WorldWideScience

Sample records for clinically relevant conditions

  1. Does transcutaneous electrical nerve stimulation (TENS have a clinically relevant analgesic effect on different pain conditions? A literature review

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    Asami Naka

    2013-07-01

    Full Text Available Transcutaneous electric nerve stimulation (TENS is a standard therapy used in different painful conditions such as low back pain, diabetic polyneuropathy or arthrosis. However, literature reviews focusing on the effects and the clinical implication of this method in various painful conditions are yet scarce. The purpose of this literature research was to determine, whether TENS provides an analgesic effect on common painful conditions in clinical practice. Literature research was performed using three data bases (Pubmed, Embase, Cochrane Database, focusing on papers published in the space of time from 2007 to 2012. Papers were evaluated from two reviewers independently concerning the clinical outcome, taking account for the level of external evidence according to the German Cochrane levels of evidence (Ia – IV. 133 papers of varying methodological quality dealing with different painful conditions were selected in total. A clinically relevant analgesic effect was described in 90 painful conditions (67%. In 30 painful states (22%, the outcome was inconclusive due to the study design. No significant analgesic effect of TENS was observed in 15 painful conditions (11%. The vast majority of the papers were classified as Cochrane evidence level Ib (n = 64; 48%, followed by level Ia (n = 23; 17%, level III (n = 18; 14%, level IV (n = 15; 11%, level IIb (n = 10; 8% and level IIa (n = 3; 2%. Most of the studies revealed an analgesic effect in various painful conditions, confirming the usefulness of TENS in clinical practice.

  2. Pulse treatment with the proteasome inhibitor bortezomib inhibits osteoclast resorptive activity in clinically relevant conditions

    DEFF Research Database (Denmark)

    Boissy, P; Levin Andersen, Thomas; Lund, T

    2008-01-01

    Myeloma bone disease is due to bone degradation by osteoclasts, and absence of repair by bone forming osteoblasts. Recent observations suggest that the anti-myeloma drug bortezomib, a proteasome inhibitor, stimulates bone formation and may inhibit bone resorption. Here, we tested bortezomib...... on cultured osteoclasts in conditions mimicking the pulse treatment used in the clinic, thereby avoiding continuous proteasome inhibition and unselective toxicity. A 3h pulse with 25nM bortezomib followed by a 3-day culture in its absence markedly inhibited osteoclast activity as evaluated through bone...... resorption, TRAcP release, and RANKL-induced NF-kappaB translocation into nuclei, an event dependent on proteasomes and critical for osteoclast function. The effect on TRAcP was maximal during the first 24h post-pulse, and then tended to subside. Importantly, applying this pulse treatment to cultured myeloma...

  3. Clinical Relevance of Adipokines

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    Matthias Blüher

    2012-10-01

    Full Text Available The incidence of obesity has increased dramatically during recent decades. Obesity increases the risk for metabolic and cardiovascular diseases and may therefore contribute to premature death. With increasing fat mass, secretion of adipose tissue derived bioactive molecules (adipokines changes towards a pro-inflammatory, diabetogenic and atherogenic pattern. Adipokines are involved in the regulation of appetite and satiety, energy expenditure, activity, endothelial function, hemostasis, blood pressure, insulin sensitivity, energy metabolism in insulin sensitive tissues, adipogenesis, fat distribution and insulin secretion in pancreatic β-cells. Therefore, adipokines are clinically relevant as biomarkers for fat distribution, adipose tissue function, liver fat content, insulin sensitivity, chronic inflammation and have the potential for future pharmacological treatment strategies for obesity and its related diseases. This review focuses on the clinical relevance of selected adipokines as markers or predictors of obesity related diseases and as potential therapeutic tools or targets in metabolic and cardiovascular diseases.

  4. Clinically Relevant Growth Conditions Alter Acinetobacter baumannii Antibiotic Susceptibility and Promote Identification of Novel Antibacterial Agents.

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    Jennifer M Colquhoun

    Full Text Available Biological processes that govern bacterial proliferation and survival in the host-environment(s are likely to be vastly different from those that are required for viability in nutrient-rich laboratory media. Consequently, growth-based antimicrobial screens performed in conditions modeling aspects of bacterial disease states have the potential to identify new classes of antimicrobials that would be missed by screens performed in conventional laboratory media. Accordingly, we performed screens of the Selleck library of 853 FDA approved drugs for agents that exhibit antimicrobial activity toward the Gram-negative bacterial pathogen Acinetobacter baumannii during growth in human serum, lung surfactant, and/or the organism in the biofilm state and compared those results to that of conventional laboratory medium. Results revealed that a total of 90 compounds representing 73 antibiotics and 17 agents that were developed for alternative therapeutic indications displayed antimicrobial properties toward the test strain in at least one screening condition. Of the active library antibiotics only four agents, rifampin, rifaximin, ciprofloxacin and tetracycline, exhibited antimicrobial activity toward the organism during all screening conditions, whereas the remainder were inactive in ≥ 1 condition; 56 antibiotics were inactive during serum growth, 25 and 38 were inactive toward lung surfactant grown and biofilm-associated cells, respectively, suggesting that subsets of antibiotics may outperform others in differing infection settings. Moreover, 9 antibiotics that are predominantly used for the treatment Gram-positive pathogens and 10 non-antibiotics lacked detectable antimicrobial activity toward A. baumannii grown in conventional medium but were active during ≥ 1 alternative growth condition(s. Such agents may represent promising anti-Acinetobacter agents that would have likely been overlooked by antimicrobial whole cell screening assays performed in

  5. Temporal dynamics of relief in avoidance conditioning and fear extinction: Experimental validation and clinical relevance.

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    Vervliet, Bram; Lange, Iris; Milad, Mohammed R

    2017-09-01

    The learning principles that guide the acquisition and extinction of avoidance are not fully understood. We developed a novel paradigm to study the temporal dynamics of relief, a putative reinforcer of avoidance, and the recovery of fear and avoidance following extinction. During conditioning, the avoidance action canceled the aversive unconditional stimulus (US), without terminating the predictive conditional stimulus (CS). Relief pleasantness was rated after fixed CS offsets, when US omission occured. Avoidance was effective to one CS, but not to another, to track stimulus-specific avoidance learning. Fear was extinguished under response prevention in a separate context. Recovery tests took place 24 h later, in both contexts and with a monetary cost added to the avoidance action. We found that avoidance gradually became stimulus-specific during conditioning, but hardly recovered during delayed testing. Across all phases, initial omissions of the aversive US triggered relief that gradually declined over consecutive omissions, in line with a theoretical prediction error signal. Participants that scored low on distress tolerance, however, displayed sustained levels of relief over continuous omissions. We propose that such forms of sustained relief may produce over-reinforcement of foregoing avoidance actions and promote the development of pathological avoidance. The current paradigm represents an efficacious tool to study the temporal dynamics of relief across avoidance learning and fear extinction and to characterize relief dysregulations in relation to psychopathology. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. [Human papillomavirus infection and its correlates with clinically relevant gynecological and obstetric conditions: A cross-sectional study].

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    López-Hernández, Daniel; Beltrán-Lagunes, Luis; Brito-Aranda, Leticia; López-Hernández, Maria de la Luz

    2016-08-05

    To analyze the prevalence of human papillomavirus (HPV) infection and the possible epidemiological association with conditions of clinical relevance in women. A cross-sectional study from Mexico City was conducted from January 2012 to December 2014. HPV molecular detection was performed on cervical samples. Data were analyzed with appropriated statistic tests. A total of 1,604 females (median 47, interquartile range 38-54) were analyzed. Global prevalence of infection for any HPV is 9.91% (95% CI 8.6-11.3). An association between infection with 16-HPV and number of abortions (NA) (OR=1.427; 95% CI 1.091-1.866), by univariate regression model (UVRM) was estimated. Moreover, menarche (OR=1.566; 95% CI 1.079-2.272), NA (OR=1.570; 95% CI 1.106-2.227) and number of pregnancies (NP) (OR=0.461; 95% CI 0.260-0.818) have a direct and inverse association with infection by genotype 18 of HPV, respectively. Also, infection with HR-HPV genotypes has an inverse association with NP (OR=0.791; 95% CI 0.707-0.884) by normal labor (OR=0.867; 95% CI 0.767-0.979) and NA (OR=0.715; 95% CI 0.534-0.959) (UVRM), and a direct association with number of sexual partners (OR=1.082; 95% CI 1.015-1.154). Onset of sexual activity has an inverse association with infection by genotype 16- (UVRM: OR=0.814; 95% CI 0.715-0.926; multinomial regression model (MNRM): OR=0.803; 95% CI 0.702-0.918) and HR-HPV (UVRM: OR=0.933; 95% CI 0.889-0.980, and MNRM: OR=0.912; 95% CI 0.867-0.959), all P values were lower than .03. Prevalence of HPV cervical infection is different according to age and it is associated with several medical conditions of clinical relevance in women. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  7. [Clinical research VI. Clinical relevance].

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    Talavera, Juan O; Rivas-Ruiz, Rodolfo

    2011-01-01

    Usually, in clinical practice the maneuver selected is the one that achieves a favorable outcome with a direct percentage of superiority of at least 10 %, or when the number needed to treat is approximately equal to 10. While this percentage difference is practical for estimating the magnitude of an association, we need to differentiate the impact measures (attributable risk, preventable fraction), measures of association (RR, OR, HR), and frequency measures (incidence and prevalence) applicable when the outcome is nominal. And we must identify ways to measure the strength of association and the magnitude of the association when the outcome variable is quantitative. It is not uncommon to interpret the measures of association as if they were impact measures. For example, for a RR of 0.68, it is common to assume a 32 % reduction of the outcome, but we must consider that this is a relative reduction, which comes from relations of 0.4/0.6, 0.04/0.06, or 0.00004/0.00006. However the direct reduction is 20 % (60 % - 40 %), 2 %, and 2 per 100,000, respectively. Therefore, to estimate the impact of a maneuver it is important to have the direct difference and/or NNT.

