Assessing the potential and side effects of ocean albedo modification in the Arctic

NASA Astrophysics Data System (ADS)

Mengis, N.; Oschlies, A.; Keller, D. P.; Martin, T.

2015-12-01

The ice albedo feedbacks in the Arctic are a key factor of the positive feedback mechanisms, which amplify climate change in the high northern latitudes. This study assesses the potential and side effects of an idealised Arctic ocean albedo modification (AOAM) experiment under varying emissions scenarios. A first finding is the fact that the decreasing trend in the Arctic summer sea ice extent could only be offset rather than reversed by the implementation of AOAM under increasing atmospheric CO2 emissions. What becomes evident in this study is that the Earth system regulates its internal heat budgets. Therefore a local cooling at the high northern latitudes causes compensatory heat fluxes in the atmosphere and the ocean. Meaning that firstly, the effectiveness of local scale climate intervention will, in the long term, be lowered by these compensatory fluxes and secondly that there are consequences, such as the subsurface warming signal found in this study, which are unexpected and unintended.

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

PubMed

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

2004-01-01

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

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

PubMed

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

2015-01-14

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

Abnormal viscoelastic behavior of side-chain liquid-crystal polymers

NASA Astrophysics Data System (ADS)

Gallani, J. L.; Hilliou, L.; Martinoty, P.; Keller, P.

1994-03-01

We show that, contrary to what is commonly believed, the isotropic phase of side-chain liquid-crystal polymers has viscoelastic properties which are totally different from those of ordinary flexible melt polymers. The results can be explained by the existence of a transient network created by the dynamic association of mesogenic groups belonging to different chains. The extremely high sensitivity of the compound to the state of the surfaces with which it is in contact offers us an unexpected method of studying surface states.

The retention of lacosamide in patients with epilepsy and intellectual disability in three specialised institutions.

PubMed

Brenner, J; Majoie, H J M; van Beek, S; Carpay, J A

2017-11-01

We describe the effectiveness of lacosamide as adjunctive therapy in patients with epilepsy and an intellectual disability. This information is relevant, as few data exist pertaining to this population with a high prevalence of (intractable) epilepsy. We performed a retrospective study in three specialised institutions. Inclusion criteria were (1) focal onset or symptomatic generalized (2) therapy-resistant epilepsy, (3) intellectual disability and (4) residence in a care-facility for people with intellectual disabilities (PWID). The primary outcome variables were the retention rates of lacosamide, estimated through Kaplan-Meier survival analysis. Secondary outcomes were reported seizure control, side effects and clinical factors influencing discontinuation. One hundred and thirty-two patients were included. The median retention time of lacosamide in our cohort was four years. The estimated one-, two- and three-year retention rates of lacosamide were 64%, 57% and 56% respectively. Severity of intellectual disability and seizure type did not influence whether lacosamide was continued. In 48.5% of patients, a reduction of seizure activity was reported. Side effects were at least part of the reason for discontinuing treatment in 26.5% of all patients. Common side effects were tiredness/somnolence (in 30.3%), aggression/agitation (24.2%), and instable gait (15.2%). Five deaths during follow-up were considered unlikely to be related to the use of lacosamide. One patient died unexpectedly within two months of treatment onset, probably this was a case of SUDEP. These retention rates of lacosamide in PWID are similar to rates of previously registered anti-epileptic drugs in PWID. Behavioural side effects were noted in a high proportion compared to the general literature on lacosamide. Other side effects were in line with this literature. Lacosamide seems effective and safe for PWID and refractory epilepsy. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-01-01

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

The human dark side: evolutionary psychology and original sin.

PubMed

Lee, Joseph; Theol, M

2014-04-01

Human nature has a dark side, something important to religions. Evolutionary psychology has been used to illuminate the human shadow side, although as a discipline it has attracted criticism. This article seeks to examine the evolutionary psychology's understanding of human nature and to propose an unexpected dialog with an enduring account of human evil known as original sin. Two cases are briefly considered: murder and rape. To further the exchange, numerous theoretical and methodological criticisms and replies of evolutionary psychology are explored jointly with original sin. Evolutionary psychology can partner with original sin since they share some theoretical likenesses and together they offer insights into the nature of what it means to be human.

Teacher ratings of resilience and peer relationships of preschoolers whose fathers died unexpectedly.

PubMed

Gülay Ogelman, Hülya; Gündoğan, Aysun; Erten Sarıkaya, Hatice; Erol, Ahmet

2016-08-01

This study endeavors to compare resilience and peer relationships of children who lost their fathers in a major mining accident in Soma with those who did not. Teachers rated 51 preschoolers whose fathers died, and 53 preschoolers whose fathers were alive. On the negative side, bereaved children had lower resilience and higher exclusion; on the positive side, bereaved children had lower peer victimization and higher prosocial behavior. Death of fathers is associated with lower resilience and more exclusion among young children, but others treat them better as well.

The "Simmie" Side of Life: Old Order Amish Youths' Affective Response to Culturally Prescribed Deviance.

ERIC Educational Resources Information Center

Reiling, Denise M.

2002-01-01

Analyzed the counterintuitive affective response Old Order Amish youth make to unique cultural prescriptions for adolescent deviance (constructed by adult Amish culture). Interview data supported the basic principles of Terror Management Theory in an unexpected, indirect fashion. Rather than functioning as a specialized cultural-anxiety buffer…

[Animal welfare and corporate welfare in pharmaceutical R&D - the future of third-party assessment].

PubMed

Suzuki, Makoto

For research and development (R&D) of new drugs, animal experimentation is indispensable, and research institutes, pharmaceutical companies, or contract research organizations routinely conduct preclinical studies of efficacy, safety, or metabolism using laboratory animals. However, animal experimentation entails some organizational risks. One is the suspension of R&D of a new drug, because in the course of clinical studies it becomes apparent that the drug has limited efficacy, unexpected side effects, and/or unexpected metabolites. Another risk is damage to the company image by development of an unfavorable reputation. Society has accepted animal experimentation as a necessary evil, but if such experimentation is not conducted with adequate concern for animal welfare, social sanctions will against that institute, company or organization will result. Once this happens, it is difficult to recover a good public image. Therefore, pharmaceutical companies must conduct animal experiments so as to obtain highly useful data without sacrificing public favor. One way to maintain a good reputation is through third-party accreditation, which verifies that the institute, company or organization and its researchers value animal welfare appropriately.

Grain refinement of high strength steels to improve cryogenic toughness

NASA Technical Reports Server (NTRS)

Rush, H. F.

1985-01-01

Grain-refining techniques using multistep heat treatments to reduce the grain size of five commercial high-strength steels were investigated. The goal of this investigation was to improve the low-temperature toughness as measured by Charpy V-notch impact test without a significant loss in tensile strength. The grain size of four of five alloys investigated was successfully reduced up to 1/10 of original size or smaller with increases in Charpy impact energy of 50 to 180 percent at -320 F. Tensile properties were reduced from 0 to 25 percent for the various alloys tested. An unexpected but highly beneficial side effect from grain refining was improved machinability.

Design, development, mechanistic elucidation, and rational optimization of a tandem Ireland Claisen/Cope rearrangement reaction for rapid access to the (iso)cyclocitrinol core.

PubMed

Plummer, Christopher W; Wei, Carolyn S; Yozwiak, Carrie E; Soheili, Arash; Smithback, Sara O; Leighton, James L

2014-07-16

An approach to the synthesis of the (iso)cyclocitrinol core structure is described. The key step is a tandem Ireland Claisen/Cope rearrangement sequence, wherein the Ireland Claisen rearrangement effects ring contraction to a strained 10-membered ring, and that strain in turn drives the Cope rearrangement under unusually mild thermal conditions. A major side product was identified as resulting from an unexpected and remarkably facile [1,3]-sigmatropic rearrangement, and a tactic to disfavor the [1,3] pathway and increase the efficiency of the tandem reaction was rationally devised.

Bending effects on magnetic properties of nearly zeromagnetostrictive Co-rich amorphous ribbons

NASA Astrophysics Data System (ADS)

Buttino, G.; Cecchetti, A.; Poppi, M.; Zini, G.

1991-06-01

In as received nearly zeromagnetostriction Co-based Metglas, magnetic properties in low magnetic field are anomalously affected by bending stresses. The behavior of Co-based alloys, in particular 2714A Metglas, is here compared with that of Fe-rich Metglas for which λ s ranges between 10 × 10 -6 and 35 × 10 -6. The specimens here analyzed are in the form of flat ribbons and tape-wound toroids with different radii. In 2714A Metglas, the bending effects on the ac initial permeability are unexpectedly large and depend on the way of winding the ribbons. These results emphasize a significant and different role of the two ribbon sides in determining the magnetomechanical properties of Co-based alloys.

Incorporating uncertainty into medical decision making: an approach to unexpected test results.

PubMed

Bianchi, Matt T; Alexander, Brian M; Cash, Sydney S

2009-01-01

The utility of diagnostic tests derives from the ability to translate the population concepts of sensitivity and specificity into information that will be useful for the individual patient: the predictive value of the result. As the array of available diagnostic testing broadens, there is a temptation to de-emphasize history and physical findings and defer to the objective rigor of technology. However, diagnostic test interpretation is not always straightforward. One significant barrier to routine use of probability-based test interpretation is the uncertainty inherent in pretest probability estimation, the critical first step of Bayesian reasoning. The context in which this uncertainty presents the greatest challenge is when test results oppose clinical judgment. It is this situation when decision support would be most helpful. The authors propose a simple graphical approach that incorporates uncertainty in pretest probability and has specific application to the interpretation of unexpected results. This method quantitatively demonstrates how uncertainty in disease probability may be amplified when test results are unexpected (opposing clinical judgment), even for tests with high sensitivity and specificity. The authors provide a simple nomogram for determining whether an unexpected test result suggests that one should "switch diagnostic sides.'' This graphical framework overcomes the limitation of pretest probability uncertainty in Bayesian analysis and guides decision making when it is most challenging: interpretation of unexpected test results.

[Regulation on EGFR function via its interacting proteins and its potential application].

PubMed

Zheng, Jun-Fang; Chen, Hui-Min; He, Jun-Qi

2013-12-01

Epidermal growth factor receptor (EGFR) is imptortant for cell activities, oncogenesis and cell migration, and EGFR inhibitor can treat cancer efficiently, but its side effects, for example, in skin, limited its usage. On the other hand, EGFR interacting proteins may also lead to oncogenesis and its interacting protein as drug targets can avoid cutaneous side effect, which implies possibly a better outcome and life quality of cancer patients. For the multiple EGFR interaction proteins, B1R enhances Erk/MAPK signaling, while PTPN12, Kek1, CEACAM1 and NHERF repress Erk/MAPK signaling. CaM may alter charge of EGFR juxamembrane domain and regulate activation of PI3K/Akt and PLC-gamma/PKC. STAT1, STAT5b are widely thought to be activated by EGFR, while there is unexpectedly inhibiting sequence within EGFR to repress the activity of STATs. LRIG1 and ACK1 enhance the internalization and degration of EGFR, while NHERF and HIP1 repress it. In this article, proteins interacting with EGFR, their interacting sites and their regulation on EGFR signal transduction will be reviewed.

Theoretical mechanics: crowd synchrony on the Millennium Bridge.

PubMed

Strogatz, Steven H; Abrams, Daniel M; McRobie, Allan; Eckhardt, Bruno; Ott, Edward

2005-11-03

Soon after the crowd streamed on to London's Millennium Bridge on the day it opened, the bridge started to sway from side to side: many pedestrians fell spontaneously into step with the bridge's vibrations, inadvertently amplifying them. Here we model this unexpected and now notorious phenomenon--which was not due to the bridge's innovative design as was first thought--by adapting ideas originally developed to describe the collective synchronization of biological oscillators such as neurons and fireflies. Our approach should help engineers to estimate the damping needed to stabilize other exceptionally crowded footbridges against synchronous lateral excitation by pedestrians.

Muscle activation in young men during a lower limb aquatic resistance exercise with different devices.

PubMed

Borreani, Sebastien; Colado, Juan Carlos; Furio, Josep; Martin, Fernando; Tella, Víctor

2014-05-01

Little research has been reported on the effects of using different devices with resistance exercises in a water environment. This study compared muscular activation of lower extremity and core muscles during leg adduction performed at maximum velocity with drag and floating devices of different sizes. A total of 24 young men (mean age 23.20 ± 1.18 years) performed 3 repetitions of leg adduction at maximum velocity using 4 different devices (ie, large/small and drag/floating). The maximum amplitude of the electromyographic root mean square of the adductor longus, rectus abdominis, external oblique on the dominant side, external oblique on the nondominant side, and erector lumbar spinae were recorded. Electromyographic signals were normalized to the maximum voluntary isometric contraction (MVIC). Unexpectedly, no significant (P > 0.05) differences were found in the neuromuscular responses among the different devices used; the average activation of agonist muscle adequate for neuromuscular conditioning was 40.95% of MVIC. In addition, external oblique activation is greater on the contralateral side to stabilize the body (average, 151.74%; P < 0.05). Therefore, if maximum muscle activation is required, the kind of device is not relevant. Thus, the choice should be based on economic factors.

Cocrystal Structures of Primed Side-Extending α-Ketoamide Inhibitors Reveal Novel Calpain-Inhibitor Aromatic Interactions

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

Qian,J.; Cuerrier, D.; Davies, P.

Calpains are intracellular cysteine proteases that catalyze the cleavage of target proteins in response to Ca2+ signaling. When Ca2+ homeostasis is disrupted, calpain overactivation causes unregulated proteolysis, which can contribute to diseases such as postischemic injury and cataract formation. Potent calpain inhibitors exist, but of these many cross-react with other cysteine proteases and will need modification to specifically target calpain. Here, we present crystal structures of rat calpain 1 protease core ({mu}I-II) bound to two a-ketoamide-based calpain inhibitors containing adenyl and piperazyl primed-side extensions. An unexpected aromatic-stacking interaction is observed between the primed-side adenine moiety and the Trp298 side chain.more » This interaction increased the potency of the inhibitor toward {mu}I-II and heterodimeric m-calpain. Moreover, stacking orients the adenine such that it can be used as a scaffold for designing novel primed-side address regions, which could be incorporated into future inhibitors to enhance their calpain specificity.« less

New pyridinium-based fluorescent dyes: A comparison of symmetry and side-group effects on G-Quadruplex DNA binding selectivity and application in live cell imaging.

PubMed

Lu, Yu-Jing; Hu, Dong-Ping; Zhang, Kun; Wong, Wing-Leung; Chow, Cheuk-Fai

2016-07-15

A series of C1-, C2-and C3-symmetric pyridinium conjugates with different styrene-like side groups were synthesized and were utilized as G-quadruplex selective fluorescent probes. The new compounds were well-characterized. Their selectivity, sensitivity, and stability towards G-quadruplex were studied by fluorescence titration, native PAGE experiments, FRET and circular dichroism (CD) analyses. These new compounds investigated in the fluorescence assays were preferentially bound with G-quadruplex DNA compared with other type of nucleic acids and it is fascinating to realize the effects of molecular symmetry and associated side groups showing unexpectedly great influence on the fluorescent signal enhancement for the discrimination of G-quadruplexes DNA from other nucleic acids. This may correlate with the pocket symmetry and shape of the G-quadruplex DNA inherently. Among the compounds, a C2-symmetric dye (2,6-bis-((E)-2-(1H-indol-3-yl)-vinyl)-1-methylpyridin-1-ium iodide) with indolyl-groups substituted was screened out from the series giving the best selectivity and sensitivity towards G-quadruplexes DNA, particularly telo21, due to its high equilibrium binding constant (K=2.17×10(5)M(-1)). In addition, the limit of detection (LOD) of the dye to determine telo21 DNA in bioassays was found as low as 33nM. The results of the study give insight and certain crucial factors, such as molecular symmetry and the associated side groups, on developing of effective fluorescent dyes for G-quadruplex DNA applications including G-quadruplex structure stabilization, biosensing and clinical applications. The compound was also demonstrated as a very selective G-quadruplex fluorescent agent for living cell staining and imaging. Copyright © 2016 Elsevier B.V. All rights reserved.

Structural differences between glycosylated, disulfide-linked heterodimeric Knob-into-Hole Fc fragment and its homodimeric Knob-Knob and Hole-Hole side products.

PubMed

Kuglstatter, A; Stihle, M; Neumann, C; Müller, C; Schaefer, W; Klein, C; Benz, J

2017-09-01

An increasing number of bispecific therapeutic antibodies are progressing through clinical development. The Knob-into-Hole (KiH) technology uses complementary mutations in the CH3 region of the antibody Fc fragment to achieve heavy chain heterodimerization. Here we describe the X-ray crystal structures of glycosylated and disulfide-engineered heterodimeric KiH Fc fragment and its homodimeric Knob-Knob and Hole-Hole side products. The heterodimer structure confirms the KiH design principle and supports the hypothesis that glycosylation stabilizes a closed Fc conformation. Both homodimer structures show parallel Fc fragment architectures, in contrast to recently reported crystal structures of the corresponding aglycosylated Fc fragments which in the absence of disulfide mutations show an unexpected antiparallel arrangement. The glycosylated Knob-Knob Fc fragment is destabilized as indicated by variability in the relative orientation of its CH3 domains. The glycosylated Hole-Hole Fc fragment shows an unexpected intermolecular disulfide bond via the introduced Y349C Hole mutation which results in a large CH3 domain shift and a new CH3-CH3 interface. The crystal structures of glycosylated, disulfide-linked KiH Fc fragment and its Knob-Knob and Hole-Hole side products reported here will facilitate further design of highly efficient antibody heterodimerization strategies. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Rate of Hanger Reflex Occurrence: Unexpected Head Rotation on Fronto-temporal Head Compression

PubMed Central

ASAHI, Takashi; SATO, Michi; KAJIMOTO, Hiroyuki; KOH, Masaki; KASHIWAZAKI, Daina; KURODA, Satoshi

When the head is encircled with a wire clothes hanger and the unilateral fronto-temporal region is compressed, the head rotates unexpectedly. As the mechanism is unclear, however, we have temporarily named this phenomenon as the “hanger reflex.” We previously reported a case wherein this phenomenon was applied to treat cervical dystonia. Because little is known about this phenomenon, we determined how often this phenomenon is observed in healthy subjects. Study participants were 120 healthy Japanese adults (60 men and 60 women) aged 19–65 years. A wire clothes hanger was applied to each subject’s head. The longer side of the hanger was attached over the volunteer’s fronto-temporal regions on both sides of the head in succession (i.e., two applications per volunteer). We evaluated whether the subjects felt the sensation of head rotation by using a questionnaire. The sensation of head rotation was observed in 95.8% of subjects. There were five non-responders (4.2%). In 85.4% of the trials, head rotation was observed in the direction that coincided with the side compressed by the hanger. There were no differences in responses between genders. The incident rate of the hanger reflex was remarkably high and most likely represents a prevalent phenomenon in humans. The mechanism underlying the reflex remains unknown. Further research should be performed to elucidate the underlying causes of the hanger reflex, which represents a potential treatment for cervical dystonia. PMID:26119894

Ring-rearrangement metathesis of nitroso Diels-Alder cycloadducts.

PubMed

Vincent, Guillaume; Kouklovsky, Cyrille

2011-03-01

Strained nitroso Diels-Alder bicyclo[2.2.1] or [2.2.2] adducts functionalized with alkene side chains of diverse length undergo a ring-rearrangement metathesis process with external alkenes and Grubbs II or Hoveyda-Grubbs II ruthenium catalysts, under microwave irradiation or classical heating, to deliver cis-fused bicycles of various ring sizes, which contain a N-O bond. These scaffolds are of synthetic relevance for the generation of molecular diversity and to the total synthesis of alkaloids. The observation of unexpected reactions, such as epimerization or one-carbon homologation of the alkene side chain, is also reported. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Complex dynamics of semantic memory access in reading.

PubMed

Baggio, Giosué; Fonseca, André

2012-02-07

Understanding a word in context relies on a cascade of perceptual and conceptual processes, starting with modality-specific input decoding, and leading to the unification of the word's meaning into a discourse model. One critical cognitive event, turning a sensory stimulus into a meaningful linguistic sign, is the access of a semantic representation from memory. Little is known about the changes that activating a word's meaning brings about in cortical dynamics. We recorded the electroencephalogram (EEG) while participants read sentences that could contain a contextually unexpected word, such as 'cold' in 'In July it is very cold outside'. We reconstructed trajectories in phase space from single-trial EEG time series, and we applied three nonlinear measures of predictability and complexity to each side of the semantic access boundary, estimated as the onset time of the N400 effect evoked by critical words. Relative to controls, unexpected words were associated with larger prediction errors preceding the onset of the N400. Accessing the meaning of such words produced a phase transition to lower entropy states, in which cortical processing becomes more predictable and more regular. Our study sheds new light on the dynamics of information flow through interfaces between sensory and memory systems during language processing.

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.

Unexpected Events Induce Motor Slowing via a Brain Mechanism for Action-Stopping with Global Suppressive Effects

PubMed Central

Aron, Adam R.

2013-01-01

When an unexpected event occurs in everyday life (e.g., a car honking), one experiences a slowing down of ongoing action (e.g., of walking into the street). Motor slowing following unexpected events is a ubiquitous phenomenon, both in laboratory experiments as well as such everyday situations, yet the underlying mechanism is unknown. We hypothesized that unexpected events recruit the same inhibition network in the brain as does complete cancellation of an action (i.e., action-stopping). Using electroencephalography and independent component analysis in humans, we show that a brain signature of successful outright action-stopping also exhibits activity following unexpected events, and more so in blocks with greater motor slowing. Further, using transcranial magnetic stimulation to measure corticospinal excitability, we show that an unexpected event has a global motor suppressive effect, just like outright action-stopping. Thus, unexpected events recruit a common mechanism with outright action-stopping, moreover with global suppressive effects. These findings imply that we can now leverage the considerable extant knowledge of the neural architecture and functional properties of the stopping system to better understand the processing of unexpected events, including perhaps how they induce distraction via global suppression. PMID:24259571

Single-molecule spectroscopy of the unexpected collapse of an unfolded protein at low pH

NASA Astrophysics Data System (ADS)

Hofmann, Hagen; Nettels, Daniel; Schuler, Benjamin

2013-09-01

The dimensions of intrinsically disordered and unfolded proteins critically depend on the solution conditions, such as temperature, pH, ionic strength, and osmolyte or denarurant concentration. However, a quantitative understanding of how the complex combination of chain-chain and chain-solvent interactions is affected by the solvent is still missing. Here, we take a step towards this goal by investigating the combined effect of pH and denaturants on the dimensions of an unfolded protein. We use single-molecule fluorescence spectroscopy to extract the dimensions of unfolded cold shock protein (CspTm) in mixtures of the denaturants urea and guanidinium chloride (GdmCl) at neutral and acidic pH. Surprisingly, even though a change in pH from 7 to 2.9 increases the net charge of CspTm from -3.8 to +10.2, the radius of gyration of the chain is very similar under both conditions, indicating that protonation of acidic side chains at low pH results in additional hydrophobic interactions. We use a simple shared binding site model that describes the joint effect of urea and GdmCl, together with polyampholyte theory and an ion cloud model that includes the chemical free energy of counterion interactions and side chain protonation, to quantify this effect.

On the globality of motor suppression: unexpected events and their influence on behavior and cognition

PubMed Central

Wessel, Jan R.; Aron, Adam R.

2016-01-01

SUMMARY Unexpected events are part of everyday experience. They come in several varieties – action errors, unexpected action outcomes, and unexpected perceptual events – and they lead to motor slowing and cognitive distraction. While different varieties of unexpected events have been studied largely independently, and many different mechanisms are thought to explain their effects on action and cognition, we suggest a unifying theory. We propose that unexpected events recruit a fronto-basal-ganglia network for stopping. This network includes specific prefrontal cortical nodes and is posited to project to the subthalamic nucleus, with a putative global suppressive effect on basal-ganglia output. We argue that unexpected events interrupt action and impact cognition, partly at least, by recruiting this global suppressive network. This provides a common mechanistic basis for different types of unexpected events, links the literatures on motor inhibition, performance-monitoring, attention, and working memory, and is relevant for understanding clinical symptoms of distractibility and mental inflexibility. PMID:28103476

On the Globality of Motor Suppression: Unexpected Events and Their Influence on Behavior and Cognition.

PubMed

Wessel, Jan R; Aron, Adam R

2017-01-18

Unexpected events are part of everyday experience. They come in several varieties-action errors, unexpected action outcomes, and unexpected perceptual events-and they lead to motor slowing and cognitive distraction. While different varieties of unexpected events have been studied largely independently, and many different mechanisms are thought to explain their effects on action and cognition, we suggest a unifying theory. We propose that unexpected events recruit a fronto-basal-ganglia network for stopping. This network includes specific prefrontal cortical nodes and is posited to project to the subthalamic nucleus, with a putative global suppressive effect on basal-ganglia output. We argue that unexpected events interrupt action and impact cognition, partly at least, by recruiting this global suppressive network. This provides a common mechanistic basis for different types of unexpected events; links the literatures on motor inhibition, performance monitoring, attention, and working memory; and is relevant for understanding clinical symptoms of distractibility and mental inflexibility. Copyright © 2017 Elsevier Inc. All rights reserved.

Thermal relaxation and critical instability of near-critical fluid microchannel flow.

PubMed

Chen, Lin; Zhang, Xin-Rong; Okajima, Junnosuke; Maruyama, Shigenao

2013-04-01

We present two-dimensional numerical investigations of the temperature and velocity evolution of a pure near-critical fluid confined in microchannels. The fluid is subjected to two sides heating after it reached isothermal steady state. We focus on the abnormal behaviors of the near-critical fluid in response to the sudden imposed heat flux. New thermal-mechanical effects dominated by fluid instability originating from the boundary and local equilibrium process are reported. Near the microchannel boundaries, the instability grows very quickly and an unexpected vortex formation mode is identified when near-critical thermal-mechanical effect is interacting with the microchannel shear flow. The mechanism of the new kind of Kelvin-Helmholtz instability induced by boundary expansion and density stratification processes is also discussed in detail. This mechanism may bring about innovations in the field of microengineering.

Thermal relaxation and critical instability of near-critical fluid microchannel flow

NASA Astrophysics Data System (ADS)

Chen, Lin; Zhang, Xin-Rong; Okajima, Junnosuke; Maruyama, Shigenao

2013-04-01

We present two-dimensional numerical investigations of the temperature and velocity evolution of a pure near-critical fluid confined in microchannels. The fluid is subjected to two sides heating after it reached isothermal steady state. We focus on the abnormal behaviors of the near-critical fluid in response to the sudden imposed heat flux. New thermal-mechanical effects dominated by fluid instability originating from the boundary and local equilibrium process are reported. Near the microchannel boundaries, the instability grows very quickly and an unexpected vortex formation mode is identified when near-critical thermal-mechanical effect is interacting with the microchannel shear flow. The mechanism of the new kind of Kelvin-Helmholtz instability induced by boundary expansion and density stratification processes is also discussed in detail. This mechanism may bring about innovations in the field of microengineering.

[A case of advanced gastric cancer with multiple liver metastases completely responding long term to paclitaxel plus S-1 therapy].

PubMed

Kanou, Mikihiro; Kurisu, Yoshihiro; Akagi, Shinji; Tanaka, Tomoko; Toge, Kunio

2010-01-01

A 69-year-old man was admitted to our hospital with complaints of loss of appetite, fatigue and dysphasia. Upper gastroscopy revealed advanced gastric cancer. Abdominal CT suggested liver metastases. At first we thought the liver metastases has been completely resected, but we found multiple liver metastases unexpectedly. So only total gastric resection and liver biopsy were performed. The pathological diagnosis was metastatic carcinoma. Paclitaxel (PTX) and S-1 combination chemotherapy was started after operation and was continued for 42 courses. A CT scan showed a complete response, and he has been well without tumor re-growth ever since. The combination of PTX and S-1 not only may be an effective regimen for gastric cancer with liver metastases, but also can be used without side effects for a long time.

Gravitropism in Higher Plant Shoots 1

PubMed Central

Wheeler, Raymond M.; White, Rosemary G.; Salisbury, Frank B.

1986-01-01

Ethylene at 1.0 and 10.0 cubic centimeters per cubic meter decreased the rate of gravitropic bending in stems of cocklebur (Xanthium strumarium L.) and tomato (Lycopersicon esculentum Mill), but 0.1 cubic centimeter per cubic meter ethylene had little effect. Treating cocklebur plants with 1.0 millimolar aminoethoxyvinylglycine (AVG) (ethylene synthesis inhibitor) delayed stem bending compared with controls, but adding 0.1 cubic centimeter per cubic meter ethylene in the surrounding atmosphere (or applying 0.1% ethephon solution) partially restored the rate of bending of AVG-treated plants. Ethylene increases in bending stems, and AVG inhibits this. Virtually all newly synthesized ethylene appeared in bottom halves of horizontal stems, where ethylene concentrations were as much as 100 times those in upright stems or in top halves of horizontal stems. This was especially true when horizontal stems were physically restrained from bending. Ethylene might promote cell elongation in bottom tissues of a horizontal stem or indicate other factors there (e.g. a large amount of `functioning' auxin). Or top and bottom tissues may become differentially sensitive to ethylene. Auxin applied to one side of a vertical stem caused extreme bending away from that side; gibberellic acid, kinetin, and abscisic acid were without effect. Acidic ethephon solutions applied to one side of young seedlings of cocklebur, tomato, sunflower (Helianthus annuus L.), and soybean (Glycine max [L.] Merr.) caused bending away from that side, but neutral ethephon solutions did not cause bending. Buffered or unbuffered acid (HCl) caused similar bending. Neutral ethephon solutions produced typical ethylene symptoms (i.e. epinasty, inhibition of stem elongation). HCl or acidic ethephon applied to the top of horizontal stems caused downward bending, but these substances applied to the bottom of such stems inhibited growth and upward bending—an unexpected result. PMID:11539089

The role of nervus intermedius in side specific nasal responses.

PubMed

Nichani, J R; Malik, V; Woolford, T J; Ramsden, R T; Homer, J J

2010-03-02

Nervus intermedius (NI) dysfunction is common in patients who have had vestibular schwannoma (VS) surgery. Such patients have a unilateral parasympathetic-denervated nasal cavity. A number of side-specific nasal reflexes have been demonstrated in normal individuals, including hand cold-water immersion. It is not understood whether these reflexes have parasympathetic or sympathic efferent pathways. We aimed to evaluate the side specific nasal reflex to cold-water immersion in post-operative VS patients with NI dysfunction, in order to determine the nature of the efferent pathway of these reflexes. Side specific responses to cold-water immersion were tested by acoustic rhinometry in 10 normal individuals and 18 patients with NI dysfunction (proven by Schirmer s test) after VS surgery. A consistent pattern of ipsilateral congestion and contralateral decongestion after the cold-water immersion was seen in normal individuals (p smaller than 0.001). We found no consistent response in VS patients both ipsilateral and contralateral to the side of NI dysfunction. We confirm the consistent side-specific nasal reflexes to cold-water hand immersion in normal individuals. This is disturbed in patients with NI dysfunction. We have also shown unexpectantly that the contralateral side-specific reflex is disturbed in these patients. These data suggest that the reflex is parasympathetic and crosses the midline.

Creep life prediction of super heater coils used in coal based thermal power plants subjected to fly ash erosion and oxide scale formation

NASA Astrophysics Data System (ADS)

Srinivasan, P.; Kushwaha, Shashank

2018-04-01

Super heater coils of the coal based thermal power plants and subjected to severe operating conditions from both steam side and gas side. Formation of oxide scale due to prolonged service lead to temperature raise of the tube and erosion due to fly ash present in the combusted gases leads to tube thinning. Both these factors lead to creep rupture of the coils much before the designed service life. Failure of super heater coils during service of the boiler leads to power loss and huge monitory loss to the power plants. An attempt is made to model the creep damage caused to the super heater coils using heat transfer analysis tube thinning due to erosive wear of the tubes. Combined effects of these parameters are taken into consideration to predict the life of the super heater coils. This model may be used to estimate the life of the coils operating under the severe operating conditions to prevent the unexpected failure of the coils.

Characterizing the Lateral Border of the Frontalis for Safe and Effective Injection of Botulinum Toxin.

PubMed

Choi, You-Jin; Won, Sung-Yoon; Lee, Jae-Gi; Hu, Kyung-Seok; Kim, Sung-Taek; Tansatit, Tanvaa; Kim, Hee-Jin

2016-03-01

The forehead is a common site for injection of botulinum neurotoxin type A (BoNT-A) to treat hyperactive facial muscles. Unexpected side effects of BoNT-A injection may occur because the anatomy of the forehead musculature is not fully characterized. The authors described the lateral border of the frontalis in terms of facial landmarks and reference lines to determine the safest and most effective forehead injection sites for BoNT-A. The hemifaces of 49 embalmed adult Korean cadavers were dissected in a morphometric analysis of the frontalis. L2 was defined in terms of FT (the most protruding point of the frontotemporal region), L0 (the line connecting the infraorbital margin with the tragus), and L1 (the line parallel to L0 and passing through FT) such that L2 was positioned 45° from L1 and passed through FT. The distance from FT to the superior margin of the orbicularis oculi was 12.3 ± 3.3 mm. The frontalis extended more than 5 cm along L2 in 49 of 49 cases (100%), more than 6 cm in 47 cases (95.9%), more than 7 cm in 34 cases (69.4%), more than 8 cm in 11 cases (22.4%), and more than 9 cm in 3 cases (6.1%). The lateral border of the frontalis ran parallel to and within 1 cm of the medial side of L2. Surface anatomy mapping can assist with predicting the lateral border of the frontalis to minimize the side effects and maximize the efficiency of BoNT-A injections into the forehead. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Characterizing the Lateral Border of the Frontalis for Safe and Effective Injection of Botulinum Toxin

PubMed Central

Choi, You-Jin; Won, Sung-Yoon; Lee, Jae-Gi; Hu, Kyung-Seok; Kim, Sung-Taek; Tansatit, Tanvaa; Kim, Hee-Jin

2016-01-01

Background The forehead is a common site for injection of botulinum neurotoxin type A (BoNT-A) to treat hyperactive facial muscles. Unexpected side effects of BoNT-A injection may occur because the anatomy of the forehead musculature is not fully characterized. Objectives The authors described the lateral border of the frontalis in terms of facial landmarks and reference lines to determine the safest and most effective forehead injection sites for BoNT-A. Methods The hemifaces of 49 embalmed adult Korean cadavers were dissected in a morphometric analysis of the frontalis. L2 was defined in terms of FT (the most protruding point of the frontotemporal region), L0 (the line connecting the infraorbital margin with the tragus), and L1 (the line parallel to L0 and passing through FT) such that L2 was positioned 45° from L1 and passed through FT. Results The distance from FT to the superior margin of the orbicularis oculi was 12.3 ± 3.3 mm. The frontalis extended more than 5 cm along L2 in 49 of 49 cases (100%), more than 6 cm in 47 cases (95.9%), more than 7 cm in 34 cases (69.4%), more than 8 cm in 11 cases (22.4%), and more than 9 cm in 3 cases (6.1%). The lateral border of the frontalis ran parallel to and within 1 cm of the medial side of L2. Conclusions Surface anatomy mapping can assist with predicting the lateral border of the frontalis to minimize the side effects and maximize the efficiency of BoNT-A injections into the forehead. PMID:26507959

Unexpected Complication after Caudal Epidural Steroid Injection: Hiccup

PubMed Central

Kaydu, Ayhan; Kılıç, Ebru Tarıkçı; Gökçek, Erhan; Akdemir, Mehmet Salim

2017-01-01

Persistent hiccup is uncommon, and the mechanism is poorly understood. We present the case of a 43-year-old male patient referred to the Algology department due to chronic back pain who developed what we believe a rare case of persistent hiccup secondary to caudal epidural steroid injection (CESI). The causes of hiccup are many and include electrolyte derangement, nutritional deficiencies, gastrointestinal disorders and instrumentation, cardiovascular disorders, renal impairment, central nervous system disorders, and drugs; however, the cause may be unknown. CESI is one of the treatments of back pain, in addition to various other modalities including surgical interventions. CESI has gained rapid and widespread acceptance for the treatment of lumbar and lower extremity pain. However, there are only a few well-designed, randomized, controlled studies on the effectiveness of steroid injections. Consequently, side effects should be considered. We aimed to present a persistent hiccup after CESI for chronic low back pain. PMID:28928587

Profound hypoglycemia-ınduced by vaccinium corymbosum juice and laurocerasus fruit

PubMed Central

Aktan, Ahmet Hamdi; Ozcelik, Abdullah; Cure, Erkan; Cure, Medine Cumhur; Yuce, Suleyman

2014-01-01

An emergency intervention was performed in a 75-year-old male patient with hypoglycemic attack and blackout. Although he was diagnosed with prediabetes before 2 years, he did not take any anti-diabetic drug or follow dietary advice. He drank Vaccinium corymbosum L (VC) juice daily with a belief that it increases sexual potency. Before the development of hypoglycemia, the patient had consumed about 500 ml VC juice in addition to eating 200-300 gram of Laurocerasus officinalis (LO) fruit. The measured plasma glucose (PG) level during loss of consciousness was 30 mg/dl. The profound hypoglycemia may be an unexpected side effect of an interaction between the chemical compositions of the two plants, occurred as a result of LO fruit intake that may have a strong PG-lowering effect or related to excessive intake of VC juice. Both plants may be considered in the alternative treatment of diabetes. PMID:25097289

Profound hypoglycemia-ınduced by vaccinium corymbosum juice and laurocerasus fruit.

PubMed

Aktan, Ahmet Hamdi; Ozcelik, Abdullah; Cure, Erkan; Cure, Medine Cumhur; Yuce, Suleyman

2014-01-01

An emergency intervention was performed in a 75-year-old male patient with hypoglycemic attack and blackout. Although he was diagnosed with prediabetes before 2 years, he did not take any anti-diabetic drug or follow dietary advice. He drank Vaccinium corymbosum L (VC) juice daily with a belief that it increases sexual potency. Before the development of hypoglycemia, the patient had consumed about 500 ml VC juice in addition to eating 200-300 gram of Laurocerasus officinalis (LO) fruit. The measured plasma glucose (PG) level during loss of consciousness was 30 mg/dl. The profound hypoglycemia may be an unexpected side effect of an interaction between the chemical compositions of the two plants, occurred as a result of LO fruit intake that may have a strong PG-lowering effect or related to excessive intake of VC juice. Both plants may be considered in the alternative treatment of diabetes.

Postmarketing surveillance: perspectives of a journal editor.

PubMed

Gelenberg, A J

1993-01-01

In the absence of a systematic monitoring program for drugs newly approved by the Food and Drug Administration (FDA), reports in clinical journals provide a legitimate forum for disseminating information about unexpected pharmacologic events. A journal editor bears the responsibility for publishing educated clinical observations that meet standards of scientific rigor while not giving premature credibility to chance and dubious reports of side effects of new drugs. Often this responsibility involves overcoming the fear of bad publicity and withstanding pressures from pharmaceutical companies to print only positive information about new products. Published preliminary observations may contribute to the problem of product liability, but they also generate testable hypotheses and healthy debate. If hypotheses later prove to be incorrect, they can be refuted by systematic studies and clarified in reviews and editorials. Our goal of effective education will be reached not by self-censorship but by scientific openness.

Complex dynamics of semantic memory access in reading

PubMed Central

Baggio, Giosué; Fonseca, André

2012-01-01

Understanding a word in context relies on a cascade of perceptual and conceptual processes, starting with modality-specific input decoding, and leading to the unification of the word's meaning into a discourse model. One critical cognitive event, turning a sensory stimulus into a meaningful linguistic sign, is the access of a semantic representation from memory. Little is known about the changes that activating a word's meaning brings about in cortical dynamics. We recorded the electroencephalogram (EEG) while participants read sentences that could contain a contextually unexpected word, such as ‘cold’ in ‘In July it is very cold outside’. We reconstructed trajectories in phase space from single-trial EEG time series, and we applied three nonlinear measures of predictability and complexity to each side of the semantic access boundary, estimated as the onset time of the N400 effect evoked by critical words. Relative to controls, unexpected words were associated with larger prediction errors preceding the onset of the N400. Accessing the meaning of such words produced a phase transition to lower entropy states, in which cortical processing becomes more predictable and more regular. Our study sheds new light on the dynamics of information flow through interfaces between sensory and memory systems during language processing. PMID:21715401

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

PubMed

Rocca, Elena

2017-02-01

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

Preparing for the unexpected: special considerations and complications after sugammadex administration.

PubMed

Iwasaki, Hajime; Renew, J Ross; Kunisawa, Takayuki; Brull, Sorin J

2017-10-17

Sugammadex, a modified gamma-cyclodextrin, has changed clinical practice of neuromuscular reversal dramatically. With the introduction of this selective relaxant binding agent, rapid and reliable neuromuscular reversal from any depth of block became possible. Sugammadex can reverse neuromuscular blockade without the muscarinic side effects typically associated with the administration of acetylcholinesterase inhibitors. However, what remained unchanged is the incidence of residual neuromuscular blockade. It is known that sugammadex cannot always prevent its occurrence, if appropriate dosing is not chosen based on the level of neuromuscular paralysis prior to administration determined by objective neuromuscular monitoring. Alternatively, excessive doses of sugammadex administered in an attempt to ensure full and sustained reversal may affect the effectiveness of rocuronium in case of immediate reoperation or reintubation. In such emergent scenarios that require onset of rapid and reliable neuromuscular blockade, the summary of product characteristics (package insert) recommends using benzylisoquinolinium neuromuscular blocking agents or a depolarizing agent. However, if rapid intubation is required, succinylcholine has a significant number of side effects, and benzylisoquinolinium agents may not have the rapid onset required. Therefore, prior administration of sugammadex introduces a new set of potential problems that require new solutions. This novel reversal agent thus presents new challenges and anesthesiologists must familiarize themselves with specific issues with its use (e.g., bleeding risk, hypermagnesemia, hypothermia). This review will address sugammadex administration in such special clinical situations.

Drug-Target Interactions: Prediction Methods and Applications.

PubMed

Anusuya, Shanmugam; Kesherwani, Manish; Priya, K Vishnu; Vimala, Antonydhason; Shanmugam, Gnanendra; Velmurugan, Devadasan; Gromiha, M Michael

2018-01-01

Identifying the interactions between drugs and target proteins is a key step in drug discovery. This not only aids to understand the disease mechanism, but also helps to identify unexpected therapeutic activity or adverse side effects of drugs. Hence, drug-target interaction prediction becomes an essential tool in the field of drug repurposing. The availability of heterogeneous biological data on known drug-target interactions enabled many researchers to develop various computational methods to decipher unknown drug-target interactions. This review provides an overview on these computational methods for predicting drug-target interactions along with available webservers and databases for drug-target interactions. Further, the applicability of drug-target interactions in various diseases for identifying lead compounds has been outlined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Inefficient postural responses to unexpected slips during walking in older adults.

PubMed

Tang, P F; Woollacott, M H

1998-11-01

Slips account for a high percentage of falls and subsequent injuries in community-dwelling older adults but not in young adults. This phenomenon suggests that although active and healthy older adults preserve a mobility level comparable to that of young adults, these older adults may have difficulty generating efficient reactive postural responses when they slip. This study tested the hypothesis that active and healthy older adults use a less effective reactive balance strategy than young adults when experiencing an unexpected forward slip occurring at heel strike during walking. This less effective balance strategy would be manifested by slower and smaller postural responses, altered temporal and spatial organization of the postural responses, and greater upper trunk instability after the slip. Thirty-three young adults (age range=19-34 yrs, mean=25+/-4 yrs) and 32 community-dwelling older adults (age range=70-87 yrs, mean=74+/-14 yrs) participated. Subjects walked across a movable forceplate which simulated a forward slip at heel strike. Surface electromyography was recorded from bilateral leg, thigh, hip, and trunk muscles. Kinematic data were collected from the right (perturbed) side of the body. Although the predominant postural muscles and the activation sequence of these muscles were similar between the two age groups, the postural responses of older adults were of longer onset latencies, smaller magnitudes, and longer burst durations compared to young adults. Older adults also showed a longer coactivation duration for the ankle, knee, and trunk agonist/antagonist pairs on the perturbed side and for the knee agonist/antagonist pair on the nonperturbed side. Behaviorally, older adults became less stable after the slips. This was manifested by a higher incidence of being tripped (21 trials in older vs 5 trials in young adults) and a greater trunk hyperextension with respect to young adults. Large arm elevation was frequently used by older adults to assist in maintaining trunk stability. In an attempt to quickly reestablish the base of support after the slips, older adults had an earlier contralateral foot strike and shortened stride length. The combination of slower onset and smaller magnitude of postural responses to slips in older adults resulted in an inefficient balance strategy. Older adults needed secondary compensatory adjustments, including a lengthened response duration and the use of the arms, to fully regain balance and prevent a fall. The shorter stride length and earlier contralateral foot strike following the slip indicate use of a more conservative balance strategy in older adults.

Inattentional blindness is influenced by exposure time not motion speed.

PubMed

Kreitz, Carina; Furley, Philip; Memmert, Daniel

2016-01-01

Inattentional blindness is a striking phenomenon in which a salient object within the visual field goes unnoticed because it is unexpected, and attention is focused elsewhere. Several attributes of the unexpected object, such as size and animacy, have been shown to influence the probability of inattentional blindness. At present it is unclear whether or how the speed of a moving unexpected object influences inattentional blindness. We demonstrated that inattentional blindness rates are considerably lower if the unexpected object moves more slowly, suggesting that it is the mere exposure time of the object rather than a higher saliency potentially induced by higher speed that determines the likelihood of its detection. Alternative explanations could be ruled out: The effect is not based on a pop-out effect arising from different motion speeds in relation to the primary-task stimuli (Experiment 2), nor is it based on a higher saliency of slow-moving unexpected objects (Experiment 3).

Orthographic Processing and Visual Sequential Memory in Unexpectedly Poor Spellers

ERIC Educational Resources Information Center

Holmes, Virginia M.; Malone, Aisling M.; Redenbach, Holly

2008-01-01

Does unexpectedly poor spelling in adults result from inferior visual sequential memory? In one experiment, unexpectedly poor spellers performed significantly worse than better spellers in the immediate reproduction of sequences of visual symbols, but in a second experiment, the effect was not replicated. Poor spellers were also no worse at the…

Sphingosine 1-Phosphate Receptor Modulators and Drug Discovery

PubMed Central

Park, Soo-Jin; Im, Dong-Soon

2017-01-01

Initial discovery on sphingosine 1-phosphate (S1P) as an intracellular second messenger was faced unexpectedly with roles of S1P as a first messenger, which subsequently resulted in cloning of its G protein-coupled receptors, S1P1–5. The molecular identification of S1P receptors opened up a new avenue for pathophysiological research on this lipid mediator. Cellular and molecular in vitro studies and in vivo studies on gene deficient mice have elucidated cellular signaling pathways and the pathophysiological meanings of S1P receptors. Another unexpected finding that fingolimod (FTY720) modulates S1P receptors accelerated drug discovery in this field. Fingolimod was approved as a first-in-class, orally active drug for relapsing multiple sclerosis in 2010, and its applications in other disease conditions are currently under clinical trials. In addition, more selective S1P receptor modulators with better pharmacokinetic profiles and fewer side effects are under development. Some of them are being clinically tested in the contexts of multiple sclerosis and other autoimmune and inflammatory disorders, such as, psoriasis, Crohn’s disease, ulcerative colitis, polymyositis, dermatomyositis, liver failure, renal failure, acute stroke, and transplant rejection. In this review, the authors discuss the state of the art regarding the status of drug discovery efforts targeting S1P receptors and place emphasis on potential clinical applications. PMID:28035084

Reasons (Not) to Spend a Few Billions More on EHRs: How Human Factors Research Can Help

PubMed Central

Aimé, X.

2014-01-01

Summary Objectives To select best medical informatics research works published in 2013 on electronic health record (EHR) adoption, design, and impact, from the perspective of human factors and organizational issues (HFOI). Methods We selected 2,764 papers by querying PubMed (Mesh and TIAB) as well as using a manual search. Papers were evaluated based on pre-defined exclusion and inclusion criteria from their title, keywords, and abstract to select 15 candidate best papers, finally reviewed by 4 external reviewers using a standard evaluation grid. Results Five papers were selected as best papers to illustrate how human factors approaches can improve EHR adoption and design. Among other contributions, these works: (i) make use of the observational and analysis methodologies of social and cognitive sciences to understand clinicians’ attitudes towards EHRs, EHR use patterns, and impact on care processes, workflows, information exchange, and coordination of care; (ii) take into account macro- (environmental) and meso- (organizational) level factors to analyze EHR adoption or lack thereof; (iii) highlight the need for qualitative studies to analyze the unexpected side effects of EHRs on cognitive and work processes as well as the persistent use of paper. Conclusion Selected papers tend to demonstrate that HFOI approaches and methodologies are essential to bridge the gap between EHR systems and end users, and to reduce regularly reported adoption failures and unexpected consequences. PMID:25123727

Reasons (not) to Spend a Few Billions More on EHRs: How Human Factors Research Can Help.

PubMed

Declerck, G; Aimé, X

2014-08-15

To select best medical informatics research works published in 2013 on electronic health record (EHR) adoption, design, and impact, from the perspective of human factors and organizational issues (HFOI). We selected 2,764 papers by querying PubMed (Mesh and TIAB) as well as using a manual search. Papers were evaluated based on pre-defined exclusion and inclusion criteria from their title, keywords, and abstract to select 15 candidate best papers, finally reviewed by 4 external reviewers using a standard evaluation grid. Five papers were selected as best papers to illustrate how human factors approaches can improve EHR adoption and design. Among other contributions, these works: (i) make use of the observational and analysis methodologies of social and cognitive sciences to understand clinicians' attitudes towards EHRs, EHR use patterns, and impact on care processes, workflows, information exchange, and coordination of care; (ii) take into account macro- (environmental) and meso- (organizational) level factors to analyze EHR adoption or lack thereof; (iii) highlight the need for qualitative studies to analyze the unexpected side effects of EHRs on cognitive and work processes as well as the persistent use of paper. Selected papers tend to demonstrate that HFOI approaches and methodologies are essential to bridge the gap between EHR systems and end users, and to reduce regularly reported adoption failures and unexpected consequences.

Early and late histamine release induced by albumin, hetastarch and polygeline: some unexpected findings.

PubMed

Celik, I; Duda, D; Stinner, B; Kimura, K; Gajek, H; Lorenz, W

2003-10-01

The perioperative use of colloidal plasma substitutes is still under discussion. We therefore conducted a prospective randomised study with three commonly used plasma substitutes to examine their histamine releasing effects in 21 volunteers. MATERIAL OR SUBJETS: 21 male volunteers were enrolled in this prospective, randomised, controlled clinical study. Endpoints were the incidence of early and late histamine release and the time course of the release kinetics. Normovolemic hemodilution technique was used with hydroxyethyl starch (n = 6), human albumin (n = 6) and polygeline (n = 9). Measurement and observation period was 240 min after the start of the plasma substitute infusion. Heart rate, blood pressure, SaO(2), clinical symptoms/signs and plasma histamine were measured during the observation period. The incidence of histamine release over the whole observation period in all three groups was 100%. Histamine release occurred frequently in all three groups until 30 min (50%-78%) and up to 240 min (late release reaction: 67%-83%) after the start of infusion. Surprisingly even hydroxyethyl starch, which is regarded as a generally safe and effective plasma substitute, caused high incidences of late histamine release (67%). Histamine release is a well known side effect of polygeline and - to a lesser extent - also of albumin, but was a novel finding for hydroxyethyl starch. We demonstrated for the first time histamine releasing effects of hydroxyethyl starch over a long period of time after administration. This perioperatively and for intensive care possibly relevant finding should make clinicians aware of late side effects not yet connected with the clinical use of these colloidal plasma substitutes.

Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine.

PubMed

Wang, Rui; Yan, Han; Tang, Xi-can

2006-01-01

Huperzine A (HupA), a novel alkaloid isolated from the Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase(AChE). Compared with tacrine, donepezil, and rivastigmine, HupA has better penetration through the blood-brain barrier, higher oral bioavailability, and longer duration of AChE inhibitory action. HupA has been found to improve cognitive deficits in a broad range of animal models. HupA possesses the ability to protect cells against hydrogen peroxide, beta-amyloid protein (or peptide), glutamate, ischemia and staurosporine-induced cytotoxicity and apoptosis. These protective effects are related to its ability to attenuate oxidative stress, regulate the expression of apoptotic proteins Bcl-2, Bax, P53, and caspase-3, protect mitochondria, upregulate nerve growth factor and its receptors, and interfere with amyloid precursor protein metabolism. Antagonizing effects of HupA on N-methyl-D-aspartate receptors and potassium currents may also contribute to its neuroprotection as well. Pharmacokinetic studies in rodents, canines, and healthy human volunteers indicated that HupA was absorbed rapidly, distributed widely in the body, and eliminated at a moderate rate with the property of slow and prolonged release after oral administration. Animal and clinical safety tests showed that HupA had no unexpected toxicity, particularly the dose-limiting hepatotoxicity induced by tacrine. The phase IV clinical trials in China have demonstrated that HupA significantly improved memory deficits in elderly people with benign senescent forgetfulness, and patients with Alzheimer disease and vascular dementia, with minimal peripheral cholinergic side effects and no unexpected toxicity. HupA can also be used as a protective agent against organophosphate intoxication.

Robust passive dynamics of the musculoskeletal system compensate for unexpected surface changes during human hopping

PubMed Central

van der Krogt, Marjolein M.; de Graaf, Wendy W.; Farley, Claire T.; Moritz, Chet T.; Richard Casius, L. J.; Bobbert, Maarten F.

2009-01-01

When human hoppers are surprised by a change in surface stiffness, they adapt almost instantly by changing leg stiffness, implying that neural feedback is not necessary. The goal of this simulation study was first to investigate whether leg stiffness can change without neural control adjustment when landing on an unexpected hard or unexpected compliant (soft) surface, and second to determine what underlying mechanisms are responsible for this change in leg stiffness. The muscle stimulation pattern of a forward dynamic musculoskeletal model was optimized to make the model match experimental hopping kinematics on hard and soft surfaces. Next, only surface stiffness was changed to determine how the mechanical interaction of the musculoskeletal model with the unexpected surface affected leg stiffness. It was found that leg stiffness adapted passively to both unexpected surfaces. On the unexpected hard surface, leg stiffness was lower than on the soft surface, resulting in close-to-normal center of mass displacement. This reduction in leg stiffness was a result of reduced joint stiffness caused by lower effective muscle stiffness. Faster flexion of the joints due to the interaction with the hard surface led to larger changes in muscle length, while the prescribed increase in active state and resulting muscle force remained nearly constant in time. Opposite effects were found on the unexpected soft surface, demonstrating the bidirectional stabilizing properties of passive dynamics. These passive adaptations to unexpected surfaces may be critical when negotiating disturbances during locomotion across variable terrain. PMID:19589956

A Technology Program that Rescues Spacecraft

NASA Astrophysics Data System (ADS)

Deutsch, Leslie J.; Lesh, J. R.

2004-03-01

There has never been a long-duration deep space mission that did not have unexpected problems during operations. JPL's Interplanetary Network Directorate (IND) Technology Program was created to develop new and improved methods of communication, navigation, and operations. A side benefit of the program is that it maintains a cadre of human talent and experimental systems that can be brought to bear on unexpected problems that may occur during mission operations. Solutions fall into four categories: applying new technology during operations to enhance science performance, developing new operational strategies, providing domain experts to help find solutions, and providing special facilities to trouble-shoot problems. These are illustrated here using five specific examples of spacecraft anomalies that have been solved using, at least in part, expertise or facilities from the IND Technology Program: Mariner 10, Voyager, Galileo, SOHO, and Cassini/Huygens. In this era of careful cost management, and emphasis on returns-on-investment, it is important to recognize this crucial additional benefit from such technology program investments.

Unexpected link between an antibiotic, pannexin channels and apoptosis.

PubMed

Poon, Ivan K H; Chiu, Yu-Hsin; Armstrong, Allison J; Kinchen, Jason M; Juncadella, Ignacio J; Bayliss, Douglas A; Ravichandran, Kodi S

2014-03-20

Plasma membrane pannexin 1 channels (PANX1) release nucleotide find-me signals from apoptotic cells to attract phagocytes. Here we show that the quinolone antibiotic trovafloxacin is a novel PANX1 inhibitor, by using a small-molecule screen. Although quinolones are widely used to treat bacterial infections, some quinolones have unexplained side effects, including deaths among children. PANX1 is a direct target of trovafloxacin at drug concentrations seen in human plasma, and its inhibition led to dysregulated fragmentation of apoptotic cells. Genetic loss of PANX1 phenocopied trovafloxacin effects, revealing a non-redundant role for pannexin channels in regulating cellular disassembly during apoptosis. Increase in drug-resistant bacteria worldwide and the dearth of new antibiotics is a major human health challenge. Comparing different quinolone antibiotics suggests that certain structural features may contribute to PANX1 blockade. These data identify a novel linkage between an antibiotic, pannexin channels and cellular integrity, and suggest that re-engineering certain quinolones might help develop newer antibacterials.

Unsteady Loss in the Stator Due to the Incoming Rotor Wake in a Highly-Loaded Transonic Compressor

NASA Technical Reports Server (NTRS)

Hah, Chunill

2015-01-01

The present paper reports an investigation of unsteady loss generation in the stator due to the incoming rotor wake in an advanced GE transonic compressor design with a high-fidelity numerical method. This advanced compressor with high reaction and high stage loading has been investigated both experimentally and analytically in the past. The measured efficiency in this advanced compressor is significantly lower than the design intention/goal. The general understanding is that the current generation of compressor design/analysis tools miss some important flow physics in this modern compressor design. To pinpoint the source of the efficiency miss, an advanced test with a detailed flow traverse was performed for the front one and a half stage at the NASA Glenn Research Center. Detailed data-match analysis by GE identified an unexpected high loss generation in the pressure side of the stator passage. Higher total temperature and lower total pressure are measured near the pressure side of the stator. Various analyses based on the RANS and URANS of the compressor stage do not calculate the measured higher total temperature and lower total pressure on the pressure side of the stator. In the present paper, a Large Eddy Simulation (LES) is applied to find the fundamental mechanism of this unsteady loss generation in the stator due to the incoming rotor wake. The results from the LES were first compared with the NASA test results and the GE interpretation of the test data. LES calculates lower total pressure and higher total temperature on the pressure side of the stator, as the measured data showed, resulting in large loss generation on the pressure side of the stator. Detailed examination of the unsteady flow field from LES shows that the rotor wake, which has higher total temperature and higher total pressure relative to the free stream, interacts quite differently with the pressure side of the blade compared to the suction side of the blade. The higher temperature in the wake remains high as the wake passes through the pressure side of the blade. On the other hand, the total temperature diffuses as it passes through near the suction surface. For the presently investigated compressor, the classical intra-stator wake transport to the pressure side of the blade by the slip velocity in the wake seems to be minor. The main causes of this phenomenon are three-dimensional unsteady vortex interactions near the blade surface. The stabilizing effect of the concave curvature on the suction side keeps the rotor wake thin. On the other hand, the destabilizing effect of the convex curvature of the pressure side makes the rotor wake thicker, which results in a higher total temperature measurement at the stator exit. Additionally, wake stretching through the stator seems to contribute to the redistribution of the total temperature and the loss generation.

Communication in crisis situations in the process of immunization.

PubMed

Ravlija, Jelena; Vasilj, Ivan

2012-09-01

Immunization is one of the most effective medical interventions in the prevention of the disease and represents the easiest and most cost-effective investment in health. The strategy of controlling contagious diseases that can be prevented through immunization has a long tradition in B&H. Mandatory immunizations are administered against ten diseases. Although the development of new technologies, the efforts of the pharmaceutical industry, the development of new vaccines provides better vaccines in terms of greater safety and effectiveness it should be pointed out that no vaccine is "absolutely effective and safe", and it will not achieve the immune response in 100% vaccinated, also there are possible side effects and unexpected reactions that could occur. Vaccination is often a media issue because previously unnoticed local, isolated events-side effects and complications of vaccination are now accompanied by media attention as there are now numerous and fast communication channels (internet, e-mail, TV1 etc.) and media evolved from being less "controlled" to more "commercial". Doubt in benefit of vaccination is growing even among health professionals who are expected to provide up-to-date, understandable information, and issue information about immunization benefits and potential risks. It is therefore important for health professionals to be well informed, to be a good source of authoritative, scientific and reasonable advice, and to speak openly about the benefits and risks of vaccination so that consumers fully understand both possible outcomes of vaccination. This takes communication skills, particularly in crisis situations connected with vaccination. Health professionals are thus faced with a changing attitude toward importance of immunization in the social climate where risk is less tolerated than ever before.

