106-118, 2013, http://dx.doi.org/10.1016/j.immuni.2012.11.004). However, hydroxylation in the ring moiety and terminal hydroxylation at the side chain also was observed in some steroids, the former favored by the absence of oxygenated groups at C-3 and by the presence of conjugated double bonds in the rings. To understand the yield and selectivity differences between the different steroids, a computational study was performed using Protein Energy Landscape Exploration (PELE) software for dynamic ligand diffusion. These simulations showed that the active-site geometry and hydrophobicity favors the entrance of the steroid side chain, while the entrance of the ring is energetically penalized. Also, a direct correlation between the conversion rate and the side chain entrance ratio could be established that explains the various reaction yields observed. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Steroid Hydroxylation by Basidiomycete Peroxygenases: a Combined Experimental and Computational Study

PubMed Central

Babot, Esteban D.; del Río, José C.; Cañellas, Marina; Sancho, Ferran; Lucas, Fátima; Guallar, Víctor; Kalum, Lisbeth; Lund, Henrik; Gröbe, Glenn; Scheibner, Katrin; Ullrich, René; Hofrichter, Martin; Martínez, Angel T.

2015-01-01

The goal of this study is the selective oxyfunctionalization of steroids under mild and environmentally friendly conditions using fungal enzymes. With this purpose, peroxygenases from three basidiomycete species were tested for the hydroxylation of a variety of steroidal compounds, using H2O2 as the only cosubstrate. Two of them are wild-type enzymes from Agrocybe aegerita and Marasmius rotula, and the third one is a recombinant enzyme from Coprinopsis cinerea. The enzymatic reactions on free and esterified sterols, steroid hydrocarbons, and ketones were monitored by gas chromatography, and the products were identified by mass spectrometry. Hydroxylation at the side chain over the steroidal rings was preferred, with the 25-hydroxyderivatives predominating. Interestingly, antiviral and other biological activities of 25-hydroxycholesterol have been reported recently (M. Blanc et al., Immunity 38:106–118, 2013, http://dx.doi.org/10.1016/j.immuni.2012.11.004). However, hydroxylation in the ring moiety and terminal hydroxylation at the side chain also was observed in some steroids, the former favored by the absence of oxygenated groups at C-3 and by the presence of conjugated double bonds in the rings. To understand the yield and selectivity differences between the different steroids, a computational study was performed using Protein Energy Landscape Exploration (PELE) software for dynamic ligand diffusion. These simulations showed that the active-site geometry and hydrophobicity favors the entrance of the steroid side chain, while the entrance of the ring is energetically penalized. Also, a direct correlation between the conversion rate and the side chain entrance ratio could be established that explains the various reaction yields observed. PMID:25862224

An Update on Modern Approaches to Localized Esophageal Cancer

PubMed Central

Welsh, James; Amini, Arya; Likhacheva, Anna; Erasmus, Jeremy; Gomez, Daniel; Davila, Marta; Mehran, Reza J; Komaki, Ritsuko; Liao, Zhongxing; Hofstetter, Wayne L; Bhutani, Manoop; Ajani, Jaffer A

2014-01-01

Esophageal cancer treatment continues to be a topic of wide debate. Based on improvements in chemotherapy drugs, surgical techniques, and radiotherapy advances, esophageal cancer treatment approaches are becoming more specific to the stage of the tumor and the overall performance status of the patient. While surgery continues to be the standard treatment option for localized disease, the current direction favors multimodality treatment including both radiation and chemotherapy with surgery. In the next few years, we will continue to see improvements in radiation techniques and proton treatment, with more minimally invasive surgical approaches minimizing postoperative side effects, and the discovery of molecular biomarkers to help deliver more specifically targeted medication to treat esophageal cancers. PMID:21365188

Stabilizing and destabilizing effects of phenylalanine --> F5-phenylalanine mutations on the folding of a small protein.

PubMed

Woll, Matthew G; Hadley, Erik B; Mecozzi, Sandro; Gellman, Samuel H

2006-12-20

We report a systematic evaluation of phenylalanine-to-pentafluorophenylalanine (Phe --> F5-Phe) mutants for the 35-residue chicken villin headpiece subdomain (c-VHP), the hydrophobic core of which features a cluster of three Phe side chains (residues 6, 10, and 17). Phe --> F5-Phe mutations are interesting because aryl-perfluoroaryl interactions of optimal geometry are intrinsically more favorable than aryl-aryl interactions and because perfluoroaryl units are more hydrophobic than are analogous aryl units. One mutant, Phe-10 --> F5-Phe, provides enhanced tertiary structural stability relative to the native sequence. The other six mutants analyzed caused a decrease in stability.

The Case for Adjunctive Monoclonal Antibody Immunotherapy in Schizophrenia.

PubMed

Miller, Brian J; Buckley, Peter F

2016-06-01

This article presents the case in favor of clinical trials of adjunctive monoclonal antibody immunotherapy in schizophrenia. Evidence for prenatal and premorbid immune risk factors for the development of schizophrenia in the offspring is highlighted. Then key evidence for immune dysfunction in patients with schizophrenia is considered. Next, previous trials of adjunctive anti-inflammatory or other immunotherapy in schizophrenia are discussed. Then evidence for psychosis as a side effect of immunotherapy for other disorders is discussed. Also presented is preliminary evidence for adjunctive monoclonal antibody immunotherapy in psychiatric disorders. Finally, important considerations in the design and implementation of clinical trials of adjunctive monoclonal antibody immunotherapy in schizophrenia are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Aeroheating Analysis for the Mars Reconnaissance Orbiter with Comparison to Flight Data

NASA Technical Reports Server (NTRS)

Liechty, Derek S.

2006-01-01

The aeroheating environment of the Mars Reconnaissance Orbiter (MRO) has been analyzed using the Direct Simulation Monte Carlo and free-molecular techniques. The results of these analyses were used to develop an aeroheating database to be used for the pre-flight planning and the in-flight operations support for the aerobraking phase of the MRO mission. The aeroheating predictions calculated for the MRO include the heat transfer coefficient (C(H)) over a range of angles-of-attack, side-slip angles, and number densities. The effects of flow chemistry were also investigated. Flight heat flux data deduced from surface temperature sensors have been compared to pre-flight predictions and agree favorably.

Asymptomatic elevation of liver enzymes due to levetiracetam: a case report.

PubMed

Sethi, Nitin K; Sethi, Prahlad K; Torgovnick, Josh; Arsura, Edward; Cukierwar, Frances

2013-01-01

Levetiracetam is a commonly used broad-spectrum anticonvulsant efficacious in both partial and generalized seizures. It has an extremely favorable side effect profile with few drug-drug interactions, low potential for hematological and hepatic toxicity, and thus has rapidly become the preferred drug in patients with traumatic brain injuries who need seizure prophylaxis. We report, here, a patient who was started on levetiracetam for seizure prophylaxis after developing large bifrontal-parietal traumatic subdural hematomas (SDH) following a fall from a horse necessitating bifrontal craniotomies for evacuation. The patient developed an asymptomatic elevation of the liver enzymes. The liver enzymes trended back to normal after levetiracetam was stopped, and topiramate was initiated in its place.

Cannabidiol as potential treatment in refractory pediatric epilepsy.

PubMed

Paolino, Maria Chiara; Ferretti, Alessandro; Papetti, Laura; Villa, Maria Pia; Parisi, Pasquale

2016-01-01

In recent years there has been great scientific and public interest focused on the therapeutic potential of compounds derived from cannabis for the treatment of refractory epilepsy in children. From in vitro and in vivo studies on animal models, cannabidiol (CBD) appears to be a promising anticonvulsant drug with a favorable side-effect profile. In humans, CBD efficacy and safety is not supported by well-designed trials and its use has been described by anecdotal reports. It will be necessary to investigate CBD safety, pharmacokinetics and interaction with other anti-epileptic drugs (AEDs) alongside performing double-blinded placebo-controlled trials in order to obtain conclusive data on its efficacy and safety in children.

Formulation and In Vitro, In Vivo Evaluation of Effervescent Floating Sustained-Release Imatinib Mesylate Tablet

PubMed Central

Kadivar, Ali; Kamalidehghan, Behnam; Javar, Hamid Akbari; Davoudi, Ehsan Taghizadeh; Zaharuddin, Nurul Dhania; Sabeti, Bahareh; Chung, Lip Yong; Noordin, Mohamed Ibrahim

2015-01-01

Introduction Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets. Methodology Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M), with Sodium alginate (SA) and Carbomer 934P (CP) as release-retarding polymers, sodium bicarbonate (NaHCO3) as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec) in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted. Results and Discussion Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours. Conclusion In conclusion, in order to suggest a better drug delivery system with constant favorable release, resulting in optimized absorption and less side effects, formulated CP-HPMC-SA based imatinib mesylate floating sustained-release tablets can be a promising candidate for cancer chemotherapy. PMID:26035710

Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial.

PubMed

Barry, Michael J; Meleth, Sreelatha; Lee, Jeannette Y; Kreder, Karl J; Avins, Andrew L; Nickel, J Curtis; Roehrborn, Claus G; Crawford, E David; Foster, Harris E; Kaplan, Steven A; McCullough, Andrew; Andriole, Gerald L; Naslund, Michael J; Williams, O Dale; Kusek, John W; Meyers, Catherine M; Betz, Joseph M; Cantor, Alan; McVary, Kevin T

2011-09-28

Saw palmetto fruit extracts are widely used for treating lower urinary tract symptoms attributed to benign prostatic hyperplasia (BPH); however, recent clinical trials have questioned their efficacy, at least at standard doses (320 mg/d). To determine the effect of saw palmetto extract (Serenoa repens, from saw palmetto berries) at up to 3 times the standard dose on lower urinary tract symptoms attributed to BPH. A double-blind, multicenter, placebo-controlled randomized trial at 11 North American clinical sites conducted between June 5, 2008, and October 10, 2010, of 369 men aged 45 years or older, with a peak urinary flow rate of at least 4 mL/s, an American Urological Association Symptom Index (AUASI) score of between 8 and 24 at 2 screening visits, and no exclusions. One, 2, and then 3 doses (320 mg/d) of saw palmetto extract or placebo, with dose increases at 24 and 48 weeks. Difference in AUASI score between baseline and 72 weeks. Secondary outcomes included measures of urinary bother, nocturia, peak uroflow, postvoid residual volume, prostate-specific antigen level, participants' global assessments, and indices of sexual function, continence, sleep quality, and prostatitis symptoms. Between baseline and 72 weeks, mean AUASI scores decreased from 14.42 to 12.22 points (-2.20 points; 95% CI, -3.04 to -1.36) [corrected]with saw palmetto extract and from 14.69 to 11.70 points (-2.99 points; 95% CI, -3.81 to -2.17) with placebo. The group mean difference in AUASI score change from baseline to 72 weeks between the saw palmetto extract and placebo groups was 0.79 points favoring placebo (upper bound of the 1-sided 95% CI most favorable to saw palmetto extract was 1.77 points, 1-sided P = .91). Saw palmetto extract was no more effective than placebo for any secondary outcome. No clearly attributable adverse effects were identified. Increasing doses of a saw palmetto fruit extract did not reduce lower urinary tract symptoms more than placebo. clinicaltrials.gov Identifier: NCT00603304.

The Statistics of Albedo and Heat Recirculation on Hot Exoplanets

NASA Astrophysics Data System (ADS)

Cowan, Nicolas B.; Agol, Eric

2011-03-01

If both the day-side and night-side effective temperatures of a planet can be measured, it is possible to estimate its Bond albedo, 0 < AB < 1, as well as its day-night heat redistribution efficiency, 0 < ɛ < 1. We attempt a statistical analysis of the albedo and redistribution efficiency for 24 transiting exoplanets that have at least one published secondary eclipse. For each planet, we show how to calculate a sub-stellar equilibrium temperature, T 0, and associated uncertainty. We then use a simple model-independent technique to estimate a planet's effective temperature from planet/star flux ratios. We use thermal secondary eclipse measurements—those obtained at λ>0.8 μm—to estimate day-side effective temperatures, T d, and thermal phase variations—when available—to estimate night-side effective temperature. We strongly rule out the "null hypothesis" of a single AB and ɛ for all 24 planets. If we allow each planet to have different parameters, we find that low Bond albedos are favored (AB < 0.35 at 1σ confidence), which is an independent confirmation of the low albedos inferred from non-detections of reflected light. Our sample exhibits a wide variety of redistribution efficiencies. When normalized by T 0, the day-side effective temperatures of the 24 planets describe a uni-modal distribution. The two biggest outliers are GJ 436b (abnormally hot) and HD 80606b (abnormally cool), and these are the only eccentric planets in our sample. The dimensionless quantity T d/T 0 exhibits no trend with the presence or absence of stratospheric inversions. There is also no clear trend between T d/T 0 and T 0. That said, the six planets with the greatest sub-stellar equilibrium temperatures (T > 2400 K) have low ɛ, as opposed to the 18 cooler planets, which show a variety of recirculation efficiencies. This hints that the very hottest transiting giant planets are qualitatively different from the merely hot Jupiters. We propose an explanation of this trend based on how a planet's radiative and advective times scale with temperature: both timescales are expected to be shorter for hotter planets, but the temperature dependence of the radiative timescale is stronger, leading to decreased heat recirculation efficiency.

Improving Relative Combat Power Estimation: The Road to Victory

DTIC Science & Technology

2014-06-13

said, “ God is on the side of the big battalions.”10 He presented a point of view that was based preferably on a favorable imbalance in numbers and...CHAPTER 4 ANALYSIS We cannot solve our problems with the same thinking we used when we created them. — Albert Einstein The purpose of this

Simplified Calculation Of Solar Fluxes In Solar Receivers

NASA Technical Reports Server (NTRS)

Bhandari, Pradeep

1990-01-01

Simplified Calculation of Solar Flux Distribution on Side Wall of Cylindrical Cavity Solar Receivers computer program employs simple solar-flux-calculation algorithm for cylindrical-cavity-type solar receiver. Results compare favorably with those of more complicated programs. Applications include study of solar energy and transfer of heat, and space power/solar-dynamics engineering. Written in FORTRAN 77.

Exploring the Emotional Side of Job Search Behavior for Younger Workforce Entrants.

ERIC Educational Resources Information Center

Linnehan, Frank; Blau, Gary

1998-01-01

A sample of 18- to 23-year-old workforce entrants (N=332) was broken into subsamples. Study 1 found support for detached and interactive job-search behavior which seemed to represent different levels of emotional involvement in the job-search process. Study 2 involved working college students (N=117) and found that extroverts favored interactive…

Number-related discrimination and summation by squirrel monkeys (Saimiri sciureus sciureus and S. boliviensus boliviensus) on the basis of the number of sides of polygons.

PubMed

Terrell, D F; Thomas, R K

1990-09-01

In Experiment 1, with the number of sides or angles of irregular polygons as cues, programmed training, and a 90% correct criterion (36 of 40), 2 squirrel monkeys' (Saimiri sciureus sciureus and S. boliviensus boliviensus) best performances were to discriminate heptagons from octagons, a 3rd's best was hexagons from heptagons, and a 4th's best was pentagons from heptagons. In Experiment 2, on most trials 2 polygons on one or both discriminanda had to be summed to determine which discrimination had the total fewer sides. Only 1 monkey met criterion (27 of 30) on the 2 tasks, 6 vs. 8 and 7 vs. 8 sides, but the other 3 performed better than chance on the 6 vs. 8 task. We conclude that previous studies of animals' discrimination of polygons in terms of complexity were minimally relevant to this work, and counting and subitizing were rejected in favor of a prototype-matching process to explain our monkeys' performances.

Efficacy and Safety of Remifentanil as an Alternative Labor Analgesic

PubMed Central

Devabhakthuni, Sandeep

2013-01-01

The objective of this review was to evaluate the clinical efficacy and safety of remifentanil in the management of labor pain. Although neuraxial analgesia is the best option during labor, alternative analgesic options are needed for patients with contraindications. Using a systematic literature search, clinical outcomes of remifentanil for labor pain have been summarized. Also, comparisons of remifentanil to other options including meperidine, epidural analgesia, fentanyl, and nitrous oxide are provided. Based on the literature review, remifentanil is associated with high overall maternal satisfaction and favorable side-effect profile. However, due to the low reporting of adverse events, large, randomized controlled trials are needed to evaluate maternal and neonatal safety adequately and determine the optimal dosing needed to provide effective analgesia. While remifentanil is a feasible alternative for patients who cannot or do not want to receive epidural analgesia, administration should be monitored closely for potential adverse effects. PMID:24665213

Intravenous apoptotic cell infusion as a cell-based therapy toward improving hematopoietic cell transplantation outcome.

PubMed

Saas, Philippe; Gaugler, Béatrice; Perruche, Sylvain

2010-10-01

Allogeneic hematopoietic cell transplantation (AHCT) is an efficient therapy for different malignant and nonmalignant hematological diseases. However, the use of this therapeutic approach is still limited by some severe toxic side effects, mainly graft-versus-host disease (GvHD). Today, the risk of fatal GvHD restrains the wider application of AHCT to many patients in need of an effective therapy for their high-risk hematologic malignancies. Thus, new strategies, including cell-based therapy approaches, are required. We propose to use intravenous donor apoptotic leukocyte infusion to improve AHCT outcome. In experimental AHCT models, we demonstrated that intravenous apoptotic leukocyte infusion, simultaneously with allogeneic bone marrow grafts, favors hematopoietic engraftment, prevents allo-immunization, and delays acute GvHD onset. Here, we review the different mechanisms and the potential beneficial effects associated with the immunomodulatory properties of apoptotic cells in the AHCT setting. © 2010 New York Academy of Sciences.

Therapeutic strategies with oral fluoropyrimidine anticancer agent, S-1 against oral cancer.

PubMed

Harada, Koji; Ferdous, Tarannum; Ueyama, Yoshiya

2017-08-01

Oral cancer has been recognized as a tumor with low sensitivity to anticancer agents. However, introduction of S-1, an oral cancer agent is improving treatment outcome for patients with oral cancer. In addition, S-1, as a main drug for oral cancer treatment in Japan can be easily available for outpatients. In fact, S-1 exerts high therapeutic effects with acceptable side effects. Moreover, combined chemotherapy with S-1 shows higher efficacy than S-1 alone, and combined chemo-radiotherapy with S-1 exerts remarkable therapeutic effects. Furthermore, we should consider the combined therapy of S-1 and molecular targeting agents right now as these combinations were reportedly useful for oral cancer treatment. Here, we describe our findings related to S-1 that were obtained experimentally and clinically, and favorable therapeutic strategies with S-1 against oral cancer with bibliographic considerations.

Why CO bonds side-on at low coverage and both side-on and upright at high coverage on the Cr(110) surface

NASA Technical Reports Server (NTRS)

Mehandru, S. P.; Anderson, A. B.

1985-01-01

An atom superposition and electron delocalization molecular orbital study of CO adsorption on the Cr(110) surface shows a high coordinate lying down orientation is favored. This is a result of the large number of empty d-band energy levels in chromium, which allows the antibonding counterparts to sigma and pi donation bonds to the surface to be empty. When lying down, backbonding to CO pi sup * orbitals is enhanced. Repulsive interactions cause additional CO to stand upright at 1/4 monolyer coverage. The results confirm the recent experimental study of Shinn and Madey.

Fused-Ring Acceptors with Asymmetric Side Chains for High-Performance Thick-Film Organic Solar Cells.

PubMed

Feng, Shiyu; Zhang, Cai'e; Liu, Yahui; Bi, Zhaozhao; Zhang, Zhe; Xu, Xinjun; Ma, Wei; Bo, Zhishan

2017-11-01

A kind of new fused-ring electron acceptor, IDT-OB, bearing asymmetric side chains, is synthesized for high-efficiency thick-film organic solar cells. The introduction of asymmetric side chains can increase the solubility of acceptor molecules, enable the acceptor molecules to pack closely in a dislocated way, and form favorable phase separation when blended with PBDB-T. As expected, PBDB-T:IDT-OB-based devices exhibit high and balanced hole and electron mobility and give a high power conversion efficiency (PCE) of 10.12%. More importantly, the IDT-OB-based devices are not very sensitive to the film thickness, a PCE of 9.17% can still be obtained even the thickness of active layer is up to 210 nm. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Scheme for generating distillation-favorable continuous-variable entanglement via three concurrent parametric down-conversions in a single χ⁽²⁾ nonlinear photonic crystal.

PubMed

Gong, Yan-Xiao; Zhang, ShengLi; Xu, P; Zhu, S N

2016-03-21

We propose to generate a single-mode-squeezing two-mode squeezed vacuum state via a single χ⁽²⁾ nonlinear photonic crystal. The state is favorable for existing Gaussian entanglement distillation schemes, since local squeezing operations can enhance the final entanglement and the success probability. The crystal is designed for enabling three concurrent quasi-phase-matching parametric-down conversions, and hence relieves the auxiliary on-line bi-side local squeezing operations. The compact source opens up a way for continuous-variable quantum technologies and could find more potential applications in future large-scale quantum networks.

Solution structure of a small protein containing a fluorinated side chain in the core

PubMed Central

Cornilescu, Gabriel; Hadley, Erik B.; Woll, Matthew G.; Markley, John L.; Gellman, Samuel H.; Cornilescu, Claudia C.

2007-01-01

We report the first high-resolution structure for a protein containing a fluorinated side chain. Recently we carried out a systematic evaluation of phenylalanine to pentafluorophenylalanine (Phe → F5-Phe) mutants for the 35-residue chicken villin headpiece subdomain (c-VHP), the hydrophobic core of which features a cluster of three Phe side chains (residues 6, 10, and 17). Phe → F5-Phe mutations are interesting because aryl–perfluoroaryl interactions of optimal geometry are intrinsically more favorable than either aryl–aryl or perfluoroaryl–perfluoroaryl interactions, and because perfluoroaryl units are more hydrophobic than are analogous aryl units. Only one mutation, Phe10 → F5-Phe, was found to provide enhanced tertiary structural stability relative to the native core (by ∼1 kcal/mol, according to guanidinium chloride denaturation studies). The NMR structure of this mutant, described here, reveals very little variation in backbone conformation or side chain packing relative to the wild type. Thus, although Phe → F5-Phe mutations offer the possibility of greater tertiary structural stability from side chain–side chain attraction and/or side chain desolvation, the constraints associated with the native c-VHP fold apparently prevent the modified polypeptide from taking advantage of this possibility. Our findings are important because they complement several studies that have shown that fluorination of saturated side chain carbon atoms can provide enhanced conformational stability. PMID:17123960

Effects of awareness interventions on children's attitudes toward peers with a visual impairment.

PubMed

Reina, Raul; López, Víctor; Jiménez, Mario; García-Calvo, Tomás; Hutzler, Yeshayahu

2011-09-01

The purpose of this study was to explore the effect of two awareness programs (6-day vs. 1-day programs) on children's attitudes toward peers with a visual impairment. Three hundred and forty-four Spanish physical education students (164 girls and 180 boys) aged 10-15 years, took part in the study. A modified version of the Attitudes Toward Disability Questionnaire (ATDQ) was used, which includes three sub-scales: (i) cognitive perceptions, (ii) emotional perception, and (iii) behavioral readiness to interact with children with disabilities. The questionnaire was filled out during the regular physical education class before and immediately after the awareness activity. The 6-day didactical unit included a lecture on visual impairments and a video describing visual impairments and the game of 5-a-side soccer (first lesson), sensibilization activities toward visual impairment (second and third lessons), training and competitive 5-a-side soccer tasks using blindfolded goggles (fourth and fifth lessons), and a sport show and chat with soccer players with a visual impairment (sixth lesson). The 1-day awareness unit only included the final session of the didactical activity. Repeated measures analysis of variance revealed significant time effects in the cognitive, emotional, and behavioral subscales. Sex also was found to demonstrate significant effects, in which women showed more favorable results than men. A time-by-group intervention effect was only demonstrated in the cognitive sub-scale, and the 6-day didactic intervention was more effective than the 1-day awareness unit.

Molprobity's ultimate rotamer-library distributions for model validation.

PubMed

Hintze, Bradley J; Lewis, Steven M; Richardson, Jane S; Richardson, David C

2016-09-01

Here we describe the updated MolProbity rotamer-library distributions derived from an order-of-magnitude larger and more stringently quality-filtered dataset of about 8000 (vs. 500) protein chains, and we explain the resulting changes and improvements to model validation as seen by users. To include only side-chains with satisfactory justification for their given conformation, we added residue-specific filters for electron-density value and model-to-density fit. The combined new protocol retains a million residues of data, while cleaning up false-positive noise in the multi- χ datapoint distributions. It enables unambiguous characterization of conformational clusters nearly 1000-fold less frequent than the most common ones. We describe examples of local interactions that favor these rare conformations, including the role of authentic covalent bond-angle deviations in enabling presumably strained side-chain conformations. Further, along with favored and outlier, an allowed category (0.3-2.0% occurrence in reference data) has been added, analogous to Ramachandran validation categories. The new rotamer distributions are used for current rotamer validation in MolProbity and PHENIX, and for rotamer choice in PHENIX model-building and refinement. The multi-dimensional χ distributions and Top8000 reference dataset are freely available on GitHub. These rotamers are termed "ultimate" because data sampling and quality are now fully adequate for this task, and also because we believe the future of conformational validation should integrate side-chain with backbone criteria. Proteins 2016; 84:1177-1189. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Mobile Apps in Oncology: A Survey on Health Care Professionals' Attitude Toward Telemedicine, mHealth, and Oncological Apps.

PubMed

Kessel, Kerstin A; Vogel, Marco Me; Schmidt-Graf, Friederike; Combs, Stephanie E

2016-11-24

Mobile apps are an evolving trend in the medical field. To date, few apps in an oncological context exist. The aim was to analyze the attitude of health care professionals (HCPs) toward telemedicine, mHealth, and mobile apps in the field of oncology. We developed and conducted an online survey with 24 questions evaluating HCPs' general attitude toward telemedicine and patients using medical mobile apps. Specific questions on the possible functionality for patients and the resulting advantages and disadvantages for both the patients' and HCPs' daily clinical routine were evaluated. A total of 108 HCPs completed the survey. In all, 88.9% (96/108) considered telemedicine useful and 84.3% (91/108) supported the idea of an oncological app complementing classical treatment. Automatic reminders, timetables, and assessment of side effects and quality of life during therapy were rated as the most important functions. In contrast, uncertainty regarding medical responsibility and data privacy were reasons mostly named by critics. Most (64.8%, 70/108) were in favor of an alert function due to data input needing further clarification, and 94% (66/70) were willing to contact the patient after a critical alert. In all, 93.5% (101/108) supported the idea of using the collected data for scientific research. Moreover, 75.0% (81/108) believed establishing a mobile app could be beneficial for the providing hospital. A majority of HCPs are in favor of telemedicine and the use of oncological apps by patients. Assessing side effects can lead to quicker response and thus lower inconvenience for patients. Clinical data, such as life quality and treatment satisfaction, could be used to evaluate and improve the therapy workflow. Eventually, a mobile app would enhance the patients' relationship to their treating department because they are in permanent contact. ©Kerstin A Kessel, Marco ME Vogel, Friederike Schmidt-Graf, Stephanie E Combs. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.11.2016.

Randomized, double-blind, placebo-controlled trial of fluoxetine treatment for elderly patients with dysthymic disorder.

PubMed

Devanand, D P; Nobler, Mitchell S; Cheng, Jocelyn; Turret, Nancy; Pelton, Gregory H; Roose, Steven P; Sackeim, Harold A

2005-01-01

The authors compared the efficacy and side effects of fluoxetine and placebo in elderly outpatients with dysthymic disorder. Patients were randomly assigned to fluoxetine (20 mg-60 mg/day) or placebo for 12 weeks in a double-blind trial. Of 90 randomized patients, 71 completed the trial. In the intent-to-treat sample, random regression analyses of the Hamilton Rating Scale for Depression (Ham-D; 24-item) and Cornell Dysthymia Rating Scale (CDRS) scores at each visit produced significant time x treatment group interactions favoring the fluoxetine group. Analysis of percentage change in Ham-D scores yielded no effect for treatment group, but a similar analysis of percentage change in CDRS scores yielded a main effect for treatment group, favoring fluoxetine over placebo. In the intent-to-treat sample, response rates were 27.3% for fluoxetine and 19.6% for placebo. In the completer sample, response rates were 37.5% for fluoxetine and 23.1% for placebo. Fluoxetine had limited efficacy in elderly dysthymic patients. The clinical features of elderly dysthymic patients are typically distinct from those of dysthymic disorder in young adults, and the findings suggest that treatments effective for young adult dysthymic patients may not be as useful in elderly dysthymic patients. Further research is needed to identify efficacious treatments for elderly patients with dysthymic disorder, and investigative tools such as electronic/computerized brain scans and neuropsychological testing may help identify the factors that moderate antidepressant treatment response and resistance.

An experimental investigation of propfan installations on an upswept supercritical wing at transonic Mach numbers

NASA Technical Reports Server (NTRS)

Bartlett, G. R.

1985-01-01

An investigation has been conducted in the Langley 16 Foot Transonic Tunnel to determine propfan installation and slipstream interference effects on an unswept supercritical wing. This data can be used for verification of existing and developing theoretical codes as well as giving an understanding of the flow interactions associated with propeller/nacelle/wing integration. The investigation was conducted over a Mach number range of 0.5 to 0.8 and at angles of attack from 0 deg to 3 deg. The propeller was powered by an air turbine simulator and the exhaust from the air turbine was used to simulate the exhaust from the propfan nacelle. Reynolds number based on wing chord varied from 3 to 4 million. Results indicate that the propfan causes an increase in the wing lift coefficient. It was found that most of the propeller induced swirl is recovered by the wing. The propeller slipstream also causes a large favorable leading edge suction peak on the upwash side and a smaller unfavorable decrease on the downwash side.

Effects of side chains in helix nucleation differ from helix propagation

PubMed Central

Miller, Stephen E.; Watkins, Andrew M.; Kallenbach, Neville R.; Arora, Paramjit S.

2014-01-01

Helix–coil transition theory connects observable properties of the α-helix to an ensemble of microstates and provides a foundation for analyzing secondary structure formation in proteins. Classical models account for cooperative helix formation in terms of an energetically demanding nucleation event (described by the σ constant) followed by a more facile propagation reaction, with corresponding s constants that are sequence dependent. Extensive studies of folding and unfolding in model peptides have led to the determination of the propagation constants for amino acids. However, the role of individual side chains in helix nucleation has not been separately accessible, so the σ constant is treated as independent of sequence. We describe here a synthetic model that allows the assessment of the role of individual amino acids in helix nucleation. Studies with this model lead to the surprising conclusion that widely accepted scales of helical propensity are not predictive of helix nucleation. Residues known to be helix stabilizers or breakers in propagation have only a tenuous relationship to residues that favor or disfavor helix nucleation. PMID:24753597

The Value of Grenz-Ray Therapy for Acne Vulgaris

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

de Groot, W. P.; Prakken, J. R.; Verbeek, Ann M. J. A.

1963-01-01

In view of recent efforts to eliminate the use of radiotherapy for benign conditions or conditions treatable by other means, to avoid the possible detrimental effects of radiation, an evaluation of this treatment of acne was made. In a controlled, double-blind study in 40 patients, one area of skin received 1800 r (in thrice weekly 100-r doses) of 10-kv x irradiation. Comparable areas of skin were shamirradiated with the x-ray apparatus shielded by lead. In no case had the acne cleared up on the irradiated side. ln about half of the cases no difference was seen between the two areas.more » The remaining showed a systematic difference in favor of the treated side 2-6 weeks after treatment. However, in the majority of cases no improvement attributable to grenz-ray irradiation could be ascertained. It is concluded that grenz-ray therapy of acne, at least at the dosage used, is ineffective. At these doses, inhibition of sebaceous gland secretion would not be expected to occur. Severe erythema followed by peeling was not seen in these patients.« less

Less power or powerless? Egocentric empathy gaps and the irony of having little versus no power in social decision making.

PubMed

Handgraaf, Michel J J; Van Dijk, Eric; Vermunt, Riël C; Wilke, Henk A M; De Dreu, Carsten K W

2008-11-01

The authors investigate the effect of power differences and associated expectations in social decision making. Using a modified ultimatum game, the authors show that allocators lower their offers to recipients when the power difference shifts in favor of the allocator. Remarkably, however, when recipients are completely powerless, offers increase. This effect is mediated by a change in framing of the situation: When the opponent is without power, feelings of social responsibility are evoked. On the recipient side, the authors show that recipients do not anticipate these higher outcomes resulting from powerlessness. They prefer more power over less, expecting higher outcomes when they are more powerful, especially when less power entails powerlessness. Results are discussed in relation to empathy gaps and social responsibility. (c) 2008 APA, all rights reserved.

Toward a redefinition and contextualization of the abortion issue.

PubMed

Hartman, A

1991-11-01

The current condition of the abortion issue is that of an ideological stalemate. Each side has retreated to defend positions that will tolerate compromise of consideration of the other's viewpoint. The result is that both sides fail to see the implications of their views. 1 reason for this current state of affairs is the effect of Roe v Wade. The decision is based in privacy rights, rather than bodily integrity, which means that women are to be left alone when it comes to abortion. This can be seen with the Harris v McRae decision which ended federal funding for abortion services and the Rust v Sullivan decision which further limited doctors to counsel, inform, or refer women about abortion if they take federal money. Both sides of the issue defended absolute, immutable rights which do not leave room for personal, civic, and collective responsibility. Both sides have inconsistencies: the pro-choice side does not recognize that while abortion as a backup to birth control is okay, abortion as a primary means of birth control is not. Yet this is the case in many countries today. The pro-life side maintains that the fetus has the right to be born, yet the conservative administration and its supporters do not want to pay for social and health programs that will give these fetuses a descent quality of life. If they care so much for life, how can they stand by while 20% of children live in poverty? The pro-life side continues to ignore that fact that the majority of Americans support the right to chose. The pro-choice side continues to ignore the fact that 40% of those that favor choice, also feel that abortion is immoral. The final result of these arguments about right, is that they do not exist in the context of the real world. They are formed without looking at the social, economic, and personal contexts in which abortion occurs. The right to abortion should not stand alone, it should be a fail safe combined with family planning education and universal contraception.

Bitemporal Versus High-Dose Unilateral Twice-Weekly Electroconvulsive Therapy for Depression (EFFECT-Dep): A Pragmatic, Randomized, Non-Inferiority Trial.

PubMed

Semkovska, Maria; Landau, Sabine; Dunne, Ross; Kolshus, Erik; Kavanagh, Adam; Jelovac, Ana; Noone, Martha; Carton, Mary; Lambe, Sinead; McHugh, Caroline; McLoughlin, Declan M

2016-04-01

ECT is the most effective treatment for severe depression. Previous efficacy studies, using thrice-weekly brief-pulse ECT, reported that high-dose (6× seizure threshold) right unilateral ECT is similar to bitemporal ECT but may have fewer cognitive side effects. The authors aimed to assess the effectiveness and cognitive side effects of twice-weekly moderate-dose (1.5× seizure threshold) bitemporal ECT with high-dose unilateral ECT in real-world practice. This was a pragmatic, patient- and rater-blinded, noninferiority trial of patients with major depression (N=138; 63% female; age=56.7 years [SD=14.8]) in a national ECT service with a 6-month follow-up. Participants were independently randomly assigned to bitemporal or high-dose unilateral ECT. The primary outcome was change in the 24-item Hamilton Depression Rating Scale (HAM-D) score after the ECT course; the prespecified noninferiority margin was 4.0 points. Secondary outcomes included response and remission rates, relapse status after 6 months, and cognition. Of the eligible patients, 69 were assigned to bitemporal ECT and 69 to unilateral ECT. High-dose unilateral ECT was noninferior to bitemporal ECT regarding the 24-item HAM-D scores after the ECT course (mean difference=1.08 points in favor of unilateral ECT [95% CI=-1.67 to 3.84]). There were no significant differences for response and remission or 6-month relapse status. Recovery of orientation was quicker following unilateral ECT (median=19.1 minutes versus 26.4 minutes). Bitemporal ECT was associated with a lower percent recall of autobiographical information (odds ratio=0.66) that persisted for 6 months. Twice-weekly high-dose unilateral ECT is not inferior to bitemporal ECT for depression and may be preferable because of its better cognitive side-effect profile.

Luliconazole for the treatment of fungal infections: an evidence-based review

PubMed Central

Khanna, Deepshikha; Bharti, Subhash

2014-01-01

Luliconazole is an imidazole antifungal agent with a unique structure, as the imidazole moiety is incorporated into the ketene dithioacetate structure. Luliconazole is the R-enantiomer, and has more potent antifungal activity than lanoconazole, which is a racemic mixture. In this review, we summarize the in vitro data, animal studies, and clinical trial data relating to the use of topical luliconazole. Preclinical studies have demonstrated excellent activity against dermatophytes. Further, in vitro/in vivo studies have also shown favorable activity against Candida albicans, Malassezia spp., and Aspergillus fumigatus. Luliconazole, although belonging to the azole group, has strong fungicidal activity against Trichophyton spp., similar to that of terbinafine. The strong clinical antifungal activity of luliconazole is possibly attributable to a combination of strong in vitro antifungal activity and favorable pharmacokinetic properties in the skin. Clinical trials have demonstrated its superiority over placebo in dermatophytosis, and its antifungal activity to be at par or even better than that of terbinafine. Application of luliconazole 1% cream once daily is effective even in short-term use (one week for tinea corporis/cruris and 2 weeks for tinea pedis). A Phase I/IIa study has shown excellent local tolerability and a lack of systemic side effects with use of topical luliconazole solution for onychomycosis. Further studies to evaluate its efficacy in onychomycosis are underway. Luliconazole 1% cream was approved in Japan in 2005 for the treatment of tinea infections. It has recently been approved by US Food and Drug Administration for the treatment of interdigital tinea pedis, tinea cruris, and tinea corporis. Topical luliconazole has a favorable safety profile, with only mild application site reactions reported occasionally. PMID:25285056

Complementary Kinesiology: Why It Is Not Wise to Choose Sides or Work Alone

ERIC Educational Resources Information Center

Kretchmar, Scott

2014-01-01

In this essay I argue in favor of a holistic vision for our field under the heading of complementary kinesiology. I argue that battles over reified dichotomies and even compromise solutions have impeded our progress as a profession. I describe the theory of complementation as an alternative. I say it is a strange and paradoxical way of…

School Quality and Social Stratification: The Determinants and Consequences of Parental School Choice.

ERIC Educational Resources Information Center

Glazerman, Steven M.

Those who favor expansion of consumer choice in education claim that competition would force schools to improve. Critics claim that it would sort students by race and class. A competitive market will provide what consumers demand, yet neither side has empirical evidence on such consumer preferences to back up their claims. This paper offers such…

Reading Habits, Perceptual Learning, and Recognition of Printed Words

ERIC Educational Resources Information Center

Nazir, Tatjana A.; Ben-Boutayab, Nadia; Decoppet, Nathalie; Deutsch, Avital; Frost, Ram

2004-01-01

The present work aims at demonstrating that visual training associated with the act of reading modifies the way we perceive printed words. As reading does not train all parts of the retina in the same way but favors regions on the side in the direction of scanning, visual word recognition should be better at retinal locations that are frequently…

Time-Dependent Solid State Polymorphism of a Series of Donor-Acceptor Dyads

PubMed Central

Peebles, Cameron; Alvey, Paul M.; Lynch, Vincent; Iverson, Brent L.

2014-01-01

In order to exploit the use of favorable electrostatic interactions between aromatic units in directing the assembly of donor-acceptor (D-A) dyads, the present work examines the ability of conjugated aromatic D-A dyads with symmetric side chains to exhibit solid-state polymorphism as a function of time during the solid formation process. Four such dyads were synthesized and their packing in the solid-state from either slower (10-20 days) or faster (1-2 days) evaporation from solvent was investigated using single crystal X-ray analysis and powder X-ray diffraction. Two of the dyads exhibited tail-to-tail (A-A) packing upon slower evaporation from solvent and head-to-tail (D-A) packing upon faster evaporation from solvent. A combination of single crystal analysis and XRD patterns were used to create models wherein a packing model for the other two dyads is proposed. Our findings suggest that while side chain interactions in asymmetric aromatic dyads can play an important role in enforcing segregated D-A dyad assembly, slowly evaporating symmetrically substituted aromatic dyads allows for favorable electrostatic interactions between the aromatic moieties to facilitate the organization of the dyads in the solid-state. PMID:24678269

Effect of long-term impact-loading on mass, size, and estimated strength of humerus and radius of female racquet-sports players: a peripheral quantitative computed tomography study between young and old starters and controls.

PubMed

Kontulainen, Saija; Sievänen, Harri; Kannus, Pekka; Pasanen, Matti; Vuori, Ilkka

2002-12-01

Bone characteristics of the humeral shaft and distal radius were measured from 64 female tennis and squash players and their 27 age-, height-, and weight-matched controls with peripheral quantitative tomography (pQCT) and DXA. The players were divided into two groups according to the starting age of their tennis or squash training (either before or after menarche) to examine the possible differences in the loading-induced changes in bone structure and volumetric density. The used pQCT variables were bone mineral content (BMC), total cross-sectional area (TotA) of bone, cross-sectional area of the marrow cavity (CavA) and that of the cortical bone (CoA), cortical wall thickness (CWT), volumetric density of the cortical bone (CoD) and trabecular bone (TrD), and torsional bone strength index (BSIt) for the shaft, and compressional bone strength index (BSIc) for the bone end. These bone strength indices were compared with the DXA-derived areal bone mineral density (aBMD) to assess how well the latter represents the effect of mechanical loading on apparent bone strength. At the humeral shaft, the loaded arm's greater BMC (an average 19% side-to-side difference in young starters and 9% in old starters) was caused by an enlarged cortex (CoA; side-to-side differences 20% and 9%, respectively). The loaded humerus seemed to have grown periosteally (the CavA did not differ between the sites) leading to 26% and 11% side-to-side BSIt difference in the young and old starters, respectively. CoD was equal between the arms (-1% difference in both player groups). The side-to-side differences in the young starters' BMC, CoA, TotA, CWT, and BSIt were 8-22% higher than those of the controls and 8-14% higher than those of the old starters. Old starters' BMC, CoA, and BSIt side-to-side differences were 6-7% greater than those in the controls. The DXA-derived side-to-side aBMD difference was 7% greater in young starters compared with that of the old starters and 14% compared with that in controls, whereas the difference between old starters and controls was 6%, in favor of the former. All these between-group differences were statistically significant. At the distal radius, the player groups differed significantly from controls in the side-to-side BMC, TrD, and aBMD differences only; the young starters' BMC difference was 9% greater, TrD and aBMD differences were 5% greater than those in the controls, and the old starters' TrD and aBMD differences were both 7% greater than those in the controls. In summary, in both of the female player groups the structural adaptation of the humeral shaft to long-term loading seemed to be achievedthrough periosteal enlargement of the bone cortex although this adaptation was clearly better in the young starters. Exercise-induced cortical enlargement was not so clear at the distal radius (a trabecular bone site), and the study suggested that at long bone ends also the TrD could be a modifiable factor to build a stronger bone structure. The conventional DXA-based aBMD measurement detected the intergroup differences in the exercise-induced bone gains, although, measuring two dimensions of bone only, it seemed to underestimate the effect of exercise on the apparent bone strength, especially if the playing had been started during the growing years.

Enhanced Broadband Electromagnetic Absorption in Silicon Film with Photonic Crystal Surface and Random Gold Grooves Reflector

PubMed Central

Chen, Zhi-Hui; Qiao, Na; Yang, Yibiao; Ye, Han; Liu, Shaoding; Wang, Wenjie; Wang, Yuncai

2015-01-01

We show a hybrid structure consisting of Si film with photonic crystal surface and random triangular gold grooves reflector at the bottom, which is capable of realizing efficient, broad-band, wide-angle optical absorption. It is numerically demonstrated that the enhanced absorption in a broad wavelength range (0.3–9.9 μm) due to the scattering effect of both sides of the structure and the created resonance modes. Larger thickness and period are favored to enhance the absorption in broader wavelength range. Substantial electric field concentrates in the grooves of surface photonic crystal and in the Si film. Our structure is versatile for solar cells, broadband photodetection and stealth coating. PMID:26238270

Brief Report: Informing Strategies to Build PrEP Capacity Among San Francisco Bay Area Clinicians.

PubMed

Bacon, Oliver; Gonzalez, Rafael; Andrew, Erin; Potter, Michael B; Iñiguez, James R; Cohen, Stephanie E; Liu, Albert Y; Fuchs, Jonathan D

2017-02-01

A large pool of clinicians are needed to meet the growing demand for HIV preexposure prophylaxis. We surveyed a mixed group of HIV specialists and nonspecialists in the San Francisco Bay Area to determine their attitudes toward and training needs regarding prescribing preexposure prophylaxis to persons at increased risk of HIV infection. Willingness to prescribe was associated with experience in caring for HIV-infected patients (adjusted odds ratio 4.76, 95% confidence interval: 1.43 to 15.76, P = 0.01). Desire for further training was associated with concerns about drug resistance (P = 0.04) and side effects (P = 0.04) and was more common among noninfectious disease specialists. Clinicians favored online and in-person training methods.

Colloidal micelles of block copolymers as nanoreactors, templates for gold nanoparticles, and vehicles for biomedical applications.

PubMed

Bakshi, Mandeep Singh

2014-11-01

Target drug delivery methodology is becoming increasingly important to overcome the shortcomings of conventional drug delivery absorption method. It improves the action time with uniform distribution and poses minimum side effects, but is usually difficult to design to achieve the desire results. Economically favorable, environment friendly, multifunctional, and easy to design, hybrid nanomaterials have demonstrated their enormous potential as target drug delivery vehicles. A combination of both micelles and nanoparticles makes them fine target delivery vehicles in a variety of biological applications where precision is primarily required to achieve the desired results as in the case of cytotoxicity of cancer cells, chemotherapy, and computed tomography guided radiation therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Deep Inspiration Breath Hold: Techniques and Advantages for Cardiac Sparing During Breast Cancer Irradiation.

PubMed

Bergom, Carmen; Currey, Adam; Desai, Nina; Tai, An; Strauss, Jonathan B

2018-01-01

Historically, heart dose from left-sided breast radiotherapy has been associated with a risk of cardiac injury. Data suggests that there is not a threshold for the deleterious effects from radiation on the heart. Over the past several years, advances in radiation delivery techniques have reduced cardiac morbidity due to treatment. Deep inspiration breath hold (DIBH) is a technique that takes advantage of a more favorable position of the heart during inspiration to minimize heart doses over a course of radiation therapy. In the accompanying review article, we outline several methods used to deliver treatment with DIBH, quantify the benefits of DIBH treatment, discuss considerations for patient selection, and identify challenges associated with DIBH techniques.

Successful Treatment with Alectinib for Choroidal Metastasis in Anaplastic Lymphoma Kinase Rearranged Non-small Cell Lung Cancer.

PubMed

Funazo, Tomoko; Morita, Kyohei; Ikegami, Naoya; Konishi, Chisato; Nakao, Satoshi; Ariyasu, Ryo; Taki, Masato; Nakagawa, Kazuhiko; Hwang, Moon Hee; Yoshimura, Chie; Wakayama, Toshiaki; Nishizaka, Yasuo

2017-09-01

Choroidal metastasis is rare in cancer patients and it may cause visual disturbances that reduce their quality of life. In non-small cell lung cancer (NSCLC), targeted therapy against actionable driver mutations has gradually replaced radiotherapy as the treatment of choice for choroidal metastasis. Recently, there have been several case reports of choroidal metastasis in patients with anaplastic lymphoma kinase (ALK)-rearranged NSCLC. We herein report the case of a 40-year-old Japanese woman diagnosed with choroidal metastasis of an ALK-rearranged NSCLC who received alectinib as the first-line chemotherapy. Alectinib may be the best treatment for choroidal metastasis in patients harboring an ALK translocation because of its favorable side effect profile involving visual disturbances.

Treatment of anorexia nervosa with long-term risperidone in an outpatient setting: case study.

PubMed

Kracke, Elsa J; Tosh, Aneesh K

2014-01-01

There are currently few studies focusing on the efficacy of long-term atypical antipsychotics to treat anorexia nervosa in the pediatric population. This case report follows the treatment of a 17 year-old female with anorexia nervosa over her four-year undergraduate career. After two years of multidisciplinary treatment, low-dose risperidone was initiated due to persistence of her disease. She expressed decreased rigidity around meal times, her weight improved and she had resumption of menses. She was compliant with treatment through graduation and maintained her weight gain. Atypical antipsychotics are a treatment option in the management of anorexia nervosa. Risperidone has not been studied as frequently as olanzapine for eating disorders. Risperidone was chosen for its more favorable side effect profile and decreased cost to the patient. Previous studies on anorexia nervosa treatment have occurred during inpatient treatment and have limited follow-up due to patients' refusal to initiate or maintain medication compliance. This case presents 17 months of outpatient data. The efficacy of risperidone therapy was evaluated with frequent weight checks, subjective decrease in rigidity, serial complete metabolic panels, and restoration of menses. In this case report, an adolescent female treated with low-dose risperidone had decreased rigid thinking, weight gain and resolution of secondary amenorrhea without medication side effects. Therefore, the atypical antipsychotic risperidone may be an effective long-term outpatient treatment option for patients with anorexia nervosa.

Psychosexual well-being in women using oral contraceptives containing drospirenone.