  8. Clinical relevance in anesthesia journals

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Møller, Ann M

    2006-01-01

    The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles.......The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles....

  9. Functionalized Magnetic Resonance Contrast Agent Selectively Binds to Glycoprotein IIb/IIIa on Activated Human Platelets under Flow Conditions and Is Detectable at Clinically Relevant Field Strengths

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    Constantin von zur Mühlen

    2008-03-01

    Full Text Available Recent progress in molecular magnetic resonance imaging (MRI provides the opportunity to image cells and cellular receptors using microparticles of iron oxide (MPIOs. However, imaging targets on vessel walls remains challenging owing to the quantity of contrast agents delivered to areas of interest under shear stress conditions. We evaluated ex vivo binding characteristics of a functional MRI contrast agent to ligand-induced binding sites (LIBSs on activated glycoprotein IIb/IIIa receptors of human platelets, which were lining rupture-prone atherosclerotic plaques and could therefore facilitate detection of platelet-mediated pathology in atherothrombotic disease. MPIOs were conjugated to anti-LIBS single-chain antibodies (LIBS-MPIO or control antibodies (control MPIO. Ex vivo binding to human platelet-rich clots in a dose-dependent manner was confirmed on a 3 T clinical MRI scanner and by histology (p < .05 for LIBS-MPIO vs control MPIO. By using a flow chamber setup, significant binding of LIBS-MPIO to a platelet matrix was observed under venous and arterial flow conditions, but not for control MPIO (p < .001. A newly generated MRI contrast agent detects activated human platelets at clinically relevant magnetic field strengths and binds to platelets under venous and arterial flow conditions, conveying high payloads of contrast to specific molecular targets. This may provide the opportunity to identify vulnerable, rupture-prone atherosclerotic plaques via noninvasive MRI.

  10. Statistical significance versus clinical relevance.

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    van Rijn, Marieke H C; Bech, Anneke; Bouyer, Jean; van den Brand, Jan A J G

    2017-04-01

    In March this year, the American Statistical Association (ASA) posted a statement on the correct use of P-values, in response to a growing concern that the P-value is commonly misused and misinterpreted. We aim to translate these warnings given by the ASA into a language more easily understood by clinicians and researchers without a deep background in statistics. Moreover, we intend to illustrate the limitations of P-values, even when used and interpreted correctly, and bring more attention to the clinical relevance of study findings using two recently reported studies as examples. We argue that P-values are often misinterpreted. A common mistake is saying that P < 0.05 means that the null hypothesis is false, and P ≥0.05 means that the null hypothesis is true. The correct interpretation of a P-value of 0.05 is that if the null hypothesis were indeed true, a similar or more extreme result would occur 5% of the times upon repeating the study in a similar sample. In other words, the P-value informs about the likelihood of the data given the null hypothesis and not the other way around. A possible alternative related to the P-value is the confidence interval (CI). It provides more information on the magnitude of an effect and the imprecision with which that effect was estimated. However, there is no magic bullet to replace P-values and stop erroneous interpretation of scientific results. Scientists and readers alike should make themselves familiar with the correct, nuanced interpretation of statistical tests, P-values and CIs. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  11. Sarcopenia: origins and clinical relevance

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    To a considerable extent, the advent of the term sarcopenia has contributed to the focus on this important condition and its effects on the quality of life and care of older persons. It is hoped that the advances in our understanding of the etiology and treatment of sarcopenia will further contribut...

  12. Valerian: No Evidence for Clinically Relevant Interactions

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    Olaf Kelber

    2014-01-01

    Full Text Available In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients.

  13. Clinical embryology teaching: is it relevant anymore?

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    Scott, Karen M; Charles, Antony Robert; Holland, Andrew J A

    2013-10-01

    Embryology finds itself jostling for precious space in the crowded medical curriculum, yet remains important for helping students understand birth defects. It has been suggested that teaching embryology through clinical scenarios can increase its relevance and interest. The aim of this research was to determine the attitudes of final-year medical students to learning embryology and whether clinical scenarios aid understanding. Final-year medical students undertaking their paediatric rotation in 2009 and 2010 were invited to attend an optional lecture on clinical embryology and participate in the research. In the lecture, three clinical scenarios were presented, in which the lecturer traced the normal development of a foetus and the abnormal development that resulted in a birth defect. Outcomes were assessed quantitatively using a paper-based survey. The vast majority of students who valued embryology teaching in their medical programme thought it would assist them with clinical management, and believed learning through case scenarios helped their understanding. Students were divided in their beliefs about when embryology should be taught in the medical programme and whether it would increase their workload. Embryology teaching appears to be a valuable part of the medical curriculum. Embryology teaching was valued when taught in the clinical environment in later years of the medical programme. Students, clinicians and medical educators should be proactive in finding clinical learning opportunities for embryology teaching. © 2013 Royal Australasian College of Surgeons.

  14. The prevalence of clinically-relevant comorbid conditions in patients with physician-diagnosed COPD: a cross-sectional study using data from NHANES 1999–2008

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    Schnell Kerry

    2012-07-01

    Full Text Available Abstract Background Treatment of chronic diseases such as chronic obstructive pulmonary disease (COPD is complicated by the presence of comorbidities. The objective of this analysis was to estimate the prevalence of comorbidity in COPD using nationally-representative data. Methods This study draws from a multi-year analytic sample of 14,828 subjects aged 45+, including 995 with COPD, from the National Health and Nutrition Examination Survey (NHANES, 1999–2008. COPD was defined by self-reported physician diagnosis of chronic bronchitis or emphysema; patients who reported a diagnosis of asthma were excluded. Using population weights, we estimated the age-and-gender-stratified prevalence of 22 comorbid conditions that may influence COPD and its treatment. Results Subjects 45+ with physician-diagnosed COPD were more likely than subjects without physician-diagnosed COPD to have coexisting arthritis (54.6% vs. 36.9%, depression (20.6% vs. 12.5%, osteoporosis (16.9% vs. 8.5%, cancer (16.5% vs. 9.9%, coronary heart disease (12.7% vs. 6.1%, congestive heart failure (12.1% vs. 3.9%, and stroke (8.9% vs. 4.6%. Subjects with COPD were also more likely to report mobility difficulty (55.6% vs. 32.5%, use of >4 prescription medications (51.8% vs. 32.1, dizziness/balance problems (41.1% vs. 23.8%, urinary incontinence (34.9% vs. 27.3%, memory problems (18.5% vs. 8.8%, low glomerular filtration rate (16.2% vs. 10.5%, and visual impairment (14.0% vs. 9.6%. All reported comparisons have p  Conclusions Our study indicates that COPD management may need to take into account a complex spectrum of comorbidities. This work identifies which conditions are most common in a nationally-representative set of COPD patients (physician-diagnosed, a necessary step for setting research priorities and developing clinical practice guidelines that address COPD within the context of comorbidity.

  15. [Clinical relevance of cardiopulmonary reflexes in anesthesiology].

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    Guerri-Guttenberg, R A; Siaba-Serrate, F; Cacheiro, F J

    2013-10-01

    The baroreflex, chemoreflex, pulmonary reflexes, Bezold-Jarisch and Bainbridge reflexes and their interaction with local mechanisms, are a demonstration of the richness of cardiovascular responses that occur in human beings. As well as these, the anesthesiologist must contend with other variables that interact by attenuating or accentuating cardiopulmonary reflexes such as, anesthetic drugs, surgical manipulation, and patient positioning. In the present article we review these reflexes and their clinical relevance in anesthesiology. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  16. Women with epilepsy: clinically relevant issues.

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    Bangar, S; Shastri, Abhishek; El-Sayeh, Hany; Cavanna, Andrea E

    2016-01-01

    Women with epilepsy (WWE) face specific challenges throughout their lifespan due to the effects of seizures and antiepileptic drugs on hormonal function, potentially affecting both sexual and reproductive health. This review article addresses the most common issues of practical relevance to clinicians treating WWE: epidemiology and clinical presentations (including catamenial epilepsy), contraception, reproductive and sexual dysfunction, pregnancy, lactation, menopause-related issues (including bone health), and mental health aspects. Awareness of these gender-specific issues and implementation/adaptation of effective interventions for WWE results in significantly improved health-related quality of life in this patient population.

  17. The clinical relevance of Tarlov cysts.

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    Langdown, Andrew John; Grundy, Julian R B; Birch, Nicholas C

    2005-02-01

    The sacral perineural cyst was first described by Tarlov in 1938 as an incidental finding at autopsy. There are very few data in the literature regarding the role of Tarlov cysts in causing symptoms, however. Most studies report low numbers, and consequently, the recommendations for treatment are vague. Our aim, therefore, is to present further detail regarding the clinical relevance of Tarlov cysts and to identify whether or not they are a cause of lumbosacral spinal canal stenosis symptoms. Over a 5-year period, 3535 patients underwent magnetic resonance imaging (MRI) scan for lumbosacral symptoms. Fifty-four patients were identified as having Tarlov cysts, and their clinical picture was correlated with the findings on MRI. The majority of Tarlov cysts (n = 38) cannot be held responsible for patients' symptoms and are clinically unimportant. However, we encountered several patients in whom Tarlov cysts (n = 9) occurred at the same level as another pathology. In these cases, the cyst itself did not require any specific therapy; treatment was directed at the other pathology, and uneventful symptom resolution occurred. A smaller subgroup of cysts (n = 7) are the main cause of patients' symptoms and may require specific treatment to facilitate local decompression. The majority of Tarlov cysts are incidental findings on MRI. Where confusion exists as to the clinical relevance of a Tarlov cyst, treatment of the primary pathology (ie, non-Tarlov lesion) is usually sufficient. Tarlov cysts may, however, be responsible for a patient's symptoms; possible mechanisms by which this may occur and treatment strategies are discussed.