The influence of the self-consistent mode structure on the Coriolis pinch effect

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

Peeters, A. G.; Camenen, Y.; Casson, F. J.

This paper discusses the effect of the mode structure on the Coriolis pinch effect [A. G. Peeters, C. Angioni, and D. Strintzi, Phys. Rev. Lett. 98, 265003 (2007)]. It is shown that the Coriolis drift effect can be compensated for by a finite parallel wave vector, resulting in a reduced momentum pinch velocity. Gyrokinetic simulations in full toroidal geometry reveal that parallel dynamics effectively removes the Coriolis pinch for the case of adiabatic electrons, while the compensation due to the parallel dynamics is incomplete for the case of kinetic electrons, resulting in a finite pinch velocity. The finite flux inmore » the case of kinetic electrons is interpreted to be related to the electron trapping, which prevents a strong asymmetry in the electrostatic potential with respect to the low field side position. The physics picture developed here leads to the discovery and explanation of two unexpected effects: First the pinch velocity scales with the trapped particle fraction (root of the inverse aspect ratio), and second there is no strong collisionality dependence. The latter is related to the role of the trapped electrons, which retain some symmetry in the eigenmode, but play no role in the perturbed parallel velocity.« less

Designing and Evaluating a Climate Change Course for Upper-Division Engineers and Scientists

NASA Astrophysics Data System (ADS)

Samson, P. J.

2002-12-01

AOSS 300, GLOBAL ENVIRONMENTAL IMPACT OF TECHNOLOGICAL CHANGE, was created to provide a mechanism for scientific exploration of the unexpected global environmental side effects of technological innovation with emphasis on issues of the atmosphere and oceans. The course is specifically designed to contribute to the desired Accreditation Board for Engineering and Technology (ABET) outcomes that engineering and science graduates possess "the broad education necessary to understand the impact of solutions in a global and societal context." To facilitate this new course a new suite of coupled Flash/PHP/MySQL tools have been created that allow personalization of the students' learning space and interaction with faculty. Using these tools students are challenged to actively participate in the construction of knowledge through development of on-line portfolios that influence course content. This paper reports on lessons learned in the first semester that will guide further course development.

Micro-controller based fall detector to assist recovering patients or senior citizens

NASA Astrophysics Data System (ADS)

Páez, Francisco; Asplund, Lars

2010-09-01

Senior citizens and patients recovering from surgery or using strong medications with severe side effects tend to fall unexpectedly. The consequences of such an uncontrolled fall could be worse than the original malady, especially when there is no communication with the care-takers. We describe a fall-detector device capable of distinguishing falls from normal daily activities. Based on three-axis accelerometer and advanced data processing, the microcontroller emits an alarm requesting help in the case of a physical fall. We design and construct the fall-detector prototype for either inside or outside use. In order to determine the device performance, fifty instances of each fall event have been evaluated; all of them detected as fall event. In the case of daily activities, the only movement that produces an alarm is the transition from standing up to lying in 5% of the occurrences.

Do you really represent my task? Sequential adaptation effects to unexpected events support referential coding for the joint Simon effect.

PubMed

Klempova, Bibiana; Liepelt, Roman

2016-07-01

Recent findings suggest that a Simon effect (SE) can be induced in Individual go/nogo tasks when responding next to an event-producing object salient enough to provide a reference for the spatial coding of one's own action. However, there is skepticism against referential coding for the joint Simon effect (JSE) by proponents of task co-representation. In the present study, we tested assumptions of task co-representation and referential coding by introducing unexpected double response events in a joint go/nogo and a joint independent go/nogo task. In Experiment 1b, we tested if task representations are functionally similar in joint and standard Simon tasks. In Experiment 2, we tested sequential updating of task co-representation after unexpected single response events in the joint independent go/nogo task. Results showed increased JSEs following unexpected events in the joint go/nogo and joint independent go/nogo task (Experiment 1a). While the former finding is in line with the assumptions made by both accounts (task co-representation and referential coding), the latter finding supports referential coding. In contrast to Experiment 1a, we found a decreased SE after unexpected events in the standard Simon task (Experiment 1b), providing evidence against the functional equivalence assumption between joint and two-choice Simon tasks of the task co-representation account. Finally, we found an increased JSE also following unexpected single response events (Experiment 2), ruling out that the findings of the joint independent go/nogo task in Experiment 1a were due to a re-conceptualization of the task situation. In conclusion, our findings support referential coding also for the joint Simon effect.

Matrix recrystallization for MALDI-MS imaging of maize lipids at high-spatial resolution

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

Duenas, Maria Emilia; Carlucci, Laura; Lee, Young Jin

Matrix recrystallization is optimized and applied to improve lipid ion signals in maize embryos and leaves. A systematic study was performed varying solvent and incubation time. During this study, unexpected side reactions were found when methanol was used as a recrystallization solvent, resulting in the formation of a methyl ester of phosphatidic acid. Furthermore, using an optimum recrystallization condition with isopropanol, there is no apparent delocalization demonstrated with a transmission electron microscopy (TEM) pattern and maize leaf images obtained at 10 μm spatial resolution.

Matrix recrystallization for MALDI-MS imaging of maize lipids at high-spatial resolution

DOE PAGES

Duenas, Maria Emilia; Carlucci, Laura; Lee, Young Jin

2016-06-27

Matrix recrystallization is optimized and applied to improve lipid ion signals in maize embryos and leaves. A systematic study was performed varying solvent and incubation time. During this study, unexpected side reactions were found when methanol was used as a recrystallization solvent, resulting in the formation of a methyl ester of phosphatidic acid. Furthermore, using an optimum recrystallization condition with isopropanol, there is no apparent delocalization demonstrated with a transmission electron microscopy (TEM) pattern and maize leaf images obtained at 10 μm spatial resolution.

Matrix Recrystallization for MALDI-MS Imaging of Maize Lipids at High-Spatial Resolution

NASA Astrophysics Data System (ADS)

Dueñas, Maria Emilia; Carlucci, Laura; Lee, Young Jin

2016-09-01

Matrix recrystallization is optimized and applied to improve lipid ion signals in maize embryos and leaves. A systematic study was performed varying solvent and incubation time. During this study, unexpected side reactions were found when methanol was used as a recrystallization solvent, resulting in the formation of a methyl ester of phosphatidic acid. Using an optimum recrystallization condition with isopropanol, there is no apparent delocalization demonstrated with a transmission electron microscopy (TEM) pattern and maize leaf images obtained at 10 μm spatial resolution.

Experimental study of supersonic viscous leeside flow over a slender delta wing

NASA Technical Reports Server (NTRS)

Szodruch, J.

1980-01-01

An investigation was conducted to study in detail the vortical flow over the leeward side of a 70 deg swept delta wing having subsonic and supersonic leading edges. Two types of flow were encountered and studied, namely leading edge separation and separation with a shock. Especially for the latter type, Reynolds number plays an important role and unexpected strong streamwise vortices were observed. An optical method is described to obtain a first aproximation of shear stress values in the streamwise direction across the wing span.

Matrix Recrystallization for MALDI-MS Imaging of Maize Lipids at High-Spatial Resolution.

PubMed

Dueñas, Maria Emilia; Carlucci, Laura; Lee, Young Jin

2016-09-01

Matrix recrystallization is optimized and applied to improve lipid ion signals in maize embryos and leaves. A systematic study was performed varying solvent and incubation time. During this study, unexpected side reactions were found when methanol was used as a recrystallization solvent, resulting in the formation of a methyl ester of phosphatidic acid. Using an optimum recrystallization condition with isopropanol, there is no apparent delocalization demonstrated with a transmission electron microscopy (TEM) pattern and maize leaf images obtained at 10 μm spatial resolution. Graphical Abstract ᅟ.

Assessment of General Education: An Unexpected (but Effective) Faculty Development Opportunity

ERIC Educational Resources Information Center

Hawthorne, Joan; Zerr, Ryan; Kelsch, Anne V.

2018-01-01

This chapter describes a collective faculty effort to administer, proctor, score, and interpret student work that created an unexpected opportunity for deep discussions of teaching, learning, and assessment.

The effectiveness and safety of amisulpride in Chinese patients with schizophrenia who switch from risperidone or olanzapine: a subgroup analysis of the ESCAPE study

PubMed Central

Liang, Ying; Yu, Xin

2017-01-01

Introduction Second-generation antipsychotics show significant interpatient variability in treatment response and side-effect profiles, and the majority of patients with schizophrenia require multiple treatment changes. This subgroup analysis of the ESCAPE study evaluated the efficacy and safety of amisulpride in Chinese patients with schizophrenia who switched from risperidone or olanzapine. Methods ESCAPE was a prospective, open-label, multicenter, single-arm Phase IV study in which Chinese patients with an ICD-10 diagnosis of schizophrenia received amisulpride for 8 weeks. This analysis included 109 patients who switched to amisulpride from risperidone (n=68) or olanzapine (n=41) and 59 treatment-naïve patients for reference. The primary effectiveness outcome was a ≥50% decrease in Positive and Negative Syndrome Scale (PANSS) Total score from Baseline to Week 8. The study was registered at ClinicalTrials.gov (NCT01795183). Results Of the patients who switched from risperidone and olanzapine, 77.9% and 56.1% achieved ≥50% reduction in PANSS Total score from Baseline to Week 8 and 57.4% and 46.3% achieved ≥20% reduction in PANSS score from Baseline to Week 2, respectively; these end points were achieved by 66.1% and 61.0% of treatment-naïve patients, respectively. No unexpected adverse events (AEs) were reported. Of the most common AEs, extrapyramidal side effects occurred in 32.4% and 14.6%, blood prolactin increase in 32.4% and 39.0%, and ≥7% increase in body weight in 4.4% and 12% of patients switching from risperidone and olanzapine, respectively. Conclusion The results of this subgroup analysis suggest that switching to amisulpride from risperidone and olanzapine is effective and generally well tolerated in Chinese patients with schizophrenia. PMID:28461752

Time related neutralization of two doses acetyl salicylic acid.

PubMed

Aguejouf, O; Malfatti, E; Belon, P; Doutremepuich, C

2000-11-15

Aspirin has a well established role in the prevention of arterial thrombosis. Discussion on the efficacy and safety of aspirin in the treatment and prophylaxis of thrombosis has become an important issue. In fact, hemorrhage complications are often associated with its use. On the other hand, previous studies showed unexpected thrombotic potencies associated with the presence of this drug at ultra low doses (ULD) in the circulation. In this study, we aimed to evaluate the effect of aspirin at ULD, injected 1, 2, or 3 hours after the administration of aspirin at 100 mg/kg, on hemostasis and bleeding in rats. We used an experimental model of thrombosis induced by laser beams to evaluate these effects. Platelet aggregation was determined by Cardinal and Flower method. Results from this investigation demonstrate that the neutralizing effect of aspirin at ULD did not operate significantly 1 hour after the injection of aspirin at 100 mg/kg. This effect was observed 2 and 3 hours after. The use of aspirin at ULD to neutralize the side effects of aspirin at high doses will reduce the hemorrhagic risk during extra corporeal circulation. The therapeutic benefit and safety of aspirin therapy in the treatment of cardiovascular diseases can be obtained.

Tolerability of high-dose topical tretinoin: the Veterans Affairs Topical Tretinoin Chemoprevention Trial.

PubMed

Geng, A; Weinstock, M A; Hall, R; Eilers, D; Naylor, M; Kalivas, J

2009-10-01

Topical tretinoin is a medication commonly used for acne that has potential application in the long-term treatment of photodamaged skin. However, there are few published data regarding the tolerability of high-dose tretinoin with long-term use. To assess the long-term tolerability of tretinoin 0.1% cream. A randomized, multicentre, double-blind, controlled trial for chemoprevention of keratinocyte carcinomas (i.e. basal cell or squamous cell carcinomas) using topical tretinoin cream to the face and ears was conducted. All participants were veterans and had a history of two or more keratinocyte carcinomas over the previous 5 years. Participants were examined (by a study dermatologist) and interviewed every 6 months (for up to 5.5 years to May 2004). Treatment comprised tretinoin 0.1% cream or vehicle control cream once daily, then twice daily as tolerated. Participants were instructed to step down application frequency to once daily or less if twice daily was not tolerated. The main outcome measures were reported side-effects, frequency of cream application and attendance at study visits. Appropriate data were available for four of the six clinical sites of this trial. Data from 736 randomized participants (mean age 71 years; 97% men) from four clinical sites were analysed. The tretinoin group more commonly reported one or more side-effects at the 6-month follow-up than the control group (61% vs. 42%, P < 0.0001). Side-effects decreased over time in both groups, but to a greater extent in the tretinoin group, and the difference became nonsignificant at 30 months. Burning was the most common side-effect (39% tretinoin vs. 17% control, P < 0.0001). There was no difference in severity of side-effects among those affected. Of the participants who reported burning in either group, most reported mild burning; only 11% of those with burning in the tretinoin group reported it as severe (mild 62% tretinoin vs. 70% placebo; severe 11% vs. 5%; P = 0.4). Itching (24% vs. 16%, P = 0.01) and other local cutaneous reactions (12% vs. 6%, P = 0.01) were also more commonly reported by the tretinoin group at 6 months. There was no difference in numbness (2% vs. 2%, P = 0.9). Participants in the tretinoin group were less likely to apply cream twice daily at 6 months (29% vs. 43%, P = 0.0002). This difference persisted over the entire duration of follow-up. There was little difference between groups in attendance at study visits or completion of telephone interviews (92% vs. 95%, P = 0.06). No unexpected adverse events were reported. Overall, the tolerability level of topical tretinoin was high in this study population, with almost 40% of the tretinoin group reporting no side-effects, and the majority (67%) tolerating at least once-daily dosing at 6-month follow-up. High-dose topical tretinoin is feasible for long-term use in this population.

Coulomb repulsion in short polypeptides.

PubMed

Norouzy, Amir; Assaf, Khaleel I; Zhang, Shuai; Jacob, Maik H; Nau, Werner M

2015-01-08

Coulomb repulsion between like-charged side chains is presently viewed as a major force that impacts the biological activity of intrinsically disordered polypeptides (IDPs) by determining their spatial dimensions. We investigated short synthetic models of IDPs, purely composed of ionizable amino acid residues and therefore expected to display an extreme structural and dynamic response to pH variation. Two synergistic, custom-made, time-resolved fluorescence methods were applied in tandem to study the structure and dynamics of the acidic and basic hexapeptides Asp6, Glu6, Arg6, Lys6, and His6 between pH 1 and 12. (i) End-to-end distances were obtained from the short-distance Förster resonance energy transfer (sdFRET) from N-terminal 5-fluoro-l-tryptophan (FTrp) to C-terminal Dbo. (ii) End-to-end collision rates were obtained for the same peptides from the collision-induced fluorescence quenching (CIFQ) of Dbo by FTrp. Unexpectedly, the very high increase of charge density at elevated pH had no dynamical or conformational consequence in the anionic chains, neither in the absence nor in the presence of salt, in conflict with the common view and in partial conflict with accompanying molecular dynamics simulations. In contrast, the cationic peptides responded to ionization but with surprising patterns that mirrored the rich individual characteristics of each side chain type. The contrasting results had to be interpreted, by considering salt screening experiments, N-terminal acetylation, and simulations, in terms of an interplay of local dielectric constant and peptide-length dependent side chain charge-charge repulsion, side chain functional group solvation, N-terminal and side chain charge-charge repulsion, and side chain-side chain as well as side chain-backbone interactions. The common picture that emerged is that Coulomb repulsion between water-solvated side chains is efficiently quenched in short peptides as long as side chains are not in direct contact with each other or the main chain.

Consequences, control and appraisal: cues and barriers to engaging in self-management among people affected by colorectal cancer - a secondary analysis of qualitative data.

PubMed

Kidd, Lisa A

2014-08-01

Little is known about peoples' self-management experiences and their desires or expectations to engage in self-management. As such, there is little understanding about individuals' perceived cues and barriers to engagement in self-management, particularly in people affected by cancer. To understand cues and barriers to people's engagement in self-management during chemotherapy treatment for colorectal cancer. Secondary analysis of qualitative data from mixed methods, longitudinal study. Eleven participants undergoing treatment for colorectal cancer. Semi-structured interviews were conducted twice with each participant, at the start and end of a 6-month course of chemotherapy treatment in a Scottish cancer centre. Cues and barriers to engagement in self-management appeared to stem from perceptions of the impact and associated severity of side effects experiences as well as the perceptions about the efficacy of chosen self-management activities and perceptions of control in minimizing the consequences of cancer treatment. Severe, episodic or unexpected side effects coupled with perceptions of uncertainty, lack of control and lack of adequate preparation to engage in self-management were identified as key barriers to engagement. Participants' reflection on, or appraisal of, their treatment-related experiences and personal abilities, confidence and preferences to manage the impact of these shaped their subsequent engagement in self-management. The findings highlight the importance of understanding individual's self-management experiences, perceptions, preferences, priorities and needs to help support, prepare and enable them to feel capable and confident to engage actively and effectively in self-management. © 2012 John Wiley & Sons Ltd.

Potential benefit of a simultaneous, side-by-side display of contrast MDCT and echocardiography over routine sequential imaging for assessment of adult congenital heart disease: A preliminary study.

PubMed

Oe, Hiroki; Watanabe, Nobuhisa; Miyoshi, Toru; Osawa, Kazuhiro; Akagi, Teiji; Kanazawa, Susumu; Ito, Hiroshi

2018-06-18

Management of adult congenital heart disease (ACHD) patients requires understanding of its complex morphology and functional features. An innovative imaging technique has been developed to display a virtual multi-planar reconstruction obtained from contrast-enhanced multidetector-computed tomography (MDCT) corresponding to the same cross-sectional image from transthoracic echocardiography (TTE). The aim of this study is to assess the usefulness of this imaging technology in ACHD patients. This study consisted of 46 consecutive patients (30 women; mean age, 52±18 years old) with ACHD who had undergone contrast MDCT. All patients underwent TTE within a week of MDCT. An experienced sonographer who did not know the results of MDCT conducted a diagnosis using TTE and, then, using the new imaging technology. We studied whether this imaging technology provided additional or unexpected findings or makes more accurate diagnosis. In this imaging technology, MDCT cross-section provides higher-resolution image to the deep compared to corresponding TTE image. Depending on the MDCT section which can be arbitrarily set under the echo guide, we can diagnose unexpected or incremental lesions or more accurately assess the severity of the lesion in 27 patients (59%) compared to TTE study alone. This imaging technology was useful in the following situations: CONCLUSIONS: This integrated imaging technology provides incremental role over TTE in complex anatomy, and allows functional information in ACHD patients. Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Ion Temperature Control of the Io Plasma Torus

NASA Technical Reports Server (NTRS)

Delamere, P. A.; Schneider, N. M.; Steffl, A. J.; Robbins, S. J.

2005-01-01

We report on observational and theoretical studies of ion temperature in the Io plasma torus. Ion temperature is a critical factor for two reasons. First, ions are a major supplier of energy to the torus electrons which power the intense EUV emissions. Second, ion temperature determines the vertical extent of plasma along field lines. Higher temperatures spread plasma out, lowers the density and slows reaction rates. The combined effects can play a controlling role in torus energetics and chemistry. An unexpected tool for the study of ion temperature is the longitudinal structure in the plasma torus which often manifests itself as periodic brightness variations. Opposite sides of the torus (especially magnetic longitudes 20 and 200 degrees) have been observed on numerous occasions to have dramatically different brightness, density, composition, ionization state, electron temperature and ion temperature. These asymmetries must ultimately be driven by different energy flows on the opposite sides, presenting an opportunity to observe key torus processes operating under different conditions. The most comprehensive dataset for the study of longitudinal variations was obtained by the Cassini UVIS instrument during its Jupiter flyby. Steffl (Ph.D. thesis, 2005) identified longitudinal variations in all the quantities listed above wit the exception of ion temperature. We extend his work by undertaking the first search for such variation in the UVIS dataset. We also report on a 'square centimeter' model of the torus which extend the traditional 'cubic centimeter' models by including the controlling effects of ion temperature more completely.

Significant differences in pediatric psychotropic side effects: Implications for school performance.

PubMed

Kubiszyn, Thomas; Mire, Sarah; Dutt, Sonia; Papathopoulos, Katina; Burridge, Andrea Backsheider

2012-03-01

Some side effects (SEs) of increasingly prescribed psychotropic medications can impact student performance in school. SE risk varies, even among drugs from the same class (e.g., antidepressants). Knowing which SEs occur significantly more often than others may enable school psychologists to enhance collaborative risk-benefit analysis, medication monitoring, data-based decision-making, and inform mitigation efforts. SE data from Full Prescribing Information (PI) on the FDA website for ADHD drugs, atypical antipsychotics, and antidepressants with pediatric indications were analyzed. Risk ratios (RR) are reported for each drug within a category compared with placebo. RR tables and graphs inform the reader about SE incidence differences for each drug and provide clear evidence of the wide variability in SE incidence in the FDA data. Breslow-Day and Cochran Mantel-Haenszel methods were used to test for drug-placebo SE differences and to test for significance across drugs within each category based on odds ratios (ORs). Significant drug-placebo differences were found for each drug compared with placebo, when odds were pooled across all drugs in a category compared with placebo, and between some drugs within categories. Unexpectedly, many large RR differences did not reach significance. Potential explanations are offered, including limitations of the FDA data sets and statistical and methodological issues. Future research directions are offered. The potential impact of certain SEs on school performance, mitigation strategies, and the potential role of the school psychologist is discussed, with consideration for ethical and legal limitations. (c) 2012 APA, all rights reserved.

Interaction between bedding and sleeping position in the sudden infant death syndrome: a population based case-control study.

PubMed Central

Fleming, P J; Gilbert, R; Azaz, Y; Berry, P J; Rudd, P T; Stewart, A; Hall, E

1990-01-01

OBJECTIVE--To determine the relation between sleeping position and quantity of bedding and the risk of sudden unexpected infant death. DESIGN--A study of all infants dying suddenly and unexpectedly and of two controls matched for age and date with each index case. The parents of control infants were interviewed within 72 hours of the index infant's death. Information was collected on bedding, sleeping position, heating, and recent signs of illness for index and control infants. SETTING--A defined geographical area comprising most of the county of Avon and part of Somerset. SUBJECTS--72 Infants who had died suddenly and unexpectedly (of whom 67 had died from the sudden infant death syndrome) and 144 control infants. RESULTS--Compared with the control infants the infants who had died from the sudden infant death syndrome were more likely to have been sleeping prone (relative risk 8.8; 95% confidence interval 7.0 to 11.0; p less than 0.001), to have been more heavily wrapped (relative risk 1.14 per tog above 8 tog; 1.03 to 1.28; p less than 0.05), and to have had the heating on all night (relative risk 2.7; 1.4 to 5.2; p less than 0.01). These differences were less pronounced in the younger infants (less than 70 days) than the older ones. The risk of sudden unexpected death among infants older than 70 days, nursed prone, and with clothing and bedding of total thermal resistance greater than 10 tog was increased by factors of 15.1 (2.6 to 89.6) and 25.2 (3.7 to 169.0) respectively compared with the risk in infants of the same age nursed supine or on their side and under less than 6 tog of bedding. CONCLUSIONS--Overheating and the prone position are independently associated with an increased risk of sudden unexpected infant death, particularly in infants aged more than 70 days. Educating parents about appropriate thermal care and sleeping position of infants may help to reduce the incidence of the sudden infant death syndrome. PMID:2390588

Functional modulation of a protein folding landscape via side-chain distortion

PubMed Central

Kelch, Brian A.; Salimi, Neema L.; Agard, David A.

2012-01-01

Ultrahigh-resolution (< 1.0 Å) structures have revealed unprecedented and unexpected details of molecular geometry, such as the deformation of aromatic rings from planarity. However, the functional utility of such energetically costly strain is unknown. The 0.83 Å structure of α-lytic protease (αLP) indicated that residues surrounding a conserved Phe side-chain dictate a rotamer which results in a ∼6° distortion along the side-chain, estimated to cost 4 kcal/mol. By contrast, in the closely related protease Streptomyces griseus Protease B (SGPB), the equivalent Phe adopts a different rotamer and is undistorted. Here, we report that the αLP Phe side-chain distortion is both functional and conserved in proteases with large pro regions. Sequence analysis of the αLP serine protease family reveals a bifurcation separating those sequences expected to induce distortion and those that would not, which correlates with the extent of kinetic stability. Structural and folding kinetics analyses of family members suggest that distortion of this side-chain plays a role in increasing kinetic stability within the αLP family members that use a large Pro region. Additionally, structural and kinetic folding studies of mutants demonstrate that strain alters the folding free energy landscape by destabilizing the transition state (TS) relative to the native state (N). Although side-chain distortion comes at a cost of foldability, it suppresses the rate of unfolding, thereby enhancing kinetic stability and increasing protein longevity under harsh extracellular conditions. This ability of a structural distortion to enhance function is unlikely to be unique to αLP family members and may be relevant in other proteins exhibiting side-chain distortions. PMID:22635267

Unexpected Solubility Enhancement of Drug Bases in the Presence of a Dimethylaminoethyl Methacrylate Copolymer.

PubMed

Saal, Wiebke; Ross, Alfred; Wyttenbach, Nicole; Alsenz, Jochem; Kuentz, Martin

2018-01-02

The methacrylate copolymer Eudragit EPO (EPO) has previously shown to greatly enhance solubilization of acidic drugs via ionic interactions and by multiple hydrophobic contacts with polymeric side chains. The latter type of interaction could also play a role for solubilization of other compounds than acids. The aim of this study was therefore to investigate the solubility of six poorly soluble bases in presence and absence of EPO by quantitative ultrapressure liquid chromatography with concomitant X-ray powder diffraction analysis of the solid state. For a better mechanistic understanding, spectra and diffusion data were obtained by 1 H nuclear magnetic resonance (NMR) spectroscopy. Unexpected high solubility enhancement (up to 360-fold) was evidenced in the presence of EPO despite the fact that bases and polymer were both carrying positive charges. This exceptional and unexpected solubilization was not due to a change in the crystalline solid state. NMR spectra and measured diffusion coefficients indicated both strong drug-polymer interactions in the bulk solution, and diffusion data suggested conformational changes of the polymer in solution. Such conformational changes may have increased the accessibility and extent of hydrophobic contacts thereby leading to increased overall molecular interactions. These initially surprising solubilization results demonstrate that excipient selection should not be based solely on simple considerations of, for example, opposite charges of drug and excipient, but it requires a more refined molecular view. Different solution NMR techniques are especially promising tools to gain such mechanistic insights.

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.

The Unexpected Effects of Inclusion on the Families of Students with Learning Disabilities: A Focus-Group Study

ERIC Educational Resources Information Center

Dyson, Lily L.

2007-01-01

This study investigated the unexpected effects of inclusion on the families of students with learning disabilities. A focus group interview was conducted with 13 parents who have children with learning disabilities. The children's ages ranged from 5 to 24 years. Findings are reported regarding participants' comments in response to two guiding…

Selective arterial chemoembolization for hepatic metastases from medullary thyroid carcinoma.

PubMed

Lorenz, Kerstin; Brauckhoff, Michael; Behrmann, Curd; Sekulla, Carsten; Ukkat, Jörg; Brauckhoff, Katrin; Gimm, Oliver; Dralle, Henning

2005-12-01

Hepatic metastases from medullary thyroid carcinoma (MTC) may impair quality of life by hypercalcitonemia-associated diarrhea and pain. In this prospective study, the effect of selective arterial chemoembolization (SACE) was evaluated. Eleven patients with hepatic metastases from MTC received 1 to 9 courses of SACE using epirubicine. Symptomatic, biochemical, and morphologic responses on SACE were recorded. Symptomatic response was observed in all symptomatic patients. However, biochemical and radiologic response occurred only in 6 patients. Liver function was not affected by SACE. One patient with unexpected concurrent pheochromocytoma metastases died after the first course. Development of side effects in the course was observed in 8 patients but were only World Health Organization grade 1. Patients' satisfaction with SACE was excellent. Long-term follow-up found 7 patients alive (1-72 months). Three patients died with tumor 6, 12, and 24 months after SACE, respectively. SACE provided good symptom palliation for the majority of patients with hepatic metastases from MTC. However, transient remission or stabilization of hepatic metastases resulted in only 60%. Further studies using a randomized protocol are required.

Microscopic Observation of the Side Surface of Dynamically-Tensile-Fractured 6061-T6 and 2219-T87 Aluminum Alloys with Pre-Fatigue

NASA Astrophysics Data System (ADS)

Itabashi, Masaaki; Nakajima, Shigeru; Fukuda, Hiroshi

After unexpected failure of metallic structure, microscopic investigation will be performed. Generally, such an investigation is limited to search striation pattern with a SEM (scanning electron microscope). But, when the cause of the failure was not severe repeated stress, this investigation is ineffective. In this paper, new microscopic observation technique is proposed to detect low cycle fatigue-impact tensile loading history. Al alloys, 6061-T6 and 2219-T87, were fractured in dynamic tension, after severe pre-fatigue. The side surface of the fractured specimens was observed with a SEM. Neighboring fractured surface, many opened cracks on the side surface have been generated. For each specimen, the number of the cracks was counted together with information of individual sizes and geometric features. For 6061-T6 alloy specimen with the pre-fatigue, the number of the cracks is greater than that for the specimen without the pre-fatigue. For 2219-T87 alloy, the same tendency can be found after a certain screening of the crack counting. Therefore, the crack counting technique may be useful to detect the existence of the pre-fatigue from the dynamically fractured specimen surface.

Exploring links between greenspace and sudden unexpected death: a spatial analysis

EPA Science Inventory

Greenspace has been increasingly recognized as having numerous health benefits. However, its effects are unknown concerning sudden unexpected death (SUD), commonly referred to as sudden cardiac death, which constitutes a large proportion of mortality in the United States. Because...

When the Sun Gets in the Way: Stereo Science Observations on the Far Side of the Sun

NASA Astrophysics Data System (ADS)

Vourlidas, A.; Thompson, W. T.; Gurman, J. B.; Luhmann, J. G.; Curtis, D. W.; Schroeder, P. C.; Mewaldt, R. A.; Davis, A. J.; Wortman, K.; Russell, C. T.; Galvin, A. B.; Popecki, M.; Kistler, L. M.; Ellis, L.; Howard, R.; Rich, N.; Hutting, L.; Maksimovic, M.; Bale, S. D.; Goetz, K.

2014-12-01

With the two STEREO spacecraft on the opposite side of the Sun from Earth, pointing the high gain antenna at Earth means that it's also pointed very close to the Sun. This has resulted in unexpectedly high temperatures in the antenna feed horns on both spacecraft, and is forcing the mission operations team to take corrective action, starting in August 2014 for STEREO Ahead, and December 2014 for STEREO Behind. By off-pointing the antennas to use one of the lower power side lobes instead of the main lobe, the feed horn temperatures can be kept at a safe level while still allowing reliable communication with the spacecraft. However, the amount of telemetry that can be brought down will be highly reduced. Even so, significant science will still be possible from STEREO's unique position on the solar far side. We will discuss the science and space weather products that will be available from each STEREO instrument, when those products will be available, and how they will be used. Some data, including the regular space weather beacon products, will be brought down for an average of a few hours each day during the daily real-time passes, while the in situ and radio beacon data will be stored on the onboard recorder to provide a continuous 24-hour coverage for eventual downlink once the spacecraft is back to normal operations.

Synthesis, antimicrobial activity and toxicity of analogs of the scorpion venom BmKn peptides.

PubMed

Bea, Roberto de la Salud; Petraglia, Adam Fine; Johnson, Laura Elena Luque de

2015-07-01

Two analogs of the natural peptide BmKn1 and four of BmKn2 found in the venom of the scorpion Buthus martensii Karsh have been synthesized and tested to compare their antimicrobial and hemolytic activity with the natural ones. Modifications of the natural sequence were done on the hydrophobic side of the alpha helix by increasing the size and hydrophobicity of the residues with alanine (BmKn2A1), valine (BmKn2V1) and leucine (BmKn2L1) respectively, and on the hydrophilic side by increasing the charge from +2 to +3 with two lysines (BmKn2K7). In order to study observed peptide aggregation, two peptides with one (BmKn1-6Lys) and two (BmKn1L2K2) positive charges respectively in the hydrophobic side have been also designed. Results show that the valine substituted analog BmKn2V1 and lysine substituted analog BmKn2K7 have in general, the highest antibiotic and hemolytic activity of the group. Introduction of one positive charge on the hydrophobic side shows a significant increase in antibacterial activity compared with the original sequence except for Bacillus and Enterobacter where, unexpectedly, the activity flats-off. In contrast, the analog with two positive charges has minimal antibacterial or hemolytic activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Central cavity of fructose-1,6-bisphosphatase and the evolution of AMP/fructose 2,6-bisphosphate synergism in eukaryotic organisms.

PubMed

Gao, Yang; Shen, Lu; Honzatko, Richard B

2014-03-21

The effects of AMP and fructose 2,6-bisphosphate (Fru-2,6-P2) on porcine fructose-1,6-bisphosphatase (pFBPase) and Escherichia coli FBPase (eFBPase) differ in three respects. AMP/Fru-2,6-P2 synergism in pFBPase is absent in eFBPase. Fru-2,6-P2 induces a 13° subunit pair rotation in pFBPase but no rotation in eFBPase. Hydrophilic side chains in eFBPase occupy what otherwise would be a central aqueous cavity observed in pFBPase. Explored here is the linkage of AMP/Fru-2,6-P2 synergism to the central cavity and the evolution of synergism in FBPases. The single mutation Ser(45) → His substantially fills the central cavity of pFBPase, and the triple mutation Ser(45) → His, Thr(46) → Arg, and Leu(186) → Tyr replaces porcine with E. coli type side chains. Both single and triple mutations significantly reduce synergism while retaining other wild-type kinetic properties. Similar to the effect of Fru-2,6-P2 on eFBPase, the triple mutant of pFBPase with bound Fru-2,6-P2 exhibits only a 2° subunit pair rotation as opposed to the 13° rotation exhibited by the Fru-2,6-P2 complex of wild-type pFBPase. The side chain at position 45 is small in all available eukaryotic FBPases but large and hydrophilic in bacterial FBPases, similar to eFBPase. Sequence information indicates the likelihood of synergism in the FBPase from Leptospira interrogans (lFBPase), and indeed recombinant lFBPase exhibits AMP/Fru-2,6-P2 synergism. Unexpectedly, however, AMP also enhances Fru-6-P binding to lFBPase. Taken together, these observations suggest the evolution of AMP/Fru-2,6-P2 synergism in eukaryotic FBPases from an ancestral FBPase having a central aqueous cavity and exhibiting synergistic feedback inhibition by AMP and Fru-6-P.

Pharmacological rescue of Ras signaling, GluA1-dependent synaptic plasticity, and learning deficits in a fragile X model.

PubMed

Lim, Chae-Seok; Hoang, Elizabeth T; Viar, Kenneth E; Stornetta, Ruth L; Scott, Michael M; Zhu, J Julius

2014-02-01

Fragile X syndrome, caused by the loss of Fmr1 gene function, is the most common form of inherited mental retardation, with no effective treatment. Using a tractable animal model, we investigated mechanisms of action of a few FDA-approved psychoactive drugs that modestly benefit the cognitive performance in fragile X patients. Here we report that compounds activating serotonin (5HT) subtype 2B receptors (5HT2B-Rs) or dopamine (DA) subtype 1-like receptors (D1-Rs) and/or those inhibiting 5HT2A-Rs or D2-Rs moderately enhance Ras-PI3K/PKB signaling input, GluA1-dependent synaptic plasticity, and learning in Fmr1 knockout mice. Unexpectedly, combinations of these 5HT and DA compounds at low doses synergistically stimulate Ras-PI3K/PKB signal transduction and GluA1-dependent synaptic plasticity and remarkably restore normal learning in Fmr1 knockout mice without causing anxiety-related side effects. These findings suggest that properly dosed and combined FDA-approved psychoactive drugs may effectively treat the cognitive impairment associated with fragile X syndrome.

Effects of pyrazole partial agonists on HCA(2) -mediated flushing and VLDL-triglyceride levels in mice.

PubMed

Li, Zhaosha; Blad, Clara C; van der Sluis, Ronald J; de Vries, Henk; Van Berkel, Theo J C; Ijzerman, Adriaan P; Hoekstra, Menno

2012-10-01

Niacin can effectively treat dyslipidaemic disorders. However, its clinical use is limited due to the cutaneous flushing mediated by the nicotinic acid receptor HCA(2) . In the current study, we evaluated two partial agonists for HCA(2) , LUF6281 and LUF6283, with respect to their anti-dyslipidaemic potential and cutaneous flushing effect. In vitro potency and efficacy studies with niacin and the two HCA(2) partial agonists were performed using HEK293T cells stably expressing human HCA(2) . Normolipidaemic C57BL/6 mice received either niacin or the HCA(2) partial agonists (400 mg·kg(-1) ·day(-1) ) once a day for 4 weeks for evaluation of their effects in vivo. Radioligand competitive binding assay showed K(i) values for LUF6281 and LUF6283 of 3 and 0.55 µM. [(35) S]-GTPγS binding revealed the rank order of their potency as niacin > LUF6283 > LUF6281. All three compounds reduced plasma VLDL-triglyceride concentrations similarly, while LUF6281 and LUF6283, in contrast to niacin, did not also exhibit the unwanted flushing side effect in C57BL/6 mice. Niacin reduced the expression of lipolytic genes HSL and ATGL in adipose tissue by 50%, whereas LUF6281 and LUF6283 unexpectedly did not. In contrast, the decrease in VLDL-triglyceride concentration induced by LUF6281 and LUF6283 was associated with a parallel >40% reduced expression of APOB within the liver. The current study identifies LUF6281 and LUF6283, two HCA(2) partial agonists of the pyrazole class, as promising drug candidates to achieve the beneficial lipid lowering effect of niacin without producing the unwanted flushing side effect. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Unexpected Presence of Graminan- and Levan-Type Fructans in the Evergreen Frost-Hardy Eudicot Pachysandra terminalis (Buxaceae): Purification, Cloning, and Functional Analysis of a 6-SST/6-SFT Enzyme1[W

PubMed Central

Van den Ende, Wim; Coopman, Marlies; Clerens, Stefan; Vergauwen, Rudy; Le Roy, Katrien; Lammens, Willem; Van Laere, André

2011-01-01

About 15% of flowering plants accumulate fructans. Inulin-type fructans with β(2,1) fructosyl linkages typically accumulate in the core eudicot families (e.g. Asteraceae), while levan-type fructans with β(2,6) linkages and branched, graminan-type fructans with mixed linkages predominate in monocot families. Here, we describe the unexpected finding that graminan- and levan-type fructans, as typically occurring in wheat (Triticum aestivum) and barley (Hordeum vulgare), also accumulate in Pachysandra terminalis, an evergreen, frost-hardy basal eudicot species. Part of the complex graminan- and levan-type fructans as accumulating in vivo can be produced in vitro by a sucrose:fructan 6-fructosyltransferase (6-SFT) enzyme with inherent sucrose:sucrose 1-fructosyltransferase (1-SST) and fructan 6-exohydrolase side activities. This enzyme produces a series of cereal-like graminan- and levan-type fructans from sucrose as a single substrate. The 6-SST/6-SFT enzyme was fully purified by classic column chromatography. In-gel trypsin digestion led to reverse transcription-polymerase chain reaction-based cDNA cloning. The functionality of the 6-SST/6-SFT cDNA was demonstrated after heterologous expression in Pichia pastoris. Both the recombinant and native enzymes showed rather similar substrate specificity characteristics, including peculiar temperature-dependent inherent 1-SST and fructan 6-exohydrolase side activities. The finding that cereal-type fructans accumulate in a basal eudicot species further confirms the polyphyletic origin of fructan biosynthesis in nature. Our data suggest that the fructan syndrome in P. terminalis can be considered as a recent evolutionary event. Putative connections between abiotic stress and fructans are discussed. PMID:21037113

Homogenization of Doppler broadening in spin-noise spectroscopy

NASA Astrophysics Data System (ADS)

Petrov, M. Yu.; Ryzhov, I. I.; Smirnov, D. S.; Belyaev, L. Yu.; Potekhin, R. A.; Glazov, M. M.; Kulyasov, V. N.; Kozlov, G. G.; Aleksandrov, E. B.; Zapasskii, V. S.

2018-03-01

The spin-noise spectroscopy, being a nonperturbative linear optics tool, is still reputed to reveal a number of capabilities specific to nonlinear optics techniques. The effect of the Doppler broadening homogenization discovered in this work essentially widens these unique properties of spin-noise spectroscopy. We investigate spin noise of a classical system—cesium atoms vapor with admixture of buffer gas—by measuring the spin-induced Faraday rotation fluctuations in the region of D 2 line. The line, under our experimental conditions, is strongly inhomogeneously broadened due to the Doppler effect. Despite that, optical spectrum of the spin-noise power has the shape typical for the homogeneously broadened line with a dip at the line center. This fact is in stark contrast with the results of previous studies of inhomogeneous quantum dot ensembles and Doppler broadened atomic systems. In addition, the two-color spin-noise measurements have shown, in a highly spectacular way, that fluctuations of the Faraday rotation within the line are either correlated or anticorrelated depending on whether the two wavelengths lie on the same side or on different sides of the resonance. The experimental data are interpreted in the frame of the developed theoretical model which takes into account both kinetics and spin dynamics of Cs atoms. It is shown that the unexpected behavior of the Faraday rotation noise spectra and effective homogenization of the optical transition in the spin-noise measurements are related to smallness of the momentum relaxation time of the atoms as compared with their spin-relaxation time. Our findings demonstrate abilities of spin-noise spectroscopy for studying dynamic properties of inhomogeneously broadened ensembles of randomly moving spins.

Unexpected side effect in mCRC: A care-compliant case report of regorafenib-induced hyperammonemic encephalopathy.

PubMed

Quirino, Michela; Rossi, Sabrina; Schinzari, Giovanni; Basso, Michele; Strippoli, Antonia; Cassano, Alessandra; Barone, Carlo

2017-04-01

Regorafenib represents a treatment option in heavily pretreated patients affected by metastatic colorectal cancer (mCRC). Its safety profile is typical of small-molecule tyrosine-kinase inhibitors (TKIs) and most adverse events are manageable. A 56 years-old Caucasian man affected by mCRC with normal hepatic reserve was treated with regorafenib as second-line treatment. After only 2 days of therapy, the patient presented to the emergency department due to impairment of both spatial and temporal orientation and motor function with bradylalia. Serum ammonia level was 191 mmol/L, liver function tests and complete blood count were normal. Regorafenib was withheld and branched chain amino acids and lactulose were administered. Serum ammonia level returned within the normal range, but when regorafenib was restarted at a lower dose level, a new episode of acute confusion arised. Discontinuation of regorafenib after confirmation of hyperammonemia is strongly recommended; reintroduction of the therapy at lower doses after resolution of symptoms related to hyperammonemic encephalopathy has to be discouraged.

The dark and bright sides of self-efficacy in predicting learning, innovative and risky performances.

PubMed

Salanova, Marisa; Lorente, Laura; Martínez, Isabel M

2012-11-01

The objective of this study is to analyze the different role that efficacy beliefs play in the prediction of learning, innovative and risky performances. We hypothesize that high levels of efficacy beliefs in learning and innovative performances have positive consequences (i.e., better academic and innovative performance, respectively), whereas in risky performances they have negative consequences (i.e., less safety performance). To achieve this objective, three studies were conducted, 1) a two-wave longitudinal field study among 527 undergraduate students (learning setting), 2) a three-wave longitudinal lab study among 165 participants performing innovative group tasks (innovative setting), and 3) a field study among 228 construction workers (risky setting). As expected, high levels of efficacy beliefs have positive or negative consequences on performance depending on the specific settings. Unexpectedly, however, we found no time x self-efficacy interaction effect over time in learning and innovative settings. Theoretical and practical implications within the social cognitive theory of A. Bandura framework are discussed.

Quantum mechanical settings inspired by RLC circuits

NASA Astrophysics Data System (ADS)

Alicata, G.; Bagarello, F.; Gargano, F.; Spagnolo, S.

2018-04-01

In some recent papers, several authors used electronic circuits to construct loss and gain systems. This is particularly interesting in the context of PT-quantum mechanics, where this kind of effects appears quite naturally. The electronic circuits used so far are simple, but not so much. Surprisingly enough, a rather trivial RLC circuit can be analyzed with the same perspective and it produces a variety of unexpected results, both from a mathematical and on a physical side. In this paper, we show that this circuit produces two biorthogonal bases associated with the Liouville matrix L used in the treatment of its dynamics, with a biorthogonality which is linked to the value of the parameters of the circuit. We also show that the related loss RLC circuit is naturally associated with a gain RLC circuit and that the relation between the two is rather naturally encoded in L . We propose a pseudo-fermionic analysis of the circuit, and we introduce the notion of m-equivalence between electronic circuits.

Combined immunotherapy and antiangiogenic therapy of cancer with microencapsulated cells.

PubMed

Cirone, Pasquale; Bourgeois, Jacqueline M; Shen, Feng; Chang, Patricia L

2004-10-01

An alternative form of gene therapy involves immunoisolation of a nonautologous cell line engineered to secrete a therapeutic product. Encapsulation of these cells in a biocompatible polymer serves to protect these allogeneic cells from host-versus-graft rejection while recombinant products and nutrients are able to pass by diffusion. This strategy was applied to the treatment of cancer with some success by delivering either interleukin 2 or angiostatin. However, as cancer is a complex, multifactorial disease, a multipronged approach is now being developed to attack tumorigenesis via multiple pathways in order to improve treatment efficacy. A combination of immunotherapy with angiostatic therapy was investigated by treating B16-F0/neu melanoma-bearing mice with intraperitoneally implanted, microencapsulated mouse myoblasts (C2C12) genetically modified to deliver angiostatin and an interleukin 2 fusion protein (sFvIL-2). The combination treatment resulted in improved survival, delayed tumor growth, and increased histological indices of antitumor activity (apoptosis and necrosis). In addition to improved efficacy, the combination treatment also ameliorated some of the undesirable side effects from the individual treatments that have led to the previous failure of the single treatments, for example, inflammatory response to IL-2 or vascular mimicry due to angiostatin. In conclusion, the combination of immuno- and antiangiogenic therapies delivered by immunoisolated cells was superior to individual treatments for antitumorigenesis activity, not only because of their known mechanisms of action but also because of unexpected protection against the adverse side effects of the single treatments. Thus, the concept of a "cocktail" strategy, with microencapsulation delivering multiple antitumor recombinant molecules to improve efficacy, is validated.

‘Rhyme or reason?’ Saying no to mass vaccination: subjective re-interpretation in the context of the A(H1N1) influenza pandemic in Sweden 2009–2010

PubMed Central

Lundgren, Britta

2015-01-01

During the swine flu pandemic of 2009–2010, all Swedish citizens were recommended to be vaccinated with the influenza vaccine Pandemrix. However, a very serious and unexpected side effect emerged during the summer of 2010: more than 200 children and young adults were diagnosed with narcolepsy after vaccination. Besides the tragic outcome for these children and their families, this adverse side effect suggests future difficulties in obtaining trust in vaccination in cases of emerging pandemics, and thus there is a growing need to find ways to understand the complexities of vaccination decision processes. This article explores written responses to a questionnaire from a Swedish folk life archive as an unconventional source for analysing vaccine decisions. The aim is to investigate how laypersons responded to and re-interpreted the message about the recommended vaccination in their answers. The answers show the confusion and complex circumstances and influences in everyday life that people reflect on when making such important decisions. The issue of confusion is traced back to the initial communications about the vaccination intervention in which both autonomy and solidarity were expected from the population. Common narratives and stories about the media or ‘big pharma capitalism’ are entangled with private memories, accidental coincidences and serendipitous associations. It is obvious that vaccination interventions that require compliance from large groups of people need to take into account the kind of personal experience narratives that are produced by the complex interplay of the factors described by the informants. PMID:26077985

Expectancy Disconfirmation and Attitude Change.

PubMed

McPeek, Robert W; Edwards, John D

1975-08-01

An experiment was conducted testing the hypothesis that sources delivering unexpected communications (long-haired males arguing against marijuana usage and seminarians arguing in its favor) would be more persuasive than communicators of expected messages (promarijuana hippies and antimarijuana seminarians). Greater attitude change for unexpected sources was found only when the message was antimarijuana. Unexpected communicators also were rated as more sincere and honest than expected sources. Possible reasons for the failure of the expectancy effect to hold for promarijuana communications were suggested, and the results were discussed in terms of a variety of social-psychological theories.

Inattentional deafness in music.

PubMed

Koreimann, Sabrina; Gula, Bartosz; Vitouch, Oliver

2014-01-01

While inattentional blindness is a modern classic in attention and perception research, analogous phenomena of inattentional deafness have been widely neglected. We here present the first investigation of inattentional deafness in and with music under controlled experimental conditions. Inattentional deafness in music is defined as the inability to consciously perceive an unexpected musical stimulus when attention is focused on a certain facet of the piece. Participants listened to a modification of the first 1'50″ of Richard Strauss' Thus Spake Zarathustra; while the control group just listened, the experimental group had to count the number of timpani beats. An e-guitar solo served as the unexpected event. In Study 1, experimental data from n = 115 participants were analyzed. Non-musicians were compared with musicians to investigate the impact of expertise. In Study 2 (n = 47), the scope of the inattentional deafness effect was investigated with a more salient unexpected stimulus. Results demonstrate an inattentional deafness effect under dynamic musical conditions. Quite unexpectedly, the effect was structurally equivalent even for musicians. Our findings clearly show that sustained inattentional deafness exists in the musical realm, in close correspondence to inattentional blindness with dynamic visual stimuli.

Multiple effects of sentential constraint on word processing

PubMed Central

Federmeier, Kara D.; Wlotko, Edward W.; De Ochoa-Dewald, Esmeralda; Kutas, Marta

2009-01-01

Behavioral and electrophysiological studies have uncovered different patterns of constraint effects on the processing of words in sentences. Whereas response time measures have indicated a reduced scope of facilitation from strongly constraining contexts, event-related brain potential (ERP) measures have instead revealed enhanced facilitation for semantically related endings in such sentences. Given this disparity, and the concomitant possibility of functionally separable stages of context effects, the current study jointly examined expectancy (cloze probability) and constraint effects on the ERP response to words. Expected and unexpected (but plausible) words completed strongly and weakly constraining sentences; unexpected items were matched for contextual fit across the two levels of constraint and were semantically unrelated to the most expected endings. N400 amplitudes were graded by expectancy but unaffected by constraint and seemed to index the benefit of contextual information. However, a later effect, in the form of increased frontal positivity from 500 to 900 ms post-stimulus-onset, indicated a possible cost associated with the processing of unexpected words in strongly constraining contexts. PMID:16901469

Striatal and midbrain connectivity with the hippocampus selectively boosts memory for contextual novelty

PubMed Central

Kafkas, Alexandros; Montaldi, Daniela

2015-01-01

The role of contextual expectation in processing familiar and novel stimuli was investigated in a series of experiments combining eye tracking, functional magnetic resonance imaging, and behavioral methods. An experimental paradigm emphasizing either familiarity or novelty detection at retrieval was used. The detection of unexpected familiar and novel stimuli, which were characterized by lower probability, engaged activity in midbrain and striatal structures. Specifically, detecting unexpected novel stimuli, relative to expected novel stimuli, produced greater activity in the substantia nigra/ventral tegmental area (SN/VTA), whereas the detection of unexpected familiar, relative to expected, familiar stimuli, elicited activity in the striatum/globus pallidus (GP). An effective connectivity analysis showed greater functional coupling between these two seed areas (GP and SN/VTA) and the hippocampus, for unexpected than for expected stimuli. Within this network of midbrain/striatal–hippocampal interactions two pathways are apparent; the direct SN–hippocampal pathway sensitive to unexpected novelty and the perirhinal–GP–hippocampal pathway sensitive to unexpected familiarity. In addition, increased eye fixations and pupil dilations also accompanied the detection of unexpected relative to expected familiar and novel stimuli, reflecting autonomic activity triggered by the functioning of these two pathways. Finally, subsequent memory for unexpected, relative to expected, familiar, and novel stimuli was characterized by enhanced recollection, but not familiarity, accuracy. Taken together, these findings suggest that a hippocampal–midbrain network, characterized by two distinct pathways, mediates encoding facilitation and most critically, that this facilitation is driven by contextual novelty, rather than by the absolute novelty of a stimulus. This contextually sensitive neural mechanism appears to elicit increased exploratory behavior, leading subsequently to greater recollection of the unexpected stimulus. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:25708843

System III variations in apparent distance of Io plasma torus from Jupiter

NASA Technical Reports Server (NTRS)

Dessler, A. J.; Sandel, B. R.

1992-01-01

System III variations in apparent distance of the Io plasma torus from Jupiter are examined on the basis of data obtained from UVS scans across Jupiter's satellite system. The displacement of the dawn and dusk ansae are found to be unexpectedly complex. The displacements are unequal and both ansae are in motion with the motion of the approaching ansa being the lesser of the two. The radial motions, as measured from either the center of Jupiter or the offset-tilted dipole, are of unequal magnitude and have the System III periodicity. It is concluded that the cross-tail electric field that causes these torus motions is concentrated on the dusk ansa, varied with the System III period, and shows magnetic-anomaly phase control. It is found that the dawn-dust asymmetry in brightness is not explained simply by the cross-tail electric field. It is concluded that there is a heating mechanism that causes the dusk side of the Io plasma torus to be brighter than the dawn side.

Non-Gaussian Correlations between Reflected and Transmitted Intensity Patterns Emerging from Opaque Disordered Media

NASA Astrophysics Data System (ADS)

Starshynov, I.; Paniagua-Diaz, A. M.; Fayard, N.; Goetschy, A.; Pierrat, R.; Carminati, R.; Bertolotti, J.

2018-04-01

The propagation of monochromatic light through a scattering medium produces speckle patterns in reflection and transmission, and the apparent randomness of these patterns prevents direct imaging through thick turbid media. Yet, since elastic multiple scattering is fundamentally a linear and deterministic process, information is not lost but distributed among many degrees of freedom that can be resolved and manipulated. Here, we demonstrate experimentally that the reflected and transmitted speckle patterns are robustly correlated, and we unravel all the complex and unexpected features of this fundamentally non-Gaussian and long-range correlation. In particular, we show that it is preserved even for opaque media with thickness much larger than the scattering mean free path, proving that information survives the multiple scattering process and can be recovered. The existence of correlations between the two sides of a scattering medium opens up new possibilities for the control of transmitted light without any feedback from the target side, but using only information gathered from the reflected speckle.

An experimental and theoretical study of reaction mechanisms between nitriles and hydroxylamine.

PubMed

Vörös, Attila; Mucsi, Zoltán; Baán, Zoltán; Timári, Géza; Hermecz, István; Mizsey, Péter; Finta, Zoltán

2014-10-28

The industrially relevant reaction between nitriles and hydroxylamine yielding amidoximes was studied in different molecular solvents and in ionic liquids. In industry, this procedure is carried out on the ton scale in alcohol solutions and the above transformation produces a significant amount of unexpected amide by-product, depending on the nature of the nitrile, which can cause further analytical and purification issues. Although there were earlier attempts to propose mechanisms for this transformation, the real reaction pathway is still under discussion. A new detailed reaction mechanistic explanation, based on theoretical and experimental proof, is given to augment the former mechanisms, which allowed us to find a more efficient, side-product free procedure. Interpreting the theoretical results obtained, it was shown that the application of specific imidazolium, phosphonium and quaternary ammonium based ionic liquids could decrease simultaneously the reaction time while eliminating the amide side-product, leading to the targeted product selectively. This robust and economic procedure now affords a fast, selective amide free synthesis of amidoximes.

Asymmetric balance control between legs for quiet but not for perturbed stance.

PubMed

Vieira, Osvaldo; Coelho, Daniel Boari; Teixeira, Luis Augusto

2014-10-01

Interlateral performance asymmetry in upright balance control was evaluated in this investigation by comparing unipedal stance on the right versus the left leg. Participants were healthy young adults, hand-foot congruent preference for the right body side. Balance performance was evaluated in unperturbed quiet stance and in the recovery of balance stability following a mechanical perturbation induced by unexpected load release. Evaluation was made under availability of full sensory information, and under deprivation of vision combined with distortion of sensory inputs from the feet soles. Results from perturbed posture revealed that muscular response latency and postural sway were symmetric between the legs. Unipedal stance was more stable when the body was supported on the right as compared with the left leg. No interaction was found between leg and sensory condition. Our findings are interpreted as resulting from specialization of the sensorimotor system controlling the right leg for continuous low-magnitude postural adjustments, while corrections to large-scale stance sway are symmetrically controlled between body sides.

An Unexpected Influence on a Quadratic

ERIC Educational Resources Information Center

Davis, Jon D.

2013-01-01

Using technology to explore the coefficients of a quadratic equation can lead to an unexpected result. This article describes an investigation that involves sliders and dynamically linked representations. It guides students to notice the effect that the parameter "a" has on the graphical representation of a quadratic function in the form…

The Influence of Attention Set, Working Memory Capacity, and Expectations on Inattentional Blindness.

PubMed

Kreitz, Carina; Furley, Philip; Memmert, Daniel; Simons, Daniel J

2016-04-01

The probability of inattentional blindness, the failure to notice an unexpected object when attention is engaged on some primary task, is influenced by contextual factors like task demands, features of the unexpected object, and the observer's attention set. However, predicting who will notice an unexpected object and who will remain inattentionally blind has proven difficult, and the evidence that individual differences in cognition affect noticing remains ambiguous. We hypothesized that greater working memory capacity might modulate the effect of attention sets on noticing because working memory is associated with the ability to focus attention selectively. People with greater working memory capacity might be better able to attend selectively to target items, thereby increasing the chances of noticing unexpected objects that were similar to the attended items while decreasing the odds of noticing unexpected objects that differed from the attended items. Our study (N = 120 participants) replicated evidence that task-induced attention sets modulate noticing but found no link between noticing and working memory capacity. Our results are largely consistent with the idea that individual differences in working memory capacity do not predict noticing of unexpected objects in an inattentional blindness task. © The Author(s) 2015.

The event-related potential effects of cognitive conflict in a Chinese character-generation task.

PubMed

Qiu, Jiang; Zhang, Qinglin; Li, Hong; Luo, Yuejia; Yin, Qinging; Chen, Antao; Yuan, Hong

2007-06-11

High-density event-related potentials were recorded to examine the electrophysiologic correlates of the evaluation of possible answers provided during a Chinese character-generation task. We examined three conditions: the character given was what participants initially generated (Consistent answer), the character given was correct (Unexpected Correct answer), or it was incorrect (Unexpected Incorrect answer). Results showed that Unexpected Correct and Incorrect answers elicited a more negative event-related potential deflection (N320) than did Consistent answers between 300 and 400 ms. Dipole source analysis of difference waves (Unexpected Correct or Incorrect minus Consistent answers) localized the generator of the N320 in the anterior cingulate cortex. The N320 therefore likely reflects the cognitive change or conflict between old and new ways of thinking while identifying and judging characters.

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

PubMed

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

2017-03-01

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

Image-guided percutaneous microwave ablation of small renal tumours: short- and mid-term outcomes.