PubMed

Nappi, Rossella E; Albani, Francesca; Tonani, Silvia; Santamaria, Valentina; Pisani, Carla; Terreno, Erica; Martini, Ellis; Polatti, Franco

2009-01-01

Considerable advances have been made in hormonal contraception in recent years, geared at maximizing compliance and minimizing discontinuation. In oral contraceptive (OC) formulations, the estrogenic component, generally ethinyl estradiol (EE), has been reduced significantly and newer progestins like dienogest and drospirenone (DRSP), compounds with different molecular structures, have been introduced; in addition, new regimens (extended, flexible, 24/4 formats instead of the standard 21/7 format) and innovative delivery systems (vaginal rings, transdermal patches, subcutaneous implants and intrauterine devices) are available. The multitude of choices allows hormonal contraception to be tailored to the individual woman in order to obtain non-contraceptive benefits, without significant side effects, and also a favorable risk/benefit profile for her general and reproductive health. Over the past few years, new OC formulations combining DRSP (3 mg), a unique progestin with both antimineralocorticoid and antiandrogenic activities, with estrogen (30 mcg or 20 mcg EE), in two regimens (24/4 and 21/7) of active pills in a 28-day cycle, have shown positive effects on water retention-related weight gain and physical, emotional and psychosexual well-being. It seems likely that the use of a low-dose, well-balanced OC and the shorter 4-day hormone-free interval may minimize the side effects that can impair quality of life and thus increase women's compliance with hormonal contraception therapy.

Development and Usability Testing of a Web-based Self-management Intervention for Oral Cancer Survivors and their Family Caregivers

PubMed Central

Badr, Hoda; Lipnick, Daniella; Diefenbach, Michael A; Posner, Marshall; Kotz, Tamar; Miles, Brett; Genden, Eric

2016-01-01

Oral cancer (OC) survivors experience debilitating side effects that affect their quality of life (QOL) and that of their caregivers. This study aimed to develop and evaluate a dyadic, web-based intervention to improve survivor self-management and survivor/caregiver QOL. A qualitative needs assessment (semi-structured interviews) with 13 OC survivors and 12 caregivers was conducted to discern information and support needs as well as preferences regarding website features and tools. Results using Grounded Theory analysis showed that OC survivors and caregivers: 1) want and need practical advice about managing side effects; 2) want to reach out to other survivors/caregivers for information and support; and, 3) have both overlapping and unique needs and preferences regarding website features. Usability testing (N=6 survivors; 5 caregivers) uncovered problems with the intuitiveness, navigation, and design of the website that were subsequently addressed. Users rated the website favorably on the dimensions of attractiveness, controllability, efficiency, intuitiveness, and learnability, and gave it a total usability score of 80/100. Overall, this study demonstrates that OC survivors and caregivers are interested in using an online program to improve QOL, and that providing tailored website content and features based on the person’s role as survivor or caregiver is important in this population. PMID:26507369

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.

Efficacy of Acupuncture versus Combined Oral Contraceptive Pill in Treatment of Moderate-to-Severe Dysmenorrhea: A Randomized Controlled Trial

PubMed Central

Sriprasert, Intira; Suerungruang, Suparerk; Athilarp, Porntip; Matanasarawoot, Anuchart

2015-01-01

This open-label randomized controlled trial was designed to compare the efficacy of acupuncture and combined oral contraceptive (COC) pill in treating moderate-to-severe primary dysmenorrhea. Fifty-two participants were randomly assigned to receive either acupuncture (n = 27) or COC (n = 25) for three menstrual cycles. Mefenamic acid was prescribed as a recue analgesic drug with both groups. The statistical approach used for efficacy and safety assessments was intention-to-treat analysis. By the end of the study, both treatments had resulted in significant improvement over baselines in all outcomes, that is, maximal dysmenorrhea pain scores, days suffering from dysmenorrhea, amount of rescue analgesic used, and quality of life assessed by SF-36 questionnaire. Over the three treatment cycles, COC caused greater reduction in maximal pain scores than acupuncture, while improvements in the remaining outcomes were comparable. Responders were defined as participants whose maximal dysmenorrhea pain scores decreased at least 33% below their baseline. Response rates following both interventions at the end of the study were not statistically different. Acupuncture commonly caused minimal local side effects but did not cause any hormone-related side effects as did COC. In conclusion, acupuncture is an alternative option for relieving dysmenorrhea, especially when COC is not a favorable choice. PMID:26346199

Simultaneous double-rod rotation technique in posterior instrumentation surgery for correction of adolescent idiopathic scoliosis.

PubMed

Ito, Manabu; Abumi, Kuniyoshi; Kotani, Yoshihisa; Takahata, Masahiko; Sudo, Hideki; Hojo, Yoshihiro; Minami, Akio

2010-03-01

The authors present a new posterior correction technique consisting of simultaneous double-rod rotation using 2 contoured rods and polyaxial pedicle screws with or without Nesplon tapes. The purpose of this study is to introduce the basic principles and surgical procedures of this new posterior surgery for correction of adolescent idiopathic scoliosis. Through gradual rotation of the concave-side rod by 2 rod holders, the convex-side rod simultaneously rotates with the the concave-side rod. This procedure does not involve any force pushing down the spinal column around the apex. Since this procedure consists of upward pushing and lateral translation of the spinal column with simultaneous double-rod rotation maneuvers, it is simple and can obtain thoracic kyphosis as well as favorable scoliosis correction. This technique is applicable not only to a thoracic single curve but also to double major curves in cases of adolescent idiopathic scoliosis.

A dynamic analysis of rotary combustion engine seals

NASA Technical Reports Server (NTRS)

Knoll, J.; Vilmann, C. R.; Schock, H. J.; Stumpf, R. P.

1984-01-01

Real time work cell pressures are incorporated into a dynamic analysis of the gas sealing grid in Rotary Combustion Engines. The analysis which utilizes only first principal concepts accounts for apex seal separation from the crochoidal bore, apex seal shifting between the sides of its restraining channel, and apex seal rotation within the restraining channel. The results predict that apex seals do separate from the trochoidal bore and shift between the sides of their channels. The results also show that these two motions are regularly initiated by a seal rotation. The predicted motion of the apex seals compares favorably with experimental results. Frictional losses associated with the sealing grid are also calculated and compare well with measurements obtained in a similar engine. A comparison of frictional losses when using steel and carbon apex seals has also been made as well as friction losses for single and dual side sealing.

Meditope-Fab interaction: threading the hole.

PubMed

Bzymek, Krzysztof P; Ma, Yuelong; Avery, Kendra N; Horne, David A; Williams, John C

2017-12-01

Meditope, a cyclic 12-residue peptide, binds to a unique binding side between the light and heavy chains of the cetuximab Fab. In an effort to improve the affinity of the interaction, it was sought to extend the side chain of Arg8 in the meditope, a residue that is accessible from the other side of the meditope binding site, in order to increase the number of interactions. These modifications included an n-butyl and n-octyl extension as well as hydroxyl, amine and carboxyl substitutions. The atomic structures of the complexes and the binding kinetics for each modified meditope indicated that each extension threaded through the Fab `hole' and that the carboxyethylarginine substitution makes a favorable interaction with the Fab, increasing the half-life of the complex by threefold compared with the unmodified meditope. Taken together, these studies provide a basis for the design of additional modifications to enhance the overall affinity of this unique interaction.

"Tell me, how bright your hypomania is, and I tell you, if you are happily in love!"--among young adults in love, bright side hypomania is related to reduced depression and anxiety, and better sleep quality.

PubMed

Brand, Serge; Foell, Stephan; Bajoghli, Hafez; Keshavarzi, Zahra; Kalak, Nadeem; Gerber, Markus; Schmidt, Norman B; Norton, Peter J; Holsboer-Trachsler, Edith

2015-03-01

Studies on adolescents and adults show that romantic love (RL) is associated with favorable emotional states. However, data on these associations are scarce for adults. The aim of the present study was, therefore, to explore the associations between RL, symptoms of depression, anxiety, hypomania (bright side and dark side), and sleep in a sample of adults. A total of 844 participants currently in love (M = 24.79 years, 75.8% females) took part in the study. They completed a series of questionnaires related to RL, symptoms of depression, anxiety, hypomania (bright side and dark side), and sleep. An increased state of RL was associated both with the bright and the dark side of hypomania (BRHYP and DAHYP). Relative to participants with BRHYP, participants with DAHYP reported stronger symptoms of depression and state anxiety, and poor sleep quality. The pattern of results adds to our knowledge that in adults RL is not entirely a joyful and happy period of life. Rather, data suggest that for young adults in love, bright versus dark side of hypomania was associated with a different quality of psychological functioning and sleep. We conclude that experiencing RL might be a critical life event associated with symptoms of depression and anxiety, and poor sleep.

Principal Eigenvalue Minimization for an Elliptic Problem with Indefinite Weight and Robin Boundary Conditions

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

Hintermueller, M., E-mail: hint@math.hu-berlin.de; Kao, C.-Y., E-mail: Ckao@claremontmckenna.edu; Laurain, A., E-mail: laurain@math.hu-berlin.de

2012-02-15

This paper focuses on the study of a linear eigenvalue problem with indefinite weight and Robin type boundary conditions. We investigate the minimization of the positive principal eigenvalue under the constraint that the absolute value of the weight is bounded and the total weight is a fixed negative constant. Biologically, this minimization problem is motivated by the question of determining the optimal spatial arrangement of favorable and unfavorable regions for a species to survive. For rectangular domains with Neumann boundary condition, it is known that there exists a threshold value such that if the total weight is below this thresholdmore » value then the optimal favorable region is like a section of a disk at one of the four corners; otherwise, the optimal favorable region is a strip attached to the shorter side of the rectangle. Here, we investigate the same problem with mixed Robin-Neumann type boundary conditions and study how this boundary condition affects the optimal spatial arrangement.« less

Chronic cannabinoid receptor 2 activation reverses paclitaxel neuropathy without tolerance or cannabinoid receptor 1-dependent withdrawal.

PubMed

Deng, Liting; Guindon, Josée; Cornett, Benjamin L; Makriyannis, Alexandros; Mackie, Ken; Hohmann, Andrea G

2015-03-01

Mixed cannabinoid receptor 1 and 2 (CB1 and CB2) agonists such as Δ(9)-tetrahydrocannabinol (Δ(9)-THC) can produce tolerance, physical withdrawal, and unwanted CB1-mediated central nervous system side effects. Whether repeated systemic administration of a CB2-preferring agonist engages CB1 receptors or produces CB1-mediated side effects is unknown. We evaluated antiallodynic efficacy, possible tolerance, and cannabimimetic side effects of repeated dosing with a CB2-preferring agonist AM1710 in a model of chemotherapy-induced neuropathy produced by paclitaxel using CB1 knockout (CB1KO), CB2 knockout (CB2KO), and wild-type (WT) mice. Comparisons were made with the prototypic classic cannabinoid Δ(9)-THC. We also explored the site and possible mechanism of action of AM1710. Paclitaxel-induced mechanical and cold allodynia developed to an equivalent degree in CB1KO, CB2KO, and WT mice. Both AM1710 and Δ(9)-THC suppressed established paclitaxel-induced allodynia in WT mice. In contrast to Δ(9)-THC, chronic administration of AM1710 did not engage CB1 activity or produce antinociceptive tolerance, CB1-mediated cannabinoid withdrawal, hypothermia, or motor dysfunction. Antiallodynic efficacy of systemic administration of AM1710 was absent in CB2KO mice and WT mice receiving the CB2 antagonist AM630, administered either systemically or intrathecally. Intrathecal administration of AM1710 also attenuated paclitaxel-induced allodynia in WT mice, but not CB2KO mice, implicating a possible role for spinal CB2 receptors in AM1710 antiallodynic efficacy. Finally, both acute and chronic administration of AM1710 decreased messenger RNA levels of tumor necrosis factor-α and monocyte chemoattractant protein 1 in lumbar spinal cord of paclitaxel-treated WT mice. Our results highlight the potential of prolonged use of CB2 agonists for managing chemotherapy-induced allodynia with a favorable therapeutic ratio marked by sustained efficacy and absence of tolerance, physical withdrawal, or CB1-mediated side effects. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Monopolar radiofrequency facial tightening: a retrospective analysis of efficacy and safety in over 600 treatments.

PubMed

Weiss, Robert A; Weiss, Margaret A; Munavalli, Girish; Beasley, Karen L

2006-09-01

Monopolar radiofrequency skin heating coupled with cryogen cooling of facial skin for skin tightening has been utilized on over 10,000 patients since 2002. In order to establish the actual rate and degree of side effects in our clinical experience, a retrospective chart review was performed. Charts and clinical images of over 600 consecutive patient treatments between May 2002 and June 2006 using a monopolar radiofrequency device (Thermacool, Thermage, Haywood, CA) for skin tightening at the Maryland Laser, Skin and Vein Institute were retrospectively reviewed. The primary presentation for treatment was skin laxity of the lower face. Treatment was delivered with a 1-cm2 standard tip at fluences of 81 to 124 J/cm2 (level of 12.5 to 15), a 1-cm2 "fast" tip at fluences of 62 to 109 J/cm2 (level of 72.0 to 76.0), a 1.5-cm2 "big fast" tip at fluences of 75 to 130 J/cm2 (level of 61.5 to 65), and a 3-cm2 "bigger" tip at equivalent fluences as each became available. As treatment algorithms evolved over 4 years, the algorithm of multiple passes at lower fluence associated with better clinical outcomes and greater patient acceptance has been adopted. The most common immediate and expected clinical effects were erythema and edema lasting less than 24 hours, although 6 patients reported edema lasting for up to 1 week. There were no permanent side effects. In total, 2.7% of treatments resulted in temporary side effects, the most significant of which was a slight depression on the cheek (n = 1), which completely resolved within 3.5 months. Other side effects included localized areas of acneiform subcutaneous erythematous papules (n = 4) and a linear superficial crust (n = 1) with the original tip, all of which resolved within 1 week. One patient reported small erythematous subcutaneous nodules resolving in 17 days. Tenderness of the neck lasting from 2 weeks (n = 2) to 3 weeks (n = 1) was also reported. Our data, obtained in an office setting without injectable anesthetic or i.v. sedation, indicate that monopolar RF for skin tightening is a very safe procedure. The treatment algorithm and tips have evolved over several years leading to increased safety and efficacy. Side effects are infrequent, self-limited, and minor, comparing favorably to other nonablative devices utilized for facial rejuvenation.

Treatment of chronically depressed patients: A multisite randomized controlled trial testing the effectiveness of 'Cognitive Behavioral Analysis System of Psychotherapy' (CBASP) for chronic depressions versus usual secondary care

PubMed Central

Wiersma, Jenneke E; van Schaik, Digna JF; van Oppen, Patricia; McCullough, James P; Schoevers, Robert A; Dekker, Jack J; Blom, Marc BJ; Maas, Kristel; Smit, Johannes H; Penninx, Brenda WJH; Beekman, Aartjan TF

2008-01-01

Background 'Cognitive Behavioral Analysis System of Psychotherapy' (CBASP) is a form of psychotherapy specifically developed for patients with chronic depression. In a study in the U.S., remarkable favorable effects of CBASP have been demonstrated. However, no other studies have as yet replicated these findings and CBASP has not been tested outside the United States. This protocol describes a randomized controlled trial on the effectiveness of CBASP in the Netherlands. Methods/Design The purpose of the present paper is to report the study protocol of a multisite randomized controlled trial testing the effectiveness of 'Cognitive Behavioral Analysis System of Psychotherapy' (CBASP) for chronic depression in the Netherlands. In this study, CBASP in combination with medication, will be tested versus usual secondary care in combination with medication. The aim is to recruit 160 patients from three mental health care organizations. Depressive symptoms will be assessed at baseline, after 8 weeks, 16 weeks, 32 weeks and 52 weeks, using the 28-item Inventory for Depressive Symptomatology (IDS). Effect modification by co morbid anxiety, alcohol consumption, general and social functioning and working alliance will be tested. GEE analyses of covariance, controlling for baseline value and center will be used to estimate the overall treatment effectiveness (difference in IDS score) at post-treatment and follow up. The primary analysis will be by 'intention to treat' using double sided tests. An economic analysis will compare the two groups in terms of mean costs and cost-effectiveness from a societal perspective. Discussion The study will provide an answer to the question whether the favorable effects of CBASP can be replicated outside the US. Trial Registration The Dutch Cochrane Center, NTR1090. PMID:18366729

Reduction of Unsteady Forcing in a Vaned, Contra-Rotating Transonic Turbine Configuration

NASA Technical Reports Server (NTRS)

Clark, John

2010-01-01

HPT blade unsteadiness in the presence of a downstream vane consistent with contra-rotation is characterized by strong interaction at the first harmonic of downstream vane passing. E An existing stage-and-one-half transonic turbine rig design was used as a baseline to investigate means of reducing such a blade-vane interaction. E Methods assessed included: Aerodynamic shaping of HPT blades 3D stacking of the downstream vane Steady pressure-side blowing E Of the methods assessed, a combination of vane bowing and steady pressure-side blowing produced the most favorable result. E Transonic turbine experiments are planned to assess predictive accuracy for the baseline turbine and any design improvements.

Microphase separation of comb copolymers with two different lengths of side chains

NASA Astrophysics Data System (ADS)

Aliev, M. A.; Kuzminyh, N. Yu.

2009-10-01

The phase behavior of the monodisperse AB comb copolymer melt contained the macromolecules of special architecture is discussed. Each macromolecule is assumed to be composed of two comb blocks which differ in numbers of side chains and numbers of monomer units in these chains. It is shown (by analysis of the structure factor of the melt) that microphase separation at two different length scales in the melt is possible. The large and small length scales correspond to separation between comb blocks and separation between monomer units in repeating fragments of blocks, respectively. The classification diagrams indicated which length scale is favored for a given parameters of chemical structure of macromolecules are constructed.

Analysis of factors affecting gas exchange in intravascular blood gas exchanger.

PubMed

Niranjan, S C; Clark, J W; San, K Y; Zwischenberger, J B; Bidani, A

1994-10-01

A mathematical model of an intravascular hollow-fiber gas-exchange device, called IVOX, has been developed using a Krogh cylinder-like approach with a repeating unit structure comprised of a single fiber with gas flowing through its lumen surrounded by a coaxial cylinder of blood flowing in the opposite direction. Species mass balances on O2 and CO2 result in a nonlinear coupled set of convective-diffusion parabolic partial differential equations that are solved numerically using an alternating-direction implicit finite-difference method. Computed results indicated the presence of a large resistance to gas transport on the external (blood) side of the hollow-fiber exchanger. Increasing gas flow through the device favored CO2 removal from but not O2 addition to blood. Increasing blood flow over the device favored both CO2 removal as well as O2 addition. The rate of CO2 removal increased linearly with the transmural PCO2 gradient imposed across the device. The effect of fiber crimping on blood phase mass transfer resistance was evaluated indirectly by varying species blood diffusivity. Computed results indicated that CO2 excretion by IVOX can be significantly enhanced with improved bulk mixing of vena caval blood around the IVOX fibers.

The Role of Grain Orientation and Grain Boundary Characteristics in the Mechanical Twinning Formation in a High Manganese Twinning-Induced Plasticity Steel

NASA Astrophysics Data System (ADS)

Shterner, Vadim; Timokhina, Ilana B.; Rollett, Anthony D.; Beladi, Hossein

2018-04-01

In the current study, the dependence of mechanical twinning on grain orientation and grain boundary characteristics was investigated using quasi in-situ tensile testing. The grains of three main orientations (i.e., <111>, <110>, and <100> parallel to the tensile axis (TA)) and certain characteristics of grain boundaries (i.e., the misorientation angle and the inclination angle between the grain boundary plane normal and the TA) were examined. Among the different orientations, <111> and <100> were the most and the least favored orientations for the formation of mechanical twins, respectively. The <110> orientation was intermediate for twinning. The annealing twin boundaries appeared to be the most favorable grain boundaries for the nucleation of mechanical twinning. No dependence was found for the inclination angle of annealing twin boundaries, but the orientation of grains on either side of the annealing twin boundary exhibited a pronounced effect on the propensity for mechanical twinning. Annealing twin boundaries adjacent to high Taylor factor grains exhibited a pronounced tendency for twinning regardless of their inclination angle. In general, grain orientation has a significant influence on twinning on a specific grain boundary.

Misperceptions About β-Blockers and Diuretics

PubMed Central

Ubel, Peter A; Jepson, Christopher; Asch, David A

2003-01-01

BACKGROUND Based on a series of clinical trials showing no difference in the effectiveness or tolerability of most major classes of antihypertensive medications, the Joint National Commission on High Blood Pressure Treatment recommends that physicians prescribe β-blockers or diuretics as initial hypertensive therapy unless there are compelling indications for another type of medication. Nevertheless, many physicians continue to favor more expensive medications like angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers as first line agents. The persistent use of these agents raises questions as to whether physicians perceive ACE inhibitors and calcium channel blockers to be better than β-blockers and diuretics. METHODS We surveyed 1,200 primary care physicians in 1997, and another 500 primary care physicians in 2000, and asked them to estimate the relative effectiveness and side effects of 4 classes of medication in treating a hypothetical patient with uncomplicated hypertension: ACE inhibitors, β-blockers, calcium channel blockers, and diuretics. In addition, we asked them to indicate whether they ever provided free samples of hypertension medications to their patients. RESULTS Perceptions of the relative effectiveness and side effects of the 4 classes of hypertension medications did not significantly change over the 3 years, nor did prescription recommendations. Physicians perceive that diuretics are less effective at lowering blood pressure than the other 3 classes (P < .001). They also perceive that β-blockers are less tolerated than the other 3 classes (P < .001). In a multivariate model, perceptions of effectiveness and tolerability displayed significant associations with prescription preference independent of background variables. The only other variable to contribute significantly to the model was provision of free medication samples to patients. CONCLUSIONS Despite numerous clinical trials showing no difference in the effectiveness or side-effect profiles of these 4 classes of drugs, most physicians believed that diuretics were less effective and β-blockers were less tolerated than other medications. Moreover, their prescription practices were associated with their provision of free samples provided by pharmaceutical representatives, even after adjusting for other demographic characteristics. Efforts to increase physicians' prescribing of β-blockers and diuretics may need to be directed at overcoming misunderstandings about the effectiveness and tolerability of these medicines. PMID:14687255

Misperceptions about beta-blockers and diuretics: a national survey of primary care physicians.

PubMed

Ubel, Peter A; Jepson, Christopher; Asch, David A

2003-12-01

Based on a series of clinical trials showing no difference in the effectiveness or tolerability of most major classes of antihypertensive medications, the Joint National Commission on High Blood Pressure Treatment recommends that physicians prescribe beta-blockers or diuretics as initial hypertensive therapy unless there are compelling indications for another type of medication. Nevertheless, many physicians continue to favor more expensive medications like angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers as first line agents. The persistent use of these agents raises questions as to whether physicians perceive ACE inhibitors and calcium channel blockers to be better than beta-blockers and diuretics. We surveyed 1,200 primary care physicians in 1997, and another 500 primary care physicians in 2000, and asked them to estimate the relative effectiveness and side effects of 4 classes of medication in treating a hypothetical patient with uncomplicated hypertension: ACE inhibitors, beta-blockers, calcium channel blockers, and diuretics. In addition, we asked them to indicate whether they ever provided free samples of hypertension medications to their patients. Perceptions of the relative effectiveness and side effects of the 4 classes of hypertension medications did not significantly change over the 3 years, nor did prescription recommendations. Physicians perceive that diuretics are less effective at lowering blood pressure than the other 3 classes (P <.001). They also perceive that beta-blockers are less tolerated than the other 3 classes (P <.001). In a multivariate model, perceptions of effectiveness and tolerability displayed significant associations with prescription preference independent of background variables. The only other variable to contribute significantly to the model was provision of free medication samples to patients. Despite numerous clinical trials showing no difference in the effectiveness or side-effect profiles of these 4 classes of drugs, most physicians believed that diuretics were less effective and beta-blockers were less tolerated than other medications. Moreover, their prescription practices were associated with their provision of free samples provided by pharmaceutical representatives, even after adjusting for other demographic characteristics. Efforts to increase physicians' prescribing of beta-blockers and diuretics may need to be directed at overcoming misunderstandings about the effectiveness and tolerability of these medicines.

A current perspective on cancer immune therapy: step-by-step approach to constructing the magic bullet.

PubMed

D'Errico, Gabriele; Machado, Heather L; Sainz, Bruno

2017-12-01

Immunotherapy is the new trend in cancer treatment due to the selectivity, long lasting effects, and demonstrated improved overall survival and tolerance, when compared to patients treated with conventional chemotherapy. Despite these positive results, immunotherapy is still far from becoming the perfect magic bullet to fight cancer, largely due to the facts that immunotherapy is not effective in all patients nor in all cancer types. How and when will immunotherapy overcome these hurdles? In this review we take a step back to walk side by side with the pioneers of immunotherapy in order to understand what steps need to be taken today to make immunotherapy effective across all cancers. While early scientists, such as Coley, elicited an unselective but effective response against cancer, the search for selectivity pushed immunotherapy to the side in favor of drugs focused on targeting cancer cells. Fortunately, the modern era would revive the importance of the immune system in battling cancer by releasing the brakes or checkpoints (anti-CTLA-4 and anti-PD-1/PD-L1) that have been holding the immune system at bay. However, there are still many hurdles to overcome before immunotherapy becomes a universal cancer therapy. For example, we discuss how the redundant and complex nature of the immune system can impede tumor elimination by teeter tottering between different polarization states: one eliciting anti-cancer effects while the other promoting cancer growth and invasion. In addition, we highlight the incapacity of the immune system to choose between a fight or repair action with respect to tumor growth. Finally we combine these concepts to present a new way to think about the immune system and immune tolerance, by introducing two new metaphors, the "push the accelerator" and "repair the car" metaphors, to explain the current limitations associated with cancer immunotherapy.

New therapeutic potentials of milk thistle (Silybum marianum).

PubMed

Milić, Natasa; Milosević, Natasa; Suvajdzić, Ljiljana; Zarkov, Marija; Abenavoli, Ludovico

2013-12-01

Silymarin is a bioflavonoid complex extract derived from dry seeds of Milk thistle [(Silybum marianum(L.) Gaemrnt. (Fam. Asteraceae/Compositaceae)] whose hepatoprotective effect has clinically been proved. Low toxicity, favorable pharmacokinetics, powerful antioxidant, detoxifying, preventive, protective and regenerative effects and side effects similar to placebo make silymarin extremely attractive and safe for therapeutic use. The medicinal properties of silymarin and its main component silibinin have been studied in the treatment of Alzheimer's disease, Parkinson's disease, sepsis, burns, osteoporosis, diabetes, cholestasis and hypercholesterolemia. Owing to its apoptotic effect, without cytotoxic effects, silymarin possesses potential applications in the treatment of various cancers. Silymarin is being examined as a neuro-, nephro- and cardio-protective in the damage of different etiologies due to its strong antioxidant potentials. Furthermore, it has fetoprotective (against the influence of alcohol) and prolactin effects and is safe to be used during pregnancy and lactation. Finally, the cosmetics industry is examining the antioxidant and UV-protective effects of silymarin. Further clinical studies and scientific evidence that silymarin and silibinin are effective in the therapy of various pathologies are indispensable in order to confirm their different flavonolignan pharmacological effects.

[Tricyclic antidepressant therapy in headache].

PubMed

Magyar, Máté; Csépány, Éva; Gyüre, Tamás; Bozsik, György; Bereczki, Dániel; Ertsey, Csaba

2015-12-01

The two most important representatives of the primary headaches are migraine and tension-type headache. More than 10% of the population suffer from migraine and even a greater part, approximately 30-40% from tension-type headache. These two headache types have a great effect both on the individual and on the society. There are two types of therapeutic approaches to headaches: the abortive and the prophylactic therapy. Prophylactic treatment is used for frequent and/or difficult-to-treat headache attacks. Although both migraine and tension-type headache are often associated with depression, for their treatment - in contrast to the widespread medical opinion - not all antidepressants were found to be effective. Amitriptyline, which is a tricyclic antidepressant, is used as a prophylactic therapy for headache since 1968. Its efficacy has been demonstrated in several double-blind, placebo-controlled studies. Although the newer types of antidepressant, such as selective serotonin reuptake inhibitors and selective serotonin-norepinephrine reuptake inhibitor, have a more favorable side-effect profile than tricyclic antidepressants, their headache prophylactic effect has not been proven yet.

A clinical trial of cranial electrotherapy stimulation for anxiety and comorbid depression.

PubMed

Barclay, Timothy H; Barclay, Raymond D

2014-08-01

Anxiety disorders are among the most prevalent mental disorders and are usually treated with medication and/or psychotherapy. When anxiety disorders are accompanied with comorbid depression, this further complicates the treatment process. Medication compliance is a common problem due to adverse side effects and new and effective treatments that have minimal side effects are needed for the treatment of anxiety and depression. This study used a randomized, double-blind, sham controlled design to examine the effectiveness of CES as a treatment for anxiety disorders and comorbid depression in a primary care setting. The study was registered at clinicaltrials.gov, NCT01533415. One hundred and fifteen participants, age 18 years and over, with a primary diagnosis of an anxiety disorder were enrolled from February 2012 to December 2012 The Hamilton Rating Scale for Anxiety (HAM-A) and the Hamilton Depression Rating Scale17 (HAM-D17) were used for baseline and outcome measures at weeks one, three, and five. Response to treatment was defined as a reduction of ≥50% or more on these measures. Analysis of covariance revealed a significant difference between the active CES group and the sham CES group on anxiety (p=0.001, d=0.94) and on depression (p=0.001, d=0.78) from baseline to endpoint of study in favor of the active CES group. CES significantly decreases anxiety and comorbid depression. Subjects reported no adverse events during the study. Copyright © 2014 Elsevier B.V. All rights reserved.

Factors governing the substitution of La3+ for Ca2+ and Mg2+ in metalloproteins: a DFT/CDM study.

PubMed

Dudev, Todor; Chang, Li-Ying; Lim, Carmay

2005-03-23

Trivalent lanthanide cations are extensively being used in biochemical experiments to probe various dication-binding sites in proteins; however, the factors governing the binding specificity of lanthanide cations for these binding sites remain unclear. Hence, we have performed systematic studies to evaluate the interactions between La3+ and model Ca2+ - and Mg2+ -binding sites using density functional theory combined with continuum dielectric methods. The calculations reveal the key factors and corresponding physical bases favoring the substitution of trivalent lanthanides for divalent Ca2+ and Mg2+ in holoproteins. Replacing Ca2+ or Mg2+ with La3+ is facilitated by (1) minimizing the solvent exposure and the flexibility of the metal-binding cavity, (2) freeing both carboxylate oxygen atoms of Asp/Glu side chains in the metal-binding site so that they could bind bidentately to La3+, (3) maximizing the number of metal-bound carboxylate groups in buried sites, but minimizing the number of metal-bound carboxylate groups in solvent-exposed sites, and (4) including an Asn/Gln side chain for sites lined with four Asp/Glu side chains. In proteins bound to both Mg2+ and Ca2+, La3+ would prefer to replace Ca2+, as compared to Mg2+. A second Mg2+-binding site with a net positive charge would hamper the Mg2+ --> La3+ exchange, as compared to the respective mononuclear site, although the La3+ substitution of the first native metal is more favorable than the second one. The findings of this work are in accord with available experimental data.

One-Sided Social Media Comments Influenced Opinions And Intentions About Home Birth: An Experimental Study.

PubMed

Witteman, Holly O; Fagerlin, Angela; Exe, Nicole; Trottier, Marie-Eve; Zikmund-Fisher, Brian J

2016-04-01

As people increasingly turn to social media to access and create health evidence, the greater availability of data and information ought to help more people make evidence-informed health decisions that align with what matters to them. However, questions remain as to whether people can be swayed in favor of or against options by polarized social media, particularly in the case of controversial topics. We created a composite mock news article about home birth from six real news articles and randomly assigned participants in an online study to view comments posted about the original six articles. We found that exposure to one-sided social media comments with one-sided opinions influenced participants' opinions of the health topic regardless of their reported level of previous knowledge, especially when comments contained personal stories. Comments representing a breadth of views did not influence opinions, which suggests that while exposure to one-sided comments may bias opinions, exposure to balanced comments may avoid such bias. Project HOPE—The People-to-People Health Foundation, Inc.

Cannabis Use in Palliative Oncology: A Review of the Evidence for Popular Indications.

PubMed

Turgeman, Ilit; Bar-Sela, Gil

2017-02-01

A flowering plant of variegated ingredients and psychoactive qualities, cannabis has long been used for medicinal and recreational purposes. Currently, cannabis is approved in several countries for indications of symptomatic alleviation. However, limited knowledge on the benefits and risks precludes inclusion of cannabis in standard treatment guidelines. This review provides a summary of the available literature on the use of cannabis and cannabinoid-based medicines in palliative oncology. Favorable outcomes are demonstrated for chemotherapy-induced nausea and vomiting and cancer-related pain, with evidence of advantageous neurological interactions. Benefit in the treatment of anorexia, insomnia and anxiety is also suggested. Short- and long-term side effects appear to be manageable and to subside after discontinuation of the drug. Finally, cannabinoids have shown anti-neoplastic effects in preclinical studies in a wide range of cancer cells and some animal models. Further research is needed before cannabis can become a part of evidence-based oncology practice.

[Exercise in arterial hypertension].

PubMed

Predel, Hans-Georg; Schramm, Thomas

2006-09-01

Regular endurance training has established itself as a major therapeutic principle in the specter of nonpharmacological measures in arterial hypertension. An initial medical check as well as an adequate technique, dosage and intensity of the prescribed exercise training are mandatory. With respect to the concomitant pharmacological treatment, it should be considered that the beneficial effects of lifestyle modification will not be counteracted by the chosen antihypertensive drug but, ideally, synergistically supported. Based on the individual clinical situation, principally all antihypertensive drugs recommended by the current European guidelines, may be prescribed as mono- or combination therapy.beta-receptor blockers are especially capable of controlling excessive exercise-induced blood pressure increase; however, they have metabolic and exercise physiological limitations. The neutrality concerning metabolic and exercise physiological parameters as well as the positive profile of side effects favor ACE inhibitors, long-acting calcium channel blockers and especially AT(1) antagonists in physically active hypertensive patients with concomitant metabolic syndrome.

Cancer nanoimmunotherapy using advanced pharmaceutical nanotechnology.

PubMed

Li, Wei; Wei, Huafeng; Li, Huafei; Gao, Jie; Feng, Si-Shen; Guo, Yajun

2014-11-01

Immunotherapy is a promising option for cancer treatment that might cure cancer with fewer side effects by primarily activating the host's immune system. However, the effect of traditional immunotherapy is modest, frequently due to tumor escape and resistance of multiple mechanisms. Pharmaceutical nanotechnology, which is also called cancer nanotechnology or nanomedicine, has provided a practical solution to solve the limitations of traditional immunotherapy. This article reviews the latest developments in immunotherapy and nanomedicine, and illustrates how nanocarriers (including micelles, liposomes, polymer-drug conjugates, solid lipid nanoparticles and biodegradable nanoparticles) could be used for the cellular transfer of immune effectors for active and passive nanoimmunotherapy. The fine engineering of nanocarriers based on the unique features of the tumor microenvironment and extra-/intra-cellular conditions of tumor cells can greatly tip the triangle immunobalance among host, tumor and nanoparticulates in favor of antitumor responses, which shows a promising prospect for nanoimmunotherapy.

Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis.

PubMed

Albaugh, V L; Judson, J G; She, P; Lang, C H; Maresca, K P; Joyal, J L; Lynch, C J

2011-05-01

Olanzapine and other atypical antipsychotics cause metabolic side effects leading to obesity and diabetes; although these continue to be an important public health concern, their underlying mechanisms remain elusive. Therefore, an animal model of these side effects was developed in male Sprague-Dawley rats. Chronic administration of olanzapine elevated fasting glucose, impaired glucose and insulin tolerance, increased fat mass but, in contrast to female rats, did not increase body weight or food intake. Acute studies were conducted to delineate the mechanisms responsible for these effects. Olanzapine markedly decreased physical activity without a compensatory decline in food intake. It also acutely elevated fasting glucose and worsened oral glucose and insulin tolerance, suggesting that these effects are adiposity independent. Hyperinsulinemic-euglycemic clamp studies measuring (14)C-2-deoxyglucose uptake revealed tissue-specific insulin resistance. Insulin sensitivity was impaired in skeletal muscle, but either unchanged or increased in adipose tissue depots. Consistent with the olanzapine-induced hyperglycemia, there was a tendency for increased (14)C-2-deoxyglucose uptake into fat depots of fed rats and, surprisingly, free fatty acid (FFA) uptake into fat depots was elevated approximately twofold. The increased glucose and FFA uptake into adipose tissue was coupled with increased adipose tissue lipogenesis. Finally, olanzapine lowered fasting plasma FFA, and as it had no effect on isoproterenol-stimulated rises in plasma glucose, it blunted isoproterenol-stimulated in vivo lipolysis in fed rats. Collectively, these results suggest that olanzapine exerts several metabolic effects that together favor increased accumulation of fuel into adipose tissue, thereby increasing adiposity.

Conformational Preferences of β– and γ–Aminated Proline Analogues

PubMed Central

Flores-Ortega, Alejandra; Casanovas, Jordi; Nussinov, Ruth; Alemán, Carlos

2010-01-01

Quantum mechanical calculations have been used to investigate how the incorporation of an amino group to the Cβ- or Cγ-positions of the pyrrolidine ring affects the intrinsic conformational properties of the proline. Specifically, a conformational study of the N-acetyl-N′-methylamide derivatives of four isomers of aminoproline, which differ not only in the β- or γ-position of the substituent but also in its cis or trans relative disposition, has been performed. In order to further understand the role of the intramolecular hydrogen bonds between the backbone carbonyl groups and the amino side group, a conformational study was also performed on the corresponding four analogues of dimethylaminoproline. In addition, the effects of solvation on aminoproline and dimethylaminoproline dipeptides have been evaluated using a Self Consistent Reaction Field model, and considering four different solvents (carbon tetrachloride, chloroform, methanol and water). Results indicate that the incorporation of the amino substituent into the pyrrolidine ring affects the conformational properties, with backbone⋯side chain intramolecular hydrogen bonds detected when it is incorporated in a cis relative disposition. In general, the incorporation of the amino side group tends to stabilize those structures where the peptide bond involving the pyrrolidine nitrogen is arranged in cis. The aminoproline isomer with the substituent attached to the Cγ-position with a cis relative disposition is the most stable in the gas-phase and in chloroform, methanol and water solutions. Replacement of the amino side group by the dimethylamino substituent produces significant changes in the potential energy surfaces of the four investigated dimethylaminoproline-containing dipeptides. Thus, these changes affect not only the number of minima, which increases considerably, but also the backbone and pseudorotational preferences. In spite of these effects, comparison of the conformational preferences, i.e. the more favored conformers, calculated for different isomers of aminoproline and dimethylaminoproline dipeptides showed a high degree of consistency for the two families of compounds. PMID:18842022

'Bright side' and 'dark side' hypomania are associated with differences in psychological functioning, sleep and physical activity in a non-clinical sample of young adults.

PubMed

Brand, Serge; Gerber, Markus; Pühse, Uwe; Holsboer-Trachsler, Edith

2011-06-01

No research has yet focused on hypomanic states in non-clinical early adult populations. The aim of the present study was therefore to assess hypomania in a large non-clinical sample of young adults. A total of 862 participants (639 females and 223 males; mean age: M=24.67; SD=5.91) took part in the study. They completed a series of validated self-report questionnaires assessing hypomania (HCL-32) and other aspects of psychological functioning, sleep, stress, quality of life, cognitive-emotional elaboration of pain, self-efficacy, and physical activity. Based on the HCL-32, 19% of the participants (n=169) were categorized as currently being in a hypomanic state. Of those, 57.6% were classified as "active/elated" ('bright side'), whereas 42.4% were classified as "irritable/risk-taking" ('dark side'). Compared to non-hypomanic participants and the 'bright side' group, 'dark side' hypomanic participants reported more depressive symptoms, sleep disturbances, somatic complaints, perceived stress, negative coping strategies, and lower self-efficacy. By contrast, 'bright side' hypomanic participants had lower stress scores, more positive self-instructions, and higher levels of exploration, self-efficacy, and physical activity. A cross-sectional design was adopted, assessing university students, who may not be representative of the stage of early adulthood. The present results underscore the notion of a continuity between a mood state and both favorable ('bright side') and unfavorable ('dark side') hypomanic states. In early adulthood, 'bright' and 'dark side' hypomania differs with respect to physical activity, psychological functioning and sleep. Copyright © 2010 Elsevier B.V. All rights reserved.

Long-term use and tolerability of irbesartan for control of hypertension

PubMed Central

Forni, Valentina; Wuerzner, Grégoire; Pruijm, Menno; Burnier, Michel

2011-01-01

In this review, we discuss the pharmacological and clinical properties of irbesartan, a noncompetitive angiotensin II receptor type 1 antagonist, successfully used for more than a decade in the treatment of essential hypertension. Irbesartan exerts its antihypertensive effect through an inhibitory effect on the pressure response to angiotensin II. Irbesartan 150–300 mg once daily confers a lasting effect over 24 hours, and its antihypertensive efficacy is further enhanced by the coadministration of hydrochlorothiazide. Additionally and partially beyond its blood pressure-lowering effect, irbesartan reduces left ventricular hypertrophy, favors right atrial remodeling in atrial fibrillation, and increases the likelihood of maintenance of sinus rhythm after cardioversion in atrial fibrillation. In addition, the renoprotective effects of irbesartan are well documented in the early and later stages of renal disease in type 2 diabetics. Furthermore, both the therapeutic effectiveness and the placebo-like side effect profile contribute to a high adherence rate to the drug. Currently, irbesartan in monotherapy or combination therapy with hydrochlorothiazide represent a rationale pharmacologic approach for arterial hypertension and early-stage and late-stage diabetic nephropathy in hypertensive type II diabetics. PMID:21949635

Quantifying Interactions of Nucleobase Atoms with Model Compounds for the Peptide Backbone and Glutamine and Asparagine Side Chains in Water.

PubMed

Cheng, Xian; Shkel, Irina A; Molzahn, Cristen; Lambert, David; Karim, Rezwana; Record, M Thomas

2018-04-17

Alkylureas display hydrocarbon and amide groups, the primary functional groups of proteins. To obtain the thermodynamic information that is needed to analyze interactions of amides and proteins with nucleobases and nucleic acids, we quantify preferential interactions of alkylureas with nucleobases differing in the amount and composition of water-accessible surface area (ASA) by solubility assays. Using an established additive ASA-based analysis, we interpret these thermodynamic results to determine interactions of each alkylurea with five types of nucleobase unified atoms (carbonyl sp 2 O, amino sp 3 N, ring sp 2 N, methyl sp 3 C, and ring sp 2 C). All alkylureas interact favorably with nucleobase sp 2 C and sp 3 C atoms; these interactions become more favorable with an increasing level of alkylation of urea. Interactions with nucleobase sp 2 O are most favorable for urea, less favorable for methylurea and ethylurea, and unfavorable for dialkylated ureas. Contributions to overall alkylurea-nucleobase interactions from interactions with each nucleobase atom type are proportional to the ASA of that atom type with proportionality constant (interaction strength) α, as observed previously for urea. Trends in α-values for interactions of alkylureas with nucleobase atom types parallel those for corresponding amide compound atom types, offset because nucleobase α-values are more favorable. Comparisons between ethylated and methylated ureas show interactions of amide compound sp 3 C with nucleobase sp 2 C, sp 3 C, sp 2 N, and sp 3 N atoms are favorable while amide sp 3 C-nucleobase sp 2 O interactions are unfavorable. Strongly favorable interactions of urea with nucleobase sp 2 O but weakly favorable interactions with nucleobase sp 3 N indicate that amide sp 2 N-nucleobase sp 2 O and nucleobase sp 3 N-amide sp 2 O hydrogen bonding (NH···O═C) interactions are favorable while amide sp 2 N-nucleobase sp 3 N interactions are unfavorable. These favorable amide-nucleobase hydrogen bonding interactions are prevalent in specific protein-nucleotide complexes.

The vagal nerve stimulation outcome, and laryngeal effect: Otolaryngologists roles and perspective.

PubMed

Al Omari, Ahmad I; Alzoubi, Firas Q; Alsalem, Mohammad M; Aburahma, Samah K; Mardini, Diala T; Castellanos, Paul F

Epilepsy is one of the most common neurologic disorders. Vagus nerve stimulation (VNS), first investigated in 1938 and subsequently studied as a potential therapy for epilepsy. The FDA approved the use of VNS in 1997 as an adjunctive non-pharmacologic symptomatic treatment option for refractory epilepsy for adults and adolescents over 12years. VNS can cause laryngeal and voice side effects that can be managed by otolaryngologists safely and effectively. This study is to review the outcomes of vagal nerve stimulator (VNS) implantation in terms of the surgical procedures, complications, seizure frequency, and the clinical effect on larynx and vocal folds motion. Series of thirty consecutive patients who had VNS implantation between 2007 and 2014 were recruited. Seizure-frequency outcome, surgical complications and device adverse effects of VNS were retrospectively reviewed. Additional evaluation included use of the Voice Handicap Index and Maximum Phonation Time (MPT) were conducted before and after the implantation. Videolaryngoscopy was used to evaluate the vocal fold mobility before and after the VNS implantation. Seizure frequency reduction over a minimum of 2years of follow up demonstrated: 100% in seizure frequency reduction in 1 patient, drastic reduction in seizure frequency (70-90%) in 9 patients, a good reduction in terms of seizure frequency (50%) in 8 patients, a 30% reduction in 5 patients, no response in 6 patients, and 1 patient had increased frequency. The most commonly reported adverse effects after VNS activation were coughing and voice changes with pitch breaks, as well as mild intermittent shortness of breath in 33% of patients. For those patients secondary supraglottic muscle tension and hyper function with reduced left vocal fold mobility were noticed on videolaryngoscopy, though none had aspiration problems. Surgical complications included a wound dehiscence in one patient (3%) which was surgically managed, minor intra-operative bleeding 3%; a superficial wound infection in one patient (3%) which was treated conservatively, none of the complications necessitated VNS removal. VNS appears to be an effective non-pharmacologic adjuvant therapy in patients with medically refractory seizures. With the favorable adverse-effect profile previously described, VNS is generally well tolerated and of a great benefit to such patients. Laryngeal side effects, of which hoarseness being of the greatest repetition, are the most common after the VNS implantation. VNS can affect the voice and reduced vocal cord motion on the implantation side with secondary supraglottic muscle tension. Otolaryngologists are not only capable of performing VNS implantation, but can also manage surgical complications, assess laryngeal side effects and treat them as needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Mineral potential tracts for orogenic, Carlin-like, and epithermal gold deposits in the Islamic Republic of Mauritania, (phase V, deliverable 69): Chapter H in Second projet de renforcement institutionnel du secteur minier de la République Islamique de Mauritanie (PRISM-II)

USGS Publications Warehouse

Goldfarb, Richard J.; Marsh, Erin; Anderson, Eric D.; Horton, John D.; Finn, Carol A.; Beaudoin, Georges

2015-01-01

A preliminary evaluation of these gold data can be used to develop broad, firstorder tracts defining favorable and permissive areas for gold resources; detailed metamorphic and structural maps are required for more detailed future tract definition. Such a first-order assessment can, nonetheless, broadly identify four tracts of gold resource potential. Three of these are favorable for discovery of new orogenic gold deposits. One tract, although not favorable, is nevertheless permissive for discovery of epithermal gold deposits. Tract 1 is defined by favorable medium metamorphic grade greenstone belts within vast areas of unfavorable high metamorphic grade, Mesoarchean and Paleoproterozoic granite-gneiss basement of the Rgueïbat Shield. Faults >200 km in length following the general strike of the greenstone belts; lineament intersections with both exposed and buried parts of greenstone belts within 500 m of the surface, as defined by aeromagnetic data (Finn and Anderson, 2015); and areas of banded iron formation (BIF) in the belts are particularly favorable areas for hosting gold resources in orogenic gold deposits within and along the margins of the greenstone belts. Tracts 2 and 3, also for orogenic gold, reflect the favorable Proterozoic-Cambrian metamorphic rocks of the Northern and Southern Mauritanides, with >200-km-long faults following the general strike of the range, and areas underlain by ultramafic and BIF rocks being particularly favorable. Outcrops of Triassic-Jurassic igneous rocks along the margins of the Taoudeni Basin define tract 4, which is permissive for epithermal gold deposits. Although extensive data are lacking for the area, carbonate units along the northern side of the Taoudeni Basin could be considered permissive host rocks for Carlin-type mineralization, but the deep-water carbonate lithologies are typically not favorable for such. 

Analytical Approach to the Characterization of Military Lubricants

DTIC Science & Technology

1976-03-01

Continue on reverse side It necessary and Identity by block number) As an integral part of the Army’s overall power train lubrication research! effort...favorable results. Technology has progressed to where it is now possible to qualitatively analyze and quantitate the major base stock components in hybrid...lubricant component to equipment performance, and identify sources of new, used, synthetic and re-refined lubricants, power train and hydraulic

JPRS Report West Europe.

DTIC Science & Technology

1988-07-25

cost-favorable manner (without making the situation of the really needy worse) if the Federal Government would pay greater attention to this aspect...policy and the ruling positions would be divide up sooner than expected. Party secretary Seppo Kaariainen is amused by the anxiety of the...34People at the party congress will divide up into two sections. One side will think that the party platform is too broad and general. Others will

JPRS Report, East Europe

DTIC Science & Technology

1991-01-30

GDR [POLITYKA 8 Dec] 16 Border Treaty, Future German Relations Viewed [GAZETA WYBORCZA 14 Nov] 18 Senator Favors Silesian Bridge-Building Role ...Slovak history was a part until 1918 . We could find parallels here to illuminate many an effort by the current Slovak political leadership. In some... Romanians , and others, on the other side. The constant pressure did not cease until after the Austro-Hungarian settlement in 1867. The Hapsburgs of Vienna

A NEW ANTIEMETIC FOR THE TREATMENT OF NAUSEA AND VOMITING ASSOCIATED WITH ROENTGEN THERAPY

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

Codiga, V.A.