  18. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

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    Danbo Yang

    2010-12-01

    Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  19. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

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    Yang, Danbo [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Yu, Lei, E-mail: yu-lei@gg.nitto.co.jp [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States); Van, Sang [Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States)

    2010-12-23

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  20. Mirror neurons and their clinical relevance.

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    Rizzolatti, Giacomo; Fabbri-Destro, Maddalena; Cattaneo, Luigi

    2009-01-01

    One of the most exciting events in neurosciences over the past few years has been the discovery of a mechanism that unifies action perception and action execution. The essence of this 'mirror' mechanism is as follows: whenever individuals observe an action being done by someone else, a set of neurons that code for that action is activated in the observers' motor system. Since the observers are aware of the outcome of their motor acts, they also understand what the other individual is doing without the need for intermediate cognitive mediation. In this Review, after discussing the most pertinent data concerning the mirror mechanism, we examine the clinical relevance of this mechanism. We first discuss the relationship between mirror mechanism impairment and some core symptoms of autism. We then outline the theoretical principles of neurorehabilitation strategies based on the mirror mechanism. We conclude by examining the relationship between the mirror mechanism and some features of the environmental dependency syndromes.

  1. Extracellular vesicles: fundamentals and clinical relevance

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    Wael Nassar

    2015-01-01

    Full Text Available All types of cells of eukaryotic organisms produce and release small nanovesicles into their extracellular environment. Early studies have described these vesicles as ′garbage bags′ only to remove obsolete cellular molecules. Valadi and colleagues, in 2007, were the first to discover the capability of circulating extracellular vesicles (EVs to horizontally transfer functioning gene information between cells. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodeling, chemoresistance, genetic exchange, and signaling pathway activation through growth factor/receptor transfer. EVs represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, signaling proteins, and RNAs. They contribute to physiology and pathology, and they have a myriad of potential clinical applications in health and disease. Moreover, vesicles can pass the blood-brain barrier and may perhaps even be considered as naturally occurring liposomes. These cell-derived EVs not only represent a central mediator of the disease microenvironment, but their presence in the peripheral circulation may serve as a surrogate for disease biopsies, enabling real-time diagnosis and disease monitoring. In this review, we′ll be addressing the characteristics of different types of extracellular EVs, as well as their clinical relevance and potential as diagnostic markers, and also define therapeutic options.

  2. Clinically Relevant Imaging in Tuberous Sclerosis

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    Rupa Radhakrishnan

    2011-01-01

    Full Text Available Tuberous sclerosis (TS, also known as Bourneville disease or Bourneville-Pringle disease, is an autosomal dominant genetic disorder classically characterized by the presence of hamartomatous growths in multiple organs. TS and tuberous sclerosis complex (TSC are different terms for the same genetic condition. Both terms describe clinical changes due to mutations involving either of the two genes named TSC1 and TSC2, which regulate cell growth. The diagnosis of TSC is established using diagnostic criteria based on clinical and imaging findings. Routine screening and surveillance of patients with TSC is needed to determine the presence and extent of organ involvement, especially the brain, kidneys, and lungs, and identify the development of associated complications. As the treatment is organ specific, imaging plays a crucial role in the management of patients with TSC.

  3. Clinical relevance of computed tomography under emergency conditions. Diagnostic accuracy, therapeutical consequences; Klinische Relevanz der Computertomographie unter Notdienstbedingungen. Diagnostische Treffsicherheit, therapeutische Konsequenzen

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    Weber, C.; Jensen, F.; Wedegaertner, U.; Adam, G. [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Radiologisches Zentrum, Klinik und Poliklinik fuer Diagnostische und Interventionelle Radiologie

    2004-01-01

    Purpose: To evaluate the diagnostic accuracy and therapeutic consequences of computed tomography performed on an emergency basis in a primary care hospital. Material and Methods: In 418 patients, 463 computed tomographies (thorax, abdomen, pelvis, spine, aorta, neck and extremities) were performed within 12 months, providing 999 diagnoses. The computed tomography diagnoses were retrospectively evaluated and correlated to surgery and discharge diagnoses. Therapeutical consequence were analyzed and allocated to a time period < 36 h (urgent) and {>=} 36-72 h (elective). Average age was 49 (1-94) years (41% female and 59% male). Discharge diagnosis was defined as gold standard, provided that it was supported by clinical, blood chemical, diagnostic and possible surgical data. Results: In 176 of 999 diagnoses (18%), the diagnoses were classified as ''noncorrelatable''. Of the 823 correlated diagnoses, 431 were true positive, 14 false positive, 66 false negative and 312 true negative. Sensitivity, specificity and diagnostic accuracy of computed tomography was 87,96 and 90%. Computed tomography had therapeutic consequences (surgery, drainage, puncture, reposition, thrombolytic therapy, chemotherapy, bronchoscopy, endoscopy, percutaneous transluminal angioplasty, coiling etc.) in 57% and no direct therapeutic interventions in 43%. Computed tomography excluded the suspected diagnosis in 36% and resulted in a conservative therapeutic regiment in 7%. Surgery was performed on 134 of the 418 patients (32%) who underwent computed tomography, with the surgery urgent in 71 (17%) and elective in 63 (15%) of the 418 patient. (orig.) [German] Ziel: Bewertung der diagnostischen Treffsicherheit und therapeutischen Konsequenzen der Computertomographie unter Notdienstbedingungen in einem Krankenhaus der Maximalversorgung. Material und Methoden: Innerhalb des definierten Studienzeitraums (12 Monate) wurden bei 418 Patienten 463 Computertomographien (Thorax, Abdomen

  4. EXTRACELLULAR VESICLES: CLASSIFICATION, FUNCTIONS AND CLINICAL RELEVANCE

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    A. V. Oberemko

    2014-12-01

    Full Text Available This review presents a generalized definition of vesicles as bilayer extracellular organelles of all celular forms of life: not only eu-, but also prokaryotic. The structure and composition of extracellular vesicles, history of research, nomenclature, their impact on life processes in health and disease are discussed. Moreover, vesicles may be useful as clinical instruments for biomarkers, and they are promising as biotechnological drug. However, many questions in this area are still unresolved and need to be addressed in the future. The most interesting from the point of view of practical health care represents a direction to study the effect of exosomes and microvesicles in the development and progression of a particular disease, the possibility of adjusting the pathological process by means of extracellular vesicles of a particular type, acting as an active ingredient. Relevant is the further elucidation of the role and importance of exosomes to the surrounding cells, tissues and organs at the molecular level, the prospects for the use of non-cellular vesicles as biomarkers of disease.

  5. Clinically relevant concentration of pregabalin has no acute inhibitory effect on excitation of dorsal horn neurons under normal or neuropathic pain conditions: An intracellular calcium-imaging study in spinal cord slices from adult rats.

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    Baba, Hiroshi; Petrenko, Andrey B; Fujiwara, Naoshi

    2016-10-01

    Pregabalin is thought to exert its therapeutic effect in neuropathic pain via binding to α2δ-1 subunits of voltage-gated calcium (Ca(2+)) channels. However, the exact analgesic mechanism after its binding to α2δ-1 subunits remains largely unknown. Whether a clinical concentration of pregabalin (≈10μM) can cause acute inhibition of dorsal horn neurons in the spinal cord is controversial. To address this issue, we undertook intracellular Ca(2+)-imaging studies using spinal cord slices with an intact attached L5 dorsal root, and examined if pregabalin acutely inhibits the primary afferent stimulation-evoked excitation of dorsal horn neurons in normal rats and in rats with streptozotocin-induced painful diabetic neuropathy. Under normal conditions, stimulation of a dorsal root evoked Ca(2+) signals predominantly in the superficial dorsal horn. Clinically relevant (10μM) and a very high concentration of pregabalin (100μM) did not affect the intensity or spread of dorsal root stimulation-evoked Ca(2+) signals, whereas an extremely high dose of pregabalin (300μM) slightly but significantly attenuated Ca(2+) signals in normal rats and in diabetic neuropathic (DN) rats. There was no difference between normal rats and DN rats with regard to the extent of signal attenuation at all concentrations tested. These results suggest that the activity of dorsal horn neurons in the spinal cord is not inhibited acutely by clinical doses of pregabalin under normal or DN conditions. It is very unlikely that an acute inhibitory action in the dorsal horn is the main analgesic mechanism of pregabalin in neuropathic pain states. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Fear conditioning to subliminal fear relevant and non fear relevant stimuli.

    Directory of Open Access Journals (Sweden)

    Ottmar V Lipp

    Full Text Available A growing body of evidence suggests that conscious visual awareness is not a prerequisite for human fear learning. For instance, humans can learn to be fearful of subliminal fear relevant images--images depicting stimuli thought to have been fear relevant in our evolutionary context, such as snakes, spiders, and angry human faces. Such stimuli could have a privileged status in relation to manipulations used to suppress usually salient images from awareness, possibly due to the existence of a designated sub-cortical 'fear module'. Here we assess this proposition, and find it wanting. We use binocular masking to suppress awareness of images of snakes and wallabies (particularly cute, non-threatening marsupials. We find that subliminal presentations of both classes of image can induce differential fear conditioning. These data show that learning, as indexed by fear conditioning, is neither contingent on conscious visual awareness nor on subliminal conditional stimuli being fear relevant.