PubMed

Genson, Pierre-Yves; Mourey, Eric; Moulin, Morgan; Favelier, Sylvain; Di Marco, Lucy; Chevallier, Olivier; Cercueil, Jean-Pierre; Krausé, Denis; Cormier, Luc; Loffroy, Romaric

2015-10-01

The purpose is to assess the short- and mid-term outcomes of microwave ablation (MWA) of small renal tumours in selected patients. From August 2012 to February 2015, 29 renal tumours in 23 patients (17 male, 6 female, mean age 75 years) were treated by percutaneous MWA under imaging guidance. The tumours were 1-4.7 cm in diameter (mean size, 2.7 cm). Therapeutic effects were assessed at follow-up with magnetic resonance imaging (MRI). All patients were followed up for 2-25 months (mean, 12.2 months) to observe the therapeutic effects and complications. Changes in renal function at day 1 after treatment were statistically analyzed using the Student paired t-test or the paired Wilcoxon test. Technical success was achieved in all cases. One severe bleeding complication post-procedure occurred leading to death. No other unexpected side effects were observed after the MWA procedures. Clinical effectiveness was 100%. None of the patients showed recurrence on MRI imaging follow-up. No significant changes in renal function were noted after treatment (P=0.57). Our preliminary study demonstrates that the use of MWA for the treatment of small renal tumours can be applied as safely and efficiently as other ablative techniques in selected patients not eligible for surgery.

Inhibition of mTOR enhances radiosensitivity of lung cancer cells and protects normal lung cells against radiation.

PubMed

Zheng, Hang; Wang, Miao; Wu, Jing; Wang, Zhi-Ming; Nan, Hai-Jun; Sun, He

2016-06-01

Radiotherapy has been used for a long time as a standard therapy for cancer; however, there have been no recent research breakthroughs. Radioresistance and various side-effects lead to the unexpected outcomes of radiation therapy. Specific and accurate targeting as well as reduction of radioresistance have been major challenges for irradiation therapy. Recent studies have shown that rapamycin shows promise for inhibiting tumorigenesis by suppressing mammalian target of rapamycin (mTOR). We found that the combination of rapamycin with irradiation significantly diminished cell viability and colony formation, and increased cell apoptosis, as compared with irradiation alone in lung cancer cell line A549, suggesting that rapamycin can enhance the effectiveness of radiation therapy by sensitizing cancer cells to irradiation. Importantly, we observed that the adverse effects of irradiation on a healthy lung cell line (WI-38) were also offset. No enhanced protein expression of mTOR signaling was observed in WI-38 cells, which is normally elevated in lung cancer cells. Moreover, DNA damage was significantly less with the combination therapy than with irradiation therapy alone. Our data suggest that the incorporation of rapamycin during radiation therapy could be a potent way to improve the sensitivity and effectiveness of radiation therapy as well as to protect normal cells from being damaged by irradiation.

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

PubMed Central

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

2017-01-01

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

Intraarticular Ankaferd blood stopper application increases cartilagedegeneration: an experimental study.

PubMed

Kaya, İbrahim; Gülabi, Deniz; Yilmaz, Murat; Baş, Ali; Çeçen, Gültekin Sıtkı Çeçen; Şener, Nurullah

2016-01-05

Ankaferd blood stopper (ABS) is a mixture of certain ratios of 5 different plant roots (Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica). The aim of this study is to evaluate the histopathological effects of ABS on articular cartilage in vitro. Twenty-one albino Sprague Dawley rats were randomly allocated to 3 groups: 0.1 mL of saline was injected in the first group, 0.1 mL of ABS was injected in the second group, and 0.1 mL of blood and 0.1 mL of ABS were injected in the third group. One month later all rats were sacrificed. Specimens were obtained for histopathological evaluation. Significant results were detected in the groups with respect to International Cartilage Repair Society and synovial proliferation scores (P < 0.05 and P < 0.01). According to inflammatory cell infiltration and fibrin formation scores, there was no significant difference between group 1 and group 2 (P < 0.01), although there was significant difference between group 3 and the other groups (P > 0.05). ABS and hemarthrosis had toxic effects on knee cartilage. The side effects were increased with the combination of hemarthrosis and ABS. As a result, ABS had unexpected effects on experimental hemarthrosis.

Short-term muscle atrophy caused by botulinum toxin-A local injection impairs fracture healing in the rat femur.

PubMed

Hao, Yongqiang; Ma, Yongcheng; Wang, Xuepeng; Jin, Fangchun; Ge, Shengfang

2012-04-01

Damaged bone is sensitive to mechanical stimulation throughout the remodeling phase of bone healing. Muscle damage and muscular atrophy associated with open fractures and subsequent fixation are not beneficial to maintaining optimum conditions for mechanical stability. The aim of this study was to investigate whether local muscle atrophy and dysfunction affect fracture healing in a rat femur fracture model. We combined the rat model of a short period atrophy of the quadriceps with femur fracture. Forty-four-month-old male Wistar rats were adopted for this study. Two units of botulinum toxin-A (BXTA) were administered locally into the right side of the quadriceps of each rat, while the same dose of saline was injected into the contralateral quadriceps. After BXTA had been fully absorbed by the quadriceps, osteotomy was performed in both femurs with intramedullary fixation. Gross observation and weighing of muscle tissue, X-ray analysis, callus histology, and bone biomechanical testing were performed at different time points up to 8 weeks post-surgery. Local injection of BXTA led to a significant decrease in the volume and weight of the quadriceps compared to the control side. At the eighth week, the left side femurs of the saline-injected quadriceps almost reached bony union, and fibrous calluses were completely calcified into woven bone. However, a gap was still visible in the BXTA-treated side on X-ray images. As showed by bone histology, there were no mature osseous calluses or woven bone on the BXTA-treated side, but a resorption pattern was evident. Biomechanical testing indicated that the femurs of the BXTA-treated side exhibited inferior mechanical properties compared with the control side. The inferior outcome following BXTA injection, compared with saline injection, in terms of callus resistance may be the consequence of unexpected load and mechanical unsteadiness caused by muscle atrophy and dysfunction. Copyright © 2011 Orthopaedic Research Society.

Illnesses and Other Causes of Unexpected Absences from Work During Residency Training.

ERIC Educational Resources Information Center

Parker, Ruth M.; And Others

1987-01-01

Unexpected absences from work among residents cause scheduling difficulties and stress among residents. University of Rochester internal medicine and pediatric residents recorded the days they had been absent from work and provided their opinions regarding the stress these absences caused and the effectiveness for the sick-call system. (Author/MLW)

A systematic review of effectiveness and safety of different regimens of levonorgestrel oral tablets for emergency contraception.

PubMed

Shohel, Mohammad; Rahman, Mohammad Mahfuzur; Zaman, Asif; Uddin, Mir Muhammad Nasir; Al-Amin, Md Mamun; Reza, Hasan Mahmud

2014-04-04

Unintended pregnancy is a complex phenomenon which raise to take an emergency decision. Low contraceptive prevalence and high user failure rates are the leading causes of this unexpected situation. High user failure rates suggest the vital role of emergency contraception to prevent unplanned pregnancy. Levonorgestrel - a commonly used progestin for emergency contraception. However, little is known about its pharmacokinetics and optimal dose for use. Hence, there is a need to conduct a systematic review of the available evidences. Randomized, double-blind trials were sought, evaluating healthy women with regular menstrual cycles, who requested emergency contraception within 72 h of unprotected coitus, to one of three regimens: 1.5 mg single dose levonorgestrel, two doses of 0.75 mg levonorgestrel given 12 h apart or two doses of 0.75 mg levonorgestrel given 24 h apart. The primary outcome was unintended pregnancy; other outcomes were side-effects and timing of next menstruation. Every trial under consideration successfully established the contraceptive effectiveness of levonorgestrel for preventing unintended pregnancy. Moreover, a single dose of levonorgestrel 1.5 mg for emergency contraception supports its safety and efficacy profile. If two doses of levonorgestrel 0.75 mg are intended for administration, the second dose can positively be taken 12-24 h after the first dose without compromising its contraceptive efficacy. The main side effect was frequent menstrual irregularities. No serious adverse events were reported. The review shows that, emergency contraceptive regimen of single-dose levonorgestrel is not inferior in efficacy to the two-dose regimen. All the regimens studied were very efficacious for emergency contraception and prevented a high proportion of pregnancies if taken within 72 h of unprotected coitus. Single levonorgestrel dose (1.5 mg) can substitute two 0.75 mg doses 12 or 24 h apart. With either regimen, the earlier the treatment is given, the more effective it seems to be.

A systematic review of effectiveness and safety of different regimens of levonorgestrel oral tablets for emergency contraception

PubMed Central

2014-01-01

Background Unintended pregnancy is a complex phenomenon which raise to take an emergency decision. Low contraceptive prevalence and high user failure rates are the leading causes of this unexpected situation. High user failure rates suggest the vital role of emergency contraception to prevent unplanned pregnancy. Levonorgestrel - a commonly used progestin for emergency contraception. However, little is known about its pharmacokinetics and optimal dose for use. Hence, there is a need to conduct a systematic review of the available evidences. Methods Randomized, double-blind trials were sought, evaluating healthy women with regular menstrual cycles, who requested emergency contraception within 72 h of unprotected coitus, to one of three regimens: 1.5 mg single dose levonorgestrel, two doses of 0.75 mg levonorgestrel given 12 h apart or two doses of 0.75 mg levonorgestrel given 24 h apart. The primary outcome was unintended pregnancy; other outcomes were side-effects and timing of next menstruation. Results Every trial under consideration successfully established the contraceptive effectiveness of levonorgestrel for preventing unintended pregnancy. Moreover, a single dose of levonorgestrel 1.5 mg for emergency contraception supports its safety and efficacy profile. If two doses of levonorgestrel 0.75 mg are intended for administration, the second dose can positively be taken 12–24 h after the first dose without compromising its contraceptive efficacy. The main side effect was frequent menstrual irregularities. No serious adverse events were reported. Conclusions The review shows that, emergency contraceptive regimen of single-dose levonorgestrel is not inferior in efficacy to the two-dose regimen. All the regimens studied were very efficacious for emergency contraception and prevented a high proportion of pregnancies if taken within 72 h of unprotected coitus. Single levonorgestrel dose (1.5 mg) can substitute two 0.75 mg doses 12 or 24 h apart. With either regimen, the earlier the treatment is given, the more effective it seems to be. PMID:24708837

Animacy, perceptual load, and inattentional blindness.

PubMed

Calvillo, Dustin P; Jackson, Russell E

2014-06-01

Inattentional blindness is the failure to notice unexpected objects in a visual scene while engaging in an attention-demanding task. We examined the effects of animacy and perceptual load on inattentional blindness. Participants searched for a category exemplar under low or high perceptual load. On the last trial, the participants were exposed to an unexpected object that was either animate or inanimate. Unexpected objects were detected more frequently when they were animate rather than inanimate, and more frequently with low than with high perceptual loads. We also measured working memory capacity and found that it predicted the detection of unexpected objects, but only with high perceptual loads. The results are consistent with the animate-monitoring hypothesis, which suggests that animate objects capture attention because of the importance of the detection of animate objects in ancestral hunter-gatherer environments.

Evolutions of elastic-plastic shock compression waves in different materials

NASA Astrophysics Data System (ADS)

Kanel, G. I.; Zaretsky, E. B.; Razorenov, S. V.; Savinykh, A. S.; Garkushin, G. V.

2017-01-01

In the paper, we discuss such unexpected features in the wave evolution in solids as a departure from self-similar development of the wave process which is accompanied with apparent sub-sonic wave propagation, changes of shape of elastic precursor wave as a result of variations in the material structure and the temperature, unexpected peculiarities of reflection of elastic-plastic waves from free surface, effects of internal friction at shock compression of glasses and some other effects.

Unexplained head tilt following surgical treatment of congenital esotropia: a postural manifestation of dissociated vertical divergence

PubMed Central

Brodsky, M C; Jenkins, R; Nucci, P

2004-01-01

Background: Strabismus surgery for congenital esotropia can be complicated by the development of a postoperative head tilt. Purpose: To determine the pathophysiology of acquired head tilting following horizontal realignment of the eyes in children with congenital esotropia. Materials and methods: Retrospective analysis of nine children with congenital esotropia who developed unexplained head tilts following horizontal realignment of the eyes. Results: Shortly after strabismus surgery, each child developed a head tilt in association with asymmetrical dissociated vertical divergence (DVD). Five children maintained a head tilt toward the side of the fixing eye (group 1), which did not serve to control the DVD. Four children maintained a head tilt toward the side of the hyperdeviating eye, which served to control the DVD (group 2). Children in group 2 had earlier horizontal muscle surgery and developed better stereopsis than those in group 1, suggesting that the higher degree of single binocular vision and stereopsis in these children may have led to a compensatory torticollis to control an asymmetrical DVD. Conclusions: The onset of an unexpected head tilt after congenital esotropia surgery is usually a postural manifestation of asymmetrical DVD. In this setting, a head tilt toward the side of the fixing eye corresponds with a postural manifestation of the underlying central vestibular imbalance that produces DVD, while a head tilt toward the side of the hyperdeviating eye serves to counteract the hyperdeviation and stabilise binocular vision. PMID:14736789

The role of domain expertise and judgment in dealing with unexpected events

NASA Astrophysics Data System (ADS)

Kochan, Janeen Adrion

Unexpected events, particularly those creating surprise, interrupt ongoing mental and behavioral processes, creating an increased potential for unwanted outcomes to the situation. Human reactions to unexpected events vary. One can hypothesize a number of reasons for this variation, including level of domain expertise, previous experience with similar events, emotional connotation, and the contextual surround of the event. Whereas interrupting ongoing activities and focusing attention temporarily on a surprising event may be a useful evolutionary response to a threatening situation, the same process may be maladaptive in today's highly dynamic world. The purpose of this study was to investigate how different aspects of expertise affected one's ability to detect and react to an unexpected event. It was hypothesized that there were two general types of expertise, domain expertise and judgment (Hammond, 2000), which influenced one's performance on dealing with an unexpected event. The goal of the research was to parse out the relative contribution of domain expertise, so the role of judgment could be revealed. The research questions for this study were: (a) Can we identify specific knowledges and skills which enhance one's ability to deal with unexpected events? (b) Are these skills "automatically" included in domain expertise? (c) How does domain expertise improve or deter one's reaction and response to unexpected events? (d) What role does judgment play in responding to surprise? The general hypothesis was that good judgment would influence the process of surprise at different stages and in different ways than would domain expertise. The conclusions from this research indicated that good judgment had a significant positive effect in helping pilots deal with unexpected events. This was most pronounced when domain expertise was low.

Effect of rear end spoiler angle of a sedan car

NASA Astrophysics Data System (ADS)

Mashud, Mohammad; Das, Rubel Chandra

2017-06-01

Automotive vehicle's performance, safety, maneuverability can be influenced by multi-disciplinary factors such as car engine, tires, aerodynamics, and ergonomics of design. With the recent years, inflation in the fuel prices & the demand to have reduced greenhouse emissions has played a significant role in redefining the car aerodynamics. The shape of the vehicle uses about 3% of fuel to overcome the resistance in urban driving, while it takes 11% of fuel for the highway driving. This considerable high value of fuel usage in highway driving attracts several design engineers to enhance the aerodynamics of the vehicle using minimal design changes. Besides, automotive vehicles have become so much faster experiencing uplift force which creates unexpected accidents. This brings the idea of using external devices, which could be attached to the present vehicle without changing the body. This paper is based on the design, developments and numeral calculation of the effects of external device, which will be spoiler that mounted at the rear side of the sedan car to make the present vehicles more aerodynamically attractive. The influence of rear spoiler on the generated lift, drag, and pressure distributions are investigated and reported using commercially available Autodesk Simulation CFD software tool.

Asymmetric pain processing in Parkinson's disease.

PubMed

Granovsky, Y; Schlesinger, I; Fadel, S; Erikh, I; Sprecher, E; Yarnitsky, D

2013-10-01

Reduced endogenous pain inhibition, as part of the degenerative process, is presumed to be the mechanism underlying the common presence of pain in patients with Parkinson's disease (PD). The present study aimed to assess an endogenous pain inhibitory system in PD using the conditioned pain modulation paradigm. Twenty-six predominantly unilateral PD patients and 19 controls underwent psychophysical pain assessment before and after patients' morning dopaminergic medication. An unexpected increase in several parameters of pain perception for PD patients was found after dopaminergic medication (e.g. for 49°C noxious heat stimulation an increase from 70.6 ± 4.0 to 77.6 ± 4.0 on the numerical pain scale, P < 0.001). This increase was seen in patients with predominantly left-sided PD, regardless of the stimulated side (for 49°C noxious heat stimulation, predominantly left-sided PD patients, pain perception increased from 73.5 ± 6.8 to 85.0 ± 6.8, P < 0.001, whereas predominantly right-sided PD patients did not show a significant increase, 68.3 ± 6.8 to 70.4 ± 6.5, P = 0.777). Baseline efficiency of conditioned pain modulation inversely correlated with age at disease onset (r = -0.522; P = 0.009) and disease severity (Unified PD Rating Scale, r = 0.447; P = 0.032) but did not differ between patients and controls. Increased sensory response causing hyperalgesia occurs after dopaminergic medication in patients with predominantly left-sided PD. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Structural Factors and Mechanisms Underlying the Improved Photodynamic Cell Killing with Silicon Phthalocyanine Photosensitizers Directed to Lysosomes Versus Mitochondria

PubMed Central

Rodriguez, Myriam E.; Zhang, Ping; Azizuddin, Kashif; Delos Santos, Grace B.; Chiu, Song-mao; Xue, Liang-yan; Berlin, Jeffery C.; Peng, Xinzhan; Wu, Hongqiao; Lam, Minh; Nieminen, Anna-Liisa; Kenney, Malcolm E.; Oleinick, Nancy L.

2012-01-01

The phthalocyanine photosensitizer Pc 4 has been shown to bind preferentially to mitochondrial and endoplasmic reticulum membranes. Upon photoirradiation of Pc 4-loaded cells, membrane components, especially Bcl-2, are photodamaged and apoptosis, as indicated by activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase, is triggered. A series of analogs of Pc 4 were synthesized, and the results demonstrate that Pcs with the aminopropylsiloxy ligand of Pc 4 or a similar one on one side of the Pc ring and a second large axial ligand on the other side of the ring have unexpected properties, including enhanced cell uptake, greater monomerization resulting in greater intracellular fluorescence and three-fold higher affinity constants for liposomes. The hydroxyl-bearing axial ligands tend to reduce aggregation of the Pc and direct it to lysosomes, resulting in four to six times more killing of cells, as defined by loss of clonogenicity, than with Pc 4. Whereas Pc 4-PDT photodamages Bcl-2 and Bcl-xL, Pc 181-PDT causes much less photodamage to Bcl-2 over the same dose–response range relative to cell killing, with earlier cleavage of Bid and slower caspase-3-dependent apoptosis. Therefore, within this series of photosensitizers, these hydroxyl-bearing axial ligands are less aggregated than is Pc 4, tend to localize to lysosomes and are more effective in overall cell killing than is Pc 4, but induce apoptosis more slowly and by a modified pathway. PMID:19508642

Data sets for manuscript titled Unexpected benefits of reducing aerosol cooling effects

EPA Pesticide Factsheets

These data sets were created using extensive model simulation results from the WRF-CMAQ model, population distributions, and through the use of an health impact assessment model - see manuscript for details.This dataset is associated with the following publication:Xing, J., J. Wang, R. Mathur , J. Pleim , S. Wang, C. Hogrefe , C. Gan, D. Wong , and J. Hao. Unexpected Benefits of Reducing Aerosol Cooling Effects. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, USA, 50(14): 7527–7534, (2016).

'Rhyme or reason?' Saying no to mass vaccination: subjective re-interpretation in the context of the A(H1N1) influenza pandemic in Sweden 2009-2010.

PubMed

Lundgren, Britta

2015-12-01

During the swine flu pandemic of 2009-2010, all Swedish citizens were recommended to be vaccinated with the influenza vaccine Pandemrix. However, a very serious and unexpected side effect emerged during the summer of 2010: more than 200 children and young adults were diagnosed with narcolepsy after vaccination. Besides the tragic outcome for these children and their families, this adverse side effect suggests future difficulties in obtaining trust in vaccination in cases of emerging pandemics, and thus there is a growing need to find ways to understand the complexities of vaccination decision processes. This article explores written responses to a questionnaire from a Swedish folk life archive as an unconventional source for analysing vaccine decisions. The aim is to investigate how laypersons responded to and re-interpreted the message about the recommended vaccination in their answers. The answers show the confusion and complex circumstances and influences in everyday life that people reflect on when making such important decisions. The issue of confusion is traced back to the initial communications about the vaccination intervention in which both autonomy and solidarity were expected from the population. Common narratives and stories about the media or 'big pharma capitalism' are entangled with private memories, accidental coincidences and serendipitous associations. It is obvious that vaccination interventions that require compliance from large groups of people need to take into account the kind of personal experience narratives that are produced by the complex interplay of the factors described by the informants. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

2D and 3D similarity landscape analysis identifies PARP as a novel off-target for the drug Vatalanib.

PubMed

Gohlke, Bjoern-Oliver; Overkamp, Tim; Richter, Anja; Richter, Antje; Daniel, Peter T; Gillissen, Bernd; Preissner, Robert

2015-09-24

Searching for two-dimensional (2D) structural similarities is a useful tool to identify new active compounds in drug-discovery programs. However, as 2D similarity measures neglect important structural and functional features, similarity by 2D might be underestimated. In the present study, we used combined 2D and three-dimensional (3D) similarity comparisons to reveal possible new functions and/or side-effects of known bioactive compounds. We utilised more than 10,000 compounds from the SuperTarget database with known inhibition values for twelve different anti-cancer targets. We performed all-against-all comparisons resulting in 2D similarity landscapes. Among the regions with low 2D similarity scores are inhibitors of vascular endothelial growth factor receptor (VEGFR) and inhibitors of poly ADP-ribose polymerase (PARP). To demonstrate that 3D landscape comparison can identify similarities, which are untraceable in 2D similarity comparisons, we analysed this region in more detail. This 3D analysis showed the unexpected structural similarity between inhibitors of VEGFR and inhibitors of PARP. Among the VEGFR inhibitors that show similarities to PARP inhibitors was Vatalanib, an oral "multi-targeted" small molecule protein kinase inhibitor being studied in phase-III clinical trials in cancer therapy. An in silico docking simulation and an in vitro HT universal colorimetric PARP assay confirmed that the VEGFR inhibitor Vatalanib exhibits off-target activity as a PARP inhibitor, broadening its mode of action. In contrast to the 2D-similarity search, the 3D-similarity landscape comparison identifies new functions and side effects of the known VEGFR inhibitor Vatalanib.

Comparative Analgesic Efficacy of Oxycodone/Acetaminophen vs Codeine/Acetaminophen for Short-Term Pain Management Following ED Discharge.

PubMed

Chang, Andrew K; Bijur, Polly E; Lupow, Jason B; Gallagher, E John

2015-12-01

To test the hypothesis that oxycodone/acetaminophen provides analgesia superior to codeine/acetaminophen following emergency department (ED) discharge. Prospective, randomized, double-blind, trial. Adult inner city ED. ED patients with acute extremity pain who were discharged home. Patients randomized to oxycodone/acetaminophen (5 mg/325 mg) or codeine/acetaminophen (30 mg/300 mg). The primary outcome, obtained via telephone one day after ED discharge, was the between-group difference in improvement in numerical rating scale (NRS) pain scores over a 2-hour period following the most recent ingestion of study drug. Secondary outcomes included proportion of patients with >50% pain reduction, side-effect profile, and patient satisfaction. Two hundred and forty patients were enrolled. Mean baseline NRS scores were 7.9 in both groups. Mean decrease over 2 hours was 4.5 NRS units in the oxycodone/acetaminophen group vs 4.2 NRS units in the codeine/acetaminophen group, for a clinically and statistically nonsignificant difference of 0.2 NRS units (95% CI -0.4-0.9 NRS units). Similarly, 66% vs 61% achieved >50% pain relief for a nonsignificant difference of 5% (95% CI -8% to 17%). Side-effect profile and patient satisfaction were similar. Our hypothesis that oxycodone/acetaminophen provides analgesia superior to codeine/acetaminophen was rejected. Although pain within each group was reduced by more than half, the between-group difference was not significant. Pending independent validation, these unexpected findings suggest that codeine/acetaminophen, a Schedule III agent, may be a clinically reasonable outpatient opioid alternative to oxycodone/acetaminophen, a more tightly restricted Schedule II agent thought to be more prone to misuse. Wiley Periodicals, Inc.

New lasers and light sources - old and new risks?

PubMed

Paasch, Uwe; Schwandt, Antje; Seeber, Nikolaus; Kautz, Gerd; Grunewald, Sonja; Haedersdal, Merete

2017-05-01

Recent developments (new wavelengths, treatment concepts, and combinations) in the field of lasers, intense pulsed light (IPL), LED, as well as new energy and light sources have opened up new therapeutic options that extend beyond mere aesthetic indications. Thus, while fractional lasers used to be employed to merely treat wrinkles, the same devices - in the context of laser-assisted drug delivery - have now become important tools in the treatment of scars, field cancerization, and epithelial tumors. The requirements posed to physicians, both with respect to establishing the indication and conducting treatment, have been growing along with the increase in technological complexity as well as the rising number of comorbidities and comedications in a patient population that continues to age. At the same time, home-use devices have been introduced for a variety of indications. These devices are characterized by low power and special safety features aimed at preventing accidents, risks, and side effects. Despite the reduced efficacy of such self-treatment devices, there is an increased risk of misuse, given that the basic prerequisite for adequate treatment cannot be ensured, to wit, the exact diagnosis and therapeutic indication. Consequently, during hair removal or anti-wrinkle treatment, pigmented lesions and cutaneous neoplasms may be altered, thus giving rise to expected, unexpected and new side effects and complications. In the aforementioned setting, it is important that all potential users of these new technologies be properly trained in a manner that ensures those treated a maximum of safety and efficacy in accordance with the guiding principle "diagnosis certa - ullae therapiae fundamentum". © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

[What's new in pediatric dermatology?

PubMed

Léauté-Labrèze, C

2016-12-01

The association of a birth defect and a segmental hemangioma is well established, a consensus concerning evaluation and monitoring of infants with PHACE or LUMBAR syndromes has been published. The efficacy of propranolol in infantile hemangioma is proven; however there were still unresolved issues concerning the safety in children; after 8 years of use on thousands of children safety data collection did not show any unexpected side effects. Topical treatment of infantile hemangiomas with beta-blockers, such as timolol, is very popular, but recent publications revealed a significant systemic absorption that could be responsible for severe side effects, such as bradycardia, in low birthweight infants. As a consequence, this therapeutic option should be considered with caution. In the last 2 years mTOR inhibitors have been tested in low-flow vascular malformations with varying success, but progress remains to be done in the treatment of vascular abnormalities. Today, genetics has led to advances in the understanding of the pathophysiology and in the future targeted therapies could probably be feasible. Skin barrier deficiency is responsible for the development of allergic phenomena in atopic patients, since it has been shown that sensibilisation, even to food, could probably be induced by skin contact. Unfortunately, the topical treatment with crisaborole, a phosphodiesterase 4 inhibitor, does not look like a revolution in children atopic dermatitis, its efficacy seems equivalent to emollient application. In the field of infectious diseases, changes in viral outbreaks are the most reported. Furthermore epidemic Zika virus, enteroviruses are responsible for expanded dermatological manifestations and also severe meningoencephalitis. Paraviral character of various eruptions, such as gloves and socks syndrome or eruptive pseudoangiomatosis is challenged. © 2016 Elsevier Masson SAS. Tous droits réservés.

The cursed duet today: Tuberculosis and HIV-coinfection.

PubMed

Tiberi, Simon; Carvalho, Anna Cristina C; Sulis, Giorgia; Vaghela, Devan; Rendon, Adrian; Mello, Fernanda C de Q; Rahman, Ananna; Matin, Nashaba; Zumla, Ali; Pontali, Emanuele

2017-03-01

The tuberculosis (TB) and HIV syndemic continues to rage and are a major public health concern worldwide. This deadly association raises complexity and represent a significant barrier towards TB elimination. TB continues to be the leading cause of death amongst HIV-infected people. This paper reports the challenges that lay ahead and outlines some of the current and future strategies that may be able to address this co-epidemic efficiently. Improved diagnostics, cheaper and more effective drugs, shorter treatment regimens for both drug-sensitive and drug-resistant TB are discussed. Also, special topics on drug interactions, TB-IRIS and TB relapse are also described. Notwithstanding the defeats and meagre investments, diagnosis and management of the two diseases have seen significant and unexpected improvements of late. On the HIV side, expansion of ART coverage, development of new updated guidelines aimed at the universal treatment of those infected, and the increasing availability of newer, more efficacious and less toxic drugs are an essential element to controlling the two epidemics. On the TB side, diagnosis of MDR-TB is becoming easier and faster thanks to the new PCR-based technologies, new anti-TB drugs active against both sensitive and resistant strains (i.e. bedaquiline and delamanid) have been developed and a few more are in the pipeline, new regimens (cheaper, shorter and/or more effective) have been introduced (such as the "Bangladesh regimen") or are being tested for MDR-TB and drug-sensitive-TB. However, still more resources will be required to implement an integrated approach, install new diagnostic tests, and develop simpler and shorter treatment regimens. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Suppression of bone resorption by miR-141 in aged rhesus monkeys.

PubMed

Yang, Shihua; Zhang, Wenhui; Cai, Mingxiang; Zhang, Yuanxu; Jin, Fujun; Yan, Sen; Baloch, Zulqurain; Fang, Zhihao; Xue, Senren; Tang, Rongping; Xiao, Jia; Huang, Qunshan; Sun, Yao; Wang, Xiaogang

2018-05-31

Aging-related osteoporosis is considered as serious public health concern. Approximately 30% of postmenopausal women suffer from osteoporosis, and more than 40% of them risk fragility fractures. Multiple types of drugs have been applied to treat osteoporosis, but they are not ideal due to insufficient curing and adverse side effects. miRNA-based gene therapy is a rapidly developed strategy in disease treatment that presents certain advantages, such as large-scale production, genetic safety and rapid effects. Until now, miRNA drugs have been used in investigations of cancer treatments. However, in primates, miRNA drugs have not yet been reported as candidates for osteoclast-targeting osteoporosis treatment. In addition, the therapeutic efficacy was limited by several shortcomings, such as low efficiency of selective delivery, insufficient expression levels in targeting cells, and unexpected side effects. Here, we identify miR-141 as a critical suppressor of osteoclastogenesis and bone resorption. The expression levels of miR-141 are positively correlated with bone mineral density and negatively correlated with aging of bones in both aged rhesus monkeys (Macaca mulatta) and osteoporotic patients. Selective delivery of miR-141 into osteoclasts of aged rhesus monkeys via a nucleic acid delivery system allowed for a gradual increase in bone mass without significant effects on health behavior and function of primary organs. Furthermore, we found that the functional mechanism of miR-141 is targeting two osteoclast differentiation players, Calcr (calcitonin receptors) and EphA2 (Ephrin type-A receptor 2 precursor). Our study suggests that miRNAs such as miR-141 could play a crucial role in suppressing bone resorption in primates and provide reliable experimental evidence for the clinical application of miRNA in osteoporosis treatment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Pharmacokinetic Herb-Drug Interactions: Insight into Mechanisms and Consequences.

PubMed

Oga, Enoche F; Sekine, Shuichi; Shitara, Yoshihisa; Horie, Toshiharu

2016-04-01

Herbal medicines are currently in high demand, and their popularity is steadily increasing. Because of their perceived effectiveness, fewer side effects and relatively low cost, they are being used for the management of numerous medical conditions. However, they are capable of affecting the pharmacokinetics and pharmacodynamics of coadministered conventional drugs. These interactions are particularly of clinically relevance when metabolizing enzymes and xenobiotic transporters, which are responsible for the fate of many drugs, are induced or inhibited, sometimes resulting in unexpected outcomes. This article discusses the general use of herbal medicines in the management of several ailments, their concurrent use with conventional therapy, mechanisms underlying herb-drug interactions (HDIs) as well as the drawbacks of herbal remedy use. The authors also suggest means of surveillance and safety monitoring of herbal medicines. Contrary to popular belief that "herbal medicines are totally safe," we are of the view that they are capable of causing significant toxic effects and altered pharmaceutical outcomes when coadministered with conventional medicines. Due to the paucity of information as well as sometimes conflicting reports on HDIs, much more research in this field is needed. The authors further suggest the need to standardize and better regulate herbal medicines in order to ensure their safety and efficacy when used alone or in combination with conventional drugs.

Total Synthesis of Ionic Liquid Systems for Dissolution of Lunar Simulant

NASA Technical Reports Server (NTRS)

Sharpe, Robert J.; Karr, Laurel J.; Paley, Mark S.

2010-01-01

For purposes of Space Resource Utilization, work in the total synthesis of a new ionic liquid system for the extraction of oxygen and metals from lunar soil is studied and described. Reactions were carried out according to procedures found in the chemical literature, analyzed via Thin-Layer Chromatography and 1H Nuclear Magnetic Resonance Spectroscopy and purified via vacuum distillation and rotary evaporation. Upon final analysis via 1H NMR, it was found that while the intermediates of the synthesis had been achieved, unexpected side products were also present. The mechanisms and constraints of the synthesis are described as well as the final results of the project and recommendations for continued study

Characterization of member of DUF1888 protein family, self-cleaving and self-assembling endopeptidase.

PubMed

Osipiuk, Jerzy; Mulligan, Rory; Bargassa, Monireh; Hamilton, John E; Cunningham, Mark A; Joachimiak, Andrzej

2012-06-01

The crystal structure of SO1698 protein from Shewanella oneidensis was determined by a SAD method and refined to 1.57 Å. The structure is a β sandwich that unexpectedly consists of two polypeptides; the N-terminal fragment includes residues 1-116, and the C-terminal one includes residues 117-125. Electron density also displayed the Lys-98 side chain covalently linked to Asp-116. The putative active site residues involved in self-cleavage were identified; point mutants were produced and characterized structurally and in a biochemical assay. Numerical simulations utilizing molecular dynamics and hybrid quantum/classical calculations suggest a mechanism involving activation of a water molecule coordinated by a catalytic aspartic acid.

System for inspecting large size structural components

DOEpatents

Birks, Albert S.; Skorpik, James R.

1990-01-01

The present invention relates to a system for inspecting large scale structural components such as concrete walls or the like. The system includes a mobile gamma radiation source and a mobile gamma radiation detector. The source and detector are constructed and arranged for simultaneous movement along parallel paths in alignment with one another on opposite sides of a structural component being inspected. A control system provides signals which coordinate the movements of the source and detector and receives and records the radiation level data developed by the detector as a function of source and detector positions. The radiation level data is then analyzed to identify areas containing defects corresponding to unexpected variations in the radiation levels detected.

Pirate Stealth or Inattentional Blindness? The Effects of Target Relevance and Sustained Attention on Security Monitoring for Experienced and Naïve Operators

PubMed Central

Näsholm, Erika; Rohlfing, Sarah; Sauer, James D.

2014-01-01

Closed Circuit Television (CCTV) operators are responsible for maintaining security in various applied settings. However, research has largely ignored human factors that may contribute to CCTV operator error. One important source of error is inattentional blindness – the failure to detect unexpected but clearly visible stimuli when attending to a scene. We compared inattentional blindness rates for experienced (84 infantry personnel) and naïve (87 civilians) operators in a CCTV monitoring task. The task-relevance of the unexpected stimulus and the length of the monitoring period were manipulated between participants. Inattentional blindness rates were measured using typical post-event questionnaires, and participants' real-time descriptions of the monitored event. Based on the post-event measure, 66% of the participants failed to detect salient, ongoing stimuli appearing in the spatial field of their attentional focus. The unexpected task-irrelevant stimulus was significantly more likely to go undetected (79%) than the unexpected task-relevant stimulus (55%). Prior task experience did not inoculate operators against inattentional blindness effects. Participants' real-time descriptions revealed similar patterns, ruling out inattentional amnesia accounts. PMID:24465932

Effects of unexpected chords and of performer's expression on brain responses and electrodermal activity.

PubMed

Koelsch, Stefan; Kilches, Simone; Steinbeis, Nikolaus; Schelinski, Stefanie

2008-07-09

There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown. This study investigates event-related brain potentials (ERPs), skin conductance responses (SCRs) and heart rate (HR) elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression), we also created versions without variations in tempo and loudness (without musical expression) to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing) and an N5 (reflecting processing of meaning information) in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses). The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function) differed between the expressive and the non-expressive condition. These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music.

Anomalous Shocks on the Measured Near-Field Pressure Signatures of Low-Boom Wind-Tunnel Models

NASA Technical Reports Server (NTRS)

Mack, Robert J.

2006-01-01

Unexpected shocks on wind-tunnel-measured pressure signatures prompted questions about design methods, pressure signature measurement techniques, and the quality of measurements in the flow fields near lifting models. Some of these unexpected shocks were the result of component integration methods. Others were attributed to the three-dimension nature of the flow around a lifting model, to inaccuracies in the prediction of the area-ruled lift, or to wing-tip stall effects. This report discusses the low-boom model wind-tunnel data where these unexpected shocks were initially observed, the physics of the lifting wing/body model's flow field, the wind-tunnel data used to evaluate the applicability of methods for calculating equivalent areas due to lift, the performance of lift prediction codes, and tip stall effects so that the cause of these shocks could be determined.

Unexpected molecular weight effect in polymer nanocomposites

DOE PAGES

Cheng, Shiwang; Holt, Adam P.; Wang, Huiqun; ...

2016-01-22

Here, the properties of the interfacial layer between the polymer matrix and nanoparticles largely determine the macroscopic properties of polymer nanocomposites (PNCs). Although the static thickness of the interfacial layer was found to increase with the molecular weight (MW), the influence of MW on segmental relaxation and the glass transition in this layer remains to be explored. In this Letter, we show an unexpected MW dependence of the interfacial properties in PNC with attractive polymer-nanoparticle interactions: the thickness of the interfacial layer with hindered segmental relaxation decreases as MW increases, in sharp constrast to theoretical predictions. Further analyses reveal amore » reduction in mass density of the interfacial layer with increasing MW, which can explain these unexpected dynamic effects. Our observations call for a significant revision of the current understandings of PNCs and suggest interesting ways to tailor their properties.« less

Geoscience in the news - sharing stories

NASA Astrophysics Data System (ADS)

Redfern, Simon

2015-04-01

Schemes such as the British Science Association media fellowships and the AGU mass media fellowships offer an opportunity for active researchers to sit side by side with journalists at the news desk. Each can learn from the other, and the mutual benefits are often unexpected. Here, I reflect on my own experiences as a media fellow at the BBC, and consider how this opportunity has altered my own views on communicated my, and others', science. Geosciences have a particular advantage in such translation to a general audience. Interest in the natural environment, the origins of life, the planetary science of the Solar System as a whole, as well as topics in resource, energy, climate and geohazards is high among the public. There are advantages in being willing to act as a "translator" of discovery and an "interpreter" of natural events that, it could be argued, should be grasped to keep the relevance of our science high in the perceptions of tax payers and policy makers. By exercising these types of communications skills, new perspectives on one's own research may be attained.

Accessory hepatic vein complicating extra-cardiac total cavopulmonary connection.

PubMed

Yoshii, Shinpei; Suzuki, Shoji; Osawa, Hiroshi; Hosaka, Shigeru; Honda, Yoshihiro; Abraham, Samuel J K; Tada, Yusuke; Sugiyama, Hisashi; Tan, Tetsushi; Kadono, Toshie; Hoshiai, Minako; Komai, Takayuki

2002-04-01

We encountered unexpected, severe hypoxia after the right heart bypass operation in a patient with isomerism. A 2-year-old girl with polysplenia had a complex cardiac anomaly consisting of a single atrium, single ventricle, pulmonary stenosis, absence of the right superior vena cava, hemiazygos continuation of the left inferior vena cava, and d-malposition of the great arteries. After a total cavopulmonary shunt, we performed an extra-cardiac total cavo-pulmonary connection with a 14 mm tube graft. The postoperative course was complicated by severe hypoxia. Angiography performed 20 days after the operation showed that contrast medium in the conduit poured into the hepatic vein, and through the intrahepatic communications, it passed into a left-sided accessory hepatic vein, which was connected directly to the left side of the aspect of the atrium. As the intrahepatic communication was adequate, we ligated the accessory hepatic vein within the pericardial cavity. The SpO2 returned to normal and no hepatic dysfunction was detected. We conclude that surgeons performing extra-cardiac total cavopulmonary connection need to pay closer attention to the possibility that an accessory hepatic vein might exist.

[Development of the unexpected reality scale for childcare training].

PubMed

Matsuda, Yuko; Shitara, Saeko; Hamada, Shoko

2016-10-01

This study aimed to develop a scale for unexpected reality for childcare training (Study 1) and examine the change and influence it exerts on the efficacy of preschool teachers (Study 2). In Study 1, the sample consisted of 571 university and junior college students enrolled in a childcare course. After exploratory factor analysis, four factors were extracted: “actual feelings for childcare as a field of study,” “difficulties faced during involvement with children,” “negative aspects of the childcare worker,” and “severity of work.” The study’s scale was shown to be internally consistent and valid. In Study 2, the sample consisted of 122 junior college students enrolled in a childcare course. The results showed that the high-scoring groups of each unexpected reality subscales experienced less unexpected reality in the subsequent training session. Moreover, the results of multiple regression showed that preschool teacher efficacy was predicted positively by “actual feelings for childcare as a field of study” and negatively by “difficulties faced during involvement with children.” Thus, we suggest that for effective pre- and post-guidance of childcare training, unexpected realities should be considered.

Central Cavity of Fructose-1,6-bisphosphatase and the Evolution of AMP/Fructose 2,6-bisphosphate Synergism in Eukaryotic Organisms*

PubMed Central

Gao, Yang; Shen, Lu; Honzatko, Richard B.

2014-01-01

The effects of AMP and fructose 2,6-bisphosphate (Fru-2,6-P2) on porcine fructose-1,6-bisphosphatase (pFBPase) and Escherichia coli FBPase (eFBPase) differ in three respects. AMP/Fru-2,6-P2 synergism in pFBPase is absent in eFBPase. Fru-2,6-P2 induces a 13° subunit pair rotation in pFBPase but no rotation in eFBPase. Hydrophilic side chains in eFBPase occupy what otherwise would be a central aqueous cavity observed in pFBPase. Explored here is the linkage of AMP/Fru-2,6-P2 synergism to the central cavity and the evolution of synergism in FBPases. The single mutation Ser45 → His substantially fills the central cavity of pFBPase, and the triple mutation Ser45 → His, Thr46 → Arg, and Leu186 → Tyr replaces porcine with E. coli type side chains. Both single and triple mutations significantly reduce synergism while retaining other wild-type kinetic properties. Similar to the effect of Fru-2,6-P2 on eFBPase, the triple mutant of pFBPase with bound Fru-2,6-P2 exhibits only a 2° subunit pair rotation as opposed to the 13° rotation exhibited by the Fru-2,6-P2 complex of wild-type pFBPase. The side chain at position 45 is small in all available eukaryotic FBPases but large and hydrophilic in bacterial FBPases, similar to eFBPase. Sequence information indicates the likelihood of synergism in the FBPase from Leptospira interrogans (lFBPase), and indeed recombinant lFBPase exhibits AMP/Fru-2,6-P2 synergism. Unexpectedly, however, AMP also enhances Fru-6-P binding to lFBPase. Taken together, these observations suggest the evolution of AMP/Fru-2,6-P2 synergism in eukaryotic FBPases from an ancestral FBPase having a central aqueous cavity and exhibiting synergistic feedback inhibition by AMP and Fru-6-P. PMID:24436333

Manufacturing Affordability

DTIC Science & Technology

2011-10-01

Effective planning early in and throughout program develop - ment is critical to enabling manufacturing affordability. There is no silver bullet and no...unexpected lessons. “Gee, this stove is hot” may be an unexpected lesson for the toddler but should not be so for the adult. All production programs...in program design efforts from day 1 of Engineer- ing and Manufacturing Development , you should be seriously worried. A program that includes the

Partial breast radiation for early-stage breast cancer.

PubMed

McCormick, Beryl

2012-02-01

This review is to provide an update on the current status of partial breast irradiation (PBI) for women presenting with early-stage breast cancer, as an alternate radiation technique to fractionated, whole breast radiation, following conservation surgery. As more women are asking for and receiving this treatment, both on and off protocols, understanding recent additions to the literature is important to physicians caring for this patient population. Newly published retrospective studies, with follow-up times out to 10 years and the status of both recently completed and still open large prospective phase III trials will be covered, with emphasis on unexpected side effects reported, and some hypothesis-generating radiobiology observations. A recent consensus treatment guideline for PBI use is also discussed. Selected retrospective studies continue to report outcomes matching those achieved with whole breast radiation; however, results from large prospective randomized trials comparing PBI to whole breast radiation have been reported only with short follow-up times, or in two studies, are still pending. A recent consensus guideline is useful at present in selecting patients for discussion of this treatment.

Drug-induced apnea.

PubMed

Boutroy, M J

1994-01-01

Drugs have been in the past and will in the future still be liable to induce apnea in neonates, infants and older children. At these different stages of development, the child may be abnormally vulnerable to respiratory disorders and apnea, and doses of drugs, without any abnormal side effects in adult patients, can be harmful in younger subjects. Drugs responsible for apnea during development are numerous, but more than half of the problems are induced by sedatives and hypnotics, among which phenothiazines, barbiturates, benzodiazepines (included transplacentally acquired) and general anesthetics are a few. Other pharmacological families are apnea inducers in the neonatal period and childhood: analgesics and opioid narcotics, agents acting at the levels of neuromuscular function and autonomic ganglia, and cardiovascular agents. The pathogenesis of these apneas depends on the disturbance of any mechanism responsible for the respiratory activity: medullary centers and brain stem structures, afferent influx to CNS, sleep stages, upper airways, lungs and respiratory muscles. At key stages such as birth and infancy, drugs may emphasize the particular sensitivity of the mechanisms responsible for inducing apnea. This might explain unexpected respiratory disorders during development.

ERP correlates of unexpected word forms in a picture–word study of infants and adults

PubMed Central

Duta, M.D.; Styles, S.J.; Plunkett, K.

2012-01-01

We tested 14-month-olds and adults in an event-related potentials (ERPs) study in which pictures of familiar objects generated expectations about upcoming word forms. Expected word forms labelled the picture (word condition), while unexpected word forms mismatched by either a small deviation in word medial vowel height (mispronunciation condition) or a large deviation from the onset of the first speech segment (pseudoword condition). Both infants and adults showed sensitivity to both types of unexpected word form. Adults showed a chain of discrete effects: positivity over the N1 wave, negativity over the P2 wave (PMN effect) and negativity over the N2 wave (N400 effect). Infants showed a similar pattern, including a robust effect similar to the adult P2 effect. These observations were underpinned by a novel visualisation method which shows the dynamics of the ERP within bands of the scalp over time. The results demonstrate shared processing mechanisms across development, as even subtle deviations from expected word forms were indexed in both age groups by a reduction in the amplitude of characteristic waves in the early auditory evoked potential. PMID:22483072

Systemic insecticide and gibberellin reduced cone damage and increased flowering in a spruce seed orchard.

PubMed

Rosenberg, O; Almqvist, C; Weslien, J

2012-06-01

Insects feeding in conifer cones are difficult to control with nonsystemic insecticides. Newly developed systemic insecticides that can be injected into tree trunks may be a possible way of reducing both insect damage and negative side-effects to the surrounding environment, compared with conventional spraying. Several insecticides that could be injected into tree stems were tested on Picea abies (L.) Karst. In one experiment, insecticides (bifenthrin, deltamethrin, abamectin, and imidacloprid) were injected during flowering; in a second experiment two of these insecticides (abamectin and imidacloprid) were injected 1 yr before the expected flowering. In the second experiment insecticide treatment was also combined with treatments with the flower stimulating hormone, gibberellin (GA(4/7)). The only insecticide that reduced damage was abamectin, both after injection during flowering and after injection 1 yr before the expected flowering. Injections with GA(4/7) increased flowering and were as efficient as the conventional application method of drilling but abamectin was not effective in combination with the drilling method. There was no negative effect of the insecticide injections on seed quality. The injections were ineffective against the seed chalcid Megastigmus strobilobius (Ratzeburg), which was found to have an unexpected, negative effect on seed quality. Our results suggest that it may be possible to reduce damage from certain insect species, and to increase flowering by injecting abamectin and GA(4/7) in the year before a cone crop.

[Case of callosal disconnection syndrome with a chief complaint of right-hand disability, despite presence of left-hand diagonistic dyspraxia].

PubMed

Okamoto, Yoko; Saida, Hisako; Yamamoto, Toru

2009-04-01

e report the case of 48-year-old right-handed male patient with an infarction affecting most part of the body and the splenium of the left half of the corpus callosum. Neuropsychological examination revealed typical signs of callosal disconnection including left-sided apraxia, diagonistic dyspraxia, left-sided agraphia, left-hand tactile anomia, left hemialexia, and right-sided constructional disability. Moreover, he complained of impairment in activities involving the right hand disability and agraphia. He could not stop behaving with his right hand when he had a vague idea. For example, he involuntarily picked up a tea bottle with his right hand when he had a desire to drink, although the action was not appropriate to that occasion. The imitation and utilization behavior did not imply this case, because his right hand behaviors were not exaggerated in response to external stimuli, such as the gestures of the examiner or the subjects in front of the patient. Unexpectedly, he complained about impairment of the activity of his right hand and was unaware of left hand apraxia or diagonistic dyspraxia; this trend continued for 6 months, at the time of this writing. We argue that the patient may have been subconsciouly aware of the symptoms of his left hand but had not verbalized them.

Biomimetic component coating on 3D scaffolds using high bioactivity of mesoporous bioactive ceramics

PubMed Central

Yun, Hui-suk; Kim, Sang-Hyun; Khang, Dongwoo; Choi, Jungil; Kim, Hui-hoon; Kang, Minji

2011-01-01

Background Mesoporous bioactive glasses (MBGs) are very attractive materials for use in bone tissue regeneration because of their extraordinarily high bone-forming bioactivity in vitro. That is, MBGs may induce the rapid formation of hydroxy apatite (HA) in simulated body fluid (SBF), which is a major inorganic component of bone extracellular matrix (ECM) and comes with both good osteoconductivity and high affinity to adsorb proteins. Meanwhile, the high bioactivity of MBGs may lead to an abrupt initial local pH variation during the initial Ca ion-leaching from MBGs at the initial transplant stage, which may induce unexpected negative effects on using them in in vivo application. In this study we suggest a new way of using MBGs in bone tissue regeneration that can improve the strength and make up for the weakness of MBGs. We applied the outstanding bone-forming bioactivity of MBG to coat the main ECM components HA and collagen on the MBG-polycarplolactone (PCL) composite scaffolds for improving their function as bone scaffolds in tissue regeneration. This precoating process can also expect to reduce initial local pH variation of MBGs. Methods and materials The MBG-PCL scaffolds were immersed in the mixed solution of the collagen and SBF at 37°C for 24 hours. The coating of ECM components on the MBG-PCL scaffolds and the effect of ECM coating on in vitro cell behaviors were confirmed. Results The ECM components were fully coated on MBG-PCL scaffolds after immersing in SBF containing dilute collagen-I solution only for 24 hours due to the high bone-forming bioactivity of MBG. Both cell affinity and osteoconductivity of MBG-PCL scaffolds were dramatically enhanced by this precoating process. Conclusion The precoating process of ECM components on MBG-PCL scaffold using a high bioactivity of MBG was not only effective in enhancing the functionality of scaffolds but also effective in eliminating the unexpected side effect. The MBG-PCL scaffold-coated ECM components ideally satisfied the required conditions of scaffold in tissue engineering, including 3D well-interconnected pore structures with high porosity, good bioactivity, enhanced cell affinity, biocompatibility, osteoconductivity, and sufficient mechanical properties, and promise excellent potential application in the field of biomaterials. PMID:22072886

Unexpected results in Chernozem soil respiration while measuring the effect of a bio-fertilizer on soil microbial activity.

PubMed

Bautista, Gabriela; Mátyás, Bence; Carpio, Isabel; Vilches, Richard; Pazmino, Karina

2017-01-01

The number of studies investigating the effect of bio-fertilizers is increasing because of their importance in sustainable agriculture and environmental quality. In our experiments, we measured the effect of different fertilizers on soil respiration. In the present study, we were looking for the cause of unexpected changes in CO2 values while examining Chernozem soil samples. We concluded that CO2 oxidizing microbes or methanotrophs may be present in the soil that periodically consume CO2 . This is unusual for a sample taken from the upper layer of well-ventilated Chernozem soil with optimal moisture content.

Unexpected results in Chernozem soil respiration while measuring the effect of a bio-fertilizer on soil microbial activity

PubMed Central

Bautista, Gabriela; Mátyás, Bence; Carpio, Isabel; Vilches, Richard; Pazmino, Karina

2017-01-01

The number of studies investigating the effect of bio-fertilizers is increasing because of their importance in sustainable agriculture and environmental quality. In our experiments, we measured the effect of different fertilizers on soil respiration. In the present study, we were looking for the cause of unexpected changes in CO2 values while examining Chernozem soil samples. We concluded that CO2 oxidizing microbes or methanotrophs may be present in the soil that periodically consume CO2 . This is unusual for a sample taken from the upper layer of well-ventilated Chernozem soil with optimal moisture content. PMID:29333243

Effects of Unexpected Chords and of Performer's Expression on Brain Responses and Electrodermal Activity

PubMed Central

Koelsch, Stefan; Kilches, Simone; Steinbeis, Nikolaus; Schelinski, Stefanie

2008-01-01

Background There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown. Methodology/Principal Findings This study investigates event-related brain potentials (ERPs), skin conductance responses (SCRs) and heart rate (HR) elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression), we also created versions without variations in tempo and loudness (without musical expression) to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing) and an N5 (reflecting processing of meaning information) in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses). The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function) differed between the expressive and the non-expressive condition. Conclusions/Significance These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music. PMID:18612459

Survey of Hatching Spines of Bee Larvae Including Those of Apis mellifera (Hymenoptera: Apoidea).

PubMed

Rozen, Jerome G; Shepard Smith, Corey; Cane, James H

2017-07-01

This article explores the occurrence of hatching spines among bee taxa and how these structures enable a larva on hatching to extricate itself from the egg chorion. These spines, arranged in a linear sequence along the sides of the first instar just dorsal to the spiracles, have been observed and recorded in certain groups of solitary and cleptoparasitic bee taxa. After eclosion, the first instar remains loosely covered by the egg chorion. The fact that this form of eclosion has been detected in five families (Table 1 identifies four of the families. The fifth family is the Andrenidae for which the presence of hatching spines in the Oxaeinae will soon be announced.) of bees invites speculation as to whether it is a fundamental characteristic of bees, or at least of solitary and some cleptoparasitic bees. The wide occurrence of these spines has prompted the authors to explore and discover their presence in the highly eusocial Apis mellifera L. Hatching spines were indeed discovered on first instar A. mellifera. The honey bee hatching process appears to differ in that the spines are displayed somewhat differently though still along the sides of the body, and the chorion, instead of splitting along the sides of the elongate egg, seems to quickly disintegrate from the emerging first instar in association with the nearly simultaneous removal of the serosa that covers and separates the first instar from the chorion. Unexpected observations of spherical bodies of various sizes perhaps containing dissolving enzymes being discharged from spiracular openings during hatching may shed future light on the process of how A. mellifera effects chorion removal during eclosion. Whereas hatching spines occur among many groups of bees, they appear to be entirely absent in the Nomadinae and parasitic Apinae, an indication of a different eclosion process. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America.

Trip-specific training enhances recovery after large postural disturbances for which there is NO expectation.

PubMed

Oludare, Simisola O; Pater, Mackenzie L; Rosenblatt, Noah J; Grabiner, Mark D

2018-03-01

Informed consent usually provides foreknowledge of experimental methods that can potentially increase expectation of stimuli and, therefore, influence the response. We determined the effects of increased expectation and trip-specific training on the recovery response following a treadmill-delivered, trip-specific disturbance. To deliver unexpected disturbances, subjects were deceived during the informed consent process. The primary hypothesis was that the recovery response following an expected postural disturbance would be characterized by trunk kinematics that have been shown to decrease the likelihood of a fall, compared to following an unexpected postural disturbance. We further hypothesized that following an unexpected postural disturbance, the recovery response of the subjects who had completed a trip-specific training protocol would be more biomechanically favorable to recovery compared to those of subjects who had not received the training. Young adults were randomized into Untrained or Trained groups. During the informed consent process, the purpose of the study was explained to subjects in both groups as being to determine the effect of trip-specific training on postural sway while performing an attention-demanding task. Untrained subjects completed two trials during which they minimized their postural sway. During the second trial, an unexpected disturbance was delivered while they performed the attention-demanding task. Trained subjects performed a pre-training postural sway trial, followed by the delivery of a series of expected, training disturbances. Finally, an unexpected disturbance was delivered while they minimized postural sway and performed the attention-demanding task. Expectation significantly improved trunk kinematics (p < .05). In addition, participation in the trip-specific training protocol following the unexpected disturbance the trunk kinematics of the Trained subjects were more biomechanically favorable to recovery than those of the Untrained subjects (p < .01). Improved trunk kinematics following trip-specific training may be independent of the extent to which the disturbance is expected. Copyright © 2018 Elsevier B.V. All rights reserved.

Large-Scale Off-Target Identification Using Fast and Accurate Dual Regularized One-Class Collaborative Filtering and Its Application to Drug Repurposing.

PubMed

Lim, Hansaim; Poleksic, Aleksandar; Yao, Yuan; Tong, Hanghang; He, Di; Zhuang, Luke; Meng, Patrick; Xie, Lei

2016-10-01

Target-based screening is one of the major approaches in drug discovery. Besides the intended target, unexpected drug off-target interactions often occur, and many of them have not been recognized and characterized. The off-target interactions can be responsible for either therapeutic or side effects. Thus, identifying the genome-wide off-targets of lead compounds or existing drugs will be critical for designing effective and safe drugs, and providing new opportunities for drug repurposing. Although many computational methods have been developed to predict drug-target interactions, they are either less accurate than the one that we are proposing here or computationally too intensive, thereby limiting their capability for large-scale off-target identification. In addition, the performances of most machine learning based algorithms have been mainly evaluated to predict off-target interactions in the same gene family for hundreds of chemicals. It is not clear how these algorithms perform in terms of detecting off-targets across gene families on a proteome scale. Here, we are presenting a fast and accurate off-target prediction method, REMAP, which is based on a dual regularized one-class collaborative filtering algorithm, to explore continuous chemical space, protein space, and their interactome on a large scale. When tested in a reliable, extensive, and cross-gene family benchmark, REMAP outperforms the state-of-the-art methods. Furthermore, REMAP is highly scalable. It can screen a dataset of 200 thousands chemicals against 20 thousands proteins within 2 hours. Using the reconstructed genome-wide target profile as the fingerprint of a chemical compound, we predicted that seven FDA-approved drugs can be repurposed as novel anti-cancer therapies. The anti-cancer activity of six of them is supported by experimental evidences. Thus, REMAP is a valuable addition to the existing in silico toolbox for drug target identification, drug repurposing, phenotypic screening, and side effect prediction. The software and benchmark are available at https://github.com/hansaimlim/REMAP.

Large-Scale Off-Target Identification Using Fast and Accurate Dual Regularized One-Class Collaborative Filtering and Its Application to Drug Repurposing

PubMed Central

Poleksic, Aleksandar; Yao, Yuan; Tong, Hanghang; Meng, Patrick; Xie, Lei

2016-01-01

Target-based screening is one of the major approaches in drug discovery. Besides the intended target, unexpected drug off-target interactions often occur, and many of them have not been recognized and characterized. The off-target interactions can be responsible for either therapeutic or side effects. Thus, identifying the genome-wide off-targets of lead compounds or existing drugs will be critical for designing effective and safe drugs, and providing new opportunities for drug repurposing. Although many computational methods have been developed to predict drug-target interactions, they are either less accurate than the one that we are proposing here or computationally too intensive, thereby limiting their capability for large-scale off-target identification. In addition, the performances of most machine learning based algorithms have been mainly evaluated to predict off-target interactions in the same gene family for hundreds of chemicals. It is not clear how these algorithms perform in terms of detecting off-targets across gene families on a proteome scale. Here, we are presenting a fast and accurate off-target prediction method, REMAP, which is based on a dual regularized one-class collaborative filtering algorithm, to explore continuous chemical space, protein space, and their interactome on a large scale. When tested in a reliable, extensive, and cross-gene family benchmark, REMAP outperforms the state-of-the-art methods. Furthermore, REMAP is highly scalable. It can screen a dataset of 200 thousands chemicals against 20 thousands proteins within 2 hours. Using the reconstructed genome-wide target profile as the fingerprint of a chemical compound, we predicted that seven FDA-approved drugs can be repurposed as novel anti-cancer therapies. The anti-cancer activity of six of them is supported by experimental evidences. Thus, REMAP is a valuable addition to the existing in silico toolbox for drug target identification, drug repurposing, phenotypic screening, and side effect prediction. The software and benchmark are available at https://github.com/hansaimlim/REMAP. PMID:27716836

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.