Thiethylperazine dimaleate was administered orally or rectally in 56 patients for treatment of nausea or vomiting associated with radiation (2000 to 5000 r). The oral form had a quicker onset of action. Fifty patients (89%) experienced satisfactory response with either oral tablets or suppositories, the latter being used when oral tolerance was poor. Only 2 complained of side effects attributable to thiethylperazine dimaleate. One patient experienced transient blurred vision and tinnitus and another noted sialorrhea plus diminished gustatory sensation. In view of the observed high percentage of favorable responses with the drug and its lack of ataractic action, the rolemore » of psychogenic factors in gastrointestinal disturbance associated with roentgen ray therapy would seem to be slight. (H.H.D.)« less

Upper-surface-blowing flow-turning performance

NASA Technical Reports Server (NTRS)

Sleeman, W. C., Jr.; Phelps, A. E., III

1976-01-01

Jet exhaust flow-turning characteristics were determined for systematic variations in upper-surface blowing exhaust nozzles and trailing-edge flap configuration variables from experimental wind-off (static) flow studies. For conditions with parallel flow exhausting from the nozzle, jet height (as indicated by nozzle exit height) and flap radius were found to be the most important parameters relating to flow turning. Nonparallel flow from the nozzle, as obtained from an internal roof angle and/or side spread angle, had a large favorable effect on flow turning. Comparisons made between static turning results and wind tunnel aerodynamic studies of identical configurations indicated that static flow-turning results can be indicative of wind-on powered lift performance for both good and poor nozzle-flap combinations but, for marginal designs, can lead to overly optimistic assessment of powered lift potential.

The GHSG Approach to Treating Hodgkin's Lymphoma.

PubMed

Bröckelmann, Paul J; Engert, Andreas

2015-09-01

Hodgkin's lymphoma (HL) is a relatively rare disease accounting for 15 % of all lymphoma. This disease has developed from an incurable disease to the adult malignancy with the most favorable prognosis. With current therapeutic approaches consisting of polychemo- and small-field radiotherapy, up to 80 % of all patients can be cured long term. In refractory or relapsed HL, intensified treatment including high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) is associated with progression-free survival (PFS) of 50 %. Evaluation of novel drugs in multiple relapsed or refractory cases, better treatment options for elderly patients and reducing treatment-related side effects are the main focus of current research. Recent clinical developments and future approaches in the treatment of HL will be discussed in this review.

Apatinib: a promising oral antiangiogenic agent in the treatment of multiple solid tumors.

PubMed

Scott, A J; Messersmith, W A; Jimeno, A

2015-04-01

Aberrant proangiogenic pathways have long been implicated in tumorigenesis and metastasis. Antiangiogenic therapies have shown efficacy in the treatment of a variety of solid tumors including lung, breast, colon, glioblastomas, and other solid tumor types. Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), is an orally bioavailable agent currently being studied in multiple tumor types. Apatinib has shown a survival benefit in gastric cancer in a phase III trial and non-small cell lung cancer in a phase II trial. With a favorable side effect profile and improved outcomes, apatinib has demonstrated a substantial potential to augment therapeutic options in a variety of tumor types. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

Hyaluronic acid-modified zirconium phosphate nanoparticles for potential lung cancer therapy.

PubMed

Li, Ranwei; Liu, Tiecheng; Wang, Ke

2017-02-01

Novel tumor-targeting zirconium phosphate (ZP) nanoparticles modified with hyaluronic acid (HA) were developed (HA-ZP), with the aim of combining the drug-loading property of ZP and the tumor-targeting ability of HA to construct a tumor-targeting paclitaxel (PTX) delivery system for potential lung cancer therapy. The experimental results indicated that PTX loading into the HA-ZP nanoparticles was as high as 20.36%±4.37%, which is favorable for cancer therapy. PTX-loaded HA-ZP nanoparticles increased the accumulation of PTX in A549 lung cancer cells via HA-mediated endocytosis and exhibited superior anticancer activity in vitro. In vivo anticancer efficacy assay revealed that HA-ZP nanoparticles possessed preferable anticancer abilities, which exhibited minimized toxic side effects of PTX and strong tumor-suppression potential in clinical application.

Successful Treatment with Alectinib for Choroidal Metastasis in Anaplastic Lymphoma Kinase Rearranged Non-small Cell Lung Cancer

PubMed Central

Funazo, Tomoko; Morita, Kyohei; Ikegami, Naoya; Konishi, Chisato; Nakao, Satoshi; Ariyasu, Ryo; Taki, Masato; Nakagawa, Kazuhiko; Hwang, Moon Hee; Yoshimura, Chie; Wakayama, Toshiaki; Nishizaka, Yasuo

2017-01-01

Choroidal metastasis is rare in cancer patients and it may cause visual disturbances that reduce their quality of life. In non-small cell lung cancer (NSCLC), targeted therapy against actionable driver mutations has gradually replaced radiotherapy as the treatment of choice for choroidal metastasis. Recently, there have been several case reports of choroidal metastasis in patients with anaplastic lymphoma kinase (ALK)-rearranged NSCLC. We herein report the case of a 40-year-old Japanese woman diagnosed with choroidal metastasis of an ALK-rearranged NSCLC who received alectinib as the first-line chemotherapy. Alectinib may be the best treatment for choroidal metastasis in patients harboring an ALK translocation because of its favorable side effect profile involving visual disturbances. PMID:28794371

CO2 laser therapy of rhinophyma

NASA Astrophysics Data System (ADS)

Voigt, Peggy; Jovanovic, Sergije; Sedlmaier, Benedikt W.

2000-06-01

Laser treatment of skin changes has become common practice in recent years. High absorption of the CO2 laser wavelength in water is responsible for its low penetration dpt in biological tissue. Shortening the tissue exposure time minimizes thermic side effects of laser radiation such as carbonization and coagulation. This can be achieved with scanner systems that move the focused laser beam over a defined area by microprocessor-controlled rapidly rotating mirrors. This enables controlled and reliable removal of certain dermal lesions, particularly hypertrophic scars, scars after common acne, wrinkles and rhinophyma. Laser ablation of rhinophyma is a stress-minimizing procedure for the surgeon and the patient, since it is nearly bloodless and can be performed under local anaesthesia. Cosmetically favorable reepithelization of the lasered surfaces is achieved within a very short period of time.

Present Status of Medical Education in Poland

PubMed Central

Selzer, Arthur

1965-01-01

In the past few years medical education in Poland has undergone considerable change, particularly at the graduate and postgraduate levels, and has shown increasing Western influences. On the negative side, a physician who was trained in pre-war Poland and is now in the United States, noted mass production of physicians with modest clinical facilities and the preponderance of didactic lecturing over semi-individual instruction—conditions rather characteristic of most European medical schools. On the positive side were well-informed, up-to-date faculties and the thoughtful planning and organization of graduate and postgraduate medical education. The overall impression was a favorable one, but the system of schooling and of evaluation of students' work made it possible for indifferent students to progress to licensure. PMID:14288146

PRESENT STATUS OF MEDICAL EDUCATION IN POLAND.

PubMed

SELZER, A

1965-04-01

In the past few years medical education in Poland has undergone considerable change, particularly at the graduate and postgraduate levels, and has shown increasing Western influences. On the negative side, a physician who was trained in pre-war Poland and is now in the United States, noted mass production of physicians with modest clinical facilities and the preponderance of didactic lecturing over semi-individual instruction-conditions rather characteristic of most European medical schools. On the positive side were well-informed, up-to-date faculties and the thoughtful planning and organization of graduate and postgraduate medical education. The overall impression was a favorable one, but the system of schooling and of evaluation of students' work made it possible for indifferent students to progress to licensure.

Beyond the classroom: using technology to meet the educational needs of multigenerational perinatal nurses.

PubMed

Gallo, Ana-Maria

2011-01-01

For the first time in history, there are 4 distinct generations of nurses working side by side at the clinical bedside: Veterans, Baby Boomers, Generation X, and Generation Y. All the generations have their unique personalities, beliefs, values, and learning styles. Approach to learning range from the traditional instructional method preferred by the Veteran's nurses to the more advanced technology (eg, Web-based, webinars, simulations, podcasts, and blogs) approach favored by Generation Y. Nurse educators and clinical nurse specialists must consider each generation's style of learning to best engage, stimulate, and promote transference and assimilations of new knowledge. This article briefly describes the generational learning style differences and explores alternative educational modalities to the traditional classroom instruction.

Direct Comparison of Amino Acid and Salt Interactions with Double-Stranded and Single-Stranded DNA from Explicit-Solvent Molecular Dynamics Simulations.

PubMed

Andrews, Casey T; Campbell, Brady A; Elcock, Adrian H

2017-04-11

Given the ubiquitous nature of protein-DNA interactions, it is important to understand the interaction thermodynamics of individual amino acid side chains for DNA. One way to assess these preferences is to perform molecular dynamics (MD) simulations. Here we report MD simulations of 20 amino acid side chain analogs interacting simultaneously with both a 70-base-pair double-stranded DNA and with a 70-nucleotide single-stranded DNA. The relative preferences of the amino acid side chains for dsDNA and ssDNA match well with values deduced from crystallographic analyses of protein-DNA complexes. The estimated apparent free energies of interaction for ssDNA, on the other hand, correlate well with previous simulation values reported for interactions with isolated nucleobases, and with experimental values reported for interactions with guanosine. Comparisons of the interactions with dsDNA and ssDNA indicate that, with the exception of the positively charged side chains, all types of amino acid side chain interact more favorably with ssDNA, with intercalation of aromatic and aliphatic side chains being especially notable. Analysis of the data on a base-by-base basis indicates that positively charged side chains, as well as sodium ions, preferentially bind to cytosine in ssDNA, and that negatively charged side chains, and chloride ions, preferentially bind to guanine in ssDNA. These latter observations provide a novel explanation for the lower salt dependence of DNA duplex stability in GC-rich sequences relative to AT-rich sequences.

High-mass twins & resolution of the reconfinement, masquerade and hyperon puzzles of compact star interiors

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

Blaschke, David; Instytut Fizyki Teoretycznej, Uniwersytet Wroclawski, 50-204 Wroclaw; Alvarez-Castillo, David E.

2016-01-22

We aim at contributing to the resolution of three of the fundamental puzzles related to the still unsolved problem of the structure of the dense core of compact stars (CS): (i) the hyperon puzzle: how to reconcile pulsar masses of 2 M{sub ⊙} with the hyperon softening of the equation of state (EoS); (ii) the masquerade problem: modern EoS for cold, high density hadronic and quark matter are almost identical; and (iii) the reconfinement puzzle: what to do when after a deconfinement transition the hadronic EoS becomes favorable again? We show that taking into account the compositeness of baryons (bymore » excluded volume and/or quark Pauli blocking) on the hadronic side and confining and stiffening effects on the quark matter side results in an early phase transition to quark matter with sufficient stiffening at high densities which removes all three present-day puzzles of CS interiors. Moreover, in this new class of EoS for hybrid CS falls the interesting case of a strong first order phase transition which results in the observable high mass twin star phenomenon, an astrophysical observation of a critical endpoint in the QCD phase diagram.« less

Vineyard Colonization by Hyalesthes obsoletus (Hemiptera: Cixiidae) Induced by Stinging Nettle Cut Along Surrounding Ditches.

PubMed

Mori, N; Pozzebon, A; Duso, C; Reggiani, N; Pavan, F

2016-02-01

Stinging nettle (Urtica dioica L.) is the most important host plant for both phytoplasma associated with Bois noir disease of the grapevine and its vector Hyalesthes obsoletus Signoret (Hemiptera: Cixiidae). Vector abundance in vineyards is favored by stinging nettle growing in surrounding areas. Nettle control by herbicides or cutting can reduce vector population in vineyards. However, chemical weeding can cause environmental problems. Many authors suggest that stinging nettle control applied during H. obsoletus flight could force adults to migrate into vineyards. We evaluate if cutting of nettle growing along ditches during adult flight favors vineyard colonization by H. obsoletus. Three different weed management regimes ("no cuts," "one cut" just before the beginning of adult flight, and "frequent cuts" over the whole vegetative season) were applied to the herbaceous vegetation in ditches bordering two vineyards. The flight dynamics of H. obsoletus were recorded by placing yellow sticky traps on the vegetation along the ditches and at different positions in the vineyards. Frequent stinging nettle cuts (compared with a single cut) in surrounding areas favored the dispersion of vectors inside the vineyards. Stinging nettle control should be based on an integration of a single herbicide application before H. obsoletus emergence followed by frequent cuts to minimize negative side effects of chemical weeding. In organic viticulture, a frequent-cuts strategy should avoid cuts during H. obsoletus flight period, at least in the first year of adoption. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Improved nine-node shell element MITC9i with reduced distortion sensitivity

NASA Astrophysics Data System (ADS)

Wisniewski, K.; Turska, E.

2017-11-01

The 9-node quadrilateral shell element MITC9i is developed for the Reissner-Mindlin shell kinematics, the extended potential energy and Green strain. The following features of its formulation ensure an improved behavior: 1. The MITC technique is used to avoid locking, and we propose improved transformations for bending and transverse shear strains, which render that all patch tests are passed for the regular mesh, i.e. with straight element sides and middle positions of midside nodes and a central node. 2. To reduce shape distortion effects, the so-called corrected shape functions of Celia and Gray (Int J Numer Meth Eng 20:1447-1459, 1984) are extended to shells and used instead of the standard ones. In effect, all patch tests are passed additionally for shifts of the midside nodes along straight element sides and for arbitrary shifts of the central node. 3. Several extensions of the corrected shape functions are proposed to enable computations of non-flat shells. In particular, a criterion is put forward to determine the shift parameters associated with the central node for non-flat elements. Additionally, the method is presented to construct a parabolic side for a shifted midside node, which improves accuracy for symmetric curved edges. Drilling rotations are included by using the drilling Rotation Constraint equation, in a way consistent with the additive/multiplicative rotation update scheme for large rotations. We show that the corrected shape functions reduce the sensitivity of the solution to the regularization parameter γ of the penalty method for this constraint. The MITC9i shell element is subjected to a range of linear and non-linear tests to show passing the patch tests, the absence of locking, very good accuracy and insensitivity to node shifts. It favorably compares to several other tested 9-node elements.

An East to West Mineralogical Trend in Mars Exploration Rover Spirit Moessbauer Spectra of Home Plate

NASA Technical Reports Server (NTRS)

Schroder, C.; Di, K.; Morris, R. V.; Klingelhofer, G.; Li, R.

2008-01-01

Home Plate is a light-toned plateau approx.90 m in diameter within the Inner Basin of the Columbia Hills in Gusev crater on Mars. It is the most extensive exposure of layered bedrock encountered by Spirit to date, and it is composed of clastic rocks of moderately altered alkali basalt composition, enriched in some highly volatile elements. Textural observations suggest an explosive origin and geochemical observations favor volcanism, probably a hydrovolcanic explosion [1]. Since it first arrived at Home Plate on sol 744, Spirit has circumnavigated the plateau (Fig. 1) and is now, since sol 1410, resting at its Winter Haven 3 location at the north end of Home Plate. Results: The MER Moessbauer spectrometers determine Fe oxidation states, identify Fe-bearing mineral phases and quantify the distribution of Fe among oxidation states and mineral phases [2]. Moessbauer spectra of Home Plate bedrock were obtained in five different locations from nine different targets (Fig. 1): Barnhill Ace, Posey Manager, and James Cool Papa Bell Stars at the northwest side of Home Plate; Pesapallo, June Emerson, and Elizabeth Emery on the east side; Texas Chili on the south side; Pecan Pie on the west side; and Chanute on the north side.

Influence of Protein Scaffold on Side-Chain Transfer Free Energies.

PubMed

Marx, Dagen C; Fleming, Karen G

2017-08-08

The process by which membrane proteins fold involves the burial of side chains into lipid bilayers. Both structure and function of membrane proteins depend on the magnitudes of side-chain transfer free energies (ΔΔG sc o ). In the absence of other interactions, ΔΔG sc o is an independent property describing the energetics of an isolated side chain in the bilayer. However, in reality, side chains are attached to the peptide backbone and surrounded by other side chains in the protein scaffold in biology, which may alter the apparent ΔΔG sc o . Previously we reported a whole protein water-to-bilayer hydrophobicity scale using the transmembrane β-barrel Escherichia coli OmpLA as a scaffold protein. To investigate how a different protein scaffold can modulate these energies, we measured ΔΔG sc o for all 20 amino acids using the transmembrane β-barrel E. coli PagP as a scaffold protein. This study represents, to our knowledge, the first instance of ΔΔG sc o measured in the same experimental conditions in two structurally and sequentially distinct protein scaffolds. Although the two hydrophobicity scales are strongly linearly correlated, we find that there are apparent scaffold induced changes in ΔΔG sc o for more than half of the side chains, most of which are polar residues. We propose that the protein scaffold affects the ΔΔG sc o of side chains that are buried in unfavorable environments by dictating the mechanisms by which the side chain can reach a more favorable environment and thus modulating the magnitude of ΔΔG sc o . Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2017-08-09

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

The Effect of Calcium Sodium Phosphosilicate on Dentin Hypersensitivity: A Systematic Review and Meta-Analysis

PubMed Central

Chen, Bin; Mei, Li; Yao, Liang; Tian, Jinhui; Li, Huang

2015-01-01

Objective To investigate the effect of calcium sodium phosphosilicate (CSPS) in treating dentin hypersensitivity (DH) and to compare this effect to that of a negative (placebo) control. Materials and Methods Several databases, including Medline, EMBASE, Web of Science, The Cochrane Library, and the Chinese Biomedical Literature Database, were searched to identify relevant articles published through January 2015; grey literature (i.e., academic literature that is not formally published) was also searched. Two authors performed data extraction independently and jointly using data collection forms. The primary outcome was the DH pain response to routine activities or to thermal, tactile, evaporative, or electrical stimuli, and the secondary outcome was the side effects of CSPS use. Each study was evaluated using the Cochrane Collaboration tool for assessing risk bias. Meta-analysis of studies with the same participant demographics, interventions, controls, assessment methods and follow-up periods was performed. The Grading of Recommendations Assessment Development and Evaluation System was used to assess the quality of the evidence and the risk of bias across studies. Results Meta-analysis demonstrated that toothpaste containing 5% CSPS was more effective than the negative control at relieving dentin sensitivity, with the level of evidence classified as “moderate”. In addition, prophylaxis paste containing 15% calcium sodium phosphosilicate was favored over the negative control at reducing post-periodontal therapy hypersensitivity, with the level of evidence categorized as “low”. Only two studies reported side effects of CSPS use. Conclusions The majority of studies found that calcium sodium phosphosilicate was more effective than the negative control at alleviating DH. Because strong evidence is scarce, high-quality, well-designed clinical trials are required in the future before definitive recommendations can be made. PMID:26544035

Endovascular Versus External Targeted Temperature Management for Patients With Out-of-Hospital Cardiac Arrest: A Randomized, Controlled Study.

PubMed

Deye, Nicolas; Cariou, Alain; Girardie, Patrick; Pichon, Nicolas; Megarbane, Bruno; Midez, Philippe; Tonnelier, Jean-Marie; Boulain, Thierry; Outin, Hervé; Delahaye, Arnaud; Cravoisy, Aurélie; Mercat, Alain; Blanc, Pascal; Santré, Charles; Quintard, Hervé; Brivet, François; Charpentier, Julien; Garrigue, Delphine; Francois, Bruno; Quenot, Jean-Pierre; Vincent, François; Gueugniaud, Pierre-Yves; Mira, Jean-Paul; Carli, Pierre; Vicaut, Eric; Baud, Frédéric J

2015-07-21

Targeted temperature management is recommended after out-of-hospital cardiac arrest. Whether advanced internal cooling is superior to basic external cooling remains unknown. The aim of this multicenter, controlled trial was to evaluate the benefit of endovascular versus basic surface cooling. Inclusion criteria were the following: age of 18 to 79 years, out-of-hospital cardiac arrest related to a presumed cardiac cause, time to return of spontaneous circulation <60 minutes, delay between return of spontaneous circulation and inclusion <240 minutes, and unconscious patient after return of spontaneous circulation and before the start of cooling. Exclusion criteria were terminal disease, pregnancy, known coagulopathy, uncontrolled bleeding, temperature on admission <30°C, in-hospital cardiac arrest, immediate need for extracorporeal life support or hemodialysis. Patients were randomized between 2 cooling strategies: endovascular femoral devices (Icy catheter, Coolgard, Zoll, formerly Alsius; n=203) or basic external cooling using fans, a homemade tent, and ice packs (n=197). The primary end point, that is, favorable outcome evaluated by survival without major neurological damage (Cerebral Performance Categories 1-2) at day 28, was not significantly different between groups (odds ratio, 1.41; 95% confidence interval, 0.93-2.16; P=0.107). Improvement in favorable outcome at day 90 in favor of the endovascular group did not reach significance (odds ratio, 1.51; 95% confidence interval, 0.96-2.35; P=0.07). Time to target temperature (33°C) was significantly shorter and target hypothermia was more strictly maintained in the endovascular than in the surface group (P<0.001). Minor side effects directly related to the cooling method were observed more frequently in the endovascular group (P=0.009). Despite better hypothermia induction and maintenance, endovascular cooling was not significantly superior to basic external cooling in terms of favorable outcome. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00392639. © 2015 American Heart Association, Inc.

H/D isotopic recognition and temperature effects in IR spectra of hydrogen-bonded cyclic dimers in crystals: 3-Methylcinnamic acid and 4-phenylbutyric acid

NASA Astrophysics Data System (ADS)

Hachuła, Barbara; Jabłońska-Czapla, Magdalena; Flakus, Henryk T.; Nowak, Maria; Kusz, Joachim

2015-01-01

In the present work, the experimental and theoretical study of the nature of the inter-hydrogen bond interactions in two different carboxylic acids, 3-methylcinnamic acid (3MCA) and 4-phenylbutyric acid (4PBA), were reported. The polarized IR spectra of 3MCA and 4PBA crystals were recorded at the frequency ranges of the νOsbnd H and νOsbnd D bands. The spectral properties of 3MCA and 4PBA interpreted with the aid of the calculations based on the "strong-coupling" model. The differences in the spectral properties of the two different dimeric systems in the crystals provide a valuable information about the existence of a direct relationship between the crystal spectral properties in IR and the electronic structure of the molecular systems. In 3MCA crystals strong vibrational exciton interactions favor a "tail-to-head" (TH)-type Davydov coupling widespread via the π-electrons, whereas in 4PBA crystals a weak "through-space" (SS) exciton coupling is responsible for a "side-to-side"-type coupling. The relative contribution of each individual exciton coupling mechanism in IR spectra generation strongly depends on temperature and molecular electronic structure. The H/D isotopic recognition effect, depending on a non-random distribution of protons and deuterons in the crystal hydrogen bridges, was also analyzed.

H/D isotopic recognition and temperature effects in IR spectra of hydrogen-bonded cyclic dimers in crystals: 3-methylcinnamic acid and 4-phenylbutyric acid.

PubMed

Hachuła, Barbara; Jabłońska-Czapla, Magdalena; Flakus, Henryk T; Nowak, Maria; Kusz, Joachim

2015-01-05

In the present work, the experimental and theoretical study of the nature of the inter-hydrogen bond interactions in two different carboxylic acids, 3-methylcinnamic acid (3MCA) and 4-phenylbutyric acid (4PBA), were reported. The polarized IR spectra of 3MCA and 4PBA crystals were recorded at the frequency ranges of the νO-H and νO-D bands. The spectral properties of 3MCA and 4PBA interpreted with the aid of the calculations based on the "strong-coupling" model. The differences in the spectral properties of the two different dimeric systems in the crystals provide a valuable information about the existence of a direct relationship between the crystal spectral properties in IR and the electronic structure of the molecular systems. In 3MCA crystals strong vibrational exciton interactions favor a "tail-to-head" (TH)-type Davydov coupling widespread via the π-electrons, whereas in 4PBA crystals a weak "through-space" (SS) exciton coupling is responsible for a "side-to-side"-type coupling. The relative contribution of each individual exciton coupling mechanism in IR spectra generation strongly depends on temperature and molecular electronic structure. The H/D isotopic recognition effect, depending on a non-random distribution of protons and deuterons in the crystal hydrogen bridges, was also analyzed. Copyright © 2014 Elsevier B.V. All rights reserved.

Favorable Response of Metastatic Merkel Cell Carcinoma to Targeted 177Lu-DOTATATE Therapy: Will PRRT Evolve to Become an Important Approach in Receptor-Positive Cases?

PubMed

Basu, Sandip; Ranade, Rohit

2016-06-01

This report illustrates an excellent partial response of Merkel cell carcinoma with multiple bilobar hepatic metastases to a single cycle of peptide receptor radionuclide therapy (PRRT) with (177)Lu-DOTATATE. This response, coupled with minimal side effects, warrants consideration of this therapy early in the disease course (rather than at an advanced stage after failure of other therapies) if the metastatic lesions exhibit adequate tracer avidity on somatostatin receptor-based imaging. Our patient showed progression of systemic disease after having undergone a second surgery and adjuvant radiotherapy to the head and neck, as well as chemotherapy, and hence was considered a candidate for PRRT. In a pretreatment study, the metastatic lesions demonstrated avidity to both somatostatin receptors and (18)F-FDG. Three months after the first cycle of treatment, when the patient was being evaluated for a second cycle, both imaging parameters showed evidence of a partial response that included nearly complete resolution of the two previously seen lesions. In view of the relatively good tolerability, minimal side effects, and targeted nature of the treatment, PRRT may evolve to become the first-line therapy for metastatic Merkel cell carcinoma and should be examined further in a larger number of patients. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Statistical theory for protein combinatorial libraries. Packing interactions, backbone flexibility, and the sequence variability of a main-chain structure.

PubMed

Kono, H; Saven, J G

2001-02-23

Combinatorial experiments provide new ways to probe the determinants of protein folding and to identify novel folding amino acid sequences. These types of experiments, however, are complicated both by enormous conformational complexity and by large numbers of possible sequences. Therefore, a quantitative computational theory would be helpful in designing and interpreting these types of experiment. Here, we present and apply a statistically based, computational approach for identifying the properties of sequences compatible with a given main-chain structure. Protein side-chain conformations are included in an atom-based fashion. Calculations are performed for a variety of similar backbone structures to identify sequence properties that are robust with respect to minor changes in main-chain structure. Rather than specific sequences, the method yields the likelihood of each of the amino acids at preselected positions in a given protein structure. The theory may be used to quantify the characteristics of sequence space for a chosen structure without explicitly tabulating sequences. To account for hydrophobic effects, we introduce an environmental energy that it is consistent with other simple hydrophobicity scales and show that it is effective for side-chain modeling. We apply the method to calculate the identity probabilities of selected positions of the immunoglobulin light chain-binding domain of protein L, for which many variant folding sequences are available. The calculations compare favorably with the experimentally observed identity probabilities.

Enzyme architecture: optimization of transition state stabilization from a cation-phosphodianion pair.

PubMed

Reyes, Archie C; Koudelka, Astrid P; Amyes, Tina L; Richard, John P

2015-04-29

The side chain cation of R269 lies at the surface of l-glycerol 3-phosphate dehydrogenase (GPDH) and forms an ion pair to the phosphodianion of substrate dihydroxyacetone phosphate (DHAP), which is buried at the nonpolar protein interior. The R269A mutation of GPDH results in a 110-fold increase in K(m) (2.8 kcal/mol effect) and a 41,000-fold decrease in k(cat) (6.3 kcal/mol effect), which corresponds to a 9.1 kcal/mol destabilization of the transition state for GPDH-catalyzed reduction of DHAP by NADH. There is a 6.7 kcal/mol stabilization of the transition state for the R269A mutant GPDH-catalyzed reaction by 1.0 M guanidinium ion, and the transition state for the reaction of the substrate pieces is stabilized by an additional 2.4 kcal/mol by their covalent attachment at wildtype GPDH. These results provide strong support for the proposal that GPDH invests the 11 kcal/mol intrinsic phosphodianion binding energy of DHAP in trapping the substrate at a nonpolar active site, where strong electrostatic interactions are favored, and obtains a 9 kcal/mol return from stabilizing interactions between the side chain cation and transition state trianion. We propose a wide propagation for the catalytic motif examined in this work, which enables strong transition state stabilization from enzyme-phosphodianion pairs.

Universal model of slow pyrolysis technology producing biochar and heat from standard biomass needed for the techno-economic assessment.

PubMed

Klinar, Dušan

2016-04-01

Biochar as a soil amendment and carbon sink becomes in last period one of the vast, interesting product of slow pyrolysis. Simplest and most used industrial process arrangement is a production of biochar and heat at the same time. Proposed mass and heat balance model consist of heat consumers (heat demand side) and heat generation-supply side. Direct burning of all generated uncondensed volatiles from biomass provides heat. Calculation of the mass and heat balance of both sides reveals the internal distribution of masses and energy inside process streams and units. Thermodynamic calculations verified not only the concept but also numerical range of the results. The comparisons with recent published scientific and vendors data prove its general applicability and reliability. The model opens the possibility for process efficiency innovations. Finally, the model was adapted to give more investors favorable results and support techno-economic assessments entirely. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evidence for an intermediate conformational state of LacY.

PubMed

Jiang, Xiaoxu; Guan, Lan; Zhou, Yonggang; Hong, Wen-Xu; Zhang, Qinghai; Kaback, H Ronald

2012-03-20

LacY mutant Cys154 → Gly exhibits a periplasmic-closed crystal structure identical to the WT, but is periplasmic-open in the membrane. The mutant hardly catalyzes transport, but binds galactosides from either side of the membrane with the same affinity and is resistant to site-directed proteolysis relative to the pseudo-WT. Site-directed alkylation was also applied to 11 single-Cys mutants in Cys154 → Gly LacY in right-side-out membrane vesicles or after solubilization and purification in dodecyl-β-D-maltopyranoside (DDM). Unlike the pseudo-WT, Cys replacements on the periplasmic side of the Cys154 → Gly mutant label rapidly in the membrane without sugar, but labeling decreases markedly after the mutant proteins are purified. Thus, Cys154 → Gly LacY likely favors a higher-energy intermediate periplasmic-open conformation in situ, but collapses to a lower-energy periplasmic-closed conformation in DDM after purification. Notably, branched-chain or neopentyl glycol maltoside detergents stabilize Cys154 → Gly LacY in the membrane-embedded form.

Collisions of plastic and foam laser-driven foils studied by orthogonal x-ray imaging.

NASA Astrophysics Data System (ADS)

Aglitskiy, Y.; Metzler, N.; Karasik, M.; Serlin, V.; Obenschain, S. P.; Schmitt, A. J.; Velikovich, A. L.; Zalesak, S. T.; Gardner, J. H.; Weaver, J.; Oh, J.; Harding, E. C.

2007-11-01

We report an experimental study of hydrodynamic Rayleigh-Taylor and Richtmyer-Meshkov-type instabilities developing at the material interface produced in double-foil collisions. Our double-foil targets consist of a plastic foil irradiated by the 4 ns Nike KrF laser pulse at ˜50 TW/cm^2 and accelerated toward a stationary plastic or foam foil. Either the rear side of the front foil or the front side of the rear foil is rippled. Orthogonal imaging, i. e., a simultaneous side-on and face-on x-ray radiography of the targets has been used in these experiments to observe the process of collision and the evolution of the areal mass amplitude modulation. Its observed evolution is similar to the case of the classical RM instability in finite thickness targets first studied by Y. Aglitsky et al., Phys. Plasmas 13, 80703 (2006). Our data are favorably compared with 1D and 2D simulation results.

GDP Release Preferentially Occurs on the Phosphate Side in Heterotrimeric G-proteins

PubMed Central

Louet, Maxime; Martinez, Jean; Floquet, Nicolas

2012-01-01

After extra-cellular stimulation of G-Protein Coupled Receptors (GPCRs), GDP/GTP exchange appears as the key, rate limiting step of the intracellular activation cycle of heterotrimeric G-proteins. Despite the availability of a large number of X-ray structures, the mechanism of GDP release out of heterotrimeric G-proteins still remains unknown at the molecular level. Starting from the available X-ray structure, extensive unconstrained/constrained molecular dynamics simulations were performed on the complete membrane-anchored Gi heterotrimer complexed to GDP, for a total simulation time overcoming 500 ns. By combining Targeted Molecular Dynamics (TMD) and free energy profiles reconstruction by umbrella sampling, our data suggest that the release of GDP was much more favored on its phosphate side. Interestingly, upon the forced extraction of GDP on this side, the whole protein encountered large, collective motions in perfect agreement with those we described previously including a domain to domain motion between the two ras-like and helical sub-domains of Gα. PMID:22829757

Biosynthetic tailoring of existing ascaroside pheromones alters their biological function in C. elegans

PubMed Central

Zhang, Xinxing; Bhar, Subhradeep; Jones Lipinski, Rachel A; Han, Jungsoo; Feng, Likui

2018-01-01

Caenorhabditis elegans produces ascaroside pheromones to control its development and behavior. Even minor structural differences in the ascarosides have dramatic consequences for their biological activities. Here, we identify a mechanism that enables C. elegans to dynamically tailor the fatty-acid side chains of the indole-3-carbonyl (IC)-modified ascarosides it has produced. In response to starvation, C. elegans uses the peroxisomal acyl-CoA synthetase ACS-7 to activate the side chains of medium-chain IC-ascarosides for β-oxidation involving the acyl-CoA oxidases ACOX-1.1 and ACOX-3. This pathway rapidly converts a favorable ascaroside pheromone that induces aggregation to an unfavorable one that induces the stress-resistant dauer larval stage. Thus, the pathway allows the worm to respond to changing environmental conditions and alter its chemical message without having to synthesize new ascarosides de novo. We establish a new model for biosynthesis of the IC-ascarosides in which side-chain β-oxidation is critical for controlling the type of IC-ascarosides produced. PMID:29863473

Efficacy of 15% azelaic acid in psoriasis vulgaris: a randomized, controlled clinical trial.

PubMed

Iraji, Fariba; Faghihi, Gita; Siadat, Amir Hossein; Enshaieh, Shahla; Shahmoradi, Zabihlah; Joia, Abolfazl; Soleimani, Fatemeh

2010-08-01

Psoriasis is a common disorder affecting 1-3 percent of the general global population. Many therapeutic modalities have been suggested for treatment of this condition, but still there is no definite treatment for this disease. The objective in this study was to evaluate the efficacy of topical azelaic acid gel versus placebo in the treatment of psoriasis vulgaris. This study was a single-blinded randomized clinical trial. Overall, 31 patients were selected and the left or right sided lesions of the patients were randomized to receive either 15% azelaic acid or gel twice daily for a one-month period. Two symmetrical lesions with almost similar severity in every patient were selected and considered as index lesions to evaluate lesion response to treatment. The severity of erythema, scaling, hyperkeratosis and pruritus of the index lesions were scored in range of 0-3 for each lesion by the investigator at the baseline and follow up visits. The percent of involvement of each side of body was also measured using rule of nines. The collected data were analyzed using statistical tests including Mann-Whitney and ANOVA tests. There was no significant difference between the two groups before treatment (P > 0.05). After treatment, however, except pruritus, there was significant difference between the two groups (P < 0.05). There was no significant difference regarding total psoriasis score between the two groups before treatment (P > 0.05). After treatment, however, there was significant difference between the two groups (P < 0.05) in favor of more efficacy for azelaic acid. There was no significant difference regarding percent of body involvement between the two groups before treatment (P > 0.05). After treatment, however, there was a significant difference between the two groups (P < 0.05) in favor of more efficacy on the part of azelaic acid gel. The results of our study showed that 15% azelaic acid gel was effective in reduction of purities, scaling and hyperkeratosis of psoriasis plaques. This treatment was also effective in reduction of skin involvement with psoriasis. It is recommended that a longer study be performed that can better evaluate the efficacy of this treatment against plaque-type psoriasis.

Deterrence with China: Avoiding Nuclear Miscalculation

DTIC Science & Technology

2014-01-01

When each nation can manage these three elements in the correct way, the cost -benefit calculations of each side should favor deterrence of a...under pressure to justify the cost of its plans to replace its SSBN fleet. After a recent 2-year delay in the planned SSBN replacement program, any...of CPGS may prove advantageous in some scenarios,31 but those advantages do not come with- out a cost to nuclear deterrence stability with China—a

A Randomized Trial Evaluating Short-term Effectiveness of Overminus Lenses in Children 3 to 6 Years of Age with Intermittent Exotropia.

PubMed

Chen, Angela M; Holmes, Jonathan M; Chandler, Danielle L; Patel, Reena A; Gray, Michael E; Erzurum, S Ayse; Wallace, David K; Kraker, Raymond T; Jensen, Allison A

2016-10-01

To evaluate the short-term effectiveness of overminus spectacles in improving control of childhood intermittent exotropia (IXT). Randomized, clinical trial. A total of 58 children aged 3 to <7 years with IXT. Eligibility criteria included a distance control score of 2 or worse (mean of 3 measures during a single examination) on a scale of 0 (exophoria) to 5 (constant exotropia) and spherical equivalent refractive error between -6.00 diopters (D) and +1.00 D. Children were randomly assigned to overminus spectacles (-2.50 D over cycloplegic refraction) or observation (non-overminus spectacles if needed or no spectacles) for 8 weeks. The primary outcome was distance control score for each child (mean of 3 measures during a single examination) assessed by a masked examiner at 8 weeks. Outcome testing was conducted with children wearing their study spectacles or plano spectacles for the children in the observation group who did not need spectacles. The primary analysis compared mean 8-week distance control score between treatment groups using an analysis of covariance model that adjusted for baseline distance control, baseline near control, prestudy spectacle wear, and prior IXT treatment. Treatment side effects were evaluated using questionnaires completed by parents. At 8 weeks, mean distance control was better in the 27 children treated with overminus spectacles than in the 31 children who were observed without treatment (2.0 vs. 2.8 points, adjusted difference = -0.75 points favoring the overminus group; 2-sided 95% confidence interval, -1.42 to -0.07 points). Side effects of headaches, eyestrain, avoidance of near activities, and blur appeared similar between treatment groups. In a pilot randomized clinical trial, overminus spectacles improved distance control at 8 weeks in children aged 3 to <7 years with IXT. A larger and longer randomized trial is warranted to assess the effectiveness of overminus spectacles in treating IXT, particularly the effect on control after overminus treatment has been discontinued. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Hidden regularity and universal classification of fast side chain motions in proteins

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

Rajeshwar, Rajitha; Smith, Jeremy C.; Krishnam, Marimuthu

Proteins display characteristic dynamical signatures that appear to be universal across all proteins regardless of topology and size. Here, we systematically characterize the universal features of fast side chain motions in proteins by examining the conformational energy surfaces of individual residues obtained using enhanced sampling molecular dynamics simulation (618 free energy surfaces obtained from 0.94 s MD simulation). The side chain conformational free energy surfaces obtained using the adaptive biasing force (ABF) method for a set of eight proteins with different molecular weights and secondary structures are used to determine the methyl axial NMR order parameters (O axis 2), populationsmore » of side chain rotamer states (ρ), conformational entropies (S conf), probability fluxes, and activation energies for side chain inter-rotameric transitions. The free energy barriers separating side chain rotamer states range from 0.3 to 12 kcal/mol in all proteins and follow a trimodal distribution with an intense peak at ~5 kcal/mol and two shoulders at ~3 and ~7.5 kcal/mol, indicating that some barriers are more favored than others by proteins to maintain a balance between their conformational stability and flexibility. The origin and the influences of the trimodal barrier distribution on the distribution of O axis 2 and the side chain conformational entropy are discussed. A hierarchical grading of rotamer states based on the conformational free energy barriers, entropy, and probability flux reveals three distinct classes of side chains in proteins. A unique nonlinear correlation is established between O axis 2 and the side chain rotamer populations (ρ). In conclusion, the apparent universality in O axis 2 versus correlation, trimodal barrier distribution, and distinct characteristics of three classes of side chains observed among all proteins indicates a hidden regularity (or commonality) in the dynamical heterogeneity of fast side chain motions in proteins.« less

Monoamine Oxidase B Inhibitors in Parkinson's Disease.

PubMed

Dezsi, Livia; Vecsei, Laszlo

2017-01-01

Parkinson's disease (PD) is a neurodegenerative disorder with a prevalence increasing with age. Oxidative stress and glutamate toxicity are involved in its pathomechanism. There are still many unmet needs of PD patients, including the alleviation of motor fluctuations and dyskinesias, and the development of therapies with neuroprotective potential. To give an overview of the pharmacological properties, the efficacy and safety of the monoamine oxidase B (MAO-B) inhibitors in the treatment of PD, with special focus on the results of randomized clinical trials. A literature search was conducted in PubMed for 'PD treatment', 'MAO-B inhibitors', 'selegiline', 'rasagiline', 'safinamide' and 'clinical trials' with 'MAO-B inhibitors' in 'Parkinson' disease'. MAO-B inhibitors have a favorable pharmacokinetic profile, improve the dopamine deficient state and may have neuroprotective properties. Safinamide exhibits an anti-glutamatergic effect as well. When applied as monotherapy, MAO-B inhibitors provide a modest, but significant improvement of motor function and delay the need for levodopa. Rasagiline and safinamide were proven safe and effective when added to a dopamine agonist in early PD. As add-on to levodopa, MAO-B inhibitors significantly reduced off-time and were comparable in efficacy to COMT inhibitors. Improvements were achieved as regards certain non-motor symptoms as well. Due to the efficacy shown in clinical trials and their favorable side-effect profile, MAO-B inhibitors are valuable drugs in the treatment of PD. They are recommended as monotherapy in the early stages of the disease and as add-on therapy to levodopa in advanced PD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Moist Climates with an Ineffective Cold Trap

NASA Astrophysics Data System (ADS)

Ding, F.; Pierrehumbert, R.

2016-12-01

The tropopause of the Earth's atmosphere behaves as a cold trap, limiting the water vapor transport from the humid sea surface to the dry regions in the atmosphere including both the upper atmosphere and the highly sub-saturated places in the free troposphere. It is hypothesized that during some period of time on Earth, the cold trap mechanism would become less effective, due to either a reduced nitrogen inventory in the atmosphere or high surface temperatures. An ineffective cold trap favors a moist upper atmosphere and will lead to rapid water loss by the ultraviolet photodissociation, which was well studied in one-dimensional models. However, the effect of an ineffective cold trap on 3D climates has not yet received much attention. Here we explore the 3D effect with an idealized general circulation model especially designed for studying condensible-rich atmospheres. We consider two scenarios based on the orbital configuration of the planet. (a) With Earth's orbital parameters, sub-saturation in the free troposphere is difficult to be produced by large-scale atmospheric flows, which implies that an ineffective cold trap also favors the onset of the runaway greenhouse. (b) For synchronous-rotating planets, water vapor is easier to be transported to the nightside, building up an atmosphere with similar column water mass as the dayside. For extrasolar habitable planets detections around M dwarfs in the future, if the water vapor contrast between the day and night side could be provided by the phase-resolved emission spectra, the contrast might be useful as a constraint for evaluating the mass of the non-condensible components in the atmosphere.

Drug-binding energetics of human α-1-acid glycoprotein assessed by isothermal titration calorimetry and molecular docking simulations

PubMed Central

Huang, Johnny X.; Cooper, Matthew A.; Baker, Mark A.; Azad, Mohammad A.K.; Nation, Roger L.; Li, Jian; Velkov, Tony

2012-01-01

This study utilizes sensitive, modern isothermal titration calorimetric (ITC) methods to characterize the microscopic thermodynamic parameters that drive the binding of basic drugs to α-1-acid glycoprotein (AGP) and thereby rationalize the thermodynamic data in relation to docking models and crystallographic structures of the drug-AGP complexes. The binding of basic compounds from the tricyclic antidepressant series, together with miaserine, chlorpromazine, disopyramide and cimetidine all displayed an exothermically driven binding interaction with AGP. The impact of protonation/deprotonation events, ionic strength, temperature and the individual selectivity of the A and F1*S AGP variants on drug-binding thermodynamics were characterized. A correlation plot of the thermodynamic parameters for all of the test compounds revealed enthalpy-entropy compensation is in effect. The exothermic binding energetics of the test compounds were driven by a combination of favorable (negative) enthalpic (ΔH°) and favorable (positive) entropic (ΔS°) contributions to the Gibbs free energy (ΔG°). Collectively, the data imply that the free energies that drive drug binding to AGP and its relationship to drug-serum residency evolve from the complex interplay of enthalpic and entropic forces from interactions with explicit combinations of hydrophobic and polar side-chain sub-domains within the multi-lobed AGP ligand binding cavity. PMID:23192962

Effect of long-term impact-loading on mass, size, and estimated strength of humerus and radius of female racquet-sports players: a peripheral quantitative computed tomography study between young and old starters and controls.

PubMed

Kontulainen, Saija; Sievänen, Harri; Kannus, Pekka; Pasanen, Matti; Vuori, Ilkka

2003-02-01

Bone characteristics of the humeral shaft and distal radius were measured from 64 female tennis and squash players and their 27 age-, height-, and weight-matched controls with peripheral quantitative tomography (pQCT) and dual energy X-ray absorptiometry (DXA). The players were divided into two groups according to the starting age of their tennis or squash training (either before or after menarche) to examine the possible differences in the loading-induced changes in bone structure and volumetric density. The following pQCT variables were used: bone mineral content, total cross-sectional area of bone (TotA), cross-sectional area of the marrow cavity (CavA) and that of the cortical bone (CoA), cortical wall thickness (CWT), volumetric density of the cortical bone (CoD) and trabecular bone (TrD), and torsional bone strength index for the shaft (BSIt) and compressional bone strength index for the bone end (BSIc). These bone strength indices were compared with the DXA-derived areal bone mineral density (aBMD) to assess how well the latter represents the effect of mechanical loading on apparent bone strength. At the humeral shaft, the loaded arm's greater bone mineral content (an average 19% side-to-side difference in young starters and 9% in old starters), was caused by an enlarged cortex (CoA; side-to-side differences 20% and 9%, respectively). The loaded humerus seemed to have grown periosteally (the CavA did not differ between the sites), leading to 26% and 11% side-to-side BSIt differences in the young and old starters, respectively. CoD was equal between the arms (-1% difference in both player groups). The side-to-side differences in the young starters' bone mineral content, CoA, TotA, CWT, and BSIt were 8-22% higher than those of the controls and 8-14% higher than those of the old starters. Old starters' bone mineral content, CoA, and BSIt side-to-side differences were 6-7% greater than those in the controls. The DXA-derived side-to-side aBMD difference was 7% greater in young starters compared with that of the old starters and 14% compared with that in controls, whereas the difference between old starters and controls was 6%, in favor of the former. All these between-group differences were statistically significant. At the distal radius, the player groups differed significantly from controls in the side-to-side bone mineral content, TrD, and aBMD differences only: the young starters' bone mineral content difference was 9% greater, TrD and aBMD differences were 5% greater than those in the controls, and the old starters' TrD and aBMD differences were both 7% greater than those in the controls. In summary, in both of the female player groups, the structural adaptation of the humeral shaft to long-term loading seemed to be achieved through periosteal enlargement of the bone cortex, although this adaptation was clearly better in the young starters. Exercise-induced cortical enlargement was not so clear at the distal radius (a trabecular bone site), and the study suggested that at long bone ends, the trabecular density could be a modifiable factor to built a stronger bone structure. Conventional DXA-based aBMD measurement detected the intergroup differences in the exercise-induced bone gains, although, because it measured two dimensions of bone only, it seemed to underestimate the effect of exercise on the apparent bone strength, especially if the playing had been started during the growing years.

Transdermal glimepiride delivery system based on optimized ethosomal nano-vesicles: Preparation, characterization, in vitro, ex vivo and clinical evaluation.

PubMed

Ahmed, Tarek A; El-Say, Khalid M; Aljaeid, Bader M; Fahmy, Usama A; Abd-Allah, Fathy I

2016-03-16

This work aimed to develop an optimized ethosomal formulation of glimepiride then loading into transdermal films to offer lower drug side effect, extended release behavior and avoid first pass effect. Four formulation factors were optimized for their effects on vesicle size (Y1), entrapment efficiency (Y2) and vesicle flexibility (Y3). Optimum desirability was identified and, an optimized formulation was prepared, characterized and loaded into transdermal films. Ex-vivo permeation study for the prepared films was conducted and, the permeation parameters and drug permeation mechanism were identified. Penetration through rat skin was studied using confocal laser microscope. In-vivo study was performed following transdermal application on human volunteers. The percent of alcohol was significantly affecting all the studied responses while the other factors and their interaction effects were varied on their effects on each response. The optimized ethosomal formulation showed observed values for Y1, Y2 and Y3 of 61 nm, 97.12% and 54.03, respectively. Ex-vivo permeation of films loaded with optimized ethosomal formulation was superior to that of the corresponding pure drug transdermal films and this finding was also confirmed after confocal laser microscope study. Permeation of glimepiride from the prepared films was in favor of Higushi-diffusion model and exhibited non-Fickian or anomalous release mechanism. In-vivo study revealed extended drug release behavior and lower maximum drug plasma level from transdermal films loaded with drug ethosomal formulation. So, the ethosomal formulation could be considered a suitable drug delivery system especially when loaded into transdermal vehicle with possible reduction in side effects and controlling the drug release. Copyright © 2016 Elsevier B.V. All rights reserved.

[Influence of the mandibular second premolar extraction on the angulation of the mandibular third molar].

PubMed

Feng, Guang-yao; Zou, Bing-shuang; Gao, Xue-mei; Zeng, Xiang-long; Wang, Xiu-jing; Yan, Yan

2013-02-18

To compare the angular changes in the developing mandibular third molars in the mandibular second premolar extraction and non-extraction cases and to determine whether the mandibular second premolar extraction causes favorable rotational changes in the angulations of the developing mandibular third molars and benefits its later eruption. Pretreatment and posttreatment panoramic radiographs were taken from 45 subjects who had been treated by the extraction of the mandibular second premolars and 48 subjects who had been treated without extraction. The horizontal reference plane was used to measure and compare the changes in the angulations of the developing mandibular third molars. The mean uprighting of the mandibular third molars seen in the extraction group was (5.9±2.5) degrees on the right side and (8.0±3.4) degrees on the left side following treatment. For the nonextraction group the mean uprighting was (1.8±2.4) degrees on the right side and (1.5±2.1) degrees on the left side. There was a statistically significant difference between the groups (P<0.05). Mandibular second premolar extraction might be a helpful procedure on the angulations of the developing mandibular third molars.