  7. Serumferritin - diagnostic relevance and clinical usefulness

    Energy Technology Data Exchange (ETDEWEB)

    Linkesch, W. (Vienna Univ. (Austria). 2. Medizinische Klinik)

    1984-01-01

    The introduction of a WHO Standard for serumferritin effected a standardisation of different methods, improving quality and security for clinical routine diagnostic purposes. Therefore the clinical evaluation of serumferritin gained even more importance. For evaluation of iron stores of children, pregnant women, population studies, patients on hemodialysis or patients with rheumatoid arthritis low serumferritin values give safe results. In addition serumferritin is of clinical usefulness in monitoring therapy of both iron deficiency and iron overload. Evaluating a single serumferritin value one should consider the total clinical situation of the patient. As some tumors can produce and secrete serumferritin, e.g. acute myeloblastic leukemia, germ cell tumors, malignant melanoma, serumferritin might be helpful in monitoring the malignant disease. The ongoing characterization of tissue isoferritin, especially acidic isoferritin, may eventually lead to a clinically significant diagnostic marker of neoplasia.

  8. Properties and clinical relevance of osteoinductive biomaterials

    NARCIS (Netherlands)

    Habibovic, Pamela

    2005-01-01

    This thesis had two main goals: (¿) to investigate parameters influencing osteoinductive potential of biomaterials in order to unravel the mechanism underlying osteoinduction and (¿¿) to investigate performance of osteoinductive biomaterials orthotopically in order to get insight into their clinical

  9. Clinical relevance of intestinal peptide uptake

    Institute of Scientific and Technical Information of China (English)

    Hugh; James; Freeman

    2015-01-01

    AIM: To determine available information on an independent peptide transporter 1(Pep T1) and its potential relevance to treatment, this evaluation was completed.METHODS: Fully published English language literature articles sourced through Pub Med related to protein digestion and absorption, specifically human peptide and amino acid transport, were accessed and reviewed.Papers from 1970 to the present, with particular emphasis on the past decade, were examined. In addition,abstracted information translated to English in Pub Med was also included. Finally, studies and reviews relevant to nutrient or drug uptake, particularly in human intestine were included for evaluation. This work represents a summary of all of these studies with particular reference to peptide transporter mediated assimilation of nutrients and pharmacologically active medications.RESULTS: Assimilation of dietary protein in humans involves gastric and pancreatic enzyme hydrolysis to luminal oligopeptides and free amino acids. During the ensuing intestinal phase, these hydrolytic products are transported into the epithelial cell and, eventually, the portal vein. A critical component of this process is the uptake of intact di-peptides and tri-peptides by an independent Pep T1. A number of "peptide-mimetic" pharmaceutical agents may also be transported through this carrier, important for uptake of different antibiotics, antiviral agents and angiotensin-converting enzyme inhibitors. In addition, specific peptide products of intestinal bacteria may also be transported by Pep T1, with initiation and persistence of an immune response including increased cytokine production and associated intestinal inflammatory changes. Interestingly, these inflammatory changes may also be attenuated with orallyadministered anti-inflammatory tripeptides administered as site-specific nanoparticles and taken up by this Pep T1 transport protein. CONCLUSION: Further evaluation of the role of this transporter in treatment of

  10. Clinical relevance of intermittent tumour blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Durand, Ralph E.; Aquino-Parsons, Christina [British Columbia Cancer Research Centre, Vancouver (Canada)

    2001-12-01

    One of the goals of translational cancer research is to understand basic 'phenomena' so that tumour response to therapy can be improved. One such phenomenon is intermittent tumour blood flow. The impact of the transient hypoxia that results from decreased tumour blood flow is now beginning to be appreciated in preclinical systems, and also receiving some attention in clinical practise. Thus in this article we review the nature and frequency of microregional blood flow changes in preclinical and clinical tumours and examine the impact of those changes on response to both radiotherapy and chemotherapy. Additionally, the implications of non-constant blood flow for both the growth of the unperturbed tumour and the regrowth of surviving tumour clonogens during and after therapy are examined.

  11. [Fragmented QRS. Relevance in clinical practice].

    Science.gov (United States)

    Steger, Alexander; Sinnecker, Daniel; Berkefeld, Anna; Müller, Alexander; Gebhardt, Josef; Dommasch, Michael; Huster, Katharina M; Barthel, Petra; Schmidt, Georg

    2015-09-01

    The QRS complex represents the electrical depolarization of ventricular myocardium. In the case of an undisturbed depolarization, the QRS complex has a normal configuration and duration, but abnormal electrical conduction leads to widening of the QRS complex. The block of one of the Tawara branches results in a typical bundle branch block pattern. A QRS complex that cannot be classified as bundle branch block due to an atypical configuration and contains notched R or S waves is called a fragmented QRS. The underlying pathophysiologies are manifold and include myocardial scars induced by ischemic heart disease, myocardial fibrosis due to other diseases, primary cardiac pathologies as well as systemic diseases with cardiac involvement. Pathologies on the cellular level, such as ion channel dysfunctions, also correlate with fragmented QRS. Besides the diagnostic relevance, fragmented QRS is known to have prognostic properties, for example in identifying high risk patients with coronary artery disease, cardiomyopathy, Brugada syndrome and acquired long QT syndrome; however, fragmented QRS may also be detected in ECGs of healthy individuals.

  12. Clinical relevance of fascial tissue and dysfunctions.

    Science.gov (United States)

    Klingler, W; Velders, M; Hoppe, K; Pedro, M; Schleip, R

    2014-01-01

    Fascia is composed of collagenous connective tissue surrounding and interpenetrating skeletal muscle, joints, organs, nerves, and vascular beds. Fascial tissue forms a whole-body, continuous three-dimensional viscoelastic matrix of structural support. The classical concept of its mere passive role in force transmission has recently been disproven. Fascial tissue contains contractile elements enabling a modulating role in force generation and also mechanosensory fine-tuning. This hypothesis is supported by in vitro studies demonstrating an autonomous contraction of human lumbar fascia and a pharmacological induction of temporary contraction in rat fascial tissue. The ability of spontaneous regulation of fascial stiffness over a time period ranging from minutes to hours contributes more actively to musculoskeletal dynamics. Imbalance of this regulatory mechanism results in increased or decreased myofascial tonus, or diminished neuromuscular coordination, which are key contributors to the pathomechanisms of several musculoskeletal pathologies and pain syndromes. Here, we summarize anatomical and biomechanical properties of fascial tissue with a special focus on fascial dysfunctions and resulting clinical manifestations. Finally, we discuss current and future potential treatment options that can influence clinical manifestations of pain syndromes associated with fascial tissues.

  13. Clinically relevant subgroups in COPD and asthma

    Directory of Open Access Journals (Sweden)

    Alice M. Turner

    2015-06-01

    Full Text Available As knowledge of airways disease has grown, it has become apparent that neither chronic obstructive pulmonary disease (COPD nor asthma is a simple, easily defined disease. In the past, treatment options for both diseases were limited; thus, there was less need to define subgroups. As treatment options have grown, so has our need to predict who will respond to new drugs. To date, identifying subgroups has been largely reported by detailed clinical characterisation or differences in pathobiology. These subgroups are commonly called “phenotypes”; however, the problem of defining what constitutes a phenotype, whether this should include comorbid diseases and how to handle changes over time has led to the term being used loosely. In this review, we describe subgroups of COPD and asthma patients whose clinical characteristics we believe have therapeutic or major prognostic implications specific to the lung, and whether these subgroups are constant over time. Finally, we will discuss whether the subgroups we describe are common to both asthma and COPD, and give some examples of how treatment might be tailored in patients where the subgroup is clear, but the label of asthma or COPD is not.

  14. HDL cholesterol: reappraisal of its clinical relevance.

    Science.gov (United States)

    März, Winfried; Kleber, Marcus E; Scharnagl, Hubert; Speer, Timotheus; Zewinger, Stephen; Ritsch, Andreas; Parhofer, Klaus G; von Eckardstein, Arnold; Landmesser, Ulf; Laufs, Ulrich

    2017-03-24

    While several lines of evidence prove that elevated concentrations of low-density lipoproteins (LDL) causally contribute to the development of atherosclerosis and its clinical consequences, high-density lipoproteins are still widely believed to exert atheroprotective effects. Hence, HDL cholesterol (HDL-C) is in general still considered as "good cholesterol". Recent research, however, suggests that this might not always be the case and that a fundamental reassessment of the clinical significance of HDL-C is warranted. This review article is based on a selective literature review. In individuals without a history of cardiovascular events, low concentrations of HDL-C are inversely associated with the risk of future cardiovascular events. This relationship may, however, not apply to patients with metabolic disorders or manifest cardiovascular disease. The classical function of HDL is to mobilise cholesterol from extrahepatic tissues for delivery to the liver for excretion. These roles in cholesterol metabolism as well as many other biological functions of HDL particles are dependent on the number as well as protein and lipid composition of HDL particles. They are poorly reflected by the HDL-C concentration. HDL can even exert negative vascular effects, if its composition is pathologically altered. High serum HDL-C is therefore no longer regarded protective. In line with this, recent pharmacological approaches to raise HDL-C concentration have not been able to show reductions of cardiovascular outcomes. In contrast to LDL cholesterol (LDL-C), HDL-C correlates with cardiovascular risk only in healthy individuals. The calculation of the ratio of LDL-C to HDL-C is not useful for all patients. Low HDL-C should prompt examination of additional metabolic and inflammatory pathologies. An increase in HDL-C through lifestyle change (smoking cessation, physical exercise) has positive effects and is recommended. However, HDL-C is currently not a valid target for drug therapy.