Characterization of Member of DUF1888 Protein Family, Self-cleaving and Self-assembling Endopeptidase*

PubMed Central

Osipiuk, Jerzy; Mulligan, Rory; Bargassa, Monireh; Hamilton, John E.; Cunningham, Mark A.; Joachimiak, Andrzej

2012-01-01

The crystal structure of SO1698 protein from Shewanella oneidensis was determined by a SAD method and refined to 1.57 Å. The structure is a β sandwich that unexpectedly consists of two polypeptides; the N-terminal fragment includes residues 1–116, and the C-terminal one includes residues 117–125. Electron density also displayed the Lys-98 side chain covalently linked to Asp-116. The putative active site residues involved in self-cleavage were identified; point mutants were produced and characterized structurally and in a biochemical assay. Numerical simulations utilizing molecular dynamics and hybrid quantum/classical calculations suggest a mechanism involving activation of a water molecule coordinated by a catalytic aspartic acid. PMID:22493430

Vortex breakdown in simple pipe bends

NASA Astrophysics Data System (ADS)

Ault, Jesse; Shin, Sangwoo; Stone, Howard

2016-11-01

Pipe bends and elbows are one of the most common fluid mechanics elements that exists. However, despite their ubiquity and the extensive amount of research related to these common, simple geometries, unexpected complexities still remain. We show that for a range of geometries and flow conditions, these simple flows experience unexpected fluid dynamical bifurcations resembling the bubble-type vortex breakdown phenomenon. Specifically, we show with simulations and experiments that recirculation zones develop within the bends under certain conditions. As a consequence, fluid and particles can remain trapped within these structures for unexpectedly-long time scales. We also present simple techniques to mitigate this recirculation effect which can potentially have impact across industries ranging from biomedical and chemical processing to food and health sciences.

Stimulated backward Raman scattering driven collectively by two picosecond laser pulses in a bi- or multi-speckle configuration

NASA Astrophysics Data System (ADS)

Glize, K.; Rousseaux, C.; Bénisti, D.; Dervieux, V.; Gremillet, L.; Baton, S. D.; Lancia, L.

2017-03-01

In this paper, we investigate, both experimentally and numerically, the backward stimulated Raman scattering (SRS) excited collectively by two laser pulses. The experiments have been carried out at the LULI facility using two co-propagating 1- μ m wavelength, 1.5- ps duration laser pulses focused in a preformed underdense plasma. A particular emphasis is laid on the configuration where the pulses are focused side-by-side, with a lateral distance of 80 - 90 μ m , but not simultaneously. It is experimentally demonstrated that a weak-intensity speckle, ineffective when fired alone in a preformed plasma, yields a significant SRS-induced reflectivity if launched a few picoseconds after a strong one. The data have been obtained by using both highly space-time resolved Thomson diagnostics and space-resolved SRS reflectivity measurements. By choosing either parallel or orthogonal polarizations for the two laser pulses, our experiments shed light on the role of either electrostatic or electromagnetic seeding in enhancing SRS from weak-intensity speckles. A major finding is that seeding operates over unexpectedly long times ( 15 - 20 ps under our experimental conditions). Similar results are obtained in lower-density plasmas, or when the weak pulse is smoothed by a random phase plate, thus leading to multiple speckle interaction, while the strong pulse is focused within the speckle pattern. The data are discussed with the help of particle-in-cell numerical simulations, which confirm the destabilizing effect of the strong pulse over the weak one after a short transient time.

Peculiarities of heat transfer at the liquid metal flow in a vertical channel in a coplanar magnetic field

NASA Astrophysics Data System (ADS)

Razuvanov, N. G.; Poddubnyi, I. I.; Kostychev, P. V.

2017-11-01

The research of hydrodynamics and heat transfer at the liquid metal (LM) downward flow and upflow in a vertical duct of a rectangular cross section with a ratio of sides ˜1/3 in a coplanar magnetic field (MF) under conditions of bilateral symmetrical heating is performed. The problem simulates the LM flow in the heat exchange channels for cooling the liquid metal module of the blanket of the thermonuclear reactor (TNR) of the TOKAMAK type. The experiments were carried out on the basis of the mercury magnetohydrodynamic test-bed (MHD) Moscow Power Engineering Institute (MPEI) - Joint Institute for High Temperatures of the Russian Academy of Sciences (JIHT RAS). The probe measurement technique was used in the flow. Profiles of averaged velocity and averaged temperature, as well as profiles of temperature pulsations in the axial planes of the channel cross-section, are obtained; the distribution of the dimensionless wall temperature along the perimeter unfolding of the channel in the section and along the length of the channel. A significant effect of thermogravitational convection (TGC), which leads to unexpected effects, is found. At the downflow in a magnetic field, in some modes, low-frequency pulsations of anomalously high intensity occur.

Hypoxia Induced Factor in Chronic Kidney Disease: Friend or Foe?

PubMed

Li, Weiying; Zhao, Yuliang; Fu, Ping

2017-01-01

Many studies have shown evidence that erythropoiesis-stimulating agents (ESAs), as a classic treatment for chronic kidney disease (CKD)-related anemia, have several disadvantages and may trigger various adverse events with long-term use. The hypoxia-induced factor (HIF) pathway has been intensively investigated in kidney disease, especially in CKD, as research has shown that HIF-mediated erythropoiesis might work as a potential therapeutic strategy for managing CKD-related anemia. Development of prolyl hydroxylase domain inhibitors (PHIs), as an effective HIF activator, is a valuable step toward finding a replacement for ESAs, which showed an effective erythropoiesis through a comprehensive and physiological approach by promoting erythropoietin production, increasing iron bioavailability and improving chronic inflammatory status. Heretofore no adverse events or obvious off-target effects have been reported in clinical trials of PHIs. Nevertheless, a cautious inspection with extended follow-up period is warranted to validate the safety of prolonged HIF elevation, especially considering its ambiguous role in fibrogenesis and inflammation responses and possible risks in accelerating vascular calcification and tumorigenesis. A weighed dosing strategy might be the key to circumvent the unexpected side-effect brought by pleotropic effects of HIF elevation and achieve a selective augmentation of HIF-mediated signaling pathway. New studies with longer follow-up period and adequate analysis about the risks for proinflammation, vascular calcification and tumorigenesis are needed to ensure the drugs are safe for long-term use before being widely accepted in daily clinical practice.

A framework for ensuring a balanced accounting of the impact of antimicrobial stewardship interventions.

PubMed

Toma, Madalina; Davey, Peter G; Marwick, Charis A; Guthrie, Bruce

2017-12-01

Drawing on a Cochrane systematic review, this paper examines the relatively limited range of outcomes measured in published evaluations of antimicrobial stewardship interventions (ASIs) in hospitals. We describe a structured framework for considering the range of consequences that ASIs can have, in terms of their desirability and the extent to which they were expected when planning an ASI: expected, desirable consequences (intervention goals); expected, undesirable consequences (intervention trade-offs); unexpected, undesirable consequences (unpleasant surprises); and unexpected, desirable consequences (pleasant surprises). Of 49 randomized controlled trials identified by the Cochrane review, 28 (57%) pre-specified increased length of stay and/or mortality as potential trade-offs of ASI, with measurement intended to provide reassurance about safety. In actuality, some studies found unexpected decreases in length of stay (a pleasant surprise). In contrast, only 11 (10%) of 110 interrupted time series studies included any information about unintended consequences, with 10 examining unexpected, undesirable outcomes (unpleasant surprises) using case-control, qualitative or cohort designs. Overall, a large proportion of the ASIs reported in the literature only assess impact on their targeted process goals-antimicrobial prescribing-with limited examination of other potential outcomes, including microbial and clinical outcomes. Achieving a balanced accounting of the impact of an ASI requires careful consideration of expected undesirable effects (potential trade-offs) from the outset, and more consideration of unexpected effects after implementation (both pleasant and unpleasant surprises, although the latter will often be more important). The proposed framework supports the systematic consideration of all types of consequences of improvement before and after implementation. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Unexpected perturbations training improves balance control and voluntary stepping times in older adults - a double blind randomized control trial.

PubMed

Kurz, Ilan; Gimmon, Yoav; Shapiro, Amir; Debi, Ronen; Snir, Yoram; Melzer, Itshak

2016-03-04

Falls are common among elderly, most of them occur while slipping or tripping during walking. We aimed to explore whether a training program that incorporates unexpected loss of balance during walking able to improve risk factors for falls. In a double-blind randomized controlled trial 53 community dwelling older adults (age 80.1±5.6 years), were recruited and randomly allocated to an intervention group (n = 27) or a control group (n = 26). The intervention group received 24 training sessions over 3 months that included unexpected perturbation of balance exercises during treadmill walking. The control group performed treadmill walking with no perturbations. The primary outcome measures were the voluntary step execution times, traditional postural sway parameters and Stabilogram-Diffusion Analysis. The secondary outcome measures were the fall efficacy Scale (FES), self-reported late life function (LLFDI), and Performance-Oriented Mobility Assessment (POMA). Compared to control, participation in intervention program that includes unexpected loss of balance during walking led to faster Voluntary Step Execution Times under single (p = 0.002; effect size [ES] =0.75) and dual task (p = 0.003; [ES] = 0.89) conditions; intervention group subjects showed improvement in Short-term Effective diffusion coefficients in the mediolateral direction of the Stabilogram-Diffusion Analysis under eyes closed conditions (p = 0.012, [ES] = 0.92). Compared to control there were no significant changes in FES, LLFDI, and POMA. An intervention program that includes unexpected loss of balance during walking can improve voluntary stepping times and balance control, both previously reported as risk factors for falls. This however, did not transferred to a change self-reported function and FES. ClinicalTrials.gov NCT01439451 .

Spectral Interferences Manganese (Mn) - Europium (Eu) Lines in X-Ray Fluorescence Spectrometry Spectrum

NASA Astrophysics Data System (ADS)

Tanc, Beril; Kaya, Mustafa; Gumus, Lokman; Kumral, Mustafa

2016-04-01

X-ray fluorescence (XRF) spectrometry is widely used for quantitative and semi quantitative analysis of many major, minor and trace elements in geological samples. Some advantages of the XRF method are; non-destructive sample preparation, applicability for powder, solid, paste and liquid samples and simple spectrum that are independent from chemical state. On the other hand, there are some disadvantages of the XRF methods such as poor sensitivity for low atomic number elements, matrix effect (physical matrix effects, such as fine versus course grain materials, may impact XRF performance) and interference effect (the spectral lines of elements may overlap distorting results for one or more elements). Especially, spectral interferences are very significant factors for accurate results. In this study, semi-quantitative analyzed manganese (II) oxide (MnO, 99.99%) was examined. Samples were pelleted and analyzed with XRF spectrometry (Bruker S8 Tiger). Unexpected peaks were obtained at the side of the major Mn peaks. Although sample does not contain Eu element, in results 0,3% Eu2O3 was observed. These result can occur high concentration of MnO and proximity of Mn and Eu lines. It can be eliminated by using correction equation or Mn concentration can confirm with other methods (such as Atomic absorption spectroscopy). Keywords: Spectral Interferences; Manganese (Mn); Europium (Eu); X-Ray Fluorescence Spectrometry Spectrum.

Quality of healing of gastric ulcers: Natural products beyond acid suppression

PubMed Central

Kangwan, Napapan; Park, Jong-Min; Kim, Eun-Hee; Hahm, Ki Baik

2014-01-01

Gastric ulcer is a chronic disease featured with unexpected complications, including bleeding, stenosis and perforation, as well as a high incidence of recurrence. Clinical treatments for gastric ulcer have allowed the rapid development of potent anti-ulcer drugs during the last several decades. Gastric ulcer healing is successful with conventional treatments including H2-receptor antagonists, and proton pump inhibitors (PPIs) have been essential for ulcer healing and prevention of complications. Additionally, Helicobacter pylori eradication therapy is effective in reducing ulcer recurrence and leads to physiological changes in the gastric mucosa which affect the ulcer healing process. However, in spite of these advancements, some patients have suffered from recurrence or intractability in spite of continuous anti-ulcer therapy. A new concept of the quality of ulcer healing (QOUH) was initiated that considers the reconstruction of the mucosal structure and its function for preventing ulcer recurrence. Although several gastroprotection provided these achievements of the QOUH, which PPI or other acid suppressants did not accomplish, we found that gastroprotection that originated from natural products, such as a newer formulation from either Artemisia or S-allyl cysteine from garlic, were very effective in the QOUH, as well as improving clinical symptoms with fewer side effects. In this review, we will introduce the importance of the QOUH in ulcer healing and the achievements from natural products. PMID:24891974

Quality of healing of gastric ulcers: Natural products beyond acid suppression.

PubMed

Kangwan, Napapan; Park, Jong-Min; Kim, Eun-Hee; Hahm, Ki Baik

2014-02-15

Gastric ulcer is a chronic disease featured with unexpected complications, including bleeding, stenosis and perforation, as well as a high incidence of recurrence. Clinical treatments for gastric ulcer have allowed the rapid development of potent anti-ulcer drugs during the last several decades. Gastric ulcer healing is successful with conventional treatments including H2-receptor antagonists, and proton pump inhibitors (PPIs) have been essential for ulcer healing and prevention of complications. Additionally, Helicobacter pylori eradication therapy is effective in reducing ulcer recurrence and leads to physiological changes in the gastric mucosa which affect the ulcer healing process. However, in spite of these advancements, some patients have suffered from recurrence or intractability in spite of continuous anti-ulcer therapy. A new concept of the quality of ulcer healing (QOUH) was initiated that considers the reconstruction of the mucosal structure and its function for preventing ulcer recurrence. Although several gastroprotection provided these achievements of the QOUH, which PPI or other acid suppressants did not accomplish, we found that gastroprotection that originated from natural products, such as a newer formulation from either Artemisia or S-allyl cysteine from garlic, were very effective in the QOUH, as well as improving clinical symptoms with fewer side effects. In this review, we will introduce the importance of the QOUH in ulcer healing and the achievements from natural products.

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.

Near-infrared (0.8-4.0 m) spectroscopy of mimas, enceladus, tethys, and rhea

USGS Publications Warehouse

Emery, J.P.; Burr, D.M.; Cruikshank, D.P.; Brown, R.H.; Dalton, J.B.

2005-01-01

Spectral measurements from the ground in the time leading up to the Cassini mission at Saturn provide important context for the interpretation of the forthcoming spacecraft data. Whereas ground-based observations cannot begin to approach the spatial scales Cassini will achieve, they do possess the benefits of better spectral resolution, a broader possible time baseline, and unique veiewing geometries not obtained by spacecraft (i.e., opposition). In this spirit, we present recent NIR reflectance spectra of four icy satellites of Saturn measured with the SpeX instrument at the IRTF. These measurements cover the range 0.8-4.0 m of both the leading and trailing sides of Tethys and the leading side of Rhea. The L-band region (2.8-4.0 m) offers new opportunities for searches of minor components on these objects. Additionally, these data include 0.8-2.5 m spectra of both the leading and trailing sides of Mimas and of the (mostly) trailing side of Enceladus. The spectrum of Enceladus shows activity near 2.25 m that we interpret as a possible signature of NH3 ice. The presence of ammonia in the Saturn system is not unexpected, and may help explain the apparent recent geologic activity of Enceladus. Analysis of leading/trailing differences inH2O band depths, spectral slopes, and albedo imply a separate regime of surface modification for Mimas and Enceladus than for the more distant icy satellites (Tethys, Dione, Rhea). Aside from the potential NH3 on Enceladus, no other minor constituents are detected in these icy surfaces.

Permeation of internal and external monovalent cations through the catfish cone photoreceptor cGMP-gated channel

PubMed Central

1995-01-01

The permeation of monovalent cations through the cGMP-gated channel of catfish cone outer segments was examined by measuring permeability and conductance ratios under biionic conditions. For monovalent cations presented on the cytoplasmic side of the channel, the permeability ratios with respect to extracellular Na followed the sequence NH4 > K > Li > Rb = Na > Cs while the conductance ratios at +50 mV followed the sequence Na approximately NH4 > K > Rb > Li = Cs. These patterns are broadly similar to the amphibian rod channel. The symmetry of the channel was tested by presenting the test ion on the extracellular side and using Na as the common reference ion on the cytoplasmic side. Under these biionic conditions, the permeability ratios with respect to Na at the intracellular side followed the sequence NH4 > Li > K > Na > Rb > Cs while the conductance ratios at +50 mV followed the sequence NH4 > K approximately Na > Rb > Li > Cs. Thus, the channel is asymmetric with respect to external and internal cations. Under symmetrical 120 mM ionic conditions, the single-channel conductance at +50 mV ranged from 58 pS in NH4 to 15 pS for Cs and was in the order NH4 > Na > K > Rb > Cs. Unexpectedly, the single-channel current-voltage relation showed sufficient outward rectification to account for the rectification observed in multichannel patches without invoking voltage dependence in gating. The concentration dependence of the reversal potential for K showed that chloride was impermeant. Anomalous mole fraction behavior was not observed, nor, over a limited concentration range, were multiple dissociation constants. An Eyring rate theory model with a single binding site was sufficient to explain these observations. PMID:8786344

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.

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.

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

Behavioral evidence for a role of chemoreception during reproduction in lake trout

USGS Publications Warehouse

Buchinger, Tyler J.; Li, Weiming; Johnson, Nicholas

2015-01-01

Chemoreception is hypothesized to influence spawning site selection, mate search, and synchronization of gamete release in chars (Salvelinus spp.), but behavioral evidence is generally lacking. Here, we provide a survey of the behavioral responses of reproductive male and female lake trout (Salvelinus namaycush) to natural conspecific chemosensory stimuli. A flow-through laboratory assay with side-by-side artificial spawning reefs was used to evaluate behavioral preferences of spawning-phase males and females for chemosensory stimuli from juveniles and from spawning-phase males and females. Males and females preferred male and juvenile stimuli over no stimuli, but only had weak preferences for female stimuli. Only females had a preference for male over juvenile stimuli when given a direct choice between the two. The unexpected observation of male attraction to male stimuli, even when offered female stimuli, indicates a fundamental difference from the existing models of chemical communication in fishes. We discuss our results from the perspectives of prespawning aggregation, mate evaluation, and spawning synchronization. Identification of specific components of the stimuli will allow confirmation of the function and may have management implications for native and invasive populations of lake trout that are ecologically and economically important.

Dynamics of Aspen Roots Colonization by Pseudomonads Reveals Strain-Specific and Mycorrhizal-Specific Patterns of Biofilm Formation

PubMed Central

Noirot-Gros, Marie-Francoise; Shinde, Shalaka; Larsen, Peter E.; Zerbs, Sarah; Korajczyk, Peter J.; Kemner, Kenneth M.; Noirot, Philippe H.

2018-01-01

Rhizosphere-associated Pseudomonas fluorescens are known plant growth promoting (PGP) and mycorrhizal helper bacteria (MHB) of many plants and ectomycorrhizal fungi. We investigated the spatial and temporal dynamics of colonization of mycorrhizal and non-mycorrhizal Aspen seedlings roots by the P. fluorescens strains SBW25, WH6, Pf0-1, and the P. protegens strain Pf-5. Seedlings were grown in laboratory vertical plates systems, inoculated with a fluorescently labeled Pseudomonas strain, and root colonization was monitored over a period of 5 weeks. We observed unexpected diversity of bacterial assemblies on seedling roots that changed over time and were strongly affected by root mycorrhization. P. fluorescens SBW25 and WH6 stains developed highly structured biofilms with internal void spaces forming channels. On mycorrhizal roots bacteria appeared encased in a mucilaginous substance in which they aligned side by side in parallel arrangements. The different phenotypic classes of bacterial assemblies observed for the four Pseudomonas strains were summarized in a single model describing transitions between phenotypic classes. Our findings also reveal that bacterial assembly phenotypes are driven by interactions with mucilaginous materials present at roots. PMID:29774013

Immediate and Latent Interlimb Transfer of Gait Stability Adaptation Following Repeated Exposure to Slips

PubMed Central

Bhatt, T.; Pai, Y.-C.

2008-01-01

The authors trained 21 participants by using blocked-and-mixed exposure to right-side slips and then caused them to slip unexpectedly on the untrained left side. Authors retested participants with a right slip and a left slip at 1 week, 2 weeks, 1 month, and 4 months. The authors found that preslip stability on the first untrained left slip improved and was significantly greater than that on the first right slip, which probably contributed to the reduction in incidence of falls from ∼30% to ∼10%. Postslip stability and base of support (BOS) slip velocity were similar to those on the first right slip and much lower than those on the last right slip. Increases in pre- and postslip stabilities and BOS slip velocity during the left slip led to reductions in backward balance loss (BLOB) from ∼95% on initial left slip to ∼60% and to ∼25% on the 1st and 3rd retest sessions, respectively. In contrast, BLOB remained at a constant ∼40% level on the right slip of the same retest sessions. The results indicate a partial immediate transfer and a possible latent transfer. PMID:18782713

Reassessing the improbability of a muscular crinoid stem

PubMed Central

Gorzelak, Przemysław; Głuchowski, Edward; Salamon, Mariusz A.

2014-01-01

Muscular articulations in modern stalked crinoids are only present in the arms. Although it has been suggested that certain coiled-stemmed fossil taxa may have been functionally adapted to utilize muscles, evidence supporting this interpretation is lacking. Here, we use cathodoluminescence and SEM to reveal the skeletal microstructure of the enigmatic coiled-stemmed taxon Ammonicrinus (Flexibilia). Based on the well-established link between skeletal microstructure and the nature of infilling soft tissues in modern echinoderms, we reconstructed the palaeoanatomy of the Middle Devonian ammonicrinids. We show that their median columnals with elongated lateral columnal enclosure extensions (LCEE) have stereom microstructure unexpectedly resembling that in the crinoid muscular arm plates. In particular, large ligamentary facets, that are present on each side of a transverse ridge, are mainly comprised of fine galleried stereom that is indicative of the mutable collagenous tissues. In contrast, fine labyrinthic stereom, commonly associated with muscles, is situated in the periphery on each side of the surface of elongated LCEE. Our findings thus strongly suggest that the muscles may have also been present in the stem of ammonicrinids. These results reassess the previous hypotheses about evolution of muscles in crinoids and provide new insights into the mode of life of Ammonicrinus. PMID:25116414

Reassessing the improbability of a muscular crinoid stem

NASA Astrophysics Data System (ADS)

Gorzelak, Przemysław; Głuchowski, Edward; Salamon, Mariusz A.

2014-08-01

Muscular articulations in modern stalked crinoids are only present in the arms. Although it has been suggested that certain coiled-stemmed fossil taxa may have been functionally adapted to utilize muscles, evidence supporting this interpretation is lacking. Here, we use cathodoluminescence and SEM to reveal the skeletal microstructure of the enigmatic coiled-stemmed taxon Ammonicrinus (Flexibilia). Based on the well-established link between skeletal microstructure and the nature of infilling soft tissues in modern echinoderms, we reconstructed the palaeoanatomy of the Middle Devonian ammonicrinids. We show that their median columnals with elongated lateral columnal enclosure extensions (LCEE) have stereom microstructure unexpectedly resembling that in the crinoid muscular arm plates. In particular, large ligamentary facets, that are present on each side of a transverse ridge, are mainly comprised of fine galleried stereom that is indicative of the mutable collagenous tissues. In contrast, fine labyrinthic stereom, commonly associated with muscles, is situated in the periphery on each side of the surface of elongated LCEE. Our findings thus strongly suggest that the muscles may have also been present in the stem of ammonicrinids. These results reassess the previous hypotheses about evolution of muscles in crinoids and provide new insights into the mode of life of Ammonicrinus.

The relation between driving experience and recognition of road signs relative to their locations.

PubMed

Borowsky, Avinoam; Shinar, David; Parmet, Yisrael

2008-04-01

Examine how driving experience and expectations affect the ability of experienced drivers to identify traffic signs--specifically, no right turn (NRT) and no left turn (NLT) at intersections. Failure to heed signs is a frequent cause of accidents, and the authors focused on the contributions of experience and expectancy to sign identification. Inexperienced and experienced drivers were connected to an eye tracker system and briefly exposed to various traffic scenes. Some of the pictures included an NRT sign at the expected location (on the right), and some included the same sign at an unexpected location (on the left). The same procedure was used with an NLT traffic sign. Experienced drivers identified traffic signs better than inexperienced drivers did when the signs were posted at the expected location but identified them worse than did inexperienced drivers when they were at unexpected locations. With experience, drivers' expectations regarding the expected location of traffic signs become so strong that violating these expectancies results in more identification errors among experienced drivers than among inexperienced drivers. To optimize experienced drivers' traffic sign identification, signs must be located in accordance with drivers' expectations--specifically, on the right side of the road. When signs are misplaced, crashes can be caused by inappropriate placement rather than inappropriate driving. Highway designers should ensure that their design conforms to standards that shape experienced drivers' expectations.

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.

Effects of automobile steering characteristics on driver/vehicle system performance in discrete maneuvers

NASA Technical Reports Server (NTRS)

Klein, R. H.; Mcruer, D. T.

1975-01-01

A series of discrete maneuver tasks were used to evaluate the effects of steering gain and directional mode dynamic parameters on driver/vehicle responses. The importance and ranking of these parameters were evaluated through changes in subjective driver ratings and performance measures obtained from transient maneuvers such as a double lane change, an emergency lane change, and an unexpected obstacle. The unexpected obstacle maneuver proved more sensitive to individual driver differences than to vehicle differences. Results were based on full scale tests with an experienced test driver evaluating many different dynamic configurations plus seventeen ordinary drivers evaluating six key configurations.

Intraday LeBaron effects

PubMed Central

Bianco, Simone; Corsi, Fulvio; Renò, Roberto

2009-01-01

We study the relation at intraday level between serial correlation and volatility of the Standard and Poor (S&P) 500 stock index futures returns. At daily and weekly levels, serial correlation and volatility forecasts have been found to be negatively correlated (LeBaron effect). After finding a significant attenuation of the original effect over time, we show that a similar but more pronounced effect holds by using intraday measures, by such as realized volatility and variance ratio. We also test the impact of unexpected volatility, defined as the part of volatility which cannot be forecasted, on the presence of intraday serial correlation in the time series by employing a model for realized volatility based on the heterogeneous market hypothesis. We find that intraday serial correlation is negatively correlated to volatility forecasts, whereas it is positively correlated to unexpected volatility.

An attention-based effective neural model for drug-drug interactions extraction.

PubMed

Zheng, Wei; Lin, Hongfei; Luo, Ling; Zhao, Zhehuan; Li, Zhengguang; Zhang, Yijia; Yang, Zhihao; Wang, Jian

2017-10-10

Drug-drug interactions (DDIs) often bring unexpected side effects. The clinical recognition of DDIs is a crucial issue for both patient safety and healthcare cost control. However, although text-mining-based systems explore various methods to classify DDIs, the classification performance with regard to DDIs in long and complex sentences is still unsatisfactory. In this study, we propose an effective model that classifies DDIs from the literature by combining an attention mechanism and a recurrent neural network with long short-term memory (LSTM) units. In our approach, first, a candidate-drug-oriented input attention acting on word-embedding vectors automatically learns which words are more influential for a given drug pair. Next, the inputs merging the position- and POS-embedding vectors are passed to a bidirectional LSTM layer whose outputs at the last time step represent the high-level semantic information of the whole sentence. Finally, a softmax layer performs DDI classification. Experimental results from the DDIExtraction 2013 corpus show that our system performs the best with respect to detection and classification (84.0% and 77.3%, respectively) compared with other state-of-the-art methods. In particular, for the Medline-2013 dataset with long and complex sentences, our F-score far exceeds those of top-ranking systems by 12.6%. Our approach effectively improves the performance of DDI classification tasks. Experimental analysis demonstrates that our model performs better with respect to recognizing not only close-range but also long-range patterns among words, especially for long, complex and compound sentences.

Effect of antipsychotics on peptides involved in energy balance in drug-naive psychotic patients after 1 year of treatment.

PubMed

Perez-Iglesias, Rocio; Vazquez-Barquero, Jose Luis; Amado, Jose Antonio; Berja, Ana; Garcia-Unzueta, Maria Teresa; Pelayo-Terán, Jose María; Carrasco-Marín, Eugenio; Mata, Ignacio; Crespo-Facorro, Benedicto

2008-06-01

Weight gain has become one of the most common and concerning side effects of antipsychotic treatment. The mechanisms whereby antipsychotics induce weight gain are not known. It has been suggested that peptides related to food intake and energy balance could play a role in weight gain secondary to antipsychotic therapy. To better understand the pathophysiology of antipsychotic-induced weight gain, we studied the effects of 3 antipsychotic drugs (haloperidol, olanzapine, and risperidone) on peptides involved in energy balance (insulin, ghrelin, leptin, adiponectin, visfatin, and resistin) in a population of drug-naive patients with first episode of psychosis.A significant increase in weight (10.16 kg [SD, 8.30 kg]; P < 0.001), body mass index (3.56 kg/m [SD, 2.89 kg/m]; P < 0.001), and fasting insulin (3.93 muU/mL [SD, 3.93 muU/mL]; P = 0.028), leptin (6.76 ng/mL [SD, 7.21 ng/mL]; P < 0.001), and ghrelin (15.47 fmol/mL [SD, 47.90 fmol/mL]; P = 0.009) plasma levels were observed. The increments in insulin and leptin concentrations were highly correlated with the increment in weight and body mass index and seem to be a consequence of the higher fat stores. The unexpected increase in ghrelin levels might be related with the causal mechanism of weight gain induced by antipsychotics. Finally, the 3 antipsychotics had similar effects in all parameters evaluated.

Imaging enhancement of malignancy by cyclophosphamide: surprising chemotherapy opposite effects

NASA Astrophysics Data System (ADS)

Yamauchi, Kensuke; Yang, Meng; Hayashi, Katsuhiro; Jiang, Ping; Xu, Mingxu; Yamamoto, Norio; Tsuchiya, Hiroyuki; Tomita, Katsuro; Moossa, A. R.; Bouvet, Michael; Hoffman, Robert M.

2008-02-01

Although side effects of cancer chemotherapy are well known, "opposite effects" of chemotherapy which enhance the malignancy of the treated cancer are not well understood. We have observed a number of steps of malignancy that are enhanced by chemotherapy pre-treatment of mice before transplantation of human tumor cells. The induction of intravascular proliferation, extravasation, and colony formation by cancer cells, critical steps of metastasis was enhanced by pretreatment of host mice with the commonly-used chemotherapy drug cyclophosphamide. Cyclophosphamide appears to interfere with a host process that inhibits intravascular proliferation, extravasation, and extravascular colony formation by at least some tumor cells. Cyclophosphamide does not directly affect the cancer cells since cyclophosphamide has been cleared by the time the cancer cells were injected. Without cyclophosphamide pretreatment, human colon cancer cells died quickly after injection in the portal vein of nude mice. Extensive clasmocytosis (destruction of the cytoplasm) of the cancer cells occurred within 6 hours. The number of apoptotic cells rapidly increased within the portal vein within 12 hours of injection. However, when the host mice were pretreated with cyclophosphamide, the cancer cells survived and formed colonies in the liver after portal vein injection. These results suggest that a cyclophosphamide-sensitive host cellular system attacked the cancer cells. This review describes an important unexpected "opposite effects" of chemotherapy that enhances critical steps in malignancy rather than inhibiting them, suggesting that certain current approaches to cancer chemotherapy should be modified.

Electrocatalytic Hydrogenation of Phenol over Platinum and Rhodium: Unexpected Temperature Effects Resolved

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

Singh, Nirala; Song, Yang; Gutiérrez, Oliver Y.

2016-11-04

Both electrocatalytic hydrogenation (ECH) and thermal hydrogenation (TH) of phenol by Pt and Rh show a roll-over in rate with increasing temperature without changing the principal reaction pathways. The negative effect of temperature for aqueous-phase phenol H2 and electrocatalytic hydrogenation on Pt and Rh is deduced to be due to the unexpected buildup of dehydrogenated phenol adsorbates, which block active sites. Rates of ECH and TH increase similarly with increasing hydrogen chemical potential whether induced by applied potential or H2 pressure, both via increasing H coverage, and indirectly by removing site blockers, a very strong effect at high temperature. Thismore » enables unprecedented rates in the TH of phenol at these temperatures.« less

Mesothelioma With a Large Prevascular Lymph Node: N1 Involvement or Something Different?

PubMed

Berzenji, Lawek; Van Schil, Paul E; Snoeckx, Annemie; Hertoghs, Marjan; Carp, Laurens

2018-05-01

A 64-year-old man presented with a large amount of right-sided pleural fluid on imaging, together with calcified pleural plaques and an enlarged nodular structure in the prevascular mediastinum, presumably an enlarged lymph node. Pleural biopsies were obtained during video-assisted thoracoscopic surgery to exclude malignancy. Histopathology showed an epithelial malignant pleural mesothelioma. Induction chemotherapy with cisplatin and pemetrexed was administered followed by an extended pleurectomy and decortication with systematic nodal dissection. Histopathology confirmed the diagnosis of a ypT3N0M0 (stage IB) mesothelioma, and an unexpected thymoma type B2 (stage II) was discovered in the prevascular nodule. Simultaneous occurrence of a mesothelioma and thymoma is extremely rare. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Collision avoidance using neural networks

NASA Astrophysics Data System (ADS)

Sugathan, Shilpa; Sowmya Shree, B. V.; Warrier, Mithila R.; Vidhyapathi, C. M.

2017-11-01

Now a days, accidents on roads are caused due to the negligence of drivers and pedestrians or due to unexpected obstacles that come into the vehicle’s path. In this paper, a model (robot) is developed to assist drivers for a smooth travel without accidents. It reacts to the real time obstacles on the four critical sides of the vehicle and takes necessary action. The sensor used for detecting the obstacle was an IR proximity sensor. A single layer perceptron neural network is used to train and test all possible combinations of sensors result by using Matlab (offline). A microcontroller (ARM Cortex-M3 LPC1768) is used to control the vehicle through the output data which is received from Matlab via serial communication. Hence, the vehicle becomes capable of reacting to any combination of real time obstacles.

A Ruptured Mitral Valve Aneurysm as Complication of a Bicuspid Aortic Valve Endocarditis.

PubMed

Muscente, Francesca; Scarano, Michele; Clemente, Daniela; Pezzuoli, Franco; Parato, Vito Maurizio

2017-01-01

We present a case of a ruptured mitral valve (MV) aneurysm as a complication of a bicuspid aortic valve (BAV) endocarditis. It is about a young 35-year-old man, admitted to Cardiology Unit because of unexpected heart failure picture. We found a BAV endocarditis complicated by anterior MV-anterior leaflet aneurysm formation and subsequent severe MV regurgitation caused by aneurysm perforation. It was a particular and rare situation characterized by an infection of anterior mitral leaflet secondary to an infected regurgitant jet of a primary aortic infective endocarditis due to a BAV. A resulting aneurysm formation on the atrial side of the mitral anterior leaflet leads later to mitral perforation. In this article, we review the more relevant medical literature on this topic.

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.

The clinical value of daily routine chest radiographs in a mixed medical-surgical intensive care unit is low.

PubMed

Graat, Marleen E; Choi, Goda; Wolthuis, Esther K; Korevaar, Johanna C; Spronk, Peter E; Stoker, Jaap; Vroom, Margreeth B; Schultz, Marcus J

2006-02-01

The clinical value of daily routine chest radiographs (CXRs) in critically ill patients is unknown. We conducted this study to evaluate how frequently unexpected predefined major abnormalities are identified with daily routine CXRs, and how often these findings lead to a change in care for intensive care unit (ICU) patients. This was a prospective observational study conducted in a 28-bed, mixed medical-surgical ICU of a university hospital. Over a 5-month period, 2,457 daily routine CXRs were done in 754 consecutive ICU patients. The majority of these CXRs did not reveal any new predefined major finding. In only 5.8% of daily routine CXRs (14.3% of patients) was one or more new and unexpected abnormality encountered, including large atelectases (24 times in 20 patients), large infiltrates (23 in 22), severe pulmonary congestion (29 in 25), severe pleural effusion (13 in 13), pneumothorax/pneumomediastinum (14 in 13), and malposition of the orotracheal tube (32 in 26). Fewer than half of the CXRs with a new and unexpected finding were ultimately clinically relevant; in only 2.2% of all daily routine CXRs (6.4% of patients) did these radiologic abnormalities result in a change to therapy. Subgroup analysis revealed no differences between medical and surgical patients with regard to the incidence of new and unexpected findings on daily routine CXRs and the effect of new and unexpected CXR findings on daily care. In the ICU, daily routine CXRs seldom reveal unexpected, clinically relevant abnormalities, and they rarely prompt action. We propose that this diagnostic examination be abandoned in ICU patients.

Safety and tolerability of extended-release niacin-laropiprant: Pooled analyses for 11,310 patients in 12 controlled clinical trials.

PubMed

McKenney, James; Bays, Harold; Gleim, Gilbert; Mitchel, Yale; Kuznetsova, Olga; Sapre, Aditi; Sirah, Waheeda; Maccubbin, Darbie

2015-01-01

The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) showed that adding extended-release niacin-laropiprant (ERN-LRPT) to statin provided no incremental cardiovascular benefit vs placebo (PBO). ERN-LRPT was also associated with an excess of serious adverse experiences (AEs), some of which were unexpected (infections and bleeding). These findings led to the withdrawal of ERN-LRPT from all markets. We examined the safety profile of ERN-LRPT vs the comparators ERN alone and statins in the ERN-LRPT development program to assess whether similar safety signals were observed to those seen in HPS-THRIVE and whether these might be attributed to ERN or LRPT. Postrandomization safety data from 12 clinical studies, 12 to 52 weeks in duration and involving 11,310 patients, were analyzed across 3 treatments: (1) ERN-LRPT; (2) ERN-NSP (ERN, Merck & Co, Inc or Niaspan [NSP], Abbott Laboratories); and (3) statin-PBO (statin or PBO). The safety profiles of ERN-LRPT and ERN-NSP were similar, except for less flushing with ERN-LRPT. Nonflushing AEs reported more frequently with ERN-LRPT or ERN-NSP than with statin-PBO were mostly nonserious and typical of niacin (nausea, diarrhea, and increased blood glucose). There was no evidence for an increased risk of serious AEs related to diabetes, muscle, infection, or bleeding. Pooled data from 11,310 patients revealed that, except for reduced flushing, the safety profile of ERN-LRPT was similar to that of ERN-NSP; LRPT did not appear to adversely affect the side-effect profile of ERN. The inability to replicate the unexpected AE findings in HPS2-THRIVE could be because of the smaller sample size and substantially shorter duration of these studies. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

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

The Nrf2 pathway in the progression of renal disease.

PubMed

Zoja, Carlamaria; Benigni, Ariela; Remuzzi, Giuseppe

2014-02-01

The Nrf2/Keap1 system regulates the transcription of antioxidant and cytoprotective genes through direct Nrf2 binding to responsive elements in the promoter region of target genes or via Keap1-induced NF-kB inhibition. The association between oxidative stress and inflammation with progression of chronic kidney diseases (CKDs) directed attention towards bardoxolone methyl and its analogues, potent Nrf2/Keap1 inducers, as a potential modality of renoprotective intervention. In a phase II clinical trial (BEAM), bardoxolone methyl was shown to increase the estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes. The study generated great interest but raised concerns as well, on the adverse event profile of the drug. Experiments in rats with type 2 diabetic nephropathy treated with bardoxolone methyl analogues reproduced some drawbacks of bardoxolone methyl therapy in humans. Despite these warnings, a long-term phase III trial (BEACON) was started that was prematurely terminated because of an excess serious adverse events and mortality. Lessons from the above studies suggest that before jumping into use in clinical practice, adequately designed experiments in animal models are needed to provide insights into pathogenetic mechanisms as well as unexpected side effects.

High pressure chemistry of red phosphorus by photoactivated simple molecules

NASA Astrophysics Data System (ADS)

Ceppatelli, Matteo; Bini, Roberto; Fanetti, Samuele; Caporali, Maria; Peruzzini, Maurizio

2013-06-01

High pressure (HP) is very effective in reducing intermolecular distances and inducing unexpected chemical reactions. In particular the photoactivation of the reactants in HP conditions can lead to very efficient and selective processes. The chemistry of phosphorus is currently based on the white molecular form. The red polymeric allotrope, despite more stable and much less toxic, has not attracted much attention so far. However, switching from the white to the red form would benefit any industrial procedure, especially from an environmental point of view. On the other side, water and ethanol are renewable, environmental friendly and largely available molecules, usable as reactants and photoactivators in HP conditions. Here we report a study on the HP photoinduced reactivity of red phosphorus with water and ethanol, showing the possibility of very efficient and selective processes, leading to molecular hydrogen and valuable phosphorus compounds. The reactions have been studied by means of FTIR and Raman spectroscopy and pressure has been generated using DAC and SAC. HP reactivity has been activated by the two-photon absorption of near-UV wavelengths and occured in total absence of solvents, catalysts and radical initiators, at room T and mild pressure conditions (0.2-1.5 GPa).

Sweet smells prepare plants for future stress: airborne induction of plant disease immunity.

PubMed

Yi, Hwe-Su; Ryu, Choong-Min; Heil, Martin

2010-05-01

Plants require protection against a wide range of attackers such as insects and pathogens. The adequate plant defense responses are regulated via sophisticated signal cascades, which are activated following the perception of specific cues of the attackers. Plants might, however, gain a significant fitness advantage when pre-empting enemy attack before it actually occurs. Monitoring cues from attacked neighbors can permit plants to reach this goal. We have recently found airborne disease resistance against a bacterial pathogen in uninfected lima bean plants when these were located close to conspecific, resistance-expressing neighbors. The emitters could be chemically induced with benzothiadiazole or biologically with an avirulent pathogen. Unexpectedly, receiver plants, although expressing a functioning resistance, did not show reduced growth rates, which represent a common side-effect of directly induced pathogen resistance. Nonanal was identified as an active volatile and, rather than directly inducing full resistance, primed defense gene expression, which became fully activated only when the plants were subsequently challenged by a virulent pathogen. Priming by airborne signals allows for a more efficient and less costly preparation of plants for future attack and airborne signaling can affect resistance against both major groups of plant enemies: herbivores and pathogens.

["Handle with care": about the potential unintended consequences of oracular artificial intelligence systems in medicine.

PubMed

Cabitza, Federico; Alderighi, Camilla; Rasoini, Raffaele; Gensini, Gian Franco

2017-10-01

Decisional support systems based on machine learning (ML) in medicine are gaining a growing interest as some recent articles have highlighted the high diagnostic accuracy exhibited by these systems in specific medical contexts. However, it is implausible that any potential advantage can be obtained without some potential drawbacks. In light of the current gaps in medical research about the side effects of the application of these new AI systems in medical practice, in this article we summarize the main unexpected consequences that may result from the widespread application of "oracular" systems, that is highly accurate systems that cannot give reasonable explanations of their advice as those endowed with predictive models developed with ML techniques usually are. These consequences range from the intrinsic uncertainty in the data that are used to train and feed these systems, to the inadequate explainability of their output; through the risk of overreliance, deskilling and context desensitization of their end-users. Although some of these issues may be currently hard to evaluate due to the still scarce adoption of these decisional systems in medical practice, we advocate the study of these potential consequences also for a more informed policy of approval beyond hype and disenchantment.

Cancer hyperthermia using magnetic nanoparticles.

PubMed

Kobayashi, Takeshi

2011-11-01

Magnetic-nanoparticle-mediated intracellular hyperthermia has the potential to achieve localized tumor heating without any side effects. The technique consists of targeting magnetic nanoparticles to tumor tissue followed by application of an external alternating magnetic field that induces heat through Néel relaxation loss of the magnetic nanoparticles. The temperature in tumor tissue is increased to above 43°C, which causes necrosis of cancer cells, but does not damage surrounding normal tissue. Among magnetic nanoparticles available, magnetite has been extensively studied. Recent years have seen remarkable advances in magnetite-nanoparticle-mediated hyperthermia; both functional magnetite nanoparticles and alternating-magnetic-field generators have been developed. In addition to the expected tumor cell death, hyperthermia treatment has also induced unexpected biological responses, such as tumor-specific immune responses as a result of heat-shock protein expression. These results suggest that hyperthermia is able to kill not only local tumors exposed to heat treatment, but also tumors at distant sites, including metastatic cancer cells. Currently, several research centers have begun clinical trials with promising results, suggesting that the time may have come for clinical applications. This review describes recent advances in magnetite nanoparticle-mediated hyperthermia. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Micelle Self-Assembled from Doxorubicin-Arabinoxylan Conjugates with pH-Cleavable Bond for Synergistic Antitumor Therapy

NASA Astrophysics Data System (ADS)

Wang, Jie; Li, Yanli; Dong, Xia; Wang, Ying; Chong, Xiaodan; Yu, Tai; Zhang, Fulei; Chen, Di; Zhang, Li; Gao, Jie; Yang, Cheng; Han, Jun; Li, Wei

2017-01-01

Nanomedicine offers new hope to overcome the low solubility and high side toxicity to normal tissue appeared in traditional chemotherapy. The biocompatibility and intracellular drug accumulation is still a big challenge for the nano-based formulations. Herein, a medical-used biocompatible arabinoxylan (AX) is used to develop to delivery chemodrug doxorubicin (DOX). The solubility of DOX is obviously enhanced via the hydrogen bond formed with AX which results in an amphiphilic AX-DOX. A micelle with pH-cleavable bond is thus self-assembled from such AX-DOX with DOX core and AX shell. The inner DOX can be easily released out at low intracellular pH, which obviously enhanced its in vitro cytotoxicity against breast cancer cells (MCF-7). Interestingly, an unexpected apoptosis is evoked except for the proliferation inhibition. Moreover, the therapeutic effects are further synergistically promoted by the enhanced permeability and retention (EPR) and intracellular pH-triggered drug release. Consequently, the in vivo intratumor accumulation of DOX, the tumor inhibition was significantly promoted after intravenous administration to the Balb/c nude mice bearing MCF-7 tumors. These in vitro/vivo results indicated that the AX-DOX micellular formulation holds high potential in cancer therapy.

Why Medical Informatics (still) Needs Cognitive and Social Sciences.

PubMed

Declerck, G; Aimé, X

2013-01-01

To summarize current excellent medical informatics research in the field of human factors and organizational issues. Using PubMed, a total of 3,024 papers were selected from 17 journals. The papers were evaluated on the basis of their title, keywords, and abstract, using several exclusion and inclusion criteria. 15 preselected papers were carefully evaluated by six referees using a standard evaluation grid. Six best papers were selected exemplifying the central role cognitive and social sciences can play in medical informatics research. Among other contributions, those studies: (i) make use of the distributed cognition paradigm to model and understand clinical care situations; (ii) take into account organizational issues to analyse the impact of HIT on information exchange and coordination processes; (iii) illustrate how models and empirical data from cognitive psychology can be used in medical informatics; and (iv) highlight the need of qualitative studies to analyze the unexpected side effects of HIT on cognitive and work processes. The selected papers demonstrate that paradigms, methodologies, models, and results from cognitive and social sciences can help to bridge the gap between HIT and end users, and contribute to limit adoption failures that are reported regularly.

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.

Conformational relaxation and water penetration coupled to ionization of internal groups in proteins.

PubMed

Damjanović, Ana; Brooks, Bernard R; García-Moreno, Bertrand

2011-04-28

Molecular dynamics simulations were used to examine the effects of ionization of internal groups on the structures of eighteen variants of staphylococcal nuclease (SNase) with internal Lys, Asp, or Glu. In most cases the RMSD values of internal ionizable side chains were larger when the ionizable moieties were charged than when they were neutral. Calculations of solvent-accessible surface area showed that the internal ionizable side chains were buried in the protein interior when they were neutral and moved toward crevices and toward the protein-water interface when they were charged. The only exceptions are Lys-36, Lys-62, and Lys-103, which remained buried even after charging. With the exception of Lys-38, the number of internal water molecules surrounding the ionizable group increased upon charging: the average number of water oxygen atoms within the first hydration shell increased by 1.7 for Lys residues, by 5.2 for Asp residues, and by 3.2 for Glu residues. The polarity of the microenvironment of the ionizable group also increased when the groups were charged: the average number of polar atoms of any kind within the first hydration shell increased by 2.7 for Lys residues, by 4.8 for Asp residues, and by 4.0 for Glu residues. An unexpected correlation was observed between the absolute value of the shifts in pK(a) values measured experimentally, and several parameters of structural relaxation: the net difference in the polarity of the microenvironment of the charged and neutral forms of the ionizable groups, the net difference in hydration of the charged and neutral forms of the ionizable groups, and the difference in RMSD values of the charged and neutral forms of the ionizable groups. The effects of ionization of internal groups on the conformation of the backbone were noticeable but mostly small and localized to the area immediately next to the internal ionizable moiety. Some variants did exhibit local unfolding.

Side-effects of domestication: cultivated legume seeds contain similar tocopherols and fatty acids but less carotenoids than their wild counterparts.

PubMed

Fernández-Marín, Beatriz; Milla, Rubén; Martín-Robles, Nieves; Arc, Erwann; Kranner, Ilse; Becerril, José María; García-Plazaola, José Ignacio

2014-12-20

Lipophilic antioxidants play dual key roles in edible seeds (i) as preservatives of cell integrity and seed viability by preventing the oxidation of fats, and (ii) as essential nutrients for human and animal life stock. It has been well documented that plant domestication and post-domestication evolution frequently resulted in increased seed size and palatability, and reduced seed dormancy. Nevertheless, and surprisingly, it is poorly understood how agricultural selection and cultivation affected the physiological fitness and the nutritional quality of seeds. Fabaceae have the greatest number of crop species of all plant families, and most of them are cultivated for their highly nutritious edible seeds. Here, we evaluate whether evolution of plants under cultivation has altered the integrated system formed by membranes (fatty acids) and lipophilic antioxidants (carotenoids and tocopherols), in the ten most economically important grain legumes and their closest wild relatives, i.e.: Arachis (peanut), Cicer (chickpea), Glycine (soybean), Lathyrus(vetch), Lens (lentil), Lupinus (lupin), Phaseolus (bean), Pisum (pea), Vicia (faba bean) and Vigna (cowpea). Unexpectedly, we found that following domestication, the contents of carotenoids, including lutein and zeaxanthin, decreased in all ten species (total carotenoid content decreased 48% in average). Furthermore, the composition of carotenoids changed, whereby some carotenoids were lost in most of the crops. An undirected change in the contents of tocopherols and fatty acids was found, with contents increasing in some species and decreasing in others, independently of the changes in carotenoids. In some species, polyunsaturated fatty acids (linolenic acid especially), α-tocopherol and γ-tocopherol decreased following domestication. The changes in carotenoids, tocopherols and fatty acids are likely side-effects of the selection for other desired traits such as the loss of seed dormancy and dispersal mechanisms, and selection for seed storability and taste. This work may serve as baseline to broaden our knowledge on the integrated changes on crop fitness and nutritional quality following domestication.

Dose and side effects of sublingual misoprostol for treatment of postpartum hemorrhage: what difference do they make?

PubMed Central

2012-01-01

Background Shivering and fever are common side effects of misoprostol. An unexpectedly high rate of fever above 40°C was documented among Ecuadorian women given treatment with 800mcg of sublingual misoprostol to manage postpartum hemorrhage (PPH) (36%). Much lower rates have been reported elsewhere (0-9%). Methods From February to July 2010, an open-label pilot study was conducted in Quito, Ecuador to determine whether a lower dose--600mcg sublingual misoprostol--would result in a lower incidence of high fever (≥40°C). Rates of shivering and fever with 600mcg sublingual regimen were compared to previously documented rates in Ecuador following PPH treatment with 800mcg sublingual misoprostol. Results The 600mcg dose resulted in a 55% lower rate of high fever compared with the 800mcg regimen (8/50; 16% vs. 58/163; 36%; relative risk 0.45 95% CI 0.23-0.88). Only one woman had severe shivering following the 600mcg dose compared with 19 women in the 800mcg cohort (2% vs. 12%; relative risk 0.17 (0.02-1.25)). No cases of delirium/altered sensorium were reported with the 600mcg dose and women’s assessment of severity/tolerability of shivering and fever was better with the lower dose. Conclusions 600mcg sublingual misoprostol was found to decrease the occurrence of high fever among Ecuadorian women when given to treat PPH. This study however was not powered to examine the efficacy of this treatment regimen and cannot be recommended at this time. Future research is needed to confirm whether other populations, outside of Quito, Ecuador, experience unusually high rates of elevated body temperature following sublingual administration of misoprostol for treatment of PPH. If indeed similar trends are found elsewhere, larger trials to confirm the efficacy of lower dosages may be justified. Trial Registration Clinical trials.gov, Registry No. NCT01080846 PMID:22769055

Dose and side effects of sublingual misoprostol for treatment of postpartum hemorrhage: what difference do they make?

PubMed

León, Wilfrido; Durocher, Jill; Barrera, Gustavo; Pinto, Ernesto; Winikoff, Beverly

2012-07-07

Shivering and fever are common side effects of misoprostol. An unexpectedly high rate of fever above 40°C was documented among Ecuadorian women given treatment with 800mcg of sublingual misoprostol to manage postpartum hemorrhage (PPH) (36%). Much lower rates have been reported elsewhere (0-9%). From February to July 2010, an open-label pilot study was conducted in Quito, Ecuador to determine whether a lower dose--600mcg sublingual misoprostol--would result in a lower incidence of high fever (≥40°C). Rates of shivering and fever with 600mcg sublingual regimen were compared to previously documented rates in Ecuador following PPH treatment with 800mcg sublingual misoprostol. The 600mcg dose resulted in a 55% lower rate of high fever compared with the 800mcg regimen (8/50; 16% vs. 58/163; 36%; relative risk 0.45 95% CI 0.23-0.88). Only one woman had severe shivering following the 600mcg dose compared with 19 women in the 800mcg cohort (2% vs. 12%; relative risk 0.17 (0.02-1.25)). No cases of delirium/altered sensorium were reported with the 600mcg dose and women's assessment of severity/tolerability of shivering and fever was better with the lower dose. 600mcg sublingual misoprostol was found to decrease the occurrence of high fever among Ecuadorian women when given to treat PPH. This study however was not powered to examine the efficacy of this treatment regimen and cannot be recommended at this time. Future research is needed to confirm whether other populations, outside of Quito, Ecuador, experience unusually high rates of elevated body temperature following sublingual administration of misoprostol for treatment of PPH. If indeed similar trends are found elsewhere, larger trials to confirm the efficacy of lower dosages may be justified. Clinical trials.gov, Registry No. NCT01080846.

Two-Year Trends of Taxane-Induced Neuropathy in Women Enrolled in a Randomized Trial of Acetyl-L-Carnitine (SWOG S0715).

PubMed

Hershman, Dawn L; Unger, Joseph M; Crew, Katherine D; Till, Cathee; Greenlee, Heather; Minasian, Lori M; Moinpour, Carol M; Lew, Danika L; Fehrenbacher, Louis; Wade, James L; Wong, Siu-Fun; Fisch, Michael J; Lynn Henry, N; Albain, Kathy S

2018-06-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and disabling side effect of taxanes. Acetyl-L-carnitine (ALC) was unexpectedly found to increase CIPN in a randomized trial. We investigated the long-term patterns of CIPN among patients in this trial. S0715 was a randomized, double-blind, multicenter trial comparing ALC (1000 mg three times a day) with placebo for 24 weeks in women undergoing adjuvant taxane-based chemotherapy for breast cancer. CIPN was measured by the 11-item neurotoxicity (NTX) component of the FACT-Taxane scale at weeks 12, 24, 36, 52, and 104. We examined NTX scores over two years using linear mixed models for longitudinal data. Individual time points were examined using linear regression. Regression analyses included stratification factors and the baseline score as covariates. All statistical tests were two-sided. Four-hundred nine subjects were eligible for evaluation. Patients receiving ALC had a statistically significantly (P = .01) greater reduction in NTX scores (worse CIPN) of -1.39 points (95% confidence interval [CI] = -2.48 to -0.30) than the placebo group. These differences were particularly evident at weeks 24 (-1.68, 95% CI = -3.02 to -0.33), 36 (-1.37, 95% CI = -2.69 to -0.04), and 52 (-1.83, 95% CI = -3.35 to -0.32). At 104 weeks, 39.5% on the ALC arm and 34.4% on the placebo arm reported a five-point (10%) decrease from baseline. For both treatment groups, 104-week NTX scores were statistically significantly different compared with baseline (P < .001). For both groups, NTX scores were reduced from baseline and remained persistently low. Twenty-four weeks of ALC therapy resulted in statistically significantly worse CIPN over two years. Understanding the mechanism of this persistent effect may inform prevention and treatment strategies. Until then, the potential efficacy and harms of commonly used supplements should be rigorously studied.

Sequence-specific, nanomolar peptide binding via cucurbit[8]uril-induced folding and inclusion of neighboring side chains.

PubMed

Smith, Lauren C; Leach, David G; Blaylock, Brittney E; Ali, Omar A; Urbach, Adam R

2015-03-18

This paper describes the molecular recognition of the tripeptide Tyr-Leu-Ala by the synthetic receptor cucurbit[8]uril (Q8) in aqueous buffer with nanomolar affinity and exceptional specificity. This combination of characteristics, which also applies to antibodies, is desirable for applications in biochemistry and biotechnology but has eluded supramolecular chemists for decades. Building on prior knowledge that Q8 binds to peptides with N-terminal aromatic residues, a library screen of 105 peptides was designed to test the effects of residues adjacent to N-terminal Trp, Phe, or Tyr. The screen used tetramethylbenzobis(imidazolium) (MBBI) as a fluorescent indicator and resulted in the unexpected discovery that MBBI can serve not only as a turn-off sensor via the simultaneous inclusion of a Trp residue but also as a turn-on sensor via the competitive displacement of MBBI upon binding of Phe- or Tyr-terminated peptides. The unusual fluorescence response of the Tyr series prompted further investigation by (1)H NMR spectroscopy, electrospray ionization mass spectrometry, and isothermal titration calorimetry. From these studies, a novel binding motif was discovered in which only 1 equiv of peptide binds to Q8, and the side chains of both the N-terminal Tyr residue and its immediate neighbor bind within the Q8 cavity. For the peptide Tyr-Leu-Ala, the equilibrium dissociation constant value is 7.2 nM, whereas that of its sequence isomer Tyr-Ala-Leu is 34 μM. The high stability, recyclability, and low cost of Q8 combined with the straightforward incorporation of Tyr-Leu-Ala into recombinant proteins should make this system attractive for the development of biological applications.

A phase III, randomized, double-blind, matched-pairs, active-controlled clinical trial and preclinical animal study to compare the durability, efficacy and safety between polynucleotide filler and hyaluronic acid filler in the correction of crow's feet: a new concept of regenerative filler.