[Comparisons of efficacy and safety of levetiracetam versus phenytoin for seizure prophylaxis in patients with brain injury: a meta analysis].

PubMed

Li, J N; Chen, Y M

2016-10-25

Objective: To systematically review the efficacy, side effects and case-fatality rate of levetiracetam (LEV) versus phenytoin (PHT) for seizure prophylaxis of brain injured patients. Methods: Randomized controlled trials of high quality about LEV versus PHT in seizure prophylaxis of brain injured patients from 2000 to 2016 were collected according to the key word PHT, LEV, brain injury in PubMed, Medline, Ovid, Springer, CNKI, Wanfang data and so on. Valid data were extracted to conduct meta-analysis by RevMan 5.3 software according to inclusion and exclusion criteria. Results: A total of 13 English articles were finally included with 2 529 patients in total.Meta-analysis showed that no significant differences were observed in LEV versus PHT at preventing the occurrence of seizures ( RR =0.88, 95% CI : 0.61-1.27). No superiority of either drug at preventing early seizures ( RR =0.74, 95% CI : 0.42-1.27). As to the occurrence of late seizures, the differences of the two drugs were not statistically significant ( RR =0.71, 95% CI : 0.43-1.20). Number of patients with side effect was not statistically significantly different between the two groups ( RR =0.73, 95% CI : 0.48-1.11). But significant difference was found between LEV and PHT in discontinuation because of side effect ( RR =0.11, 95% CI : 0.06-0.23); no significant differences were noted in the case-fatality rate of patients received pretreatment between the two drugs ( RR =1.57, 95% CI : 0.92-2.67). There were no significant differences between the two groups in the length of stay ( WMD =-1.03, 95% CI : -4.97-2.91). Conclusions: LEV and PHT demonstrate equal efficacy in seizure prevention after brain injury. The differences are insignificant in the side effect, the case-fatality rate and the length of stay between LEV and PH treatment, but adverse drug reactions requiring change in therapy occur more in PHT. Phenytoin remains the first choice for seizure prevention after brain injury based on the existing evidence, while levetiracetam seems to be a favorable choice where there is risk of drug-drug interactions and drug toxicity. However, very few randomized controlled trials on this topic were found, and larger prospective trials are warranted.

Tissue Engineering of the Urethra: A Systematic Review and Meta-analysis of Preclinical and Clinical Studies.

PubMed

Versteegden, Luuk R M; de Jonge, Paul K J D; IntHout, Joanna; van Kuppevelt, Toin H; Oosterwijk, Egbert; Feitz, Wout F J; de Vries, Rob B M; Daamen, Willeke F

2017-10-01

Urethra repair by tissue engineering has been extensively studied in laboratory animals and patients, but is not routinely used in clinical practice. To systematically investigate preclinical and clinical evidence of the efficacy of tissue engineering for urethra repair in order to stimulate translation of preclinical studies to the clinic. A systematic search strategy was applied in PubMed and EMBASE. Studies were independently screened for relevance by two reviewers, resulting in 80 preclinical and 23 clinical studies of which 63 and 13 were selected for meta-analysis to assess side effects, functionality, and study completion. Analyses for preclinical and clinical studies were performed separately. Full circumferential and inlay procedures were assessed independently. Evaluated parameters included seeding of cells and type of biomaterial. Meta-analysis revealed that cell seeding significantly reduced the probability of encountering side effects in preclinical studies. Remarkably though, cells were only sparsely used in the clinic (4/23 studies) and showed no significant reduction of side effects. ln 21 out of 23 clinical studies, decellularized templates were used, while in preclinical studies other biomaterials showed promising outcomes as well. No direct comparison to current clinical practice could be made due to the limited number of randomized controlled studies. Due to a lack of controlled (pre)clinical studies, the efficacy of tissue engineering for urethra repair could not be determined. Meta-analysis outcome measures were similar to current treatment options described in literature. Surprisingly, it appeared that favorable preclinical results, that is inclusion of cells, were not translated to the clinic. Improved (pre)clinical study designs may enhance clinical translation. We reviewed all available literature on urethral tissue engineering to assess the efficacy in preclinical and clinical studies. We show that improvements to (pre)clinical study design is required to improve clinical translation of tissue engineering technologies. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Reliability of Measurement of Glenohumeral Internal Rotation, External Rotation, and Total Arc of Motion in 3 Test Positions

PubMed Central

Kevern, Mark A.; Beecher, Michael; Rao, Smita

2014-01-01

Context: Athletes who participate in throwing and racket sports consistently demonstrate adaptive changes in glenohumeral-joint internal and external rotation in the dominant arm. Measurements of these motions have demonstrated excellent intrarater and poor interrater reliability. Objective: To determine intrarater reliability, interrater reliability, and standard error of measurement for shoulder internal rotation, external rotation, and total arc of motion using an inclinometer in 3 testing procedures in National Collegiate Athletic Association Division I baseball and softball athletes. Design: Cross-sectional study. Setting: Athletic department. Patients or Other Participants Thirty-eight players participated in the study. Shoulder internal rotation, external rotation, and total arc of motion were measured by 2 investigators in 3 test positions. The standard supine position was compared with a side-lying test position, as well as a supine test position without examiner overpressure. Results: Excellent intrarater reliability was noted for all 3 test positions and ranges of motion, with intraclass correlation coefficient values ranging from 0.93 to 0.99. Results for interrater reliability were less favorable. Reliability for internal rotation was highest in the side-lying position (0.68) and reliability for external rotation and total arc was highest in the supine-without-overpressure position (0.774 and 0.713, respectively). The supine-with-overpressure position yielded the lowest interrater reliability results in all positions. The side-lying position had the most consistent results, with very little variation among intraclass correlation coefficient values for the various test positions. Conclusions: The results of our study clearly indicate that the side-lying test procedure is of equal or greater value than the traditional supine-with-overpressure method. PMID:25188316

Does the primary site of colorectal cancer impact outcomes for patients with metastatic disease?

PubMed

Price, Timothy J; Beeke, Carol; Ullah, Shahid; Padbury, Robert; Maddern, Guy; Roder, David; Townsend, Amanda R; Moore, James; Roy, Amitesh; Tomita, Yoko; Karapetis, Christos

2015-03-15

Previous reports have described differences in biology and outcome for colorectal cancer based on whether the primary is right or left sided. Further division by right, left, and rectum or even exact primary site has also been explored. Possible differences in response to biological agents have also been reported based on side of primary lesion. We explored the South Australian registry for metastatic colorectal cancer to assess if there were any differences in patient characteristics, prognostic markers, and treatment received and outcomes based on whether the primary was right or left sided. We also explored if differences exist based on left colon and rectum and by exact primary site. Two thousand nine hundred seventy-two patients were analyzed. Thirty-five percent had a right-sided primary. The median overall survival for the entire group right versus left was 9.6 versus 20.3 months (P < .001). Multivariate analysis confirmed side of primary as an independent prognostic factor. For the group that had active therapy, defined as chemotherapy (± metastasis resection), median overall survival was right, 18.2 months; and left, 29.4 months (P < .001). Importantly, we found no suggestion of major differences if left side was divided by left colon and rectum, and trends by individual site still supported a left and right division. Patients with a right-sided primary have more negative prognostic factors and indeed have inferior outcomes compared with those with a left-sided primary. Our data with further breakdown by exact site still favor a simple left-versus-right division moving forward for metastatic colorectal cancer. © 2014 American Cancer Society.

Restoring conjunctival tolerance by topical nuclear factor-κB inhibitors reduces preservative-facilitated allergic conjunctivitis in mice.

PubMed

Guzmán, Mauricio; Sabbione, Florencia; Gabelloni, María Laura; Vanzulli, Silvia; Trevani, Analía Silvina; Giordano, Mirta Nilda; Galletti, Jeremías Gastón

2014-09-04

To evaluate the role of nuclear factor-κB (NF-κB) activation in eye drop preservative toxicity and the effect of topical NF-κB inhibitors on preservative-facilitated allergic conjunctivitis. Balb/c mice were instilled ovalbumin (OVA) combined with benzalkonium chloride (BAK) and/or NF-κB inhibitors in both eyes. After immunization, T-cell responses and antigen-induced ocular inflammation were evaluated. Nuclear factor-κB activation and associated inflammatory changes also were assessed in murine eyes and in an epithelial cell line after BAK exposure. Benzalkonium chloride promoted allergic inflammation and leukocyte infiltration of the conjunctiva. Topical NF-κB inhibitors blocked the disruptive effect of BAK on conjunctival immunological tolerance and ameliorated subsequent ocular allergic reactions. In line with these findings, BAK induced NF-κB activation and the secretion of IL-6 and granulocyte-monocyte colony-stimulating factor in an epithelial cell line and in the conjunctiva of instilled mice. In addition, BAK favored major histocompatibility complex (MHC) II expression in cultured epithelial cells in an NF-κB-dependent fashion after interaction with T cells. Benzalkonium chloride triggers conjunctival epithelial NF-κB activation, which seems to mediate some of its immune side effects, such as proinflammatory cytokine release and increased MHC II expression. Breakdown of conjunctival tolerance by BAK favors allergic inflammation, and this effect can be prevented in mice by topical NF-κB inhibitors. These results suggest a new pharmacological target for preservative toxicity and highlight the importance of conjunctival tolerance in ocular surface homeostasis. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Backbone and stereospecific (13)C methyl Ile (δ1), Leu and Val side-chain chemical shift assignments of Crc.

PubMed

Sharma, Rakhi; Sahu, Bhubanananda; Ray, Malay K; Deshmukh, Mandar V

2015-04-01

Carbon catabolite repression (CCR) allows bacteria to selectively assimilate a preferred compound among a mixture of several potential carbon sources, thus boosting growth and economizing the cost of adaptability to variable nutrients in the environment. The RNA-binding catabolite repression control (Crc) protein acts as a global post-transcriptional regulator of CCR in Pseudomonas species. Crc triggers repression by inhibiting the expression of genes involved in transport and catabolism of non-preferred substrates, thus indirectly favoring assimilation of preferred one. We report here a nearly complete backbone and stereospecific (13)C methyl side-chain chemical shift assignments of Ile (δ1), Leu and Val of Crc (~ 31 kDa) from Pseudomonas syringae Lz4W.

RF-Phos: A Novel General Phosphorylation Site Prediction Tool Based on Random Forest.

PubMed

Ismail, Hamid D; Jones, Ahoi; Kim, Jung H; Newman, Robert H; Kc, Dukka B

2016-01-01

Protein phosphorylation is one of the most widespread regulatory mechanisms in eukaryotes. Over the past decade, phosphorylation site prediction has emerged as an important problem in the field of bioinformatics. Here, we report a new method, termed Random Forest-based Phosphosite predictor 2.0 (RF-Phos 2.0), to predict phosphorylation sites given only the primary amino acid sequence of a protein as input. RF-Phos 2.0, which uses random forest with sequence and structural features, is able to identify putative sites of phosphorylation across many protein families. In side-by-side comparisons based on 10-fold cross validation and an independent dataset, RF-Phos 2.0 compares favorably to other popular mammalian phosphosite prediction methods, such as PhosphoSVM, GPS2.1, and Musite.

Effective model approach to the dense state of QCD matter

NASA Astrophysics Data System (ADS)

Fukushima, Kenji

2011-12-01

The first-principle approach to the dense state of QCD matter, i.e. the lattice-QCD simulation at finite baryon density, is not under theoretical control for the moment. The effective model study based on QCD symmetries is a practical alternative. However the model parameters that are fixed by hadronic properties in the vacuum may have unknown dependence on the baryon chemical potential. We propose a new prescription to constrain the effective model parameters by the matching condition with the thermal Statistical Model. In the transitional region where thermal quantities blow up in the Statistical Model, deconfined quarks and gluons should smoothly take over the relevant degrees of freedom from hadrons and resonances. We use the Polyakov-loop coupled Nambu-Jona-Lasinio (PNJL) model as an effective description in the quark side and show how the matching condition is satisfied by a simple ansäatz on the Polyakov loop potential. Our results favor a phase diagram with the chiral phase transition located at slightly higher temperature than deconfinement which stays close to the chemical freeze-out points.

Effect of combined topical heparin and steroid on corneal neovascularization in children.

PubMed

Michels, Rike; Michels, Stephan; Kaminski, Stephan

2012-01-01

To demonstrate the effect of topical heparin combined with topical steroid on corneal neovascularization (CN) in children. Four children (5 eyes) with new-onset progressive CN in at least one eye received topical rimexolone or dexamethasone in combination with heparin until complete regression of CN was obtained. The regression of CN was documented by slit-lamp or anterior segment photography. All 5 eyes showed complete regression of CN within 5 months. An anti-angiogenic effect was found as early as 1 week after starting topical combination treatment. No ocular and systemic side effects were detected and treatment was well tolerated by all children. In the 3 eyes with involvement of the optical axis, symmetrical visual acuity was obtained by amblyopia treatment. Recurrence of the CN was detectable in 2 eyes at 1 and 6 months, respectively, after ending combination therapy. Both eyes responded favorably to re-treatment. Combination of topical heparin and steroid leads to rapid regression and complete inactivity of CN. This therapeutic approach is promising, especially in children with limited therapeutic alternatives and a high risk for amblyopia. Copyright 2012, SLACK Incorporated.

Comparative study of flux of FITC-labeled Dextran 4000 on normal (iso)- and hyper-osmolarity in basal side in caco-2 cell monolayers.

PubMed

Ohkubo, Rie; Tomita, Mikio; Hotta, Yoshiyuki; Nagira, Mayuko; Hayashi, Masahiro

2003-01-01

We have shown previously that the flux of fluorescein isothiocyanate dextran 4000 (FD-4) is transported across the Caco-2 cell monolayers in a polarized fashion favoring the basal to apical direction under normal conditions (i.e., isotonic solution in basal side). Furthermore, FD-4 transport may occur via a process that included a certain degree of substrate specificity for polysaccharide and transcytosis. In the present study, we compared the flux of FD-4 in the basal to apical direction (efflux) and the apical to basal direction (influx) in stress conditions (i.e., hyperosmolarity in basal side) to those in normal conditions (i.e., iso-osmolarity in basal side). The efflux of FD-4 was increased by hyperosmolarity in basal side, but the influx was decreased when compared with normal conditions. Neither dextran 10, 000 nor colchicine inhibited the efflux of FD-4 in hyperosmolarity conditions. The inhibition of efflux of FD-4 was observed not by S-nitroso-N-acetylpenicillamine but by sodium nitroprusside and sodium ferrocyanide. These results collectively suggest that hyperosmolarity in basal side accelerates the efflux of FD-4 across the transcellular route but not across the paracellular route in Caco-2 cell monolayers. And it is indicated that cyanide rather than nitric oxide is involved in dysfunction of the FD-4 efflux system irrespective of conditions such as normal osmolarity or hyperosmolarity.

Update on Middle Ear Barotrauma after Hyperbaric Oxygen Therapy—Insights on Pathophysiology

PubMed Central

Lima, Marco Antônio Rios; Farage, Luciano; Cury, Maria Cristina Lancia; Bahamad, Fayez

2014-01-01

Introduction Middle ear barotrauma is the most common side effect of hyperbaric oxygen therapy. Knowledge and understanding of its pathophysiology are crucial for an accurate diagnosis and proper decision making about treatment and prevention. Objective Describe up-to-date information on pathophysiology of middle ear barotrauma after hyperbaric oxygen therapy considering the physiology of pressure variation of the middle ear. Data Synthesis Middle ear barotrauma occurs especially during the compression phase of hyperbaric oxygen therapy. The hyperoxic environment in hyperbaric oxygen therapy leads to ventilatory dysfunction of the eustachian tube, especially in monoplace chambers, where the patients are pressurized with 100% O2, favoring middle ear barotrauma. Conclusion The eustachian tube, the tympanic cavity, and mastoid work together in a neural controlled feedback system in which various mechanisms concur for middle ear pressure regulation. PMID:25992091

[Self defense instead of offense - Immunotherapy in lung cancer].

PubMed

Moldvay, Judit; Ostoros, Gyula

2016-03-02

Lung cancer is the leading cause of cancer death worldwide and also in Hungary, therefore new therapeutic strategies are of great importance. Among immunotherapeutic approaches immune checkpoint inhibition appears to be the most promising. Recent studies have shown efficacy of immunotherapy, especially in squamous cell lung cancer, which is a big step forward in the treatment of this histological subtype. Unlike in the molecularly targeted therapies, the patient selection method has not yet been developed, although some studies indicate the predictive value of tumor cell PD-L1 immunopositivity, especially in lung adenocarcinoma. Introduction of immunotherapy carries challenge for clinicians regarding the radiological assessment of therapeutic efficiency as well as the management of side effects of new profile. The favorable results of recent studies, however, provide hope in this malignancy still presenting a major therapeutic challenge.

Nabumetone in the treatment of skin and soft tissue injury.

PubMed

Jenner, P N

1987-10-30

Nabumetone, a new nonsteroidal anti-inflammatory agent, has been evaluated for the treatment of skin and soft tissue injury, including sports injury, in clinical trials involving nearly 1,000 patients. Its efficacy, safety, and tolerance in these patients is reviewed. The efficacy of nabumetone in the treatment of soft tissue injury has been demonstrated to be similar to that of soluble aspirin, ibuprofen, and naproxen. It was not possible in these studies to demonstrate a definite advantage over placebo, and the reasons for this are discussed along with some suggestions for future studies. There were no serious adverse experiences reported, and nabumetone was well tolerated and compared favorably with the other agents used, including placebo. It caused significantly fewer gastrointestinal side effects than soluble aspirin. Nabumetone is an appropriate choice of nonsteroidal anti-inflammatory drug for the treatment of sports injury.

[Alemtuzumab for relapsing-remitting multiple sclerosis. Results of two randomized controlled phase III studies].

PubMed

Klotz, L; Meuth, S G; Kieseier, B; Wiendl, H

2013-08-01

In November 2012 the results of 2 clinical phase III trials were published which addressed the effects of alemtuzumab in patients with relapsing-remitting multiple sclerosis (MS). In the CARE-MS-I study patients with early untreated MS (EDSS ≤ 3.0, disease duration < 5 years) were included, whereas CARE-MS-II investigated the effects of alemtuzumab in patients with persisting disease activity under standard disease-modifying treatment (EDSS ≤ 5.0, disease duration < 10 years). These groups were compared to patients under treatment with frequently applied interferon β 1a (3 times  44 µg subcutaneous). Both studies clearly demonstrated a superiority of alemtuzumab compared to interferon in terms of reduction of relapse rate as well as the number of new or enlarging T2 lesions and gadolinium-enhancing lesions. Moreover, the CARE-MS-II study showed a significant delay in disease progression by alemtuzumab. The portfolio and the frequency of relevant side effects, such as infusion-related reactions, development of secondary autoimmunity or infections were within the expected range. Taken together these studies confirm the high anti-inflammatory efficacy of alemtuzumab and hence provide the first evidence of superiority of a monotherapy in direct comparison to standard disease-modifying treatment in two phase III trials in relapsing-remitting MS. These data in the context of the mode of action of alemtuzumab provide evidence for the relevance of immune cells, especially T cells, in the pathophysiology of MS. Experience with long-term effects of alemtuzumab, e.g. from the phase II extension trial as well as the side effect profile argue in favor of a sustained reprogramming of the immune system as a consequence of immune cell depletion by alemtuzumab.

The dual nature of retinoic acid in pemphigus and its therapeutic potential: Special focus on all-trans Retinoic Acid.

PubMed

Tavakolpour, Soheil; Daneshpazhooh, Maryam; Mahmoudi, Hamid Reza; Balighi, Kamran

2016-07-01

The efficient treatment of pemphigus with no certain side effect remained a controversial issue. Although there are various options for controlling disease severity, the majority of them may cause serious side effects. Retinoic acid (RA), an active metabolite converted from vitamin A, plays an active role in immune functions. Effects of RA, especially all-trans-Retinoic Acid (ATRA) on different types of cells involved in immune responses were analyzed in vitro and in vivo. RAs could affect the differentiation of T helper (Th) cells, B cells responses, stabilization of both natural regulatory T cells (nTregs) and regulatory B cells (Bregs) populations, and regulating the expression of critical genes in immune responses. The role of RA, based on major immune cells involved in pemphigus has not been addressed so far. In this study, we sought to determine the possible effects of RA, with a special focus on ATRA in pemphigus. All the evidences of ATRA effects on the immune system were collected and their association with the pemphigus was analyzed. According to the previous results, ATRA causes a decline in Th17 populations; increase in CD4+ induced regulatory T cells (iTregs), stabilization of nTregs, and promotion of suppressive B cells, which are critical in the improvement of pemphigus. Nevertheless, it also causes shifting of the Th1:Th2 balance toward Th2 cells, which is not favorable for pemphigus patients. In conclusion, ATRA acts via different ways in pemphigus. Due to increase in the suppressive function via iTregs, nTregs, and Bregs, it is suggested that patients with pemphigus may benefit from systemic ATRA therapy. To clarify this issue, further studies, such as clinical trials are needed. Copyright © 2016 Elsevier B.V. All rights reserved.

Air Warfare and Air Base Defense 1914-1973

DTIC Science & Technology

1988-01-01

ground commanders diluted German efforts. Rommel described the prob- lem in organizational terms: " One thing that worked very seriously against us was...exerted severe pressure on the Marines. Japanese attempts at reinforcing their garri - son were constant and could be defeated only by air attacks on the...and in many cases pure chance that favors one side over the other. In response to a request by the Air Force Director of Plans, the Office of Air Force

Simple phalanx pattern leads to energy saving in cohesive fish schooling.

PubMed

Ashraf, Intesaaf; Bradshaw, Hanaé; Ha, Thanh-Tung; Halloy, José; Godoy-Diana, Ramiro; Thiria, Benjamin

2017-09-05

The question of how individuals in a population organize when living in groups arises for systems as different as a swarm of microorganisms or a flock of seagulls. The different patterns for moving collectively involve a wide spectrum of reasons, such as evading predators or optimizing food prospection. Also, the schooling pattern has often been associated with an advantage in terms of energy consumption. In this study, we use a popular aquarium fish, the red nose tetra fish, Hemigrammus bleheri , which is known to swim in highly cohesive groups, to analyze the schooling dynamics. In our experiments, fish swim in a shallow-water tunnel with controlled velocity, and stereoscopic video recordings are used to track the 3D positions of each individual in a school, as well as their tail-beating kinematics. Challenging the widespread idea of fish favoring a diamond pattern to swim more efficiently [Weihs D (1973) Nature 241:290-291], we observe that when fish are forced to swim fast-well above their free-swimming typical velocity, and hence in a situation where efficient swimming would be favored-the most frequent configuration is the "phalanx" or "soldier" formation, with all individuals swimming side by side. We explain this observation by considering the advantages of tail-beating synchronization between neighbors, which we have also characterized. Most importantly, we show that schooling is advantageous as compared with swimming alone from an energy-efficiency perspective.

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.

Debris-free rear-side picosecond laser ablation of thin germanium wafers in water with ethanol

NASA Astrophysics Data System (ADS)

Zhang, Dongshi; Gökce, Bilal; Sommer, Steffen; Streubel, René; Barcikowski, Stephan

2016-03-01

In this paper, we perform liquid-assisted picosecond laser cutting of 150 μm thin germanium wafers from the rear side. By investigating the cutting efficiency (the ability to allow an one-line cut-through) and quality (characterized by groove morphologies on both sides), the pros and cons of this technique under different conditions are clarified. Specifically, with laser fluence fixed, repetition rate and scanning speed are varied to show quality and efficiency control by means of laser parameter modulation. It is found that low repetition rate ablation in liquid gives rise to a better cut quality on the front side than high repetition rate ablation since it avoids dispersed nanoparticles redeposition resulting from a bubble collapse, unlike the case of 100 kHz which leads to large nanorings near the grooves resulting from a strong interaction of bubbles and the case of 50 kHz which leads to random cutting due to the interaction of the former pulse induced cavitation bubble and the subsequent laser pulse. Furthermore, ethanol is mixed with pure distilled water to assess the liquid's impact on the cutting efficiency and cutting quality. The results show that increasing the ethanol fraction decreases the ablation efficiency but simultaneously, greatly improves the cutting quality. The improvement of cut quality as ethanol ratio increases may be attributed to less laser beam interference by a lower density of bubbles which adhere near the cut kerf during ablation. A higher density of bubbles generated from ethanol vaporization during laser ablation in liquid will cause stronger bubble shielding effect toward the laser beam propagation and therefore result in less laser energy available for the cut, which is the main reason for the decrease of cut efficiency in water-ethanol mixtures. Our findings give an insight into under which condition the rear-side laser cutting of thin solar cells should be performed: high repetition, pure distilled water and high laser power are favorable for high-speed rough cutting but the cut kerf suffers from strong side effects of ripples, nanoredeposition occurrence, while low laser power at low repetition rate (10 kHz), mixed solution (1 wt% ethanol in water) and moderate scanning speed (100 μm/s) are preferable for ultrafine high-quality debris-free cutting. The feasibility of high-quality cut is a good indication of using rear laser ablation in liquid to cut thinner wafers. More importantly, this technique spares any post cleaning steps to reduce the risk to the contamination or crack of the thin wafers.

UAS in the NAS Air Traffic Controller Acceptability Study-1: The Effects of Horizontal Miss Distances on Simulated UAS and Manned Aircraft Encounters

NASA Technical Reports Server (NTRS)

Ghatas, Rania W.; Comstock, James R., Jr.; Consiglio, Maria C.; Chamberlain, James P.; Hoffler, Keith D.

2015-01-01

This study examined air traffic controller acceptability ratings based on the effects of differing horizontal miss distances (HMDs) for encounters between UAS and manned aircraft. In a simulation of the Dallas/Fort Worth (DFW) East-side airspace, the CAS-1 experiment at NASA Langley Research Center enlisted fourteen recently retired DFW air traffic controllers to rate well-clear volumes based on differing HMDs that ranged from 0.5 NM to 3.0 NM. The controllers were tasked with rating these HMDs from "too small" to "too excessive" on a defined, 1-5, scale and whether these distances caused any disruptions to the controller and/or to the surrounding traffic flow. Results of the study indicated a clear favoring towards a particular HMD range. Controller workload was also measured. Data from this experiment and subsequent experiments will play a crucial role in the FAA's establishment of rules, regulations, and procedures to safely and efficiently integrate UAS into the NAS.

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.

Angiotensin receptor blockers for management of hypertension.

PubMed

Catanzaro, Daniel F; Frishman, William H

2010-07-01

The renin-angiotensin-aldosterone system (RAAS) plays a major role in blood pressure regulation and is thus an important therapeutic target in the management of hypertension. Angiotensin receptor blockers (ARBs), which interrupt RAAS overactivity by blocking a specific receptor that mediates the pathogenic activity of angiotensin II, represent a major addition to the clinician's armamentarium for the management of hypertension. A solid body of clinical evidence demonstrates that ARBs are effective in the management of hypertension as monotherapy or in combination with other agents. Although comparable to angiotensin-converting enzyme inhibitors and other major classes of antihypertensive agents in the treatment of hypertension, the favorable tolerability profile of ARBs make them an attractive alternative for many patients. Recent evidence suggests that treatment persistence with ARB therapy during a 12-month period is typically higher than with other antihypertensive classes, a finding perhaps driven by fewer treatment-limiting side effects. The combination of clinical efficacy and tolerability should render ARBs as a major treatment alternative for hypertension.

Apatinib treatment combined with chemotherapy for advanced epithelial ovarian cancer: a case report.

PubMed

Deng, Linghui; Wang, Yue; Lu, Wenbin; Liu, Qian; Wu, Jie; Jin, Jianhua

2017-01-01

Apatinib is a novel oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has been proved by clinical trials to be effective and safe for patients with chemotherapy-refractory gastric cancer. To date, there is no study or case report on apatinib treatment for patients with ovarian cancer. Here, we present the case of a 50-year-old Chinese woman with advanced ovarian cancer, who received apatinib at a daily dose of 500 mg for 28 days per cycle after failure of fourth-line chemotherapy. Favorable oncologic outcome was achieved in this case after treatment with apatinib. The patient's progression-free survival is now 11.3 months, and she is taking apatinib and capecitabine as maintenance treatment. The common side effect of apatinib was fatigue; however, the toxicity of apatinib was controllable and tolerable. Thus, apatinib may be an option for chemotherapy-refractory advanced epithelial ovarian cancer, but this still warrants further investigation.

Ablation of dermal and mucosal lesions with a new CO2 laser application system

NASA Astrophysics Data System (ADS)

Jovanovic, Sergije; Sedlmaier, Benedikt W.; Fuehrer, Ariane

1997-05-01

Laser treatment of skin changes has become common practice in recent years. The high absorption of the wavelength of the carbon-dioxide laser (10600 nm) is responsible for its low penetration depth in biological tissue. Shortening the exposure time minimizes thermic side effects such as carbonization and coagulation. This effect can be achieved with the SilkTouchTM scanner 767, since the focused laser beam is moved over a defined area by rapidly rotating mirrors. This enables controlled and reliable removal of certain dermal lesions, particularly hypertrophic scars, scars after common acne, wrinkles, rhinophyma and benign neoplasms like verruca vulgaris. Cosmetically favorable reepithelialization of the lasered surfaces results within a very short period of time. Benign mucosal changes of the upper aerodigestive tract can also be treated. Ablation is less traumatic for papillomas, fibromas, hyperplasias in the area of Waldeyer's tonsillar ring and certain laryngotracheal pathologies. Clinical examples demonstrate the advantages of this new mode of application.

Herbal panacea: The need for today in dentistry

PubMed Central

Seal, Mukut; Rishi, Rahul; Satish, G.; Divya, K. T.; Talukdar, Pratim; Maniyar, Radhika

2016-01-01

Among ancient civilizations, India has been known to be a rich repository of medicinal plants. Herbal extracts have been used in traditional medicine for several thousand years. Some plants contain phytochemicals that have effects on the body. The use of phytotherapy is staging a comeback and an era of herbal renaissance is being revolutionized all over the globe. Herbs are a class of plants that are devoid of the woody tissue characteristic of shrubs or trees and have been known for their aromatic, flavoring, and medicinal values over the past centuries. Since the birth of contemporary practices, many have turned away from herbal therapies in favor of synthetic drugs. But these synthetic medicines can alter microbiota and have several side effects. However, the blind dependence on synthetics is over and people are returning to the naturals with the hope of safety and security. Hence, the search for alternative natural products continue. This review includes a few herbs, which can be used in dentistry as alternatives to allopathic medicines. PMID:27114947

Biaryls as potent, tunable dual neurokinin 1 receptor antagonists and serotonin transporter inhibitors.

PubMed

Degnan, Andrew P; Tora, George O; Han, Ying; Rajamani, Ramkumar; Bertekap, Robert; Krause, Rudolph; Davis, Carl D; Hu, Joanna; Morgan, Daniel; Taylor, Sarah J; Krause, Kelly; Li, Yu-Wen; Mattson, Gail; Cunningham, Melissa A; Taber, Matthew T; Lodge, Nicholas J; Bronson, Joanne J; Gillman, Kevin W; Macor, John E

2015-08-01

Depression is a serious illness that affects millions of patients. Current treatments are associated with a number of undesirable side effects. Neurokinin 1 receptor (NK1R) antagonists have recently been shown to potentiate the antidepressant effects of serotonin-selective reuptake inhibitors (SSRIs) in a number of animal models. Herein we describe the optimization of a biaryl chemotype to provide a series of potent dual NK1R antagonists/serotonin transporter (SERT) inhibitors. Through the choice of appropriate substituents, the SERT/NK1R ratio could be tuned to afford a range of target selectivity profiles. This effort culminated in the identification of an analog that demonstrated oral bioavailability, favorable brain uptake, and efficacy in the gerbil foot tap model. Ex vivo occupancy studies with compound 58 demonstrated the ability to maintain NK1 receptor saturation (>88% occupancy) while titrating the desired level of SERT occupancy (11-84%) via dose selection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Does the use of efficacy or effectiveness evidence in cost-effectiveness analysis matter?

PubMed

Dilokthornsakul, Piyameth; Chaiyakunapruk, Nathorn; Campbell, Jonathan D

2017-01-02

To test the association of clinical evidence type, efficacy-based or effectiveness-based ("E"), versus whether or not asthma interventions' cost-effectiveness findings are favorable. We conducted a systematic review of PubMed, EMBASE, Tufts CEA registry, Cochrane CENTRAL, and the UK National Health Services Economic Evaluation Database from 2009 to 2014. All cost-effectiveness studies evaluating asthma medication(s) were included. Clinical evidence type, "E," was classified as efficacy-based if the evidence was from an explanatory randomized controlled trial(s) or meta-analysis, while evidence from pragmatic trial(s) or observational study(s) was classified as effectiveness-based. We defined three times the World Health Organization cost-effectiveness willingness-to-pay (WTP) threshold or less as a favorable cost-effectiveness finding. Logistic regression tested the likelihood of favorable versus unfavorable cost-effectiveness findings against the type of "E." 25 cost-effectiveness studies were included. Ten (40.0%) studies were effectiveness-based, yet 15 (60.0%) studies were efficacy-based. Of 17 studies using endpoints that could be compared to WTP threshold, 7 out of 8 (87.5%) effectiveness-based studies yielded favorable cost-effectiveness results, whereas 4 out of 9 (44.4%) efficacy-based studies yielded favorable cost-effectiveness results. The adjusted odds ratio was 15.12 (95% confidence interval; 0.59 to 388.75) for effectiveness-based versus efficacy-based achieving favorable cost-effectiveness findings. More asthma cost-effectiveness studies used efficacy-based evidence. Studies using effectiveness-based evidence trended toward being more likely to disseminate favorable cost-effective findings than those using efficacy. Health policy decision makers should pay attention to the type of clinical evidence used in cost-effectiveness studies for accurate interpretation and application.

Matching Automatic Gain Control Across Devices in Bimodal Cochlear Implant Users.

PubMed

Veugen, Lidwien C E; Chalupper, Josef; Snik, Ad F M; Opstal, A John van; Mens, Lucas H M

2016-01-01

The purpose of this study was to improve bimodal benefit in listeners using a cochlear implant (CI) and a hearing aid (HA) in contralateral ears, by matching the time constants and the number of compression channels of the automatic gain control (AGC) of the HA to the CI. Equivalent AGC was hypothesized to support a balanced loudness for dynamically changing signals like speech and improve bimodal benefit for speech understanding in quiet and with noise presented from the side(s) at 90 degree. Fifteen subjects participated in the study, all using the same Advanced Bionics Harmony CI processor and HA (Phonak Naida S IX UP). In a 3-visit crossover design with 4 weeks between sessions, performance was measured using a HA with a standard AGC (syllabic multichannel compression with 1 ms attack time and 50 ms release time) or an AGC that was adjusted to match that of the CI processor (dual AGC broadband compression, 3 and 240 msec attack time, 80 and 1500 msec release time). In all devices, the AGC was activated above the threshold of 63 dB SPL. The authors balanced loudness across the devices for soft and loud input sounds in 3 frequency bands (0 to 548, 548 to 1000, and >1000 Hz). Speech understanding was tested in free field in quiet and in noise for three spatial speaker configurations, with target speech always presented from the front. Single-talker noise was either presented from the CI side or the HA side, or uncorrelated stationary speech-weighted noise or single-talker noise was presented from both sides. Questionnaires were administered to assess differences in perception between the two bimodal fittings. Significant bimodal benefit over the CI alone was only found for the AGC-matched HA for the speech tests with single-talker noise. Compared with the standard HA, matched AGC characteristics significantly improved speech understanding in single-talker noise by 1.9 dB when noise was presented from the HA side. AGC matching increased bimodal benefit insignificantly by 0.6 dB when noise was presented from the CI implanted side, or by 0.8 (single-talker noise) and 1.1 dB (stationary noise) in the more complex configurations with two simultaneous maskers from both sides. In questionnaires, subjects rated the AGC-matched HA higher than the standard HA for understanding of one person in quiet and in noise, and for the quality of sounds. Listening to a slightly raised voice, subjects indicated increased listening comfort with matched AGCs. At the end of the study, 9 of 15 subjects preferred to take home the AGC-matched HA, 1 preferred the standard HA and 5 subjects had no preference. For bimodal listening, the AGC-matched HA outperformed the standard HA in speech understanding in noise tasks using a single competing talker and it was favored in questionnaires and in a subjective preference test. When noise was presented from the HA side, AGC matching resulted in a 1.9 dB SNR additional benefit, even though the HA was at the least favorable SNR side in this speaker configuration. Our results possibly suggest better binaural processing for matched AGCs.

Protein unfolding in detergents: effect of micelle structure, ionic strength, pH, and temperature.

PubMed Central

Otzen, Daniel E

2002-01-01

The 101-residue monomeric protein S6 unfolds in the anionic detergent sodium dodecyl sulfate (SDS) above the critical micelle concentration, with unfolding rates varying according to two different modes. Our group has proposed that spherical micelles lead to saturation kinetics in unfolding (mode 1), while cylindrical micelles prevalent at higher SDS concentrations induce a power-law dependent increase in the unfolding rate (mode 2). Here I investigate in more detail how micellar properties affect protein unfolding. High NaCl concentrations, which induce cylindrical micelles, favor mode 2. This is consistent with our model, though other effects such as electrostatic screening cannot be discounted. Furthermore, unfolding does not occur in mode 2 in the cationic detergent LTAB, which is unable to form cylindrical micelles. A strong retardation of unfolding occurs at higher LTAB concentrations, possibly due to the formation of dead-end protein-detergent complexes. A similar, albeit much weaker, effect is seen in SDS in the absence of salt. Chymotrypsin inhibitor 2 exhibits the same modes of unfolding in SDS as S6, indicating that this type of protein unfolding is not specific for S6. The unfolding process in mode 1 has an activation barrier similar in magnitude to that in water, while the activation barrier in mode 2 is strongly concentration-dependent. The strong pH-dependence of unfolding in SDS and LTAB suggests that the rate of unfolding in anionic detergent is modulated by repulsion between detergent headgroups and anionic side chains, while cationic side chains modulate unfolding rates in cationic detergents. PMID:12324439

Evaluation of safety in clinical use of generic paclitaxel [NK] for injection.

PubMed

Tsukiyama, Ikuto; Hotta, Kazuo; Takeuchi, Masayuki; Onishi, Masahumi; Toyama, Yukio; Saito, Hiroko; Sai, Yoshimichi; Miyamoto, Ken-Ichi; Hasegawa, Takaaki

2012-04-01

The introduction of generic drugs is a favored strategy in reducing medical costs, but some clinicians are often reluctant to use them because of lack of information with regard to their side effects. Generic paclitaxel [NK] differs from the proprietary version, Taxol®, in containing added citric acid and a more pure form of castor oil. However, little information exists regarding the effects of these additives on adverse events such as vascular pain, phlebitis, hypersensitivity and hepatic dysfunction. To compensate for this lack of information and to validate the safety of using generic paclitaxel, we investigated adverse events in response to generic paclitaxel [NK]. Our investigation focused on patients treated with both the proprietary formulation (Taxol® for injection) and the generic version(paclitaxel [NK] for injection)sequentially from April 2008 to March 2009. Adverse events were investigated retrospectively. Incidence of vascular pain, phlebitis and hypersensitivity was similar to that with the original product. Although the expression of some liver enzymes was slightly increased and some gastrointestinal events were reduced following generic paclitaxel [NK] treatment there was no statistically significant difference. The profiles of other adverse events were not significantly different. Increased vascular pain and phlebitis, predicted due to low pH conditions caused by citric acid, were not observed. Similarly, the pure castor oil included in generic paclitaxel [NK] did not influence hypersensitivity and hepatic function. We found no significant differences in our study of proprietary and generic paclitaxel [NK]. Thus, clinicians have no reason for prejudice against using generic paclitaxel [NK] on the basis of increased risk of side effects.

ADX: a high field, high power density, Advanced Divertor test eXperiment

NASA Astrophysics Data System (ADS)

Vieira, R.; Labombard, B.; Marmar, E.; Irby, J.; Shiraiwa, S.; Terry, J.; Wallace, G.; Whyte, D. G.; Wolfe, S.; Wukitch, S.; ADX Team

2014-10-01

The MIT PSFC and collaborators are proposing an advanced divertor experiment (ADX) - a tokamak specifically designed to address critical gaps in the world fusion research program on the pathway to FNSF/DEMO. This high field (6.5 tesla, 1.5 MA), high power density (P/S ~ 1.5 MW/m2) facility would utilize Alcator magnet technology to test innovative divertor concepts for next-step DT fusion devices (FNSF, DEMO) at reactor-level boundary plasma pressures and parallel heat flux densities while producing high performance core plasma conditions. The experimental platform would also test advanced lower hybrid current drive (LHCD) and ion-cyclotron range of frequency (ICRF) actuators and wave physics at the plasma densities and magnetic field strengths of a DEMO, with the unique ability to deploy launcher structures both on the low-magnetic-field side and the high-field side - a location where energetic plasma-material interactions can be controlled and wave physics is most favorable for efficient current drive, heating and flow drive. This innovative experiment would perform plasma science and technology R&D necessary to inform the conceptual development and accelerate the readiness-for-deployment of FNSF/DEMO - in a timely manner, on a cost-effective research platform. Supported by DE-FC02-99ER54512.

Comparative particle recoveries by the retracting rotorod, rotoslide and Burkard spore trap sampling in a compact array

NASA Astrophysics Data System (ADS)

Solomon, W. R.; Burge, H. A.; Boise, J. R.; Becker, M.

1980-06-01

An array comprising 4 intermittent (retracting) rotorods, 3 (“swingshield”) rotoslides and one Burkard (Hirst) automatic volumetric spore trap was operated on an urban rooftop during 70 periods of 9, 15 or 24 hours in late summer. Standard sampling procedures were utilized and recoveries of pollens as well as spores of Alternaria, Epicoccum, Pithomyces and Ganoderma species compared. Differences between paired counts from each sampler type showed variances increasing with levels of particle prevalence (and deposition). In addition, minimal, non-random, side-to-side and intersampler differences were noted for both impactor types. Exclusion of particles between operating intervals by rotoslides and rotorods was virtually complete. Spore trap recoveries for all particle categories, per m3, exceeded those by both impactors. The greatest (7-fold) difference was noted for the smallest type examined ( Ganoderma). For ragweed pollen, an overall spore trap/impactor ratio approached 1.5. Rain effects were difficult to discern but seemed to influence rotoslides least. Overall differences between impactors were quite small but generally favored the rotoslide in this comparison. Our data confirm the relative advantages of suction traps for small particles. Both impactors and spore traps are suited to pollen and large spore collection, and, with some qualification, data from both may be compared.

A density functional theory model of mechanically activated silyl ester hydrolysis

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

Pill, Michael F.; Schmidt, Sebastian W.; Institut für Physikalische Chemie, Christian-Albrechts-Universität zu Kiel, Olshausenstraße 40, 24098 Kiel

2014-01-28

To elucidate the mechanism of the mechanically activated dissociation of chemical bonds between carboxymethylated amylose (CMA) and silane functionalized silicon dioxide, we have investigated the dissociation kinetics of the bonds connecting CMA to silicon oxide surfaces with density functional calculations including the effects of force, solvent polarizability, and pH. We have determined the activation energies, the pre-exponential factors, and the reaction rate constants of candidate reactions. The weakest bond was found to be the silyl ester bond between the silicon and the alkoxy oxygen atom. Under acidic conditions, spontaneous proton addition occurs close to the silyl ester such that neutralmore » reactions become insignificant. Upon proton addition at the most favored position, the activation energy for bond hydrolysis becomes 31 kJ mol{sup −1}, which agrees very well with experimental observation. Heterolytic bond scission in the protonated molecule has a much higher activation energy. The experimentally observed bi-exponential rupture kinetics can be explained by different side groups attached to the silicon atom of the silyl ester. The fact that different side groups lead to different dissociation kinetics provides an opportunity to deliberately modify and tune the kinetic parameters of mechanically activated bond dissociation of silyl esters.« less

The choice of the speed of an airship

NASA Technical Reports Server (NTRS)

Munk, Max M

1922-01-01

The favorable speed of an airship is chiefly determined by the condition of the consumption of the least amount of fuel per unit of traveled distance, although other conditions come into play. The resulting rules depend on the character of the wind and on the variability of the efficiency of the engine propeller units. This investigation resulted in the following rules. 1) Always keep the absolute course and steer at such an angle with reference to it as to neutralize the side wind. 2) In a strong contrary wind, take a speed one and one half times the velocity of the wind. 3) As a general rule, take the velocity of the wind and the velocity of the course component of the wind. Add them together if the wind has a contrary component, but subtract them from each other if the wind has a favorable component.

The Evolution of Sexually Antagonistic Phenotypes

PubMed Central

Perry, Jennifer C.; Rowe, Locke

2015-01-01

Sexual conflict occurs whenever there is sexually antagonistic selection on shared traits. When shared traits result from interactions (e.g., mating rate) and have a different genetic basis in each sex (i.e., interlocus conflict), then sex-specific traits that shift the value of these interaction traits toward the sex-specific optimum will be favored. Male traits can be favored that increase the fitness of their male bearers, but decrease the fitness of interacting females. Likewise, female traits that reduce the costs of interacting with harmful males may simultaneously impose costs on males. If the evolution of these antagonistic traits changes the nature of selection acting on the opposite sex, interesting coevolutionary dynamics will result. Here we examine three current issues in the study of sexually antagonistic interactions: the female side of sexual conflict, the ecological context of sexual conflict, and the strength of evidence for sexually antagonistic coevolution. PMID:26032715

Internal friction and absence of dilatancy of packings of frictionless polygons.

PubMed

Azéma, Émilien; Radjaï, Farhang; Roux, Jean-Noël

2015-01-01

By means of numerical simulations, we show that assemblies of frictionless rigid pentagons in slow shear flow possess an internal friction coefficient (equal to 0.183±0.008 with our choice of moderately polydisperse grains) but no macroscopic dilatancy. In other words, despite side-side contacts tending to hinder relative particle rotations, the solid fraction under quasistatic shear coincides with that of isotropic random close packings of pentagonal particles. Properties of polygonal grains are thus similar to those of disks in that respect. We argue that continuous reshuffling of the force-bearing network leads to frequent collapsing events at the microscale, thereby causing the macroscopic dilatancy to vanish. Despite such rearrangements, the shear flow favors an anisotropic structure that is at the origin of the ability of the system to sustain shear stress.

The effect of basal channels on oceanic ice-shelf melting

NASA Astrophysics Data System (ADS)

Millgate, Thomas; Holland, Paul R.; Jenkins, Adrian; Johnson, Helen L.

2013-12-01

The presence of ice-shelf basal channels has been noted in a number of Antarctic and Greenland ice shelves, but their impact on basal melting is not fully understood. Here we use the Massachusetts Institute of Technology general circulation model to investigate the effect of ice-shelf basal channels on oceanic melt rate for an idealized ice shelf resembling the floating tongue of Petermann Glacier in Greenland. The introduction of basal channels prevents the formation of a single geostrophically balanced boundary current; instead the flow is diverted up the right-hand (Coriolis-favored) side of each channel, with a return flow in the opposite direction on the left-hand side. As the prescribed number of basal channels is increased the mean basal melt rate decreases, in agreement with previous studies. For a small number of relatively wide channels the subice flow is found to be a largely geostrophic horizontal circulation. The reduction in melt rate is then caused by an increase in the relative contribution of weakly melting channel crests and keels. For a larger number of relatively narrow channels, the subice flow changes to a vertical overturning circulation. This change in circulation results in a weaker sensitivity of melt rates to channel size. The transition between the two regimes is governed by the Rossby radius of deformation. Our results explain why basal channels play an important role in regulating basal melting, increasing the stability of ice shelves.

Preliminary in vivo evaluation of [131I]-2-iodo-D-phenylalanine as a potential radionuclide therapeutic agent in R1M-fluc rhabdomyosarcoma tumor-bearing NuNu mice using bioluminescent imaging.

PubMed

Bauwens, Matthias; Wimana, Lena; Keyaerts, Marleen; Peleman, Cindy; Lahoutte, Tony; Kersemans, Ken; Snykers, Sarah; Vinken, Mathieu; Mertens, John; Bossuyt, Axel

2010-04-01

Carrier-added [(123)I]-2-iodo-D-phenylalanine (CA [(123)I]-2-I-D-Phe) was previously found to have a preferential retention in tumors with a high tumor background contrast in animal models. A previous human dosimetry study demonstrated a favorable biodistribution and radiation burden in human subjects. The aim of this study was to investigate the potential of CA [(131)I]-2-I-D-Phe as an agent for radionuclide therapy. Sixty (60) nude athymic mice were inoculated subcutaneously with firefly luciferase-transduced R1M rhabdomyosarcoma cells. The mice in the therapy group were injected intravenously (i.v.) with 148 MBq [(131)I]-2-I-D-Phe (432 GBq/mmol) in kit solution. Controls were injected with kit solution without radioactivity, with physiological saline, or with 148 MBq [(131)I](-) in physiological saline. Tumor growth was quantified using bioluminescent imaging and caliper measurements. [(131)I]-2-I-D-Phe clearly reduced tumor growth in the treated mice compared with the control groups. A tumor growth-rate reduction of at least 33% was found for mice receiving a therapeutic dose. There were no serious adverse side-effects of the therapy. In conclusion, i.v. injection of CA 148 MBq [(131)I]-2-I-D-Phe specifically reduces tumor growth in athymic nude mice without relevant side-effects on the animals' health.