  15. Trustworthiness and relevance in web-based clinical question answering.

    Science.gov (United States)

    Cruchet, Sarah; Boyer, Célia; van der Plas, Lonneke

    2012-01-01

    Question answering systems try to give precise answers to a user's question posed in natural language. It is of utmost importance that the answers returned are relevant to the user's question. For clinical QA, the trustworthiness of answers is another important issue. Limiting the document collection to certified websites helps to improve the trustworthiness of answers. On the other hand, limited document collections are known to harm the relevancy of answers. We show, however, in a comparative evaluation, that promoting trustworthiness has no negative effect on the relevance of the retrieved answers in our clinical QA system. On the contrary, the answers found are in general more relevant.

  16. Development of Clinically Relevant Implantable Pressure Sensors: Perspectives and Challenges

    Science.gov (United States)

    Clausen, Ingelin; Glott, Thomas

    2014-01-01

    This review describes different aspects to consider when developing implantable pressure sensor systems. Measurement of pressure is in general highly important in clinical practice and medical research. Due to the small size, light weight and low energy consumption Micro Electro Mechanical Systems (MEMS) technology represents new possibilities for monitoring of physiological parameters inside the human body. Development of clinical relevant sensors requires close collaboration between technological experts and medical clinicians. Site of operation, size restrictions, patient safety, and required measurement range and resolution, are only some conditions that must be taken into account. An implantable device has to operate under very hostile conditions. Long-term in vivo pressure measurements are particularly demanding because the pressure sensitive part of the sensor must be in direct or indirect physical contact with the medium for which we want to detect the pressure. New sensor packaging concepts are demanded and must be developed through combined effort between scientists in MEMS technology, material science, and biology. Before launching a new medical device on the market, clinical studies must be performed. Regulatory documents and international standards set the premises for how such studies shall be conducted and reported. PMID:25248071

  17. Development of Clinically Relevant Implantable Pressure Sensors: Perspectives and Challenges

    Directory of Open Access Journals (Sweden)

    Ingelin Clausen

    2014-09-01

    Full Text Available This review describes different aspects to consider when developing implantable pressure sensor systems. Measurement of pressure is in general highly important in clinical practice and medical research. Due to the small size, light weight and low energy consumption Micro Electro Mechanical Systems (MEMS technology represents new possibilities for monitoring of physiological parameters inside the human body. Development of clinical relevant sensors requires close collaboration between technological experts and medical clinicians.  Site of operation, size restrictions, patient safety, and required measurement range and resolution, are only some conditions that must be taken into account. An implantable device has to operate under very hostile conditions. Long-term in vivo pressure measurements are particularly demanding because the pressure sensitive part of the sensor must be in direct or indirect physical contact with the medium for which we want to detect the pressure. New sensor packaging concepts are demanded and must be developed through combined effort between scientists in MEMS technology, material science, and biology. Before launching a new medical device on the market, clinical studies must be performed. Regulatory documents and international standards set the premises for how such studies shall be conducted and reported.

  18. Clinical relevance of hepatitis B virus variants

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The hepatitis B virus (HBV) is a global public health problem with more than 240 million people chronicallyinfected worldwide, who are at risk for end-stage liverdisease and hepatocellular carcinoma. There are anestimated 600000 deaths annually from complications ofHBV-related liver disease. Antiviral therapy with nucleos/tide analogs (NA) targeting the HBV polymerase (P) caninhibit disease progression by long-term suppression ofHBV replication. However, treatment may fail with firstgeneration NA therapy due to the emergence of drugresistantmutants, as well as incomplete medicationadherence. The HBV replicates via an error-prone reversetranscriptase leading to quasispecies. Due to overlappingopen reading frames mutations within the HBV P cancause concomitant changes in the HBV surface gene (S )and vice versa. HBV quasispecies diversity is associatedwith response to antiviral therapy, disease severity andlong-term clinical outcomes. Specific mutants havebeen associated with antiviral drug resistance, immuneescape, liver fibrosis development and tumorgenesis.An understanding of HBV variants and their clinicalrelevance may be important for monitoring chronichepatitis B disease progression and treatment response.In this review, we will discuss HBV molecular virology,mechanism of variant development, and their potentialclinical impact.

  19. Pathobiology of human cerebrovascular malformations: basic mechanisms and clinical relevance.

    Science.gov (United States)

    Gault, Judith; Sarin, Hemant; Awadallah, Nabil A; Shenkar, Robert; Awad, Issam A

    2004-07-01

    Cerebrovascular malformations affect more than 3% of the population, exposing them to a lifetime risk of hemorrhagic stroke, seizures, and focal neurological deficits. Cerebral cavernous malformations (CCMs) exhibit an immature vessel wall, a brittle hemorrhagic tendency, and epileptogenesis, whereas arteriovenous malformations (AVMs) lack capillary beds and manifest apoplectic bleeding under high-flow conditions. There are also more benign venous anomalies, capillary malformations, and lesions with mixed and transitional features. Advances have been made toward understanding the natural history, radiological and pathological correlates, and clinical management. Yet, mechanisms of lesion genesis and clinical manifestations remain largely unknown, and the clinical behavior in individual patients is highly unpredictable. Lesion pathogenesis likely involves abnormal assembly or maintenance of blood vessels, resulting in dysmorphic vessel phenotypes. Familial CCM disease is in part caused by mutations in a cytoskeletal-related protein that is likely integral to interendothelial cell connectivity and maturation of the vascular wall. Rare familial forms of AVM disease have been correlated with two different transforming growth factor-beta receptor components, possibly causing disturbance in signaling during vascular assembly. Relevance of these mechanisms to the more common and otherwise identical sporadic CCM and AVM lesions is being explored. In this report, basic mechanisms of vasculogenesis and angiogenesis and how they possibly relate to the common cerebrovascular malformation lesions are reviewed. Novel concepts are discussed related to the cellular, molecular, and genetic substrates in CCM and AVM as well as to how this knowledge can be applied to predict, explain, and possibly modify clinical disease manifestations.

  20. Quantifying the clinical relevance of a laboratory observer performance paradigm.

    Science.gov (United States)

    Chakraborty, D P; Haygood, T M; Ryan, J; Marom, E M; Evanoff, M; McEntee, M F; Brennan, P C

    2012-09-01

    Laboratory observer performance measurements, receiver operating characteristic (ROC) and free-response ROC (FROC) differ from actual clinical interpretations in several respects, which could compromise their clinical relevance. The objective of this study was to develop a method for quantifying the clinical relevance of a laboratory paradigm and apply it to compare the ROC and FROC paradigms in a nodule detection task. The original prospective interpretations of 80 digital chest radiographs were classified by the truth panel as correct (C=1) or incorrect (C=0), depending on correlation with additional imaging, and the average of C was interpreted as the clinical figure of merit. FROC data were acquired for 21 radiologists and ROC data were inferred using the highest ratings. The areas under the ROC and alternative FROC curves were used as laboratory figures of merit. Bootstrap analysis was conducted to estimate conventional agreement measures between laboratory and clinical figures of merit. Also computed was a pseudovalue-based image-level correctness measure of the laboratory interpretations, whose association with C as measured by the area (rAUC) under an appropriately defined relevance ROC curve, is as a measure of the clinical relevance of a laboratory paradigm. Low correlations (e.g. κ=0.244) and near chance level rAUC values (e.g. 0.598), attributable to differences between the clinical and laboratory paradigms, were observed. The absolute width of the confidence interval was 0.38 for the interparadigm differences of the conventional measures and 0.14 for the difference of the rAUCs. The rAUC measure was consistent with the traditional measures but was more sensitive to the differences in clinical relevance. A new relevance ROC method for quantifying the clinical relevance of a laboratory paradigm is proposed.

  1. Placebo interventions for all clinical conditions

    DEFF Research Database (Denmark)

    Hróbjartsson, Asbjørn; Gøtzsche, Peter C

    2010-01-01

    Placebo interventions are often claimed to substantially improve patient-reported and observer-reported outcomes in many clinical conditions, but most reports on effects of placebos are based on studies that have not randomised patients to placebo or no treatment. Two previous versions...... of this review from 2001 and 2004 found that placebo interventions in general did not have clinically important effects, but that there were possible beneficial effects on patient-reported outcomes, especially pain. Since then several relevant trials have been published....

  2. Placebo interventions for all clinical conditions

    DEFF Research Database (Denmark)

    Hróbjartsson, Asbjørn; Gøtzsche, Peter C

    2010-01-01

    Placebo interventions are often claimed to substantially improve patient-reported and observer-reported outcomes in many clinical conditions, but most reports on effects of placebos are based on studies that have not randomised patients to placebo or no treatment. Two previous versions...... of this review from 2001 and 2004 found that placebo interventions in general did not have clinically important effects, but that there were possible beneficial effects on patient-reported outcomes, especially pain. Since then several relevant trials have been published....

  3. Proprioceptive deficits after ACL injury : are they clinically relevant?

    NARCIS (Netherlands)

    Gokeler, Alli; Benjaminse, Anne; Hewett, Timothy E.; Lephart, Scott M.; Engebretsen, Lars; Ageberg, Eva; Engelhardt, Martin; Arnold, Markus P.; Postema, Klaas; Otten, Egbert; Dijkstra, Pieter U.