PubMed

Pak, Chang Sik; Lee, Jongho; Lee, Hobin; Jeong, Jaehoon; Kim, Eun-Hee; Jeong, Jinwook; Choi, Hyeyeon; Kim, Byunghwi; Oh, Sujin; Kim, Iksoo; Heo, Chan Yeong

2014-11-01

The Rejuran® is a new filler product made from purified polynucleotides. Here we present data from an animal study and a clinical trial to examine the durability, efficacy and safety of the Rejuran® on crow's feet. For the animal study, 25 mice were divided into three groups: Group 1 received phosphate buffered saline (PBS); Group 2 were treated with Yvoire®; and Group 3 were treated with Rejuran®. The durability and efficacy of each treatment were assessed by microscopy and staining. In the clinical trial, 72 patients were randomized to receive Rejuran® treatment for crow's feet on one side and Yvoire-Hydro® on the contralateral side, at a ratio of 1:1. Repeated treatments were performed every two weeks for a total of three times, over a total of 12 weeks' observation. All injections and observations of efficacy and safety were performed by the same two investigators. In the animal study, the Rejuran® group showed similar durability and inflammatory response to the Yvoire® group. Upon efficacy assessment, the Rejuran® group showed the greatest elasticity and collagen composition, and a significant difference in skin surface roughness and wrinkle depth. In the clinical trial, the primary and secondary objective efficacy outcome measure showed no statistical significance between the two groups, and in safety outcomes there were no unexpected adverse effects. Our data suggest that the Rejuran®, as a new regenerative filler, can be useful to reduce wrinkles, by showing evidence for its efficacy and safety.

[Off-label drug prescriptions among outpatient children and adolescents in Germany--a database analysis].

PubMed

Sonntag, D; Trebst, D; Kiess, W; Kapellen, T; Bertsche, T; Kostev, K

2013-10-01

Due to lack of respective studies children often receive medication that is applied beyond the approved indication. The consequence of this off-label use is often an increased risk of unexpected and undesirable side effects. This study deals with the amount of off-label drug prescriptions among children and adolescents receiving outpatient treatment in Germany. The aim is to outline age-, gender-, region-, and insurance specific differences and to determine risk factors for an off-label prescription. This is a retrospective study that has been conducted by means of the IMS Patient Database Disease Analyzer for the year 2010 considering three therapy classes (analgesics, antibiotics and antidepressants). The evaluation of the risk factors for an off-label prescription resulted from a multivariate logistic regression. Age- and dose-specific prescriptions were analyzed but not indication-specific prescriptions. In total 189,285 children and adolescents with analgesics-, 147,089 with antibiotics-, and 15,405 with antidepressants prescriptions were identified. The percentage of patients with off-label prescriptions amounted to 0.9 % for analgesics, 2.5 % for antibiotics and 8.5 % for antidepressants. The off-label prescriptions made by general practitioners were significantly higher than those made by pediatricians and child psychiatrists. The number of off-label prescriptions in country sides was higher than in cities. In eastern states more off-label prescriptions were made than in western states of Germany. The study shows that outpatient treatment of children and adolescents occurs widely with drugs corresponding to age and dosage. Off-label prescriptions not conform to indication were not determined. However, off-label drug use should be reduced further for outpatient treatment to ensure a safe and low-risk medical treatment for children and adolescents. © Georg Thieme Verlag KG Stuttgart · New York.

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

Theory of mind for processing unexpected events across contexts.

PubMed

Dungan, James A; Stepanovic, Michael; Young, Liane

2016-08-01

Theory of mind, or mental state reasoning, may be particularly useful for making sense of unexpected events. Here, we investigated unexpected behavior across both social and non-social contexts in order to characterize the precise role of theory of mind in processing unexpected events. We used functional magnetic resonance imaging to examine how people respond to unexpected outcomes when initial expectations were based on (i) an object's prior behavior, (ii) an agent's prior behavior and (iii) an agent's mental states. Consistent with prior work, brain regions for theory of mind were preferentially recruited when people first formed expectations about social agents vs non-social objects. Critically, unexpected vs expected outcomes elicited greater activity in dorsomedial prefrontal cortex, which also discriminated in its spatial pattern of activity between unexpected and expected outcomes for social events. In contrast, social vs non-social events elicited greater activity in precuneus across both expected and unexpected outcomes. Finally, given prior information about an agent's behavior, unexpected vs expected outcomes elicited an especially robust response in right temporoparietal junction, and the magnitude of this difference across participants correlated negatively with autistic-like traits. Together, these findings illuminate the distinct contributions of brain regions for theory of mind for processing unexpected events across contexts. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

“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.

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.

Effect of sudden addition of PCE and bioreactor coupling to ZVI filters on performance of fluidized bed bioreactors operated in simultaneous electron acceptor modes.

PubMed

Moreno-Medina, C U; Poggi-Varaldo, Hector M; Breton-Deval, L; Rinderknecht-Seijas, N

2017-11-01

The present work evaluated the effects of (i) feeding a water contaminated with 80 mg/L PCE to bioreactors seeded with inoculum not acclimated to PCE, (ii) coupling ZVI side filters to bioreactors, and (iii) working in different biological regimes, i.e., simultaneous methanogenic aeration and simultaneous methanogenic-denitrifying regimes, on fluidized bed bioreactor performance. Simultaneous electron acceptors refer to the simultaneous presence of two compounds operating as final electron acceptors in the biological respiratory chain (e.g., use of either O 2 or NO 3 - in combination with a methanogenic environment) in a bioreactor or environmental niche. Four lab-scale, mesophilic, fluidized bed bioreactors (bioreactors) were implemented. Two bioreactors were operated as simultaneous methanogenic-denitrifying (MD) units, whereas the other two were operated in partially aerated methanogenic (PAM) mode. In the first period, all bioreactors received a wastewater with 1 g chemical oxygen demand of methanol per liter (COD-methanol/L). In a second period, all the bioreactors received the wastewater plus 80 mg perchloroethylene (PCE)/L; at the start of period 2, one MD and one PAM were coupled to side sand-zero valent iron filters (ZVI). All bioreactors were inoculated with a microbial consortium not acclimated to PCE. In this work, the performance of the full period 1 and the first 60 days of period 2 is reported and discussed. The COD removal efficiency and the nitrate removal efficiency of the bioreactors essentially did not change between period 1 and period 2, i.e., upon PCE addition. On the contrary, specific methanogenic activity in PAM bioreactors (both with and without coupled ZVI filter) significantly decreased. This was consistent with a sharp fall of methane productivity in those bioreactors in period 2. During period 2, PCE removals in the range 86 to 97 % were generally observed; the highest removal corresponded to PAM bioreactors along with the highest dehalogenation efficiency (94 %). Principal component analysis as well as cluster analysis confirmed the trends mentioned above, i.e., the better performance of PAM over MD, and the unexpected no effect of the ZVI side filters on PCE removal and dehalogenation efficiencies. To the best of our knowledge, this is the first report on the combined treatment ZVI-biological of a water polluted with PCE, where the biological operation relied on simultaneous electron acceptors.

Herbal-drug interaction induced rhabdomyolysis in a liposarcoma patient receiving trabectedin

PubMed Central

2013-01-01

Background Rhabdomyolysis is an uncommon side effect of trabectedin which is used for the second line therapy of metastatic sarcoma after anthracycline and ifosfamide failure. This side effect may be due to pharmacokinetic interactions caused by shared mechanisms of metabolism involving the cytochrome P450 (CYP) system in the liver. Here, for the first time in literature, we describe the unexpected onset of heavy toxicity, including rhabdomyolysis, after the fourth course of trabectedin in a patient with retroperitoneal liposarcoma who at the same time was taking an alternative herbal medicine suspected of triggering this adverse event. Case presentation This is the case of a 56 year old Caucasian man affected by a relapsed de-differentiated liposarcoma who, after the fourth cycle of second-line chemotherapy with trabectedin, complained of sudden weakness, difficulty walking and diffuse muscle pain necessitating complete bed rest. Upon admission to our ward the patient showed grade (G) 4 pancytopenia and a marked increase in liver lytic enzymes, serum levels of myoglobin, creatine phosphokinase (CPK) and lactate dehydrogenase. No cardiac or kidney function injuries were present. Based on these clinical and laboratory features, our conclusive diagnosis was of rhabdomyolysis induced by trabectedin. The patient did not report any trauma or muscular overexertion and no co-morbidities were present. He had not received any drugs during treatment with trabectedin, but upon further questioning the patient informed us he had been taking a folk medicine preparation of chokeberry (Aronia melanocarpa) daily during the last course of trabectedin and in the 2 subsequent weeks. One week after hospitalization and cessation of intake of chokeberry extract, CPK and other markers of myolysis slowly returned to standard range, and the patient noted a progressive recovery of muscle strength. The patient was discharged on day 14 when a blood transfusion and parenteral hydration gradually lowered general toxicity. Progressive mobilization of the patient was obtained as well as a complete normalization of the laboratory findings. Conclusions The level of evidence of drug interaction leading to the adverse event observed in our patient was 2 (probable). Thus our case underlines the importance of understanding rare treatment-related toxicities such as trabectedin-induced rhabdomyolysis and the possible role of the drug-drug interactions in the pathogenesis of this rare side effect. Furthermore, this report draws attention to a potential problem of particular concern, that of nutritional supplements and complementary and alternative drug interactions. These are not widely recognized and can cause treatment failure. PMID:23899130

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 ...

A remote palm domain residue of RB69 DNA polymerase is critical for enzyme activity and influences the conformation of the active site.

PubMed

Jacewicz, Agata; Trzemecka, Anna; Guja, Kip E; Plochocka, Danuta; Yakubovskaya, Elena; Bebenek, Anna; Garcia-Diaz, Miguel

2013-01-01

Non-conserved amino acids that are far removed from the active site can sometimes have an unexpected effect on enzyme catalysis. We have investigated the effects of alanine replacement of residues distant from the active site of the replicative RB69 DNA polymerase, and identified a substitution in a weakly conserved palm residue (D714A), that renders the enzyme incapable of sustaining phage replication in vivo. D714, located several angstroms away from the active site, does not contact the DNA or the incoming dNTP, and our apoenzyme and ternary crystal structures of the Pol(D714A) mutant demonstrate that D714A does not affect the overall structure of the protein. The structures reveal a conformational change of several amino acid side chains, which cascade out from the site of the substitution towards the catalytic center, substantially perturbing the geometry of the active site. Consistent with these structural observations, the mutant has a significantly reduced k pol for correct incorporation. We propose that the observed structural changes underlie the severe polymerization defect and thus D714 is a remote, non-catalytic residue that is nevertheless critical for maintaining an optimal active site conformation. This represents a striking example of an action-at-a-distance interaction.

Experimental and modeling study of chloride ingress into concrete and reinforcement corrosion initiation

NASA Astrophysics Data System (ADS)

Yu, Hui

Effects of reinforcement and coarse aggregate on chloride ingression into concrete and reinforcement corrosion initiation have been studied with experimental and modeling (finite element method) analyses. Once specimens were fabricated and exposed to a chloride solution, various experimental techniques were employed to determine the effect of reinforcement and coarse aggregate on time-to-corrosion and chloride ingress and concentration at corrosion locations. Model analyses were performed to verify and explain the experimental results. Based upon the results, it was determined that unexpectedly higher chloride concentrations were present on the top of the rebar trace than that to the side at the same depth and an inverse concentration gradient (increasing [ Cl-] with increasing depth) occurred near the top of rebars. Also, coarse aggregate volume profile in close proximity to the rebar and spatial distribution of these aggregates, in conjunction with the physical obstruction afforded by reinforcement to chloride flow, complicates concrete sampling for Cl- intended to define the critical concentration of this species to initiate corrosion. Modeling analyses that considered cover thickness, chloride threshold concentration, reinforcement size and shape, and coarse aggregate type and percolation confirmed the experimental findings. The results, at least in part, account for the relatively wide spread in chloride corrosion threshold values reported in the literature and illustrate that more consistent chloride threshold concentrations can be acquired from mortar or paste specimens than from concrete ones.

Pharmacokinetic Interactions between Drugs and Botanical Dietary Supplements

PubMed Central

Sprouse, Alyssa A.

2016-01-01

The use of botanical dietary supplements has grown steadily over the last 20 years despite incomplete information regarding active constituents, mechanisms of action, efficacy, and safety. An important but underinvestigated safety concern is the potential for popular botanical dietary supplements to interfere with the absorption, transport, and/or metabolism of pharmaceutical agents. Clinical trials of drug–botanical interactions are the gold standard and are usually carried out only when indicated by unexpected consumer side effects or, preferably, by predictive preclinical studies. For example, phase 1 clinical trials have confirmed preclinical studies and clinical case reports that St. John’s wort (Hypericum perforatum) induces CYP3A4/CYP3A5. However, clinical studies of most botanicals that were predicted to interact with drugs have shown no clinically significant effects. For example, clinical trials did not substantiate preclinical predictions that milk thistle (Silybum marianum) would inhibit CYP1A2, CYP2C9, CYP2D6, CYP2E1, and/or CYP3A4. Here, we highlight discrepancies between preclinical and clinical data concerning drug–botanical interactions and critically evaluate why some preclinical models perform better than others in predicting the potential for drug–botanical interactions. Gaps in knowledge are also highlighted for the potential of some popular botanical dietary supplements to interact with therapeutic agents with respect to absorption, transport, and metabolism. PMID:26438626

Pharmacokinetic Interactions between Drugs and Botanical Dietary Supplements.

PubMed

Sprouse, Alyssa A; van Breemen, Richard B

2016-02-01

The use of botanical dietary supplements has grown steadily over the last 20 years despite incomplete information regarding active constituents, mechanisms of action, efficacy, and safety. An important but underinvestigated safety concern is the potential for popular botanical dietary supplements to interfere with the absorption, transport, and/or metabolism of pharmaceutical agents. Clinical trials of drug-botanical interactions are the gold standard and are usually carried out only when indicated by unexpected consumer side effects or, preferably, by predictive preclinical studies. For example, phase 1 clinical trials have confirmed preclinical studies and clinical case reports that St. John's wort (Hypericum perforatum) induces CYP3A4/CYP3A5. However, clinical studies of most botanicals that were predicted to interact with drugs have shown no clinically significant effects. For example, clinical trials did not substantiate preclinical predictions that milk thistle (Silybum marianum) would inhibit CYP1A2, CYP2C9, CYP2D6, CYP2E1, and/or CYP3A4. Here, we highlight discrepancies between preclinical and clinical data concerning drug-botanical interactions and critically evaluate why some preclinical models perform better than others in predicting the potential for drug-botanical interactions. Gaps in knowledge are also highlighted for the potential of some popular botanical dietary supplements to interact with therapeutic agents with respect to absorption, transport, and metabolism. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Appliance-induced osteopenia of dentoalveolar bone in the rat: effect of reduced bone strains on serum bone markers and the multifunctional hormone leptin.

PubMed

Vinoth, Jayaseelan K; Patel, Kaval J; Lih, Wei-Song; Seow, Yian-San; Cao, Tong; Meikle, Murray C

2013-12-01

To understand, in greater detail, the molecular mechanisms regulating the complex relationship between mechanical strain and alveolar bone metabolism during orthodontic treatment, passive cross-arch palatal springs were bonded to the maxillary molars of 6-wk-old rats, which were killed after 4 and 8 d. Outcome measures included serum assays for markers of bone formation and resorption and for the multifunctional hormone leptin, and histomorphometry of the inter-radicular bone. The concentration of the bone-formation marker alkaline phosphatase (ALP) was significantly reduced at both time points in the appliance group, accompanied by a 50% reduction in inter-radicular bone volume; however, osteocalcin (bone Gla protein) levels remained unaffected. Bone collagen deoxypyridinoline (DPD) crosslinks increased 2.3-fold at 4 d only, indicating a transient increase in bone resorption; in contrast, the level of the osteoclast-specific marker, tartrate-resistant acid phosphatase 5b (TRACP 5b), was unchanged. Leptin levels closely paralleled ALP reductions at both time points, suggesting an important role in the mechanostat negative-feedback loop required to normalize bone mass. These data suggest that an orthodontic appliance, in addition to remodeling the periodontal ligament (PDL)-bone interface, may exert unexpected side-effects on the tooth-supporting alveolar bone, and highlights the importance of recognizing that bone strains can have negative, as well as positive, effects on bone mass. © 2013 Eur J Oral Sci.

Mobile phone use during driving: Effects on speed and effectiveness of driver compensatory behaviour.

PubMed

Choudhary, Pushpa; Velaga, Nagendra R

2017-09-01

This study analysed and modelled the effects of conversation and texting (each with two difficulty levels) on driving performance of Indian drivers in terms of their mean speed and accident avoiding abilities; and further explored the relationship between speed reduction strategy of the drivers and their corresponding accident frequency. 100 drivers of three different age groups (young, mid-age and old-age) participated in the simulator study. Two sudden events of Indian context: unexpected crossing of pedestrians and joining of parked vehicles from road side, were simulated for estimating the accident probabilities. Generalized linear mixed models approach was used for developing linear regression models for mean speed and binary logistic regression models for accident probability. The results of the models showed that the drivers significantly compensated the increased workload by reducing their mean speed by 2.62m/s and 5.29m/s in the presence of conversation and texting tasks respectively. The logistic models for accident probabilities showed that the accident probabilities increased by 3 and 4 times respectively when the drivers were conversing or texting on a phone during driving. Further, the relationship between the speed reduction patterns and their corresponding accident frequencies showed that all the drivers compensated differently; but, among all the drivers, only few drivers, who compensated by reducing the speed by 30% or more, were able to fully offset the increased accident risk associated with the phone use. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Do Rare Stimuli Evoke Large P3s by Being Unexpected? A Comparison of Oddball Effects Between Standard-Oddball and Prediction-Oddball Tasks

PubMed Central

Verleger, Rolf; Śmigasiewicz, Kamila

2016-01-01

The P3 component of event-related potentials increases when stimuli are rarely presented. It has been assumed that this oddball effect (rare-frequent difference) reflects the unexpectedness of rare stimuli. The assumption of unexpectedness and its link to P3 amplitude were tested here. A standard- oddball task requiring alternative key-press responses to frequent and rare stimuli was compared with an oddball-prediction task where stimuli had to be first predicted and then confirmed by key-pressing. Oddball effects in the prediction task depended on whether the frequent or the rare stimulus had been predicted. Oddball effects on P3 amplitudes and error rates in the standard oddball task closely resembled effects after frequent predictions. This corroborates the notion that these effects occur because frequent stimuli are expected and rare stimuli are unexpected. However, a closer look at the prediction task put this notion into doubt because the modifications of oddball effects on P3 by expectancies were entirely due to effects on frequent stimuli, whereas the large P3 amplitudes evoked by rare stimuli were insensitive to predictions (unlike response times and error rates). Therefore, rare stimuli cannot be said to evoke large P3 amplitudes because they are unexpected. We discuss these diverging effects of frequency and expectancy, as well as general differences between tasks, with respect to concepts and hypotheses about P3b’s function and conclude that each discussed concept or hypothesis encounters some problems, with a conception in terms of subjective relevance assigned to stimuli offering the most consistent account of these basic effects. PMID:27512527

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.

Obscure Severe Infrarenal Aortoiliac Stenosis With Severe Transient Lactic Acidosis

PubMed Central

Nantsupawat, Teerapat; Mankongpaisarnrung, Charoen; Soontrapa, Suthipong; Limsuwat, Chok

2013-01-01

A 57-year-old man presented with sudden onset of leg pain, right-sided weakness, aphasia, confusion, drooling, and severe lactic acidosis (15 mmol/L). He had normal peripheral pulses and demonstrated no pain, pallor, poikilothermia, paresthesia, or paralysis. Empiric antibiotics, aspirin, full-dose enoxaparin, and intravenous fluid were initiated. Lactic acid level decreased to 2.5 mmol/L. The patient was subsequently extubated and was alert and oriented with no complaints of leg or abdominal pain. Unexpectedly, the patient developed cardiac arrest, rebound severe lactic acidosis (8.13 mmol/L), and signs of acute limb ischemia. Emergent computed tomography of the aorta confirmed infrarenal aortoiliac thrombosis. Transient leg pain and transient severe lactic acidosis can be unusual presentations of severe infrarenal aortoiliac stenosis. When in doubt, vascular studies should be implemented without delay to identify this catastrophic diagnosis. PMID:26425569

A Causal Role for the Cortical Frontal Eye Fields in Microsaccade Deployment

PubMed Central

Dash, Suryadeep; Lomber, Stephen G.

2016-01-01

Microsaccades aid vision by helping to strategically sample visual scenes. Despite the importance of these small eye movements, no cortical area has ever been implicated in their generation. Here, we used unilateral and bilateral reversible inactivation of the frontal eye fields (FEF) to identify a cortical drive for microsaccades. Unexpectedly, FEF inactivation altered microsaccade metrics and kinematics. Such inactivation also impaired microsaccade deployment following peripheral cue onset, regardless of cue side or inactivation configuration. Our results demonstrate that the FEF provides critical top-down drive for microsaccade generation, particularly during the recovery of microsaccades after disruption by sensory transients. Our results constitute the first direct evidence, to our knowledge, for the contribution of any cortical area to microsaccade generation, and they provide a possible substrate for how cognitive processes can influence the strategic deployment of microsaccades. PMID:27509130

A Causal Role for the Cortical Frontal Eye Fields in Microsaccade Deployment.

PubMed

Peel, Tyler R; Hafed, Ziad M; Dash, Suryadeep; Lomber, Stephen G; Corneil, Brian D

2016-08-01

Microsaccades aid vision by helping to strategically sample visual scenes. Despite the importance of these small eye movements, no cortical area has ever been implicated in their generation. Here, we used unilateral and bilateral reversible inactivation of the frontal eye fields (FEF) to identify a cortical drive for microsaccades. Unexpectedly, FEF inactivation altered microsaccade metrics and kinematics. Such inactivation also impaired microsaccade deployment following peripheral cue onset, regardless of cue side or inactivation configuration. Our results demonstrate that the FEF provides critical top-down drive for microsaccade generation, particularly during the recovery of microsaccades after disruption by sensory transients. Our results constitute the first direct evidence, to our knowledge, for the contribution of any cortical area to microsaccade generation, and they provide a possible substrate for how cognitive processes can influence the strategic deployment of microsaccades.

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.

Neural circuit activity in freely behaving zebrafish (Danio rerio).

PubMed

Issa, Fadi A; O'Brien, Georgeann; Kettunen, Petronella; Sagasti, Alvaro; Glanzman, David L; Papazian, Diane M

2011-03-15

Examining neuronal network activity in freely behaving animals is advantageous for probing the function of the vertebrate central nervous system. Here, we describe a simple, robust technique for monitoring the activity of neural circuits in unfettered, freely behaving zebrafish (Danio rerio). Zebrafish respond to unexpected tactile stimuli with short- or long-latency escape behaviors, which are mediated by distinct neural circuits. Using dipole electrodes immersed in the aquarium, we measured electric field potentials generated in muscle during short- and long-latency escapes. We found that activation of the underlying neural circuits produced unique field potential signatures that are easily recognized and can be repeatedly monitored. In conjunction with behavioral analysis, we used this technique to track changes in the pattern of circuit activation during the first week of development in animals whose trigeminal sensory neurons were unilaterally ablated. One day post-ablation, the frequency of short- and long-latency responses was significantly lower on the ablated side than on the intact side. Three days post-ablation, a significant fraction of escapes evoked by stimuli on the ablated side was improperly executed, with the animal turning towards rather than away from the stimulus. However, the overall response rate remained low. Seven days post-ablation, the frequency of escapes increased dramatically and the percentage of improperly executed escapes declined. Our results demonstrate that trigeminal ablation results in rapid reconfiguration of the escape circuitry, with reinnervation by new sensory neurons and adaptive changes in behavior. This technique is valuable for probing the activity, development, plasticity and regeneration of neural circuits under natural conditions.

Neural circuit activity in freely behaving zebrafish (Danio rerio)

PubMed Central

Issa, Fadi A.; O'Brien, Georgeann; Kettunen, Petronella; Sagasti, Alvaro; Glanzman, David L.; Papazian, Diane M.

2011-01-01

Examining neuronal network activity in freely behaving animals is advantageous for probing the function of the vertebrate central nervous system. Here, we describe a simple, robust technique for monitoring the activity of neural circuits in unfettered, freely behaving zebrafish (Danio rerio). Zebrafish respond to unexpected tactile stimuli with short- or long-latency escape behaviors, which are mediated by distinct neural circuits. Using dipole electrodes immersed in the aquarium, we measured electric field potentials generated in muscle during short- and long-latency escapes. We found that activation of the underlying neural circuits produced unique field potential signatures that are easily recognized and can be repeatedly monitored. In conjunction with behavioral analysis, we used this technique to track changes in the pattern of circuit activation during the first week of development in animals whose trigeminal sensory neurons were unilaterally ablated. One day post-ablation, the frequency of short- and long-latency responses was significantly lower on the ablated side than on the intact side. Three days post-ablation, a significant fraction of escapes evoked by stimuli on the ablated side was improperly executed, with the animal turning towards rather than away from the stimulus. However, the overall response rate remained low. Seven days post-ablation, the frequency of escapes increased dramatically and the percentage of improperly executed escapes declined. Our results demonstrate that trigeminal ablation results in rapid reconfiguration of the escape circuitry, with reinnervation by new sensory neurons and adaptive changes in behavior. This technique is valuable for probing the activity, development, plasticity and regeneration of neural circuits under natural conditions. PMID:21346131

The morphology of the coronary sinus in patients with congenitally corrected transposition: implications for cardiac catheterisation and re-synchronisation therapy.

PubMed

Aiello, Vera D; Ferreira, Flávia C N; Scanavacca, Mauricio I; Anderson, Robert H; D'Avila, André

2016-02-01

Patients with congenitally corrected transposition frequently benefit from re-synchronisation therapy or ablation procedures. This is likely to require catheterisation of the coronary sinus. Its anatomy, however, is not always appreciated, despite being well-described. With this caveat in mind, we have evaluated its location and structure in hearts with congenitally corrected transposition in order to reinforce the guidance needed by the cardiac interventionist. We dissected and inspected the coronary sinus, the oblique vein of the left atrium, and the left-sided-circumflex venous channel in eight heart specimens with corrected transposition and eight controls, measuring the orifice and length of the sinus and the atrioventricular valves. In two-thirds of the malformed hearts, the sinus deviated from its anticipated course in the atrioventricular groove, ascending obliquely on the left atrial inferior wall to meet the left oblique vein. The maximal deviation coincided in all hearts with the point where the left oblique vein joined the left-sided-circumflex vein to form the coronary sinus. We describe a circumflex vein, rather than the great cardiac vein, as the latter venous channel is right-sided in the setting of corrected transposition. The length of the sinus correlated positively with the diameter of the tricuspid valve (p=0.02). Compared with controls, the left oblique vein in the malformed hearts joined the circumflex venous channel significantly closer to the mouth of the sinus. The unexpected course of the coronary sinus in corrected transposition and the naming of the cardiac veins have important implications for venous cannulation and interpretation of images.

Design and evaluation of novel interferon lambda analogs with enhanced antiviral activity and improved drug attributes

PubMed Central

Yu, Debin; Zhao, Mingzhi; Dong, Liwei; Zhao, Lu; Zou, Mingwei; Sun, Hetong; Zhang, Mengying; Liu, Hongyu; Zou, Zhihua

2016-01-01

Type III interferons (IFNs) (also called IFN-λ: IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4) are critical players in the defense against viral infection of mucosal epithelial cells, where the activity of type I IFNs is weak, and unlike type I IFNs that are associated with severe and diverse side effects, type III IFNs cause minimal side effects due to the highly restricted expression of their receptors, and thus appear to be promising agents for the treatment and prevention of respiratory and gastrointestinal viral infection. However, the antiviral potency of natural type III IFNs is weak compared to type I and, although IFN-λ3 possesses the highest bioactivity among the type III IFNs, IFN-λ1, instead of IFN-λ3, is being developed as a therapeutic drug due to the difficulty to express IFN-λ3 in the prokaryotic expression system. Here, to develop optimal IFN-λ molecules with improved drug attributes, we designed a series of IFN-λ analogs by replacing critical amino acids of IFN-λ1 with the IFN-λ3 counterparts, and vice versa. Four of the designed analogs were successfully expressed in Escherichia coli with high yield and were easily purified from inclusion bodies. Interestingly, all four analogs showed potent activity in inducing the expression of the antiviral genes MxA and OAS and two of them, analog-6 and -7, displayed an unexpected high potency that is higher than that of type I IFN (IFN-α2a) in activating the IFN-stimulated response element (ISRE)-luciferase reporter. Importantly, both analog-6 and -7 effectively inhibited replication of hepatitis C virus in Huh-7.5.1 cells, with an IC50 that is comparable to that of IFN-α2a; and consistent with the roles of IFN-λ in mucosal epithelia, both analogs potently inhibited replication of H3N2 influenza A virus in A549 cells. Together, these studies identified two IFN-λ analogs as candidates to be developed as novel antiviral biologics. PMID:26792983

Evaluating minimalist mimics by exploring key orientations on secondary structures (EKOS)☟

PubMed Central

Xin, Dongyue; Ko, Eunhwa; Perez, Lisa M.; Ioerger, Thomas R.; Burgess, Kevin

2013-01-01

Peptide mimics that display amino acid side-chains on semi-rigid scaffolds (not peptide polyamides) can be referred to as minimalist mimics. Accessible conformations of these scaffolds may overlay with secondary structures giving, for example, “minimalist helical mimics”. It is difficult for researchers who want to apply minimalist mimics to decide which one to use because there is no widely accepted protocol for calibrating how closely these compounds mimic secondary structures. Moreover, it is also difficult for potential practitioners to evaluate which ideal minimalist helical mimics are preferred for a particular set of side-chains. For instance, what mimic presents i, i+4, i+7 side-chains in orientations that best resemble an ideal α-helix, and is a different mimic required for a i, i+3, i+7 helical combination? This article describes a protocol for fitting each member of an array of accessible scaffold conformations on secondary structures. The protocol involves: (i) use quenched molecular dynamics (QMD) to generate an ensemble consisting of hundreds of accessible, low energy conformers of the mimics; (ii) representation of each of these as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds;(iii) similar representation of each combination of three side-chains in each ideal secondary structure as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; and, (iv) overlay Cα and Cβ coordinates of all the conformers on all the sets of side-chain “triads” in the ideal secondary structures and express the goodness of fit in terms of root mean squared deviation (RMSD, Å) for each overlay. We refer to this process as Exploring Key Orientations on Secondary structures (EKOS). Application of this procedure reveals the relative bias of a scaffold to overlay on different secondary structures, the “side-chain correspondences” (eg i, i+4, i+7 or i, i+3, i+4) of those overlays, and the energy of this state relative to the minimum located. This protocol was tested on some of the most widely cited minimalist α-helical mimics (1 – 8 in the text). The data obtained indicates several of these compounds preferentially exist in conformations that resemble other secondary structures as well as α-helices, and many of the α-helical conformations have unexpected side-chain correspondences. These observations imply the featured minimalist mimics have more scope for disrupting PPI interfaces than previously anticipated. Finally, the same simulation method was used to match preferred conformations of minimalist mimics with actual protein/peptide structures at interfaces providing quantitative comparisons of predicted fits of the test mimics at protein-protein interaction sites. PMID:24121516

Evaluating minimalist mimics by exploring key orientations on secondary structures (EKOS).

PubMed

Xin, Dongyue; Ko, Eunhwa; Perez, Lisa M; Ioerger, Thomas R; Burgess, Kevin

2013-11-28

Peptide mimics that display amino acid side-chains on semi-rigid scaffolds (not peptide polyamides) can be referred to as minimalist mimics. Accessible conformations of these scaffolds may overlay with secondary structures giving, for example, "minimalist helical mimics". It is difficult for researchers who want to apply minimalist mimics to decide which one to use because there is no widely accepted protocol for calibrating how closely these compounds mimic secondary structures. Moreover, it is also difficult for potential practitioners to evaluate which ideal minimalist helical mimics are preferred for a particular set of side-chains. For instance, what mimic presents i, i + 4, i + 7 side-chains in orientations that best resemble an ideal α-helix, and is a different mimic required for a i, i + 3, i + 7 helical combination? This article describes a protocol for fitting each member of an array of accessible scaffold conformations on secondary structures. The protocol involves: (i) use quenched molecular dynamics (QMD) to generate an ensemble consisting of hundreds of accessible, low energy conformers of the mimics; (ii) representation of each of these as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; (iii) similar representation of each combination of three side-chains in each ideal secondary structure as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; and, (iv) overlay Cα and Cβ coordinates of all the conformers on all the sets of side-chain "triads" in the ideal secondary structures and express the goodness of fit in terms of root mean squared deviation (RMSD, Å) for each overlay. We refer to this process as Exploring Key Orientations on Secondary structures (EKOS). Application of this procedure reveals the relative bias of a scaffold to overlay on different secondary structures, the "side-chain correspondences" (e.g. i, i + 4, i + 7 or i, i + 3, i + 4) of those overlays, and the energy of this state relative to the minimum located. This protocol was tested on some of the most widely cited minimalist α-helical mimics (1-8 in the text). The data obtained indicates several of these compounds preferentially exist in conformations that resemble other secondary structures as well as α-helices, and many of the α-helical conformations have unexpected side-chain correspondences. These observations imply the featured minimalist mimics have more scope for disrupting PPI interfaces than previously anticipated. Finally, the same simulation method was used to match preferred conformations of minimalist mimics with actual protein/peptide structures at interfaces providing quantitative comparisons of predicted fits of the test mimics at protein-protein interaction sites.

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.

An ancient revisits cosmology.

PubMed Central

Greenstein, J L

1993-01-01

In this after-dinner speech, a somewhat light-hearted attempt is made to view the observational side of physical cosmology as a subdiscipline of astrophysics, still in an early stage of sophistication and in need of more theoretical understanding. The theoretical side of cosmology, in contrast, has its deep base in general relativity. A major result of observational cosmology is that an expansion of the Universe arose from a singularity some 15 billion years ago. This has had an enormous impact on the public's view of both astronomy and theology. It places on cosmologists an extra responsibility for clear thinking and interpretation. Recently, gravitational physics caused another crisis from an unexpected observational result that nonbaryonic matter appears to dominate. Will obtaining information about this massive nonbaryonic component require that astronomers cease to rely on measurement of photons? But 40 years ago after radio astronomical techniques uncovered the high-energy universe, we happily introduced new subfields, with techniques from physics and engineering still tied to photon detection. Another historical example shows how a subfield of cosmology, big bang nucleosynthesis, grew in complexity from its spectroscopic astrophysics beginning 40 years ago. Determination of primordial abundances of lighter nuclei does illuminate conditions in the Big Bang, but the observational results faced and overcame many hurdles on the way. PMID:11607403

An Ancient Revisits Cosmology

NASA Astrophysics Data System (ADS)

Greenstein, Jesse L.

1993-06-01

In this after-dinner speech, a somewhat light-hearted attempt is made to view the observational side of physical cosmology as a subdiscipline of astrophysics, still in an early stage of sophistication and in need of more theoretical understanding. The theoretical side of cosmology, in contrast, has its deep base in general relativity. A major result of observational cosmology is that an expansion of the Universe arose from a singularity some 15 billion years ago. This has had an enormous impact on the public's view of both astronomy and theology. It places on cosmologists an extra responsibility for clear thinking and interpretation. Recently, gravitational physics caused another crisis from an unexpected observational result that nonbaryonic matter appears to dominate. Will obtaining information about this massive nonbaryonic component require that astronomers cease to rely on measurement of photons? But 40 years ago after radio astronomical techniques uncovered the high-energy universe, we happily introduced new subfields, with techniques from physics and engineering still tied to photon detection. Another historical example shows how a subfield of cosmology, big bang nucleosynthesis, grew in complexity from its spectroscopic astrophysics beginning 40 years ago. Determination of primordial abundances of lighter nuclei does illuminate conditions in the Big Bang, but the observational results faced and overcame many hurdles on the way.

Release of inattentional blindness by high working memory load: elucidating the relationship between working memory and selective attention.

PubMed

de Fockert, Jan W; Bremner, Andrew J

2011-12-01

An unexpected stimulus often remains unnoticed if attention is focused elsewhere. This inattentional blindness has been shown to be increased under conditions of high memory load. Here we show that increasing working memory load can also have the opposite effect of reducing inattentional blindness (i.e., improving stimulus detection) if stimulus detection is competing for attention with a concurrent visual task. Participants were required to judge which of two lines was the longer while holding in working memory either one digit (low load) or six digits (high load). An unexpected visual stimulus was presented once alongside the line judgment task. Detection of the unexpected stimulus was significantly improved under conditions of higher working memory load. This improvement in performance prompts the striking conclusion that an effect of cognitive load is to increase attentional spread, thereby enhancing our ability to detect perceptual stimuli to which we would normally be inattentionally blind under less taxing cognitive conditions. We discuss the implications of these findings for our understanding of the relationship between working memory and selective attention. Copyright © 2011 Elsevier B.V. All rights reserved.

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.

Effects of Inconsistent Behaviors on Person Impressions: A Multidimensional Study.

ERIC Educational Resources Information Center

Vonk, Roos

1995-01-01

Examined effects of unexpected behavioral information on person impressions. Inconsistency was manipulated with respect to Implicit Personality Theory. Found that behaviors with inconsistent evaluation implications did not affect impressions and that effects of inconsistent information depended on dimension of contrast, valence of initial…

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.

Unexpected findings and promoting monocausal claims, a cautionary tale.

PubMed

Copeland, Samantha Marie

2017-10-01

Stories of serendipitous discoveries in medicine incorrectly imply that the path from an unexpected observation to major discovery is straightforward or guaranteed. In this paper, I examine a case from the field of research about chronic fatigue syndrome (CFS). In Norway, an unexpected positive result during clinical care has led to the development of a research programme into the potential for the immunosuppressant drug rituximab to relieve the symptoms of CFS. The media and public have taken up researchers' speculations that their research results indicate a causal mechanism for CFS - consequently, patients now have great hope that 'the cause' of CFS has been found, and thus, a cure is sure to follow. I argue that a monocausal claim cannot be correctly asserted, either on the basis of the single case of an unexpected, although positive, result or on the basis of the empirical research that has followed up on that result. Further, assertion and promotion of this claim will have specific harmful effects: it threatens to inappropriately narrow the scope of research on CFS, might misdirect research altogether, and could directly and indirectly harm patients. Therefore, the CFS case presents a cautionary tale, illustrating the risks involved in drawing a theoretical hypothesis from an unexpected observation. Further, I draw attention to the tendency in contemporary clinical research with CFS to promote new research directions on the basis of reductive causal models of that syndrome. Particularly, in the case of CFS research, underdetermination and causal complexity undermine the potential value of a monocausal claim. In sum, when an unexpected finding occurs in clinical practice or medical research, the value of following up on that finding is to be found not in the projected value of a singular causal relationship inferred from the finding but rather in the process of research that follows. © 2016 John Wiley & Sons, Ltd.

A new therapeutic effect of simvastatin revealed by functional improvement in muscular dystrophy.

PubMed

Whitehead, Nicholas P; Kim, Min Jeong; Bible, Kenneth L; Adams, Marvin E; Froehner, Stanley C

2015-10-13

Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disease with no effective treatment. DMD muscle pathogenesis is characterized by chronic inflammation, oxidative stress, and fibrosis. Statins, cholesterol-lowering drugs, inhibit these deleterious processes in ischemic diseases affecting skeletal muscle, and therefore have potential to improve DMD. However, statins have not been considered for DMD, or other muscular dystrophies, principally because skeletal-muscle-related symptoms are rare, but widely publicized, side effects of these drugs. Here we show positive effects of statins in dystrophic skeletal muscle. Simvastatin dramatically reduced damage and enhanced muscle function in dystrophic (mdx) mice. Long-term simvastatin treatment vastly improved overall muscle health in mdx mice, reducing plasma creatine kinase activity, an established measure of muscle damage, to near-normal levels. This reduction was accompanied by reduced inflammation, more oxidative muscle fibers, and improved strength of the weak diaphragm muscle. Shorter-term treatment protected against muscle fatigue and increased mdx hindlimb muscle force by 40%, a value comparable to current dystrophin gene-based therapies. Increased force correlated with reduced NADPH Oxidase 2 protein expression, the major source of oxidative stress in dystrophic muscle. Finally, in old mdx mice with severe muscle degeneration, simvastatin enhanced diaphragm force and halved fibrosis, a major cause of functional decline in DMD. These improvements were accompanied by autophagy activation, a recent therapeutic target for DMD, and less oxidative stress. Together, our findings highlight that simvastatin substantially improves the overall health and function of dystrophic skeletal muscles and may provide an unexpected, novel therapy for DMD and related neuromuscular diseases.

Parental and grandparental ages in the autistic spectrum disorders: a birth cohort study.

PubMed

Golding, Jean; Steer, Colin; Pembrey, Marcus

2010-04-01

A number of studies have assessed ages of parents of children with autistic spectrum disorders (ASD), and reported both maternal and paternal age effects. Here we assess relationships with grandparental ages. We compared the parental and grandparental ages of children in the population-based Avon Longitudinal Study of Parents and Children (ALSPAC), according to their scores in regard to 4 autistic trait measures and whether they had been given a diagnosis of ASD. Mean maternal and paternal ages of ASD cases were raised, but this appears to be secondary to a maternal grandmother age effect (P = 0.006): OR = 1.66[95%CI 1.16, 2.37] for each 10-year increase in the grandmother's age at the birth of the mother. Trait measures also revealed an association between the maternal grandmother's age and the major autistic trait-the Coherence Scale (regression coefficient b = 0.142, [95%CI = 0.057, 0.228]P = 0.001). After allowing for confounders the effect size increased to b = 0.217[95%CI 0.125, 0.308](P<0.001) for each 10 year increase in age. Although the relationship between maternal grandmother's age and ASD and a major autistic trait was unexpected, there is some biological plausibility, for the maternal side at least, given that the timing of female meiosis I permits direct effects on the grandchild's genome during the grandmother's pregnancy. An alternative explanation is the meiotic mismatch methylation (3 M) hypothesis, presented here for the first time. Nevertheless the findings should be treated as hypothesis generating pending corroborative results from other studies.

A new therapeutic effect of simvastatin revealed by functional improvement in muscular dystrophy

PubMed Central

Whitehead, Nicholas P.; Kim, Min Jeong; Bible, Kenneth L.; Adams, Marvin E.; Froehner, Stanley C.

2015-01-01

Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disease with no effective treatment. DMD muscle pathogenesis is characterized by chronic inflammation, oxidative stress, and fibrosis. Statins, cholesterol-lowering drugs, inhibit these deleterious processes in ischemic diseases affecting skeletal muscle, and therefore have potential to improve DMD. However, statins have not been considered for DMD, or other muscular dystrophies, principally because skeletal-muscle-related symptoms are rare, but widely publicized, side effects of these drugs. Here we show positive effects of statins in dystrophic skeletal muscle. Simvastatin dramatically reduced damage and enhanced muscle function in dystrophic (mdx) mice. Long-term simvastatin treatment vastly improved overall muscle health in mdx mice, reducing plasma creatine kinase activity, an established measure of muscle damage, to near-normal levels. This reduction was accompanied by reduced inflammation, more oxidative muscle fibers, and improved strength of the weak diaphragm muscle. Shorter-term treatment protected against muscle fatigue and increased mdx hindlimb muscle force by 40%, a value comparable to current dystrophin gene-based therapies. Increased force correlated with reduced NADPH Oxidase 2 protein expression, the major source of oxidative stress in dystrophic muscle. Finally, in old mdx mice with severe muscle degeneration, simvastatin enhanced diaphragm force and halved fibrosis, a major cause of functional decline in DMD. These improvements were accompanied by autophagy activation, a recent therapeutic target for DMD, and less oxidative stress. Together, our findings highlight that simvastatin substantially improves the overall health and function of dystrophic skeletal muscles and may provide an unexpected, novel therapy for DMD and related neuromuscular diseases. PMID:26417069

Design of an impact evaluation using a mixed methods model--an explanatory assessment of the effects of results-based financing mechanisms on maternal healthcare services in Malawi.

PubMed

Brenner, Stephan; Muula, Adamson S; Robyn, Paul Jacob; Bärnighausen, Till; Sarker, Malabika; Mathanga, Don P; Bossert, Thomas; De Allegri, Manuela

2014-04-22

In this article we present a study design to evaluate the causal impact of providing supply-side performance-based financing incentives in combination with a demand-side cash transfer component on equitable access to and quality of maternal and neonatal healthcare services. This intervention is introduced to selected emergency obstetric care facilities and catchment area populations in four districts in Malawi. We here describe and discuss our study protocol with regard to the research aims, the local implementation context, and our rationale for selecting a mixed methods explanatory design with a quasi-experimental quantitative component. The quantitative research component consists of a controlled pre- and post-test design with multiple post-test measurements. This allows us to quantitatively measure 'equitable access to healthcare services' at the community level and 'healthcare quality' at the health facility level. Guided by a theoretical framework of causal relationships, we determined a number of input, process, and output indicators to evaluate both intended and unintended effects of the intervention. Overall causal impact estimates will result from a difference-in-difference analysis comparing selected indicators across intervention and control facilities/catchment populations over time.To further explain heterogeneity of quantitatively observed effects and to understand the experiential dimensions of financial incentives on clients and providers, we designed a qualitative component in line with the overall explanatory mixed methods approach. This component consists of in-depth interviews and focus group discussions with providers, service user, non-users, and policy stakeholders. In this explanatory design comprehensive understanding of expected and unexpected effects of the intervention on both access and quality will emerge through careful triangulation at two levels: across multiple quantitative elements and across quantitative and qualitative elements. Combining a traditional quasi-experimental controlled pre- and post-test design with an explanatory mixed methods model permits an additional assessment of organizational and behavioral changes affecting complex processes. Through this impact evaluation approach, our design will not only create robust evidence measures for the outcome of interest, but also generate insights on how and why the investigated interventions produce certain intended and unintended effects and allows for a more in-depth evaluation approach.

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.

Encountering unexpected difficult airway: relationship with the intubation difficulty scale

PubMed Central

Koh, Wonuk; Kim, Hajung; Kim, Kyongsun; Ro, Young-Jin

2016-01-01

Background An unexpected difficult intubation can be very challenging and if it is not managed properly, it may expose the encountered patient to significant risks. The intubation difficulty scale (IDS) has been used as a validated method to evaluate a global degree of intubation difficulty. The aims of this study were to evaluate the prevalence and characteristics of unexpected difficult intubation using the IDS. Methods We retrospectively reviewed 951 patients undergoing elective surgery in a single medical center. Patients expected to have a difficult intubation or who had history of difficult intubation were excluded. Each patient was assessed by the IDS scoring system with seven variables. Total prevalence of difficult intubation and the contributing individual factors were further analyzed. Results For the 951 patients, the difficult intubation cases presenting IDS > 5 was 5.8% of total cases (n = 55). The prevalence of Cormack-Lehane Grade 3 or 4 was 16.2% (n = 154). Most of the difficult intubation cases were managed by simple additional maneuvers and techniques such as stylet application, additional lifting force and laryngeal pressure. Conclusions Unexpected difficult airway was present in 5.8% of patients and most was managed effectively. Among the components of IDS, the Cormack-Lehane grade was most sensitive for predicting difficult intubation. PMID:27274369

Nurses' Experiences With Patients Who Die From Failure to Rescue After Surgery.

PubMed

Bacon, Cynthia Thornton

2017-05-01

To describe the lived experiences of hospital nurses caring for surgical patients who died from failure to rescue (FTR). A qualitative phenomenologic approach was used. Methods to ensure rigor and trustworthiness were incorporated into the design. The investigator conducted one-on-one semistructured interviews with 14 nurses, and data were analyzed using Colaizzi's methods. Six themes were identified: (a) the environment surrounding the FTR was unexpected; (b) FTR was unexpected but not preventable; (c) nurses were emotionally ill-prepared for the FTR; (d) nurse outcomes are different in unexpected versus expected death; (e) nurses' roles as protectors are important; and (f) FTR effects future nursing practice. Nurses' reactions after an FTR surgical death may be different when there is no identified nursing error contributing to the event. There may be key differences between deaths that are simply unexpected and those that involve FTR. The importance of mentoring junior nurses in protective surveillance skills is vital. Developing an understanding of nurses' experiences with FTR can assist nurse leaders to better support nurses who experience FTR deaths. Insight into the environment surrounding FTR deaths provides a foundation for future research aimed at improving patient safety and quality through an improved working environment for nurses. © 2017 Sigma Theta Tau International.

[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.

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.

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

Radiation Therapy Side Effects

Cancer.gov

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

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

PubMed

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

2017-03-01

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

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2001-12-01

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

Geometrical illusions are not always where you think they are: a review of some classical and less classical illusions, and ways to describe them.

PubMed

Ninio, Jacques

2014-01-01

Geometrical illusions are known through a small core of classical illusions that were discovered in the second half of the nineteenth century. Most experimental studies and most theoretical discussions revolve around this core of illusions, as though all other illusions were obvious variants of these. Yet, many illusions, mostly described by German authors at the same time or at the beginning of the twentieth century have been forgotten and are awaiting their rehabilitation. Recently, several new illusions were discovered, mainly by Italian authors, and they do not seem to take place into any current classification. Among the principles that are invoked to explain the illusions, there are principles relating to the metric aspects (contrast, assimilation, shrinkage, expansion, attraction of parallels) principles relating to orientations (regression to right angles, orthogonal expansion) or, more recently, to gestalt effects. Here, metric effects are discussed within a measurement framework, in which the geometric illusions are the outcome of a measurement process. There would be a main "convexity" bias in the measures: the measured value m(x) of an extant x would grow more than proportionally with x. This convexity principle, completed by a principle of compromise for conflicting measures can replace, for a large number of patterns, both the assimilation and the contrast effects. We know from evolutionary theory that the most pertinent classification criteria may not be the most salient ones (e.g., a dolphin is not a fish). In order to obtain an objective classification of illusions, I initiated with Kevin O'Regan systematic work on "orientation profiles" (describing how the strength of an illusion varies with its orientation in the plane). We showed first that the Zöllner illusion already exists at the level of single stacks, and that it does not amount to a rotation of the stacks. Later work suggested that it is best described by an "orthogonal expansion"-an expansion of the stacks applied orthogonally to the oblique segments of the stacks, generating an apparent rotation effect. We showed that the Poggendorff illusion was mainly a misangulation effect. We explained the hierarchy of the illusion magnitudes found among variants of the Poggendorff illusion by the existence of control devices that counteract the loss of parallelism or the loss of collinearity produced by the biased measurements. I then studied the trapezium illusion. The oblique sides, but not the bases, were essential to the trapezium illusion, suggesting the existence of a common component between the trapezium and the Zöllner illusion. Unexpectedly, the trapeziums sometimes appeared as twisted surfaces in 3d. It also appeared impossible, using a nulling procedure, to make all corresponding sides of two trapeziums simultaneously equal. The square-diamond illusion is usually presented with one apex of the diamond pointing toward the square. I found that when the figures were displayed more symmetrically, the illusion was significantly reduced. Furthermore, it is surpassed, for all subjects, by an illusion that goes in the opposite direction, in which the diagonal of a small diamond is underestimated with respect to the side of a larger square. In general, the experimental work generated many unexpected results. Each illusory stimulus was compared to a number of control variants, and often, I measured larger distortions in a variant than in the standard stimulus. In the Discussion, I will stress what I think are the main ordering principle in the metric and the orientation domains for illusory patterns. The convexity bias principle and the orthogonal expansion principles help to establish unsuspected links between apparently unrelated stimuli, and reduce their apparently extreme heterogeneity. However, a number of illusions (e.g., those of the twisted cord family, or the Poggendorff illusions) remain unpredicted by the above principles. Finally, I will develop the idea that the brain is constructing several representations, and the one that is commonly used for the purpose of shape perception generates distortions inasmuch as it must satisfy a number of conflicting constraints, such as the constraint of producing a stable shape despite the changing perspectives produced by eye movements.

Is anybody doing it? An experimental study of the effect of normative messages on intention to do physical activity.

PubMed

van Bavel, René; Esposito, Gabriele; Baranowski, Tom

2014-07-31

The study explores whether messages about the physical activity levels of the majority (i.e. normative messages) affect young adults' intention to engage in regular physical activity. An experimental survey among 16 to 24 year-olds in Bulgaria, Croatia and Romania (n = 1200) was conducted in March 2013. A control group received no message; one treatment group was told that the majority was physically active (positive message); and another treatment group was told that the majority was not physically active (negative message). Both the positive and (unexpectedly) the negative normative messages showed a significant and positive effect on intention to be physically active. There was no difference between the effects of the messages. Normative messages affect intention, which is encouraging for public health campaigns. The effect of the positive message confirms previous findings on conformity to the norm; the effect of the negative message is unexpected and requires further research to be understood.

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.

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.

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.

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

Cardiac and electro-cortical concomitants of social feedback processing in women

PubMed Central

van der Molen, Melle J. W.; Gunther Moor, Bregtje; van der Veen, Frederik M.; van der Molen, Maurits W.

2015-01-01

This study provides a joint analysis of the cardiac and electro-cortical—early and late P3 and feedback-related negativity (FRN)—responses to social acceptance and rejection feedback. Twenty-five female participants performed on a social- and age-judgment control task, in which they received feedback with respect to their liking and age judgments, respectively. Consistent with previous reports, results revealed transient cardiac slowing to be selectively prolonged to unexpected social rejection feedback. Late P3 amplitude was more pronounced to unexpected relative to expected feedback. Both early and late P3 amplitudes were shown to be context dependent, in that they were more pronounced to social as compared with non-social feedback. FRN amplitudes were more pronounced to unexpected relative to expected feedback, irrespective of context and feedback valence. This pattern of findings indicates that social acceptance and rejection feedback have widespread effects on bodily state and brain function, which are modulated by prior expectancies. PMID:25870439

Unexpected nerve gas exposure in the city of Matsumoto: report of rescue activity in the first sarin gas terrorism.

PubMed

Okudera, H; Morita, H; Iwashita, T; Shibata, T; Otagiri, T; Kobayashi, S; Yanagisawa, N

1997-09-01

This report describes the rescue activities and the exposure of rescue and hospital personnel from the first unexpected nerve gas terrorist attack using sarin (isopropyl methylphophonofluoridate) in the city of Matsumoto at midnight on June 27, 1994. The details of the emergency activities in the disaster were studied based on the records from emergency departments of the affiliated hospitals and records from the firehouse. About 600 people, including residents and rescue staff, were exposed to sarin gas. Fifty-eight residents were admitted to hospitals, and 7 died. Among 95 rescuers and the duty doctor from the doctor car, 8 had mild symptoms of poisoning. All the rescue activity took place without gas masks or decontamination procedures. In this case of unexpected mass exposure to sarin gas, the emergency rescue system for a large disaster in Matsumoto city, which had been established for a conflagration or a local earthquake, was effective.

Making psycholinguistics musical: Self-paced reading time evidence for shared processing of linguistic and musical syntax

PubMed Central

Robert Slevc, L.; Rosenberg, Jason C.; Patel, Aniruddh D.

2009-01-01

Linguistic processing–especially syntactic processing–is often considered a hallmark of human cognition, thus the domain-specificity or domain-generality of syntactic processing has attracted considerable debate. These experiments address this issue by simultaneously manipulating syntactic processing demands in language and music. Participants performed self-paced reading of garden-path sentences in which structurally unexpected words cause temporary syntactic processing difficulty. A musical chord accompanied each sentence segment, with the resulting sequence forming a coherent chord progression. When structurally unexpected words were paired with harmonically unexpected chords, participants showed substantially enhanced garden-path effects. No such interaction was observed when the critical words violated semantic expectancy, nor when the critical chords violated timbral expectancy. These results support a prediction of the shared syntactic integration resource hypothesis (SSIRH, Patel, 2003), which suggests that music and language draw on a common pool of limited processing resources for integrating incoming elements into syntactic structures. PMID:19293110

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.

The Cenozoic Cooling - continental signals from the Atlantic and Pacific side of Eurasia

NASA Astrophysics Data System (ADS)

Utescher, Torsten; Bondarenko, Olesya V.; Mosbrugger, Volker

2015-04-01

The evolution of Cenozoic continental climate signals from the Atlantic and Pacific side of Eurasia can be assessed for the first time by comparing climate records obtained for two mid-latitudinal regions. For the West, a detailed climate record over the past 45 Ma, based on palaeofloras from two Northern German Cenozoic basins (Mosbrugger et al., 2005) revealed major trends and shorter-term events throughout the Cenozoic Cooling, thus testifying the close correlation of continental and marine temperature evolution as derived from oxygen isotopes (Zachos et al., 2008). Using the same methodology, we analyze a total of 14 floral horizons originating from continental strata of Southern Primory'e (Russia) in order to study the evolution at the eastern side of the continent. The Primory'e record spans the middle Eocene to early Pleistocene. As the coeval record for the Atlantic side, it reflects major global signals of Cenozoic climate change such as the temperature decline throughout the late Eocene, coinciding with the growth of Antarctic Ice-sheets, warming during the Mid-Miocene Climatic Optimum, and step-wise cooling throughout the later Neogene. The comparison of both records reveals differing regional patterns. The considerable longitudinal temperature gradient, currently existing between both study areas, already began to evolve during the Aquitanian, and was very significant during the Mid-Miocene Climatic Optimum. The temperature offset between East and West is likely attributable to an effective North Atlantic Current, already operational from the late early Miocene onwards bringing about mild winters and low seasonality in Western Europe, while in Primory'e, seasonality steadily increased from the late Oligocene on. The strong late Pliocene decline of cold month mean temperatures recorded in Primory'e is supposed to coincide with the establishment of the Siberian High as semi-permanent structure of the Northern Hemisphere circulation pattern. When comparing the precipitation records obtained for both study areas, an unexpected co-variability at the longer-term (in the order of 5-20 Ma) is noted, pointing to continent-wide hydrological changes. The steady decline of mean annual precipitation in the Primory'e record, beginning in the Bartonian and culminating in the Aquitanian, coincides with an aridity increase reported from coeval Chinese inland localities of the mid-latitudes. The seasonality patterns of rainfall point to progressive intensification of the East Asian Summer Monsoon in Primory'e since the later Tortonian while the post-Zanclean decline of the precipitation of the dry season can be related to an increasing impact of the winter monsoon.

High pressure chemistry of red phosphorus by photo-activated simple molecules

NASA Astrophysics Data System (ADS)

Ceppatelli, M.; Fanetti, S.; Bini, R.; Caporali, M.; Peruzzini, M.

2014-05-01

High pressure (HP) is very effective in reducing intermolecular distances and inducing unexpected chemical reactions. In addition the photo-activation of the reactants in HP conditions can lead to very efficient and selective processes. The chemistry of phosphorus is currently based on the white molecular form. The red polymeric allotrope, despite more stable and much less toxic, has not attracted much attention so far. However, switching from the white to the red form would benefit any industrial procedure, especially from an environmental point of view. On the other side, water and ethanol are renewable, environmental friendly and largely available molecules, usable as reactants and photo-activators in HP conditions. Here we report a study on the HP photo-induced reactivity of red phosphorus with water and ethanol, showing the possibility of very efficient and selective processes, leading to molecular hydrogen and valuable phosphorus compounds. The reactions have been studied by means of FTIR and Raman spectroscopy and pressure has been generated using membrane Diamond (DAC) and Sapphire (SAC) anvil cells. HP reactivity has been activated by the two-photon absorption of near-UV wavelengths and occurred in total absence of solvents, catalysts and radical initiators, at room T and mild pressure conditions (0.2-1.5 GPa).

Distributed microscopic actuation analysis of deformable plate membrane mirrors

NASA Astrophysics Data System (ADS)

Lu, Yifan; Yue, Honghao; Deng, Zongquan; Tzou, Hornsen

2018-02-01

To further reduce the areal density of optical mirrors used in space telescopes and other space-borne optical structures, the concept of flexible membrane deformable mirror has been proposed. Because of their high flexibility, poor stiffness and low damping properties, environmental excitations such as orbital maneuver, path changing, and non-uniform heating may induce unexpected vibrations and thus reduce working performance. Therefore, active vibration control is essential for these membrane mirrors. In this paper, two different mirror models, i.e., the plate membrane model and pure membrane model, are studied respectively. In order to investigate the modal vibration characteristics of the mirror, a piezoelectric layer is fully laminated on its non-reflective side to serve as actuators. Dynamic equations of the mirror laminated with piezoelectric actuators are presented first. Then, the actuator induced modal control force is defined. When the actuator area shrinks to infinitesimal, the expressions of microscopic local modal control force and its two components are obtained to predict the spatial microscopic actuation behavior of the mirror. Different membrane pretension forces are also applied to reveal the tension effects on the actuation of the mirror. Analyses indicate that the spatial distribution of modal micro-control forces is exactly the same with the sensing signals distribution of the mirror, which provides crucial guidelines for optimal actuator placement of membrane deformable mirrors.