Description of an Audio-Based Paced Respiration Intervention for Vasomotor Symptoms

PubMed Central

Burns, Debra S.; Drews, Michael R.; Carpenter, Janet S.

2013-01-01

Millions of women experience menopause-related hot flashes or flushes that may have a negative effect on their quality of life. Hormone therapy is an effective treatment, however, it may be contraindicated or unacceptable for some women based on previous health complications or an undesirable risk–benefit ratio. Side effects and the unacceptability of hormone therapy have created a need for behavioral interventions to reduce hot flashes. A variety of complex, multimodal behavioral, relaxation-based interventions have been studied with women (n = 88) and showed generally favorable results. However, currently extensive resource commitments reduce the translation of these interventions into standard care. Slow, deep breathing is a common component in most interventions and may be the active ingredient leading to reduced hot flashes. This article describes the content of an audio-based program designed to teach paced breathing to reduce hot flashes. Intervention content was based on skills training theory and music entrainment. The audio intervention provides an efficient way to deliver a breathing intervention that may be beneficial to other clinical populations. PMID:23914283

Strontium 89 in the treatment of pain due to diffuse osseous metastases: a university hospital experience.

PubMed Central

Ashayeri, Ebrahim; Omogbehin, Adedamola; Sridhar, Rajagopalan; Shankar, Ravi A.

2002-01-01

More than two-thirds of the patients with osseous metastases experience debilitating bone pain, requiring some form of pain relief. Analgesics are limited in their efficacy. Palliative application of hemi-body external beam radiation therapy in the treatment of multiple osseous metastases also is limited due to toxicity associated with large treatment ports. Intravenous injections of bone seeking radioisotopes are effective in the palliation of pain with fewer side effects. Forty-one patients with multiple osseous metastases due to prostate and breast cancer were treated with strontium chloride 89 (89Sr) at the department of radiation oncology, in a university hospital. A retrospective analysis of these patients indicated that all subjects had severe pain that diminished their quality of life. Most of these patients had multiple co-morbid factors. Many were on opioids leading to adverse effects such as nausea, constipation, and drowsiness that required additional medication. Objective findings and evaluation of the responses were not always available for all patients. Following treatmentwith 89Sr, over two-thirds of the patients responded favorably and required lower doses of opioids. PMID:12152927

``Effect of Polyalkylthiophene Microstructure on Physical and Optoelectronic Properties''

NASA Astrophysics Data System (ADS)

Minkler, Michael J., Jr.; Beckingham, Bryan S.

Conjugated polymers have been of widespread interest as flexible semiconductors for organic electronic devices such as solar cells, field effect transistor,s and light-emitting diodes. Of particular interest have been alkyl-substituted polythiophenes due to their well-controlled synthesis, favorable optoelectronic properties, and solubility in organic solvents. Importantly, relatively small changes to the chemical microstructure in poly(3-alkylthiophenes) (P3ATs) can have a significant effect on the resulting physical and optoelectronic properties. For instance, the addition of aliphatic side chains onto unsubstituted polythiophene provides solubility but also greatly decreases conductivity in comparison to unsubstituted polythiophene (PT). In this work, we use Grignard metathesis polymerization to synthesize poly(3-hexylthiophene) (P3HT), PT, and statistical copolymers (P[3HT-co-T]) over a range of compositions. We examine the physical properties (melting temperature, crystallinity, etc) by differential scanning calorimetry and wide angle X-ray scattering, optoelectronic properties by UV/Vis spectroscopy, and solubility in organic solvents of these copolymers in order to gain insights into the interplay of microstructure and properties in this class of materials.

Effects of substrate voltage on noise characteristics and hole lifetime in SOI metal-oxide-semiconductor field-effect transistor photon detector.

PubMed

Putranto, Dedy Septono Catur; Priambodo, Purnomo Sidi; Hartanto, Djoko; Du, Wei; Satoh, Hiroaki; Ono, Atsushi; Inokawa, Hiroshi

2014-09-08

Low-frequency noise and hole lifetime in silicon-on-insulator (SOI) metal-oxide-semiconductor field-effect transistors (MOSFETs) are analyzed, considering their use in photon detection based on single-hole counting. The noise becomes minimum at around the transition point between front- and back-channel operations when the substrate voltage is varied, and increases largely on both negative and positive sides of the substrate voltage showing peculiar Lorentzian (generation-recombination) noise spectra. Hole lifetime is evaluated by the analysis of drain current histogram at different substrate voltages. It is found that the peaks in the histogram corresponding to the larger number of stored holes become higher as the substrate bias becomes larger. This can be attributed to the prolonged lifetime caused by the higher electric field inside the body of SOI MOSFET. It can be concluded that, once the inversion channel is induced for detection of the photo-generated holes, the small absolute substrate bias is favorable for short lifetime and low noise, leading to high-speed operation.

Does Israel Have a Need to Retain the Golan Heights? (The View from Israel).

DTIC Science & Technology

1980-06-06

the west side of the Jordan River .18 At the zenith of their power, their kingdom included the whole area west of the Jordan River , the Jordan Valley ...Israeli armistice demarcation lines changed from the mandatory borders in some areas east of the Jordan River and the Yarmuk Valley in Syria’s favor. The...Yarmuk Valley to the Jordan River . The Israelis gained control of the entire Golan Heights and impeded the Syrian artillery dominance of the valley to

FLARE: The Far Side Lunar Research Expedition. A design of a far side lunar observatory

NASA Technical Reports Server (NTRS)

Bishop, David W.; Chakrabarty, Rudhmala P.; Hannula, Dawn M.; Hargus, William A., Jr.; Melendrez, A. Dean; Niemann, Christopher J.; Neuenschwander, Amy L.; Padgett, Brett D.; Patel, Sanjiv R.; Wiesehuegel, Leland J.

1991-01-01

This document outlines the design completed by members of Lone Star Aerospace, Inc. (L.S.A.) of a lunar observatory on the far side of the Moon. Such a base would not only establish a long term human presence on the Moon, but would also allow more accurate astronomical data to be obtained. A lunar observatory is more desirable than an Earth based observatory for the following reasons: instrument weight is reduced due to the Moon's weaker gravity; near vacuum conditions exist on the Moon; the Moon has slow rotation to reveal the entire sky; and the lunar surface is stable for long baseline instruments. All the conditions listed above are favorable for astronomical data recording. The technical aspects investigated in the completion of this project included site selection, mission scenario, scientific instruments, communication and power systems, habitation and transportation, cargo spacecraft design, thermal systems, robotic systems, and trajectory analysis. The site selection group focused its efforts on finding a suitable location for the observatory. Hertzsprung, a large equatorial crater on the eastern limb, was chosen as the base site.

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.

Does Guided Bone Regeneration Prevent Unfavorable Bone Shapes in Distraction Gap?

PubMed

Demetoglu, Umut; Alkan, Alper; Kiliç, Erdem; Ozturk, Mustafa; Bilge, Suheyb

2018-03-01

Complications related to distraction osteogenesis can cause degradation of newly regenerated bone. Additionally, an unfavorable shape of the regenerated bone at the distraction gap can reduce the quantity of regenerated bone. The aim of the present study was to report on the prevention of unfavorable shapes of regenerated bone using guided bone regeneration during distraction. Bilateral alveolar distraction was performed in 10 beagle dog mandibles. One side of the mandible formed the experimental group and the other side served as the control group. In the experimental group, guided bone regeneration was performed simultaneously with distraction osteogenesis. In the control group, only alveolar distraction was applied. At the end of a 1-week latent period, all mandibles were distracted 10 mm (1 mm/day). After the distraction period, 3 months were allowed for consolidation. After consolidation, all the dogs were euthanized, and the shape of the regenerated bone was determined to be either favorable or unfavorable. Densitometric evaluation and area measurements were performed using computed tomography scans. Statistical evaluation was performed using the independent t test, with a significance level of P < .05. In the experimental group, no unfavorable bone shape developed in the distraction gap, and the new bone had a surface and volume similar to those of the segments. In contrast, in the control group, 4 mandibles had an unfavorable bone shape in the distraction gap and 4 showed favorable bone healing with no defect. The surface area of the regenerating bone in the experimental group was significantly greater than that in the control group. Also, the surface area differed significantly between the experimental and control groups (P < .05). However, the densitometric values did not differ between the 2 groups (P < .05). Concomitant use of guided bone regeneration with distraction osteogenesis could be an optimal method for generating a favorable bone shape within the distraction gap. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Lithium manganese oxide spinel electrodes

NASA Astrophysics Data System (ADS)

Darling, Robert Mason

Batteries based oil intercalation eletrodes are currently being considered for a variety of applications including automobiles. This thesis is concerned with the simulation and experimental investigation of one such system: spinel LiyMn2O4. A mathematical model simulating the behavior of an electrochemical cell containing all intercalation electrode is developed and applied to Li yMn2O4 based systems. The influence of the exchange current density oil the propagation of the reaction through the depth of the electrode is examined theoretically. Galvanostatic cycling and relaxation phenomena on open circuit are simulated for different particle-size distributions. The electrode with uniformly sized particles shows the best performance when the current is on, and relaxes towards equilibrium most quickly. The impedance of a porous electrode containing a particle-size distribution at low frequencies is investigated with all analytic solution and a simplified version of the mathematical model. The presence of the particle-size distribution leads to an apparent diffusion coefficient which has all incorrect concentration dependence. A Li/1 M LiClO4 in propylene carbonate (PC)/ LiyMn 2O4 cell is used to investigate the influence of side reactions oil the current-potential behavior of intercalation electrodes. Slow cyclic voltammograms and self-discharge data are combined to estimate the reversible potential of the host material and the kinetic parameters for the side reaction. This information is then used, together with estimates of the solid-state diffusion coefficient and main-reaction exchange current density, in a mathematical model of the system. Predictions from the model compare favorably with continuous cycling results and galvanostatic experiments with periodic current interruptions. The variation with respect to composition of' the diffusion coefficient of lithium in LiyMn2O4 is estimated from incomplete galvanostatic discharges following open-circult periods. The results compared favorably with those available in the literature. Dynamic Monte Carlo simulations were conducted to investigate the concentration dependence of the diffusion coefficient fundamentally. The dynamic Monte Carlo predictions compare favorably with the experimental data.

Isoflavonoid-based bone-sparing treatments exert a low activity on reproductive organs and on hepatic metabolism of estradiol in ovariectomized rats

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

Phrakonkham, Pascal; Chevalier, Joelle; Desmetz, Catherine

2007-10-15

The use of soy isoflavones is a potential alternative to hormone replacement therapy in post-menopausal bone-loss prevention. Nevertheless, phytoestrogens can target other organs and may disrupt cell proliferation, or could modify endogenous steroid hormone metabolism. These mechanisms could be linked to an increased risk of developing cancer. We therefore studied the possible side effects of such treatments in an experimental model of menopause. Forty adult female Wistar rats were ovariectomized and fed with a genistein-, daidzein- or equol-supplemented diet at bone-sparing levels (10 mg/kg BW/day) for 3 months. The estrogenic effects were assessed by histological and molecular analyses on reproductivemore » organs. The impact on the oxidative metabolism of estradiol and on associated cytochrome P450 (CYP) activities was evaluated in liver microsomes. The relative wet weights of both the uterus and the vagina were increased in the equol group, but no significant changes in proliferating cell nuclear antigen or hormone receptor mRNA expression were noticed. In contrast, genistein and daidzein did not induce uterotrophy but caused an overexpression of estrogen receptor {alpha} mRNA which could correspond to a long-lasting effect of physiological concentrations of estrogens. The hepatic metabolism of estradiol was influenced by daidzein which increased the synthesis of putative mutagenic derivatives. At the same time, genistein favored estrogen 2-hydroxylation, and equol decreased 4-hydroxyestrogen production. Surprisingly, no significant alteration in hepatic CYP activities was detected. Taken together, these results demonstrate that isoflavonoid-based bone-sparing treatments are able to cause side effects on other estrogen-sensitive target organs when given in the long-term.« less

Neural Correlates of Opposing Effects of Emotional Distraction on Perception and Episodic Memory: An Event-Related fMRI Investigation

PubMed Central

Shafer, Andrea T.; Dolcos, Florin

2012-01-01

A main question in emotion and memory literature concerns the relationship between the immediate impact of emotional distraction on perception and the long-term impact of emotion on memory. While previous research shows both automatic and resource-mediated mechanisms to be involved in initial emotion processing and memory, it remains unclear what the exact relationship between the immediate and long-term effects is, and how this relationship may change as a function of manipulations at perception favoring the engagement of either more automatic or mediated mechanisms. Using event-related functional magnetic resonance imaging, we varied the degree of resource availability for processing task-irrelevant emotional information, to determine how the initial (impairing) impact of emotional distraction related to the long-term (enhancing) impact of emotion on memory. Results showed that a direct relationship between emotional distraction and memory was dependent on automatic mechanisms, as this was found only under conditions of limited resource availability and engagement of amygdala (AMY)-hippocampal (HC) mechanisms to both impairing and enhancing effects. A hemispheric disassociation was also identified in AMY-HC, where while both sides were associated with emotional distraction and left AMY and anterior HC were linked to emotional memory, functional asymmetry was only identified in the posterior HC, with only the left side contributing to emotional memory. Finally, areas dissociating between the two opposing effects included the medial frontal, precentral, superior temporal, and middle occipital gyri (linked to emotional distraction), and the superior parietal cortex (linked to emotional memory). These findings demonstrate the relationship between emotional distraction and memory is context dependent and that specific brain regions may be more or less susceptible to the direction of emotional modulation (increased or decreased), depending on the task manipulation, and processes investigated. PMID:23049502

Vaccination and allergy.

PubMed

Rottem, Menachem; Shoenfeld, Yehuda

2004-06-01

Vaccines have had a major effect on controlling the spread of infectious diseases, but use of certain vaccines was linked to potential allergic and autoimmune side effects in healthy and often in certain high-risk populations. In this review the authors summarize the current knowledge of such risks. Immediate systemic allergic reactions after vaccination with commonly used vaccines are extremely rare. Use of certain vaccines was linked to potential allergic side effects in healthy and often in certain high-risk populations. The authors review the data on the risk associated with important vaccines including influenza, smallpox, pneumococcus, Japanese encephalitis, Bacille Calmette-Guerin, pertussis, and measles, mumps, and rubella. Two main components were identified as a source for allergic reactions in vaccines: gelatin and egg protein. There is growing interest in the potential interactions between infant vaccination and risk for development of atopic disease. In addition, there is concern that genetic risk for atopy influences capacity to respond to vaccination during infancy. There is no evidence that vaccines such as Bacille Calmette-Guerin; pertussis; influenza; measles, mumps, and rubella; or smallpox have an effect on the risk of the development of atopy later in life. Immunotherapy provides an efficacious and safe method for the treatment of allergic conditions by immunomodulation of the immune system. The possibility of vaccination triggering or unmasking autoimmunity in genetically susceptible individuals cannot be ruled out, but for the general population the risk-to-benefit ratio is overwhelmingly in favor of vaccinations. Childhood vaccination remains an essential part of child health programs and should not be withheld, even from children predisposed to allergy. Vaccinations are safe, but special attention should be taken in high-risk individuals with anaphylactic reactions to foods, and in patients with autoimmune diseases.

A double-blind randomized placebo-controlled trial with short-term beta-glucuronidase therapy in children with chronic rhinoconjunctivitis and/or asthma due to dust mite allergy.

PubMed

Galli, E; Bassi, M S; Mora, E; Martelli, M; Gianni, S; Auricchio, G; Arabito, E; Rossi, P

2006-01-01

Enzyme potentiated desensitization, in which beta-glucuronidase (BG) is administered with low doses of mixed allergens, was proposed in the 1970s for specific immunotherapy. The BG currently commercially available in a purified and standardized preparation devoid of any allergen has been suggested as a regulator in the allergic immune response, acting on the cytokine-network of type 2 helper T cells. A double-blind trial with a single-dose of BG proved effective in preventing symptoms in adult patients with rhinoconjunctivitis due to grass pollens. The aim of this randomized double-blind placebo-controlled trial was to confirm the safety and effectiveness of double-dose intradermal BG immunotherapy in preventing symptoms in children suffering from chronic rhinoconjunctivitis and/or asthma due to dust mite. We randomized 125 children with dust-mite related chronic rhinoconjunctivitis and/or asthma to the BG treated group (67) or the placebo group (58). All patients were screened before treatment (TO), at BG or placebo administration (T1 and T3), and at 3 and 9 months after T1 (T2 and T4). Drug intake and bronchial, nasal and ocular symptoms were recorded in a diary. Patients in both groups completed the study and BG treatment was well tolerated without side effects. Significant differences in symptoms were observed, in particular for conjunctivitis (P= .008). The total drug intake for allergic symptoms was significantly lower in the treated group than in the placebo group (P<. 01). BG immunotherapy is efficacious, safe, and well tolerated in allergic children. Moreover, good compliance with the administration of 2 doses per year and the lack of significant side effects makes the benefit/risk ratio of this treatment particularly favorable.

Molecular basis of the osmolyte effect on protein stability: a lesson from the mechanical unfolding of lysozyme.

PubMed

Adamczak, Beata; Wieczór, Miłosz; Kogut, Mateusz; Stangret, Janusz; Czub, Jacek

2016-10-15

Osmolytes are a class of small organic molecules that shift the protein folding equilibrium. For this reason, they are accumulated by organisms under environmental stress and find applications in biotechnology where proteins need to be stabilized or dissolved. However, despite years of research, debate continues over the exact mechanisms underpinning the stabilizing and denaturing effect of osmolytes. Here, we simulated the mechanical denaturation of lysozyme in different solvent conditions to study the molecular mechanism by which two biologically relevant osmolytes, denaturing (urea) and stabilizing (betaine), affect the folding equilibrium. We found that urea interacts favorably with all types of residues via both hydrogen bonds and dispersion forces, and therefore accumulates in a diffuse solvation shell around the protein. This not only provides an enthalpic stabilization of the unfolded state, but also weakens the hydrophobic effect, as hydrophobic forces promote the association of urea with nonpolar residues, facilitating the unfolding. In contrast, we observed that betaine is excluded from the protein backbone and nonpolar side chains, but is accumulated near the basic residues, yielding a nonuniform distribution of betaine molecules at the protein surface. Spatially resolved solvent-protein interaction energies further suggested that betaine behaves in a ligand- rather than solvent-like manner and its exclusion from the protein surface arises mostly from the scarcity of favorable binding sites. Finally, we found that, in the presence of betaine, the reduced ability of water molecules to solvate the protein results in an additional enthalpic contribution to the betaine-induced stabilization. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Evaluating the longer-term cognitive effects of adjunctive perampanel compared to lacosamide in a naturalistic outpatient setting.

PubMed

Meschede, Carolin; Witt, Juri-Alexander; Rademacher, Michael; von Wrede, Randi D; Elger, Christian E; Helmstaedter, Christoph

2018-04-22

This retrospective longitudinal study aims to compare the longer-term cognitive and behavioral side effects of adjunctive antiepileptic treatment with perampanel (PER) and lacosamide (LCM), two third generation antiepileptic drugs with suggested favorable cognitive profiles. The two drugs were monitored according to a previously established routine diagnostic protocol (Helmstaedter et al. E&B 2013;26:182-7) which facilitates the retrospective comparison of antiepileptic drug tolerability in a naturalistic outpatient setting. Records from 94 patients were evaluated who underwent neuropsychological assessment before and under adjunctive treatment with either PER (n = 57) or LCM (n = 37). Cognition was assessed using the EpiTrack screening for executive functions and a VLMT short form for verbal memory. Subjective assessments included a German QOLIE-10 adaptation (quality of life) and an extended Adverse Events Profile (AEP). The median follow-up interval was 36 weeks. Multivariate repeated measures statistics revealed a non-significant trend towards an interaction effect "time - treatment arm" on both executive function and memory. When analyzed separately executive functions and memory scores significantly improved under LCM (t = -2.76 p < 0.01 and t = -2.44 p < 0.05 respectively). Subjectively, PER was associated with improvements in 2/18 physiological domains and in the LCM group 1/9 cognitive domains deteriorated. Seizure freedom was achieved for five patients treated with LCM (14%) and 15 treated with PER (26%, χ 2  = 2.2, n.s.). In a naturalistic outpatient setting, chronic adjunctive treatment with PER and LCM did not negatively affect cognition and LCM may even improve cognition. Neither drug increased self-reported irritability or aggression. This suggests favorable longer-term tolerability. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Joint lavage associated with triamcinolone hexacetonide injection in knee osteoarthritis: a randomized double-blind controlled study.

PubMed

Parmigiani, Leandro; Furtado, Rita N V; Lopes, Roberta V; Ribeiro, Luiza H C; Natour, Jamil

2010-11-01

Compare the medium-term effectiveness and tolerance between joint lavage (JL) in combination with triamcinolone hexacetonide (TH) intra-articular injection (IAI) and IAI with TH alone for treatment of primary osteoarthritis (OA) of the knee. A randomized, double-blind, controlled study was carried out on 60 patients with primary OA of the knee, randomized into two intervention groups: JL/TH group, joint lavage in combination with TH intra-articular injection and TH group, TH intra-articular injection. Patients were followed for 12 weeks by a blind observer using the following outcome measurements: visual analogue scale for pain at rest and in movement, goniometry, WOMAC, Lequesne's index, timed 50-ft walk, perception of improvement, Likert scale for improvement assessment, use of nonsteroidal anti-inflammatory drugs and analgesics, and local side effects. There were no statistical differences in the inter-group analysis for any of the variables studied over the 12-week period. Although both groups demonstrated statistical improvement in the intra-group evaluation (except for Likert scale according to patient and the use of anti-inflammatory drugs). In the Kellgren-Lawrence scale (KL) 2 and 3 sub-analysis, there was a statistical difference regarding joint flexion among patients classified as KL 2, favoring the TH group (p=0.03). For the KL 3 patients, there were statistical differences favoring the JL/TH group regarding Lequesne (p=0.021), WOMAC pain score (p=0.01), and Likert scale according to the patient (p=0.028) and the physician (p=0.034). The combination of joint lavage and IAI with TH was not more effective than IAI with TH alone in the treatment of primary OA of the knee. However, KL 3 patients may receive a major benefit from this combination.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-01

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

Improved Modeling of Side-Chain–Base Interactions and Plasticity in Protein–DNA Interface Design

PubMed Central

Thyme, Summer B.; Baker, David; Bradley, Philip

2012-01-01

Combinatorial sequence optimization for protein design requires libraries of discrete side-chain conformations. The discreteness of these libraries is problematic, particularly for long, polar side chains, since favorable interactions can be missed. Previously, an approach to loop remodeling where protein backbone movement is directed by side-chain rotamers predicted to form interactions previously observed in native complexes (termed “motifs”) was described. Here, we show how such motif libraries can be incorporated into combinatorial sequence optimization protocols and improve native complex recapitulation. Guided by the motif rotamer searches, we made improvements to the underlying energy function, increasing recapitulation of native interactions. To further test the methods, we carried out a comprehensive experimental scan of amino acid preferences in the I-AniI protein–DNA interface and found that many positions tolerated multiple amino acids. This sequence plasticity is not observed in the computational results because of the fixed-backbone approximation of the model. We improved modeling of this diversity by introducing DNA flexibility and reducing the convergence of the simulated annealing algorithm that drives the design process. In addition to serving as a benchmark, this extensive experimental data set provides insight into the types of interactions essential to maintain the function of this potential gene therapy reagent. PMID:22426128

Accelerated cell sheet detachment by copolymerizing hydrophilic PEG side chains into PNIPAm nanocomposite hydrogels.

PubMed

Liu, Dan; Wang, Tao; Liu, Xinxing; Tong, Zhen

2012-10-01

One-end-connected short poly(ethylene glycol) (PEG) side chains were facilely introduced into the poly(N-isopropylacrylamide) (PNIPAm) nanocomposite hydrogel (NC gel) via in situ copolymerization of NIPAm monomer and PEG macromonomer in the aqueous suspension of hectorite clay Laponite XLS. The NC gels were characterized with Fourier transform infrared and x-ray photoelectron spectroscopy for the composition, DSC and transmittance for the phase separation temperature, dynamic mechanical spectra and swelling ratio for the interaction. Increasing the PEG content led to a small increase in the storage modulus and the lower critical solution temperature (LCST) of the copolymerized NC gels, and the LCST of the copolymerized NC gels was still below 37 °C. The L929 cell adhesion and proliferation on the surface of these NC gels were not suppressed by the incorporation of hydrophilic PEG side chains. By lowering temperature below the LCST, the cell sheet spontaneously detached from the copolymerized NC gels. The surface morphology and surface wettability of the NC gels were detected by atom force microscope and contact angle measurement. A rough and hydrophilic surface induced by a small amount of PEG side chains was found to be favorable to accelerate the cell sheet detachment, probably due to the enhanced water permeation into the gel-cell sheet interface.

Improved modeling of side-chain--base interactions and plasticity in protein--DNA interface design.

PubMed

Thyme, Summer B; Baker, David; Bradley, Philip

2012-06-08

Combinatorial sequence optimization for protein design requires libraries of discrete side-chain conformations. The discreteness of these libraries is problematic, particularly for long, polar side chains, since favorable interactions can be missed. Previously, an approach to loop remodeling where protein backbone movement is directed by side-chain rotamers predicted to form interactions previously observed in native complexes (termed "motifs") was described. Here, we show how such motif libraries can be incorporated into combinatorial sequence optimization protocols and improve native complex recapitulation. Guided by the motif rotamer searches, we made improvements to the underlying energy function, increasing recapitulation of native interactions. To further test the methods, we carried out a comprehensive experimental scan of amino acid preferences in the I-AniI protein-DNA interface and found that many positions tolerated multiple amino acids. This sequence plasticity is not observed in the computational results because of the fixed-backbone approximation of the model. We improved modeling of this diversity by introducing DNA flexibility and reducing the convergence of the simulated annealing algorithm that drives the design process. In addition to serving as a benchmark, this extensive experimental data set provides insight into the types of interactions essential to maintain the function of this potential gene therapy reagent. Published by Elsevier Ltd.

Needle Acupuncture for Substance Use Disorders: A Systematic Review

DTIC Science & Technology

2015-01-01

RCTs). We did identify statistically significant, clinically medium effects in favor of acupuncture (as an adjunctive or monotherapy) versus any...statistically significant, clinically medium effects in favor of acupuncture (as an adjunctive or monotherapy) versus any comparator at...at postintervention. We did identify statistically significant, clinically medium effects in favor of acupuncture (as an adjunctive or monotherapy

Side effects associated with anti-HIV drugs.

PubMed

Highleyman, L

1998-04-01

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

Emerging commercial molecular tests for the diagnosis of bloodstream infection.

PubMed

Mwaigwisya, Solomon; Assiri, Rasha Assad M; O'Grady, Justin

2015-05-01

Bloodstream infection (BSI) by microorganisms can lead to sepsis. This condition has a high mortality rate, which rises significantly with delays in initiation of appropriate antimicrobial treatment. Current culture methods for diagnosing BSI have long turnaround times and poor clinical sensitivity. While clinicians wait for culture diagnosis, patients are treated empirically, which can result in inappropriate treatment, undesirable side effects and contribute to drug resistance development. Molecular diagnostics assays that target pathogen DNA can identify pathogens and resistance markers within hours. Early diagnosis improves antibiotic stewardship and is associated with favorable clinical outcomes. Nonetheless, limitations of current molecular diagnostic methods are substantial. This article reviews recent commercially available molecular methods that use pathogen DNA to diagnose BSI, either by testing positive blood cultures or directly testing patient blood. We critically assess these tests and their application in clinical microbiology. A view of future directions in BSI diagnosis is also provided.

Mesoscale numerical modeling of meteorological events in a strong topographic gradient in the northeastern part of Mexico

NASA Astrophysics Data System (ADS)

Pineda-Martinez, Luis F.; Carbajal, Noel

2009-08-01

A series of numerical experiments were carried out to study the effect of meteorological events such as warm and cold air masses on climatic features and variability of a understudied region with strong topographic gradients in the northeastern part of Mexico. We applied the mesoscale model MM5. We investigated the influence of soil moisture availability in the performance of the model under two representative events for winter and summer. The results showed that a better resolution in land use cover improved the agreement among observed and calculated data. The topography induces atmospheric circulation patterns that determine the spatial distribution of climate and seasonal behavior. The numerical experiments reveal regions favorable to forced convection on the eastern side of the mountain chains Eastern Sierra Madre and Sierra de Alvarez. These processes affect the vertical and horizontal structure of the meteorological variables along the topographic gradient.

Theoretical analysis of rotating two phase detonation in a rocket motor

NASA Technical Reports Server (NTRS)

Shen, I.; Adamson, T. C., Jr.

1973-01-01

Tangential mode, non-linear wave motion in a liquid propellant rocket engine is studied, using a two phase detonation wave as the reaction model. Because the detonation wave is followed immediately by expansion waves, due to the side relief in the axial direction, it is a Chapman-Jouguet wave. The strength of this wave, which may be characterized by the pressure ratio across the wave, as well as the wave speed and the local wave Mach number, are related to design parameters such as the contraction ratio, chamber speed of sound, chamber diameter, propellant injection density and velocity, and the specific heat ratio of the burned gases. In addition, the distribution of flow properties along the injector face can be computed. Numerical calculations show favorable comparison with experimental findings. Finally, the effects of drop size are discussed and a simple criterion is found to set the lower limit of validity of this strong wave analysis.

A Case of Recurrent Anaplastic Meningioma of the Skull Base with Radiologic Response to Hydroxyurea

PubMed Central

Gurberg, Joshua; Bouganim, Nathaniel; Shenouda, George; Zeitouni, Anthony

2014-01-01

Anaplastic meningiomas are rare and aggressive tumors with a high propensity for local recurrence. Surgical resection and postoperative radiotherapy are the standard of care for primary disease and local recurrences. Refractory disease is managed with chemotherapy with limited success. A highly efficacious, well-tolerated chemotherapeutic agent has yet to be found for this disease entity. Hydroxyurea is currently receiving renewed attention because of its efficacy in inducing apoptosis of meningioma cells in vitro and its favorable side-effect profile. Thus far, in humans, this agent has only induced stable disease. We describe the first patient showing a near complete/partial clinical and radiological regression after 5 months of 25 mg/kg of hydroxyurea once daily, given within 1 month after stereotactic fractionated reirradiation of a previously irradiated and operated anaplastic meningioma of the skull base. Magnetic resonance imaging showed a significant and sustained response with tumor shrinkage and cavitation. PMID:25083390

Canagliflozin-current status in the treatment of type 2 diabetes mellitus with focus on clinical trial data

PubMed Central

Bhatia, Jagriti; Gamad, Nanda; Bharti, Saurabh; Arya, Dharamvir Singh

2014-01-01

Canagliflozin (CFZ) is a member of new class of glucose lowering agents, sodium-glucose co-transporter (SGLT) inhibitors, which got approval by food and drug administration. It has insulin independent action by blocking the transporter protein SGLT2 in the kidneys, resulting in urinary glucose excretion and reduction in blood glucose levels. In clinical trials, CFZ significantly decreased HbA1c level when administered either as monotherapy or as combined therapy with other anti-diabetic drugs. Intriguingly, it showed additional benefits like weight reduction and lowering of blood pressure. The commonly observed side effects were urinary and genital infections. It has exhibited favorable pharmacokinetic and pharmacodynamic profiles even in patients with renal and hepatic damage. Hence, this review purports to outline CFZ as a newer beneficial drug for type 2 diabetes mellitus. PMID:24936262

Solvent-Exposed Salt Bridges Influence the Kinetics of α-Helix Folding and Unfolding.

PubMed

Meuzelaar, Heleen; Tros, Martijn; Huerta-Viga, Adriana; van Dijk, Chris N; Vreede, Jocelyne; Woutersen, Sander

2014-03-06

Salt bridges are known to play an essential role in the thermodynamic stability of the folded conformation of many proteins, but their influence on the kinetics of folding remains largely unknown. Here, we investigate the effect of Glu-Arg salt bridges on the kinetics of α-helix folding using temperature-jump transient-infrared spectroscopy and steady-state UV circular dichroism. We find that geometrically optimized salt bridges (Glu - and Arg + are spaced four peptide units apart, and the Glu/Arg order is such that the side-chain rotameric preferences favor salt-bridge formation) significantly speed up folding and slow down unfolding, whereas salt bridges with unfavorable geometry slow down folding and slightly speed up unfolding. Our observations suggest a possible explanation for the surprising fact that many biologically active proteins contain salt bridges that do not stabilize the native conformation: these salt bridges might have a kinetic rather than a thermodynamic function.

Nontuberculous Mycobacterial Infection after Fractionated CO2 Laser Resurfacing

PubMed Central

Culton, Donna A.; Miller, Becky A.; Miller, Melissa B.; MacKuen, Courteney; Groben, Pamela; White, Becky; Cox, Gary M.; Stout, Jason E.

2013-01-01

Nontuberculous mycobacteria are increasingly associated with cutaneous infections after cosmetic procedures. Fractionated CO2 resurfacing, a widely used technique for photorejuvenation, has been associated with a more favorable side effect profile than alternative procedures. We describe 2 cases of nontuberculous mycobacterial infection after treatment with a fractionated CO2 laser at a private clinic. Densely distributed erythematous papules and pustules developed within the treated area within 2 weeks of the laser procedure. Diagnosis was confirmed by histologic analysis and culture. Both infections responded to a 4-month course of a multidrug regimen. An environmental investigation of the clinic was performed, but no source of infection was found. The case isolates differed from each other and from isolates obtained from the clinic, suggesting that the infection was acquired by postprocedure exposure. Papules and pustules after fractionated CO2 resurfacing should raise the suspicion of nontuberculous mycobacterial infection. PMID:23628077

Emergency contraceptive pills over-the-counter: a population-based survey of young Swedish women.

PubMed

Larsson, Margareta; Eurenius, Karin; Westerling, Ragnar; Tydén, Tanja

2004-04-01

One year after emergency contraceptive pills (ECP) had become prescription-free, we sent a questionnaire to 800 randomly selected women in mid-Sweden. The aim was to investigate women's knowledge, attitudes and practices regarding the method. The response rate was 71% (n = 564). The majority of the women, 65%, would prefer to purchase ECP over-the-counter (OTC) in a pharmacy. Attitudes toward the method were predominantly positive, but one fourth (24%) had worries about side effects and one third (33%) considered ECP to be a kind of abortion. Logistic regression showed that correct knowledge of and positive attitudes toward ECP contributed to estimated future use of ECP. Although women favored the OTC option, persistent misunderstanding about ECP implies that routine information from gynecologists and health professionals as well as media campaigns is needed along with the deregulation in order to make ECP an accepted and properly used contraceptive method.

Cetuximab And The Head And Neck Squamous Cell Cancer.

PubMed

Concu, Riccardo; Cordeiro, Maria Natalia Dias Soeiro

2018-01-12

The head and neck squamous cell cancer (HNSCC) is the most common type of head and neck cancer (more than 90%), and all over the world more than a half million people have been developing this cancer in the last years. This type of cancer is usually marked by a poor prognosis with a really significant morbidity and mortality. Cetuximab received early favor as an exciting and promising new therapy with relatively mild side effect, and due to this received authorization in the 2004 from the European Medicines Agency (EMA) and in the 2006 from the Food and Drug Association (FDA) for the treatment of patients with squamous cell cancer of the head and neck in combination with radiation therapy for locally advanced disease. In this work we will review the application and the efficacy of the Cetuximab in the treatment of the HNSCC. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A new biphasic osteoinductive calcium composite material with a negative Zeta potential for bone augmentation

PubMed Central

Smeets, Ralf; Kolk, Andreas; Gerressen, Marcus; Driemel, Oliver; Maciejewski, Oliver; Hermanns-Sachweh, Benita; Riediger, Dieter; Stein, Jamal M

2009-01-01

The aim of the present study was to analyze the osteogenic potential of a biphasic calcium composite material (BCC) with a negative surface charge for maxillary sinus floor augmentation. In a 61 year old patient, the BCC material was used in a bilateral sinus floor augmentation procedure. Six months postoperative, a bone sample was taken from the augmented regions before two titanium implants were inserted at each side. We analyzed bone neoformation by histology, bone density by computed tomography, and measured the activity of voltage-activated calcium currents of osteoblasts and surface charge effects. Control orthopantomograms were carried out five months after implant insertion. The BCC was biocompatible and replaced by new mineralized bone after being resorbed completely. The material demonstrated a negative surface charge (negative Zeta potential) which was found to be favorable for bone regeneration and osseointegration of dental implants. PMID:19523239

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

PubMed

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

2017-04-01

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

Side Effect Perceptions and their Impact on Treatment Decisions in Women

PubMed Central

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

2016-01-01

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

The α-Terpineol to 1,8-Cineole Cyclization Reaction of Tobacco Terpene Synthases1

PubMed Central

Piechulla, Birgit; Bartelt, Richard; Brosemann, Anne; Bouwmeester, Harro; Hippauf, Frank

2016-01-01

Flowers of Nicotiana species emit a characteristic blend including the cineole cassette monoterpenes. This set of terpenes is synthesized by multiproduct enzymes, with either 1,8-cineole or α-terpineol contributing most to the volatile spectrum, thus referring to cineole or terpineol synthase, respectively. To understand the molecular and structural requirements of the enzymes that favor the biochemical formation of α-terpineol and 1,8-cineole, site-directed mutagenesis, in silico modeling, and semiempiric calculations were performed. Our results indicate the formation of α-terpineol by a nucleophilic attack of water. During this attack, the α-terpinyl cation is stabilized by π-stacking with a tryptophan side chain (tryptophan-253). The hypothesized catalytic mechanism of α-terpineol-to-1,8-cineole conversion is initiated by a catalytic dyad (histidine-502 and glutamate-249), acting as a base, and a threonine (threonine-278) providing the subsequent rearrangement from terpineol to cineol by catalyzing the autoprotonation of (S)-(−)-α-terpineol, which is the favored enantiomer product of the recombinant enzymes. Furthermore, by site-directed mutagenesis, we were able to identify amino acids at positions 147, 148, and 266 that determine the different terpineol-cineole ratios in Nicotiana suaveolens cineole synthase and Nicotiana langsdorffii terpineol synthase. Since amino acid 266 is more than 10 Å away from the active site, an indirect effect of this amino acid exchange on the catalysis is discussed. PMID:27729471

Mature Results of the Ottawa Phase II Study of Intermittent Androgen-Suppression Therapy in Prostate Cancer: Clinical Predictors of Outcome

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

Malone, Shawn; Perry, Gad; Eapen, Libni

2007-07-01

Purpose: To present the mature experience of a phase II trial of intermittent androgen suppression (IAS). Methods and Materials: Intermittent androgen-suppression therapy was initiated in prostate-cancer patients to delay hormone resistance and minimize potential side effects of androgen-deprivation therapy (ADT). Patients received cyclical periods of ADT and observation (off-treatment interval [OTI]). Androgen-deprivation therapy was reinitiated when the level of prostate-specific antigen (PSA) rose above 10 ng/ml, or for disease progression. Associations between clinical factors and eligibility for OTI were measured. Kaplan-Meier and Cox regression analyses were used to determine factors predicting the duration of OTIs. Results: Ninety-five patients completed 187more » cycles of treatment. The median duration of OTIs was 8.5 months. Patients with higher PSA and metastatic disease were less likely to be eligible for the first OTI (p < 0.01). In multivariate analysis, patients with higher PSA and local relapse had significantly longer OTIs (p < 0.01) compared with metastatic patients. The median time to withdrawal from the study was 37 months. Conclusions: Intermittent androgen suppression appears to be a favorable treatment option for patients with biochemically (according to level of PSA) or locally recurrent prostate cancer with favorable long-term survival, a high probability of eligibility for OTIs, and durable OTIs.« less

The first ANDES elements: 9-DOF plate bending triangles

NASA Technical Reports Server (NTRS)

Militello, Carmelo; Felippa, Carlos A.

1991-01-01

New elements are derived to validate and assess the assumed natural deviatoric strain (ANDES) formulation. This is a brand new variant of the assumed natural strain (ANS) formulation of finite elements, which has recently attracted attention as an effective method for constructing high-performance elements for linear and nonlinear analysis. The ANDES formulation is based on an extended parametrized variational principle developed in recent publications. The key concept is that only the deviatoric part of the strains is assumed over the element whereas the mean strain part is discarded in favor of a constant stress assumption. Unlike conventional ANS elements, ANDES elements satisfy the individual element test (a stringent form of the patch test) a priori while retaining the favorable distortion-insensitivity properties of ANS elements. The first application of this formulation is the development of several Kirchhoff plate bending triangular elements with the standard nine degrees of freedom. Linear curvature variations are sampled along the three sides with the corners as gage reading points. These sample values are interpolated over the triangle using three schemes. Two schemes merge back to conventional ANS elements, one being identical to the Discrete Kirchhoff Triangle (DKT), whereas the third one produces two new ANDES elements. Numerical experiments indicate that one of the ANDES element is relatively insensitive to distortion compared to previously derived high-performance plate-bending elements, while retaining accuracy for nondistorted elements.

Functionalization of PCL-3D Electrospun Nanofibrous Scaffolds for Improved BMP2-Induced Bone Formation.

PubMed

Miszuk, Jacob M; Xu, Tao; Yao, Qingqing; Fang, Fang; Childs, Josh D; Hong, Zhongkui; Tao, Jianning; Fong, Hao; Sun, Hongli

2018-03-01

Bone morphogenic protein 2 (BMP2) is a key growth factor for bone regeneration, possessing FDA approval for orthopedic applications. BMP2 is often required in supratherapeutic doses clinically, yielding adverse side effects and substantial treatment costs. Considering the crucial role of materials for BMPs delivery and cell osteogenic differentiation, we devote to engineering an innovative bone-matrix mimicking niche to improve low dose of BMP2-induced bone formation. Our previous work describes a novel technique, named thermally induced nanofiber self-agglomeration (TISA), for generating 3D electrospun nanofibrous (NF) polycaprolactone (PCL) scaffolds. TISA process could readily blend PCL with PLA, leading to increased osteogenic capabilities in vitro , however, these bio-inert synthetic polymers produced limited BMP2-induced bone formation in vivo. We therefore hypothesize that functionalization of NF 3D PCL scaffolds with bone-like hydroxyapatite (HA) and BMP2 signaling activator phenamil will provide a favorable osteogenic niche for bone formation at low doses of BMP2. Compared to PCL-3D scaffolds, PCL/HA-3D scaffolds demonstrated synergistically enhanced osteogenic differentiation capabilities of C2C12 cells with phenamil. Importantly, in vivo studies showed this synergism was able to generate significantly increased new bone in an ectopic mouse model, suggesting PCL/HA-3D scaffolds act as a favorable synthetic extracellular matrix for bone regeneration.

Influence of Glu/Arg, Asp/Arg, and Glu/Lys Salt Bridges on α-Helical Stability and Folding Kinetics.

PubMed

Meuzelaar, Heleen; Vreede, Jocelyne; Woutersen, Sander

2016-06-07

Using a combination of ultraviolet circular dichroism, temperature-jump transient-infrared spectroscopy, and molecular dynamics simulations, we investigate the effect of salt bridges between different types of charged amino-acid residue pairs on α-helix folding. We determine the stability and the folding and unfolding rates of 12 alanine-based α-helical peptides, each of which has a nearly identical composition containing three pairs of positively and negatively charged residues (either Glu(-)/Arg(+), Asp(-)/Arg(+), or Glu(-)/Lys(+)). Within each set of peptides, the distance and order of the oppositely charged residues in the peptide sequence differ, such that they have different capabilities of forming salt bridges. Our results indicate that stabilizing salt bridges (in which the interacting residues are spaced and ordered such that they favor helix formation) speed up α-helix formation by up to 50% and slow down the unfolding of the α-helix, whereas salt bridges with an unfavorable geometry have the opposite effect. Comparing the peptides with different types of charge pairs, we observe that salt bridges between side chains of Glu(-) and Arg(+) are most favorable for the speed of folding, probably because of the larger conformational space of the salt-bridging Glu(-)/Arg(+) rotamer pairs compared to Asp(-)/Arg(+) and Glu(-)/Lys(+). We speculate that the observed impact of salt bridges on the folding kinetics might explain why some proteins contain salt bridges that do not stabilize the final, folded conformation. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Cryotherapy Treatment After Unicompartmental and Total Knee Arthroplasty: A Review.

PubMed

Chughtai, Morad; Sodhi, Nipun; Jawad, Michael; Newman, Jared M; Khlopas, Anton; Bhave, Anil; Mont, Michael A

2017-12-01

Cryotherapy is widely utilized to enhance recovery after knee surgeries. However, the outcome parameters often vary between studies. Therefore, the purpose of this review is to compare (1) no cryotherapy vs cryotherapy; (2) cold pack cryotherapy vs continuous flow device cryotherapy; (3) various protocols of application of these cryotherapy methods; and (4) cost-benefit analysis in patients who had unicompartmental knee arthroplasty (UKA) or total knee arthroplasty (TKA). A search for "knee" and "cryotherapy" using PubMed, EBSCO Host, and SCOPUS was performed, yielding 187 initial reports. After selecting for RCTs relevant to our study, 16 studies were included. Of the 8 studies that compared the immediate postoperative outcomes between patients who did and did not receive cryotherapy, 5 studies favored cryotherapy (2 cold packs and 3 continuous cold flow devices). Of the 6 studies comparing the use of cold packs and continuous cold flow devices in patients who underwent UKA or TKA, 3 favor the use of continuous flow devices. There was no difference in pain, postoperative opioid consumption, or drain output between 2 different temperature settings of continuous cold flow device. The optimal device to use may be one that offers continuous circulating cold flow, as there were more studies demonstrating better outcomes. In addition, the pain relieving effects of cryotherapy may help minimize pain medication use, such as with opioids, which are associated with numerous potential side effects as well as dependence and addiction. Meta-analysis on the most recent RCTs should be performed next. Copyright © 2017 Elsevier Inc. All rights reserved.

Secondary Intracranial Hypertension in Pediatric Patients With Leukemia.

PubMed

Fernández-García, Miguel Ángel; Cantarín-Extremera, Verónica; Andión-Catalán, Maitane; Duat-Rodríguez, Anna; Jiménez-Echevarría, Saioa; Bermejo-Arnedo, Ignacio; Hortigüela-Saeta, Montesclaros; Rekarte-García, Saray; Babín-López, Lara; Ruano Domínguez, David

2017-12-01

We investigated the clinical characteristics of a pediatric population with hemato-oncological disease and intracranial hypertension, analyze the therapeutic response and outcome, and compare its characteristics with respect to a control group with idiopathic intracranial hypertension. We retrospectively analyzed patients with hemato-oncological disease and secondary intracranial hypertension in our center during the past five years. We compared these individuals with a historical cohort with idiopathic intracranial hypertension from our institution (control group). We identified eight patients, all with leukemia, and 21 controls. Mean age at diagnosis was 10.6 years, and 62% of individuals were female. Most of them were under treatment with drugs (62% corticosteroids, 75% active chemotherapy). Mean opening pressure of cerebrospinal fluid was 35 cm H 2 O. All had headache, but only 28% complained of visual symptoms. Only 12.5% exhibited papilledema at the time of diagnosis (versus 71% in controls). All of them were treated with acetazolamide, with average therapy duration of nine months, and all had a favorable outcome (versus 57% of controls who needed second-line treatment). None of them showed long-term visual complications (versus 20% of controls). Patients with hemato-oncological disease and secondary intracranial hypertension may not develop typical symptomatology. Thus, diagnosis and recognition of this entity among this cohort may be difficult. Associated factors are diverse and do not show an obvious causal relationship. A high index of suspicion must be maintained for diagnosis, because a favorable outcome is expected with prompt treatment. Acetazolamide is effective as a first-line therapy and caused few side effects. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-10-25

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

Side Fenestrations Provide an "Anchor" for a Stable Binding of A1899 to the Pore of TASK-1 Potassium Channels.

PubMed

Ramírez, David; Arévalo, Bárbara; Martínez, Gonzalo; Rinné, Susanne; Sepúlveda, Francisco V; Decher, Niels; González, Wendy

2017-07-03

A1899 is a potent and selective inhibitor of the two-pore domain potassium (K 2P ) channel TASK-1. It was previously reported that A1899 acts as an open-channel blocker and binds to residues of the P1 and P2 regions, the M2 and M4 segments, and the halothane response element. The recently described crystal structures of K 2P channels together with the newly identified side fenestrations indicate that residues relevant for TASK-1 inhibition are not purely facing the central cavity as initially proposed. Accordingly, the TASK-1 binding site and the mechanism of inhibition might need a re-evaluation. We have used TASK-1 homology models based on recently crystallized K 2P channels and molecular dynamics simulation to demonstrate that the highly potent TASK-1 blocker A1899 requires binding to residues located in the side fenestrations. Unexpectedly, most of the previously described residues that interfere with TASK-1 blockade by A1899 project their side chains toward the fenestration lumina, underlining the relevance of these structures for drug binding in K 2P channels. Despite its hydrophobicity, A1899 does not seem to use the fenestrations to gain access to the central cavity from the lipid bilayer. In contrast, binding of A1899 to residues of the side fenestrations might provide a physical "anchor", reflecting an energetically favorable binding mode that after pore occlusion stabilizes the closed state of the channels.

Structural Model Error and Decision Relevancy

NASA Astrophysics Data System (ADS)

Goldsby, M.; Lusk, G.