    2012-01-01

    Objective To establish the clinical relevance of proprioceptive deficits reported after anterior cruciate ligament (ACL) injury. Material and methods A literature search was done in electronic databases from January 1990 to June 2009. Inclusion criteria for studies were ACL deficient (ACL-D) and ACL

  4. Interfacial shear rheology of DPPC under physiologically relevant conditions.

    Science.gov (United States)

    Hermans, Eline; Vermant, Jan

    2014-01-07

    Lipids, and phosphatidylcholines in particular, are major components in cell membranes and in human lung surfactant. Their ability to encapsulate or form stable layers suggests a significant role of the interfacial rheological properties. In the present work we focus on the surface rheological properties of dipalmitoylphosphatidylcholine (DPPC). Literature results are confusing and even contradictory; viscosity values have been reported differ by several orders of magnitude. Moreover, even both purely viscous and gel-like behaviours have been described. Assessing the literature critically, a limited experimental window has been explored correctly, which however does not yet include conditions relevant for the physiological state of DPPC in vivo. A complete temperature and surface pressure analysis of the interfacial shear rheology of DPPC is performed, showing that the monolayer behaves as a viscoelastic liquid with a domain structure. At low frequencies and for a thermally structured monolayer, the interaction of the molecules within the domains can be probed. The low frequency limit of the complex viscosity is measured over a wide range of temperatures and surface pressures. The effects of temperature and surface pressure on the low frequency viscosity can be analysed in terms of the effects of free molecular area. However, at higher frequencies or following a preshear at high shear rates, elasticity becomes important; most probably elasticity due to defects at the edge of the domains in the layer is probed. Preshearing refines the structure and induces more defects. As a result, disagreeing interfacial rheology results in various publications might be due to different pre-treatments of the interface. The obtained dataset and scaling laws enable us to describe the surface viscosity, and its dependence under physiological conditions of DPPC. The implications on functioning of lung surfactants and lung surfactant replacements will be discussed.

  5. Clinical relevance of pharmacist intervention in an emergency department.

    Science.gov (United States)

    Pérez-Moreno, Maria Antonia; Rodríguez-Camacho, Juan Manuel; Calderón-Hernanz, Beatriz; Comas-Díaz, Bernardino; Tarradas-Torras, Jordi

    2017-08-01

    To evaluate the clinical relevance of pharmacist intervention on patient care in emergencies, to determine the severity of detected errors. Second, to analyse the most frequent types of interventions and type of drugs involved and to evaluate the clinical pharmacist's activity. A 6-month observational prospective study of pharmacist intervention in the Emergency Department (ED) at a 400-bed hospital in Spain was performed to record interventions carried out by the clinical pharmacists. We determined whether the intervention occurred in the process of medication reconciliation or another activity, and whether the drug involved belonged to the High-Alert Medications Institute for Safe Medication Practices (ISMP) list. To evaluate the severity of the errors detected and clinical relevance of the pharmacist intervention, a modified assessment scale of Overhage and Lukes was used. Relationship between clinical relevance of pharmacist intervention and the severity of medication errors was assessed using ORs and Spearman's correlation coefficient. During the observation period, pharmacists reviewed the pharmacotherapy history and medication orders of 2984 patients. A total of 991 interventions were recorded in 557 patients; 67.2% of the errors were detected during medication reconciliation. Medication errors were considered severe in 57.2% of cases and 64.9% of pharmacist intervention were considered relevant. About 10.9% of the drugs involved are in the High-Alert Medications ISMP list. The severity of the medication error and the clinical significance of the pharmacist intervention were correlated (Spearman's ρ=0.728/pclinical pharmacists identified and intervened on a high number of severe medication errors. This suggests that emergency services will benefit from pharmacist-provided drug therapy services. 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/.

  6. Clinical Relevance of Brain Volume Measures in Multiple Sclerosis

    DEFF Research Database (Denmark)

    De Stefano, Nicola; Airas, Laura; Grigoriadis, Nikolaos

    2014-01-01

    (e.g. SIENA [Structural Image Evaluation using Normalization of Atrophy]). Although these methods are sensitive and reproducible, caution must be exercised when interpreting brain volume data, as numerous factors (e.g. pseudoatrophy) may have a confounding effect on measurements, especially...... therefore have important clinical implications affecting treatment decisions, with several clinical trials now demonstrating an effect of disease-modifying treatments (DMTs) on reducing brain volume loss. In clinical practice, it may therefore be important to consider the potential impact of a therapy...... on reducing the rate of brain volume loss. This article reviews the measurement of brain volume in clinical trials and practice, the effect of DMTs on brain volume change across trials and the clinical relevance of brain volume loss in MS....

  7. Juxtaposed atrial appendages: A curiosity with some clinical relevance

    Directory of Open Access Journals (Sweden)

    Anil Kumar Singhi

    2016-01-01

    Full Text Available If the atrial appendages lie adjacent to each other on same side of the great arteries, instead of encircling their roots, they are referred as juxtaposed. Right juxtaposition of atrial appendages is less common than left juxtaposition. The images demonstrate the classical radiological, echocardiographic, and surgical images of juxtaposed atrial appendages. Their clinical incidence, associations, and relevance during interventional and surgical procedures are discussed.

  8. Empirical Relevance of the Hillman Condition and Comparative Advantage

    NARCIS (Netherlands)

    J. Hinloopen (Jeroen); J.G.M. van Marrewijk (Charles)

    2004-01-01

    textabstractWe analyze the empirical violation of the Hillman condition, a necessary and sufficient condition for the correspondence between comparative advantage and pre-trade relative prices. Our comprehensive data set allows us to investigate the Hillman condition for virtually all countries of t

  9. Hazelnut Allergens: Molecular Characterization, Detection, and Clinical Relevance.

    Science.gov (United States)

    Costa, Joana; Mafra, Isabel; Carrapatoso, Isabel; Oliveira, Maria Beatriz P P

    2016-11-17

    In last few years, special attention has been given to food-induced allergies, in which hazelnut allergy is highlighted. Hazelnut is one of the most commonly consumed tree nuts, being largely used by the food industry in a variety of processed foods. It has been regarded as a food with potential health benefits, but also as a source of allergens capable of inducing mild to severe allergic reactions in sensitized individuals. Considering the great number of reports addressing hazelnut allergens, with an estimated increasing trend, this review intends to assemble all the relevant information available so far on the following main issues: prevalence of tree nut allergy, clinical threshold levels, molecular characterization of hazelnut allergens (Cor a 1, Cor a 2, Cor a 8, Cor a 9, Cor a 10, Cor a 11, Cor a 12, Cor a 14, and Cor a TLP) and their clinical relevance, and methodologies for detection of hazelnut allergens in foods. A comprehensive overview of the current data about the molecular characterization of hazelnut allergens is presented, relating to biochemical classification and biological function with clinical importance. Recent advances in hazelnut allergen detection methodologies are summarized and compared, including all the novel protein-based and DNA-based approaches.

  10. Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes.

    OpenAIRE

    García Aymerich, Judith; Gomez, F. P.; Benet Mora, Marta; Farrero, E.; Basagaña, Xavier; Gayete, A.; Pare i Bardera, J. Carles; Freixa, X.; Ferrer, J.; Ferrer Monreal, Antonio; Roca Elias, Josep; Galdiz, J. P.; Sauleda, J. E.; Monso, E; Gea Guiral, Joaquim

    2010-01-01

    Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomark...

  11. Sensitization to lupine flour: is it clinically relevant?

    Science.gov (United States)

    de Jong, N W; van Maaren, M S; Vlieg-Boersta, B J; Dubois, A E J; de Groot, H; Gerth van Wijk, R

    2010-10-01

    Lupinus angustifolius (blue lupine) is used for human and animal consumption. Currently, the lupine content in bread varies from 0% to 10% and from 0.5% to 3% in pastry. Although lupine flour is present in many products, anaphylaxis on lupine flour is rarely seen. The aim of our study was to determine the clinical relevance of sensitization to lupine flour. From October 2004 until October 2005, we performed skin prick tests (SPT) with lupine flour, peanut and soy extracts in consecutive patients attending our allergy clinic with a suspected food allergy. In patients sensitized to lupine flour, double-blind placebo-controlled food challenges (DBPCFC) were performed and specific IgE was measured. We tested 372 patients. SPTs with peanut, soy and lupine flour were positive in 135, 58 and 22 patients, respectively. Nine patients with sensitization to lupine flour underwent DBPCFC, which was negative in eight cases. In contrast, one patient experienced significant symptoms. Four of these nine patients suspected lupine by history. Two other patients with a positive history to lupine declined from challenges. In these patients, a 3-day dietary record showed that they could consume lupine without symptoms. Specific IgE in the serum was positive for L. angustifolius, peanut and soy in all nine patients. These results demonstrate that clinical lupine allergy is very uncommon, even in the presence of sensitization to lupine flour. The estimated prevalence of lupine allergy, among patients with a suspected food allergy, referred to a tertiary allergy centre in the Netherlands is 0.27-0.81%. In most, although not all cases, sensitization is not clinically relevant and is most likely caused by cross-sensitization to peanut. In selected cases, eliciting doses are low, making significant reactions possible. © 2010 Blackwell Publishing Ltd.