The Effect of Measurement Area on Modelling UVR Dose to the Inner Canthus

NASA Astrophysics Data System (ADS)

Birt, Benjamin; Cowling, Ian; Coyne, Steve

People are exposed to varying amounts of UVR throughout their life from both natural and artificial light sources. The dose and rate of UVR exposure required for the formation of non-melanoma skin cancers is inconclusive. Certain regions on the face appear to exhibit a high rate of occurrence of Basal Cell Carcinomas (BCCs) in relation to the perceived dose of UVR. One of these regions is the inner canthus located on the medial side of the eye. The inner canthus appears to be well protected from large direct doses of ultraviolet radiation (UVR). Facial features such as eyelids, eye brow ridge, nasal bridge and cheek, combine to limit the solid angle of the field of view of the inner canthus to UVR from overhead sources. To explain the unexpected high rate of BCCs it is hypothesized that a percentage of the radiation incident on the eye is reflected onto the inner canthus. This paper showed that a portion of the radiation incident onto the eye was reflected towards the inner canthus. The percentage increase above the direct dose was only 2% across the whole region. As the detector elements decrease in size it is observed on a cellular level that some of the cells dose increased by 30% when the reflections were considered.

Nanoindentation mapping of a wood-adhesive bond

NASA Astrophysics Data System (ADS)

Konnerth, J.; Valla, A.; Gindl, W.

2007-08-01

A mapping experiment of a wood phenol-resorcinol-formaldehyde adhesive bond was performed by means of grid nanoindentation. The variability of the modulus of elasticity and the hardness was evaluated for an area of 17 μm by 90 μm. Overall, the modulus of elasticity of the adhesive was clearly lower than the modulus of wood cell walls, whereas the hardness of the adhesive was slightly higher compared to cell walls. A very slight trend of decreasing modulus of elasticity was found with increasing distance from the immediate bond line. However, the trend was superimposed by a high variability of the modulus of elasticity in dependence on the position in the wood cell wall. The unexpectedly high variation of the modulus between 12 and 24 GPa may be explained by the interaction between the helical orientation of the cellulose microfibrils in the S2 layer of the wood cell wall and the geometry of the three-sided Berkovich type indenter pyramid used. Corresponding to the very slight decrease in modulus with increasing distance from the bond line, a similar but clearer trend was found for hardness. Both trends of changing mechanical properties of wood cell walls with varying distance from the bond line are attributed to effects of adhesive penetration into the wood cell wall.

Drug metabolising enzyme polymorphisms in Middle- and Eastern-European Slavic populations.

PubMed

Hubacek, Jaroslav A

2014-01-01

Inter-individual differences in genes for drug metabolising enzymes and drug transporters are important for understanding efficacy in drug therapy. These differences are important both for the timely estimation of the dosage that should be prescribed to a patient and for the detection of individuals who are prone to side effects from the drug at normal doses. This review summarises the literature concerning the gene variants within nine major drug metabolising enzymes and drug transporters (i.e., CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, and MDR-1) in the Middle European region. Notably, published data are not extensive, and most studies were performed on relatively low numbers of individuals. No country has a complete coverage of all genes. Two variants (C2677T/A and C3435T) within the multidrug resistance-1 (MDR-1) gene and variants within the CYP2C9 gene were analysed within most Slavic populations. Nevertheless, even from this incomplete coverage (where unexpectedly high variability was at times seen both between and within populations), it could be extrapolated that the variants within the drug metabolising enzyme genes are present in roughly the same frequencies as in neighbouring countries.

Does oral exposure to cadmium and lead mediate susceptibility to colitis? The dark-and-bright sides of heavy metals in gut ecology

NASA Astrophysics Data System (ADS)

Breton, Jérôme; Daniel, Catherine; Vignal, Cécile; Body-Malapel, Mathilde; Garat, Anne; Plé, Coline; Foligné, Benoît

2016-01-01

Although the heavy metals cadmium (Cd) and lead (Pb) are known environmental health concerns, their long-term impacts on gut ecology and susceptibility to gastrointestinal autoimmune diseases have not been extensively investigated. We sought to determine whether subchronic oral exposure to Cd or Pb is a risk factor for the development and progression of inflammatory bowel disease (IBD). Mice were exposed to various doses of CdCl2 or PbCl2 in drinking water for 1, 4 or 6 weeks prior to infection with Salmonella, the induction of colitis with dextran sodium sulfate (DSS) or trinitrobenzene sulfonic acid (TNBS). In human cell-based models, exposure to Cd and Pb is associated with reduced transepithelial electric resistance and changes in bacteria-induced cytokine responses. Although 1- and 6-week exposures did not have clear effects on the response to Salmonella infectious challenges, 1-week short-term treatments with CdCl2 tended to enhance intestinal inflammation in mice. Unexpectedly, subchronic exposure to Cd and (to a lesser extent) Pb significantly mitigated some of the symptoms of DSS-induced colitis and reduced the severity of TNBS colitis in a dose-dependent manner. The possible adaptive and immunosuppressive mechanisms by which heavy metals might reduce intestinal inflammation are explored and discussed.

Short-circuit current improvement in thin cells with a gridded back contact

NASA Technical Reports Server (NTRS)

Giuliano, M.; Wohlgemuth, J.

1980-01-01

The use of gridded back contact on thin silicon solar cells 50 micrometers was investigated. An unexpected increase in short circuit current of almost 10 percent was experienced for 2 cm x 2 cm cells. Control cells with the standard continuous contact metallization were fabricated at the same time as the gridded back cells with all processes identical up to the formation of the back contact. The gridded back contact pattern was delineated by evaporation of Ti-Pd over a photo-resist mask applied to the back of the wafer; the Ti-Pd film on the controls was applied in the standard fashion in a continuous layer over the back of the cell. The Ti-Pd contacts were similarly applied to the front of the wafer, and the grid pattern on both sides of the cell was electroplated with 8-10 micrometers of silver.

Selfie-Takers Prefer Left Cheeks: Converging Evidence from the (Extended) selfiecity Database

PubMed Central

Manovich, Lev; Ferrari, Vera; Bruno, Nicola

2017-01-01

According to previous reports, selfie takers in widely different cultural contexts prefer poses showing the left cheek more than the right cheek. This posing bias may be interpreted as evidence for a right-hemispheric specialization for the expression of facial emotions. However, earlier studies analyzed selfie poses as categorized by human raters, which raises methodological issues in relation to the distinction between frontal and three-quarter poses. Here, we provide converging evidence by analyzing the (extended) selfiecity database which includes automatic assessments of head rotation and of emotional expression. We confirm a culture- and sex-independent left-cheek bias and report stronger expression of negative emotions in selfies showing the left cheek. These results are generally consistent with a psychobiological account of a left cheek bias in self-portraits but reveal possible unexpected facts concerning the relation between side bias and lateralization of emotional expression. PMID:28928683

Beyond the Observatory: Reflections on the Centennial

NASA Astrophysics Data System (ADS)

Devorkin, D. H.

1999-05-01

One of the many unexpected side-benefits of acting as editor of the AAS centennial volume was the chance to take a fresh look at some of the personalities who helped to shape the American Astronomical Society. A common characteristic of these people was their energy, compassion and drive to go "Beyond the Observatory," to borrow a phrase from Harlow Shapley. But what did going `beyond the observatory' mean to Shapley, or to the others who shaped and maintained the Society in its first one hundred years of life? Just as the discipline of astronomy has changed in profound ways in the past century, so has the American Astronomical Society changed, along with the people who have been its leaders and its sustainers and the culture that has fostered it. The Centennial meeting of the Society offers a chance to reflect on the people who have given American astronomy its sense of community identity.

A Three-Dimensional Mediastinal Model Created with Rapid Prototyping in a Patient with Ectopic Thymoma

PubMed Central

Nakada, Takeo; Inagaki, Takuya

2014-01-01

Preoperative three-dimensional (3D) imaging of a mediastinal tumor using two-dimensional (2D) axial computed tomography is sometimes difficult, and an unexpected appearance of the tumor may be encountered during surgery. In order to evaluate the preoperative feasibility of a 3D mediastinal model that used the rapid prototyping technique, we created a model and report its results. The 2D image showed some of the relationship between the tumor and the pericardium, but the 3D mediastinal model that was created using the rapid prototyping technique showed the 3D lesion in the outer side of the extrapericardium. The patient underwent a thoracoscopic resection of the tumor, and the pathological examination showed a rare middle mediastinal ectopic thymoma. We believe that the construction of mediastinal models is useful for thoracoscopic surgery and other complicated surgeries of the chest diseases. PMID:24633133

A three-dimensional mediastinal model created with rapid prototyping in a patient with ectopic thymoma.

PubMed

Akiba, Tadashi; Nakada, Takeo; Inagaki, Takuya

2015-01-01

Preoperative three-dimensional (3D) imaging of a mediastinal tumor using two-dimensional (2D) axial computed tomography is sometimes difficult, and an unexpected appearance of the tumor may be encountered during surgery. In order to evaluate the preoperative feasibility of a 3D mediastinal model that used the rapid prototyping technique, we created a model and report its results. The 2D image showed some of the relationship between the tumor and the pericardium, but the 3D mediastinal model that was created using the rapid prototyping technique showed the 3D lesion in the outer side of the extrapericardium. The patient underwent a thoracoscopic resection of the tumor, and the pathological examination showed a rare middle mediastinal ectopic thymoma. We believe that the construction of mediastinal models is useful for thoracoscopic surgery and other complicated surgeries of the chest diseases.

Well-Defined High Molecular Weight Polystyrene with High Rates and High Livingness Synthesized via Two-Stage RAFT Emulsion Polymerization.

PubMed

Yan, Kun; Gao, Xiang; Luo, Yingwu

2015-07-01

A highly living polymer with over 100 kg mol(-1) molecular weight is very difficult to achieve by controlled radical polymerization since the unavoidable side reactions of irreversible radical termination and radical chain transfer to monomer reaction become significant. It is reported that over 500 kg mol(-1) polystyrene with high livingness and low dispersity could be synthesized by a facile two-stage reversible addition-fragmentation transfer emulsion polymerization. The monomer conversion reaches 90% within 10 h. High livingness of the product is ascribed to the extremely low initiator concentration and the chain transfer constant for monomer unexpectedly much lower than the well-accepted values in the conventional radical polymerization. The two-stage monomer feeding policy much decreases the dispersity of the product. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Functional correlates of musical and visual ability in frontotemporal dementia.

PubMed

Miller, B L; Boone, K; Cummings, J L; Read, S L; Mishkin, F

2000-05-01

The emergence of new skills in the setting of dementia suggests that loss of function in one brain area can release new functions elsewhere. To characterise 12 patients with frontotemporal dementia (FTD) who acquired, or sustained, new musical or visual abilities despite progression of their dementia. Twelve patients with FTD who acquired or maintained musical or artistic ability were compared with 46 patients with FTD in whom new or sustained ability was absent. The group with musical or visual ability performed better on visual, but worse on verbal tasks than did the other patients with FTD. Nine had asymmetrical left anterior dysfunction. Nine showed the temporal lobe variant of FTD. Loss of function in the left anterior temporal lobe may lead to facilitation of artistic or musical skills. Patients with the left-sided temporal lobe variant of FTD offer an unexpected window into the neurological mediation of visual and musical talents.

Mechanisms of Lethal Cerebrovascular Accidents in Turner Syndrome.

PubMed

Byard, Roger W

2016-05-01

A case of intracerebral hemorrhage in Turner syndrome is reported with an analysis of possible causes of cerebrovascular accidents in this condition. A 42-year-old woman with known Turner syndrome died soon after hospital admission having been found unconscious at her home address. At autopsy, she showed typical features of Turner syndrome with short stature, webbing of the neck, underdeveloped breasts, and an increased carrying angle of the arm. Death was due to a large left-sided intracerebral hemorrhage extending from the left basal ganglia into the white matter of the frontal lobe and lateral ventricle. Cases of unexpected death in Turner syndrome may arise from occult cerebrovascular accidents which may be hemorrhagic or nonhemorrhagic. Associated features include hypertension, vascular malformations, accelerated atherogenesis, cystic medial necrosis, and moyamoya syndrome. The possibility of Turner syndrome should be considered in cases where there has been a lethal cerebrovascular event in a younger woman. © 2016 American Academy of Forensic Sciences.

Substrate specificity of the ubiquitin and Ubl proteases

PubMed Central

Ronau, Judith A; Beckmann, John F; Hochstrasser, Mark

2016-01-01

Conjugation and deconjugation of ubiquitin and ubiquitin-like proteins (Ubls) to cellular proteins are highly regulated processes integral to cellular homeostasis. Most often, the C-termini of these small polypeptides are attached to lysine side chains of target proteins by an amide (isopeptide) linkage. Deubiquitinating enzymes (DUBs) and Ubl-specific proteases (ULPs) comprise a diverse group of proteases that recognize and remove ubiquitin and Ubls from their substrates. How DUBs and ULPs distinguish among different modifiers, or different polymeric forms of these modifiers, remains poorly understood. The specificity of ubiquitin/Ubl-deconjugating enzymes for particular substrates depends on multiple factors, ranging from the topography of specific substrate features, as in different polyubiquitin chain types, to structural elements unique to each enzyme. Here we summarize recent structural and biochemical studies that provide insights into mechanisms of substrate specificity among various DUBs and ULPs. We also discuss the unexpected specificities of non-eukaryotic proteases in these families. PMID:27012468

The N400 and the P300 are not all that independent.

PubMed

Arbel, Yael; Spencer, Kevin M; Donchin, Emanuel

2011-06-01

This study assessed whether two ERP components that are elicited by unexpected events interact. The conditions that are known to elicit the N400 and the P300 ERP components were applied separately and in combination to terminal-words in sentences. Each sentence ended with a terminal-word that was highly expected, semantically unexpected, physically deviant, or both semantically unexpected and physically deviant. In addition, we varied the level of semantic relatedness between the unexpected terminal-words and the expected exemplars. Physically deviant words elicited a P300, whereas semantically unexpected words elicited an N400, whose amplitude was sensitive to the level of semantic relatedness. Words that were both semantically unexpected and physically deviant elicited both an N400 with enhanced amplitude, and a P300 with reduced amplitude. These results suggest an interaction between the processes manifested by the two components. Copyright © 2010 Society for Psychophysiological Research.

Relating drug–protein interaction network with drug side effects

PubMed Central

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

2012-01-01

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

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

PubMed

Robbins, Erin; Shepard, Jason; Rochat, Philippe

2017-07-01

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

Out of place, out of mind: Schema-driven false memory effects for object-location bindings.

PubMed

Lew, Adina R; Howe, Mark L

2017-03-01

Events consist of diverse elements, each processed in specialized neocortical networks, with temporal lobe memory systems binding these elements to form coherent event memories. We provide a novel theoretical analysis of an unexplored consequence of the independence of memory systems for elements and their bindings, 1 that raises the paradoxical prediction that schema-driven false memories can act solely on the binding of event elements despite the superior retrieval of individual elements. This is because if 2, or more, schema-relevant elements are bound together in unexpected conjunctions, the unexpected conjunction will increase attention during encoding to both the elements and their bindings, but only the bindings will receive competition with evoked schema-expected bindings. We test our model by examining memory for object-location bindings in recognition (Study 1) and recall (Studies 2 and 3) tasks. After studying schema-relevant objects in unexpected locations (e.g., pan on a stool in a kitchen scene), participants who then viewed these objects in expected locations (e.g., pan on stove) at test were more likely to falsely remember this object-location pairing as correct, compared with participants that viewed a different unexpected object-location pairing (e.g., pan on floor). In recall, participants were more likely to correctly remember individual schema-relevant objects originally viewed in unexpected, as opposed to expected locations, but were then more likely to misplace these items in the original room scene to expected places, relative to control schema-irrelevant objects. Our theoretical analysis and novel paradigm provide a tool for investigating memory distortions acting on binding processes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

PubMed

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

2014-10-01

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

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

PubMed

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

2017-10-19

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

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

NASA Astrophysics Data System (ADS)

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

2017-08-01

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

Comparison of commercial and noncommercial endotracheal tube-securing devices.

PubMed

Fisher, Daniel F; Chenelle, Christopher T; Marchese, Andrew D; Kratohvil, Joseph P; Kacmarek, Robert M

2014-09-01

Tracheal intubation is used to establish a secure airway in patients who require mechanical ventilation. Unexpected extubation can have serious complications, including airway trauma and death. Various methods and devices have been developed to maintain endotracheal tube (ETT) security. Associated complications include pressure ulcers due to decreased tissue perfusion. Device consideration includes ease of use, rapid application, and low exerted pressure around the airway. Sixteen ETT holders were evaluated under a series of simulated clinical conditions. ETT security was tested by measuring distance displaced after a tug. Nine of the 16 methods could be evaluated for speed of moving the ETT to the opposite side of the mouth. Sensors located on a mannequin measured applied forces when the head was rotated vertically or horizontally. Data were analyzed using multivariate analysis of variance, with P < .05. Median displacement of the ETT by the tug test was 0 cm (interquartile range of 0.0-0.10 cm, P < .001). The mean time to move the ETT from one side of the mouth to the other ranged from 1.25 ± 0.2 s to 34.4 ± 3.4 s (P < .001). Forces applied to the face with a vertical head lift ranged from < 0.2 newtons (N) to a maximum of 3.52 N (P < .001). Forces applied to the face with a horizontal rotation ranged from < 0.2 N to 3.52 N (P < .001). Commercial devices produced greater force than noncommercial devices. Noncommercial airway holders exert less force on a patient's face than commercial devices. Airway stability is affected by the type of securing method. Many commercial holders allow for rapid but secure movement of the artificial airway from one side of the mouth to the other. Copyright © 2014 by Daedalus Enterprises.

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

PubMed

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

2016-01-01

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

Interactions between mood and the structure of semantic memory: event-related potentials evidence

PubMed Central

Pinheiro, Ana P.; del Re, Elisabetta; Nestor, Paul G; McCarley, Robert W.; Gonçalves, Óscar F.

2013-01-01

Recent evidence suggests that affect acts as modulator of cognitive processes and in particular that induced mood has an effect on the way semantic memory is used on-line. We used event-related potentials (ERPs) to examine affective modulation of semantic information processing under three different moods: neutral, positive and negative. Fifteen subjects read 324 pairs of sentences, after mood induction procedure with 30 pictures of neutral, 30 pictures of positive and 30 pictures of neutral valence: 108 sentences were read in each mood induction condition. Sentences ended with three word types: expected words, within-category violations, and between-category violations. N400 amplitude was measured to the three word types under each mood induction condition. Under neutral mood, a congruency (more negative N400 amplitude for unexpected relative to expected endings) and a category effect (more negative N400 amplitude for between- than to within-category violations) were observed. Also, results showed differences in N400 amplitude for both within- and between-category violations as a function of mood: while positive mood tended to facilitate the integration of unexpected but related items, negative mood made their integration as difficult as unexpected and unrelated items. These findings suggest the differential impact of mood on access to long-term semantic memory during sentence comprehension. PMID:22434931

Interactions between mood and the structure of semantic memory: event-related potentials evidence.

PubMed

Pinheiro, Ana P; del Re, Elisabetta; Nestor, Paul G; McCarley, Robert W; Gonçalves, Óscar F; Niznikiewicz, Margaret

2013-06-01

Recent evidence suggests that affect acts as modulator of cognitive processes and in particular that induced mood has an effect on the way semantic memory is used on-line. We used event-related potentials (ERPs) to examine affective modulation of semantic information processing under three different moods: neutral, positive and negative. Fifteen subjects read 324 pairs of sentences, after mood induction procedure with 30 pictures of neutral, 30 pictures of positive and 30 pictures of neutral valence: 108 sentences were read in each mood induction condition. Sentences ended with three word types: expected words, within-category violations, and between-category violations. N400 amplitude was measured to the three word types under each mood induction condition. Under neutral mood, a congruency (more negative N400 amplitude for unexpected relative to expected endings) and a category effect (more negative N400 amplitude for between- than to within-category violations) were observed. Also, results showed differences in N400 amplitude for both within- and between-category violations as a function of mood: while positive mood tended to facilitate the integration of unexpected but related items, negative mood made their integration as difficult as unexpected and unrelated items. These findings suggest the differential impact of mood on access to long-term semantic memory during sentence comprehension.

Unexpected angular or rotational deformity after corrective osteotomy

PubMed Central

2014-01-01

Background Codman’s paradox reveals a misunderstanding of geometry in orthopedic practice. Physicians often encounter situations that cannot be understood intuitively during orthopedic interventions such as corrective osteotomy. Occasionally, unexpected angular or rotational deformity occurs during surgery. This study aimed to draw the attention of orthopedic surgeons toward the concepts of orientation and rotation and demonstrate the potential for unexpected deformity after orthopedic interventions. This study focused on three situations: shoulder arthrodesis, femoral varization derotational osteotomy, and femoral derotation osteotomy. Methods First, a shoulder model was generated to calculate unexpected rotational deformity to demonstrate Codman’s paradox. Second, femoral varization derotational osteotomy was simulated using a cylinder model. Third, a reconstructed femoral model was used to calculate unexpected angular or rotational deformity during femoral derotation osteotomy. Results Unexpected external rotation was found after forward elevation and abduction of the shoulder joint. In the varization and derotation model, closed-wedge osteotomy and additional derotation resulted in an unexpected extension and valgus deformity, namely, under-correction of coxa valga. After femoral derotational osteotomy, varization and extension of the distal fragment occurred, although the extension was negligible. Conclusions Surgeons should be aware of unexpected angular deformity after surgical procedure involving bony areas. The degree of deformity differs depending on the context of the surgical procedure. However, this study reveals that notable deformities can be expected during orthopedic procedures such as femoral varization derotational osteotomy. PMID:24886469

New product trial, use of edibles, and unexpected highs among marijuana and hashish users in Colorado.

PubMed

Allen, Jane A; Davis, Kevin C; Duke, Jennifer C; Nonnemaker, James M; Bradfield, Brian R; Farrelly, Matthew C

2017-07-01

This study examines the relationships between trial of new marijuana or hashish products and unexpected highs, and use of edible products and unexpected highs. We conducted an online survey of 634 adult, past-year marijuana users in Colorado. We used logistic regression models to examine the relationship between new product trial or edible use and unexpected highs. In the first year that recreational marijuana was legal in Colorado, 71.4% of respondents tried a new marijuana or hashish product, and 53.6% used an edible product. Trial of new products was associated with greater odds of experiencing an unexpected high after controlling for age, gender, education, mental health status, current marijuana or hashish use, and mean amount of marijuana or hashish consumed in the past month (OR=2.13, p<0.001). Individuals who reported having used edibles had greater odds of experiencing an unexpected high, after controlling for the same set of variables (OR=1.56, p<0.05). People who try new marijuana or hashish products, or use edible marijuana or hashish products, are at greater risk for an unexpected high. It is possible that some negative outcomes associated with marijuana use and unexpected highs may be averted through a better understanding of how to use product packaging to communicate with consumers. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2012-03-20

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

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

PubMed Central

2012-01-01

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

Hunting for unexpected post-translational modifications by spectral library searching with tier-wise scoring.

PubMed

Ma, Chun Wai Manson; Lam, Henry

2014-05-02

Discovering novel post-translational modifications (PTMs) to proteins and detecting specific modification sites on proteins is one of the last frontiers of proteomics. At present, hunting for post-translational modifications remains challenging in widely practiced shotgun proteomics workflows due to the typically low abundance of modified peptides and the greatly inflated search space as more potential mass shifts are considered by the search engines. Moreover, most popular search methods require that the user specifies the modification(s) for which to search; therefore, unexpected and novel PTMs will not be detected. Here a new algorithm is proposed to apply spectral library searching to the problem of open modification searches, namely, hunting for PTMs without prior knowledge of what PTMs are in the sample. The proposed tier-wise scoring method intelligently looks for unexpected PTMs by allowing mass-shifted peak matches but only when the number of matches found is deemed statistically significant. This allows the search engine to search for unexpected modifications while maintaining its ability to identify unmodified peptides effectively at the same time. The utility of the method is demonstrated using three different data sets, in which the numbers of spectrum identifications to both unmodified and modified peptides were substantially increased relative to a regular spectral library search as well as to another open modification spectral search method, pMatch.

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

PubMed

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

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

Central nervous system side effects associated with zolpidem treatment.

PubMed

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

2000-01-01

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

Nasal irrigation as an adjunctive treatment in allergic rhinitis: a systematic review and meta-analysis.

PubMed

Hermelingmeier, Kristina E; Weber, Rainer K; Hellmich, Martin; Heubach, Christine P; Mösges, Ralph

2012-01-01

Saline nasal irrigation (SNI) is often recommended as additional nonpharmacologic treatment, having proven its efficacy in acute and chronic rhinosinusitis and for therapy after sinonasal surgery. To date, however, no systematic review or meta-analysis exists showing the influence of SNI on allergic rhinitis (AR). This study aimed to establish the impact of SNI on symptoms of AR in different patient groups. We conducted a systematic search of Medline, Embase, Cochrane Central Register of Controlled Trials, and ISI Web of Science databases for literature published from 1994 to 2010 on SNI in AR. Prospective, randomized, controlled trials that assessed the effects of SNI on four different outcome parameters were included. The evaluation focused on primary (symptom score) and secondary parameters (medicine consumption, mucociliary clearance, and quality of life). Three independent reviewers chose 10 originals that satisfied the inclusion criteria (>400 participants total) from 50 relevant trials. SNI performed regularly over a limited period of up to 7 weeks was observed to have a positive effect on all investigated outcome parameters in adults and children with AR. SNI produced a 27.66% improvement in nasal symptoms, a 62.1% reduction in medicine consumption, a 31.19% acceleration of mucociliary clearance time, and a 27.88% improvement in quality of life. SNI using isotonic solution can be recommended as complementary therapy in AR. It is well tolerated, inexpensive, easy to use, and there is no evidence showing that regular, daily SNI adversely affects the patient's health or causes unexpected side effects.

Anti-Fas Antibody Conjugated Nanoparticles Enhancing the Antitumor Effect of Camptothecin by Activating the Fas-FasL Apoptotic Pathway.

PubMed

Yu, Hongliang; He, Jian; Lu, Qian; Huo, Da; Yuan, Shanmei; Zhou, Zhengyang; Xu, Peipei; Hu, Yong

2016-11-09

Emerging evidence suggest that the introduction of Fas ligand (FasL) can enhance the Fas-dependent apoptosis and induce durable immune responses against tumor. However, selective triggering of apoptosis in tumor cells while sparing normal cells remains a great challenge for the application of FasL-based therapeutic strategies. Herein, smart nanoparticles (NPs) with a sandwich structure were fabricated. These NPs consist of a matrix metalloproteinase (MMP) cleavable PEG outer layer, an anti-Fas antibody middle layer, and a camptothecin (CPT)-loaded inner core. They could accumulate at a tumor site by the enhanced permeability and retention (EPR) effect. The removable PEG layer protects the cytotoxic anti-Fas antibody from premature contact with normal tissues, thus avoiding the unexpected lethal side effect before they reach the tumor site. Due to the high level of MMP expressed by tumor cells inside the tumor tissue, these NPs would shed their PEG layers, resulting in the exposure of anti-Fas antibody to bind the Fas receptor and triggering the apoptosis of tumor cells. Results of Western blot confirmed that these NPs could mimic the function of activated cytotoxic lymphocyte (CTL) to activate the Fas-FasL apoptosis pathway of tumor cells. With the aid of CPT payload, these anti-Fas antibody conjugated NPs achieved a high tumor inhibition in the B16 allograft tumor animal model. The design of these NPs provides a method for delivering cytotoxic ligand to targeting tissue, which may be valuable in cancer therapy.

Pharmacologic Treatment Assigned for Niemann Pick Type C1 Disease Partly Changes Behavioral Traits in Wild-Type Mice.

PubMed

Schlegel, Victoria; Thieme, Markus; Holzmann, Carsten; Witt, Martin; Grittner, Ulrike; Rolfs, Arndt; Wree, Andreas

2016-11-09

Niemann-Pick Type C1 (NPC1) is an autosomal recessive inherited disorder characterized by accumulation of cholesterol and glycosphingolipids. Previously, we demonstrated that BALB/c-npc1 nih Npc1 -/- mice treated with miglustat, cyclodextrin and allopregnanolone generally performed better than untreated Npc1 -/- animals. Unexpectedly, they also seemed to accomplish motor tests better than their sham-treated wild-type littermates. However, combination-treated mutant mice displayed worse cognition performance compared to sham-treated ones. To evaluate effects of these drugs in healthy BALB/c mice, we here analyzed pharmacologic effects on motor and cognitive behavior of wild-type mice. For combination treatment mice were injected with allopregnanolone/cyclodextrin weekly, starting at P7. Miglustat injections were performed daily from P10 till P23. Starting at P23, miglustat was embedded in the chow. Other mice were treated with miglustat only, or sham-treated. The battery of behavioral tests consisted of accelerod, Morris water maze, elevated plus maze, open field and hot-plate tests. Motor capabilities and spontaneous motor behavior were unaltered in both drug-treated groups. Miglustat-treated wild-type mice displayed impaired spatial learning compared to sham- and combination-treated mice. Both combination- and miglustat-treated mice showed enhanced anxiety in the elevated plus maze compared to sham-treated mice. Additionally, combination treatment as well as miglustat alone significantly reduced brain weight, whereas only combination treatment reduced body weight significantly. Our results suggest that allopregnanolone/cyclodextrin ameliorate most side effects of miglustat in wild-type mice.

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

PubMed

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

2017-01-01

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

Unexpected finite size effects in interfacial systems: Why bigger is not always better—Increase in uncertainty of surface tension with bulk phase width

NASA Astrophysics Data System (ADS)

Longford, Francis G. J.; Essex, Jonathan W.; Skylaris, Chris-Kriton; Frey, Jeremy G.

2018-06-01

We present an unexpected finite size effect affecting interfacial molecular simulations that is proportional to the width-to-surface-area ratio of the bulk phase Ll/A. This finite size effect has a significant impact on the variance of surface tension values calculated using the virial summation method. A theoretical derivation of the origin of the effect is proposed, giving a new insight into the importance of optimising system dimensions in interfacial simulations. We demonstrate the consequences of this finite size effect via a new way to estimate the surface energetic and entropic properties of simulated air-liquid interfaces. Our method is based on macroscopic thermodynamic theory and involves comparing the internal energies of systems with varying dimensions. We present the testing of these methods using simulations of the TIP4P/2005 water forcefield and a Lennard-Jones fluid model of argon. Finally, we provide suggestions of additional situations, in which this finite size effect is expected to be significant, as well as possible ways to avoid its impact.

Side Effects (Management)

MedlinePlus

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

Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of patients with ErbB2-positive metastatic breast cancer pretreated with anti-HER2 therapy.

PubMed

Awada, A; Dirix, L; Manso Sanchez, L; Xu, B; Luu, T; Diéras, V; Hershman, D L; Agrapart, V; Ananthakrishnan, R; Staroslawska, E

2013-01-01

Neratinib (HKI-272) is a potent irreversible pan-ErbB tyrosine kinase inhibitor with clinical activity in patients with ErbB2/HER2-positive breast cancer. Phase I of this open-label, phase I/II study investigated the maximum tolerated dose (MTD) of oral neratinib (160 or 240 mg/day) plus vinorelbine (25 mg/m2; days 1 and 8 of each 21-day cycle) in patients with solid tumors. Phase II assessed the safety, clinical activity, and pharmacokinetics of the combination in patients with HER2-positive metastatic breast cancer; the primary efficacy end point was objective response (OR). In phase I (n=12), neratinib (240 mg) plus vinorelbine (25 mg/m2) was established as the MTD. In phase II, 79 patients with HER2-positive metastatic breast cancer were treated at the MTD. The most common treatment-related adverse events were diarrhea (96%), neutropenia (54%), and nausea (50%). Three patients discontinued treatment due to diarrhea. No clinically important skin side-effects were observed. The OR rate in assessable phase II patients was 41% (no prior lapatinib) and 8% (prior lapatinib). There was no evidence of pharmacokinetic interaction between neratinib and vinorelbine. Neratinib plus vinorelbine showed promising antitumor activity and no unexpected toxic effects in HER2-positive metastatic breast cancer patients. Trial registration ClinicalTrials.gov #NCT00706030.

Physicochemical and Pharmacological Characterization of Permanently Charged Opioids.

PubMed

Mazak, Karoly; Noszal, Bela; Hosztafi, Sandor

2017-01-01

The main aim of synthesizing permanently charged opioids is to ensure that they do not enter the central nervous system. Such drugs can provide analgesic activity with reduced sedation and other side effects on the central nervous system. We undertook a search of bibliographic databases for peer-reviewed research literature and also summarized our published results in this field. The present review focuses on the characterization of permanently charged opioids by various physicochemical methods, and in vitro as well as in vivo tests. The basicity and lipophilicity of opioid alkaloids are discussed at the microscopic, speciesspecific level. Glucuronide conjugates of opioids are also reviewed. Whereas the primary metabolite morphine-3-glucuronide does not bind to opioid receptors with high affinity, morphine-6-glucuronide is a potent analgesic, at least, partly due to its unexpectedly high lipophilicity. We discuss the quaternary ammonium opioid derivatives of a permanent positive charge, detailing their antinociceptive activity and effects on gastrointestinal motility in various in vivo animal tests and in vitro studies. Compounds with antagonistic activity are also reviewed. The last part of our study concentrates on sulfate conjugates of morphine derivatives that display unique pharmacological properties because they carry a negative charge at any pH value in the human body. In conclusion, the findings of this review confirm the importance of permanently charged opioids in the investigated fields of pharmacology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The need for interaction between assisted reproduction technology and genetics: recommendations of the European Societies of Human Genetics and Human Reproduction and Embryology.

PubMed

2006-08-01

Infertility and reproductive genetic risk are both increasing in our societies because of lifestyle changes and possibly environmental factors. Owing to the magnitude of the problem, they have implications not only at the individual and family levels but also at the community level. This leads to an increasing demand for access to assisted reproduction technology (ART) and genetic services, especially when the cause of infertility may be genetic in origin. The increasing application of genetics in reproductive medicine and vice versa requires closer collaboration between the two disciplines. ART and genetics are rapidly evolving fields where new technologies are currently introduced without sufficient knowledge of their potential long-term effects. As for any medical procedures, there are possible unexpected effects which need to be envisaged to make sure that the balance between benefits and risks is clearly on the benefit side. The development of ART and genetics as scientific activities is creating an opportunity to understand the early stages of human development, which is leading to new and challenging findings/knowledge. However, there are opinions against investigating the early stages of development in humans who deserve respect and attention. For all these reasons, these two societies, European Society of Human Genetics (ESHG) and European Society of Human Reproduction and Embryology (ESHRE), have joined efforts to explore the issues at stake and to set up recommendations to maximize the benefit for the couples in need and for the community.

Role of structurally and magnetically modified nanoclusters in colossal magnetoresistance

PubMed Central

Tao, Jing; Niebieskikwiat, Dario; Jie, Qing; Schofield, Marvin A.; Wu, Lijun; Li, Qiang; Zhu, Yimei

2011-01-01

It is generally accepted that electronic and magnetic phase separation is the origin of many of exotic properties of strongly correlated electron materials, such as colossal magnetoresistance (CMR), an unusually large variation in the electrical resistivity under applied magnetic field. In the simplest picture, the two competing phases are those associated with the material state on either side of the phase transition. Those phases would be paramagnetic insulator and ferromagnetic metal for the CMR effect in doped manganites. It has been speculated that a critical component of the CMR phenomenon is nanoclusters with quite different properties than either of the terminal phases during the transition. However, the role of these nanoclusters in the CMR effect remains elusive because the physical properties of the nanoclusters are hard to measure when embedded in bulk materials. Here we show the unexpected behavior of the nanoclusters in the CMR compound La1-xCaxMnO3 (0.4 ≤ x < 0.5) by directly correlating transmission electron microscopy observations with bulk measurements. The structurally modified nanoclusters at the CMR temperature were found to be ferromagnetic and exhibit much higher electrical conductivity than previously proposed. Only at temperatures much below the CMR transition, the nanoclusters are antiferromagnetic and insulating. These findings substantially alter the current understanding of these nanoclusters on the material’s functionality and would shed light on the microscopic study on the competing spin-lattice-charge orders in strongly correlated systems. PMID:22160678

Gastrointestinal causes of sudden unexpected death: A review.

PubMed

Menezes, Ritesh G; Ahmed, Saba; Pasha, Syed Bilal; Hussain, Syed Ather; Fatima, Huda; Kharoshah, Magdy A; Madadin, Mohammed

2018-01-01

Gastrointestinal conditions are a less common cause of sudden unexpected death when compared to other conditions such as cardiovascular conditions, but they are equally important. Various congenital and acquired gastrointestinal conditions that have resulted in sudden unexpected death are discussed. The possible lethal mechanisms behind each condition, along with any associated risk factors or secondary diseases, have been described. Through this article, we aim to highlight the need for physicians to prevent death in such conditions by ensuring that subclinical cases are diagnosed correctly before it is too late and by providing timely and efficacious treatment to the patient concerned. In addition, this review would certainly benefit the forensic pathologist while dealing with cases of sudden unexpected death due to gastrointestinal causes. This article is a review of the major gastrointestinal causes of sudden unexpected death. In addition, related fatal cases encountered occasionally in forensic autopsy practice are also included. There are several unusual and rare causes of life-threatening gastrointestinal bleeding that may lead to sudden unexpected death to cover all the entities in detail. Nevertheless, this article is a general guide to the topic of gastrointestinal causes of sudden unexpected death.

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

PubMed

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

2017-10-01

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

Confronting the unexpected: temporal, situational, and attributive dimensions of distressing symptom experience for breast cancer survivors.

PubMed

Rosedale, Mary; Fu, Mei R

2010-01-01

To describe women's unexpected and distressing symptom experiences after breast cancer treatment. Qualitative and descriptive. Depending upon their preference, participants were interviewed in their homes or in a private office space in a nearby library. Purposive sample of 13 women 1-18 years after breast cancer treatment. Secondary analysis of phenomenologic data (constant comparative method). Breast cancer symptom distress, ongoing symptoms, and unexpected experiences. Women described experiences of unexpected and distressing symptoms in the years following breast cancer treatment. Symptoms included pain, loss of energy, impaired limb movement, cognitive disturbance, changed sexual experience, and lymphedema. Four central themes were derived: living with lingering symptoms, confronting unexpected situations, losing precancer being, and feeling like a has-been. Distress intensified when women expected symptoms to disappear but symptoms persisted instead. Increased distress also was associated with sudden and unexpected situations or when symptoms elicited feelings of loss about precancer being and feelings of being a has been. Findings suggest that symptom distress has temporal, situational, and attributive dimensions. Breast cancer survivors' perceptions of ongoing and unexpected symptoms have important influences on quality of life. Understanding temporal, situational, and attributive dimensions of symptom distress empowers nurses and healthcare professionals to help breast cancer survivors prepare for subsequent ongoing or unexpected experiences in the years after breast cancer treatment. Follow-up care for breast cancer survivors should foster dialogue about ways that symptoms might emerge and that unexpected situations might occur. Prospective studies are needed to examine symptom distress in terms of temporal, situational, and attributive dimensions and explore the relationship between symptom distress and psychological distress after breast cancer treatment.

Managing Chemotherapy Side Effects: Constipation

MedlinePlus

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

HIV Medicines and Side Effects

MedlinePlus

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

Angular dependence of DRAM upset susceptibility

NASA Technical Reports Server (NTRS)

Guertin, S. M.; Swift, G. M.; Edmonds, L. D.

2000-01-01

Heavy ion irradiations of two types of commercial DRAMs reveal unexpected angular responses. One device's cross section varied by two orders of magnitude with azimuthal angle. Accurate prediction of space rates requires accommodating this effect.

Detecting the unexpected: a research framework for ocean acidification.

PubMed

Pfister, Catherine A; Esbaugh, Andrew J; Frieder, Christina A; Baumann, Hannes; Bockmon, Emily E; White, Meredith M; Carter, Brendan R; Benway, Heather M; Blanchette, Carol A; Carrington, Emily; McClintock, James B; McCorkle, Daniel C; McGillis, Wade R; Mooney, T Aran; Ziveri, Patrizia

2014-09-02

The threat that ocean acidification (OA) poses to marine ecosystems is now recognized and U.S. funding agencies have designated specific funding for the study of OA. We present a research framework for studying OA that describes it as a biogeochemical event that impacts individual species and ecosystems in potentially unexpected ways. We draw upon specific lessons learned about ecosystem responses from research on acid rain, carbon dioxide enrichment in terrestrial plant communities, and nitrogen deposition. We further characterize the links between carbon chemistry changes and effects on individuals and ecosystems, and enumerate key hypotheses for testing. Finally, we quantify how U.S. research funding has been distributed among these linkages, concluding that there is an urgent need for research programs designed to anticipate how the effects of OA will reverberate throughout assemblages of species.

Predictive teratology: teratogenic risk-hazard identification partnered in the discovery process.

PubMed

Augustine-Rauch, K A

2008-11-01

Unexpected teratogenicity is ranked as one of the most prevalent causes for toxicity-related attrition of drug candidates. Without proactive assessment, the liability tends to be identified relatively late in drug development, following significant investment in compound and engagement in pre clinical and clinical studies. When unexpected teratogenicity occurs in pre-clinical development, three principle questions arise: Can clinical trials that include women of child bearing populations be initiated? Will all compounds in this pharmacological class produce the same liability? Could this effect be related to the chemical structure resulting in undesirable off-target adverse effects? The first question is typically addressed at the time of the unexpected finding and involves considering the nature of the teratogenicity, whether or not maternal toxicity could have had a role in onset, human exposure margins and therapeutic indication. The latter two questions can be addressed proactively, earlier in the discovery process as drug target profiling and lead compound optimization is taking place. Such proactive approaches include thorough assessment of the literature for identification of potential liabilities and follow-up work that can be conducted on the level of target expression and functional characterization using molecular biology and developmental model systems. Developmental model systems can also be applied in the form of in vitro teratogenicity screens, and show potential for effective hazard identification or issue resolution on the level of characterizing teratogenic mechanism. This review discusses approaches that can be applied for proactive assessment of compounds for teratogenic liability.

Probiotics: Safety and Side Effects

MedlinePlus

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

Managing Chemotherapy Side Effects: Pain

MedlinePlus

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

Managing Chemotherapy Side Effects: Memory Changes

MedlinePlus

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

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

PubMed

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

2018-05-31

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

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

PubMed

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

2001-10-01

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

A hierarchical anatomical classification schema for prediction of phenotypic side effects

PubMed Central

Kanji, Rakesh

2018-01-01

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

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

PubMed

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

2018-01-01

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

More Fluorous Surface Modifier Makes it Less Oleophobic: Fluorinated-Siloxane Copolymer/PDMS Coatings

PubMed Central

Zhang, Wei; Zheng, Ying; Orsini, Lorenzo; Morelli, Andrea; Galli, Giancarlo; Chiellini, Emo; Carpenter, Everett E.; Wynne, Kenneth J.

2010-01-01

A copolyacrylate with semifluorinated and polydimethylsiloxane side chains (D5-3) was used as a surface modifier for a condensation cured PDMS coating. The decyl fluorous group is represented by “D”; “5” is a 5 kDa silicone, and “3” the mole ratio of fluorous to silicone side chain. Wetting behavior was assessed by dynamic contact angle (DCA) analysis using isopropanol, which differentiates silicone and fluorous wetting behavior. Interestingly, a maximum in surface oleophobicity was found at low D5-3 concentration (0.4 wt%). Higher concentrations result in decreased oleophobicity reflected in decreased contact angles. To understand this unexpected observation, dynamic light scattering (DLS) studies were initiated on a model system consisting of hydroxyl-terminated PDMS (18 kDa) containing varying amounts of D5-3. DLS revealed D5-3 aggregation as a function of temperature and concentration. A model is proposed by which D5-3 surface concentration is depleted via phase separation favoring D5-3 aggregation at concentrations >0.4 wt%, that is, the CMC. This model suggests increasing aggregate / micelle concentrations at increased D5-3 concentration. Bulk morphologies studied by scanning electron microscopy (SEM) and atomic force microscopy (AFM) support this model by showing increased aggregate concentrations with increased D5-3 >0.4 wt%. PMID:20000339

Trajectory analysis for the nucleus and dust of comet C/2013 A1 (Siding Spring)

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

Farnocchia, Davide; Chesley, Steven R.; Chodas, Paul W.

Comet C/2013 A1 (Siding Spring) will experience a high velocity encounter with Mars on 2014 October 19 at a distance of 135,000 km ± 5000 km from the planet center. We present a comprehensive analysis of the trajectory of both the comet nucleus and the dust tail. The nucleus of C/2013 A1 cannot impact on Mars even in the case of unexpectedly large nongravitational perturbations. Furthermore, we compute the required ejection velocities for the dust grains of the tail to reach Mars as a function of particle radius and density and heliocentric distance of the ejection. A comparison between ourmore » results and the most current modeling of the ejection velocities suggests that impacts are possible only for millimeter to centimeter size particles released more than 13 AU from the Sun. However, this level of cometary activity that far from the Sun is considered extremely unlikely. The arrival time of these particles spans a 20-minute time interval centered at 2014 October 19 at 20:09 TDB, i.e., around the time that Mars crosses the orbital plane of C/2013 A1. Ejection velocities larger than currently estimated by a factor >2 would allow impacts for smaller particles ejected as close as 3 AU from the Sun. These particles would reach Mars from 19:13 TDB to 20:40 TDB.« less

Surgical outcome of Fontan conversion and arrhythmia surgery: Need a pacemaker?

PubMed

Terada, Takafumi; Sakurai, Hajime; Nonaka, Toshimichi; Sakurai, Takahisa; Sugiura, Junya; Taneichi, Tetsuyoshi; Ohtsuka, Ryohei

2014-07-01

Atrial tachyarrhythmias are frequent complications in the late period after the Fontan procedure, and important risk factors for a poor prognosis. The impact of Fontan conversion and arrhythmia surgery in failed Fontan patients has been described in many reports. We evaluated our experience with Fontan conversion procedures, concomitant arrhythmia surgery, and pacemaker implantation. We reviewed the hospital records of 25 consecutive patients who underwent a Fontan conversion procedure from January 2004 to March 2012. Twenty-four patients had arrhythmia surgery using cryoablation and radiofrequency ablation at the time of conversion. A bilateral atrial maze procedure was performed in 6 patients, right-side maze in 15, and isthmus block in 3. Three patients with a diagnosis of corrected transposition of the great arteries underwent simultaneous pacemaker implantation electively. There was no early death and one late death during a mean follow-up period of 21.2 months. Three tachyarrhythmia recurrences developed, and there were 4 occurrences of sinus bradycardia. Five of these patients required postoperative pacemaker implantation. The mid-term results of Fontan conversion and arrhythmia surgery in our institute were satisfactory. The occurrence of unexpected postoperative pacemaker requirement was high in the patients who underwent a right atrial or bilateral atrial maze procedure. Pacemaker or lead implantation is recommended for patients planned to undergo a right-side or full maze procedure. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Identification of the Viscous Superlayer on the Low-Speed Side of a Single-Stream Shear Layer

NASA Astrophysics Data System (ADS)

Foss, John; Peabody, Jason

2010-11-01

Image pairs (elevation/plan views) have been acquired of a smoke streakline originating in the irrotational region on the low-speed side of a high Re single-stream shear layer of Morris and Foss (2003). The viscous superlayer (VSL) is identified as the terminus of the streak; 1800 such images provide VSL position statistics. Hot-wire data acquired concurrently at the shear layer edge and interior are used to investigate the relationship between these velocity magnitudes and the large-scale motions. Distinctive features (plumes) along the streakline are tracked between images to provide discrete irrotational region velocity magnitudes and material trajectories. A non-diffusive marker, introduced in the separating (high speed) boundary layer and imaged at x/θo=352, has revealed an unexpected bias in the streak-defined VSL locations. The interpretation of this bias clarifies the induced flow patterns in the entrainment region. The observations are consistent with a conception of the large-scale shear layer motions as "billows" of vortical fluid separated by re-entrant "wedges" of irrotational fluid, per Phillips (1972). Morris, S.C. and Foss, J.F. (2003). "Turbulent Boundary Layer to Single Stream Shear Layer: The Transition Region." Journal of Fluid Mechanics. Vol. 494, pp. 187-221. Phillips, O. M. (1972). "The Entrainment Interface." Journal of Fluid Mechanics. Vol. 51, pp. 97-118.

The changing concept of sudden infant death syndrome: diagnostic coding shifts, controversies regarding the sleeping environment, and new variables to consider in reducing risk.

PubMed

2005-11-01

There has been a major decrease in the incidence of sudden infant death syndrome (SIDS) since the American Academy of Pediatrics (AAP) released its recommendation in 1992 that infants be placed down for sleep in a nonprone position. Although the SIDS rate continues to fall, some of the recent decrease of the last several years may be a result of coding shifts to other causes of unexpected infant deaths. Since the AAP published its last statement on SIDS in 2000, several issues have become relevant, including the significant risk of side sleeping position; the AAP no longer recognizes side sleeping as a reasonable alternative to fully supine sleeping. The AAP also stresses the need to avoid redundant soft bedding and soft objects in the infant's sleeping environment, the hazards of adults sleeping with an infant in the same bed, the SIDS risk reduction associated with having infants sleep in the same room as adults and with using pacifiers at the time of sleep, the importance of educating secondary caregivers and neonatology practitioners on the importance of "back to sleep," and strategies to reduce the incidence of positional plagiocephaly associated with supine positioning. This statement reviews the evidence associated with these and other SIDS-related issues and proposes new recommendations for further reducing SIDS risk.

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

ERIC Educational Resources Information Center

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

2010-01-01

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

The erythropoietin-derived peptide MK-X and erythropoietin have neuroprotective effects against ischemic brain damage

PubMed Central

Yoo, Seung-Jun; Cho, Bongki; Lee, Deokho; Son, Gowoon; Lee, Yeong-Bae; Soo Han, Hyung; Kim, Eunjoo; Moon, Chanil; Moon, Cheil

2017-01-01

Erythropoietin (EPO) has been well known as a hematopoietic cytokine over the past decades. However, recent reports have demonstrated that EPO plays a neuroprotective role in the central nervous system, and EPO has been considered as a therapeutic target in neurodegenerative diseases such as ischemic stroke. Despite the neuroprotective effect of EPO, clinical trials have shown its unexpected side effects, including undesirable proliferative effects such as erythropoiesis and tumor growth. Therefore, the development of EPO analogs that would confer neuroprotection without adverse effects has been attempted. In this study, we examined the potential of a novel EPO-based short peptide, MK-X, as a novel drug for stroke treatment in comparison with EPO. We found that MK-X administration with reperfusion dramatically reduced brain injury in an in vivo mouse model of ischemic stroke induced by middle cerebral artery occlusion, whereas EPO had little effect. Similar to EPO, MK-X efficiently ameliorated mitochondrial dysfunction followed by neuronal death caused by glutamate-induced oxidative stress in cultured neurons. Consistent with this effect, MK-X significantly decreased caspase-3 cleavage and nuclear translocation of apoptosis-inducing factor induced by glutamate. MK-X completely mimicked the effect of EPO on multiple activation of JAK2 and its downstream PI3K/AKT and ERK1/2 signaling pathways, and this signaling process was involved in the neuroprotective effect of MK-X. Furthermore, MK-X and EPO induced similar changes in the gene expression patterns under glutamate-induced excitotoxicity. Interestingly, the most significant difference between MK-X and EPO was that MK-X better penetrated into the brain across the brain–blood barrier than did EPO. In conclusion, we suggest that MK-X might be used as a novel drug for protection from brain injury caused by ischemic stroke, which penetrates into the brain faster in comparison with EPO, even though MK-X and EPO have similar protective effects against excitotoxicity. PMID:28817120

Managing Chemotherapy Side Effects: Anemia

MedlinePlus

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

Chemotherapy Side Effects: A Cause of Heart Disease?

MedlinePlus

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

Managing Chemotherapy Side Effects: Skin and Nail Changes

MedlinePlus

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

Cutaneous side effects of doxycycline: a pediatric case series.

PubMed

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

2017-06-01

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

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

PubMed

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

2018-03-01

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

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

PubMed

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

2017-08-01

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

Anaesthesiological considerations on tocolytic and uterotonic therapy in obstetrics.

PubMed

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

2009-07-01

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

Field studies on pesticides and birds: Unexpected and unique relations

USGS Publications Warehouse

Blus, L.J.; Henny, Charles J.

1997-01-01

We review the advantages and disadvantages of experimental and field studies for determining effects of pesticides on birds. Important problems or principles initially discovered in the field include effects of DDT (through its metabolite DDE) on eggshell thickness, reproductive success, and population stability; trophic-level bioaccumulation of the lipid-soluble organochlorine pesticides; indirect effects on productivity and survival through reductions in the food supply and cover by herbicides and insecticides; unexpected toxic effects and routes of exposure of organophosphorus compounds such as famphur and dimethoate; effects related to simultaneous application at full strength of several pesticides of different classes; and others. Also, potentially serious bird problems with dicofol, based on laboratory studies, later proved negligible in the field. In refining field tests of pesticides, the selection of a species or group of species to study is important, because exposure routes may vary greatly, and 10-fold interspecific differences in sensitivity to pesticides are relatively common. Although there are limitations with field investigations, particularly uncontrollable variables that must be addressed, the value of a well-designed field study far outweighs its shortcomings.

Field studies on pesticides and birds: unexpected and unique relations

USGS Publications Warehouse

Blus, L.J.; Henny, C.J.

1997-01-01

We review the advantages and disadvantages of experimental and field studies for determining effects of pesticides on birds. Important problems or principles initially discovered in the field include effects of DDT (through its metabolite DDE) on eggshell thickness, reproductive success, and population stability; trophic-level bioaccumulation of the lipid-soluble organochlorine pesticides; indirect effects on productivity and survival through reductions in the food supply and cover by herbicides and insecticides; unexpected toxic effects and routes of exposure of organophosphorus compounds such as famphur and dimethoate; effects related to simultaneous application at full strength of several pesticides of different classes; and others. Also, potentially serious bird problems with dicofol, based on laboratory studies, later proved negligible in the field. In refining field tests of pesticides, the selection of a species or group of species to study is important, because exposure routes may vary greatly, and 10-fold interspecific differences in sensitivity to pesticides are relatively common. Although there are limitations with field investigations, particularly uncontrollable variables that must be addressed, the value of a well-designed field study far outweighs its shortcomings

Influence of Nose Shape and L/D Ratio on Projectile Penetration in Frozen Soil

DTIC Science & Technology

1980-04-01

unexpected when soil properties are considered. Decreasing temperature below -10%C by 100 or 150 has little effect on the constitutive properties of... Effect ....... ............ ............. 10 L/D Influence .......................... .10 Target Temperature Effects ...10. Effect of L/D ratio and mass on flat nose pro- jectile penetration (the solid lines are least square curve fits to the data

Effects of color vision deficiency on detection of color-highlighted targets in a simulated air traffic control display.

DOT National Transportation Integrated Search

1992-01-01

The present study sought to evaluate the effects of color vision deficiency on the gain in conspicuity that is realized when color-highlighting is added as a redundant cue to indicate the presence of unexpected, nontracked aircraft intruding in contr...

When Feedback Harms and Collaboration Helps in Computer Simulation Environments: An Expertise Reversal Effect

ERIC Educational Resources Information Center

Nihalani, Priya K.; Mayrath, Michael; Robinson, Daniel H.

2011-01-01

We investigated the effects of feedback and collaboration on undergraduates' transfer performance when using a computer networking training simulation. In Experiment 1, 65 computer science "novices" worked through an instructional protocol individually (control), individually with feedback, or collaboratively with feedback. Unexpectedly,…

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

PubMed

Enblom, Anna; Johnsson, Anna

2017-12-01

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

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

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

Wang, Yang; Chen, Xiaolong; Ye, Weiguang

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

Making psycholinguistics musical: self-paced reading time evidence for shared processing of linguistic and musical syntax.

PubMed

Slevc, L Robert; Rosenberg, Jason C; Patel, Aniruddh D

2009-04-01

Linguistic processing, especially syntactic processing, is often considered a hallmark of human cognition; thus, the domain specificity or domain generality of syntactic processing has attracted considerable debate. The present experiments address this issue by simultaneously manipulating syntactic processing demands in language and music. Participants performed self-paced reading of garden path sentences, in which structurally unexpected words cause temporary syntactic processing difficulty. A musical chord accompanied each sentence segment, with the resulting sequence forming a coherent chord progression. When structurally unexpected words were paired with harmonically unexpected chords, participants showed substantially enhanced garden path effects. No such interaction was observed when the critical words violated semantic expectancy or when the critical chords violated timbral expectancy. These results support a prediction of the shared syntactic integration resource hypothesis (Patel, 2003), which suggests that music and language draw on a common pool of limited processing resources for integrating incoming elements into syntactic structures. Notations of the stimuli from this study may be downloaded from pbr.psychonomic-journals.org/content/supplemental.

Driving performance changes of middle-aged experienced taxi drivers due to distraction tasks during unexpected situations.

PubMed

Kim, Hyung-Sik; Choi, Mi-Hyun; Choi, Jin-Seung; Kim, Hyun-Joo; Hong, Sang-Pyo; Jun, Jae-Hoon; Tack, Gye-Rae; Kim, Boseong; Min, Ung-Chan; Lim, Dae-Woon; Chung, Soon-Cheol

2013-10-01

This study investigated the effects of distraction taskssuch as sending a text message with a cellphone and searching navigation with car navigation system-on the driving performance of 29 highly experienced taxi drivers in their 50s. All participants were instructed to drive using a driving simulator for 2 min. while maintaining a constant distance from the vehicle in front and a constant speed. Participants drove without any distractions for the first minute. For an additional minute, they performed Driving Only or performed a task while driving (Driving + Sending Text Message or Driving + Searching Navigation). An unexpected situation, in which the participant had to stop abruptly due to a sudden stop of the preceding vehicle, occurred during this period. Driving performance during the unexpected situation was evaluated by car control variables, medial-lateral coefficient of variation and brake time, and by motion variables such as the jerk-cost function. Compared to Driving Only, jerk-cost function, medial-lateral coefficient of variation, and brake time increased during Driving + Sending Text Message or Driving + Searching Navigation.

Unexpected inhibition of CO 2 gas hydrate formation in dilute TBAB solutions and the critical role of interfacial water structure

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

Nguyen, Ngoc N.; Nguyen, Anh V.; Nguyen, Khoi T.

Gas hydrates formed under moderated conditions open up novel approaches to tackling issues related to energy supply, gas separation, and CO 2 sequestration. Several additives like tetra-n-butylammonium bromide (TBAB) have been empirically developed and used to promote gas hydrate formation. Here we report unexpected experimental results which show that TBAB inhibits CO 2 gas hydrate formation when used at minuscule concentration. We also used spectroscopic techniques and molecular dynamics simulation to gain further insights and explain the experimental results. They have revealed the critical role of water alignment at the gas-water interface induced by surface adsorption of tetra-n-butylammonium cation (TBAmore » +) which gives rise to the unexpected inhibition of dilute TBAB solution. The water perturbation by TBA + in the bulk is attributed to the promotion effect of high TBAB concentration on gas hydrate formation. We explain our finding using the concept of activation energy of gas hydrate formation. Our results provide a step toward to mastering the control of gas hydrate formation.« less

Integration of a computerized two-finger gripper for robot workstation safety

NASA Technical Reports Server (NTRS)

Sneckenberger, John E.; Yoshikata, Kazuki

1988-01-01

A microprocessor-based controller has been developed that continuously monitors and adjusts the gripping force applied by a special two-finger gripper. This computerized force sensing gripper system enables the endeffector gripping action to be independently detected and corrected. The gripping force applied to a manipulated object is real-time monitored for problem situations, situations which can occur during both planned and errant robot arm manipulation. When unspecified force conditions occur at the gripper, the gripping force controller initiates specific reactions to cause dynamic corrections to the continuously variable gripping action. The force controller for this intelligent gripper has been interfaced to the controller of an industrial robot. The gripper and robot controllers communicate to accomplish the successful completion of normal gripper operations as well as unexpected hazardous situations. An example of an unexpected gripping condition would be the sudden deformation of the object being manipulated by the robot. The capabilities of the interfaced gripper-robot system to apply workstation safety measures (e.g., stop the robot) when these unexpected gripping effects occur have been assessed.