2017-12-01

The extent to which climate models can underwrite specific climate policies has long been a contentious issue. Skeptics frequently deny that climate models are trustworthy in an attempt to undermine climate action, whereas policy makers often desire information that exceeds the capabilities of extant models. While not skeptics, a group of mathematicians and philosophers [Frigg et al. (2014)] recently argued that even tiny differences between the structure of a complex dynamical model and its target system can lead to dramatic predictive errors, possibly resulting in disastrous consequences when policy decisions are based upon those predictions. They call this result the Hawkmoth effect (HME), and seemingly use it to rebuke rightwing proposals to forgo mitigation in favor of adaptation. However, a vigorous debate has emerged between Frigg et al. on one side and another philosopher-mathematician pair [Winsberg and Goodwin (2016)] on the other. On one hand, Frigg et al. argue that their result shifts the burden to climate scientists to demonstrate that their models do not fall prey to the HME. On the other hand, Winsberg and Goodwin suggest that arguments like those asserted by Frigg et al. can be, if taken seriously, "dangerous": they fail to consider the variety of purposes for which models can be used, and thus too hastily undermine large swaths of climate science. They put the burden back on Frigg et al. to show their result has any effect on climate science. This paper seeks to attenuate this debate by establishing an irenic middle position; we find that there is more agreement between sides than it first seems. We distinguish a `decision standard' from a `burden of proof', which helps clarify the contributions to the debate from both sides. In making this distinction, we argue that scientists bear the burden of assessing the consequences of HME, but that the standard Frigg et al. adopt for decision relevancy is too strict.

Response of seabirds to fluctuations in forage fish density

USGS Publications Warehouse

Piatt, John F.

2002-01-01

Following the Exxon Valdez Oil Spill (EVOS), one concern was that prevailing ecological conditions in the Gulf of Alaska (GOA) would not favor recovery of damaged seabird populations. To address this issue, we examined relationships between oceanography, forage fish and seabirds near three seabird colonies in lower Cook Inlet (LCI) in 1995-1999 (some colony work continued until 2001). Upwelling of cold, nutrient-rich GOA waters at the entrance to the shallow LCI estuary supports a high density of juvenile pollock, sand lance, and capelin; which in turn are exploited by high densities of breeding seabirds (murres, kittiwakes, puffins, etc.) on the east side of LCI. Waters on the west side of LCI are oceanographically distinct (warmer, less saline, outflowing), and much less productive for forage fish and seabirds. Patterns of seabird foraging behavior, productivity and population change reflected patterns of forage fish abundance and distribution, which in turn depended on local oceanography. Most seabird parameters varied with forage fish density in a non-linear (e.g., sigmoidal, exponential) fashion, and in some areas and years, productivity was limited by food availability.  Current and projected ecological conditions favor recovery of seabirds from the EVOS at some colonies. In 14 chapters, this report summarizes data and compiles it into 247 tables, figures and appendices. Chapter 14 provides a thorough synthesis of overall project findings. Final analyses and interpretations of data will be published later in peer-reviewed journals (in addition to 61 articles already completed).

A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting.

PubMed

Viljoen, Estelle; Visser, Janicke; Koen, Nelene; Musekiwa, Alfred

2014-03-19

Nausea and vomiting during pregnancy (NVP) occur commonly. Possible harmful side-effects of conventional medicine to the fetus create the need for alternative options to relieve NVP. This systematic review (SR) investigated current evidence regarding orally administered ginger for the treatment of NVP. The primary objective was to assess the effectiveness of ginger in treating NVP. The secondary objective was to assess the safety of ginger during pregnancy. A comprehensive electronic bibliographic database search was carried out. Randomized controlled trials (RCTs) of the efficacy of orally administered ginger, as treatment for NVP in pregnant women at any stage of pregnancy, published in English, were included. Two researchers independently extracted data and assessed trial quality. RevMan5 software (Cochrane Collaboration) was used for data analysis. p < 0.05 was considered statistically significant. Twelve RCTs involving 1278 pregnant women were included. Ginger significantly improved the symptoms of nausea when compared to placebo (MD 1.20, 95% CI 0.56-1.84, p = 0.0002, I² = 0%). Ginger did not significantly reduce the number of vomiting episodes during NVP, when compared to placebo, although there was a trend towards improvement (MD 0.72, 95% CI -0.03-1.46, p = 0.06, I² = 71%). Subgroup analyses seemed to favor the lower daily dosage of <1500 mg ginger for nausea relief. Ginger did not pose a significant risk for spontaneous abortion compared to placebo (RR 3.14, 95% CI 0.65-15.11, p = 0.15; I² = 0%), or to vitamin B₆ (RR 0.49, 95% CI 0.17-1.42, p = 0.19, I² = 40%). Similarly, ginger did not pose a significant risk for the side-effects of heartburn or drowsiness. This review suggests potential benefits of ginger in reducing nausea symptoms in pregnancy (bearing in mind the limited number of studies, variable outcome reporting and low quality of evidence). Ginger did not significantly affect vomiting episodes, nor pose a risk for side-effects or adverse events during pregnancy. Based on evidence from this SR, ginger could be considered a harmless and possibly effective alternative option for women suffering from NVP. International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42011001237.

A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting

PubMed Central

2014-01-01

Background and objectives Nausea and vomiting during pregnancy (NVP) occur commonly. Possible harmful side-effects of conventional medicine to the fetus create the need for alternative options to relieve NVP. This systematic review (SR) investigated current evidence regarding orally administered ginger for the treatment of NVP. The primary objective was to assess the effectiveness of ginger in treating NVP. The secondary objective was to assess the safety of ginger during pregnancy. Methods A comprehensive electronic bibliographic database search was carried out. Randomized controlled trials (RCTs) of the efficacy of orally administered ginger, as treatment for NVP in pregnant women at any stage of pregnancy, published in English, were included. Two researchers independently extracted data and assessed trial quality. RevMan5 software (Cochrane Collaboration) was used for data analysis. p < 0.05 was considered statistically significant. Results Twelve RCTs involving 1278 pregnant women were included. Ginger significantly improved the symptoms of nausea when compared to placebo (MD 1.20, 95% CI 0.56-1.84, p = 0.0002, I2 = 0%). Ginger did not significantly reduce the number of vomiting episodes during NVP, when compared to placebo, although there was a trend towards improvement (MD 0.72, 95% CI -0.03-1.46, p = 0.06, I2 = 71%). Subgroup analyses seemed to favor the lower daily dosage of <1500 mg ginger for nausea relief. Ginger did not pose a significant risk for spontaneous abortion compared to placebo (RR 3.14, 95% CI 0.65-15.11, p = 0.15; I2 = 0%), or to vitamin B6 (RR 0.49, 95% CI 0.17-1.42, p = 0.19, I2 = 40%). Similarly, ginger did not pose a significant risk for the side-effects of heartburn or drowsiness. Conclusions This review suggests potential benefits of ginger in reducing nausea symptoms in pregnancy (bearing in mind the limited number of studies, variable outcome reporting and low quality of evidence). Ginger did not significantly affect vomiting episodes, nor pose a risk for side-effects or adverse events during pregnancy. Based on evidence from this SR, ginger could be considered a harmless and possibly effective alternative option for women suffering from NVP. International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42011001237. PMID:24642205

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

PubMed

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

2017-09-01

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

Delicaflavone induces autophagic cell death in lung cancer via Akt/mTOR/p70S6K signaling pathway.

PubMed

Sui, Yuxia; Yao, Hong; Li, Shaoguang; Jin, Long; Shi, Peiying; Li, Zhijun; Wang, Gang; Lin, Shilan; Wu, Youjia; Li, Yuxiang; Huang, Liying; Liu, Qicai; Lin, Xinhua

2017-03-01

Searching for potential anticancer agents from natural sources is an effective strategy for developing novel chemotherapeutic agents. In this study, data supporting the in vitro and in vivo anticancer effects of delicaflavone, a rarely occurring biflavonoid from Selaginella doederleinii, were reported. Delicaflavone exhibited favorable anticancer properties, as shown by the MTT assay and xenograft model of human non-small cell lung cancer in male BALB/c nude mice without observable adverse effect. By transmission electron microscopy with acridine orange and Cyto-ID®Autophagy detection dyes, Western blot analysis, and RT-PCR assay, we confirmed that delicaflavone induces autophagic cell death by increasing the ratio of LC3-II to LC3-I, which are autophagy-related proteins, and promoting the generation of acidic vesicular organelles and autolysosomes in the cytoplasm of human lung cancer A549 and PC-9 cells in a time- and dose-dependent manner. Delicaflavone downregulated the expression of phospho-Akt, phospho-mTOR, and phospho-p70S6K in a time- and dose-dependent manner, suggesting that it induced autophagy by inhibiting the Akt/mTOR/p70S6K pathway in A549 and PC-9 cells. Delicaflavone is a potential anticancer agent that can induce autophagic cell death in human non-small cell lung cancer via the Akt/mTOR/p70S6K signaling pathway. Delicaflavone showed anti-lung cancer effects in vitro and in vivo. Delicaflavone induced autophagic cell death via Akt/mTOR/p70S6K signaling pathway. Delicaflavone did not show observable side effects in a xenograft mouse model. Delicaflavone may represent a potential therapeutic agent for lung cancer. Delicaflavone showed anti-lung cancer effects in vitro and in vivo. Delicaflavone induced autophagic cell death via Akt/mTOR/p70S6K signaling pathway. Delicaflavone did not show observable side effects in a xenograft mouse model. Delicaflavone may represent a potential therapeutic agent for lung cancer.

Rationale for combination therapy in hypertension management: focus on angiotensin receptor blockers and thiazide diuretics.

PubMed

Nash, David T

2007-04-01

Despite recognition that hypertension is a major risk factor for cardiovascular events and mortality, blood pressure control rates remain low in the US population. Reflecting clinical trial results, hypertension management guidelines assert the clinical benefit of achieving current blood pressure goals and indicate that most patients will require 2 or more drugs to reach goal. Well-designed drug combinations counter hypertension via complementary mechanisms that increase antihypertensive efficacy, potentially with lower rates of adverse events than higher dose monotherapy regimens. Lower adverse event rates, in turn, may contribute to greater adherence with treatment. The combination of a low-dose diuretic with agents that block the effects of the renin-angiotensin system (RAS), such as angiotensin receptor blockers, has been found in numerous clinical trials to be highly effective for lowering blood pressure in patients with uncomplicated as well as high-risk hypertension, with a comparable favorable side effect profile compared with monotherapy. Moreover, agents that block the RAS are associated with a lower risk of new-onset diabetes mellitus than other antihypertensive classes. Complementary combinations of antihypertensive agents provide an efficient and effective approach to hypertension management.

Explanations for side effect aversion in preventive medical treatment decisions

PubMed Central

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

2008-01-01

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

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

Bhattarai, Bishnu; Kouzelis, Konstantinos; Mendaza, Iker

The gradual active load penetration in low voltage distribution grids is expected to challenge their network capacity in the near future. Distribution system operators should for this reason resort to either costly grid reinforcements or to demand side management mechanisms. Since demand side management implementation is usually cheaper, it is also the favorable solution. To this end, this article presents a framework for handling grid limit violations, both voltage and current, to ensure a secure and qualitative operation of the distribution grid. This framework consists of two steps, namely a proactive centralized and subsequently a reactive decentralized control scheme. Themore » former is employed to balance the one hour ahead load while the latter aims at regulating the consumption in real-time. In both cases, the importance of fair use of electricity demand flexibility is emphasized. Thus, it is demonstrated that this methodology aids in keeping the grid status within preset limits while utilizing flexibility from all flexibility participants.« less

Two-Dimensional Model of Scrolled Packings of Molecular Nanoribbons

NASA Astrophysics Data System (ADS)

Savin, A. V.; Mazo, M. A.

2018-04-01

A simplified model of the in-plane molecular chain, allowing the description of folded and scrolled packings of molecular nanoribbons of different structures, is proposed. Using this model, possible steady states of single-layer nanoribbons scrolls of graphene, graphane, fluorographene, and fluorographane (graphene hydrogenated on the one side and fluorinated on the other side) are obtained. Their stability is demonstrated and their energy is calculated as a function of the nanoribbon length. It is shown that the scrolled packing is the most energetically favorable nanoribbon conformation at long lengths. The existences of scrolled packings for fluorographene nanoribbons and the existence of two different scroll types corresponding to left- and right-hand Archimedean spirals for fluorographane nanoribbons in the chain model are shown for the first time. The simplicity of the proposed model makes it possible to consider the dynamics of scrolls of rather long molecular nanoribbons at long enough time intervals.

Heat transfer and pressure drop in a compact pin-fin heat exchanger with pin orientation at 18 deg to the flow direction

NASA Technical Reports Server (NTRS)

Olson, D. A.

1991-01-01

The heat transfer and pressure drop characteristics of a novel, compact heat exchanger in helium gas were measured at 3.5 MPa and Reynolds numbers of 450 to 12,000. The pin-fin specimen consisted of pins, 0.51 mm high and spaced 2.03 mm on centers, spanning a channel through which the helium flows; the angle of the row of pins to the flow direction was 18 deg. The specimen was radiatively heated on the top side at heat fluxes up to 74 W/sq cm and insulated on the back side. Correlations were developed for the friction factor and Nusselt number. The Nusselt number compares favorably to those of past studies of staggered pin-fins, when the measured temperatures are extrapolated to the temperature of the wall-fluid interface.

Comparisons between designs for single-sided linear electric motors: Homopolar synchronous and induction

NASA Astrophysics Data System (ADS)

Nondahl, T. A.; Richter, E.

1980-09-01

A design study of two types of single sided (with a passive rail) linear electric machine designs, namely homopolar linear synchronous machines (LSM's) and linear induction machines (LIM's), is described. It is assumed the machines provide tractive effort for several types of light rail vehicles and locomotives. These vehicles are wheel supported and require tractive powers ranging from 200 kW to 3735 kW and top speeds ranging from 112 km/hr to 400 km/hr. All designs are made according to specified magnetic and thermal criteria. The LSM advantages are a higher power factor, much greater restoring forces for track misalignments, and less track heating. The LIM advantages are no need to synchronize the excitation frequency precisely to vehicle speed, simpler machine construction, and a more easily anchored track structure. The relative weights of the two machine types vary with excitation frequency and speed; low frequencies and low speeds favor the LSM.

Determining the orientation of depth-rotated familiar objects.

PubMed

Niimi, Ryosuke; Yokosawa, Kazuhiko

2008-02-01

How does the human visual system determine the depth-orientation of familiar objects? We examined reaction times and errors in the detection of 15 degrees differences in the depth orientations of two simultaneously presented familiar objects, which were the same objects (Experiment 1) or different objects (Experiment 2). Detection of orientation differences was best for 0 degrees (front) and 180 degrees (back), while 45 degrees and 135 degrees yielded poorer results, and 90 degrees (side) showed intermediate results, suggesting that the visual system is tuned for front, side and back orientations. We further found that those advantages are due to orientation-specific features such as horizontal linear contours and symmetry, since the 90 degrees advantage was absent for objects with curvilinear contours, and asymmetric object diminished the 0 degrees and 180 degrees advantages. We conclude that the efficiency of visually determining object orientation is highly orientation-dependent, and object orientation may be perceived in favor of front-back axes.

Strong π-π interaction of porphyrins on (6,5) carbon nanotubes with full surface coverage: Ab-initio calculations

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

Orellana, Walter, E-mail: worellana@unab.cl

2014-07-14

The stability, electronic, and optical properties of (6,5) single-walled carbon nanotubes (CNTs) functionalized with free-base tetraphenylporphyrin (TPP) molecules through π-stacking interactions are studied by ab-initio calculations. The stability and optical response of the CNT-TPP compounds for increasing CNT-surface coverage are investigated. Our results show that four TPP molecules forming a ring around the CNT is the most stable configuration, showing strong binding energies of about 2.5 eV/TPP. However, this binding energy can increase even more after additional molecules assemble side by side along the CNT, favoring the formation of a full single layer of TPP, as experimentally suggested. The strong π-πmore » attractive forces induce molecular distortions that move the TPP higher-occupied molecular orbital levels inside the CNT bandgap, changing the optical response of the TPP molecules stacked on the CNT.« less

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

PubMed

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

2017-03-21

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

Sexual side effects associated with conventional and atypical antipsychotics.

PubMed

Compton, M T; Miller, A H

2001-01-01

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

IFN-γ promotes transendothelial migration of CD4+ T cells across the blood-brain barrier.

PubMed

Sonar, Sandip Ashok; Shaikh, Shagufta; Joshi, Nupura; Atre, Ashwini N; Lal, Girdhari

2017-10-01

Transendothelial migration (TEM) of Th1 and Th17 cells across the blood-brain barrier (BBB) has a critical role in the development of experimental autoimmune encephalomyelitis (EAE). How cytokines produced by inflammatory Th1 and Th17 cells damage the endothelial BBB and promote transendothelial migration of immune cells into the central nervous system (CNS) during autoimmunity is not understood. We therefore investigated the effect of various cytokines on brain endothelial cells. Among the various cytokines tested, such as Th1 (IFN-γ, IL-1α, IL-1β, TNF-α, IL-12), Th2 (IL-3, IL-4, IL-6 and IL-13), Th17 (IL-17A, IL-17F, IL-21, IL-22, IL-23, GM-CSF) and Treg-specific cytokines (IL-10 and TGF-β), IFN-γ predominantly showed increased expression of ICAM-1, VCAM-1, MAdCAM-1, H2-K b and I-A b molecules on brain endothelial cells. Furthermore, IFN-γ induced transendothelial migration of CD4 + T cells from the apical (luminal side) to the basal side (abluminal side) of the endothelial monolayer to chemokine CCL21 in a STAT-1-dependent manner. IFN-γ also favored the transcellular route of TEM of CD4 + T cells. Multicolor immunofluorescence and confocal microscopic analysis showed that IFN-γ induced relocalization of ICAM-1, PECAM-1, ZO-1 and VE-cadherin in the endothelial cells, which affected the migration of CD4 + T cells. These findings reveal that the IFN-γ produced during inflammation could contribute towards disrupting the BBB and promoting TEM of CD4 + T cells. Our findings also indicate that strategies that interfere with the activation of CNS endothelial cells may help in controlling neuroinflammation and autoimmunity.

NMR Insights into the Structure-Function Relationships in the Binding of Melanocortin Analogues to the MC1R Receptor.

PubMed

Morais, Maurício; Zamora-Carreras, Héctor; Raposinho, Paula D; Oliveira, Maria Cristina; Pantoja-Uceda, David; Correia, João D G; Jiménez, M Angeles

2017-07-15

Linear and cyclic analogues of the α-melanocyte stimulating hormone (α-MSH) targeting the human melanocortin receptor 1 (MC1R) are of pharmacological interest for detecting and treating melanoma. The central sequence of α-MSH (His-Phe-Arg-Trp) has been identified as being essential for receptor binding. To deepen current knowledge on the molecular basis for α-MSH bioactivity, we aimed to understand the effect of cycle size on receptor binding. To that end, we synthesised two macrocyclic isomeric α-MSH analogues, c[NH-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Lys]-Lys-NH₂ ( CycN-K6 ) and c[NH-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Lys-Lys]-NH₂ ( CycN-K7 ). Their affinities to MC1R receptor were determined by competitive binding assays, and their structures were analysed by ¹H and 13 C NMR. These results were compared to those of the previously reported analogue c[S-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Cys]-Lys-NH₂ ( CycS-C6 ). The MC1R binding affinity of the 22-membered macrocyclic peptide CycN-K6 (IC 50 = 155 ± 16 nM) is higher than that found for the 25-membered macrocyclic analogue CycN-K7 (IC 50 = 495 ± 101 nM), which, in turn, is higher than that observed for the 19-membered cyclic analogue CycS-C6 (IC 50 = 1770 ± 480 nM). NMR structural study indicated that macrocycle size leads to changes in the relative dispositions of the side chains, particularly in the packing of the Arg side chain relative to the aromatic rings. In contrast to the other analogues, the 22-membered cycle's side chains are favorably positioned for receptor interaction.

Planned nerve preservation to reduce positive surgical margins during robot-assisted laparoscopic radical prostatectomy.

PubMed

Zorn, Kevin C; Gofrit, Ofer N; Steinberg, Gary P; Taxy, Jerome B; Zagaja, Gregory P; Shalhav, Arieh L

2008-06-01

The main objective of radical prostatectomy (RP) is optimal oncologic resection with preservation of sexual function (SF). During our initial experience with robot-assisted laparoscopic radical prostatectomy (RLRP), we noted a high rate of posterolateral location of positive surgical margins (PSM) with nerve preservation (NP). With its magnified view of the surgical field and improved instrument precision, one potential advantage of RLRP is the ability to tailor the degree of NP. We evaluated the effect of a protocol for side-specific NP based on preoperative variables on PSM rates and SF outcomes. Between June and November 2006, 150 consecutive RLRPs were performed using a surgical protocol to select side-specific NP techniques (interfascial [IF], partial extrafascial [pEF], and wide extrafascial resection [WEFR]) based on preoperative risk factors (clinical stage, biopsy Gleason score, percentage of positive cores and maximal core cancer percentage, and preoperative PSA). Pathologic and SF outcomes in these patients were compared with those of a control group of 245 consecutive RLRPs in whom non-selective IF dissection was performed. All data were prospectively collected. Mean patient age, PSA, clinical stage, biopsy Gleason score and positive core involvement, pathologic Gleason score, and stage were comparable among the two groups. The overall PSM rate (12.6% nu 20.4%; P = 0.04) and posterolateral location of PSMs (37% nu 70%; P = 0.04) were significantly lower in the study group. At 12 months, potency was reported in 80%, 67%, and 11% of men undergoing bilateral IFNP, partial extrafascial nerve preservation (pEFNP), and WEFR, respectively (P = 0.27). Planning side-specific NP during RLRP, according to selected preoperative variables, can significantly reduce overall and posterolateral PSM rates. Furthermore, partial nerve sparing (pEFNP) also appears to confer favorable early SF outcomes.

High intensity focused ultrasound (HIFU).

PubMed

Barkin, Jack

2011-04-01

Curative treatments for localized prostate cancer, from least invasive to most invasive, include brachytherapy, cryosurgery, three-dimensional conformal radiation therapy, external beam radiation therapy, and radical prostatectomy. A patient with localized, low risk or intermediate risk prostate cancer who is diagnosed at an early age and receives one of these treatments has only an approximately 50% chance of maintaining an undetectable prostate-specific antigen (PSA) level, good spontaneous erections, and total continence by 5 years after treatment. This article discusses transrectal high intensity focused ultrasound (HIFU) treatment of localized prostate cancer using the Sonablate 500 (Focus Surgery, Indianapolis, IN, USA) device, which the author has adopted in favor of the Ablatherm (EDAP, TMS S. A., Lyons, France) device, the other HIFU device approved for use in Canada. Characteristics of the ideal prostate cancer include stage T1-T2b, less than 40 cc in size, and with an anterior-posterior dimension of up to 35 mm high. The anterior zone of the prostate is treated before the posterior zone. The procedure involves 2 to 3 second bursts of ultrasound energy, followed by 3 second cooling cycles. In each treatment lesion, the physician achieves a temperature of 100 C at the focal point. The device allows for real-time visualization of tissue response following the delivery of ultrasound energy. HIFU is a minimally invasive, outpatient treatment for localized prostate cancer that provides similar short term and medium term cure rates and considerably less morbidity and side effects than other treatments. Although the effectiveness of HIFU has not yet been demonstrated in large, long term studies, this treatment option should be discussed with patients who have just been diagnosed with low risk or intermediate risk prostate cancer and desire aggressive, noninvasive, curative therapy, with potentially a lower incidence of side effects compared to conventional therapy.

Effects of pitolisant, a histamine H3 inverse agonist, in drug-resistant idiopathic and symptomatic hypersomnia: a chart review.

PubMed

Leu-Semenescu, Smaranda; Nittur, Nandy; Golmard, Jean-Louis; Arnulf, Isabelle

2014-06-01

To evaluate the benefits and risks of pitolisant (a wake-enhancing drug that increases the histamine release in the brain by blocking presynaptic H3 histamine reuptake) in patients with idiopathic (IH) and symptomatic (SH) hypersomnia plus sleepiness refractory to available stimulants (modafinil, methylphenidate, mazindol, sodium oxybate, and d-amphetamine). Through retrospective analyses of patient files, the benefit (the score from the Epworth Sleepiness Scale [ESS], authorization renewal) and tolerance (side-effects) of pitolisant were assessed. A total of 78 patients with IH (n=65%, 78% women) and SH (n=13%, 54% women) received pitolisant 5-50 mg once per day over the course of five days to 37 months. The median (interquartile range) ESS scores of patients with IH decreased from 17 (15.5-18.5) to 14 (12-17). There were 36% responders (ESS fall of > or =3). The improvement in ESS score (-1.9±2.6) was different from 0 in IH without long sleep time (P<0.002) and in IH with a long sleep time (P<0.0001), but not in SH. Forty-four (63%) patients with IH and 12 (77%) patients with SH stopped pitolisant, mostly due to a lack of efficacy. Side-effects included gastrointestinal pain (15.4%), increased appetite and weight gain (14.1%), headache (12.8%), insomnia (11.5%), and anxiety (9%), as well as exceptional reports of depression and persistent genital arousal. Pitolisant had a long-term favorable benefit/risk ratio in 23-38% of drug-resistant patients with IH and SH, suggesting that histamine neurons can be stimulated in severe idiopathic and symptomatic hypersomnia. Copyright © 2014 Elsevier B.V. All rights reserved.

Problems associated with restorative materials--dentists' views in Finland and Sweden.

PubMed

Widström, E; Sundberg, H

1991-01-01

During the past 10-15 years the possible side-effects of dental restorative materials, especially due to amalgam fillings, have caused a lively debate in Sweden. There is an extensive literature on the chemical and biological properties of dental materials but no investigations have dealt with the providers' attitudes. The purpose of this study was to find out the dentists' experiences of and attitudes to patients who state they have problems related to dental restorative materials and compare the dentists' subjective assessments of those side-effects in two neighboring countries, Finland and Sweden. Information was collected by postal questionnaires addressed to dentists chosen at random in Finland (n = 625) and in Sweden (n = 960). The response rate was 73 per cent and 72 per cent respectively. The results showed that 99 per cent of the respondents had patients questioning the safety of dental materials. The number of such patients was estimated to be three times higher in Sweden (124 patients per dentist in 1989) than in Finland (39 patients per dentist). More than 90 per cent of the questions from the patients regarded amalgam fillings. Statistically significant differences were found between the respondents' opinions of amalgam, 81 per cent of the Finnish contrary to 59 per cent of the Swedish respondents considered the risk of side-effects to be low when using this material. About 90 per cent of the respondents considered glass-ionomer, gold and ceramic restorations safe, but only half of them were convinced of the safety of composite. A great majority of the Swedish respondents (79 per cent) claimed that the patients should get their fillings changed without odontologic indications if they insisted on it and paid for the treatment in comparison to 22 per cent of the Finnish respondents (p less than 0.001). In case dental insurance was to pay for this kind of treatment it was accepted by 6 per cent of the Finns and 25 per cent of the Swedes. The attitude to amalgam was in general less favorable among the dentists in Sweden than in Finland.

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

PubMed

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

2017-09-03

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

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

PubMed Central

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

2014-01-01

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

Herb Medicines against Osteoporosis: Active Compounds & Relevant Biological Mechanisms.

PubMed

Wu, Lei; Ling, Zhuoyan; Feng, Xueqin; Mao, Caiping; Xu, Zhice

2017-01-01

Osteoporosis is one of common bone disorders, affecting millions of people worldwide. Treatments of osteoporosis consist of pharmacotherapy and non-pharmacological interventions, such as mineral supplementation, lifestyle changes, and exercise programs. Due to the minimum side effects and favorable cost-effective therapeutic effects, herbal medicine has been widely applied in clinical practices for more than 2,000 years in China. Of the many traditional formulas reported for treating bone diseases, 4 single herbs namely (1) Herba Epimedii, (2) Rhizoma Drynariae, (3) Fructus Psoraleae, and (4) Cortex Eucommiae, are considered as the featured "Kidney-Yang" tonics, and frequently and effectively applied for preventing and treating osteoporosis. With the accruing development of modern chemistry, hundreds of active compounds have been identified and isolated for their anti-osteoporotic effects. This review would first sketch the phytochemistry of these featured "Kidney- Yang" tonics and present the pharmacological characteristics of the most abundant and bioactive compounds derived from the herb Herba Epimedii and Rhizoma Drynariae, including icariin and naringin. Then, the cellular and molecular underpinnings under anti-osteoporotic effects of icariin and naringin are discussed. The concerned structure-function relationships of the featured active herbal compounds would also be reviewed so as to pave the way for future drug design in treating osteoporosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Azilsartan as a Potent Antihypertensive Drug with Possible Pleiotropic Cardiometabolic Effects: A Review Study

PubMed Central

Georgiopoulos, Georgios; Katsi, Vasiliki; Oikonomou, Dimitrios; Vamvakou, Georgia; Koutli, Evangelia; Laina, Aggeliki; Tsioufis, Constantinos; Nihoyannopoulos, Petros; Tousoulis, Dimitrios

2016-01-01

Background: Hypertension related cardiovascular (CV) complications could be amplified by the presence of metabolic co-morbidities. Azilsartan medoxomil (AZL-M) is the eighth approved member of angiotensin II receptor blockers (ARBs), a drug class of high priority in the management of hypertensive subjects with diabetes mellitus type II (DMII). Methods: Under this prism, we performed a systematic review of the literature for all relevant articles in order to evaluate the efficacy, safety, and possible clinical role of AZL-M in hypertensive diabetic patients. Results: AZL-M was found to be more effective in terms of reducing indices of blood pressure over alternative ARBs or angiotensin-converting enzyme (ACE) inhibitors with minimal side effects. Preclinical studies have established pleiotropic effects for AZL-M beyond its primary antihypertensive role through differential gene expression, up-regulation of membrane receptors and favorable effect on selective intracellular biochemical and pro-atherosclerotic pathways. Conclusion: Indirect but accumulating evidence from recent literature supports the efficacy and safety of AZL-M among diabetic patients. However, no clinical data exist to date that evince a beneficial role of AZL-M in patients with metabolic disorders on top of its antihypertensive effect. Further clinical studies are warranted to assess the pleiotropic cardiometabolic benefits of AZL-M that are derived from preclinical research. PMID:27536242

Azilsartan as a Potent Antihypertensive Drug with Possible Pleiotropic Cardiometabolic Effects: A Review Study.

PubMed

Georgiopoulos, Georgios; Katsi, Vasiliki; Oikonomou, Dimitrios; Vamvakou, Georgia; Koutli, Evangelia; Laina, Aggeliki; Tsioufis, Constantinos; Nihoyannopoulos, Petros; Tousoulis, Dimitrios

2016-01-01

Hypertension related cardiovascular (CV) complications could be amplified by the presence of metabolic co-morbidities. Azilsartan medoxomil (AZL-M) is the eighth approved member of angiotensin II receptor blockers (ARBs), a drug class of high priority in the management of hypertensive subjects with diabetes mellitus type II (DMII). Under this prism, we performed a systematic review of the literature for all relevant articles in order to evaluate the efficacy, safety, and possible clinical role of AZL-M in hypertensive diabetic patients. AZL-M was found to be more effective in terms of reducing indices of blood pressure over alternative ARBs or angiotensin-converting enzyme (ACE) inhibitors with minimal side effects. Preclinical studies have established pleiotropic effects for AZL-M beyond its primary antihypertensive role through differential gene expression, up-regulation of membrane receptors and favorable effect on selective intracellular biochemical and pro-atherosclerotic pathways. Indirect but accumulating evidence from recent literature supports the efficacy and safety of AZL-M among diabetic patients. However, no clinical data exist to date that evince a beneficial role of AZL-M in patients with metabolic disorders on top of its antihypertensive effect. Further clinical studies are warranted to assess the pleiotropic cardiometabolic benefits of AZL-M that are derived from preclinical research.

DXA and pQCT predict pertrochanteric and not femoral neck fracture load in a human side-impact fracture model.

PubMed

Gebauer, Matthias; Stark, Olaf; Vettorazzi, Eik; Grifka, Joachim; Püschel, Klaus; Amling, Michael; Beckmann, Johannes

2014-01-01

The validity of dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) measurements as predictors of pertrochanteric and femoral neck fracture loads was compared in an experimental simulation of a fall on the greater trochanter. 65 proximal femora were harvested from patients at autopsy. All specimens were scanned with use of DXA for areal bone mineral density and pQCT for volumetric densities at selected sites of the proximal femur. A three-point bending test simulating a side-impact was performed to determine fracture load and resulted in 16 femoral neck and 49 pertrochanteric fractures. Regression analysis revealed that DXA BMD trochanter was the best variable at predicting fracture load of pertrochanteric fractures with an adjusted R(2) of 0.824 (p < 0.0001). There was no correlation between densitometric parameters and the fracture load of femoral neck fractures. A significant correlation further was found between body weight, height, femoral head diameter, and neck length on the one side and fracture load on the other side, irrespective of the fracture type. Clinically, the DXA BMD trochanter should be favored and integrated routinely as well as biometric and geometric parameters, particularly in elderly people with known osteoporosis at risk for falls. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

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

PubMed Central

Holmes, Dave

2016-01-01

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

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

PubMed

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

2011-04-21

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

The amiodarone derivative KB130015 activates hERG1 potassium channels via a novel mechanism

PubMed Central

Gessner, Guido; Macianskiene, Regina; Starkus, John G.; Schönherr, Roland; Heinemann, Stefan H.

2010-01-01

Human ether à go-go related gene (hERG1) potassium channels underlie the repolarizing IKr current in the heart. Since they are targets of various drugs with cardiac side effects we tested whether the amiodarone derivative 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015) blocks hERG1 channels like its parent compound. Using patch-clamp and two-electrode voltage-clamp techniques we found that KB130015 blocks native and recombinant hERG1 channels at high voltages, but it activates them at low voltages. The activating effect has an apparent EC50 value of 12 μM and is brought about by an about 4-fold acceleration of activation kinetics and a shift in voltage-dependent activation by −16 mV. Channel activation was not use-dependent and was independent of inactivation gating. KB130015 presumably binds to the hERG1 pore from the cytosolic side and functionally competes with hERG1 block by amiodarone, E4031 (N-[4-[[1-[2-(6-methyl-2-pyridinyl)ethyl] -4-piperidinyl] carbonyl] phenyl] methanesulfonamide dihydrochloride), and sertindole. Vice versa, amiodarone attenuates hERG1 activation by KB130015. Based on synergic channel activation by mallotoxin and KB130015 we conclude that the hERG1 pore contains at least two sites for activators that are functionally coupled among each other and to the cavity-blocker site. KB130015 and amiodarone may serve as lead structures for the identification of hERG1 pore-interacting drugs favoring channel activation vs. block. PMID:20097192

Attitudes Toward Medical Cannabis Legalization Among Serbian Medical Students.

PubMed

Vujcic, Isidora; Pavlovic, Aleksandar; Dubljanin, Eleonora; Maksimovic, Jadranka; Nikolic, Aleksandra; Sipetic-Grujicic, Sandra

2017-07-29

Currently, medical cannabis polices are experiencing rapid changes, and an increasing number of nations around the world legalize medical cannabis for certain groups of patients, including those in Serbia. To determine medical students' attitudes toward medical cannabis legalization and to examine the factors influencing their attitudes. Fourth-year medical students at the Faculty of Medicine, University of Belgrade, had participated in a cross-sectional study. Data were collected by an anonymous questionnaire. Overall, 63.4% students supported medical cannabis legalization, and only 20.8% supported its legalization for recreational use. Students who previously used marijuana (p <.001) and alcohol (p =.004) were significantly more in favor of medical cannabis legalization compared with students who never used them. Support for marijuana recreational use was also related to prior marijuana (p <.001) and alcohol consumption (p =.006). Only cancer (90.4%) and chronic pain (74.2%) were correctly reported approved medical indications by more than half the students. Students who supported medical cannabis legalization showed better knowledge about indications, in contrast to opponents for legalization who showed better knowledge about side effects. Beliefs that using medical cannabis is safe and has health benefits were correlated with support for legalization, and previous marijuana and alcohol use, while beliefs that medical cannabis poses health risks correlated most strongly with previous marijuana use. Conclusions/Importance: The medical students' attitudes toward medical cannabis legalization were significantly correlated with previous use of marijuana and alcohol, knowledge about medical indications and side effects, and their beliefs regarding medical cannabis health benefits and risks.

Prediction of Heat and Mass Transfer in a Rotating Ribbed Coolant Passage With a 180 Degree Turn

NASA Technical Reports Server (NTRS)

Rigby, David L.

1999-01-01

Numerical results are presented for flow in a rotating internal passage with a 180 degree turn and ribbed walls. Reynolds numbers ranging from 5200 to 7900, and Rotation numbers of 0.0 and 0.24 were considered. The straight sections of the channel have a square cross section, with square ribs spaced one hydraulic diameter (D) apart on two opposite sides. The ribs have a height of 0.1D and are not staggered from one side to the other. The full three dimensional Reynolds Averaged Navier-Stokes equations are solved combined with the Wilcox k-omega turbulence model. By solving an additional equation for mass transfer, it is possible to isolate the effect of buoyancy in the presence of rotation. That is, heat transfer induced buoyancy effects can be eliminated as in naphthalene sublimation experiments. Heat transfer, mass transfer and flow field results are presented with favorable agreement with available experimental data. It is shown that numerically predicting the reattachment between ribs is essential to achieving an accurate prediction of heat/mass transfer. For the low Reynolds numbers considered, the standard turbulence model did not produce reattachment between ribs. By modifying the wall boundary condition on omega, the turbulent specific dissipation rate, much better agreement with the flow structure and heat/ mass transfer was achieved. It is beyond the scope of the present work to make a general recommendation on the omega wall boundary condition. However, the present results suggest that the omega boundary condition should take into account the proximity to abrupt changes in geometry.

Side Effects

Cancer.gov

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

Examining Innovative Divertor and Main Chamber Options for a National Divertor Test Tokamak

NASA Astrophysics Data System (ADS)

Labombard, B.; Umansky, M.; Brunner, D.; Kuang, A. Q.; Marmar, E.; Wallace, G.; Whyte, D.; Wukitch, S.

2016-10-01

The US fusion community has identified a compelling need for a National Divertor Test Tokamak. The 2015 Community Planning Workshop on PMI called for a national working group to develop options. Important elements of a NDTT, adopted from the ADX concept, include the ability to explore long-leg divertor `solutions for power exhaust and particle control' (Priority Research Direction B) and to employ inside-launch RF actuators combined with double-null topologies as `plasma solution for main chamber wall components, including tools for controllable sustained operation' (PRD-C). Here we examine new information on these ideas. The projected performance of super-X and X-point target long-leg divertors is looking very promising; a stable fully-detached divertor condition handling an order-of-magnitude increase in power handling over conventional divertors may be possible. New experiments on Alcator C-Mod are addressing issues of high-field side versus low-field side heat flux sharing in double-null topologies and the screening of impurities that might originate from RF actuators placed in the high-field side - both with favorable results. Supported by USDoE Awards DE-FC02-99ER54512 and DE-AC52-07NA27344.

Phase Change Material Heat Exchanger Life Test

NASA Technical Reports Server (NTRS)

Lillibridge, Sean; Stephan, Ryan

2009-01-01

Low Lunar Orbit (LLO) poses unique thermal challenges for the orbiting space craft, particularly regarding the performance of the radiators. The IR environment of the space craft varies drastically from the light side to the dark side of the moon. The result is a situation where a radiator sized for the maximal heat load in the most adverse situation is subject to freezing on the dark side of the orbit. One solution to this problem is to implement Phase Change Material (PCM) Heat Exchangers. PCM Heat Exchangers act as a "thermal capacitor," storing thermal energy when there is too much being produced by the space craft to reject to space, and then feeding that energy back into the thermal loop when conditions are more favorable. Because they do not use an expendable resource, such as the feed water used by sublimators and evaporators, PCM Heat Exchangers are ideal for long duration LLO missions. In order to validate the performance of PCM Heat Exchangers, a life test is being conducted on four n-Pentadecane, carbon filament heat exchangers. Fluid loop performance, repeatability, and measurement of performance degradation over 2500 melt-freeze cycles will be performed.

Correlation between polymer architecture, mesoscale structure and photovoltaic performance in side-chain-modified PAE-PAV:fullerene bulk-heterojunction solar cells

NASA Astrophysics Data System (ADS)

Rathgeber, S.; Kuehnlenz, F.; Hoppe, H.; Egbe, D. A. M.; Tuerk, S.; Perlich, J.; Gehrke, R.

2012-02-01

A poly(arylene-ethynylene)-alt-poly(arylene-vinylene) statistical copolymer carrying linear and branched alkoxy side chains along the conjugated backbone in a random manner, yields, compared to its regular substituted counterparts, an improved performance in polymer:fullerene bulk-heterojunction solar cells. Results obtained from GiWAXS experiments show that the improved performance of the statistical copolymer may be attributed to the following structural characteristics: 1) Well, ordered stacked domains that promote backbone planarization and thus improve the ππ-overlap. 2) Partly face-on alignment of domains relative to the electrodes for an improved active layer electrode charge transfer. Branched side chains seem to promote face-on domain orientation. Most likely they can minimize their unfavorable contact with the interface by just bringing the CH3 groups of the branches into direct contact with the surface so that favorable phenylene-substrate interaction can promote face-on orientation. 3) A more isotropic domain orientation throughout the active layer to ensure that the backbone alignment direction has components perpendicular and parallel to the electrodes in order to compromise between light absorption and efficient intra-chain charge transport.

Gaia DR1 Evidence of Disrupting the Perseus Arm

NASA Astrophysics Data System (ADS)

Baba, Junichi; Kawata, Daisuke; Matsunaga, Noriyuki; Grand, Robert J. J.; Hunt, Jason A. S.

2018-02-01

We have discovered a clear sign of the disruption phase of the Perseus arm in the Milky Way using Cepheid variables, taking advantage of the accurately measured distances of Cepheids and the proper motions from Gaia Data Release 1. Both the Galactocentric radial and rotation velocities of 77 Cepheids within 1.5 kpc of the Perseus arm are correlated with their distances from the locus of the Perseus arm, as the trailing side is rotating faster and moving inward compared to the leading side. We also found a negative vertex deviation for the Cepheids on the trailing side, ‑27.°6 ± 2.°4, in contrast to the positive vertex deviation in the solar neighborhood. This is, to our knowledge, the first direct evidence that the vertex deviation around the Perseus arm is affected by the spiral arm. We compared these observational trends with our N-body/hydrodynamics simulations based on a static density-wave spiral scenario and with those based on a transient dynamic spiral scenario. Although our comparisons are limited to qualitative trends, they strongly favor the conclusion that the Perseus arm is in the disruption phase of a transient arm.

Quasi-steady acoustic response of wall perforations subject to a grazing-bias flow combination

NASA Astrophysics Data System (ADS)

Tonon, D.; Moers, E. M. T.; Hirschberg, A.

2013-04-01

Well known examples of acoustical dampers are the aero-engine liners, the IC-engine exhaust mufflers, and the liners in combustion chambers. These devices comprise wall perforations, responsible for their sound absorbing features. Understanding the effect of the flow on the acoustic properties of a perforation is essential for the design of acoustic dampers. In the present work the effect of a grazing-bias flow combination on the impedance of slit shaped wall perforations is experimentally investigated by means of a multi-microphone impedance tube. Measurements are carried out for perforation geometries relevant for in technical applications. The focus of the experiments is on the low Strouhal number (quasi-steady) behavior. Analytical models of the steady flow and of the low frequency aeroacoustic behavior of a two-dimensional wall perforation are proposed for the case of a bias flow directed from the grazing flow towards the opposite side of the perforated wall. These theoretical results compare favorably with the experiments, when a semi-empirical correction is used to obtain the correct limit for pure bias flow.

Adverse CNS-effects of beta-adrenoceptor blockers.

PubMed

Gleiter, C H; Deckert, J

1996-11-01

In 1962 propranolol, the first beta adrenoceptor antagonist (beta blocker), was brought on to the market. There is now a host of different beta blockers available, and these compounds are among the most commonly prescribed groups of drugs. The efficacy of beta blockers has been proven predominantly for the treatment of cardiovascular diseases. Beta blockers are also used for certain types of CNS disorders, such as anxiety disorders, essential tremor and migraine. While low toxicity means that they have a favorable risk-benefit ratio, given the high intensity of use, it is essential to have a comprehensive knowledge of adverse events. Adverse events of beta blockers that can be related to the CNS are quite often neglected, even in textbooks of clinical pharmacology or review articles, and thus often misdiagnosed. The following article, therefore, after summarizing the use of beta blockers for CNS indications, critically reviews the literature on centrally mediated adverse events. General pharmacological features of beta blockers and their molecular basis of action will briefly be addressed to the extent that they are or may become relevant for central nervous pharmacotherapy and side-effects.

Pharmacology of Ramelteon, a Selective MT1/MT2 Receptor Agonist: A Novel Therapeutic Drug for Sleep Disorders

PubMed Central

Miyamoto, Masaomi

2009-01-01

An estimated one-third of the general population is affected by insomnia, and this number is increasing due to more stressful working conditions and the progressive aging of society. However, current treatment of insomnia with hypnotics, gamma-aminobutyric acid A (GABAA) receptor modulators, induces various side effects, including cognitive impairment, motor disturbance, dependence, tolerance, hangover, and rebound insomnia. Ramelteon (Rozerem; Takeda Pharmaceutical Company Limited, Osaka, Japan) is an orally active, highly selective melatonin MT1/MT2 receptor agonist. Unlike the sedative hypnotics that target GABAA receptor complexes, ramelteon is a chronohypnotic that acts on the melatonin MT1 and MT2 receptors, which are primarily located in the suprachiasmatic nucleus, the body's “master clock.” As such, ramelteon possesses the first new therapeutic mechanism of action for a prescription insomnia medication in over three decades. Ramelteon has demonstrated sleep-promoting effects in clinical trials, and coupled with its favorable safety profile and lack of abuse potential or dependence, this chronohypnotic provides an important treatment option for insomnia. PMID:19228178

Combination therapy of apatinib with icotinib for primary acquired icotinib resistance in patients with advanced pulmonary adenocarcinoma with EGFR mutation.

PubMed

Xia, Pinghui; Cao, Jinlin; Lv, Xiayi; Wang, Luming; Lv, Wang; Hu, Jian

2018-05-01

Multi-targeted agents represent the next generation of targeted therapies for solid tumors, and patients with acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) may also benefit from their combination with TKI therapy. Third-generation targeted drugs, such as osimertinib, are very expensive, thus a more economical solution is required. The aim of this study was to explore the use of apatinib combined with icotinib therapy for primary acquired resistance to icotinib in three patients with advanced pulmonary adenocarcinoma with EGFR mutations. We achieved favorable oncologic outcomes in all three patients, with progression-free survival of four to six months. Unfortunately, the patients ultimately had to cease combination therapy because of intolerable adverse effects of hand and foot syndrome and oral ulcers. Combination therapy of apatinib with icotinib for primary acquired resistance to icotinib may be an option for patients with advanced pulmonary adenocarcinoma with EGFR mutations, but physicians must also be aware of the side effects caused by such therapy. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Side Effects of HIV Medicines: HIV and Lactic Acidosis

MedlinePlus

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

Reconnaissance investigation of high-calcium marble in the Beaver Creek area, St. Lawrence County, New York

USGS Publications Warehouse

Brown, C. Ervin

1978-01-01

Three belts of marble of the Grenville Series were mapped in the Beaver Creek drainage basin, St. Lawrence County, N.Y. One of these, on the west side of Beaver Creek, consists of coarsely crystalline pure calcitic marble that occurs in a zone at least 10 by 0.8 km in extent. Samples of marble show CaCO3 content to be greater than 93 percent, and some samples contain greater than 96 percent, and only small amounts of MgO and Fe203 are present. Marble in two other belts to the east of Beaver Creek are variable in composition, but locally have high content of calcium carbonate material. The marble deposit west of Beaver Creek has a chemical composition favorable for specialized chemical, industrial, and metallurgical uses. Another favorable aspect of the deposit is its proximity to inexpensive water transportation on the St. Lawrence Seaway only 27.5 km away by road, at Ogdensburg, N.Y.

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

PubMed

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

1996-11-01

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

Side Effects of Leukotriene Receptor Antagonists in Asthmatic Children.

PubMed

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

2015-10-01

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

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.

Targeting the aryl hydrocarbon receptor nuclear translocator complex with DMOG and Stemregenin 1 improves primitive hematopoietic stem cell expansion.

PubMed

Jackson, Carlo Stephan; Durandt, Chrisna; Janse van Rensburg, Ilse; Praloran, Vincent; Brunet de la Grange, Philippe; Pepper, Michael Sean

2017-05-01

Culture conditions used for the expansion of hematopoietic stem and progenitor cells (HSCs and HPCs, collectively HSPCs) should ideally favor the self renewal of long-term HSCs. At 20% O 2 , the synthesis of HIF-1α is balanced by its hydroxylation and proteasomal degradation. This favors HSPC differentiation, but can be prevented by culturing CD34+ cord blood cells in the presence of dimethyloxaloylglycine (DMOG). This differentiation may also be reduced by culturing the cells in the presence of Stemregenin 1, an antagonist of the aryl hydrocarbon receptor (AhR). The objective of this study was to investigate how hypoxia, DMOG and Stemregenin 1 might affect the expansion of HSPCs with the aim of identifying optimal conditions for expansion in culture. It was found that DMOG decreased proliferation but was effective in preserving the number of cells in the primitive hematopoietic sub-populations in vitro. The effect of DMOG was similar to hypoxia, although differences were observed with regard to the side population and CD34+ sub-populations. Stemregenin 1 on the other hand increased the size of the primitive as well as the other HSC sub-populations. The use of Stemregenin 1 with DMOG increased the proportion of primitive HSCs to 3.54% compared to 2.61% for Stemregenin 1 alone. In vivo engraftment studies confirmed these findings and showed that fewer cells (3710) are required for long-term engraftment when HSCs are grown in Stemregenin 1 together with hypoxia than in Stemregenin 1 under conditions of normoxia (13430). Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

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.