  12. Clinically relevant drug interactions with anti-Alzheimer's drugs.

    Science.gov (United States)

    Caraci, Filippo; Sultana, Janet; Drago, Filippo; Spina, Edoardo

    2017-03-03

    The aging world population had led to an increase in the prevalence of Alzheimer's disease (AD). The drugs used to slow down the onset of AD, galantamine, donepezil, rivastigmine and memantine, are generally well-tolerated. However, drug interactions between these drugs and other drugs are an important aspect of patient safety that should be borne in mind, particularly given the high burden of polypharmacy in the elderly. The aim of this review is to provide an updated review of clinically significant drug-drug interactions concerning drugs approved for AD. PubMed was searched for relevant keywords. No time limit was imposed but only articles in English published in peer-reviewed journals were selected. Relevant literature was also identified from the references of identified articles. Further information was obtained from drug summary of product characteristics. The major pharmacokinetic interactions identified concerned fluoxetine, paroxetine and ketoconazole when used with galantamine or donepezil. On the other hand, the major potential pharmacodynamic interactions concerned anti-dementia drugs and general anesthesia agents, anti-cholinergic drugs, conventional antipsychotics and bradycardia-inducing drugs. In clinical practice memantine shows a lower potential for pharmacodynamic drug-drug interactions (DDIs) compared to other drug classes. In conclusion, the concomitant use of anti-dementia drugs with other drugs can have variable clinical effects, making appropriate prescribing of these drugs very challenging. A simple and coherent way of presenting evidence on complex drug interaction information from heterogenous sources to clinicians is needed in order for the voluminous data available to have an impact on clinical practice.

  13. Diamond coatings exposure to fusion-relevant plasma conditions

    NARCIS (Netherlands)

    Porro, S.; De Temmerman, G.; Lisgo, S.; Rudakov, D. L.; Litnovsky, A.; Petersson, P.; John, P.; Wilson, J. I. B.

    2011-01-01

    Several types of diamond layers have been deposited on molybdenum tiles by chemical vapour deposition techniques, and exposed under erosion-dominated conditions in the SOL of TEXTOR in order to assess them as a suitable candidate for plasma-facing material. Post-exposure characterisation of physical

  14. The clinically relevant pharmacogenomic changes in acute myelogenous leukemia.

    Science.gov (United States)

    Emadi, Ashkan; Karp, Judith E

    2012-08-01

    Acute myelogenous leukemia (AML) is an extremely heterogeneous neoplasm with several clinical, pathological, genetic and molecular subtypes. Combinations of various doses and schedules of cytarabine and different anthracyclines have been the mainstay of treatment for all forms of AMLs in adult patients. Although this combination, with the addition of an occasional third agent, remains effective for treatment of some young-adult patients with de novo AML, the prognosis of AML secondary to myelodysplastic syndromes or myeloproliferative neoplasms, treatment-related AML, relapsed or refractory AML, and AML that occurs in older populations remains grim. Taken into account the heterogeneity of AML, one size does not and should not be tried to fit all. In this article, the authors review currently understood, applicable and relevant findings related to cytarabine and anthracycline drug-metabolizing enzymes and drug transporters in adult patients with AML. To provide a prime-time example of clinical applicability of pharmacogenomics in distinguishing a subset of patients with AML who might be better responders to farnesyltransferase inhibitors, the authors also reviewed findings related to a two-gene transcript signature consisting of high RASGRP1 and low APTX, the ratio of which appears to positively predict clinical response in AML patients treated with farnesyltransferase inhibitors.

  15. Streptococcus pyogenes biofilms – formation, biology,and clinical relevance

    Directory of Open Access Journals (Sweden)

    Tomas eFiedler

    2015-02-01

    Full Text Available Streptococcus pyogenes (group A streptococci, GAS is an exclusive human bacterial pathogen. The virulence potential of this species is tremendous. Interactions with humans range from asymptomatic carriage over mild and superficial infections of skin and mucosal membranes up to systemic purulent toxic-invasive disease manifestations. Particularly the latter are a severe threat for predisposed patients and lead to significant death tolls worldwide. This places GAS among the most important Gram-positive bacterial pathogens. Many recent reviews have highlighted the GAS repertoire of virulence factors, regulators and regulatory circuits/networks that enable GAS to colonize the host and to deal with all levels of the host immune defense. This covers in vitro and in vivo studies, including animal infection studies based on mice and more relevant, macaque monkeys. It is now appreciated that GAS, like many other bacterial species, do not necessarily exclusively live in a planktonic lifestyle. GAS is capable of microcolony and biofilm formation on host cells and tissues. We are now beginning to understand that this feature significantly contributes to GAS pathogenesis. In this review we will discuss the current knowledge on GAS biofilm formation, the biofilm-phenotype associated virulence factors, regulatory aspects of biofilm formation, the clinical relevance, and finally contemporary treatment regimens and future treatment options.

  16. Streptococcus pyogenes biofilms-formation, biology, and clinical relevance.

    Science.gov (United States)

    Fiedler, Tomas; Köller, Thomas; Kreikemeyer, Bernd

    2015-01-01

    Streptococcus pyogenes (group A streptococci, GAS) is an exclusive human bacterial pathogen. The virulence potential of this species is tremendous. Interactions with humans range from asymptomatic carriage over mild and superficial infections of skin and mucosal membranes up to systemic purulent toxic-invasive disease manifestations. Particularly the latter are a severe threat for predisposed patients and lead to significant death tolls worldwide. This places GAS among the most important Gram-positive bacterial pathogens. Many recent reviews have highlighted the GAS repertoire of virulence factors, regulators and regulatory circuits/networks that enable GAS to colonize the host and to deal with all levels of the host immune defense. This covers in vitro and in vivo studies, including animal infection studies based on mice and more relevant, macaque monkeys. It is now appreciated that GAS, like many other bacterial species, do not necessarily exclusively live in a planktonic lifestyle. GAS is capable of microcolony and biofilm formation on host cells and tissues. We are now beginning to understand that this feature significantly contributes to GAS pathogenesis. In this review we will discuss the current knowledge on GAS biofilm formation, the biofilm-phenotype associated virulence factors, regulatory aspects of biofilm formation, the clinical relevance, and finally contemporary treatment regimens and future treatment options.

  17. Clinical relevance of advanced glycation endproducts for vascular surgery.

    Science.gov (United States)

    Meerwaldt, R; van der Vaart, M G; van Dam, G M; Tio, R A; Hillebrands, J-L; Smit, A J; Zeebregts, C J

    2008-08-01

    Atherosclerosis is the main contributor to cardiovascular disease and leads to intimal plaque formation, which may progress to plaque rupture with subsequent thromboembolic events and/or occlusion of the arterial lumen. There is increasing evidence that the development or progression of atherosclerosis is associated with advanced glycation endproducts (AGEs). AGEs are a heterogeneous group of compounds formed by the non-enzymatic reaction of reducing sugars with proteins, lipids, and nucleic acids. An increased understanding of the mechanisms of formation and interaction of AGEs has allowed the development of several potential anti-AGE strategies. This review summarizes AGE formation and biochemistry, the pathogeneic role of AGEs in cardiovascular disease, anti-AGE therapies and clinical relevance to vascular surgery.

  18. Making the history of psychology clinically and philosophically relevant.

    Science.gov (United States)

    Vande Kemp, Hendrika

    2002-08-01

    The author discusses ways to make the history of psychology course relevant for a clinical psychology doctoral program within a multidenominational Protestant theological seminary. She uses a personalist orientation to emphasize the need to integrate psychology, philosophy, and theology. She differentiates among the intrapersonal, interpersonal, impersonal, and transpersonal dimensions of experience. She illustrates the rich multidisciplinary historical roots of contemporary psychology by tracing the the history of the term psychology and examining its meanings in the existential psychology of Søren Kierkegaard and in the 19th-century novel. She includes brief histories of the "new psychology" and of the unconscious. She describes how she uses the field of psychotheological integration to illustrate principles of historiography and summarizes resources used to supplement traditional textbooks.

  19. [Relevance of nutrition knowledge on clinical practice: medical opinion survey].

    Science.gov (United States)

    Alvares, Luísa; Moreira, Isabel; Oliveira, António

    2007-01-01

    Although previous studies show that physicians generally agree that nutrition knowledge is important for their daily clinical practice, several other studies report their poor knowledge of the subject. One of the strongest reasons given for this is the non-incorporation of Nutrition as a compulsory subject for the medical sciences degree. Dietary counselling and assessment of the patients' nutritional status don't seem to be systematic. The aim of this study is to asses how relevant physicians consider Nutrition to be in the successful running of a good practice. The study was undertaken at the general hospital of Vila Real/Peso da Régua (CHVR/PR) by distribution of a self- administered questionnaire to 153 of the physicians of the clinical body. Mean values were compared with the Student's t test and proportions with the Chi-square test. Of the 153 physicians, 108 replies were received (70,6%). Of these 108 replies, 53,3% consider nutrition knowledge important although 29,6% state their knowledge is poor. More than half say that Clinical Nutrition should be a compulsory subject of the Medical Sciences syllabus, and 99,1% deem it important to assess the patient's nutritional status. About 95% stated they provided written or verbal nutritional guidance, and most of the physicians had already sought the assistance of a nutritionist. This study shows that the clinical body of the CHVR/PR is aware of the importance nutrition knowledge has in their daily practice. It must be noted, though, that although almost one third of the physicians rate their nutrition knowledge poor, most of them provide nutritional guidance to their patients.

  20. Recycling cellulases for cellulosic ethanol production at industrial relevant conditions

    DEFF Research Database (Denmark)

    Lindedam, Jane; Haven, Mai Østergaard; Chylenski, Piotr

    2013-01-01

    to preserve enzymatic activity. Best results for enzyme recycling at 25% DM was 59% and 41% of original enzyme load for a Celluclast:Novozyme188 mixture and a modern cellulase preparation, respectively. However, issues with stability of enzymes and their strong adsorption to residual solids still pose......Different versions of two commercial cellulases were tested for their recyclability of enzymatic activity at high dry matter processes (12% or 25% DM). Recyclability was assessed by measuring remaining enzyme activity in fermentation broth and the ability of enzymes to hydrolyse fresh, pretreated...... wheat straw. Industrial conditions were used to study the impact of hydrolysis temperature (40 or 50. °C) and residence time on recyclability. Enzyme recycling at 12% DM indicated that hydrolysis at 50. °C, though ideal for ethanol yield, should be kept short or carried out at lower temperature...