Assessing the influence of a passive, upper extremity exoskeletal vest for tasks requiring arm elevation: Part II - "Unexpected" effects on shoulder motion, balance, and spine loading.

PubMed

Kim, Sunwook; Nussbaum, Maury A; Mokhlespour Esfahani, Mohammad Iman; Alemi, Mohammad Mehdi; Jia, Bochen; Rashedi, Ehsan

2018-03-07

Adopting a new technology (exoskeletal vest designed to support overhead work) in the workplace can be challenging since the technology may pose unexpected safety and health consequences. A prototype exoskeletal vest was evaluated for potential unexpected consequences with a set of evaluation tests for: usability (especially, donning & doffing), shoulder range of motion (ROM), postural control, slip & trip risks, and spine loading during overhead work simulations. Donning/doffing the vest was easily done by a wearer alone. The vest reduced the max. shoulder abduction ROM by ∼10%, and increased the mean center of pressure velocity in the anteroposterior direction by ∼12%. However, vest use had minimal influences on trip-/slip-related fall risks during level walking, and significantly reduced spine loadings (up to ∼30%) especially during the drilling task. Use of an exoskeletal vest can be beneficial, yet the current evaluation tests should be expanded for more comprehensiveness, to enable the safe adoption of the technology. Copyright © 2018 Elsevier Ltd. All rights reserved.

Subjective experience and mental side-effects of antipsychotic treatment.

PubMed

Gerlach, J; Larsen, E B

1999-01-01

Many schizophrenic patients have a negative attitude towards antipsychotic drugs. This attitude is not only due to lack of insight into the disease, lack of recognition of the beneficial effects of the drugs, and to objective side-effects. The negative attitude is to a high degree due to mental side-effects and a sceptical opinion about antipsychotic medication in general. In a study of 53 chronic schizophrenic out-patients receiving maintenance depot antipsychotic treatment, we found that 60% were positive about the treatment, 32% were ambivalent and 8% had a negative attitude. Only 60% complained of side-effects, even though 94% had objective side-effects. Mental side-effects such as subjective akathisia, dysphoria and emotional indifference were most often observed by the patients, while hypokinesia and hyperkinesia were least noticed by them, but most often observed by the physician. No correlation was found between the patients' subjective assessment of their quality of life and the degree of psychosis and side-effects. With the new atypical antipsychotics this situation seems to be changing. These new drugs are primarily characterized by a lower level of motor extrapyramidal side-effects (EPS), and with fewer motor EPS, fewer mental EPS can be expected. In recent studies comparing the new antipsychotics with haloperidol, better effects have been observed with regard to negative symptoms and depression, and this may at least in part be a reflection of a lower level of mental side-effects of the atypical antipsychotics. This improved clinical profile of new antipsychotics is extremely valuable in the context of an integrated treatment in schizophrenia, consisting of early intervention, psychosocial rehabilitation and family/patient psycho-education.

Ayurveda for chemo-radiotherapy induced side effects in cancer patients.

PubMed

Metri, Kashinath; Bhargav, Hemant; Chowdhury, Praerna; Koka, Prasad S

2013-01-01

Chemotherapy drugs and radiotherapy are highly toxic and both damage adjacent healthy cells. Side effects may be acute (occurring within few weeks after therapy), intermediate or late (occurring months or years after the therapy). Some important side effects of chemotherapy are: nausea, vomiting, diarrhea, mucositis, alopecia, constipation etc; whereas radiation therapy though administered locally, can produce systemic side effects such as fatigue, anorexia, nausea, vomiting, alteration in the taste, sleep disturbance, headache, anemia, dry skin, constipation etc. Late complications of these therapies also include pharyngitis, esophagitis, laryngitis, persistent dysphagia, fatigue, hepatotoxicity, infertility and cognitive deficits. These arrays of side effects have a devastating effect on the quality of life of cancer survivors. Due to the inadequacy of most of the radio-protectors and chemo-protectors in controlling the side effects of conventional cancer therapy the complementary and alternative medicines have attracted the view of researchers and medical practitioners more recently. This review aims at providing a comprehensive management protocol of above mentioned chemo-radiotherapy induced side effects based on Ayurveda, which is an ancient system of traditional medicine practiced in Indian peninsula since 5000 BC. When the major side effects of chemo-radiotherapy are looked through an ayurvedic perspective, it appears that they are the manifestations of aggravated pitta dosha, especially under the group of disorders called Raktapitta (haemorrhage) or Raktadushti (vascular inflammation). Based on comprehensive review of ancient vedic literature and modern scientific evidences, ayurveda based interventions are put forth. This manuscript should help clinicians and people suffering from cancer to combat serious chemo-radiotherapy related side effects through simple but effective home-based ayurveda remedies. The remedies described are commonly available and safe. These simple ayurveda based solutions may act as an important adjuvant to chemo-radiotherapy and enhance the quality of life of cancer patients.

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

PubMed

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

2018-03-29

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

Selective serotonin reuptake inhibitor discontinuation: side effects and other factors that influence medication adherence.

PubMed

Goethe, John W; Woolley, Stephen B; Cardoni, Alex A; Woznicki, Brenda A; Piez, Deborah A

2007-10-01

Patients with major depression discontinue taking their antidepressants for many reasons. Although side effects are often cited as the reason for discontinuation, few prospective studies have addressed this question, and none has specifically examined discontinuation in patients with severe depression. Inpatients and outpatients treated with a selective serotonin reuptake inhibitor for major depressive disorder were identified after admission. Three months later, patients were contacted and interviewed to determine antidepressant usage and the side effects experienced, including when these were experienced and their severity. Between October 2001 and April 2003, 406 English- or Spanish-speaking patients aged 18 to 75 years were followed up. One in 4 patients discontinued the index antidepressant. Among specific side effects noted, only "change in weight" and "anxiety" were significant predictors of discontinuation after controlling for confounders. Experiencing 1 or more "extremely" bothersome side effects was associated with more than a doubling of the risk of discontinuation, but the presence of side effects and side effects less severe than "extremely" bothersome were not significant predictors. There were no differences among selective serotonin reuptake inhibitor antidepressants in either the presence/absence of side effects or in the discontinuation rates. The results suggest that the contribution of side effects to antidepressant discontinuation is more complex than previously suggested. Disparate findings from earlier studies may reflect aspects of study design, such as examining populations whose severity of depression varied widely or not controlling for important confounding factors. Future research should separately examine high-risk groups (or control for severity of depression) and carefully rule out other potential contributors to discontinuation.

Deep-tow magnetic survey above large exhumed mantle domains of the eastern Southwest Indian ridge

NASA Astrophysics Data System (ADS)

Bronner, A.; Munschy, M.; Carlut, J. H.; Searle, R. C.; Sauter, D.; Cannat, M.

2011-12-01

The recent discovery of a new type of seafloor, the "smooth seafloor", formed with no or very little volcanic activity along the ultra-slow spreading Southwest Indian ridge (SWIR) shows an unexpected complexity in processes of generation of the oceanic lithosphere. There, detachment faulting is thought to be a mechanism for efficient exhumation of deep-seated mantle rocks. We present here a deep-tow geological-geophysical survey over smooth seafloor at the eastern SWIR (62-64°N) combining magnetic data, geology mapping from side-scan sonar images and results from dredge sampling. We introduce a new type of calibration approach for deep-tow fluxgate magnetometer. We show that magnetic data can be corrected from the magnetic effect of the vehicle with no recourse to its attitude (pitch, roll and heading) but only using the 3 components recorded by the magnetometer and an approximation of the scalar intensity of the Earth magnetic field. The collected dredge samples as well as the side-scan images confirm the presence of large areas of exhumed mantle-derived peridodites surrounded by a few volcanic constructions. This allows us to hypothesis that magnetic anomalies are caused by serpentinized peridotites or magmatic intrusions. We show that the magnetic signature of the smooth seafloor is clearly weaker than the surrounding volcanic areas. Moreover, the calculated magnetization of a source layer as well as the comparison between deep-tow and sea-surface magnetic data argue for strong East-West variability in the distribution of the magnetized sources. This variability may results from fluid-rocks interaction along the detachment faults as well as from the repartition of the volcanic material and thus questions the seafloor spreading origin of the corresponding magnetic anomalies. Finally, we provide magnetic arguments, as calculation of block rotation or spreading asymmetry in order to better constrain tectonic mechanisms that occur during the formation of this peculiar seafloor.

Effects of side lying on lung function in older individuals.

PubMed

Manning, F; Dean, E; Ross, J; Abboud, R T

1999-05-01

Body positioning exerts a strong effect on pulmonary function, but its effect on other components of the oxygen transport pathway are less well understood, especially the effects of side-lying positions. This study investigated the interrelationships between side-lying positions and indexes of lung function such as spirometry, alveolar diffusing capacity, and inhomogeneity of ventilation in older individuals. Nineteen nonsmoking subjects (mean age=62.8 years, SD=6.8, range=50-74) with no history of cardiac or pulmonary disease were tested over 2 sessions. The test positions were sitting and left side lying in one session and sitting and right side lying in the other session. In each of the positions, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), single-breath pulmonary diffusing capacity (DLCO/VA), and the slope of phase III (DN2%/L) of the single-breath nitrogen washout test to determine inhomogeneity of ventilation were measured. Compared with measurements obtained in the sitting position, FVC and FEV1 were decreased equally in the side-lying positions, but no change was observed in DLCO/VA or DN2%/L. Side-lying positions resulted in decreases in FVC and FEV1, which is consistent with the well-documented effects of the supine position. These findings further support the need for prescriptive rather than routine body positioning of patients with risks of cardiopulmonary compromise and the need to use upright positions in which lung volumes and capacities are maximized.

Control of retinoic acid synthesis and FGF expression in the nasal pit is required to pattern the craniofacial skeleton.

PubMed

Song, Y; Hui, J N; Fu, K K; Richman, J M

2004-12-15

Endogenous retinoids are important for patterning many aspects of the embryo including the branchial arches and frontonasal region of the embryonic face. The nasal placodes express retinaldehyde dehydrogenase-3 (RALDH3) and thus retinoids from the placode are a potential patterning influence on the developing face. We have carried out experiments that have used Citral, a RALDH antagonist, to address the function of retinoid signaling from the nasal pit in a whole embryo model. When Citral-soaked beads were implanted into the nasal pit of stage 20 chicken embryos, the result was a specific loss of derivatives from the lateral nasal prominences. Providing exogenous retinoic acid residue development of the beak demonstrating that most Citral-induced defects were produced by the specific blocking of RA synthesis. The mechanism of Citral effects was a specific increase in programmed cell death on the lateral (lateral nasal prominence) but not the medial side (frontonasal mass) of the nasal pit. Gene expression studies were focused on the Bone Morphogenetic Protein (BMP) pathway, which has a well-established role in programmed cell death. Unexpectedly, blocking RA synthesis decreased rather than increased Msx1, Msx2, and Bmp4 expression. We also examined cell survival genes, the most relevant of which was Fgf8, which is expressed around the nasal pit and in the frontonasal mass. We found that Fgf8 was not initially expressed along the lateral side of the nasal pit at the start of our experiments, whereas it was expressed on the medial side. Citral prevented upregulation of Fgf8 along the lateral edge and this may have contributed to the specific increase in programmed cell death in the lateral nasal prominence. Consistent with this idea, exogenous FGF8 was able to prevent cell death, rescue most of the morphological defects and was able to prevent a decrease in retinoic acid receptorbeta (Rarbeta) expression caused by Citral. Together, our results demonstrate that endogenous retinoids act upstream of FGF8 and the balance of these two factors is critical for regulating programmed cell death and morphogenesis in the face. In addition, our data suggest a novel role for endogenous retinoids from the nasal pit in controlling the precise downregulation of FGF in the center of the frontonasal mass observed during normal vertebrate development.

Effects and Side Effects of Flemish School Inspection

ERIC Educational Resources Information Center

Penninckx, Maarten; Vanhoof, Jan; De Maeyer, Sven; Van Petegem, Peter

2016-01-01

Despite the increased importance of school inspection in recent years, the current knowledge base does not provide a clear view on the effects and side effects of being inspected. More evidence is needed in more diverse educational contexts. This article responds to this need with a quantitative study on the effects and side effects of school…

Chemotherapy

MedlinePlus

... cells to get better. Because everyone's different, some people will have fewer side effects than others. Common side effects of chemo are ... infections easily. Medicines are available that can help people feel better if they have side effects from chemo. Doctors, nurses, and other members of ...

Predicting new drug indications from network analysis

NASA Astrophysics Data System (ADS)

Mohd Ali, Yousoff Effendy; Kwa, Kiam Heong; Ratnavelu, Kurunathan

This work adapts centrality measures commonly used in social network analysis to identify drugs with better positions in drug-side effect network and drug-indication network for the purpose of drug repositioning. Our basic hypothesis is that drugs having similar phenotypic profiles such as side effects may also share similar therapeutic properties based on related mechanism of action and vice versa. The networks were constructed from Side Effect Resource (SIDER) 4.1 which contains 1430 unique drugs with side effects and 1437 unique drugs with indications. Within the giant components of these networks, drugs were ranked based on their centrality scores whereby 18 prominent drugs from the drug-side effect network and 15 prominent drugs from the drug-indication network were identified. Indications and side effects of prominent drugs were deduced from the profiles of their neighbors in the networks and compared to existing clinical studies while an optimum threshold of similarity among drugs was sought for. The threshold can then be utilized for predicting indications and side effects of all drugs. Similarities of drugs were measured by the extent to which they share phenotypic profiles and neighbors. To improve the likelihood of accurate predictions, only profiles such as side effects of common or very common frequencies were considered. In summary, our work is an attempt to offer an alternative approach to drug repositioning using centrality measures commonly used for analyzing social networks.

Sudden unexpected death under acute influence of cannabis.

PubMed

Hartung, Benno; Kauferstein, Silke; Ritz-Timme, Stefanie; Daldrup, Thomas

2014-04-01

The acute toxicity of cannabinoids is said to be low and there is little public awareness of the potentially hazardous cardiovascular effects of cannabis, e.g. marked increase in heart rate or supine blood pressure. We describe the cases of two young, putative healthy men who died unexpectedly under the acute influence of cannabinoids. To our knowledge, these are the first cases of suspected fatal cannabis intoxications where full postmortem investigations, including autopsy, toxicological, histological, immunohistochemical and genetical examinations, were carried out. The results of these examinations are presented. After exclusion of other causes of death we assume that the young men experienced fatal cardiovascular complications evoked by smoking cannabis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2015-03-29

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

The impact of tamoxifen brand switch on side effects and patient compliance in hormone receptor positive breast cancer patients.

PubMed

Zeidan, B; Anderson, K; Peiris, L; Rainsbury, D; Laws, S

2016-10-01

In 2006 Nolvadex was discontinued and replaced by a variety of alternative generic tamoxifen brands for the adjuvant treatment of breast cancer. Anecdotally, patients are switching brands and taking alternative medications to reduce treatment related symptoms. Nevertheless, more severe side effects may equate to better relapse prevention. This study evaluates generic tamoxifen adherence and its correlation with side effects and brand switch. Consecutive disease free ER positive patients (stage I-III) were invited to respond to a questionnaire. 165 of 327 questionnaires were returned (50% response). Pearson's Chi Square test was used for data analysis. 63 patients (38%) reported a switch between generic tamoxifen. 59% of all patients experienced side effects associated with tamoxifen treatment of which 53% were severe. Patients experiencing differential symptoms dependent on tamoxifen brand reported more severe side effects (p = 0.02). Non-prescribed supplements were taken by 42% of all patients with no significant improvement in climacteric symptoms (p = 0.05). The concomitant use of SSRIs appeared to have no effect on symptoms. A significant number of patients considered discontinuing tamoxifen because of the side effects (p = 0.001), yet this did not translate into discontinuation or non-adherence (p = 0.8 and 0.08 respectively). Severe tamoxifen side effects are commonly experienced by breast cancer patients and can be significantly altered by change in tamoxifen brand. Most patients will continue to take tamoxifen, despite side effects to avoid cancer relapse. Supplementation and antidepressants did not improve tamoxifen related side effects in our cohort. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Traditional Therapies for Skin Wound Healing.

PubMed

Pereira, Rúben F; Bártolo, Paulo J

2016-05-01

Significance: The regeneration of healthy and functional skin remains a huge challenge due to its multilayer structure and the presence of different cell types within the extracellular matrix in an organized way. Despite recent advances in wound care products, traditional therapies based on natural origin compounds, such as plant extracts, honey, and larvae, are interesting alternatives. These therapies offer new possibilities for the treatment of skin diseases, enhancing the access to the healthcare, and allowing overcoming some limitations associated to the modern products and therapies, such as the high costs, the long manufacturing times, and the increase in the bacterial resistance. This article gives a general overview about the recent advances in traditional therapies for skin wound healing, focusing on the therapeutic activity, action mechanisms, and clinical trials of the most commonly used natural compounds. New insights in the combination of traditional products with modern treatments and future challenges in the field are also highlighted. Recent Advances: Natural compounds have been used in skin wound care for many years due to their therapeutic activities, including anti-inflammatory, antimicrobial, and cell-stimulating properties. The clinical efficacy of these compounds has been investigated through in vitro and in vivo trials using both animal models and humans. Besides the important progress regarding the development of novel extraction methods, purification procedures, quality control assessment, and treatment protocols, the exact mechanisms of action, side effects, and safety of these compounds need further research. Critical Issues: The repair of skin lesions is one of the most complex biological processes in humans, occurring throughout an orchestrated cascade of overlapping biochemical and cellular events. To stimulate the regeneration process and prevent the wound to fail the healing, traditional therapies and natural products have been used with promising results. Although these products are in general less expensive than the modern treatments, they can be sensitive to the geographic location and season, and exhibit batch-to-batch variation, which can lead to unexpected allergic reactions, side effects, and contradictory clinical results. Future Directions: The scientific evidence for the use of traditional therapies in wound healing indicates beneficial effects in the treatment of different lesions. However, specific challenges remain unsolved. To extend the efficacy and the usage of natural substances in wound care, multidisciplinary efforts are necessary to prove the safety of these products, investigate their side effects, and develop standard controlled trials. The development of good manufacturing practices and regulatory legislation also assume a pivotal role in order to improve the use of traditional therapies by the clinicians and to promote their integration into the national health system. Current trends move to the development of innovative wound care treatments, combining the use of traditional healing agents and modern products/practices, such as nanofibers containing silver nanoparticles, Aloe vera loaded into alginate hydrogels, propolis into dressing films, and hydrogel sheets containing honey.

Traditional Therapies for Skin Wound Healing

PubMed Central

Pereira, Rúben F.; Bártolo, Paulo J.

2016-01-01

Significance: The regeneration of healthy and functional skin remains a huge challenge due to its multilayer structure and the presence of different cell types within the extracellular matrix in an organized way. Despite recent advances in wound care products, traditional therapies based on natural origin compounds, such as plant extracts, honey, and larvae, are interesting alternatives. These therapies offer new possibilities for the treatment of skin diseases, enhancing the access to the healthcare, and allowing overcoming some limitations associated to the modern products and therapies, such as the high costs, the long manufacturing times, and the increase in the bacterial resistance. This article gives a general overview about the recent advances in traditional therapies for skin wound healing, focusing on the therapeutic activity, action mechanisms, and clinical trials of the most commonly used natural compounds. New insights in the combination of traditional products with modern treatments and future challenges in the field are also highlighted. Recent Advances: Natural compounds have been used in skin wound care for many years due to their therapeutic activities, including anti-inflammatory, antimicrobial, and cell-stimulating properties. The clinical efficacy of these compounds has been investigated through in vitro and in vivo trials using both animal models and humans. Besides the important progress regarding the development of novel extraction methods, purification procedures, quality control assessment, and treatment protocols, the exact mechanisms of action, side effects, and safety of these compounds need further research. Critical Issues: The repair of skin lesions is one of the most complex biological processes in humans, occurring throughout an orchestrated cascade of overlapping biochemical and cellular events. To stimulate the regeneration process and prevent the wound to fail the healing, traditional therapies and natural products have been used with promising results. Although these products are in general less expensive than the modern treatments, they can be sensitive to the geographic location and season, and exhibit batch-to-batch variation, which can lead to unexpected allergic reactions, side effects, and contradictory clinical results. Future Directions: The scientific evidence for the use of traditional therapies in wound healing indicates beneficial effects in the treatment of different lesions. However, specific challenges remain unsolved. To extend the efficacy and the usage of natural substances in wound care, multidisciplinary efforts are necessary to prove the safety of these products, investigate their side effects, and develop standard controlled trials. The development of good manufacturing practices and regulatory legislation also assume a pivotal role in order to improve the use of traditional therapies by the clinicians and to promote their integration into the national health system. Current trends move to the development of innovative wound care treatments, combining the use of traditional healing agents and modern products/practices, such as nanofibers containing silver nanoparticles, Aloe vera loaded into alginate hydrogels, propolis into dressing films, and hydrogel sheets containing honey. PMID:27134765

3 CFR - Unexpected Urgent Refugee and Migration Needs

Code of Federal Regulations, 2013 CFR

2013-01-01

... 3 The President 1 2013-01-01 2013-01-01 false Unexpected Urgent Refugee and Migration Needs... Unexpected Urgent Refugee and Migration Needs Memorandum for the Secretary of State By the authority vested...) of the Migration and Refugee Assistance Act of 1962 (the “Act”), as amended, (22 U.S.C. 2601(c)(1...

3 CFR - Unexpected Urgent Refugee and Migration Needs

Code of Federal Regulations, 2013 CFR

2013-01-01

... 3 The President 1 2013-01-01 2013-01-01 false Unexpected Urgent Refugee and Migration Needs Presidential Documents Other Presidential Documents Presidential Determination No. 2012-6 of April 3, 2012 Unexpected Urgent Refugee and Migration Needs Memorandum for the Secretary of State By the authority vested in me as President by the Constitution...

77 FR 21389 - Unexpected Urgent Refugee and Migration Needs

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-10

... April 3, 2012 Unexpected Urgent Refugee and Migration Needs Memorandum for the Secretary of State By the... 2(c)(1) of the Migration and Refugee Assistance Act of 1962 (the ``Act''), as amended, (22 U.S.C... United States Emergency Refugee and Migration Assistance Fund, for the purpose of meeting unexpected and...

Inattentional blindness in older adults: Effects of attentional set and to-be-ignored distractors.

PubMed

Horwood, Sally; Beanland, Vanessa

2016-04-01

Inattentional blindness (IB) involves failing to detect an unexpected visual stimulus while undertaking another task. Previous research has predominantly investigated IB using young adult samples, with few studies exploring whether or how an observer's age affects their detection of unexpected events. To help address this gap, we compared younger adults (18-25 years of age) and older adults (60-80 years of age) on two IB tasks: one dynamic, one static. In the static task, older age was associated with substantially increased IB rates: 89 % for older adults versus 5 % for younger adults. In the dynamic task, we systematically manipulated the presence of to-be-ignored distractors and whether the unexpected stimulus color matched the observers' attentional set. We found a main effect of age on IB: As in the static task, older age was associated with increased IB rates (38 % for older adults vs. 8 % for younger adults). The presence of to-be-ignored distractors and attentional set mismatch interacted to substantially increase IB rates, but age did not interact with either factor. Overall, the results indicate that older age is associated with large increases in IB rates across a range of tasks. The pattern of results is consistent with attentional capacity models of cognitive aging, suggesting that older adults' reduced cognitive resources result in failure to consciously process stimuli that are inconsistent with their attentional set.

Bicarbonate enhances the in vitro antibiotic activity of kanamycin in Escherichia coli.

PubMed

Gutiérrez-Huante, M; Martínez, H; Bustamante, V H; Puente, J L; Sánchez, J

2015-05-01

Growth of enteropathogenic Escherichia coli E2348/69 was inhibited by bicarbonate in a dose-dependent manner, showing approximately 5% growth reduction at 5 mmol l(-1) while kanamycin at 3·12 μg ml(-1) inhibited growth by 15%, yet when kanamycin and bicarbonate were combined at these concentrations, inhibition increased to 80%. Unexpectedly, at bicarbonate concentrations >20 mmol l(-1) enhancement of the antibiotic activity virtually disappeared, i.e. there was a paradoxical Eagle-like effect. How bicarbonate acts is unclear, but neutral or alkaline pH also enhanced the activity of kanamycin. However, several differences indicated a separate effect of bicarbonate. First, bicarbonate inhibited growth more than the corresponding increments in pH. Second, at low concentration, the antibiotic enhancing effect of bicarbonate was stronger than the effect of pH alone. Third, 5 mmol l(-1) bicarbonate significantly enhanced the activity of kanamycin while the corresponding pH had no effect. Fourth, the Eagle-like effect was exclusive of bicarbonate because changes in pH did not induce an analogous behaviour. Notwithstanding the mechanism, the enhancing effect of bicarbonate was indubitable. Consequently, it seems worthwhile to explore further its potential to improve the efficacy of aminoglycosides and maybe even other antibiotics. Bicarbonate at a low concentration enhanced the in vitro antibiotic activity of kanamycin and gentamicin. Even though the action mechanism of bicarbonate is hitherto unknown, it seems worthwhile to explore further its capacity to improve the efficacy of aminoglycosides. Clearly, the well-known harmful side-effects of aminoglycosides are a concern. However, it has recently been shown in a fish model that bicarbonate may protect ciliary cells against the damage caused by aminoglycosides. So, it seems possible that bicarbonate could help reduce aminoglycoside dosage at the same time that it might help lessen the damage to auditory ciliary cells in humans. © 2015 The Society for Applied Microbiology.

Light-controlled inhibition of malignant glioma by opsin gene transfer

PubMed Central

Yang, F; Tu, J; Pan, J-Q; Luo, H-L; Liu, Y-H; Wan, J; Zhang, J; Wei, P-F; Jiang, T; Chen, Y-H; Wang, L-P

2013-01-01

Glioblastomas are aggressive cancers with low survival rates and poor prognosis because of their highly proliferative and invasive capacity. In the current study, we describe a new optogenetic strategy that selectively inhibits glioma cells through light-controlled membrane depolarization and cell death. Transfer of the engineered opsin ChETA (engineered Channelrhodopsin-2 variant) gene into primary human glioma cells or cell lines, but not normal astrocytes, unexpectedly decreased cell proliferation and increased mitochondria-dependent apoptosis, upon light stimulation. These optogenetic effects were mediated by membrane depolarization-induced reductions in cyclin expression and mitochondrial transmembrane potential. Importantly, the ChETA gene transfer and light illumination in mice significantly inhibited subcutaneous and intracranial glioma growth and increased the survival of the animals bearing the glioma. These results uncover an unexpected effect of opsin ion channels on glioma cells and offer the opportunity for the first time to treat glioma using a light-controllable optogenetic approach. PMID:24176851

Light-controlled inhibition of malignant glioma by opsin gene transfer.

PubMed

Yang, F; Tu, J; Pan, J-Q; Luo, H-L; Liu, Y-H; Wan, J; Zhang, J; Wei, P-F; Jiang, T; Chen, Y-H; Wang, L-P

2013-10-31

Glioblastomas are aggressive cancers with low survival rates and poor prognosis because of their highly proliferative and invasive capacity. In the current study, we describe a new optogenetic strategy that selectively inhibits glioma cells through light-controlled membrane depolarization and cell death. Transfer of the engineered opsin ChETA (engineered Channelrhodopsin-2 variant) gene into primary human glioma cells or cell lines, but not normal astrocytes, unexpectedly decreased cell proliferation and increased mitochondria-dependent apoptosis, upon light stimulation. These optogenetic effects were mediated by membrane depolarization-induced reductions in cyclin expression and mitochondrial transmembrane potential. Importantly, the ChETA gene transfer and light illumination in mice significantly inhibited subcutaneous and intracranial glioma growth and increased the survival of the animals bearing the glioma. These results uncover an unexpected effect of opsin ion channels on glioma cells and offer the opportunity for the first time to treat glioma using a light-controllable optogenetic approach.

Unexpected lower testosterone in faster growing farmed saltwater crocodile (Crocodylus porosus) hatchlings.

PubMed

Finger, John W; Thomson, Peter C; Isberg, Sally R

2016-01-15

Agricultural production of the saltwater crocodile (Crocodylus porosus) is an emergent industry in northern Australia with many of the factors affecting production remaining unknown. In this study, we sought to expand upon our previous findings of reference corticosterone and immune function by reporting baseline sex hormone levels [testosterone (TEST) and estradiol (ESTR)] and their association with growth. This was achieved by sampling 253 hatchling crocodiles repeatedly at 3, 6, and 9months of age. Sampling age had a significant effect on both TEST (p<0.001) and ESTR (p<0.001) suggesting climatic/abiotic factors have an influence even in prepubescent crocodiles. Stress, as measured by plasma corticosterone, had no detectable effect on plasma ESTR or TEST levels. Unexpectedly however, TEST was higher in slower-growing crocodiles, which is contrary to what has been reported for the American alligator. ESTR was not associated with growth. Copyright © 2015 Elsevier Inc. All rights reserved.

The Association of Long-term Treatment-related Side Effects With Cancer-specific and General Quality of Life Among Prostate Cancer Survivors

PubMed Central

Davis, Kimberly M.; Kelly, Scott P.; Luta, George; Tomko, Catherine; Miller, Anthony B.; Taylor, Kathryn L.

2018-01-01

OBJECTIVE To examine the association between treatment-related side effects and cancer-specific and general quality of life (QOL) among long-term prostate cancer survivors. MATERIALS AND METHODS Within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we conducted telephone interviews with prostate cancer survivors (N = 518) who were 5-10 years after diagnosis. We assessed demographic and clinical information, sexual, urinary, and bowel treatment-related side effects (Expanded Prostate Cancer Index Composite), cancer-specific QOL (Functional Assessment of Cancer Therapy—total score), and general QOL (the Medical Outcomes Study Short Form 12’s physical and mental subscales). RESULTS Participants were aged 74.6 years on average, primarily White (88.4%), and married (81.7%). Pearson correlation coefficients between the 3 treatment-related side effect domains (urinary, sexual, and bowel) and QOL ranged between 0.14 and 0.42 (P <.0001). Multivariable linear regression analyses revealed that poorer urinary and sexual functioning and greater bowel side effects were independently associated with poorer cancer-specific QOL (P <.0001). Bowel and urinary functions were also associated with poorer general QOL on the Medical Outcomes Study Short Form 12’s physical component summary and mental component summary (P <.05). Bowel side effects demonstrated the strongest association with all QOL outcomes. CONCLUSION Treatment-related side effects persisted for up to 10 years after diagnosis and continued to be associated with men’s QOL. These results suggest that each of the treatment-related side effects was independently associated with cancer-specific QOL. Compared with the other Expanded Prostate Cancer Index Composite domains, bowel side effects had the strongest association with cancer-specific and general QOL. These associations emphasize the tremendous impact that bowel side effects continue to have for men many years after their initial diagnosis. PMID:24975711

French women's knowledge of and attitudes towards cervical cancer prevention and the acceptability of HPV vaccination among those with 14 - 18 year old daughters: a quantitative-qualitative study.

PubMed

Haesebaert, Julie; Lutringer-Magnin, Delphine; Kalecinski, Julie; Barone, Giovanna; Jacquard, Anne-Carole; Régnier, Véronique; Leocmach, Yann; Vanhems, Philippe; Chauvin, Franck; Lasset, Christine

2012-11-27

In France, it is recommended that girls and women aged 14-23 are vaccinated against the human papillomavirus (HPV). However, French women's knowledge of and attitude towards the vaccine has been little studied. Thirty-nine general practitioners, representative of those working in the large Rhône-Alpes region, offered a self-administered questionnaire on cervical cancer (CC) prevention to all 18-65 year-old women who came for consultation during June and July 2008. In addition, semi-structured interviews were undertaken with a sample of those who had daughters aged 14-18. Of the 1,478 women who completed the questionnaire, only 16.9% mentioned HPV as the cause of CC, even though 76.2% knew of the vaccine. 210 women had daughters aged 14-18, and 32 were interviewed. Compared with the wider group, more of these women were aware of the HPV vaccine (91.4%). 44.8% knew the target population and 17.1% the recommended ages for vaccination. 54.3% favoured HPV vaccination; 37.2% were undecided and only 0.9% were opposed. The main barrier to acceptance was the recency of the vaccine's introduction and concern about possible side effects (54.9%); 14.1% preferred to rely on their GP's decision. Factors associated with acceptance of the HPV vaccine were having previously vaccinated a child against pneumococcus (OR=3.28 [1.32-8.11]) and knowing the target population for HPV vaccination (OR=2.12 [1.15-3.90]). Knowing the recommended frequency of Papanicolaou smear testing (Pap test) screening was associated with lower acceptance (OR=0.32 [0.13-0.82]). Few mothers are opposed to HPV vaccination. Factors associated with acceptability were knowledge about the vaccine, acceptance of other vaccines and, unexpectedly, lack of knowledge about the recommended frequency of Pap testing. On multivariate analysis, compliance with recommendations for Pap test screening and socioeconomic factors had no effect on views about HPV vaccination. Given that concern about possible side effects is the major barrier to wider acceptance of the HPV vaccine in France, GPs have a key role in providing information.

Consumer confusion between prescription drug precautions and side effects.

PubMed

Amoozegar, Jacqueline B; Rupert, Douglas J; Sullivan, Helen W; O'Donoghue, Amie C

2017-06-01

Multiple studies have identified consumers' difficulty correctly interpreting risk information provided about prescription drugs, whether in printed format or online. This study's purpose was to explore whether consumers can distinguish between prescription drug precautions and side effects presented on brand-name drug websites. Participants (n=873) viewed fictitious drug websites that presented both precautions and side effects for one of four drugs, and they completed a survey assessing recall and comprehension. We coded open-ended recall data to identify whether drug precautions were mentioned and, if so, how they were interpreted. Approximately 15% of participants mentioned at least one drug precaution. The majority (59.7%) misinterpreted precautions as potential side effects. Participants who misinterpreted precautions rated the drugs as significantly more likely to cause side effects than participants who accurately interpreted the precautions. Age, education, literacy, and other factors did not appear to predict precaution interpretation. At least some consumers are likely to interpret precautions on drug websites as potential side effects, which might affect consumer preferences, treatment decisions, and medication safety. Healthcare providers should be aware of this potential confusion, assess patients' understanding of precautions and potential side effects, and address any misunderstandings. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2003-08-01

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

Fast image decompression for telebrowsing of images

NASA Technical Reports Server (NTRS)

Miaou, Shaou-Gang; Tou, Julius T.

1993-01-01

Progressive image transmission (PIT) is often used to reduce the transmission time of an image telebrowsing system. A side effect of the PIT is the increase of computational complexity at the viewer's site. This effect is more serious in transform domain techniques than in other techniques. Recent attempts to reduce the side effect are futile as they create another side effect, namely, the discontinuous and unpleasant image build-up. Based on a practical assumption that image blocks to be inverse transformed are generally sparse, this paper presents a method to minimize both side effects simultaneously.

A potential role for adjunctive vitamin D therapy in the management of weight gain and metabolic side effects of second-generation antipsychotics

PubMed Central

Nwosu, Benjamin U.; Meltzer, Bruce; Maranda, Louise; Ciccarelli, Carol; Reynolds, Daniel; Curtis, Laura; King, Jean; Frazier, Jean A.; Lee, Mary M.

2014-01-01

Second-generation antipsychotic (SGA) medications introduced about 20 years ago are increasingly used to treat psychiatric illnesses in children and adolescents. There has been a five-fold increase in the use of these medications in U.S. children and adolescents in the past decade. However, there has also been a parallel rise in the incidence of side effects associated with these medications, such as obesity, dyslipidemia, insulin resistance, and diabetes mellitus. Despite the severity of these complications and their financial impact on the national healthcare budget, there is neither a clear understanding of the mechanisms contributing to these side effects nor the best ways to address them. Studies that examined lifestyle modification and pharmaceutical agents have yielded mixed results. Therefore, clinical studies using agents, such as vitamin D, which are inexpensive, readily available, with low side effects profile, and have mechanisms to counteract the metabolic side effects of SGA agents, are warranted. Vitamin D is a prohormone with skeletal and extraskeletal properties that could potentially reduce the severity of these metabolic side effects. Its role as an adjunctive therapy for the management of metabolic side effects of SGA agents has not been adequately studied. Effective strategies to curb these side effects will improve the overall health of youths with psychiatric illnesses who receive SGAs. Herein we present a pilot study on the use of vitamin D in patients on treatment with SGAs. PMID:22145446

Choreatic Side Effects of Deep Brain Stimulation of the Anteromedial Subthalamic Nucleus for Treatment-Resistant Obsessive-Compulsive disorder.

PubMed

Mulders, Anne E P; Leentjens, Albert F G; Schruers, Koen; Duits, Annelien; Ackermans, Linda; Temel, Yasin

2017-08-01

Patients with treatment-resistant obsessive-compulsive disorder (OCD) are potential candidates for deep brain stimulation (DBS). The anteromedial subthalamic nucleus (STN) is among the most commonly used targets for DBS in OCD. We present a patient with a 30-year history of treatment-resistant OCD who underwent anteromedial STN-DBS. Despite a clear mood-enhancing effect, stimulation caused motor side effects, including bilateral hyperkinesia, dyskinesias, and sudden large amplitude choreatic movements of arms and legs when stimulating at voltages greater than approximately 1.5 V. DBS at lower amplitudes and at other contact points failed to result in a significant reduction of obsessions and compulsions without inducing motor side effects. Because of this limitation in programming options, we decided to reoperate and target the ventral capsule/ventral striatum (VC/VS), which resulted in a substantial reduction in key obsessive and compulsive symptoms without serious side effects. Choreatic movements and hemiballismus have previously been linked to STN dysfunction and have been incidentally reported as side effects of DBS of the dorsolateral STN in Parkinson disease (PD). However, in PD, these side effects were usually transient, and they rarely interfered with DBS programming. In our patient, the motor side effects were persistent, and they made optimal DBS programming impossible. To our knowledge, such severe and persistent motor side effects have not been described previously for anteromedial STN-DBS. Copyright © 2017 Elsevier Inc. All rights reserved.

Measurement of Side Effects of Drugs

PubMed Central

Huskisson, E. C.; Wojtulewski, J. A.

1974-01-01

In a clinical trial of two antirheumatic agents two methods of collection of side effects were used, one with and the other without a check list of possible symptoms. Findings suggested that the use of a check list interfered with the collection of side effects. Known side effects of aspirin—tinnitus, deafness, and gastrointestinal disturbance—were more efficiently shown and symptoms not included in the check list were more likely to be reported when a check list was not used. PMID:4853118

[Interest of scopolamine as a treatment of major depressive disorder].

PubMed

Rigal, A; Mouchabac, S; Peretti, C S

2016-12-01

The number of patients with depression in the world is 350 millions according to estimates. The search for new treatments, particularly in forms of resistant depression, is necessary given the growing number of patients experiencing treatment failure and resistance. Scopolamine, an anticholinergic antimuscarinic molecule, is one of the treatments under evaluation. It falls within the assumptions of cholinergic disruption of the pathophysiology of depression, at different levels (genetic, receptorial [muscarinic and glutamate receptors], hormonal, synaptic…). In 2006, a pilot study made to evaluate the role of the cholinergic system in cognitive symptoms of depression found unexpected results regarding the antidepressant effect of scopolamine in depressive patients. Since that time other studies have been conducted to evaluate the benefits of treatment with intravenous injections of scopolamine. Our main objective was to evaluate the interest of scopolamine as an antidepressant treatment in depressed populations. We conducted a literature review with the aim of assessing the effectiveness of treatment with scopolamine in uni- and bipolar patients with depressive symptoms. The protocol consisted of two injection blocks (each block consisting of three injections spaced fifteen minutes apart within three to five days) of active ingredient or placebo crossover. The selected patients were between 18 and 45years and had the DSM-IV major depressive disorder or bipolar disorder criteria. Regarding the methods of measurement, the primary endpoint was the reduction in scores of the Montgomery Asberg Depression Rating Scale (MADRS) with a total response defined by a decrease of more than 50 % of the score and remission corresponding to a MADRS score<10. Seven sessions of evaluations were performed. The published results are promising in terms of efficiency with rapid antidepressant effect, a total response rate ranging from 59-64% and a remission rate of between 37 and 55% in uni- and bipolar patients, which persists at least 15days. The treatment was well tolerated by patients with relatively mild and transient side effects the most common being the sensation of sleepiness that was also found in the placebo group. There were no serious side effects such as heart failure or confusion. In terms of mood, there was no becoming manic or hypomanic even for bipolar patients. The results are encouraging, but there is concern for the moment because of the few studies, so to date there is little data on the subject including medium and long term. Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Comparison of hair removal efficacy and side effect of neodymium:Yttrium-aluminum-garnet laser and intense pulsed light systems (18-month follow-up).

PubMed

Szima, Georgina Zita; Janka, Eszter Anna; Kovács, Anikó; Bortély, Blanka; Bodnár, Edina; Sawhney, Irina; Szabó, Éva; Remenyik, Éva

2017-06-01

Photothermal destruction of hair shaft melanin with intense pulsed light (IPL) and neodymium:yttrium-aluminum-garnet (Nd:YAG) laser has become an effective treatment of hair removal. Our aim was to compare efficacy, satisfactory levels, safety, and side effects of Nd:YAG and IPL in hair reduction. This was a prospective randomized intrapatient, right-left, assessor-blinded comparison of Nd:YAG vs IPL. There were 38 volunteers recruited. Seven sessions were performed. Hair count, efficacy, and side effects were compared before and after each treatment and 6 months after the last treatment. In respect of 12 volunteers, we have examined the reduction in hair after 18 months. Initially, there was no significant difference between the numbers of hair follicles. There was significant hair reduction after each treatment on the Nd:YAG-treated side. The hair reduction became significant after the third treatment with IPL. Comparison of the efficacy of the two devices on each visits showed no significant difference. There was statistically lower pain score on the IPL-treated side and statistically higher erythema, burning sensation, and edema on the Nd:YAG-treated side. Statistically lower side effect score was observed on the IPL-treated side. Eight months after the last treatment, there was significant hair reduction both on the Nd:YAG and on the IPL-treated side, and there was no difference between the efficacy. The patient satisfaction scores were higher with the IPL. Unwanted hair can be reduced by both systems safely and effectively; however, IPL has less side effects and higher satisfaction scores. © 2017 Wiley Periodicals, Inc.

Side effects during subcutaneous immunotherapy in children with allergic diseases.

PubMed

Tophof, Max A; Hermanns, Anne; Adelt, Thomas; Eberle, Peter; Gronke, Christine; Friedrichs, Frank; Knecht, Roland; Mönter, Ernst; Schöpfer, Helmut; Schwerk, Nicolaus; Steinbach, Jörg; Umpfenbach, Hans-Ulrich; Weißhaar, Christian; Wilmsmeyer, Brigitte; Bufe, Albrecht

2018-05-01

Allergen-specific immunotherapy is the only causal form of therapy for IgE-mediated allergic diseases. Subcutaneous immunotherapy (SCIT) is considered safe and well tolerated in adults, yet there is less evidence of safety in the pediatric population. A non-interventional prospective observing longitudinal study was carried out to determine the incidence of local and systemic side effects by SCIT, routinely performed in pediatric patients. A total of 581 pediatric patients were observed in 18 study centers between March 2012 and October 2014, recording 8640 treatments and 10 015 injections. A total of 54.6% of the patients experienced immediate local side effects at least once; delayed local side effects were seen in 56.1%. Immediate systemic adverse reactions occurred in 2.2% of patients; 7.4% experienced delayed systemic side effects. However, severe systemic side effects (grade III in the classification of Ring and Messmer) were seen in 0.03% of all treatments, all appearing within 30 minutes after the injections. No grade IV reactions were observed. In addition, many potential risk factors were investigated, yet only a few were found to be associated with the occurrence of side effects. Subcutaneous immunotherapy is a safe form of therapy in pediatric patients, with similar rates of local side effects compared to adult patients and low rates of severe systemic side effects. However, local and systemic reactions occurring later than 30 minutes after injection were observed more often than expected, which makes it essential to be attentive on behalf of pediatricians, patients, and parents. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

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

PubMed

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

2017-08-01

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

Specific expectancies are associated with symptomatic outcomes and side effect burden in a trial of chamomile extract for Generalized Anxiety Disorder

PubMed Central

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

2017-01-01

Objective Patient expectancies are hypothesized to contribute to the efficacy and side effects of psychiatric treatments, but little research has investigated this hypothesis in the context of psychopharmacological therapies for anxiety. We prospectively investigated whether expectancies predicted efficacy and adverse events in oral therapy for Generalized Anxiety Disorder (GAD), controlling for confounding patient characteristics correlating with outcomes. Methods Expectancies regarding treatment efficacy and side effects were assessed at baseline of an eight week open-label phase of a trial of chamomile for Generalized Anxiety Disorder (GAD). The primary outcome was patient-reported GAD-7 scores, with clinical response and treatment-emergent side-effects as secondary outcomes. Expectancies were used to predict symptomatic and side-effect outcomes. Results Very few baseline patient characteristics predicted either type of expectancy. Controlling for a patient’s predicted recovery based on their baseline characteristics, higher efficacy expectancies at baseline predicted greater change on the GAD-7 (adjusted β = −0.19, p = 0.011). Efficacy expectancies also predicted a higher likelihood of attaining clinical response (adjusted odds ratio = 1.69, p = 0.002). Patients with higher side effect expectancies reported more side effects (adjusted log expected count = 0.26, p = 0.038). Efficacy expectancies were unrelated to side effect reports (log expected count = −0.05, p = 0.680), and side effect expectancies were unrelated to treatment efficacy (β = 0.08, p = 0.306). Conclusions Patients entering chamomile treatment for GAD with more favorable self-generated expectancies for the treatment experience greater improvement and fewer adverse events. Aligning patient expectancies with treatment selections may optimize outcomes. PMID:27716513

Distraction and Facilitation--Two Faces of the Same Coin?

ERIC Educational Resources Information Center

Wetzel, Nicole; Widmann, Andreas; Schroger, Erich

2012-01-01

Unexpected and task-irrelevant sounds can capture our attention and may cause distraction effects reflected by impaired performance in a primary task unrelated to the perturbing sound. The present auditory-visual oddball study examines the effect of the informational content of a sound on the performance in a visual discrimination task. The…

An Unexpected Effect: Restitution Maintains Object Throwing.

ERIC Educational Resources Information Center

Jensen, Mary

1988-01-01

This study examined effects of restitution on object throwing behavior of an adolescent male with severe mental retardation. Restitution was shown to maintain throwing behavior. When the subject was not forced to pick up what he threw (no restitution), throwing dropped to zero and was maintained at a very low rate. (Author/PB)

An Unexpected Heat Engine

ERIC Educational Resources Information Center

Trout, K. P.; Gaston, Charles A.

2012-01-01

It's common knowledge that light can produce chemical and electronic changes (photography is based on those effects); however, many people consider light to have no mechanical effect. Some are familiar with the novelty of a radiometer that spins when placed in the light. Fewer are aware that a cymbal will vibrate audibly if hit by the light from a…

[Extrapyramidal side-effects: avoidance, diagnosis and treatment].

PubMed

Fleischhacker, W Wolfgang; Widschwendter, Christian

2005-04-01

Acute extrapyramidal side-effects (EPS) are a common phenomenon of treatment with antipsychotics. They are associated with a substantial reduction of the patient's quality of life and of compliance with the treatment. This article gives an overview of the different forms of EPS. It outlines strategies to avoid these side-effects and discusses problems in diagnosis and treatment. In comparison to conventional compounds, the clearest advantage of new generation antipsychotics is a reduced risk of the occurrence of extrapyramidal side-effects (EPS). Many studies have found that newer antipsychotics have a lesser propensity to causes EPS. Nevertheless, there are some conflicting results on this topic. This article discusses some of these results and sheds light on methodological problems in the evaluation of side-effects of antipsychotic treatment.

Phosphorothioate backbone modifications of nucleotide-based drugs are potent platelet activators

PubMed Central

Flierl, Ulrike; Nero, Tracy L.; Lim, Bock; Arthur, Jane F.; Yao, Yu; Jung, Stephanie M.; Gitz, Eelo; Pollitt, Alice Y.; Zaldivia, Maria T.K.; Jandrot-Perrus, Martine; Schäfer, Andreas; Nieswandt, Bernhard; Andrews, Robert K.; Parker, Michael W.; Gardiner, Elizabeth E.

2015-01-01

Nucleotide-based drug candidates such as antisense oligonucleotides, aptamers, immunoreceptor-activating nucleotides, or (anti)microRNAs hold great therapeutic promise for many human diseases. Phosphorothioate (PS) backbone modification of nucleotide-based drugs is common practice to protect these promising drug candidates from rapid degradation by plasma and intracellular nucleases. Effects of the changes in physicochemical properties associated with PS modification on platelets have not been elucidated so far. Here we report the unexpected binding of PS-modified oligonucleotides to platelets eliciting strong platelet activation, signaling, reactive oxygen species generation, adhesion, spreading, aggregation, and thrombus formation in vitro and in vivo. Mechanistically, the platelet-specific receptor glycoprotein VI (GPVI) mediates these platelet-activating effects. Notably, platelets from GPVI function–deficient patients do not exhibit binding of PS-modified oligonucleotides, and platelet activation is fully abolished. Our data demonstrate a novel, unexpected, PS backbone–dependent, platelet-activating effect of nucleotide-based drug candidates mediated by GPVI. This unforeseen effect should be considered in the ongoing development programs for the broad range of upcoming and promising DNA/RNA therapeutics. PMID:25646267

3 CFR - Unexpected Urgent Refugee and Migration Needs Relating to Syria

Code of Federal Regulations, 2014 CFR

2014-01-01

... 3 The President 1 2014-01-01 2014-01-01 false Unexpected Urgent Refugee and Migration Needs Relating to Syria Presidential Documents Other Presidential Documents Presidential Determination No. 2013-4 of January 29, 2013 Unexpected Urgent Refugee and Migration Needs Relating to Syria Memorandum for the Secretary of State By the authority vested i...

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to Libya

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Unexpected Urgent Refugee and Migration Needs Related to Libya Presidential Documents Other Presidential Documents Presidential Determination No. 2011-8 of March 7, 2011 Unexpected Urgent Refugee and Migration Needs Related to Libya Memorandum for the Secretary of State By the authority vested in me...

3 CFR - Unexpected Urgent Refugee and Migration Needs Resulting from Flooding in Pakistan

Code of Federal Regulations, 2011 CFR

2011-01-01

... 3 The President 1 2011-01-01 2011-01-01 false Unexpected Urgent Refugee and Migration Needs... Determination No. 2010-14 of September 3, 2010 Unexpected Urgent Refugee and Migration Needs Resulting from... the Constitution and the laws of the United States, including section 2(c)(1) of the Migration and...

3 CFR - Unexpected Urgent Refugee and Migration Needs Resulting from Violence in Kyrgyzstan

Code of Federal Regulations, 2011 CFR

2011-01-01

... 3 The President 1 2011-01-01 2011-01-01 false Unexpected Urgent Refugee and Migration Needs... Determination No. 2010-12 of August 26, 2010 Unexpected Urgent Refugee and Migration Needs Resulting from... the Constitution and the laws of the United States, including section 2(c)(1) of the Migration and...

Effects of anxiety sensitivity and expectations on the modulation of the startle eyeblink response during a caffeine challenge.

PubMed

Benke, Christoph; Blumenthal, Terry D; Modeß, Christiane; Hamm, Alfons O; Pané-Farré, Christiane A

2015-09-01

The way in which the tendency to fear somatic arousal sensations (anxiety sensitivity), in interaction with the created expectations regarding arousal induction, might affect defensive responding to a symptom provocation challenge is not yet understood. The present study investigated the effect of anxiety sensitivity on autonomic arousal, startle eyeblink responses, and reported arousal and alertness to expected vs. unexpected caffeine consumption. To create a match/mismatch of expected and experienced arousal, high and low anxiety sensitive participants received caffeine vs. no drug either mixed in coffee (expectation of arousal induction) or in bitter lemon soda (no expectation of arousal induction) on four separate occasions. Autonomic arousal (heart rate, skin conductance level), respiration (end-tidal CO2, minute ventilation), defensive reflex responses (startle eyeblink), and reported arousal and alertness were recorded prior to, immediately and 30 min after beverage ingestion. Caffeine increased ventilation, autonomic arousal, and startle response magnitudes. Both groups showed comparable levels of autonomic and respiratory responses. The startle eyeblink responses were decreased when caffeine-induced arousal occurred unexpectedly, e.g., after administering caffeine in bitter lemon. This effect was more accentuated in high anxiety sensitive persons. Moreover, in high anxiety sensitive persons, the expectation of arousal (coffee consumption) led to higher subjective alertness when administering caffeine and increased arousal even if no drug was consumed. Unexpected symptom provocation leads to increased attention allocation toward feared arousal sensations in high anxiety sensitive persons. This finding broadens our understanding of modulatory mechanisms in defensive responding to bodily symptoms.

Adaptation of muscles of the lumbar spine to sudden imbalance in patients with lower back pain caused by military training.

PubMed

Gao, Ying; Shi, Jian-guo; Ye, Hong; Liu, Zhi-rong; Zheng, Long-bao; Ni, Zhi-ming; Fan, Liang-quan; Wang, Jian; Hou, Zhen-hai

2014-11-01

This study aims to investigate the effects of sudden load changes (expected and unexpected imbalance) on the activity of muscles of the lumbar spine and their central motor control strategy in military personnel with or without chronic low back pain (LBP). Bilateral sudden imbalance was examined (2 × 2 factorial design). The 117th PLA Hospital, Hangzhou, China Twenty-one male subjects with lower back pain and 21 male healthy control subjects were active members of the Nanjing Military Region land forces. Independent variables: LBP vs. healthy controls and imbalance anticipation (expected and unexpected imbalance). rapid reaction time (RRT) and intensity of rapid reaction (IRR) of bilateral lumbar (L3-L4) erector spinae (ES), lumbar (L5-S1) multifidus (MF), and abdominal external oblique muscles. Results Under expected or unexpected sudden imbalance conditions, subjects with LBP demonstrated significantly greater IRR than healthy controls in ipsilateral and contralateral ES and MF, respectively (P < 0.05 for all). IRR of contralateral ES was significantly larger than that of the ipsilateral ES. A significant group effect of RRT of both ipsilateral and contralateral ES muscles and a significant time expectation effect on RRT of contralateral MF muscles were also observed. RRT of the contralateral ES muscles was significantly lower than that of the ipsilateral ES muscles (P < 0.001). Sudden imbalance prolonged RRT of selected trunk muscles in patients with chronic LBP. The activation amplitude increased. The results may provide a theoretical basis for a study on the pathogenesis of chronic LBP.

Unexpectedly increased anorexigenic postprandial responses of PYY and GLP-1 to fast ice cream consumption in adult patients with Prader-Willi syndrome.

PubMed

Rigamonti, A E; Bini, S; Grugni, G; Agosti, F; De Col, A; Mallone, M; Cella, S G; Sartorio, A

2014-10-01

The effect of eating rate on the release of anorexigenic gut peptides in Prader-Willi syndrome (PWS), a neurogenetic disorder clinically characterized by hyperphagia and excessive obesity, has not been investigated so far. Postprandial PYY and GLP-1 levels to fast (5 min) and slow (30 min) ice cream consumption were measured in PWS adult patients and age-matched patients with simple obesity and normal-weighted subjects. Visual analog scales (VASs) were used to evaluate the subjective feelings of hunger and satiety. Fast ice cream consumption stimulated GLP-1 release in normal subjects, a greater increase being observed with slow feeding. Fast or slow feeding did not change circulating levels of GLP-1 in obese patients, while, unexpectedly, fast feeding (but not slow feeding) stimulated GLP-1 release in PWS patients. Plasma PYY concentrations increased in all groups, irrespective of the eating rate. Slow feeding was more effective in stimulating PYY release in normal subjects, while fast feeding was more effective in PWS patients. Slow feeding evoked a lower hunger and higher satiety compared with fast feeding in normal subjects, this finding being not evident in obese patients. Unexpectedly, fast feeding evoked a lower hunger and higher satiety in PWS patients in comparison with slow feeding. Fast feeding leads to higher concentrations of anorexigenic gut peptides and favours satiety in PWS adult patients, this pattern being not evident in age-matched patients with simple obesity, thus suggesting the existence of a different pathophysiological substrate in these two clinical conditions. © 2013 John Wiley & Sons Ltd.

Anxiety sensitivity and expectation of arousal differentially affect the respiratory response to caffeine.

PubMed

Pané-Farré, Christiane A; Alius, Manuela G; Modeß, Christiane; Methling, Karen; Blumenthal, Terry; Hamm, Alfons O

2015-06-01

This study aimed to test how expectations and anxiety sensitivity influence respiratory and autonomic responses to caffeine. The current study investigated the effects of expected vs. unexpected caffeine ingestion in a group of persons prone to the anxiety-provoking effect of caffeine (high anxiety sensitive persons, that is, persons scoring at least one SD above the mean on the Anxiety Sensitivity Index (Peterson and Reiss 1992)) as compared to low-anxious controls. Autonomic arousal (heart rate, skin conductance level), respiratory responding (expired CO2, minute ventilation), and subjective report were assessed in high and low anxiety sensitive participants immediately after beverage consumption and at absorption peak (30 min post-consumption) in four separate sessions during which either coffee (expectation of caffeine) or bitter lemon soda (no expectation of caffeine) was crossed with 4 mg/kg caffeine vs. no drug. High and low anxiety sensitive persons showed comparable autonomic arousal and symptom reports to caffeine which was modulated by expectation, i.e., greater for coffee. Respiratory responding (CO2 decrease, minute ventilation increase) was more accentuated when caffeine was both expected and administered in the low anxiety sensitive group but more accentuated when caffeine was unexpectedly administered in the high anxiety sensitive group. Autonomic arousal and respiratory effects were observable within a few minutes after caffeine administration and were most pronounced at maximum absorption. The results highlight the modulating role of expectancies in respiratory responding to caffeine in low vs. high anxiety sensitive persons and might have important implications for the better understanding of unexpected panic attacks.

Oral health impacts of medications used to treat mental illness.

PubMed

Cockburn, N; Pradhan, A; Taing, M W; Kisely, S; Ford, P J

2017-12-01

Many psychotropic medications affect oral health. This review identified oral side effects for antidepressant, antipsychotic, anticonvulsant, antianxiety and sedative drugs that are recommended in Australia for the management of common mental illnesses and provides recommendations to manage these side-effects. The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat common mental health conditions. For each medication, the generic name, class, and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (eMIMs) and UpToDate databases. Meyler's Side Effect of Drugs Encyclopaedia was used to identify additional oral adverse reactions to these medications. Fifty-seven drugs were identified: 23 antidepressants, 22 antipsychotics or mood stabilisers, and 12 anxiolytic or sedative medications. Xerostomia (91%) the most commonly reported side effect among all classes of medications of the 28 identified symptoms. Other commonly reported adverse effects included dysguesia (65%) for antidepressants, and tardive dyskinesia (94%) or increased salivation (78%) for antipsychotic medications. While xerostomia has often been reported as a common adverse effect of psychotropic drugs, this review has identified additional side effects including dysguesia from antidepressants and tardive dyskinesia and increased salivation from antipsychotics. Clinicians should consider oral consequences of psychotropic medication in addition to other side-effects when prescribing. For antidepressants, this would mean choosing duloxetine, agomelatine and any of the serotonin re-uptake inhibitors except sertraline. In the case of antipsychotics and mood stabilisers, atypical agents have less oral side effects than older alternatives. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed Central

2011-01-01

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

Impact of present and past antipsychotic side effects on attitude toward typical antipsychotic treatment and adherence.