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

PubMed

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

2017-12-01

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

Effect of Shockwave Curvature on Run Distance Observed with a Modified Wedge Test

NASA Astrophysics Data System (ADS)

Lee, Richard; Dorgan, Robert; Sutherland, Gerrit; Benedetta, Ashley; Milby, Christopher

2011-06-01

The effect of wave curvature on shock initiation in PBXN-110 was investigated using a modified wedge test configuration. Various thicknesses of PBXN-110 donor slabs were used to define the shockwave curvature introduced to wedge samples of the same explosive. The donor slabs were initiated with line-wave generators so that the introduced shock would be the same shape, magnitude and duration across the entire input surface of the wedge. The shock parameters were varied for a given donor thickness via different widths of PMMA spacers placed between the donor and the wedge. A framing camera was used to observe where initiation occurred along the face of the wedge. Initiation always occurred at the center of the shock front instead of the sides like that reported by others using a much smaller test format. Results were compared to CTH calculations to indicate if there were effects associated with highly curved shock fronts that could not be adequately predicted. The run distance predicted in CTH for a 50.8 mm thick donor slab (low curvature) compared favorably with experimental results. However, results from thinner donor slabs (higher curvature) indicate a more sensitive behavior than the simulations predicted.

Effect of shockwave curvature on run distance observed with a modified wedge test

NASA Astrophysics Data System (ADS)

Lee, Richard; Dorgan, Robert J.; Sutherland, Gerrit; Benedetta, Ashley; Milby, Christopher

2012-03-01

The effect of wave curvature on shock initiation in PBXN-110 was investigated using a modified wedge test configuration. Various widths of PBXN-110 donor slabs were used to define the shockwave curvature introduced to wedge samples of the same explosive. The donor slabs were initiated with line-wave generators so that the shock from the donor would be the same shape, magnitude and duration across the entire input surface of the wedge. The shock parameters were varied for a given donor with PMMA spacers placed between the donor and the wedge sample. A high-speed electronic framing camera was used to observe where initiation occurred along the face of the wedge. Initiation always occurred at the center of the shock front instead of along the sides like that reported by others using a much smaller test format. Results were compared to CTH calculations to indicate if there were effects associated with highly curved shock fronts that could not be adequately predicted. The run distance predicted in CTH for a 50.8 mm wide donor slab (low curvature) compared favorably with experimental results. However, results from thinner donor slabs (higher curvature) indicate a more sensitive behavior than the simulations predicted.

Advances in treating psoriasis in the elderly with small molecule inhibitors.

PubMed

Cline, Abigail; Cardwell, Leah A; Feldman, Steven R

2017-12-01

Due to the chronic nature of psoriasis, the population of elderly psoriasis patients is increasing. However, many elderly psoriatic patients are not adequately treated because management is challenging as a result of comorbidities, polypharmacy, and progressive impairment of organ systems. Physicians may hesitate to use systemic or biologic agents in elderly psoriasis patients because of an increased risk of adverse events in this patient population. Small molecule medications are emerging as promising options for elderly patients with psoriasis and other inflammatory conditions. Areas covered: Here we review the efficacy, safety and tolerability of small molecule inhibitors apremilast, tofacitinib, ruxolitinib, baricitinib, and peficitinib in the treatment of psoriasis, with focus on their use in the elderly population. Expert opinion: Although small molecule inhibitors demonstrate efficacy in elderly patients with psoriasis, they will require larger head-to-head studies and post-marketing registries to evaluate their effectiveness and safety in specific patient populations. Apremilast, ruxolitinib, and peficitinib are effective agents with favorable side effect profiles; however, physicians should exercise caution when prescribing tofacitinib or baricitinib in elderly populations due to adverse events. The high cost of these drugs in the U.S. is likely to limit their use.

Hub nodes inhibit the outbreak of epidemic under voluntary vaccination

NASA Astrophysics Data System (ADS)

Zhang, Haifeng; Zhang, Jie; Zhou, Changsong; Small, Michael; Wang, Binghong

2010-02-01

It is commonly believed that epidemic spreading on scale-free networks is difficult to control and that the disease can spread even with a low infection rate, lacking an epidemic threshold. In this paper, we study epidemic spreading on complex networks under the framework of game theory, in which a voluntary vaccination strategy is incorporated. In particular, individuals face the 'dilemma' of vaccination: they have to decide whether or not to vaccinate according to the trade-off between the risk and the side effects or cost of vaccination. Remarkably and quite excitingly, we find that disease outbreak can be more effectively inhibited on scale-free networks than on random networks. This is because the hub nodes of scale-free networks are more inclined to take self-vaccination after balancing the pros and cons. This result is encouraging as it indicates that real-world networks, which are often claimed to be scale free, can be favorably and easily controlled under voluntary vaccination. Our work provides a way of understanding how to prevent the outbreak of diseases under voluntary vaccination, and is expected to provide valuable information on effective disease control and appropriate decision-making.

Tanezumab in the treatment of chronic musculoskeletal conditions.

PubMed

Jayabalan, Prakash; Schnitzer, Thomas J

2017-02-01

The management of pain associated with chronic musculoskeletal conditions represents a significant challenge for the clinician. There remains a need for novel medications that have a significant analgesic benefit and are also safe and well tolerated. Both pre-clinical and clinical data have provided evidence of the role of nerve growth factor (NGF) in a multitude of pain eliciting conditions. Therefore, the development of monoclonal antibodies to NGF for chronic painful musculoskeletal conditions has generated interest. Areas covered: This manuscript is a review that examines both the pharmacological properties and clinical studies of tanezumab, the most widely studied antibody to NGF, for management of osteoarthritis (OA) and low back pain. In addition, the safety and tolerability profile and development history of tanezumab are also discussed. Expert opinion: Most studies provide strong support for the ability of tanezumab to provide clinically meaningful pain relief in individuals with these conditions, with longer-term studies suggesting durability of effect. The adverse event profile appears favorable, assuming the risk mitigation strategies are effective at reducing the incidence of joint-related side effects. Further data are being collected to define the optimal dose and dosing strategy in both OA and chronic low back pain.

Prostate-Specific Membrane Antigen-Targeted Site-Directed Antibody-Conjugated Apoferritin Nanovehicle Favorably Influences In Vivo Side Effects of Doxorubicin.

PubMed

Dostalova, Simona; Polanska, Hana; Svobodova, Marketa; Balvan, Jan; Krystofova, Olga; Haddad, Yazan; Krizkova, Sona; Masarik, Michal; Eckschlager, Tomas; Stiborova, Marie; Heger, Zbynek; Adam, Vojtech

2018-06-11

Herein, we describe the in vivo effects of doxorubicin (DOX) encapsulated in ubiquitous protein apoferritin (APO) and its efficiency and safety in anti-tumor treatment. APODOX is both passively (through Enhanced Permeability and Retention effect) and actively targeted to tumors through prostate-specific membrane antigen (PSMA) via mouse antibodies conjugated to the surface of horse spleen APO. To achieve site-directed conjugation of the antibodies, a HWRGWVC heptapeptide linker was used. The prostate cancer-targeted and non-targeted nanocarriers were tested using subcutaneously implanted LNCaP cells in athymic mice models, and compared to free DOX. Prostate cancer-targeted APODOX retained the high potency of DOX in attenuation of tumors (with 55% decrease in tumor volume after 3 weeks of treatment). DOX and non-targeted APODOX treatment caused damage to liver, kidney and heart tissues. In contrast, no elevation in liver or kidney enzymes and negligible changes were revealed by histological assessment in prostate cancer-targeted APODOX-treated mice. Overall, we show that the APO nanocarrier provides an easy encapsulation protocol, reliable targeting, high therapeutic efficiency and very low off-target toxicity, and is thus a promising delivery system for translation into clinical use.

Adoptive natural killer cell therapy is effective in reducing pulmonary metastasis of Ewing sarcoma

PubMed Central

Tong, Alexander A.; Hashem, Hasan; Eid, Saada; Allen, Frederick; Kingsley, Daniel

2017-01-01

ABSTRACT The survival of patients with metastatic or relapsed Ewing sarcoma (ES) remains dismal despite intensification of combination chemotherapy and radiotherapy, precipitating the need for novel alternative therapies with minimal side effects. Natural killer (NK) cells are promising additions to the field of cellular immunotherapy. Adoptive NK cell therapy has shown encouraging results in hematological malignancies. Despite these initial promising successes, however, NK cell therapy for solid tumors remains to be investigated using in vivo tumor models. The purpose of this study is to evaluate the efficacy of ex vivo expanded human NK cells in controlling primary and metastatic ES tumor growth in vitro and in vivo. Using membrane-bound IL-21 containing K562 (K562-mbIL-21) expansion platform, we were able to obtain sufficient numbers of expanded NK (eNK) cells that display favorable activation phenotypes and inflammatory cytokine secretion, along with a strong in vitro cytotoxic effect against ES. Furthermore, eNK therapy significantly decreased lung metastasis without any significant therapeutic effect in limiting primary tumor growth in an in vivo xenograft model. Our data demonstrate that eNK may be effective against pulmonary metastatic ES, but challenges remain to direct proper trafficking and augmenting the cytotoxic function of eNK to target primary tumor sites. PMID:28507811

The development of new radiation protocols for insect sterilization using long wavelength x-rays

NASA Astrophysics Data System (ADS)

Urquidi, Jacob; Brar, Ramaninder K.; Rodriguez, Stacy; Hansen, Immo

2015-07-01

Control of insect species for the protection of crops, livestock, and prevention of disease such as dengue fever and malaria is a high priority in today's global economy. Traditional methods such as pesticides have fallen out of favor because its effects are indiscriminate as well as adverse and unpredictable impacts on the environment. Modern novel techniques such as genetic modification have had trouble gaining traction due to ethics concerns and the potential for unforeseen side effects. One approach that has gained traction and has proven its efficacy is the use of ionizing radiation to affect sterility in insect species in order to scale back their population. Known as Sterile Insect Technique (SIT), it has proven very effective in eradicating certain dipteran insect populations. However, when standard sterilization methods developed for dipertans are applied to mosquito populations significant complications arise, such as an inability to compete with non-irradiated males and high mortality rates. We have investigated the effect of treatment with x-rays of different wavelengths on x-ray sterilized mosquito males. Our results have demonstrated that longer wavelength x-rays have a significant effect on the outcome of the sterile males' longevity as well as an increase on the efficacy of sterilization while employing a substantially lower dose.

The development of new radiation protocols for insect sterilization using long wavelength x-rays

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

Urquidi, Jacob, E-mail: jurquidi@nmsu.edu; Brar, Ramaninder K.; Rodriguez, Stacy

Control of insect species for the protection of crops, livestock, and prevention of disease such as dengue fever and malaria is a high priority in today’s global economy. Traditional methods such as pesticides have fallen out of favor because its effects are indiscriminate as well as adverse and unpredictable impacts on the environment. Modern novel techniques such as genetic modification have had trouble gaining traction due to ethics concerns and the potential for unforeseen side effects. One approach that has gained traction and has proven its efficacy is the use of ionizing radiation to affect sterility in insect species inmore » order to scale back their population. Known as Sterile Insect Technique (SIT), it has proven very effective in eradicating certain dipteran insect populations. However, when standard sterilization methods developed for dipertans are applied to mosquito populations significant complications arise, such as an inability to compete with non-irradiated males and high mortality rates. We have investigated the effect of treatment with x-rays of different wavelengths on x-ray sterilized mosquito males. Our results have demonstrated that longer wavelength x-rays have a significant effect on the outcome of the sterile males’ longevity as well as an increase on the efficacy of sterilization while employing a substantially lower dose.« less

Transport characteristics of expiratory droplets and droplet nuclei in indoor environments with different ventilation airflow patterns.

PubMed

Wan, M P; Chao, C Y H

2007-06-01

Expiratory droplets and droplet nuclei can be pathogen carriers for airborne diseases. Their transport characteristics were studied in detail in two idealized floor-supply-type ventilation flow patterns: Unidirectional-upward and single-side-floor, using a multiphase numerical model. The model was validated by running interferometric Mie imaging experiments using test droplets with nonvolatile content, which formed droplet nuclei, ultimately, in a class-100 clean-room chamber. By comparing the droplet dispersion and removal characteristics with data of two other ceiling-supply ventilation systems collected from a previous work, deviations from the perfectly mixed ventilation condition were found to exist in various cases to different extent. The unidirectional-upward system was found to be more efficient in removing the smallest droplet nuclei (formed from 1.5 mum droplets) by air extraction, but it became less effective for larger droplets and droplet nuclei. Instead, the single-side-floor system was shown to be more favorable in removing these large droplets and droplet nuclei. In the single-side-floor system, the lateral overall dispersion coefficients for the small droplets and nuclei (initial size

Systematic Review: Rectal Therapies for the Treatment of Distal Forms of Ulcerative Colitis.

PubMed

Cohen, Russell D; Dalal, Sushila R

2015-07-01

Many therapeutic options are available for patients with distal forms of ulcerative colitis (UC). Rectal therapies (e.g., suppositories, foams, gels, and enemas) may be recommended either alone or in combination with oral treatment. Compared with oral therapies, rectal therapies are underused in patients with distal forms of UC, although rectal therapies have favorable efficacy and safety profiles. This systematic review identified 48 articles for inclusion after a comprehensive PubMed search and the identification of additional relevant articles through other sources. Inclusion criteria were clinical studies examining efficacy and safety of 5-aminosalicylic acid, corticosteroid, and non-5-aminosalicylic acid rectal therapies (suppositories, foams, gels, and enemas) that induce or maintain remission in patients with ulcerative proctitis, ulcerative proctosigmoiditis, or left-sided colitis (i.e., distal forms of UC). The quality of the evidence presented was evaluated using the GRADE system. Overall, a greater percentage of patients with distal forms of UC receiving 5-aminosalicylic acids or corticosteroid rectal formulations derived greater therapeutic benefit after treatment compared with patients receiving placebo. Furthermore, most uncontrolled studies of rectal therapies reported that patients with distal forms of UC had marked improvement from baseline after treatment. The overall safety profile of rectal therapies was favorable. Treatment with second-generation corticosteroids, such as budesonide and beclomethasone dipropionate, did not increase the incidence of steroid-related adverse effects. The current literature supports the use of rectal therapies for both induction and maintenance of remission in patients with distal forms of UC.

Persistent predator-prey dynamics revealed by mass extinction.

PubMed

Sallan, Lauren Cole; Kammer, Thomas W; Ausich, William I; Cook, Lewis A

2011-05-17

Predator-prey interactions are thought by many researchers to define both modern ecosystems and past macroevolutionary events. In modern ecosystems, experimental removal or addition of taxa is often used to determine trophic relationships and predator identity. Both characteristics are notoriously difficult to infer in the fossil record, where evidence of predation is usually limited to damage from failed attacks, individual stomach contents, one-sided escalation, or modern analogs. As a result, the role of predation in macroevolution is often dismissed in favor of competition and abiotic factors. Here we show that the end-Devonian Hangenberg event (359 Mya) was a natural experiment in which vertebrate predators were both removed and added to an otherwise stable prey fauna, revealing specific and persistent trophic interactions. Despite apparently favorable environmental conditions, crinoids diversified only after removal of their vertebrate consumers, exhibiting predatory release on a geological time scale. In contrast, later Mississippian (359-318 Mya) camerate crinoids declined precipitously in the face of increasing predation pressure from new durophagous fishes. Camerate failure is linked to the retention of obsolete defenses or "legacy adaptations" that prevented coevolutionary escalation. Our results suggest that major crinoid evolutionary phenomena, including rapid diversification, faunal turnover, and species selection, might be linked to vertebrate predation. Thus, interactions observed in small ecosystems, such as Lotka-Volterra cycles and trophic cascades, could operate at geologic time scales and higher taxonomic ranks. Both trophic knock-on effects and retention of obsolete traits might be common in the aftermath of predator extinction.

Links between the Prophet Muhammad (PBUH) recommended foods and disease management: A review in the light of modern superfoods.

PubMed

Ali, Sharique A; Parveen, Naima; Ali, Ayesha S

2018-01-01

Nutrition and other bioactive natural products present in specific foods within a balanced diet play an indispensable role in maintaining and promoting human health. Plants are rich sources of a balanced nutrition because of high content of bioactive products; hence, most of them recently have acquired the status of superfoods. It has been used since ancient times for the treatment of various ailments, and these traditional medicines still remain as one of the most affordable and easily accessible sources of treatment in the primary health-care system. The scientifically based use of these superfoods date back to the era of Prophet Muhammad along with other historical uses of plant products. Prescription of a large number of herbal foods such as dates, pomegranate, olives, figs, grapes, and black seeds was successfully proposed by him. These recently have become superfoods with their powerful healing properties and act as favorable dietary interventions for disease prevention as well as for the good maintenance of health. The use of these foods as ingredients of natural origin with fewer side effects seems to be more favorable than the chemical treatment, which is often complicated. The present review is an attempt to provide a brief survey of the literature on scientifically based significance of these superfoods carried out by various researchers and exploration of a wide spectrum of their pharmacological actions which include antidiabetic, anticancer, immune modulator, analgesic, anti-inflammatory, and hepatoprotective properties.

Focal application of low-dose-rate brachytherapy for prostate cancer: a pilot study

PubMed Central

Spadinger, Ingrid T.; Salcudean, Septimiu E.; Kozlowski, Piotr; Chang, Silvia D.; Ng, Tony; Lobo, Julio; Nir, Guy; Moradi, Hamid; Peacock, Michael; Morris, W. James

2017-01-01

Purpose To evaluate the feasibility and to report the early outcomes of focal treatment of prostate cancer using low-dose-rate brachytherapy (LDR-PB). Material and methods Seventeen patients were screened with multi-parametric magnetic resonance imaging (mpMRI), 14 of whom proceeded to receive trans-perineal template mapping biopsy (TTMB). Focal LDR-PB was performed on five eligible patients using dual air kerma strength treatment plans based on planning target volumes derived from cancer locations and determined by TTMB. Patient follow-up includes prostate specific antigen (PSA) measurements, urinary and sexual function questionnaires, repeated imaging and TTMB at specific intervals post-treatment. Results Feasibility of focal LDR-PB was shown and short-term outcomes are promising. While the detection rate of tumors, a majority of which were low grade GS 3 + 3, was found to be low on mpMRI (sensitivity of 37.5%), our results suggest the potential of mpMRI in detecting the presence of higher grade (GS ≥ 3 + 4), and bilateral disease indicating its usefulness as a screening tool for focal LDR-PB. Conclusions Low-dose-rate brachytherapy is a favorable ablation option for focal treatment of prostate cancer, requiring minimal modification to the standard (whole gland) LDR-PB treatment, and appears to have a more favorable side effect profile. Further investigation, in the form of a larger study, is needed to assess the methods used and the long-term outcomes of focal LDR-PB. PMID:28725242

Links between the Prophet Muhammad (PBUH) recommended foods and disease management: A review in the light of modern superfoods

PubMed Central

Ali, Sharique A.; Parveen, Naima; Ali, Ayesha S.

2018-01-01

Nutrition and other bioactive natural products present in specific foods within a balanced diet play an indispensable role in maintaining and promoting human health. Plants are rich sources of a balanced nutrition because of high content of bioactive products; hence, most of them recently have acquired the status of superfoods. It has been used since ancient times for the treatment of various ailments, and these traditional medicines still remain as one of the most affordable and easily accessible sources of treatment in the primary health-care system. The scientifically based use of these superfoods date back to the era of Prophet Muhammad along with other historical uses of plant products. Prescription of a large number of herbal foods such as dates, pomegranate, olives, figs, grapes, and black seeds was successfully proposed by him. These recently have become superfoods with their powerful healing properties and act as favorable dietary interventions for disease prevention as well as for the good maintenance of health. The use of these foods as ingredients of natural origin with fewer side effects seems to be more favorable than the chemical treatment, which is often complicated. The present review is an attempt to provide a brief survey of the literature on scientifically based significance of these superfoods carried out by various researchers and exploration of a wide spectrum of their pharmacological actions which include antidiabetic, anticancer, immune modulator, analgesic, anti-inflammatory, and hepatoprotective properties. PMID:29599697

MCCE analysis of the pKas of introduced buried acids and bases in staphylococcal nuclease.

PubMed

Gunner, M R; Zhu, Xuyu; Klein, Max C

2011-12-01

The pK(a)s of 96 acids and bases introduced into buried sites in the staphylococcal nuclease protein (SNase) were calculated using the multiconformation continuum electrostatics (MCCE) program and the results compared with experimental values. The pK(a)s are obtained by Monte Carlo sampling of coupled side chain protonation and position as a function of pH. The dependence of the results on the protein dielectric constant (ε(prot)) in the continuum electrostatics analysis and on the Lennard-Jones non-electrostatics parameters was evaluated. The pK(a)s of the introduced residues have a clear dependence on ε(prot,) whereas native ionizable residues do not. The native residues have electrostatic interactions with other residues in the protein favoring ionization, which are larger than the desolvation penalty favoring the neutral state. Increasing ε(prot) scales both terms, which for these residues leads to small changes in pK(a). The introduced residues have a larger desolvation penalty and negligible interactions with residues in the protein. For these residues, changing ε(prot) has a large influence on the calculated pK(a). An ε(prot) of 8-10 and a Lennard-Jones scaling of 0.25 is best here. The X-ray crystal structures of the mutated proteins are found to provide somewhat better results than calculations carried out on mutations made in silico. Initial relaxation of the in silico mutations by Gromacs and extensive side chain rotamer sampling within MCCE can significantly improve the match with experiment. Copyright © 2011 Wiley-Liss, Inc.

New Insights into Vitamin D Sterol-VDR Proteolysis, Allostery, Structure-Function from the Perspective of a Conformational Ensemble Model

PubMed Central

Mizwicki, Mathew T.; Bula, Craig M.; Bishop, June E.; Norman, Anthony W.

2007-01-01

Recently, we have developed a vitamin D sterol (VDS)-VDR conformational ensemble model. This model can be broken down into three individual, yet interlinked parts: a) the conformationally flexible VDS, b) the apo/holo-VDR helix-12 (H12) conformational ensemble, and c) the presence of two VDR ligand binding pockets (LBPs); one thermodynamically favored (the genomic pocket, G-pocket) and the other kinetically favored by VDSs (the alternative pocket, A-pocket). One focus of this study is to use directed VDR mutagenesis to 1) demonstrate H12 is stabilized in the transcriptionally active closed conformation (hVDR-c1) by three salt-bridges that span the length of H12 (cationic residues R154, K264 and R402), 2) to elucidate the VDR trypsin sites [R173 (hVDR-c1), K413 (hVDR-c2) and R402 (hVDR-c3)] and 3) demonstrate the apo-VDR H12 equilibrium can be shifted. The other focus of this study is to apply the model to generate a mechanistic understanding to discrepancies observed in structure-function data obtained with a variety of 1α,25(OH)2-vitamin D3 (1,25D) A-ring and side-chain analogs, and side-chain metabolites. We will demonstrate that these structure-function conundrums can be rationalized, for the most part by focusing on alterations in the VDS conformational flexibility and the elementary interaction between the VDS and the VDR A- and G-pockets, relative to the control, 1,25D. PMID:17368177

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

PubMed

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

2017-04-01

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

Medications and Side Effects

MedlinePlus

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

Cancer Treatment for Women: Possible Sexual Side Effects

MedlinePlus

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

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

PubMed

Gagnon, Marilou

2018-03-12

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

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

PubMed

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

2017-09-01

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

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

PubMed

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

2018-03-02

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

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

PubMed

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

2018-02-01

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

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

PubMed

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

2017-02-01

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

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

PubMed

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

2012-01-01

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

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

PubMed

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

2018-05-21

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

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

PubMed

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

2017-08-01

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

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

PubMed

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

2011-05-01

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

Liquid Drop Actuation by Photoelectrowetting

NASA Astrophysics Data System (ADS)

Palma, Cesar

In electrowetting an electric potential is applied between a droplet of electrolyte and a conductor separated by an insulator. The repulsion of like charges deforms and spreads the droplet until capillary and electric forces are in equilibrium. Photoelectrowetting is a light-triggered version of electrowetting where the conductor is replaced by a moderately-doped semiconductor. The electrolyte-insulator-semiconductor stack resembles a metal-insulator-semiconductor capacitor, which has the special property that the amount of charge that can be injected into it increases when exposed to light. Thus in photoelectrowetting the exposure of light spreads the droplet further than in unilluminated conditions. In this thesis a scheme is presented for moving drops on a surface using photoelectrowetting. In order to understand photoelectrowetting I conducted a study of electrowetting with semiconductors. Devices were constructed using moderately-doped p-type silicon wafers (Na = 8.6 x 1014 cm-3) coated with a bilayer composed of thermal oxide (100 nm) and teflon (265 nm). Electric biases (< 40 V) were applied between droplets of electrolyte (10 microliter, 10 mM NaCl) and the silicon wafer, resulting in deformations of the droplet. These changes were quantified with contact angle measurements which varied from 120° at zero bias to 90° at 40V depending on the conditions of the experiment. Three regimes were observed depending on the polarity of the bias and above-bandgap illumination impinging on the droplet, corresponding to the charge regimes of an MIS capacitor: accumulation, inversion and deep-depletion. I present a model for these wetting changes based on a balance of capillary and electrostatic forces. After accounting for various non-ideal effects, I find that the model agrees with the data. I demonstrate that it is essential to account for interface traps in our devices (1.8 x 1011 cm-2) in the deep-depletion regime, leading to a 33% (4?) correction to the prediction at 40V. I elucidate the nature of the photoelectrowetting effect and find that contrary to reports in the literature the transition is not reversible by light alone. In the next phase of my thesis, I demonstrate how photoelectrowetting triggered with a light beam on one side moves the droplet along a surface. Comparable with traditional electrowetting-based devices, I achieve speeds of up to 12 mm/s with 10 microliter drops of electrolyte (1% w/w NaCl) with a surfactant (5 mM NaCl) using an oscillating electric potential composed of an AC bias of magnitude 32.5 Vpp and a DC offset of -7 V cycled at a frequency of 15 kHz and a laser intensity of 40 mW/cm2 (lambda = 660nm). I measure the speed for varying magnitude and frequency of the bias, laser intensity, droplet size and viscosity. The optimal cycling frequency is set by competing effects: on the low frequency side (< 15 kHz) the speed is limited by migration of carriers from the illuminated to the non-illuminated regions under the drop, and on the high frequency side (> 15 kHz) the speed is limited by the laser intensity. I present a model for the speed incorporating these effects that compares favorably with experiment. I present results of simulations of minority charge carrier concentrations in depletion regions. These exhibit self-similarity in space and time. The front of the concentrations follows a power law in time with an exponent that depends on the dopant concentration. Predictions from the power laws compare favorably with experiment.

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

PubMed

Petrova, N N; Kucher, E O

2012-01-01

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

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

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

PubMed

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

2014-10-01

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

Repacking the Core of T4 lysozyme by automated design.

PubMed

Mooers, Blaine H M; Datta, Deepshikha; Baase, Walter A; Zollars, Eric S; Mayo, Stephen L; Matthews, Brian W

2003-09-19

Automated protein redesign, as implemented in the program ORBIT, was used to redesign the core of phage T4 lysozyme. A total of 26 buried or partially buried sites in the C-terminal domain were allowed to vary both their sequence and side-chain conformation while the backbone and non-selected side-chains remained fixed. A variant with seven substitutions ("Core-7") was identified as having the most favorable energy. The redesign experiment was repeated with a penalty for the presence of methionine residues. In this case the redesigned protein ("Core-10") had ten amino acid changes. The two designed proteins, as well as the constituent single mutants, and several single-site revertants were over-expressed in Escherichia coli, purified, and subjected to crystallographic and thermal analyses. The thermodynamic and structural data show that some repacking was achieved although neither redesigned protein was more stable than the wild-type protein. The use of the methionine penalty was shown to be effective. Several of the side-chain rotamers in the predicted structure of Core-10 differ from those observed. Rather than changing to new rotamers predicted by the design process, side-chains tend to maintain conformations similar to those seen in the native molecule. In contrast, parts of the backbone change by up to 2.8A relative to both the designed structure and wild-type. Water molecules that are present within the lysozyme molecule were removed during the design process. In the redesigned protein the resultant cavities were, to some degree, re-occupied by side-chain atoms. In the observed structure, however, water molecules were still bound at or near their original sites. This suggests that it may be preferable to leave such water molecules in place during the design procedure. The results emphasize the specificity of the packing that occurs within the core of a typical protein. While point substitutions within the core are tolerated they almost always result in a loss of stability. Likewise, combinations of substitutions may also be tolerated but usually destabilize the protein. Experience with T4 lysozyme suggests that a general core repacking methodology with retention or enhancement of stability may be difficult to achieve without provision for shifts in the backbone.

Molecular basis for defect in Alix-binding by alternatively spliced isoform of ALG-2 (ALG-2DeltaGF122) and structural roles of F122 in target recognition.

PubMed

Inuzuka, Tatsutoshi; Suzuki, Hironori; Kawasaki, Masato; Shibata, Hideki; Wakatsuki, Soichi; Maki, Masatoshi

2010-08-06

ALG-2 (a gene product of PDCD6) belongs to the penta-EF-hand (PEF) protein family and Ca2+-dependently interacts with various intracellular proteins including mammalian Alix, an adaptor protein in the ESCRT system. Our previous X-ray crystal structural analyses revealed that binding of Ca2+ to EF3 enables the side chain of R125 to move enough to make a primary hydrophobic pocket (Pocket 1) accessible to a short fragment of Alix. The side chain of F122, facing a secondary hydrophobic pocket (Pocket 2), interacts with the Alix peptide. An alternatively spliced shorter isoform, designated ALG-2DeltaGF122, lacks Gly121Phe122 and does not bind Alix, but the structural basis of the incompetence has remained to be elucidated. We solved the X-ray crystal structure of the PEF domain of ALG-2DeltaGF122 in the Ca2+-bound form and compared it with that of ALG-2. Deletion of the two residues shortened alpha-helix 5 (alpha5) and changed the configuration of the R125 side chain so that it partially blocked Pocket 1. A wall created by the main chain of 121-GFG-123 and facing the two pockets was destroyed. Surprisingly, however, substitution of F122 with Ala or Gly, but not with Trp, increased the Alix-binding capacity in binding assays. The F122 substitutions exhibited different effects on binding of ALG-2 to other known interacting proteins, including TSG101 (Tumor susceptibility gene 101) and annexin A11. The X-ray crystal structure of the F122A mutant revealed that removal of the bulky F122 side chain not only created an additional open space in Pocket 2 but also abolished inter-helix interactions with W95 and V98 (present in alpha4) and that alpha5 inclined away from alpha4 to expand Pocket 2, suggesting acquirement of more appropriate positioning of the interacting residues to accept Alix. We found that the inability of the two-residue shorter ALG-2 isoform to bind Alix is not due to the absence of bulky side chain of F122 but due to deformation of a main-chain wall facing pockets 1 and 2. Moreover, a residue at the position of F122 contributes to target specificity and a smaller side chain is preferable for Alix binding but not favored to bind annexin A11.

The association of funding source on effect size in randomized controlled trials: 2013-2015 - a cross-sectional survey and meta-analysis.

PubMed

Falk Delgado, Alberto; Falk Delgado, Anna

2017-03-14

Trials financed by for-profit organizations have been associated with favorable outcomes of new treatments, although the effect size of funding source impact on outcome is unknown. The aim of this study was to estimate the effect size for a favorable outcome in randomized controlled trials (RCTs), stratified by funding source, that have been published in general medical journals. Parallel-group RCTs published in The Lancet, New England Journal of Medicine, and JAMA between 2013 and 2015 were identified. RCTs with binary primary endpoints were included. The primary outcome was the OR of patients' having a favorable outcome in the intervention group compared with the control group. The OR of a favorable outcome in each trial was calculated by the number of positive events that occurred in the intervention and control groups. A meta-analytic technique with random effects model was used to calculate summary OR. Data were stratified by funding source as for-profit, mixed, and nonprofit. Prespecified sensitivity, subgroup, and metaregression analyses were performed. Five hundred nine trials were included. The OR for a favorable outcome in for-profit-funded RCTs was 1.92 (95% CI 1.72-2.14), which was higher than mixed source-funded RCTs (OR 1.34, 95% CI 1.25-1.43) and nonprofit-funded RCTs (OR 1.32, 95% CI 1.26-1.39). The OR for a favorable outcome was higher for both clinical and surrogate endpoints in for-profit-funded trials than in RCTs with other funding sources. Excluding drug trials lowered the OR for a favorable outcome in for-profit-funded RCTs. The OR for a favorable surrogate outcome in drug trials was higher in for-profit-funded trials than in nonprofit-funded trials. For-profit-funded RCTs have a higher OR for a favorable outcome than nonprofit- and mixed source-funded RCTs. This difference is associated mainly with the use of surrogate endpoints in for-profit-financed drug trials.

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

PubMed

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

2018-06-02

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

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

PubMed Central

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

2015-01-01

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

Huang-Lian-Jie-Du-Decotion induced protective autophagy against the injury of cerebral ischemia/reperfusion via MAPK-mTOR signaling pathway.

PubMed

Wang, Peng-Ran; Wang, Jun-Song; Zhang, Chao; Song, Xing-Fang; Tian, Na; Kong, Ling-Yi

2013-08-26

Huang-Lian-Jie-Du-Decotion (HLJDD, Hwangryun-Hae-Dok-Decotion in Japan), an ancient antipyretic and detoxifying traditional Chinese medicine formula, was reported to have protective effect on ischemic stroke. To investigate the therapeutic effect of HLJDD on ischemic stroke and explore its mode of action. A model of ischemic stroke in the rat was established after transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Rats were assigned randomly to groups of control, sham, transient ischemia/reperfusion (I/R), and three treatment groups by HLJDD at 2.5, 5.0, 10.0mg/kg. The neurological deficit, the cerebral infarct size, morphology abnormality, biochemical parameters were examined, and the levels of relevant proteins were determined by immunoblotting analysis to evaluate the protective effects of HLJDD on ischemic stroke and explore the underlying mechanism. Compared with I/R group, HLJDD significantly ameliorated neurological deficit and histopathology changes, decreased infarct area, and restored the levels of biochemical indicators including nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), total superoxide dismutase (T-SOD), Cu/Zn-SOD, Mn-SOD and glutathione peroxidase (GSH-PX). HLJDD also notably elevated the levels of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1, and other autophagy related genes (Atgs), promoted the activation of extracellular signal-regulated kinases (ERK), protein kinase B (Akt), 3-phosphoinositide-dependent kinase (PDK1), and inhibited the activation of mammalian target of rapamycin (mTOR), c-Jun N-terminal protein kinases (JNK), p38, phosphatase and tensin homolog (PTEN). HLJDD showed neuroprotective effects on ischemic stroke, at least in part to the induced protective autophagy via the regulation of mitogen-activated protein kinase (MAPK) signals. This Akt-independent protective autophagy is favorable in the treatment of stroke, avoiding unfavorable side-effects associated with the inactivation of Akt. The efficacy of HLJDD on ischemic stroke and its safety warranted by its long-term clinical use in traditional Chinese medicine favored further study to develop HLJDD as an effective therapeutic agent to treat ischemic stroke. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

Radiation Therapy Side Effects

Cancer.gov

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

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

PubMed

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

2017-03-01

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

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

PubMed Central

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

2017-01-01

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

Understanding speech in noise after correction of congenital unilateral aural atresia: effects of age in the emergence of binaural squelch but not in use of head-shadow.

PubMed

Gray, Lincoln; Kesser, Bradley; Cole, Erika

2009-09-01

Unilateral hearing loss causes difficulty hearing in noise (the "cocktail party effect") due to absence of redundancy, head-shadow, and binaural squelch. This study explores the emergence of the head-shadow and binaural squelch effects in children with unilateral congenital aural atresia undergoing surgery to correct their hearing deficit. Adding patients and data from a similar study previously published, we also evaluate covariates such as the age of the patient, surgical outcome, and complexity of the task that might predict the extent of binaural benefit--patients' ability to "use" their new ear--when understanding speech in noise. Patients with unilateral congenital aural atresia were tested for their ability to understand speech in noise before and again 1 month after surgery to repair their atresia. In a sound-attenuating booth participants faced a speaker that produced speech signals with noise 90 degrees to the side of the normal (non-atretic) ear and again to the side of the atretic ear. The Hearing in Noise Test (HINT for adults or HINT-C for children) was used to estimate the patients' speech reception thresholds. The speech-in-noise test (SPIN) or the Pediatric Speech Intelligibility (PSI) Test was used in the previous study. There was consistent improvement, averaging 5dB regardless of age, in the ability to take advantage of head-shadow in understanding speech with noise to the side of the non-atretic (normal) ear. There was, in contrast, a strong negative linear effect of age (r(2)=.78, selecting patients over 8 years) in the emergence of binaural squelch to understand speech with noise to the side of the atretic ear. In patients over 8 years, this trend replicated over different studies and different tests. Children less than 8 years, however, showed less improvement in the HINT-C than in the PSI after surgery with noise toward their atretic ear (effect size=3). No binaural result was correlated with degree of hearing improvement after surgery. All patients are able to take advantage of a favorable signal-to-noise ratio in their newly opened ear; that is with noise toward the side of the normal ear (but this physical, bilateral, head-shadow effect need not involve true central binaural processing). With noise toward the atretic ear, the emergence of binaural squelch replicates between two studies for all but the youngest patients. Approximately 2dB of binaural gain is lost for each decade that surgery is delayed, and zero (or poorer) binaural benefit is predicted after 38 years of age. Older adults do more poorly, possibly secondary to their long period of auditory deprivation. At the youngest ages, however, binaural results are different in open- and closed-set speech tests; the more complex hearing tasks may involve a greater cognitive load. Other cognitive abilities (late evoked potentials, grey matter in auditory cortex, and multitasking) show similar effects of age, peaking at the same late-teen/young-adult period. Longer follow-up is likely critical for the understanding of these data. Getting a new ear may be--like multitasking--challenging for the youngest and oldest subjects.

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

PubMed

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

2001-12-01

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

Slow dynamics of electron glasses: The role of disorder

NASA Astrophysics Data System (ADS)

Ovadyahu, Z.

2017-04-01

We examine in this work the role of disorder in contributing to the sluggish relaxation observed in intrinsic electron glasses. Our approach is guided by several empirical observations: First and foremost, Anderson localization is a pre-requisite for observing these nonequilibrium phenomena. Secondly, sluggish relaxation appears to favor Anderson insulators with relatively large Fermi energies (hence proportionally large disorder). These observations motivated us to consider a way to measure the underlying disorder in a realistic Anderson insulator. Optical studies using a series of amorphous indium oxide (InxO ) establish a simple connection between carrier concentration and the disorder necessary to approach the metal-insulator transition from the insulating side. This is used to estimate the typical magnitude of the quenched potential fluctuation in the electron-glass phase of this system. The implications of our findings on the slow dynamics of Anderson insulators are discussed. In particular, the reason for the absence of a memory dip and the accompanying electron-glass effects in lightly-doped semiconductors emerges as a natural consequence of their weak disorder.

Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-one substituted with ibuprofen: novel non-steroidal anti-inflammatory agents with favorable gastrointestinal tolerance.

PubMed

Uzgören-Baran, Ayşe; Tel, Banu Cahide; Sarıgöl, Deniz; Oztürk, Elif İnci; Kazkayası, Inci; Okay, Gürol; Ertan, Mevlüt; Tozkoparan, Birsen

2012-11-01

In an effort to establish new candidates with improved analgesic and anti-inflammatory activities and lower ulcerogenic risk, a series of thiazolo[3,2-b]-1,2,4-triazole-5(6H)-one derivatives of ibuprofen were synthesized. All compounds were evaluated for their in vivo anti-inflammatory and analgesic activities in mice. Furthermore, the ulcerogenic risks of the compounds were determined. In general, none of the compounds represent a risk for developing stomach injury as much as observed in the reference drugs ibuprofen and indomethacin. The compounds carrying a 3-phenyl-2-propenylidene (1a), (biphenyl-4-yl)methylidene (1f) and (1-methylpyrrol-2-yl)methylidene (1n) at the 6th position of the fused ring have been evaluated as potential analgesic/anti-inflammatory agents without a gastrointestinal side effect. These new compounds, therefore, deserve further attention to develop new lead drugs. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Refraction and Shielding of Noise in Non-Axisymmetric Jets

NASA Technical Reports Server (NTRS)

Khavaran, Abbas

1996-01-01

This paper examines the shielding effect of the mean flow and refraction of sound in non-axisymmetric jets. A general three-dimensional ray-acoustic approach is applied. The methodology is independent of the exit geometry and may account for jet spreading and transverse as well as streamwise flow gradients. We assume that noise is dominated by small-scale turbulence. The source correlation terms, as described by the acoustic analogy approach, are simplified and a model is proposed that relates the source strength to 7/2 power of turbulence kinetic energy. Local characteristics of the source such as its strength, time- or length-scale, convection velocity and characteristic frequency are inferred from the mean flow considerations. Compressible Navier Stokes equations are solved with a k-e turbulence model. Numerical predictions are presented for a Mach 1.5, aspect ratio 2:1 elliptic jet. The predicted sound pressure level directivity demonstrates favorable agreement with reported data, indicating a relative quiet zone on the side of the major axis of the elliptic jet.

Vapor-based interferometric measurement of local evaporation rate and interfacial temperature of evaporating droplets.

PubMed

Dehaeck, Sam; Rednikov, Alexey; Colinet, Pierre

2014-03-04

The local evaporation rate and interfacial temperature are two quintessential characteristics for the study of evaporating droplets. Here, it is shown how one can extract these quantities by measuring the vapor concentration field around the droplet with digital holographic interferometry. As a concrete example, an evaporating freely receding pending droplet of 3M Novec HFE-7000 is analyzed at ambient conditions. The measured vapor cloud is shown to deviate significantly from a pure-diffusion regime calculation, but it compares favorably to a new boundary-layer theory accounting for a buoyancy-induced convection in the gas and the influence upon it of a thermal Marangoni flow. By integration of the measured local evaporation rate over the interface, the global evaporation rate is obtained and validated by a side-view measurement of the droplet shape. Advective effects are found to boost the global evaporation rate by a factor of 4 as compared to the diffusion-limited theory.

Feasibility demonstration for electroplating ultra-thin polyimide film. [fabricating film for space erectable structures

NASA Technical Reports Server (NTRS)

Schneier, R.; Braswell, T. V.; Vaughn, R. W.

1978-01-01

The effect of electrodeposition variables on film thickness was investigated using a dilute polyimide solution as a bath into which aluminum (as foil or as a vapor deposited coating) was immersed. The electrodeposited film was dried for 2 hours at 93 C (primarily to remove solvent) and cured for 18 hours at 186 C. Infrared studies indicate that imide formation (curing) occurs at 149 C under vacuum. From a conceptual viewpoint, satisfactory film metallized on one side can be obtained by this method. The cured ultra thin polyimide film exhibits properties equivalent to those of commercial film, and the surface appearance of the strippable polyimide film compares favorably with that of a sample of commercial film of thicker gauge. The feasibility of manufacturing approximately one million sq m of ultra thin film capable of being joined to fabricate an 800 m by 9 800 m square from starting material 0.5 to 1 m wide for space erectable structures was demonstrated.

Molecular mechanisms of the naringin low uptake by intestinal Caco-2 cells.

PubMed

Tourniaire, Franck; Hassan, Meryl; André, Marc; Ghiringhelli, Odette; Alquier, Christian; Amiot, Marie-Josèphe

2005-10-01

Naringin, the main flavanone of grapefruit, was reported to display numerous biological effects: antioxidant, hypocholesteremic, anti-atherogenic and favoring drug absorption. Naringin absorption mechanisms were studied in Caco-2 cells (TC7 clone). We investigated the possible involvement of several membrane transporters implicated in polyphenolic compounds intestinal transport (sodium-dependent glucose transporter 1, monocarboxylate transporter, multidrug-associated resistance proteins 1 and 2, and P-glycoprotein). Naringin was poorly absorbed by Caco-2 cells, according to its low value of apparent permeability coefficient (P(app) = 8.1 +/- 0.9 x 10(-8) cm/s). In the presence of verapamil, a specific inhibitor of P-glycoprotein, cellular uptake was increased by almost threefold after 5 min, and P(app) was doubled after 30 min. Our results indicated the involvement of P-glycoprotein, an ATP-driven efflux pump, capable of transporting naringin from the Caco-2 cell to the apical side. This phenomenon could explain, at least in part, the low absorption of this flavanone at the upper intestinal level.

Positive Effect of Acupuncture and Cupping in Infertility Treatment.

PubMed

Wang, Jun-Xiang; Yang, Yang; Song, Yue; Ma, Liang-Xiao

2018-04-01

Background: Infertility is clinically defined as the failure to conceive after 12 months of unprotected sexual intercourse. Organic disorders and lifestyle factors are highly associated with infertility. Generally, acupuncture and its related methods can be applied for treating infertility, according to the theory of Traditional Chinese Medicine. Successful cases of acupuncture-treated infertility without concomitant use of any medication are rare. This article presents a case of an infertile woman having a favorable response to acupuncture treatment. Case: A 39-year-old Mexican woman presented with infertility following right-side fallopian-tube obstruction. She had no significant physical feelings of discomfort apart from work-related stress. Her syndrome was first diagnosed as Deficiency of Spleen and Kidney Qi, accompanied by obstruction of channels due to accumulation of Dampness. Acupuncture, accompanied by cupping therapy, was primarily practiced for this patient. Results: After 28 treatment sessions, she was finally able to conceive. Conclusions: Acupuncture could help treat infertility. Further large-scale, randomized clinical trials are needed to verify the efficacy of acupuncture for treating female infertility.

[Cosmetic eyelid surgery].

PubMed

Ruban, J-M; Barbier, J; Malet, T; Baggio, E

2014-01-01

Cosmetic eyelid surgery is becoming increasingly popular. It can rejuvenate the patient's appearance with relatively minor side effects. Its risk/benefit ratio is one of the best in facial cosmetic surgery. However, the patient does not always accurately assess the aesthetic appearance of his or her eyelids. This underscores the importance of clinical examination in order to determine the patient's wishes, and then make an accurate diagnosis and potential surgical plan. We currently oppose, in general, surgical techniques involving tissue removal (skin-muscle and/or fat) in favor of those involving tissue repositioning and grafting (autologous fat pearl transposition, obtained by liposuction, and lipostructure). Furthermore, the place of adjuvant therapies to blepharoplasty is steadily increasing. They mainly include surface treatments (peels and lasers), dermal fillers and anti-wrinkle botulinum toxin injections. They are also increasingly used in isolation in novel ways. In all cases, a perfect knowledge of anatomy and relevant skills and experience remain necessary. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Promoting healthy timing and spacing of pregnancy with young married women in Northern Nigeria: a short report.

PubMed

Lane, Cate; Joof, Yaikah M; Hassan, Aisha Ahmed; Pryor, Shannon

2012-06-01

The persistence of early and closely spaced pregnancies in Northern Nigeria contributes to maternal and child morbidity and mortality. A technical working group to WHO recommended that following a birth, a woman should space her next pregnancy by at least 24 months, and following a miscarriage or abortion, a woman space her next pregnancy by at least six months. UNICEF, UNFPA and WHO also recommend that a woman delay her first pregnancy until 18. These recommendations comprise the concept of Healthy Timing and Spacing of Pregnancy. The Extending Service Delivery Project (ESD) partnered with the Federation of Muslim Women Association of Nigeria and religious leaders to educate communities about the benefits of using family planning to practice HTSP in five local government areas. Informal discussions with 148 women and 28 men found high recall of the HTSP recommendations and favorable attitudes toward spacing and family planning although many remain concerned about the side effects of contraceptive methods.

Tuning the Wettability of Halloysite Clay Nanotubes by Surface Carbonization for Optimal Emulsion Stabilization.

PubMed

Owoseni, Olasehinde; Zhang, Yueheng; Su, Yang; He, Jibao; McPherson, Gary L; Bose, Arijit; John, Vijay T

2015-12-29

The carbonization of hydrophilic particle surfaces provides an effective route for tuning particle wettability in the preparation of particle-stabilized emulsions. The wettability of naturally occurring halloysite clay nanotubes (HNT) is successfully tuned by the selective carbonization of the negatively charged external HNT surface. The positively charge chitosan biopolymer binds to the negatively charged external HNT surface by electrostatic attraction and hydrogen bonding, yielding carbonized halloysite nanotubes (CHNT) on pyrolysis in an inert atmosphere. Relative to the native HNT, the oil emulsification ability of the CHNT at intermediate levels of carbonization is significantly enhanced due to the thermodynamically more favorable attachment of the particles at the oil-water interface. Cryogenic scanning electron microscopy (cryo-SEM) imaging reveals that networks of CHNT attach to the oil-water interface with the particles in a side-on orientation. The concepts advanced here can be extended to other inorganic solids and carbon sources for the optimal design of particle-stabilized emulsions.

Under-Pressured and Avoiding Interaction: How Magmatic Storage Regions Can Deflect Dikes

NASA Astrophysics Data System (ADS)

Pansino, S.; Taisne, B.

2017-12-01

It has been shown through numerical techniques that ascending dikes can be attracted to a pressurized magma storage region. This is due to the state of stresses around such a region, in which the minimum compressive stress is tangential to reservoir boundary and dikes thereby prefer to propagate radially. We show that the reverse scenario has a reverse effect. A storage region that has under-pressurized, perhaps due to an eruption, rotates the stresses in the crust to deflect dikes away; this inhibits interaction with the reservoir and favors other behaviors like intrusion or monogenetic eruptions. We demonstrate through analogue experiments the ability for a dike to avoid a magmatic reservoir, which depends in part on the internal pressure as well as on the initial dike orientation. We show that dikes have the potential to change orientation, curling and twisting to avoid the pressure sink, or to propagate preferentially at their sides, allowing them to slide away laterally.