PubMed

Lambert, M; Conus, P; Eide, P; Mass, R; Karow, A; Moritz, S; Golks, D; Naber, D

2004-11-01

(1) determine which antipsychotic side effects (SE) schizophrenic patients consider the most distressing during treatment with typical antipsychotics, (2) measure the impact of actual and past SE on patients' attitude toward antipsychotics and (3) assess the influence of both on adherence. The 213 schizophrenics, treated with conventional antipsychotics, were recruited in two psychiatric hospitals in Hamburg. Subjects were assessed about type and severity of present and past side effects and their attitude and adherence to antipsychotic treatment. The 82 (39%) patients presented present SE while 131 (61%) did not. Sexual dysfunctions (P < 0.001), extrapyramidal (P < 0.05) and psychic side effects (P < 0.05) were rated as significantly subjectively more distressing than sedation or vegetative side effects. Patients presenting with present SE compared with patients without present SE had a significantly more negative general attitude toward antipsychotics (P < 0.05), were more doubtful about their efficacy (P < 0.01) and were less likely to encourage a relative to take such a medication in case of need (P < 0.001). A regression analysis indicated that nonadherence was mainly influenced by negative general and efficacy attitudes toward antipsychotics and the experience of past or present antipsychotic side effects. All antipsychotic side effects, present or past, can have a durable negative impact on patient's attitude toward antipsychotic treatment and adherence. Non-adherence is mainly determined, among other factors, by these negative attitudes, which are partly influenced by the experience of past or present antipsychotic-induced side effects.

Should I stay or should I go? Attentional disengagement from visually unique and unexpected items at fixation.

PubMed

Brockmole, James R; Boot, Walter R

2009-06-01

Distinctive aspects of a scene can capture attention even when they are irrelevant to one's goals. The authors address whether visually unique, unexpected, but task-irrelevant features also tend to hold attention. Observers searched through displays in which the color of each item was irrelevant. At the start of search, all objects changed color. Critically, the foveated item changed to an unexpected color (it was novel), became a color singleton (it was unique), or both. Saccade latency revealed the time required to disengage overt attention from this object. Singletons resulted in longer latencies, but only if they were unexpected. Conversely, unexpected items only delayed disengagement if they were singletons. Thus, the time spent overtly attending to an object is determined, at least in part, by task-irrelevant stimulus properties, but this depends on the confluence of expectation and visual salience. (c) 2009 APA, all rights reserved.

Reflections on a Time-Limited Mother-Baby Yoga Program at the Wee Ones Nursery

ERIC Educational Resources Information Center

Pickholtz, Naomi

2012-01-01

This brief article discusses a yoga program offered to mothers and babies who were participating in a prison nursery. The author describes the goals and the sometimes unexpected effects of the program.

Dose escalation pharmacokinetics of intranasal scopolamine gel formulation.

PubMed

Wu, Lei; Boyd, Jason L; Daniels, Vernie; Wang, Zuwei; Chow, Diana S-L; Putcha, Lakshmi

2015-02-01

Astronauts experience Space Motion Sickness requiring treatment with an anti-motion sickness medication, scopolamine during space missions. Bioavailability after oral administration of scopolamine is low and variable, and absorption form transdermal patch is slow and prolonged. Intranasal administration achieves faster absorption and higher bioavailability of drugs that are subject to extrahepatic, first pass metabolism after oral dosing. We examined pharmacokinetics of 0.1, 0.2, and 0.4 mg doses of the Investigational New Drug formulation of intranasal scopolamine gel (INSCOP) in 12 healthy subjects using a randomized, double-blind cross-over study design. Subjects received one squirt of 0.1 g of gel containing either 0.1 mg or 0.2 mg/0.1 mL scopolamine or placebo in each nostril. Serial blood samples and total urine voids were collected after dosing and drug concentrations were determined using a modified LC-MS-MS method. Results indicate dose-linear pharmacokinetics of scopolamine with linear increases in Cmax and AUC within the dose range tested. Plasma drug concentrations were significantly lower in females than in males after administration of 0.4 dose. All three doses were well tolerated with no unexpected or serious adverse side effects reported. These results suggest that intranasal scopolamine gel formulation (INSCOP) offers a fast, reliable, and safe alternative for the treatment of motion sickness. © 2014, The American College of Clinical Pharmacology.

Retinal S-opsin dominance in Ansell's mole-rats (Fukomys anselli) is a consequence of naturally low serum thyroxine.

PubMed

Henning, Yoshiyuki; Mladěnková, Nella; Burda, Hynek; Szafranski, Karol; Begall, Sabine

2018-03-12

Mammals usually possess a majority of medium-wavelength sensitive (M-) and a minority of short-wavelength sensitive (S-) opsins in the retina, enabling dichromatic vision. Unexpectedly, subterranean rodents from the genus Fukomys exhibit an S-opsin majority, which is exceptional among mammals, albeit with no apparent adaptive value. Because thyroid hormones (THs) are pivotal for M-opsin expression and metabolic rate regulation, we have, for the first time, manipulated TH levels in the Ansell's mole-rat (Fukomys anselli) using osmotic pumps. In Ansell's mole-rats, the TH thyroxine (T4) is naturally low, likely as an adaptation to the harsh subterranean ecological conditions by keeping resting metabolic rate (RMR) low. We measured gene expression levels in the eye, RMR, and body mass (BM) in TH-treated animals. T4 treatment increased both, S- and M-opsin expression, albeit M-opsin expression at a higher degree. However, this plasticity was only given in animals up to approximately 2.5 years. Mass-specific RMR was not affected following T4 treatment, although BM decreased. Furthermore, the T4 inactivation rate is naturally higher in F. anselli compared to laboratory rodents. This is the first experimental evidence that the S-opsin majority in Ansell's mole-rats is a side effect of low T4, which is downregulated to keep RMR low.

Dopamine agonist therapy in low-response children following traumatic brain injury.

PubMed

Patrick, Peter D; Blackman, James A; Mabry, Jennifer L; Buck, Marcia L; Gurka, Matthew J; Conaway, Mark R

2006-10-01

The objective of this study was to determine whether a dopamine agonist could improve mental status among children in a low-response state following traumatic brain injury. In an 8-week, prospective, double-blind, randomized trial, 10 children and adolescents ages 8 to 21 years (X = 16.7 years) with traumatic brain injury sustained at least 1 month previously and remaining in a low-response state (Rancho Los Amigos Scale level pound 3) received pramipexole or amantadine. Medication dosage was increased over 4 weeks, weaned over 2 weeks, and then discontinued. At baseline and weekly during the study, subjects were evaluated with the Coma Near Coma Scale, Western NeuroSensory Stimulation Profile, and Disability Rating Scale. Scores improved significantly from baseline to the medication phase on the Coma Near Coma Scale, Western NeuroSensory Stimulation Profile, and Disability Rating Scale (P < .005). The weekly rate of change was significantly better for all three measures on medication than off medication (P < .05). Rancho Los Amigos Scale levels improved significantly on medication as well (P < .05). There was no difference in efficacy between amantadine and pramipexole. No unexpected or significant side effects were observed with either drug. This clinical trial supports the benefit of two dopamine agonists in the restoration of functional arousal, awareness, and communication. These drugs can be helpful in accelerating eligibility for acute rehabilitation among children and adolescents who have sustained significant brain injuries.

Development of (6R)-2-Nitro-6-[4-(trifluoromethoxy)phenoxy]-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (DNDI-8219): A New Lead for Visceral Leishmaniasis

PubMed Central

2018-01-01

Discovery of the potent antileishmanial effects of antitubercular 6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazoles and 7-substituted 2-nitro-5,6-dihydroimidazo[2,1-b][1,3]oxazines stimulated the examination of further scaffolds (e.g., 2-nitro-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]oxazepines), but the results for these seemed less attractive. Following the screening of a 900-compound pretomanid analogue library, several hits with more suitable potency, solubility, and microsomal stability were identified, and the superior efficacy of newly synthesized 6R enantiomers with phenylpyridine-based side chains was established through head-to-head assessments in a Leishmania donovani mouse model. Two such leads (R-84 and R-89) displayed promising activity in the more stringent Leishmania infantum hamster model but were unexpectedly found to be potent inhibitors of hERG. An extensive structure–activity relationship investigation pinpointed two compounds (R-6 and pyridine R-136) with better solubility and pharmacokinetic properties that also provided excellent oral efficacy in the same hamster model (>97% parasite clearance at 25 mg/kg, twice daily) and exhibited minimal hERG inhibition. Additional profiling earmarked R-6 as the favored backup development candidate. PMID:29461823

CCC meets ICU: redefining the role of critical care of cancer patients.

PubMed

von Bergwelt-Baildon, Michael; Hallek, Michael J; Shimabukuro-Vornhagen, Alexander A; Kochanek, Matthias

2010-11-08

Currently the majority of cancer patients are considered ineligible for intensive care treatment and oncologists are struggling to get their patients admitted to intensive care units. Critical care and oncology are frequently two separate worlds that communicate rarely and thus do not share novel developments in their fields. However, cancer medicine is rapidly improving and cancer is eventually becoming a chronic disease. Oncology is therefore characterized by a growing number of older and medically unfit patients that receive numerous novel drug classes with unexpected side effects. All of these changes will generate more medically challenging patients in acute distress that need to be considered for intensive care. An intense exchange between intensivists, oncologists, psychologists and palliative care specialists is warranted to communicate the developments in each field in order to improve triage and patient treatment. Here, we argue that "critical care of cancer patients" needs to be recognized as a medical subspecialty and that there is an urgent need to develop it systematically. As prognosis of cancer improves, novel therapeutic concepts are being introduced and more and more older cancer patients receive full treatment the number of acutely ill patients is growing significantly. This development a major challenge to current concepts of intensive care and it needs to be redefined who of these patients should be treated, for how long and how intensively.

Blood RNA biomarker panel detects both left- and right-sided colorectal neoplasms: a case-control study.

PubMed

Chao, Samuel; Ying, Jay; Liew, Gailina; Marshall, Wayne; Liew, Choong-Chin; Burakoff, Robert

2013-07-23

Colonoscopy is widely regarded to be the gold standard for colorectal cancer (CRC) detection. Recent studies, however, suggest that the effectiveness of colonoscopy is mostly confined to tumors on the left side of the colon (descending, sigmoid, rectum), and that the technology has poor tumor detection for right-sided (cecum, ascending, transverse) lesions. A minimally invasive test that can detect both left-sided and right-sided lesions could increase the effectiveness of screening colonoscopy by revealing the potential presence of neoplasms in the right-sided "blind spot". We previously reported on a seven-gene, blood-based biomarker panel that effectively stratifies a patient's risk of having CRC. For the current study, we assessed the effectiveness of the seven-gene panel for the detection of left- and right-sided CRC lesions. Results were evaluated for 314 patients with CRC (left-sided: TNM I, 65; TNM II, 57; TNM III, 60; TNM IV, 17; unknown, 9. right-sided: TNM I, 28; TNM II, 29; TNM III, 38; TNM IV, 12; unknown, 1 and including two samples with both left and right lesions) and 328 control samples. Blood samples were obtained prior to clinical staging and therapy. Most CRC subjects had localized disease (stages I and II, 58%); regional (stage III) and systemic (stage IV) disease represented 32% and 9%, respectively, of the study population. The panel detected left-sided (74%, 154/208) and right-sided (85%, 92/108) lesions with an overall sensitivity of 78% (215/316) at a specificity of 66% (215/328). Treatable cancer (stages I to III) was detected with left-sided lesion sensitivity of 76% (138/182) and right-sided sensitivity of 84% (80/95). This seven-gene biomarker panel detected right-sided CRC lesions across all cancer stages with a sensitivity that is at least equal to that for left-sided lesions. This study supports the use of this panel as the basis for a patient-friendly, blood-based test that can be easily incorporated into a routine physical examination in advance of colonoscopy to provide a convenient companion diagnostic and a pre-screening alert, ultimately leading to enhanced CRC screening effectiveness.

Psychiatric side effects of antihypertensive drugs other than reserpine.

PubMed

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

1982-02-01

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

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

PubMed

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

2017-06-01

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

Enquiry into the Side Effects of School Inspection in a "Low-Stakes" Inspection Context

ERIC Educational Resources Information Center

Penninckx, Maarten; Vanhoof, Jan; De Maeyer, Sven; Van Petegem, Peter

2016-01-01

This article describes a qualitative study into the occurrence of the side effects of school inspection through in-depth interviews in five case schools. The study investigates the extent to which strategic activities, disturbing effects and emotional side effects occur in the case schools. The study also aims to understand features that may…

Inferring protein domains associated with drug side effects based on drug-target interaction network.

PubMed

Iwata, Hiroaki; Mizutani, Sayaka; Tabei, Yasuo; Kotera, Masaaki; Goto, Susumu; Yamanishi, Yoshihiro

2013-01-01

Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions. In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, which we call "pharmacogenomic features," based on the drug-target interaction network. We detect drug side effects and protein domains that appear jointly in known drug-target interactions, which is made possible by using classifiers with sparse models. It is shown that the inferred pharmacogenomic features can be used for predicting potential drug-target interactions. We also discuss advantages and limitations of the pharmacogenomic features, compared with the chemogenomic features that are the associations between drug chemical substructures and protein domains. The inferred side effect-domain association network is expected to be useful for estimating common drug side effects for different protein families and characteristic drug side effects for specific protein domains.

Vedolizumab is an effective alternative in inflammatory bowel disease patients with anti-TNF-alpha therapy-induced dermatological side effects.

PubMed

Pijls, Philippe A R R; Gilissen, Lennard P L

2016-11-01

The treatment of patients with inflammatory bowel diseases has been revolutionized by the introduction of biological therapy with TNF-alpha blockers. However, TNF-alpha blockers are also associated with a wide variety of dermatological side effects, such as local skin infections, psoriasis and eczema. A new biological therapy, targeting the gut-specific adhesion molecule alpha4beta7 integrin, is the humanized monoclonal IgG1 antibody vedolizumab. Vedolizumab prevents leukocyte migration to the gastrointestinal tract, thereby reducing inflammation. This gut-specific therapy has the potential to reduce systemic side effects, including dermatological ones. We describe 3 inflammatory bowel disease patients who experience anti-TNF-alpha therapy-induced dermatological side effects, consisting of hidradenitis suppurativa, a folliculitis, scalp psoriasis and a dissecting folliculitis. In all patients, anti-TNF-alpha therapy-induced dermatological side effects diminished after switching to vedolizumab. Vedolizumab may be a viable alternative biological therapy in inflammatory bowel disease patients who experience anti-TNF-alpha therapy-induced dermatological side effects. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Experimental Study of Wake / Flap Interaction Noise and the Reduction of Flap Side Edge Noise

NASA Technical Reports Server (NTRS)

Hutcheson, Florence V.; Stead, Daniel J.; Plassman, Gerald E.

2016-01-01

The effects of the interaction of a wake with a half-span flap on radiated noise are examined. The incident wake is generated by bars of various widths and lengths or by a simplified landing gear model. Single microphone and phased array measurements are used to isolate the effects of the wake interaction on the noise radiating from the flap side edge and flap cove regions. The effects on noise of the wake generator's geometry and relative placement with respect to the flap are assessed. Placement of the wake generators upstream of the flap side edge is shown to lead to the reduction of flap side edge noise by introducing a velocity deficit and likely altering the instabilities in the flap side edge vortex system. Significant reduction in flap side edge noise is achieved with a bar positioned directly upstream of the flap side edge. The noise reduction benefit is seen to improve with increased bar width, length and proximity to the flap edge. Positioning of the landing gear model upstream of the flap side edge also leads to decreased flap side edge noise. In addition, flap cove noise levels are significantly lower than when the landing gear is positioned upstream of the flap mid-span. The impact of the local flow velocity on the noise radiating directly from the landing gear is discussed. The effects of the landing gear side-braces on flap side edge, flap cove and landing gear noise are shown.

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to Cote d'Ivoire

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Unexpected Urgent Refugee and Migration Needs Related to Cote d'Ivoire Presidential Documents Other Presidential Documents Presidential Determination No. 2011-7 of March 7, 2011 Unexpected Urgent Refugee and Migration Needs Related to Cote d'Ivoire Memorandum for the Secretary of State By the...

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to the Horn of Africa

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Unexpected Urgent Refugee and Migration Needs Related to the Horn of Africa Presidential Documents Other Presidential Documents Presidential Determination No. 2011-12 of August 8, 2011 Unexpected Urgent Refugee and Migration Needs Related to the Horn of Africa Memorandum for the Secretary of State By...

3 CFR - Unexpected Urgent Refugee and Migration Needs Related to Somalia and Food Pipeline Breaks for...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 3 The President 1 2011-01-01 2011-01-01 false Unexpected Urgent Refugee and Migration Needs... 8, 2010 Unexpected Urgent Refugee and Migration Needs Related to Somalia and Food Pipeline Breaks... section 2(c)(1) of the Migration and Refugee Assistance Act of 1962 (the “Act”), as amended, (22 U.S.C...

Investigating Teachers' Appraisal of Unexpected Moments and Underlying Values: An Exploratory Case in the Context of Changing Mathematics Classroom Discourse

ERIC Educational Resources Information Center

Cavanna, Jillian M.; Herbel-Eisenmann, Beth; Seah, Wee Tiong

2015-01-01

This article provides an exploratory case study that examines what one teacher indicated as unexpected as she worked to become more purposeful about her classroom discourse practices. We found that she highlighted three areas as being unexpected: (1) aspects of lesson enactment; (2) characteristics of student learning and (3) her own…

The detection of faked identity using unexpected questions and mouse dynamics.

PubMed

Monaro, Merylin; Gamberini, Luciano; Sartori, Giuseppe

2017-01-01

The detection of faked identities is a major problem in security. Current memory-detection techniques cannot be used as they require prior knowledge of the respondent's true identity. Here, we report a novel technique for detecting faked identities based on the use of unexpected questions that may be used to check the respondent identity without any prior autobiographical information. While truth-tellers respond automatically to unexpected questions, liars have to "build" and verify their responses. This lack of automaticity is reflected in the mouse movements used to record the responses as well as in the number of errors. Responses to unexpected questions are compared to responses to expected and control questions (i.e., questions to which a liar also must respond truthfully). Parameters that encode mouse movement were analyzed using machine learning classifiers and the results indicate that the mouse trajectories and errors on unexpected questions efficiently distinguish liars from truth-tellers. Furthermore, we showed that liars may be identified also when they are responding truthfully. Unexpected questions combined with the analysis of mouse movement may efficiently spot participants with faked identities without the need for any prior information on the examinee.

Antipsychotic Drug Side Effects for Persons with Intellectual Disability

ERIC Educational Resources Information Center

Matson, Johnny L.; Mahan, Sara

2010-01-01

Antipsychotic drugs are the most frequently prescribed of the psychotropic drugs among the intellectually disabled (ID) population. Given their widespread use, efforts to systematically assess and report side effects are warranted. Specific scaling methods such as the "Matson Evaluation of Side Effects" ("MEDS"), the "Abnormal Inventory Movement…

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

PubMed Central

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

2014-01-01

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

CHECKPOINT INHIBITOR IMMUNE THERAPY: Systemic Indications and Ophthalmic Side Effects.

PubMed

Dalvin, Lauren A; Shields, Carol L; Orloff, Marlana; Sato, Takami; Shields, Jerry A

2018-06-01

To review immune checkpoint inhibitor indications and ophthalmic side effects. A literature review was performed using a PubMed search for publications between 1990 and 2017. Immune checkpoint inhibitors are designed to treat system malignancies by targeting one of three ligands, leading to T-cell activation for attack against malignant cells. These ligands (and targeted drug) include cytotoxic T-lymphocyte antigen-4 (CTLA-4, ipilimumab), programmed death protein 1 (PD-1, pembrolizumab, nivolumab), and programmed death ligand-1 (PD-L1, atezolizumab, avelumab, durvalumab). These medications upregulate the immune system and cause autoimmune-like side effects. Ophthalmic side effects most frequently manifest as uveitis (1%) and dry eye (1-24%). Other side effects include myasthenia gravis (n = 19 reports), inflammatory orbitopathy (n = 11), keratitis (n = 3), cranial nerve palsy (n = 3), optic neuropathy (n = 2), serous retinal detachment (n = 2), extraocular muscle myopathy (n = 1), atypical chorioretinal lesions (n = 1), immune retinopathy (n = 1), and neuroretinitis (n = 1). Most inflammatory side effects are managed with topical or periocular corticosteroids, but advanced cases require systemic corticosteroids and cessation of checkpoint inhibitor therapy. Checkpoint inhibitors enhance the immune system by releasing inhibition on T cells, with risk of autoimmune-like side effects. Ophthalmologists should include immune-related adverse events in their differential when examining cancer patients with new ocular symptoms.

Body-drug assemblages: theorizing the experience of side effects in the context of HIV treatment.

PubMed

Gagnon, Marilou; Holmes, Dave

2016-10-01

Each of the antiretroviral drugs that are currently used to stop the progression of HIV infection causes its own specific side effects. Despite the expansion, multiplication, and simplification of treatment options over the past decade, side effects continue to affect people living with HIV. Yet, we see a clear disconnect between the way side effects are normalized, routinized, and framed in clinical practice and the way they are experienced by people living with HIV. This paper builds on the premise that new approaches are needed to understand side effects in a manner that is more reflective of the subjective accounts of people living with HIV. Drawing on the work of Deleuze and Guattari, it offers an original application of the theory of 'assemblage'. This theory offers a new way of theorizing side effects, and ultimately the relationship between the body and antiretroviral drugs (as technologies). Combining theory with examples derived from empirical data, we examine the multiple ways in which the body connects not only to the drugs but also to people, things, and systems. Our objective is to illustrate how this theory dares us to think differently about side effects and allows us to originally (re)think the experience of taking antiretroviral drugs. © 2016 The Authors. Nursing Philosophy Published by John Wiley & Sons Ltd.

Cost-effectiveness of screening women with familial risk for breast cancer with magnetic resonance imaging.

PubMed

Saadatmand, Sepideh; Tilanus-Linthorst, Madeleine M A; Rutgers, Emiel J T; Hoogerbrugge, Nicoline; Oosterwijk, Jan C; Tollenaar, Rob A E M; Hooning, Maartje; Loo, Claudette E; Obdeijn, Inge-Marie; Heijnsdijk, Eveline A M; de Koning, Harry J

2013-09-04

To reduce mortality, women with a family history of breast cancer are often screened with mammography before age 50 years. Additional magnetic resonance imaging (MRI) improves sensitivity and is cost-effective for BRCA1/2 mutation carriers. However, for women with a family history without a proven mutation, cost-effectiveness is unclear. We evaluated data of the largest prospective MRI screening study (MRISC). Between 1999 and 2007, 1597 women (8370 woman-years at risk) aged 25 to 70 years with an estimated cumulative lifetime risk of 15% to 50% for breast cancer were screened with clinical breast examination every 6 months and with annual mammography and MRI. We calculated the cost per detected and treated breast cancer. After incorporating MRISC data into a microsimulation screening analysis model (MISCAN), different schemes were evaluated, and cost per life-year gained (LYG) was estimated in comparison with the Dutch nationwide breast cancer screening program (biennial mammography from age 50 to 75 years). All statistical tests were two-sided. Forty-seven breast cancers (9 ductal carcinoma in situ) were detected. Screening with additional MRI costs $123 672 (€93 639) per detected breast cancer. In increasing age-cohorts, costs per detected and treated breast cancer decreased, but, unexpectedly, the percentage of MRI-only detected cancers increased. Screening under the MRISC-scheme from age 35 to 50 years was estimated to reduce breast cancer mortality by 25% at $134 932 (€102 164) per LYG (3.5% discounting) compared with 17% mortality reduction at $54 665 (€41 390) per LYG with mammography only. Screening with MRI may improve survival for women with familial risk for breast cancer but is expensive, especially in the youngest age categories.

Salinity-dependent in vitro effects of homologous natriuretic peptides on the pituitary-interrenal axis in eels.

PubMed

Ventura, Albert; Kusakabe, Makoto; Takei, Yoshio

2011-08-01

We examined the effects of atrial, B-type, ventricular and C-type natriuretic peptides (ANP, BNP, VNP and CNP1, 3, 4) on cortisol secretion from interrenal tissue in vitro in both freshwater (FW) and seawater (SW)-acclimated eels. We first localized the interrenal and chromaffin cells in the eel head kidney using cell specific markers (cholesterol side-chain cleavage enzyme (P450ssc) and tyrosine hydroxylase (TH), respectively) and established the in vitro incubation system for eel interrenal tissue. Unexpectedly, none of the NPs given alone to the interrenal tissue of FW and SW eels stimulated cortisol secretion. However, ANP and VNP, but not BNP and three CNPs, enhanced the steroidogenic action of ACTH in SW interrenal preparations, while CNP1 and CNP4, but not ANP, BNP, VNP and CNP3, potentiated the ACTH action in FW preparations. These salinity dependent effects of NPs are consistent with the previous in vivo study in the eel where endogenous ACTH can act with the injected NPs. 8-Br-cGMP also enhanced the ACTH action in both FW and SW eel preparations, suggesting that the NP actions were mediated by the guanylyl cyclase-coupled NP receptors (GC-A and B) that were localized in the eel interrenal. Further, ANP and CNP1 stimulated ACTH secretion from isolated pituitary glands of SW and/or FW eels. In summary, the present study revealed complex mechanisms of NP action on corticosteroidogenesis through the pituitary-interrenal axis in eels, thereby providing a deeper insight into the role of the NP family in the acclimation of this euryhaline teleost to diverse salinity environments. Copyright © 2011 Elsevier Inc. All rights reserved.

Antiepileptic treatment in paediatric oncology--an interdisciplinary challenge.

PubMed

Tibussek, D; Distelmaier, F; Schönberger, S; Göbel, U; Mayatepek, E

2006-01-01

Epileptic seizures are a common and clinically relevant problem in paediatric oncology. Attributable to the heterogeneity of this group of patients and a number of possible comorbidities antiepileptic treatment in paediatric oncology poses a number of diagnostic and therapeutic challenges. This requires a close interdisciplinary approach to the seizing child or adolescent. A prompt and detailed diagnostic work-up is needed in every case in order to establish the diagnosis and, equally important, to detect secondary aetiological factors, e. g. epileptogenic drugs or any acute underlying pathology, such as metabolic or toxic encephalopathies, CNS-infections or cerebrovascular events. This might offer the opportunity for a specific causative treatment and thus prevent unnecessary long-term antiepileptic drug (AED) treatment. If AED treatment is initiated several aspects have to be taken into account. Most importantly, AEDs and chemotherapeutic drugs (CTDs) may interact. Depending on the comedication this may result in reduced tumour or seizure control or unexpected toxicity of AEDs or CTDs. Understanding these interactions will allow to anticipate clinically relevant adverse effects. AED may be further complicated by side-effects, some of them of particular concern for children or adolescents, such as cognitive effects, myelotoxicity, serious rashes, endocrinological disturbances, and many more. Beside critically questioning the need for AED treatment it is therefore important to prefer AED with a good safety-profile in this population. Enzyme-inducing and inhibiting AED should be avoided if possible. Preliminary studies indicate that gabapentin and levetiracetam may provide good options in terms of efficacy and safety. However, more properly designed clinical studies are warranted to raise the level of evidence for robust clinical recommendations. Until that time, clinicians will need to continue to question current policies and adapt their daily practice to evolving scientific data.

Human T-Cell Leukemia Virus I Tax Protein Sensitizes p53-Mutant Cells to DNA Damage

PubMed Central

Mihaylova, Valia T.; Green, Allison M.; Khurgel, Moshe; Semmes, Oliver J.; Kupfer, Gary M.

2018-01-01

Mutations in p53 are a common cause of resistance of cancers to standard chemotherapy and, thus, treatment failure. Reports have shown that Tax, a human T-cell leukemia virus type I encoded protein that has been associated with genomic instability and perturbation of transcription and cell cycle, sensitizes HeLa cells to UV treatment. The extent to which Tax can sensitize cells and the mechanism by which it exerts its effect are unknown. In this study, we show that Tax sensitizes p53-mutant cells to a broad range of DNA-damaging agents, including mitomycin C, a bifunctional alkylator, etoposide, a topoisomerase II drug, and UV light, but not ionizing radiation, a double-strand break agent, or vinblastine, a tubulin poison. Tax caused hypersensitivity in all p53-deleted cell lines and several, but not all, mutant-expressed p53–containing cell lines, while unexpectedly being protective in p53 wild-type (wt) cells. The effect observed in p53-deleted lines could be reversed for this by transfection of wt p53. We also show that Tax activates a p53-independent proapoptotic program through decreased expression of the retinoblastoma protein and subsequent increased E2F1 expression. The expression of several proapoptotic proteins was also induced by Tax, including Puma and Noxa, culminating in a substantial increase in Bax dimerization. Our results show that Tax can sensitize p53-mutant cells to DNA damage while protecting p53 wt cells, a side benefit that might result in reduced toxicity in normal cells. Such studies hold the promise of a novel adjunctive therapy that could make cancer chemotherapy more effective. PMID:18559532

The Coordinated Noninvasive Studies (CNS) Project. Phase 1

DTIC Science & Technology

1991-12-01

may reveal functional asymmetries that represent the influence of two factors: 1) the "contralateral effect ," based on the side -of-space source of...asymmetries, where processing on that side of the CNS opposite the side of input is favored, and 2) an effect based J.L. Lauter [CNS Project/AFOSR 88-0352...extent that these exist over and above sidedness bias as well as side -of-space asymmetries -- since in these experiments, contralateral effects are

Psychological factors associated with uptake of the childhood influenza vaccine and perception of post-vaccination side-effects: A cross-sectional survey in England.

PubMed

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

2017-04-04

To identify predictors of: uptake of the childhood influenza vaccine in the 2015-2016 influenza season, parental perceptions of side-effects from the influenza vaccine and intention to vaccinate one's child for influenza in the 2016-2017 influenza season. Cross-sectional online survey. Data were collected in England shortly after the end of the 2015-2016 immunization campaign. 1001 parents or guardians of children aged between two and seven. Self-reported uptake of the childhood influenza vaccine in the 2015-2016 influenza season, perception of side-effects from the influenza vaccine and intention to vaccinate one's child in the 2016-2017 influenza season. Self-reported uptake of the childhood influenza vaccine was 52.8%. Factors strongly positively associated with uptake included the child having previously been vaccinated against influenza, perceiving the vaccine to be effective and perceiving the child to be susceptible to flu. Factors strongly negatively associated with uptake included perceiving the vaccine to be unsafe, to cause short-term side-effects or long-term health problems and believing that yearly vaccination may overload the immune system. Predictors of intended vaccine uptake in 2016-2017 were similar. Participants who perceived side-effects after the 2015-2016 vaccination reported being less likely to vaccinate their child next year. Side-effects were more likely to be reported in first-born children, by participants who knew another child who had side-effects, those who thought that the vaccine would interact with medication that the child was currently taking, and those who believed the vaccine causes short-term side-effects. Perceptions about the childhood influenza vaccine show strong associations with uptake, intended uptake and perception of side-effects. Attempts to improve uptake rates from their current low levels must address these perceptions. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Persuading drivers to refrain from speeding: Effects of message sidedness and regulatory fit.

PubMed

Pierro, Antonio; Giacomantonio, Mauro; Pica, Gennaro; Giannini, Anna Maria; Kruglanski, Arie W; Higgins, E Tory

2013-01-01

Building on regulatory fit theory (Higgins, 2000, 2005), we tested whether two-sided ads were more effective than one-sided ads in changing intentions toward driving behavior when message recipients were high in assessment orientation rather than locomotion orientation. In one study either a locomotion or an assessment orientation were situationally induced (Study 1) and in another study these different orientations were chronic predispositions (Study 2). As predicted, both studies found that for participants high in assessment, two-sided ads were more effective than one-sided ads, as reflected in stronger engagement with the persuasive message and stronger intentions to reduce driving speed. In contrast, for participants high in locomotion, one-sided ads were more effective than two-sided ads. There was also evidence that the fit effect on intentions to comply was mediated by strength of engagement with the message. Implications for persuasion concerning driving behaviors are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Side effects of methylphenidate in childhood cancer survivors: a randomized placebo-controlled trial.

PubMed

Conklin, Heather M; Lawford, Joanne; Jasper, Bruce W; Morris, E Brannon; Howard, Scott C; Ogg, Susan W; Wu, Shengjie; Xiong, Xiaoping; Khan, Raja B

2009-07-01

To investigate the frequency and severity of side effects of methylphenidate among childhood survivors of acute lymphoblastic leukemia and brain tumors and identify predictors of higher adverse effect levels. Childhood cancer survivors (N = 103) identified as having attention and learning problems completed a randomized, double-blind, 3-week, home-crossover trial of placebo, low-dose methylphenidate (0.3 mg/kg; 10 mg twice daily maximum) and moderate-dose methylphenidate (0.6 mg/kg; 20 mg twice daily maximum). Caregivers completed the Barkley Side Effects Rating Scale (SERS) at baseline and each week during the medication trial. Siblings of cancer survivors (N = 49) were recruited as a healthy comparison group. There was a significantly higher number and severity of symptoms endorsed on the SERS when patients were taking moderate dose compared with placebo or low dose, but not low dose compared with placebo. The number of side effects endorsed on the SERS was significantly lower during all 3 home-crossover weeks (placebo, low dose, moderate dose) when compared with baseline symptom scores. The severity of side effects was also significantly lower, compared with baseline screening, during placebo and low-dose weeks but not moderate-dose weeks. Both the number and severity of symptoms endorsed at baseline were significantly higher for patients compared with siblings. Female gender and lower IQ were associated with higher adverse effect levels. Methylphenidate is generally well tolerated by childhood cancer survivors. There is a subgroup at increased risk for side effects that may need to be closely monitored or prescribed a lower medication dose. The seemingly paradoxical findings of increased "side effects" at baseline must be considered when monitoring side effects and designing clinical trials.

Driver response to unexpected situations when using and in-vehicle information system

DOT National Transportation Integrated Search

1999-12-01

This investigation is one of a series of studies aimed at investigating Advanced Traveler Information Systems (ATIS) and Commercial Vehicle Operations (CVO) applications and their effect on driver behavior and performance. A field experiment was cond...

The Next Step: Managing Your District's Technology Operations.

ERIC Educational Resources Information Center

Pereus, Stephen C.

2001-01-01

Discusses benefits and especially risks involved with educational technology: unexpected costs; possible negative effects on student achievement; legal, ethical, and security issues; and resistance to change. Success ensues from providing leadership and vision, updating technology planning, evaluating alternatives, setting standards, involving…

Unexpected Benefits of Reducing Aerosol Cooling Effects

EPA Science Inventory

Impacts of aerosol cooling are not limited to changes in surface temperature since modulation of atmospheric dynamics resulting from the increased stability can deteriorate local air quality and impact human health. Health impacts from two manifestations of the aerosol direct eff...

Test-potentiated learning: three independent replications, a disconfirmed hypothesis, and an unexpected boundary condition.

PubMed

Wissman, Kathryn T; Rawson, Katherine A

2018-04-01

Arnold and McDermott [(2013). Test-potentiated learning: Distinguishing between direct and indirect effects of testing. Journal of Experimental Psychology: Learning, Memory, and Cognition, 39, 940-945] isolated the indirect effects of testing and concluded that encoding is enhanced to a greater extent following more versus fewer practice tests, referred to as test-potentiated learning. The current research provided further evidence for test-potentiated learning and evaluated the covert retrieval hypothesis as an alternative explanation for the observed effect. Learners initially studied foreign language word pairs and then completed either one or five practice tests before restudy occurred. Results of greatest interest concern performance on test trials following restudy for items that were not correctly recalled on the test trials that preceded restudy. Results replicate Arnold and McDermott (2013) by demonstrating that more versus fewer tests potentiate learning when trial time is limited. Results also provide strong evidence against the covert retrieval hypothesis concerning why the effect occurs (i.e., it does not reflect differential covert retrieval during pre-restudy trials). In addition, outcomes indicate that the magnitude of the test-potentiated learning effect decreases as trial length increases, revealing an unexpected boundary condition to test-potentiated learning.

Alemtuzumab-induced thyroid dysfunction exhibits distinctive clinical and immunological features.

PubMed

Pariani, Nadia; Willis, Mark; Muller, Ilaria; Healy, Sarah; Nasser, Taha; McGowan, Anne; Lyons, Greta; Jones, Joanne; Chatterjee, Krishna; Dayan, Colin; Robertson, Neil; Coles, Alasdair; Moran, Carla

2018-06-06

Alemtuzumab, a highly effective treatment for multiple sclerosis (MS), predisposes to Graves' disease (GD) with a reportedly indolent course. To determine the type, frequency and course of thyroid dysfunction (TD) in a cohort of alemtuzumab-treated MS patients in the UK. Case records of alemtuzumab-treated patients who developed TD were reviewed. 41.1% (102/248; 80F, 22M) of patients developed TD, principally GD (71.6%). Median onset was 17 months (range 2-107) following last dose; the majority (89%) within 3 years. Follow-up data (range 6-251 months) was available in 71 cases, of whom 52 (73.2%) developed GD: 10 of these (19.2%) had fluctuating TD. All 52 GD patients commenced anti-thyroid drugs (ATD): 3 required radioiodine (RAI) due to ATD side-effects, drug therapy is ongoing in 2; of those who completed a course, 16 are in remission, 1 developed spontaneous hypothyroidism, and 30 (64%) required definitive or long-term treatment (RAI n=17, thyroidectomy n=5, long-term ATDs n=8). 3 cases of thyroiditis and 16 cases of hypothyroidism were documented; 5 with anti-TPO antibody positivity only, 10 with positive TRAb, 1 hypothyroidism (uncertain aetiology). Bioassay confirmed both stimulating and blocking TRAb in a subset of fluctuating GD cases. Contrary to published literature, we have recorded frequent occurrence of GD that required definitive or prolonged antithyroid drug treatment. Furthermore, fluctuating thyroid status in GD and unexpectedly high frequency of TRAb-positive hypothyroidism suggested changing activity of TRAb in this clinical context; we have documented the existence of both blocking and stimulating TRAb in these patients.

Long-chain omega-3 fatty acids in aneurysmal subarachnoid hemorrhage: A randomized pilot trial of pharmaconutrition.

PubMed

Saito, Geisi; Zapata, Rodrigo; Rivera, Rodrigo; Zambrano, Héctor; Rojas, David; Acevedo, Hernán; Ravera, Franco; Mosquera, John; Vásquez, Juan E; Mura, Jorge

2017-01-01

Functional recovery after aneurysmal subarachnoid hemorrhage (SAH) remains a significant problem. We tested a novel therapeutic approach with long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) to assess the safety and feasibility of an effectiveness trial. We conducted a multicentre, parallel, randomized, open-label pilot trial. Patients admitted within 72 hours after SAH with modified Fisher scale scores of 3 or 4 who were selected for scheduled aneurysm clipping were allocated to receive either n-3 PUFA treatment (parenteral perioperative: 5 days; oral: 8 weeks) plus usual care or usual care alone. Exploratory outcome measures included major postoperative intracranial bleeding complications (PIBCs), cerebral infarction caused by delayed cerebral ischemia, shunt-dependent hydrocephalus, and consent rate. The computed tomography evaluator was blinded to the group assignment. Forty-one patients were randomized, but one patient had to be excluded after allocation. Twenty patients remained for intention to treat analysis in each trial arm. No PIBs (95% confidence interval [CI]: 0.00 to 0.16) or other unexpected harm were observed in the intervention group (IG). No patient suspended the intervention due to side effects. There was a trend towards improvements in all benefit-related outcomes in the IG. The overall consent rate was 0.91 (95% CI: 0.78 to 0.96), and there was no consent withdrawal. Although the balance between the benefit and harm of the intervention appears highly favourable, further testing on SAH patients is required. We recommend proceeding with amendments in a dose-finding trial to determine the optimal duration of parenteral treatment.

Scaffold hopping in drug discovery using inductive logic programming.

PubMed

Tsunoyama, Kazuhisa; Amini, Ata; Sternberg, Michael J E; Muggleton, Stephen H

2008-05-01

In chemoinformatics, searching for compounds which are structurally diverse and share a biological activity is called scaffold hopping. Scaffold hopping is important since it can be used to obtain alternative structures when the compound under development has unexpected side-effects. Pharmaceutical companies use scaffold hopping when they wish to circumvent prior patents for targets of interest. We propose a new method for scaffold hopping using inductive logic programming (ILP). ILP uses the observed spatial relationships between pharmacophore types in pretested active and inactive compounds and learns human-readable rules describing the diverse structures of active compounds. The ILP-based scaffold hopping method is compared to two previous algorithms (chemically advanced template search, CATS, and CATS3D) on 10 data sets with diverse scaffolds. The comparison shows that the ILP-based method is significantly better than random selection while the other two algorithms are not. In addition, the ILP-based method retrieves new active scaffolds which were not found by CATS and CATS3D. The results show that the ILP-based method is at least as good as the other methods in this study. ILP produces human-readable rules, which makes it possible to identify the three-dimensional features that lead to scaffold hopping. A minor variant of a rule learnt by ILP for scaffold hopping was subsequently found to cover an inhibitor identified by an independent study. This provides a successful result in a blind trial of the effectiveness of ILP to generate rules for scaffold hopping. We conclude that ILP provides a valuable new approach for scaffold hopping.

Management of land use conflicts in the United States Rocky Mountains

USGS Publications Warehouse

Baron, Jill S.; Theobald, D.M.; Fagre, D.B.

2000-01-01

People have long been attracted to the beauty and grandeur of the Rocky Mountains. Until very recently, however, the Rocky Mountain region was sparsely populated and its use mostly extractive. Commodities removed in massive quantities included first beaver, then precious metals, timber, energy, and finally water. There has been a fundamental change in migration patterns since the 1980s. Populations are expanding not only in urban areas; many rural areas are also growing faster. In an affluent and mobile society, Americans are moving to the West for aesthetic reasons, often based on perceptions that have little to do with regional roots, family ties, or economic opportunities.Wallace Stegner described the West into the 1980s as a colony for the rest of the nation. “It seems to be almost like a continuous repetitive act of God that the western resources should be mined …, that populations should rush in and have to rush out again, or trickle out again…. Get in, get rich, get out….Every boom and bust leaves the West physically a little poorer, a little worse damaged” (Stegner 1996).In an article about actor and director Robert Redford, writer Richard Raynor talks about unexpected side effects Redford's movies have had on American behavior. “A River Runs Through It" dangerously swelled the banks of American rivers with novice fishermen. It seems likely that Redford's loving rendition of ranch life in The Horse Whisperer … will have a similar effect on western Montana, filling it with even more people in a nostalgic search for American rapture and simplicity” (1998).

Potential negative effects of anti-histamines on male reproductive function.

PubMed

Mondillo, Carolina; Varela, María Luisa; Abiuso, Adriana María Belén; Vázquez, Ramiro

2018-05-01

Histamine (HA) is a pleiotropic biogenic amine synthesized exclusively by histidine decarboxylase (HDC) in most mammalian tissues. The literature on the role of HA within the male gonad has expanded over the last years, attracting attention to potential unexpected side-effects of anti-histamines on testicular function. In this regard, HA receptors (HRH1, HRH2 and HRH4) have been described in Leydig cells of different species, including human. Via these receptors, HA has been reported to trigger positive or negative interactions with the LH/hCG signaling pathway depending upon its concentration, thereby contributing to the local control of testicular androgen levels. It should then be considered that anti-histamines may affect testicular homeostasis by increasing or decreasing steroid production. Additionally, HRH1 and HRH2 receptors are present in peritubular and germ cells, and HRH2 antagonists have been found to negatively affect peritubular cells and reduce sperm viability. The potential negative impact of anti-histamines on male reproduction becomes even more dramatic if we consider that HA has also been associated with human sexual behavior and penile erection. What is more, although testicular mast cells are the major source of locally produced HA, recent studies have described HDC expression in macrophages, Leydig cells and germ cells, revealing the existence of multiple sources of HA within the testis. Undoubtedly, the more we learn about the testicular histaminergic system, the more opportunities there will be for rational design of drugs aimed at treating HA-related pathologies, with minimum or nule negative impact on fertility. © 2018 Society for Reproduction and Fertility.

Chronic Activation of FXR in Transgenic Mice Caused Perinatal Toxicity and Sensitized Mice to Cholesterol Toxicity

PubMed Central

Cheng, Qiuqiong; Inaba, Yuka; Lu, Peipei; Xu, Meishu; He, Jinhan; Zhao, Yueshui; Guo, Grace L.; Kuruba, Ramalinga; de la Vega, Rona; Evans, Rhobert W.; Li, Song

2015-01-01

The nuclear receptor farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4, or NR1H4) is highly expressed in the liver and intestine. Previous reports have suggested beneficial functions of FXR in the homeostasis of bile acids, lipids, and glucose, as well as in promoting liver regeneration and inhibiting carcinogenesis. To investigate the effect of chronic FXR activation in vivo, we generated transgenic mice that conditionally and tissue specifically express the activated form of FXR in the liver and intestine. Unexpectedly, the transgenic mice showed several intriguing phenotypes, including partial neonatal lethality, growth retardation, and spontaneous liver toxicity. The transgenic mice also displayed heightened sensitivity to a high-cholesterol diet-induced hepatotoxicity but resistance to the gallstone formation. The phenotypes were transgene specific, because they were abolished upon treatment with doxycycline to silence the transgene expression. The perinatal toxicity, which can be rescued by a maternal vitamin supplement, may have resulted from vitamin deficiency due to low biliary bile acid output as a consequence of inhibition of bile acid formation. Our results also suggested that the fibroblast growth factor-inducible immediate-early response protein 14 (Fn14), a member of the proinflammatory TNF family, is a FXR-responsive gene. However, the contribution of Fn14 induction in the perinatal toxic phenotype of the transgenic mice remains to be defined. Because FXR is being explored as a therapeutic target, our results suggested that a chronic activation of this nuclear receptor may have an unintended side effect especially during the perinatal stage. PMID:25719402

Juvenile Atlantic cod behavior appears robust to near-future CO2 levels.

PubMed

Jutfelt, Fredrik; Hedgärde, Maria

2015-01-01

Ocean acidification caused by the anthropogenic release of CO2 is considered a major threat to marine ecosystems. One unexpected impact of elevated water CO2 levels is that behavioral alterations may occur in tropical reef fish and certain temperate fish species. These effects appear to alter many different types of sensory and cognitive functions; if widespread and persistent, they have the potential to cause ecosystem changes. We investigated whether economically and ecologically important Atlantic cod also display behavioral abnormalities by exposing 52 juvenile cod to control conditions (500 μatm, duplicate tanks) or an end-of-the-century ocean acidification scenario (1000 μatm, duplicate tanks) for one month, during which time the fish were examined for a range of behaviors that have been reported to be affected by elevated CO2 in other fish. The behaviors were swimming activity, as measured by number of lines crossed per minute, the emergence from shelter, determined by how long it took the fish to exit a shelter after a disturbance, relative lateralization (a measure of behavioral turning side preference), and absolute lateralization (the strength of behavioral symmetry). We found no effect of CO2 treatment on any of the four behaviors tested: activity (F = 1.61, p = 0.33), emergence from shelter (F = 0.13, p = 0.76), relative lateralization (F = 2.82, p = 0.50), and absolute lateralization (F = 0.80, p = 0.26). Our results indicate that the behavior of Atlantic cod could be resilient to the impacts of near-future levels of water CO2.

Switching effect of the side chain on quantum walks on triple graphs

NASA Astrophysics Data System (ADS)

Du, Yi-Mu; Lu, Li-Hua; Li, You-Quan

2015-07-01

We consider a continuous-time quantum walk on a triple graph and investigate the influence of the side chain on propagation in the main chain. Calculating the interchange of the probabilities between the two parts of the main chain, we find that a switching effect appears if there is an odd number of points in the side chain when concrete conditions between the length of the main chain and the position of the side chain are satisfied. However, such an effect does not occur if there is an even number of points in the side chain. We also suggest two proposals for experiments to demonstrate this effect, which may be employed to design a new type of switching device.

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

PubMed

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

2012-08-01

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

The Relationship among Side Effects Associated with Anti-Epileptic Medications in Those with Intellectual Disability

ERIC Educational Resources Information Center

Sipes, Megan; Matson, Johnny L.; Belva, Brian; Turygin, Nicole; Kozlowski, Alison M.; Horovitz, Max

2011-01-01

Seizures are fairly common in those with intellectual disabilities. In order to treat these seizures, antiepileptic drugs (AEDs) are often used and in many cases are effective. However, these medications often create a variety of associated side effects. In order to monitor these side effects, measures such as the SEIZES-B have been used. While…

[Side Effects of Occupational Group Therapy].

PubMed

Flöge, B; Fay, D; Jöbges, M; Linden, M; Muschalla, B

2016-12-01

Background: Occupational therapy is an important co-therapy in psychiatric therapy. It is a common belief that no risks are associated with occupational therapy. Negative effects caused by group therapy, especially occupational therapy, have not been in the focus of research yet. In this study we want to illustrate possible types and intensities of group side effects through occupational therapy. Patients and Methods: Patients of an inpatient rehabilitation facility filled out the Adverse Treatment Reaction Group Checklist. The checklist contains 47 items divided in six dimensions: group size, content, group participants, group outcome and global. The self-rating used a 5-point likert scale (0 = not at all; 4 = very much, extremely stressful) and gives information about types and intensities of the side effects. Results: 88.9 % of 45 patients reported negative effects of occupational group therapy. 28.9 % of the patients rated the side effect as at least severe. Discussion: Occupational therapy is associated with side effects as every other group therapy. Possible side effects caused by group therapy should be considered while planning and implementing occupational therapy. © Georg Thieme Verlag KG Stuttgart · New York.

The effect of qualifying language on perceptions of drug appeal, drug experience, and estimates of side-effect incidence in DTC advertising.

PubMed

Davis, Joel

2007-01-01

This study examined how the use of qualifying language in direct-to-consumer (DTC) pharmaceutical advertising affects consumers' perceptions of drug appeal, anticipated pleasantness of drug usage, and the expected incidence of side-effect occurrence. A sample of 669 individuals participated in a 2 x 8 complete factorial design. The design manipulated the number of side effects associated with drug use and the type of qualifying language used to describe the side effects. The eight experimental qualifying language cells represented one control condition (no qualifying language), three cells where each of three types of qualifying language were presented individually, and four cells where qualifying language was combined. The results indicate that qualifying language has a profound effect on drug perceptions, especially when used in combination. Drug appeal and the anticipated drug-using experience almost always were more positive in the presence of qualifying language. Qualifying language appears to exert its influence by causing individuals to reduce their estimate of the likelihood of experiencing individual side effects. Policy implications of the research, particularly for evaluation of "fair balance" and the reporting of side effects, are presented.

The differences in the assessments of side effects at an oncology outpatient clinic.

PubMed

Bayraktar-Ekincioglu, A; Kucuk, E

2018-04-01

Background There is a growing interest in the use of targeted and immunotherapies in oncology. However, the assessment of side effects can be different due to interpretation of patients' health status by healthcare professionals in oncology outpatient clinics. Objective To demonstrate the differences in the assessments of side effects conducted independently by a clinical pharmacist and nurses in patients who receive targeted therapies at an oncology outpatient clinic. Setting The study was conducted at the University Oncology Hospital in an outpatient clinic from October 2015 to March 2016. Method Patients receiving ipilimumab, nivolumab, pembrolizumab, bevacizumab, panitumumab or cetuximab during study period were included. The assessment of side effects was conducted by a pharmacist and nurse independently using the NCI-CTCAE version-2. Main outcome measure To compare the severity assessments of side effects between a clinical pharmacist and nurses in an outpatient clinic. Results During the study, 204 visits for 43 patients with a total of 5508 side effect assessments were recorded where 1137 (20.64%) assessments were graded differently. Out of 1137 assessments, 473 of them were graded higher by a clinical pharmacist whereas 664 were graded higher by nurses. Statistically significant differences were detected in the assessment of vomiting, taste changes, sense changes, alopecia, fatigue, mood changes, anxiety, hearing impairment, and allergic reactions. Conclusion An assessment of side effects by healthcare providers in patients with cancer may be challenging due to an increased workload in clinics and undistinguishable symptoms of side effects and cancer itself. Therefore, a new care model which increases an interprofessional communication may improve pharmaceutical care in oncology outpatient clinics.

Period Prevalence and Perceived Side Effects of Hormonal Contraceptive Use and the Menstrual Cycle in Elite Athletes.

PubMed

Martin, Daniel; Sale, Craig; Cooper, Simon B; Elliott-Sale, Kirsty J

2017-12-28

To identify the period prevalence of hormonal contraceptive (HC) use and characterise the perceived side effects associated with the menstrual cycle and HC use. 430 elite female athletes completed a questionnaire to assess; the period prevalence of HC use, the reasons for initiation and discontinuation of HCs and the side effects experienced by HC and non-HC users. Descriptive statistics, between-group comparisons and associations between categorical variables were calculated. 49.5% of athletes were currently using HCs and 69.8% had used HCs at some point. Combined oral contraceptives were most commonly used (68.1%), with 30.0% using progestin-only contraceptives (implant = 13.1%; injection = 3.7%; intrauterine system = 2.8%). Perceived negative side effects were more common with progestin-only HC use (39.1%) compared to combined HC use (17.8%; P = 0.001) and were most prevalent in implant users (53.6%; P = 0.004). HC users reported perceived positive side effects relating to the ability to predict and/or manipulate the timing, frequency and amount of menstrual bleeding. Non-HC users had a menstrual cycle length of 29 ± 5 d and 77.4% reported negative side effects during their menstrual cycle, primarily during days 1-2 of menstruation (81.6%). Approximately half of elite athletes used HCs and progestin-only contraceptive users reported greater incidences of negative side effects, especially with the implant. Due to the high inter-individual variability in reported side effects, athletes and practitioners should maintain an open dialogue to pursue the best interests of the athlete.

Sampling Martian Soil

NASA Technical Reports Server (NTRS)

2004-01-01

Scientists were using the Moessbauer spectrometer on NASA's Mars Exploration Rover Spirit when something unexpected happened. The instrument's contact ring had been placed onto the ground as a reference point for placement of another instrument, the alpha particle X-ray spectrometer, for analyzing the soil. After Spirit removed the Moessbauer from the target, the rover's microscopic imager revealed a gap in the imprint left behind in the soil. The gap, about a centimeter wide (less than half an inch), is visible on the left side of this mosaic of images. Scientists concluded that a small chunk of soil probably adhered to the contact ring on the front surface of the Moessbauer. Before anyone saw that soil may have adhered to the Moessbauer, that instrument was placed to analyze martian dust collected by a magnet on the rover. The team plans to take images to see if any soil is still attached to the Moessbauer. Spirit took these images on the rover's 240th martian day, or sol (Sept. 4, 2004).

A homeostatic clock sets daughter centriole size in flies

PubMed Central

Aydogan, Mustafa G.; Steinacker, Thomas L.; Novak, Zsofia A.; Baumbach, Janina; Muschalik, Nadine

2018-01-01

Centrioles are highly structured organelles whose size is remarkably consistent within any given cell type. New centrioles are born when Polo-like kinase 4 (Plk4) recruits Ana2/STIL and Sas-6 to the side of an existing “mother” centriole. These two proteins then assemble into a cartwheel, which grows outwards to form the structural core of a new daughter. Here, we show that in early Drosophila melanogaster embryos, daughter centrioles grow at a linear rate during early S-phase and abruptly stop growing when they reach their correct size in mid- to late S-phase. Unexpectedly, the cartwheel grows from its proximal end, and Plk4 determines both the rate and period of centriole growth: the more active the centriolar Plk4, the faster centrioles grow, but the faster centriolar Plk4 is inactivated and growth ceases. Thus, Plk4 functions as a homeostatic clock, establishing an inverse relationship between growth rate and period to ensure that daughter centrioles grow to the correct size. PMID:29500190

A Topside Equatorial Ionospheric Density and Composition Climatology During and After Extreme Solar Minimum

NASA Technical Reports Server (NTRS)

Klenzing, J. H.; Simoes, F.; Ivanov, S.; Heelis, R. A.; Bilitza, D.; Pfaff, R. F.; Rowland, D. E.

2011-01-01

During the recent solar minimum, solar activity reached the lowest levels observed during the space age. This extremely low solar activity has accompanied a number of unexpected observations in the Earth's ionosphere and thermosphere when compared to previous solar minima. Among these are the fact that the ionosphere is significantly contracted beyond expectations based on empirical models. Climatological altitude profiles of ion density and composition measurements near the magnetic dip equator are constructed from the C/NOFS satellite to characterize the shape of the top side ionosphere during the recent solar minimum and into the new solar cycle. The variation of the profiles with respect to local time, season, and solar activity are compared to the IRI-2007 model. Building on initial results reported by Heelis et al. [2009], here we describe the extent of the contracted ionosphere, which is found to persist throughout 2009. The shape of the ionosphere during 2010 is found to be consistent with observations from previous solar minima.

Unexpected findings at diagnostic laparoscopy: caecal incarceration with concurrent appendicitis in a patient with bilateral broad ligament defects

PubMed Central

Onida, S; Lynes, K; Whitehouse, PA

2010-01-01

Internal herniations through broad ligament defects are very rare. We present the first report of the triad of broad ligament defect, internal herniation of the caecum and appendicitis. A 36-year-old woman with phocomelia presented with right iliac fossa pain and vomiting. The patient had no previous history of trauma or surgery. Abdominal ultrasound showed a small amount of free fluid. At laparoscopy, bilateral broad ligament defects were found, with herniation of the caecum and an inflamed appendix through the right-sided defect. A laparoscopic salpingo-oophorectomy was required for reduction of the herniated bowel, and an appendicectomy was performed. Broad ligament defects may be congenital or acquired. In this case, in light of the limb abnormality and absence of previous surgery, a congenital aetiology is more likely. Ultrasound scan is not reliable and, although computed tomography may be of help, a diagnostic laparoscopy is the best investigation. PMID:20566032

Evidence for cis Amide Bonds in Peptoid Nanosheets.

PubMed

Hudson, Benjamin C; Battigelli, Alessia; Connolly, Michael D; Edison, John; Spencer, Ryan K; Whitelam, Stephen; Zuckermann, Ronald N; Paravastu, Anant K

2018-05-17

Peptoid nanosheets are supramolecular protein-mimetic materials that form from amphiphilic polypeptoids with aromatic and ionic side chains. Nanosheets have been studied at the nanometer scale, but the molecular structure has been difficult to probe. We report the use of 13 C- 13 C dipolar recoupling solid-state NMR measurements to reveal the configuration of backbone amide bonds selected by 13 C isotopic labeling of adjacent α-carbons. Measurements on the same molecules in the amorphous state and in nanosheets revealed that amide bonds in the center of the amino block of peptoid (NaeNpe) 7 -(NceNpe) 7 (B28) favor the trans configuration in the amorphous state and the cis configuration in the nanosheet. This unexpected result contrasts with previous NMR and theoretical studies of short solvated peptoids. Furthermore, examination of the amide bond at the junction of the two charged blocks within B28 revealed a mixture of both cis and trans configurational states, consistent with the previously predicted brickwork-like intermolecular organization.

Phoenix Rising: The Helen Sawyer Hogg Telescope Finds a New Home in Argentina.

NASA Astrophysics Data System (ADS)

Garrison, R. F.; Levato, O. H.

2004-12-01

For 26 years (1971-1997), the University of Toronto operated a very productive 60-cm optical telescope on Carnegie's Cerro Las Campanas in north-central Chile. Due to a series of cutbacks in subsidies through NSERC, Canada's research-funding agency, the doors were closed on 01 July 1997 (Canada Day). Following an agreement between astronomers at DDO (Canada) and CASLEO, Argentina, the telescope and dome were relocated on Cerro Burek in Parque Nacional El Leoncita, Argentina, just on the other side of the Andes from Ovalle, Chile. The new building is 3 meters higher and has a dozen ventilating windows. The result is unexpectedly superior seeing. The average point spread function is 0.7 arcseconds. During construction of the building and rebuilding of the telescope, all decisions were made with the intention of operating the telescope remotely, initially from the warmroom of the CASLEO 2.15 meter telescope and ultimately from Toronto and San Juan.