Catalytic in vivo protein knockdown by small-molecule PROTACs

PubMed Central

Bondeson, Daniel P; Mares, Alina; Smith, Ian E D; Ko, Eunhwa; Campos, Sebastien; Miah, Afjal H; Mulholland, Katie E; Routly, Natasha; Buckley, Dennis L; Gustafson, Jeffrey L; Zinn, Nico; Grandi, Paola; Shimamura, Satoko; Bergamini, Giovanna; Faelth-Savitski, Maria; Bantscheff, Marcus; Cox, Carly; Gordon, Deborah A; Willard, Ryan R; Flanagan, John J; Casillas, Linda N; Votta, Bartholomew J; den Besten, Willem; Famm, Kristoffer; Kruidenier, Laurens; Carter, Paul S; Harling, John D; Churcher, Ian; Crews, Craig M

2015-01-01

The current predominant theapeutic paradigm is based on maximizing drug-receptor occupancy to achieve clinical benefit. This strategy, however, generally requires excessive drug concentrations to ensure sufficient occupancy, often leading to adverse side effects. Here, we describe major improvements to the proteolysis targeting chimeras (PROTACs) method, a chemical knockdown strategy in which a heterobifunctional molecule recruits a specific protein target to an E3 ubiquitin ligase, resulting in the target’s ubiquitination and degradation. These compounds behave catalytically in their ability to induce the ubiquitination of super-stoichiometric quantities of proteins, providing efficacy that is not limited by equilibrium occupancy. We present two PROTACs that are capable of specifically reducing protein levels by >90% at nanomolar concentrations. In addition, mouse studies indicate that they provide broad tissue distribution and knockdown of the targeted protein in tumor xenografts. Together, these data demonstrate a protein knockdown system combining many of the favorable properties of small-molecule agents with the potent protein knockdown of RNAi and CRISPR. PMID:26075522

Atomic magnetometer for human magnetoencephalograpy.

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

Schwindt, Peter; Johnson, Cort N.

2010-12-01

We have developed a high sensitivity (<5 fTesla/{radical}Hz), fiber-optically coupled magnetometer to detect magnetic fields produced by the human brain. This is the first demonstration of a noncryogenic sensor that could replace cryogenic superconducting quantum interference device (SQUID) magnetometers in magnetoencephalography (MEG) and is an important advance in realizing cost-effective MEG. Within the sensor, a rubidium vapor is optically pumped with 795 laser light while field-induced optical rotations are measured with 780 nm laser light. Both beams share a single optical axis to maximize simplicity and compactness. In collaboration with neuroscientists at The Mind Research Network in Albuquerque, NM, themore » evoked responses resulting from median nerve and auditory stimulation were recorded with the atomic magnetometer and a commercial SQUID-based MEG system with signals comparing favorably. Multi-sensor operation has been demonstrated with two AMs placed on opposite sides of the head. Straightforward miniaturization would enable high-density sensor arrays for whole-head magnetoencephalography.« less

Ophthalmic preservatives: focus on polyquaternium-1.

PubMed

Rolando, Maurizio; Crider, Julie Y; Kahook, Malik Y

2011-11-01

Ophthalmic preservatives, such as polyquaternium-1 (PQ-1), are critical for the inhibition of growth of microbial contaminants in multi-dose bottles of topical medications. These antimicrobial agents must have a high efficacy against pathogenic organisms, while maintaining a favorable tolerability and safety profile. This review focuses on the ophthalmic preservative PQ-1. For comparison purposes, the most commonly used preservative, benzalkonium chloride (BAK), is also discussed. This survey focuses primarily on data collected during the past 10 years. Effective drug delivery requires more than just an active ingredient that achieves its desired biological effect on end-target tissues. In addition, drugs must be stable in the containers that they are stored in, and must possess minimal undesired local and systemic side effects that can cause patients to decrease their adherence. In addressing these concerns, specifically in topical ophthalmic drops, one must take into account the active ingredients, vehicle components and preservatives. Medications with fewer adverse effects may lead to enhanced adherence to therapy; therefore, the induction of such adverse outcomes must be considered by physicians when treating patients with chronic ocular disease. Although BAK will continue to be used in ophthalmic medications, due to its familiarity and compatibility with a broad range of topical ocular formulations, PQ-1 is certainly a viable alternative in the preservative formulary armamentarium.

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

Optimal management of orthodontic pain.

PubMed

Topolski, Francielle; Moro, Alexandre; Correr, Gisele Maria; Schimim, Sasha Cristina

2018-01-01

Pain is an undesirable side effect of orthodontic tooth movement, which causes many patients to give up orthodontic treatment or avoid it altogether. The aim of this study was to investigate, through an analysis of the scientific literature, the best method for managing orthodontic pain. The methodological aspects involved careful definition of keywords and diligent search in databases of scientific articles published in the English language, without any restriction of publication date. We recovered 1281 articles. After the filtering and classification of these articles, 56 randomized clinical trials were selected. Of these, 19 evaluated the effects of different types of drugs for the control of orthodontic pain, 16 evaluated the effects of low-level laser therapy on orthodontic pain, and 21 evaluated other methods of pain control. Drugs reported as effective in orthodontic pain control included ibuprofen, paracetamol, naproxen sodium, aspirin, etoricoxib, meloxicam, piroxicam, and tenoxicam. Most studies report favorable outcomes in terms of alleviation of orthodontic pain with the use of low-level laser therapy. Nevertheless, we noticed that there is no consensus, both for the drug and for laser therapy, on the doses and clinical protocols most appropriate for orthodontic pain management. Alternative methods for orthodontic pain control can also broaden the clinician's range of options in the search for better patient care.

Optimal management of orthodontic pain

PubMed Central

Topolski, Francielle; Moro, Alexandre; Correr, Gisele Maria; Schimim, Sasha Cristina

2018-01-01

Pain is an undesirable side effect of orthodontic tooth movement, which causes many patients to give up orthodontic treatment or avoid it altogether. The aim of this study was to investigate, through an analysis of the scientific literature, the best method for managing orthodontic pain. The methodological aspects involved careful definition of keywords and diligent search in databases of scientific articles published in the English language, without any restriction of publication date. We recovered 1281 articles. After the filtering and classification of these articles, 56 randomized clinical trials were selected. Of these, 19 evaluated the effects of different types of drugs for the control of orthodontic pain, 16 evaluated the effects of low-level laser therapy on orthodontic pain, and 21 evaluated other methods of pain control. Drugs reported as effective in orthodontic pain control included ibuprofen, paracetamol, naproxen sodium, aspirin, etoricoxib, meloxicam, piroxicam, and tenoxicam. Most studies report favorable outcomes in terms of alleviation of orthodontic pain with the use of low-level laser therapy. Nevertheless, we noticed that there is no consensus, both for the drug and for laser therapy, on the doses and clinical protocols most appropriate for orthodontic pain management. Alternative methods for orthodontic pain control can also broaden the clinician’s range of options in the search for better patient care. PMID:29588616

Lighting the darkness of addiction: can phototherapy enhance contingency-management-based treatment of substance-related and addictive disorders?

PubMed

Siporin, Sheldon

2014-01-01

Maladaptive patterns of substance use are serious social problems. Both pharmacological and nonpharmacological treatments are available, but nondrug options may be preferable because they avoid the expense and adverse side effects of psychotropic medication. Contingency management (CM) and nondrug social and recreational activities (NDSRAs) are based on operant conditioning principles and seek to decrease substance use by means of nondrug rewards. However, their efficacy may be hindered where brain reward circuitry is dysfunctional. Research shows that substance abuse biases neural reward systems in favor of drug-induced highs, while disrupting circadian-based rhythms. Circadian systems also have been found to influence human reward pathways. Possibly, a bidirectional relationship exists between circadian disturbance and substance abuse effects. If so, repair of abnormal circadian rhythms might help normalize reward response in substance abusers, with positive effects on CM or NDSRA treatment outcomes. Phototherapy has been effective in repairing circadian rhythms in persons with seasonal affective disorder and other chronobiological conditions. This article proposes that it similarly may repair circadian response in substance abusers, thereby normalizing brain reward systems. By doing so, it would enhance the efficacy of CM and NDSRA therapies and may also help prevent relapse. Given its low cost and ease of administration, phototherapy seems a promising avenue to pursue.

Accelerated Blood Clearance (ABC) Phenomenon Favors the Accumulation of Tartar Emetic in Pegylated Liposomes in BALB/c Mice Liver.

PubMed

Lopes, Tamara C M; Silva, Débora F; Costa, Walyson C; Frézard, Frédéric; Barichello, José M; Silva-Barcellos, Neila M; de Lima, Wanderson G; Rezende, Simone A

2018-01-01

Tartar emetic (TE) was the first drug used to treat leishmaniasis. However, its use was discontinued due to high toxicity. Association of TE with liposomes is a strategy to reduce its side effects. Pegylated liposomes (Lpeg) present lower rates of uptake by macrophages and prolonged circulation compared to their nonpegylated counterparts. However, repeated administration of Lpeg can cause an Accelerated Blood Clearance (ABC) phenomenon, whereby recognition of liposomes by antibodies results in faster phagocytosis. This work evaluated the effect of TE administration on histopathological aspects and the effect of the ABC phenomenon on targeting and toxicity in mice. Our results show that treatment with free or liposomal TE had no effect on the erythrocyte count, on liver and spleen weight, and on hepatic, splenic, and cardiac histology in mice. Severe lesions were observed on the kidneys of animals treated with a single dose of free TE. Treatment with TE in Lpeg after induction of ABC phenomenon caused a significant increase in Sb level in the liver without toxicity. Furthermore, mice treated with TE in liposomes showed normal renal histopathology. These results suggest site-specific targeting of Sb to the liver after induction of ABC phenomenon with no toxicity to other organs.

The influence of physical characteristics on ablation effects in UV laser assisted micro-engineering

NASA Astrophysics Data System (ADS)

Ostendorf, Andreas; Kulik, Christian J.; Temme, Thorsten; Otte, Frank; Samm, Katja

2004-10-01

The development of the recent years led to an increased importance of frequency-converted diode-pumped solid-state lasers (DPSSL) for industrial drilling, cutting and structuring applications. The UV laser systems show favorable beam absorption in a broad range of MEMS and MOEMS relevant materials like ceramics, metals and polymers. Their short pulses in the range of tH = 20 nanoseconds and the excellent beam quality offer the possibility of manufacturing with a minimum heat affected zone (HAZ) in the surrounding material and thereby a decreasing of initial fusing and debris. To obtain the reachable ablation quality, especially on metals, in this paper copper, tungsten, tantalum, molybdenum, nickel, iron, aluminum and titanium were machined under identical conditions. Material properties like heat conductivity, optical and thermal penetration depth, are decisive for the magnitude of the mentioned side-effects. The correlation of these physical values of different metals to those effects is the subject of this paper. Results of systematically accomplished experiences using a frequency tripled DPSSL with a wavelength of λ = 355 nm in order to investigate this correlation are presented. Due to thermal effects, the ablation quality of metals differ from each other extremely. These information enable a prediction of the reachable quality of the desired structure.

Response to apatinib in chemotherapy-failed advanced spindle cell breast carcinoma.

PubMed

Zhou, Na; Liu, Congmin; Hou, Helei; Zhang, Chuantao; Liu, Dong; Wang, Guanqun; Liu, Kewei; Zhu, Jingjuan; Lv, Hongying; Li, Tianjun; Zhang, Xiaochun

2016-11-01

Spindle cell carcinoma of the breast is a rare subtype of metaplastic carcinoma, and no effective chemotherapy special for metaplastic carcinoma exists until now. As spindle cell carcinomas of the breast are typically "Triple Negative", endocrine therapy and molecular therapy targeted to Her2 might not be favorable, resulting in poor prognosis. Apatinib is currently being tested in patients with breast or lung cancers. Here we report a successful case using Apatinib to treat spindle cell carcinoma of breast.A 52- year- old woman presented with a gradually enlarged lump in left breast, which was revealed to be a triple-negative spindle cell carcinoma, underwent a modified radical mastectomy. After the first line chemotherapy with Cyclophosphamide and Epirubicin, multiple metastases in bilateral lung and left anterior thoracic wall appeared. After disease progressed with therapy of Bevacizumab combined with Albumin-bound Paclitaxel and Cisplatin, we treated the patient with Apatinib according to her VEGFR expression, which showed nearly complete response and controllable and tolerated side effects. Next-generation sequencing analysis of the tumor specimen and real time ctDNA was performed to observe the mutated gene numbers matched with therapeutic effect. The present case can help to provide a new and effective therapy strategy to treat advanced spindle cell carcinoma.

Response to apatinib in chemotherapy-failed advanced spindle cell breast carcinoma

PubMed Central

Zhou, Na; Liu, Congmin; Hou, Helei; Zhang, Chuantao; Liu, Dong; Wang, Guanqun; Liu, Kewei; Zhu, Jingjuan; Lv, Hongying; Li, Tianjun; Zhang, Xiaochun

2016-01-01

Spindle cell carcinoma of the breast is a rare subtype of metaplastic carcinoma, and no effective chemotherapy special for metaplastic carcinoma exists until now. As spindle cell carcinomas of the breast are typically “Triple Negative”, endocrine therapy and molecular therapy targeted to Her2 might not be favorable, resulting in poor prognosis. Apatinib is currently being tested in patients with breast or lung cancers. Here we report a successful case using Apatinib to treat spindle cell carcinoma of breast. A 52- year- old woman presented with a gradually enlarged lump in left breast, which was revealed to be a triple-negative spindle cell carcinoma, underwent a modified radical mastectomy. After the first line chemotherapy with Cyclophosphamide and Epirubicin, multiple metastases in bilateral lung and left anterior thoracic wall appeared. After disease progressed with therapy of Bevacizumab combined with Albumin-bound Paclitaxel and Cisplatin, we treated the patient with Apatinib according to her VEGFR expression, which showed nearly complete response and controllable and tolerated side effects. Next-generation sequencing analysis of the tumor specimen and real time ctDNA was performed to observe the mutated gene numbers matched with therapeutic effect. The present case can help to provide a new and effective therapy strategy to treat advanced spindle cell carcinoma. PMID:27738308

Accelerated Blood Clearance (ABC) Phenomenon Favors the Accumulation of Tartar Emetic in Pegylated Liposomes in BALB/c Mice Liver

PubMed Central

Lopes, Tamara C. M.; Silva, Débora F.; Costa, Walyson C.; Barichello, José M.; Silva-Barcellos, Neila M.; de Lima, Wanderson G.

2018-01-01

Tartar emetic (TE) was the first drug used to treat leishmaniasis. However, its use was discontinued due to high toxicity. Association of TE with liposomes is a strategy to reduce its side effects. Pegylated liposomes (Lpeg) present lower rates of uptake by macrophages and prolonged circulation compared to their nonpegylated counterparts. However, repeated administration of Lpeg can cause an Accelerated Blood Clearance (ABC) phenomenon, whereby recognition of liposomes by antibodies results in faster phagocytosis. This work evaluated the effect of TE administration on histopathological aspects and the effect of the ABC phenomenon on targeting and toxicity in mice. Our results show that treatment with free or liposomal TE had no effect on the erythrocyte count, on liver and spleen weight, and on hepatic, splenic, and cardiac histology in mice. Severe lesions were observed on the kidneys of animals treated with a single dose of free TE. Treatment with TE in Lpeg after induction of ABC phenomenon caused a significant increase in Sb level in the liver without toxicity. Furthermore, mice treated with TE in liposomes showed normal renal histopathology. These results suggest site-specific targeting of Sb to the liver after induction of ABC phenomenon with no toxicity to other organs. PMID:29593857

Weighting for China, Counting on the United States: Asia’s China Debate and U.S. Interests

DTIC Science & Technology

2003-12-01

political stability . Unease exists about ethnic Chinese migration and diasporas and the possible reassertion of China s historical dominance. The United States has a prime opportunity to influence Asia s China debate because the debate is ongoing, and the United States remains regarded as fundamental to national and regional calculations including about China. Extreme U.S.-China tensions and possible pressures by either to choose sides are unwelcome. No Asian country expects or desires China to supplant U.S. regional pre-eminence. At worst, some favor a balance of great

Synthesis and Evaluation of Chirally Defined Side Chain Variants of 7-Chloro-4-Aminoquinoline To Overcome Drug Resistance in Malaria Chemotherapy

PubMed Central

Dola, Vasantha Rao; Soni, Awakash; Agarwal, Pooja; Ahmad, Hafsa; Raju, Kanumuri Siva Rama; Rashid, Mamunur; Wahajuddin, Muhammad; Srivastava, Kumkum; Haq, W.; Dwivedi, A. K.; Puri, S. K.

2016-01-01

ABSTRACT A novel 4-aminoquinoline derivative [(S)-7-chloro-N-(4-methyl-1-(4-methylpiperazin-1-yl)pentan-2-yl)-quinolin-4-amine triphosphate] exhibiting curative activity against chloroquine-resistant malaria parasites has been identified for preclinical development as a blood schizonticidal agent. The lead molecule selected after detailed structure-activity relationship (SAR) studies has good solid-state properties and promising activity against in vitro and in vivo experimental malaria models. The in vitro absorption, distribution, metabolism, and excretion (ADME) parameters indicate a favorable drug-like profile. PMID:27956423

Synchronous Pulmonary Malignancies: Atypical Presentation of Mantle Cell Lymphoma Masking a Lung Malignancy

PubMed Central

Masha, Luke; Zinchuk, Andrey; Boosalis, Valia

2015-01-01

We present a case of a pleural space malignancy masked by an atypical presentation of mantle cell lymphoma. Our patient presented with a large pleural effusion and right sided pleural studding, initially attributed to a new diagnosis of mantle cell lymphoma. Rare atypical epithelial cells were also seen amongst the clonal population of lymphocytes. The patient lacked systemic manifestations of mantle cell lymphoma and did not improve with chemotherapy. A pleural biopsy ultimately revealed the presence of an undifferentiated carcinoma, favoring a lung primary. A discussion of synchronous pleural space malignancies involving lymphomas is given. PMID:26500732

Synchronous Pulmonary Malignancies: Atypical Presentation of Mantle Cell Lymphoma Masking a Lung Malignancy.

PubMed

Masha, Luke; Zinchuk, Andrey; Boosalis, Valia

2015-09-07

We present a case of a pleural space malignancy masked by an atypical presentation of mantle cell lymphoma. Our patient presented with a large pleural effusion and right sided pleural studding, initially attributed to a new diagnosis of mantle cell lymphoma. Rare atypical epithelial cells were also seen amongst the clonal population of lymphocytes. The patient lacked systemic manifestations of mantle cell lymphoma and did not improve with chemotherapy. A pleural biopsy ultimately revealed the presence of an undifferentiated carcinoma, favoring a lung primary. A discussion of synchronous pleural space malignancies involving lymphomas is given.

Dismounted Complex Blast Injury.

PubMed

Andersen, Romney C; Fleming, Mark; Forsberg, Jonathan A; Gordon, Wade T; Nanos, George P; Charlton, Michael T; Ficke, James R

2012-01-01

The severe Dismounted Complex Blast Injury (DCBI) is characterized by high-energy injuries to the bilateral lower extremities (usually proximal transfemoral amputations) and/or upper extremity (usually involving the non-dominant side), in addition to open pelvic injuries, genitourinary, and abdominal trauma. Initial resuscitation and multidisciplinary surgical management appear to be the keys to survival. Definitive treatment follows general principals of open wound management and includes decontamination through aggressive and frequent debridement, hemorrhage control, viable tissue preservation, and appropriate timing of wound closure. These devastating injuries are associated with paradoxically favorable survival rates, but associated injuries and higher amputation levels lead to more difficult reconstructive challenges.

SpRoUTS (Space Robot Universal Truss System): Reversible Robotic Assembly of Deployable Truss Structures of Reconfigurable Length

NASA Technical Reports Server (NTRS)

Jenett, Benjamin; Cellucci, Daniel; Cheung, Kenneth

2015-01-01

Automatic deployment of structures has been a focus of much academic and industrial work on infrastructure applications and robotics in general. This paper presents a robotic truss assembler designed for space applications - the Space Robot Universal Truss System (SpRoUTS) - that reversibly assembles a truss from a feedstock of hinged andflat-packed components, by folding the sides of each component up and locking onto the assembled structure. We describe the design and implementation of the robot and show that the assembled truss compares favorably with prior truss deployment systems.

Origins of pressure-induced protein transitions.

PubMed

Chalikian, Tigran V; Macgregor, Robert B

2009-12-18

The molecular mechanisms underlying pressure-induced protein denaturation can be analyzed based on the pressure-dependent differences in the apparent volume occupied by amino acids inside the protein and when they are exposed to water in an unfolded conformation. We present here an analysis for the peptide group and the 20 naturally occurring amino acid side chains based on volumetric parameters for the amino acids in the interior of the native state, the micelle-like interior of the pressure-induced denatured state, and the unfolded conformation modeled by N-acetyl amino acid amides. The transfer of peptide groups from the protein interior to water becomes increasingly favorable as pressure increases. Thus, solvation of peptide groups represents a major driving force in pressure-induced protein denaturation. Polar side chains do not appear to exhibit significant pressure-dependent changes in their preference for the protein interior or solvent. The transfer of nonpolar side chains from the protein interior to water becomes more unfavorable as pressure increases. We conclude that a sizeable population of nonpolar side chains remains buried inside a solvent-inaccessible core of the pressure-induced denatured state. At elevated pressures, this core may become packed almost as tightly as the interior of the native state. The presence and partial disappearance of large intraglobular voids is another driving force facilitating pressure-induced denaturation of individual proteins. Our data also have implications for the kinetics of protein folding and shed light on the nature of the folding transition state ensemble.

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

PubMed

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

2014-02-01

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

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

PubMed

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

2010-05-01

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

Find novel dual-agonist drugs for treating type 2 diabetes by means of cheminformatics.

PubMed

Liu, Lei; Ma, Ying; Wang, Run-Ling; Xu, Wei-Ren; Wang, Shu-Qing; Chou, Kuo-Chen

2013-01-01

The high prevalence of type 2 diabetes mellitus in the world as well as the increasing reports about the adverse side effects of the existing diabetes treatment drugs have made developing new and effective drugs against the disease a very high priority. In this study, we report ten novel compounds found by targeting peroxisome proliferator-activated receptors (PPARs) using virtual screening and core hopping approaches. PPARs have drawn increasing attention for developing novel drugs to treat diabetes due to their unique functions in regulating glucose, lipid, and cholesterol metabolism. The reported compounds are featured with dual functions, and hence belong to the category of dual agonists. Compared with the single PPAR agonists, the dual PPAR agonists, formed by combining the lipid benefit of PPARα agonists (such as fibrates) and the glycemic advantages of the PPARγ agonists (such as thiazolidinediones), are much more powerful in treating diabetes because they can enhance metabolic effects while minimizing the side effects. This was observed in the studies on molecular dynamics simulations, as well as on absorption, distribution, metabolism, and excretion, that these novel dual agonists not only possessed the same function as ragaglitazar (an investigational drug developed by Novo Nordisk for treating type 2 diabetes) did in activating PPARα and PPARγ, but they also had more favorable conformation for binding to the two receptors. Moreover, the residues involved in forming the binding pockets of PPARα and PPARγ among the top ten compounds are explicitly presented, and this will be very useful for the in-depth conduction of mutagenesis experiments. It is anticipated that the ten compounds may become potential drug candidates, or at the very least, the findings reported here may stimulate new strategies or provide useful insights for designing new and more powerful dual-agonist drugs for treating type 2 diabetes.

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.

Acoustic resonance in MEMS scale cylindrical tubes with side branches

NASA Astrophysics Data System (ADS)

Schill, John F.; Holthoff, Ellen L.; Pellegrino, Paul M.; Marcus, Logan S.

2014-05-01

Photoacoustic spectroscopy (PAS) is a useful monitoring technique that is well suited for trace gas detection. This method routinely exhibits detection limits at the parts-per-million (ppm) or parts-per-billion (ppb) level for gaseous samples. PAS also possesses favorable detection characteristics when the system dimensions are scaled to a microelectromechanical system (MEMS) design. One of the central issues related to sensor miniaturization is optimization of the photoacoustic cell geometry, especially in relationship to high acoustical amplification and reduced system noise. Previous work relied on a multiphysics approach to analyze the resonance structures of the MEMS scale photo acoustic cell. This technique was unable to provide an accurate model of the acoustic structure. In this paper we describe a method that relies on techniques developed from musical instrument theory and electronic transmission line matrix methods to describe cylindrical acoustic resonant cells with side branches of various configurations. Experimental results are presented that demonstrate the ease and accuracy of this method. All experimental results were within 2% of those predicted by this theory.

Marine biofouling resistance of polyurethane with biodegradation and hydrolyzation.

PubMed

Xu, Wentao; Ma, Chunfeng; Ma, Jielin; Gan, Tiansheng; Zhang, Guangzhao

2014-03-26

We have prepared polyurethane with poly(ε-caprolactone) (PCL) as the segments of the main chain and poly(triisopropylsilyl acrylate) (PTIPSA) as the side chains by a combination of radical polymerization and a condensation reaction. Quartz crystal microbalance with dissipation studies show that polyurethane can degrade in the presence of enzyme and the degradation rate decreases with the PTIPSA content. Our studies also demonstrate that polyurethane is able to hydrolyze in artificial seawater and the hydrolysis rate increases as the PTIPSA content increases. Moreover, hydrolysis leads to a hydrophilic surface that is favorable to reduction of the frictional drag under dynamic conditions. Marine field tests reveal that polyurethane has good antifouling ability because polyurethane with a biodegradable PCL main chain and hydrolyzable PTIPSA side chains can form a self-renewal surface. Polyurethane was also used to carry and release a relatively environmentally friendly antifoulant, and the combined system exhibits a much higher antifouling performance even in a static marine environment.

Smart Grid Constraint Violation Management for Balancing and Regulating Purposes

DOE PAGES

Bhattarai, Bishnu; Kouzelis, Konstantinos; Mendaza, Iker; ...

2017-03-29

The gradual active load penetration in low voltage distribution grids is expected to challenge their network capacity in the near future. Distribution system operators should for this reason resort to either costly grid reinforcements or to demand side management mechanisms. Since demand side management implementation is usually cheaper, it is also the favorable solution. To this end, this article presents a framework for handling grid limit violations, both voltage and current, to ensure a secure and qualitative operation of the distribution grid. This framework consists of two steps, namely a proactive centralized and subsequently a reactive decentralized control scheme. Themore » former is employed to balance the one hour ahead load while the latter aims at regulating the consumption in real-time. In both cases, the importance of fair use of electricity demand flexibility is emphasized. Thus, it is demonstrated that this methodology aids in keeping the grid status within preset limits while utilizing flexibility from all flexibility participants.« less

Probing energetics of Abeta fibril elongation by molecular dynamics simulations.

PubMed

Takeda, Takako; Klimov, Dmitri K

2009-06-03

Using replica exchange molecular dynamics simulations and an all-atom implicit solvent model, we probed the energetics of Abeta(10-40) fibril growth. The analysis of the interactions between incoming Abeta peptides and the fibril led us to two conclusions. First, considerable variations in fibril binding propensities are observed along the Abeta sequence. The peptides in the fibril and those binding to its edge interact primarily through their N-termini. Therefore, the mutations affecting the Abeta positions 10-23 are expected to have the largest impact on fibril elongation compared with those occurring in the C-terminus and turn. Second, we performed weak perturbations of the binding free energy landscape by scanning partial deletions of side-chain interactions at various Abeta sequence positions. The results imply that strong side-chain interactions--in particular, hydrophobic contacts--impede fibril growth by favoring disordered docking of incoming peptides. Therefore, fibril elongation may be promoted by moderate reduction of Abeta hydrophobicity. The comparison with available experimental data is presented.

Interaction between perylene-derivated molecules observed by low temperature scanning tunneling microscopy

NASA Astrophysics Data System (ADS)

Vernisse, Loranne; Guillermet, Olivier; Gourdon, André; Coratger, Roland

2018-03-01

Derivative perylene molecules deposited on Ag(111) and on NaCl(001) ultrathin layers have been investigated using low temperature STM and NC-AFM. When the metallic substrate is held at ambient temperature during evaporation, the molecules form characteristic trimers on the Ag(111) surface and interact through their polar groups. Close to the steps, the molecules form linear structures and seems to stand side by side. On the other hand, after deposition on a substrate cooled at liquid helium temperature, single molecules are observed both on metal and on NaCl. On the ultrathin insulator layers, the STM images present characteristic contrasts related to the molecular orbitals which favors the localization of aldehyde groups. In this case, the lateral molecular interactions may induce the formation of small assemblies in which the electronic levels are slightly shifted. A possible interpretation of this phenomenon is to take into account polar interactions and charge transfer between neighboring molecules.

The pedicled masseter muscle transfer for smile reconstruction in facial paralysis: repositioning the origin and insertion.

PubMed

Matic, Damir B; Yoo, John

2012-08-01

The pedicled masseter muscle transfer (PMMT) is introduced as a new reconstructive option for dynamic smile restoration in patients with facial paralysis. The masseter muscle is detached from both its origin and insertion and transferred to a new position to imitate the function of the native zygomaticus major muscle. Part one of this study consisted of cadaveric dissections of 4 heads (eight sides) in order to determine whether the masseter muscle could be (a) pedicled solely by its dominant neurovascular bundle and (b) repositioned directly over the native zygomaticus major. The second part of the study consisted of clinical assessments in three patients in order to confirm the applicability of this muscle transfer. Commissure excursion and vector of contraction following PMMT were compared to the non-paralyzed side. In all eight sides, the masseter muscles were successfully isolated on their pedicle and transposed on top of and in-line with the ipsilateral zygomaticus major. The mean length of the masseter and its angle from Frankfurt's horizontal line after transposition compared favorably to the native zygomaticus major muscle. In the clinical cases, the mean commissure movements of the paralyzed and normal sides were 7 mm and 12 mm respectively. The mean angles of commissural movement for the paralyzed and normal sides were 62° and 59° respectively. The PMMT can be used as a dynamic reconstruction for patients with permanent facial paralysis. As we gain experience with the PMMT, it may be possible to use it as a first-line option for patients not eligible for free micro-neurovascular reconstruction. Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Similar Outcome After Colonic Pouch and Side-to-End Anastomosis in Low Anterior Resection for Rectal Cancer

PubMed Central

Machado, Mikael; Nygren, Jonas; Goldman, Sven; Ljungqvist, Olle

2003-01-01

Objectives To compare a colonic J-pouch or a side-to-end anastomosis after low-anterior resection for rectal cancer with regard to functional and surgical outcome. Summary Background Data: A complication after restorative rectal surgery with a straight anastomosis is low- anterior resection syndrome with a postoperatively deteriorated anorectal function. The colonic J-reservoir is sometimes used with the purpose of reducing these symptoms. An alternative method is to use a simple side-to-end anastomosis. Methods: One-hundred patients with rectal cancer undergoing total mesorectal excision and colo-anal anastomosis were randomized to receive either a colonic pouch or a side-to-end anastomosis using the descending colon. Surgical results and complications were recorded. Patients were followed with a functional evaluation at 6 and 12 months postoperatively. Results: Fifty patients were randomized to each group. Patient characteristics in both groups were very similar regarding age, gender, tumor level, and Dukes’ stages. A large proportion of the patients received short-term preoperative radiotherapy (78%). There was no significant difference in surgical outcome between the 2 techniques with respect to anastomotic height (4 cm), perioperative blood loss (500 ml), hospital stay (11 days), postoperative complications, reoperations or pelvic sepsis rates. Comparing functional results in the 2 study groups, only the ability to evacuate the bowel in <15 minutes at 6 months reached a significant difference in favor of the pouch procedure. Conclusions: The data from this study show that either a colonic J-pouch or a side-to-end anastomosis performed on the descending colon in low-anterior resection with total mesorectal excision are methods that can be used with similar expected functional and surgical results. PMID:12894014

Side Chain Engineering on Medium Bandgap Copolymers to Suppress Triplet Formation for High-Efficiency Polymer Solar Cells.

PubMed

Xue, Lingwei; Yang, Yankang; Xu, Jianqiu; Zhang, Chunfeng; Bin, Haijun; Zhang, Zhi-Guo; Qiu, Beibei; Li, Xiaojun; Sun, Chenkai; Gao, Liang; Yao, Jia; Chen, Xiaofeng; Yang, Yunxu; Xiao, Min; Li, Yongfang

2017-10-01

Suppression of carrier recombination is critically important in realizing high-efficiency polymer solar cells. Herein, it is demonstrated difluoro-substitution of thiophene conjugated side chain on donor polymer can suppress triplet formation for reducing carrier recombination. A new medium bandgap 2D-conjugated D-A copolymer J91 is designed and synthesized with bi(alkyl-difluorothienyl)-benzodithiophene as donor unit and fluorobenzotriazole as acceptor unit, for taking the advantages of the synergistic fluorination on the backbone and thiophene side chain. J91 demonstrates enhanced absorption, low-lying highest occupied molecular orbital energy level, and higher hole mobility, in comparison with its control polymer J52 without fluorination on the thiophene side chains. The transient absorption spectra indicate that J91 can suppress the triplet formation in its blend film with n-type organic semiconductor acceptor m-ITIC (3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone)-5,5,11,11-tetrakis(3-hexylphenyl)-dithieno[2,3-d:2,3'-d']-s-indaceno[1,2-b:5,6-b']-dithiophene). With these favorable properties, a higher power conversion efficiency of 11.63% with high V OC of 0.984 V and high J SC of 18.03 mA cm -2 is obtained for the polymer solar cells based on J91/m-ITIC with thermal annealing. The improved photovoltaic performance by thermal annealing is explained from the morphology change upon thermal annealing as revealed by photoinduced force microscopy. The results indicate that side chain engineering can provide a new solution to suppress carrier recombination toward high efficiency, thus deserves further attention. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reducing Aversion to Side Effects in Preventive Medical Treatment Decisions

ERIC Educational Resources Information Center

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

2007-01-01

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

Systematic identification of proteins that elicit drug side effects

PubMed Central

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

2013-01-01

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

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

PubMed

Fan, Jun; Yang, Jing; Jiang, Zhenran

2018-04-01

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

Engineering acyclic stereocontrol in the alkylation of vinylglycine-derived dianions: asymmetric synthesis of higher alpha-vinyl amino acids.

PubMed

Berkowitz, D B; McFadden, J M; Sloss, M K

2000-05-19

A generalizable synthesis of higher L-alpha-vinyl amino acids is presented. The strategy pursued here involves the introduction of the amino acid side chain via the alkylation of a chiral, vinylglycine-derived dianionic dienolate, bearing the (-)-8-(beta-naphthyl)menthyl (d'Angelo) auxiliary. A model is presented that postulates a favored "exo-entended" conformation for this dienolate, leading to C(alpha)-alkylation at the si face. The model invokes internal amidate chelation to control ester enolate geometry and soft-soft interactions between the polarizable beta-naphthyl ring of the auxiliary and the extended pi-system of the dienolate to shield the re face. Heats of formation for four conformers of this dianion were calculated for their semiempirical optimized geometries (PM3). The results support the notion that in these vinylglycine-derived dianionic dienolates, "exo" conformations are considerable lower in energy than their "endo" counterparts, with the "exo-entended" conformation being most favorable. In fact, the d'Angelo auxiliary gives a greater degree of acyclic stereocontrol in this system when compared with the (-)-8-phenylmenthyl (Corey) and trans-2-(beta-naphthyl)cyclohexyl auxiliaries, using isobutyl iodide and benzyl bromide as model electrophiles. These dianions are generated from the corresponding dehydrobutyrine esters via sequential deprotonation with LDA and n-BuLi (2 equiv). When alkylations are carried out at -78 degrees C in THF-HMPA, they proceed in 65-81% yields, with both regiocontrol (deconjugative alpha-alkylation is preferred over gamma-alkylation) and a great degree of acyclic stereocontrol [91:9 to >/=98:2 diastereomeric ratios (10 examples)]. The auxiliary may be recovered in high yield (generally 90%) using a modification of Gassman's "anhydrous hydroxide" conditions, in which considerably higher temperatures are employed. Among the side chains introduced directly are those of butyrine, leucine, ornithine, phenylalanine, aspartate, valine, and norvaline. The lysine side chain is elaborated via a 4-step sequence from the alkylation product obtained with 1-chloro-4-iodobutane as electrophile. Importantly, to our knowledge, this work represents the first asymmetric synthesis of L-alpha-vinyl analogues of m-tyrosine, ornithine, and lysine, known time-dependent inhibitors for amino acid decarboxylases.

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

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

PubMed

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

2010-12-01

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

Benefits of remote real-time side-effect monitoring systems for patients receiving cancer treatment.

PubMed

Kofoed, Sarah; Breen, Sibilah; Gough, Karla; Aranda, Sanchia

2012-03-05

In Australia, the incidence of cancer diagnoses is rising along with an aging population. Cancer treatments, such as chemotherapy, are increasingly being provided in the ambulatory care setting. Cancer treatments are commonly associated with distressing and serious side-effects and patients often struggle to manage these themselves without specialized real-time support. Unlike chronic disease populations, few systems for the remote real-time monitoring of cancer patients have been reported. However, several prototype systems have been developed and have received favorable reports. This review aimed to identify and detail systems that reported statistical analyses of changes in patient clinical outcomes, health care system usage or health economic analyses. Five papers were identified that met these criteria. There was wide variation in the design of the monitoring systems in terms of data input method, clinician alerting and response, groups of patients targeted and clinical outcomes measured. The majority of studies had significant methodological weaknesses. These included no control group comparisons, small sample sizes, poor documentation of clinical interventions or measures of adherence to the monitoring systems. In spite of the limitations, promising results emerged in terms of improved clinical outcomes (e.g. pain, depression, fatigue). Health care system usage was assessed in two papers with inconsistent results. No studies included health economic analyses. The diversity in systems described, outcomes measured and methodological issues all limited between-study comparisons. Given the acceptability of remote monitoring and the promising outcomes from the few studies analyzing patient or health care system outcomes, future research is needed to rigorously trial these systems to enable greater patient support and safety in the ambulatory setting.

Opioid Rotation in Cancer Pain Treatment.

PubMed

Schuster, Michael; Bayer, Oliver; Heid, Florian; Laufenberg-Feldmann, Rita

2018-03-02

Rotating several different WHO level III opioid drugs is a therapeutic option for patients with chronic cancer-related pain who suffer from inadequate analgesia and/or intolerable side effects. The evidence favoring opioid rotation is controversial, and the current guidelines in Germany and other countries contain only weak recommendations for it. This review is based on pertinent publications retrieved by a systematic review of the literature on opioid rotation for adult patients with chronic cancerrelated pain who are regularly taking WHO level III opioids by the oral or trans - dermal route. 9 individual studies involving a total of 725 patients were included in the analysis, and 3 previous systematic reviews of studies involving a total of 2296 patients were also analyzed. Morphine, oxycodone, fentanyl, hydromorphone, and buprenorphine were used as first-line opioid drugs, and hydromorphone, bupre - norphine, tapentadol, fentanyl, morphine, oxymorphone, and methadone were used as second-line opioid drugs. In all of the studies, pain control was achieved for 14 days after each rotation. In most of them, the dose of the new drug introduced in each rotation needed to be increased above the dose initially calculated from a rotation ratio, with the exception of rotations to methadone. The frequency of side effects was only rarely lessened, but patients largely considered the result of opioid rotation to be positive. No particular opioid drug was found to be best. Opioid rotation can improve analgesia and patient satisfaction. The success of opioid rotation appears to depend on the magnitude of the initial dose, among other factors. Tables of equianalgesic doses should be considered no more than a rough guide for determining the dose of the new drug. Rotations to methadone should be carried out under clinical supervision in experienced hands.

Pharmacokinetics of Intranasal Scopolamine Gel Formulation (Inscop)

NASA Technical Reports Server (NTRS)

Boyd, Jason L.; Du, Brian; Daniels, Vernie; Simmons, Rita; Buckey, Jay; Putcha, Lakshmi

2009-01-01

Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during early flight days of space missions. Orally administered scopolamine is commonly used by astronauts to prevent SMS. Bioavailability of oral (PO) SMS medications is often low and highly variable. Intranasal (IN) administration of medications achieves higher and more reliable bioavailability than from an equivalent PO dose. Methods: To test the safety and reliability of INSCOP, two clinical studies were performed, a dose escalation study and a comparison study administering INSCOP during normal ambulation and head down tilt bedrest. Efficacy was evaluated by testing INSCOP with two, different motion sickness inducing paradigms. Results: Preliminary results indicate that INSCOP demonstrates linear pharmacokinetics and a low side effect profile. In head down tilt bedrest, relative bioavailability of INSCOP was increased for females at both doses (0.2 and 0.4 mg) and for males at the higher dose (0.4 mg) but is reduced at the lower dose (0.2 mg) compared to normal ambulation. INSCOP displays gender specific differences during ABR. One of the treatment efficacy trials conducted at Dartmouth Hitchcock Medical Center demonstrated that INSCOP is efficacious at both doses (0.2 and 0.4 mg) in suppressing motion sickness symptoms as indicated by longer chair ride times with INSCOP administration than with placebo, and efficacy increases with dose. Similar results were seen using another motion sickness simulator, the motion simulator dome, at the Naval Aerospace Medical Research Laboratory, with significantly increased time in the dome in motion-susceptible subjects when using INSCOP compared to untreated controls. Conclusion: Higher bioavailability, linear pharmacokinetics, a low incidence of side effects, and a favorable efficacy profile make INSCOP a desirable formulation for prophylactic and rescue treatment of astronauts in space and military personnel on duty.

A Phase III Study of Conventional Radiation Therapy Plus Thalidomide Versus Conventional Radiation Therapy for Multiple Brain Metastases (RTOG 0118)

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

Knisely, Jonathan P.S.; Berkey, Brian; Chakravarti, Arnab

2008-05-01

Purpose: To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery. Patients and Methods: Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints includedmore » overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines. Results: Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects. Conclusion: Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects.« less

Family planning decisions, perceptions and gender dynamics among couples in Mwanza, Tanzania: a qualitative study

PubMed Central

2013-01-01

Background Contraceptive use is low in developing countries which are still largely driven by male dominated culture and patriarchal values. This study explored family planning (FP) decisions, perceptions and gender dynamics among couples in Mwanza region of Tanzania. Methods Twelve focus group discussions and six in-depth interviews were used to collect information from married or cohabiting males and females aged 18–49. The participants were purposively selected. Qualitative methods were used to explore family planning decisions, perceptions and gender dynamics among couples. A guide with questions related to family planning perceptions, decisions and gender dynamics was used. The discussions and interviews were tape-recorded, transcribed verbatim and analyzed manually and subjected to content analysis. Results Four themes emerged during the study. First, “risks and costs” which refer to the side effects of FP methods and the treatment of side -effects as well as the costs inherit in being labeled as an unfaithful spouse. Second, “male involvement” as men showed little interest in participating in family planning issues. However, the same men were mentioned as key decision-makers even on the number of children a couple should have and the child spacing of these children. Third, “gender relations and communication” as participants indicated that few women participated in decision-making on family planning and the number of children to have. Fourth, “urban–rural differences”, life in rural favoring having more children than urban areas therefore, the value of children depended on the place of residence. Conclusion Family Planning programs should adapt the promotion of communication as well as joint decision-making on FP among couples as a strategy aimed at enhancing FP use. PMID:23721196

Coronally advanced flap and connective tissue graft with or without plasma rich in growth factors (PRGF) in treatment of gingival recession

PubMed Central

Jenabian, Niloofar; Motallebnejad, Mina; Zahedi, Ehsan; Angelov, Nikola

2018-01-01

Background Several researchers have tried to improve the results of gingival recession treatment techniques. One of the methods is to use growth factors The present study was undertaken to evaluate the effect of CAF (coronally advanced flap) + CTG (connective tissue graft) + PRGF (plasma rich in growth factors) in the treatment of Miller Class I buccal gingival recession. Material and Methods Twenty-two teeth with Miller Class I gingival recession in 6 patients 26 ‒ 47 years of age were included in a split-mouth designed randomized controlled trial (RCT). In each patient, one side was treated with CAF + CTG + PRGF (test) and the other side was treated with CAF + CTG (control). The following parameters were measured before surgery and up to 6 months after surgery on the mid-buccal surface of the tooth: keratinized tissue width (KTW), clinical attachment level (CAL), probing depth (PD), vertical recession depth (VRD), recession depth (RD), gingival thickness (GT), root coverage in percentage (RC%) and the distance between the CEJ and mucogingival junction (MGJL). Data were analyzed with paired t-test and repeated measures ANOVA. Results After 6 months noticeable improvements were observed in both groups in all the variables measured except for PD; however, the differences between the two groups were not significant. RC% was 80 ± 25% and 67 ± 28% in the test and control groups, respectively, after 6 months. Conclusions Both CAF + CTG + PRGF and CAF + CTG treatment modalities resulted in favorable root coverage; however, the addition of PRGF added no measurable significant effect. Key words:Connective tissue graft, dental root coverage, gingival recession, growth factors, mucogingival surgery, periodontal plastic surgery. PMID:29849966

Coronally advanced flap and connective tissue graft with or without plasma rich in growth factors (PRGF) in treatment of gingival recession.

PubMed

Jenabian, Niloofar; Motallebnejad, Mina; Zahedi, Ehsan; Sarmast, Nima D; Angelov, Nikola

2018-05-01

Several researchers have tried to improve the results of gingival recession treatment techniques. One of the methods is to use growth factors The present study was undertaken to evaluate the effect of CAF (coronally advanced flap) + CTG (connective tissue graft) + PRGF (plasma rich in growth factors) in the treatment of Miller Class I buccal gingival recession. Twenty-two teeth with Miller Class I gingival recession in 6 patients 26 ‒ 47 years of age were included in a split-mouth designed randomized controlled trial (RCT). In each patient, one side was treated with CAF + CTG + PRGF (test) and the other side was treated with CAF + CTG (control). The following parameters were measured before surgery and up to 6 months after surgery on the mid-buccal surface of the tooth: keratinized tissue width (KTW), clinical attachment level (CAL), probing depth (PD), vertical recession depth (VRD), recession depth (RD), gingival thickness (GT), root coverage in percentage (RC%) and the distance between the CEJ and mucogingival junction (MGJL). Data were analyzed with paired t-test and repeated measures ANOVA. After 6 months noticeable improvements were observed in both groups in all the variables measured except for PD; however, the differences between the two groups were not significant. RC% was 80 ± 25% and 67 ± 28% in the test and control groups, respectively, after 6 months. Both CAF + CTG + PRGF and CAF + CTG treatment modalities resulted in favorable root coverage; however, the addition of PRGF added no measurable significant effect. Key words: Connective tissue graft, dental root coverage, gingival recession, growth factors, mucogingival surgery, periodontal plastic surgery.

HFSRT of the resection cavity in patients with brain metastases.

PubMed

Specht, Hanno M; Kessel, Kerstin A; Oechsner, Markus; Meyer, Bernhard; Zimmer, Claus; Combs, Stephanie E

2016-06-01

Aim of this single center, retrospective study was to assess the efficacy and safety of linear accelerator-based hypofractionated stereotactic radiotherapy (HFSRT) to the resection cavity of brain metastases after surgical resection. Local control (LC), locoregional control (LRC = new brain metastases outside of the treatment volume), overall survival (OS) as well as acute and late toxicity were evaluated. 46 patients with large (> 3 cm) or symptomatic brain metastases were treated with HFSRT. Median resection cavity volume was 14.16 cm(3) (range 1.44-38.68 cm(3)) and median planning target volume (PTV) was 26.19 cm(3) (range 3.45-63.97 cm(3)). Patients were treated with 35 Gy in 7 fractions prescribed to the 95-100 % isodose line in a stereotactic treatment setup. LC and LRC were assessed by follow-up magnetic resonance imaging. The 1-year LC rate was 88 % and LRC was 48 %; 57% of all patients showed cranial progression after HFSRT (4% local, 44% locoregional, 9% local and locoregional). The median follow-up was 19 months; median OS for the whole cohort was 25 months. Tumor histology and recursive partitioning analysis score were significant predictors for OS. HFSRT was tolerated well without any severe acute side effects > grade 2 according to CTCAE criteria. HFSRT after surgical resection of brain metastases was tolerated well without any severe acute side effects and led to excellent LC and a favorable OS. Since more than half of the patients showed cranial progression after local irradiation of the resection cavity, close patient follow-up is warranted. A prospective evaluation in clinical trials is currently being performed.

Multiple Non-Equivalent Interfaces Mediate Direct Activation of GABAA Receptors by Propofol.

PubMed

Eaton, Megan M; Germann, Allison L; Arora, Ruby; Cao, Lily Q; Gao, Xiaoyi; Shin, Daniel J; Wu, Albert; Chiara, David C; Cohen, Jonathan B; Steinbach, Joe Henry; Evers, Alex S; Akk, Gustav

2016-01-01

Propofol is a sedative agent that at clinical concentrations acts by allosterically activating or potentiating the γ-aminobutyric acid type A (GABAA) receptor. Mutational, modeling, and photolabeling studies with propofol and its analogues have identified potential interaction sites in the transmembrane domain of the receptor. At the &quot;+&quot; of the β subunit, in the β-α interface, meta-azipropofol labels the M286 residue in the third transmembrane domain. Substitution of this residue with tryptophan results in loss of potentiation by propofol. At the &quot;-&quot; side of the β subunit, in the α-β interface (or β-β interface, in the case of homomeric β receptors), ortho-propofol diazirine labels the H267 residue in the second transmembrane domain. Structural modeling indicates that the β(H267) residue lines a cavity that docks propofol with favorable interaction energy. We used two-electrode voltage clamp to determine the functional effects of mutations to the "+" and "-" sides of the β subunit on activation of the α1β3 GABAA receptor by propofol. We found that while the individual mutations had a small effect, the combination of the M286W mutation with tryptophan mutations of selected residues at the α-β interface leads to strong reduction in gating efficacy for propofol. We conclude that α1β3 GABAA receptors can be activated by propofol interactions with the β-β, α-β, and β-α interfaces, where distinct, non-equivalent regions control channel gating. Any interface can mediate activation, hence substitutions at all interfaces are required for loss of activation by propofol.