  1. Volcanic ash melting under conditions relevant to ash turbine interactions.

    Science.gov (United States)

    Song, Wenjia; Lavallée, Yan; Hess, Kai-Uwe; Kueppers, Ulrich; Cimarelli, Corrado; Dingwell, Donald B

    2016-03-02

    The ingestion of volcanic ash by jet engines is widely recognized as a potentially fatal hazard for aircraft operation. The high temperatures (1,200-2,000 °C) typical of jet engines exacerbate the impact of ash by provoking its melting and sticking to turbine parts. Estimation of this potential hazard is complicated by the fact that chemical composition, which affects the temperature at which volcanic ash becomes liquid, can vary widely amongst volcanoes. Here, based on experiments, we parameterize ash behaviour and develop a model to predict melting and sticking conditions for its global compositional range. The results of our experiments confirm that the common use of sand or dust proxy is wholly inadequate for the prediction of the behaviour of volcanic ash, leading to overestimates of sticking temperature and thus severe underestimates of the thermal hazard. Our model can be used to assess the deposition probability of volcanic ash in jet engines.

  2. Resveratrol and calcium signaling: molecular mechanisms and clinical relevance.

    Science.gov (United States)

    McCalley, Audrey E; Kaja, Simon; Payne, Andrew J; Koulen, Peter

    2014-06-05

    Resveratrol is a naturally occurring compound contributing to cellular defense mechanisms in plants. Its use as a nutritional component and/or supplement in a number of diseases, disorders, and syndromes such as chronic diseases of the central nervous system, cancer, inflammatory diseases, diabetes, and cardiovascular diseases has prompted great interest in the underlying molecular mechanisms of action. The present review focuses on resveratrol, specifically its isomer trans-resveratrol, and its effects on intracellular calcium signaling mechanisms. As resveratrol's mechanisms of action are likely pleiotropic, its effects and interactions with key signaling proteins controlling cellular calcium homeostasis are reviewed and discussed. The clinical relevance of resveratrol's actions on excitable cells, transformed or cancer cells, immune cells and retinal pigment epithelial cells are contrasted with a review of the molecular mechanisms affecting calcium signaling proteins on the plasma membrane, cytoplasm, endoplasmic reticulum, and mitochondria. The present review emphasizes the correlation between molecular mechanisms of action that have recently been identified for resveratrol and their clinical implications.

  3. Clinical relevance of stem cell therapies in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Amit K Srivastava

    2014-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS, characterized by the progressive loss of both upper and lower motor neurons, is a fatal neurodegenerative disorder. This disease is often accompanied by a tremendous physical and emotional burden not only for the patients, but also for their families and friends as well. There is no clinically relevant treatment available for ALS. To date, only one Food and Drug Administration (FDA-approved drug, Riluzole, licensed 18 years ago, has been proven to marginally prolong patients′ survival without improving the quality of their lives. Because of the lack of an effective drug treatment and the promising outcomes from several preclinical studies, researchers have highlighted this disease as a suitable candidate for stem cell therapy. This review article highlights the finding of key preclinical studies that present a rationale for the use of different types of stem cells for the treatment of ALS, and the most recent updates on the stem cell-based ALS clinical trials around the world.

  4. Resveratrol and Calcium Signaling: Molecular Mechanisms and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Audrey E. McCalley

    2014-06-01

    Full Text Available Resveratrol is a naturally occurring compound contributing to cellular defense mechanisms in plants. Its use as a nutritional component and/or supplement in a number of diseases, disorders, and syndromes such as chronic diseases of the central nervous system, cancer, inflammatory diseases, diabetes, and cardiovascular diseases has prompted great interest in the underlying molecular mechanisms of action. The present review focuses on resveratrol, specifically its isomer trans-resveratrol, and its effects on intracellular calcium signaling mechanisms. As resveratrol’s mechanisms of action are likely pleiotropic, its effects and interactions with key signaling proteins controlling cellular calcium homeostasis are reviewed and discussed. The clinical relevance of resveratrol’s actions on excitable cells, transformed or cancer cells, immune cells and retinal pigment epithelial cells are contrasted with a review of the molecular mechanisms affecting calcium signaling proteins on the plasma membrane, cytoplasm, endoplasmic reticulum, and mitochondria. The present review emphasizes the correlation between molecular mechanisms of action that have recently been identified for resveratrol and their clinical implications.

  5. Natural killer cells: Biology, functions and clinical relevance

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2010-01-01

    Full Text Available Introduction. Natural Killer cells (NK cells represent the subset of peripheral lymphocytes that play critical role in the innate immune response to virus-infected and tumor transformed cells. Lysis of NK sensitive target cells could be mediated independently of antigen stimulation and without requirement of peptide presentation by the major histocompatibility complex (MHC molecules. NK cell activity and functions are controlled by a considerable number of cell surface receptors, which exist in both inhibitory and activating isoforms. There are several groups of NK cell surface receptors: 1 killer immunoglobulin like receptors-KIR, 2 C-type lectin receptors,3natural citotoxicity receptors-NCR and 4 Toll-like receptors-TLR. Functions of NK receptors. Defining the biology of NK cell surface receptors has contributed to the concept of the manner how NK cells selectively recognize and lyse tumor and virally infected cells while sparing normal cells. Further, identification of NK receptor ligands and their expression on the normal and transformed cells has led to the development of clinical approaches to manipulating receptor/ligand interactions that showed clinical benefit. NK cells are the first lymphocyte subset that reconstitute the peripheral blood following allogeneic HSCT and multiple roles for alloreactive donor NK cells have been demonstrated, in diminishing Graft vs. Host Disease (GvHD through selective killing recipient dendritic cells, prevention of graft rejection by killing recipient T cells and participation in Graft vs. Leukaemia (GvL effect through destruction of residual host tumor cells. Conclusion. Besides their role in HSCT, NK cell receptors have an important clinical relevance that reflects from the fact that they play a crucial role in the development of some diseases as well as in possibilities of managing all NK receptors through selective expansion and usage of NK cells in cancer immunotherapy.

  6. The clinical relevance of orthostatic hypotension in elderly patients.

    Science.gov (United States)

    Hartog, Laura; Kleefstra, Nanne; Luigies, Rene; de Rooij, Sophia; Bilo, Henk; van Hateren, Kornelis

    2017-02-22

    Orthostatic hypotension (OH) is highly prevalent in old age. The impact of OH on orthostatic complaints and falling is questionable. We wondered if the consensus definition of OH plays an essential role in the accuracy and direction of the prediction of these endpoints. We aimed to explore the relation between different definitions of OH, including relative decrease of blood pressure, and orthostatic complaints and falling. A cross-sectional study was performed with 1415 participants aged ≥65 years visiting a mobile fall-prevention team. The CAREFALL Triage Instrument and data on blood pressure, orthostatic complaints and previous fall incidents were collected. Multivariate binary logistic regression analyses were performed to assess the association of different definitions of OH and orthostatic complaints or falling. Ten different definitions of OH based on different relative declines of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were defined. The 2011 consensus definition of OH was not related to orthostatic complaints (Odds Ratio (OR) 1.07 (95 % Confidence Interval (CI) 0.68-1.69)) or previous fall incidents (OR 1.08 (95%CI 0.83-1.41)). A ≥ 25 % SBP decrease was significantly related to orthostatic complaints (OR 2.81 (95%CI 1.31-6.05)) and a ≥ 25 % DBP decrease was related to previous fall incidents (OR 2.56 (95%CI 1.08-6.09)). With the exception of a decrease of ≥25 % SBP or DBP, the clinical relevance of incidental OH blood pressure measurements seems very limited with respect to orthostatic complaints or fall incidents in elderly patients. Using relative decreases may be more appropriate in clinical practice. Geriatr Gerontol Int 2016; ••: ••-••. © 2017 Japan Geriatrics Society.

  7. Sulindac sulfide suppresses 5-lipoxygenase at clinically relevant concentrations.

    Science.gov (United States)

    Steinbrink, Svenja D; Pergola, Carlo; Bühring, Ulrike; George, Sven; Metzner, Julia; Fischer, Astrid S; Häfner, Ann-Kathrin; Wisniewska, Joanna M; Geisslinger, Gerd; Werz, Oliver; Steinhilber, Dieter; Maier, Thorsten J

    2010-03-01

    Sulindac is a non-selective inhibitor of cyclooxygenases (COX) used to treat inflammation and pain. Additionally, non-COX targets may account for the drug's chemo-preventive efficacy against colorectal cancer and reduced gastrointestinal toxicity. Here, we demonstrate that the pharmacologically active metabolite of sulindac, sulindac sulfide (SSi), targets 5-lipoxygenase (5-LO), the key enzyme in the biosynthesis of proinflammatory leukotrienes (LTs). SSi inhibited 5-LO in ionophore A23187- and LPS/fMLP-stimulated human polymorphonuclear leukocytes (IC(50) approximately 8-10 microM). Importantly, SSi efficiently suppressed 5-LO in human whole blood at clinically relevant plasma levels (IC(50) = 18.7 microM). SSi was 5-LO-selective as no inhibition of related lipoxygenases (12-LO, 15-LO) was observed. The sulindac prodrug and the other metabolite, sulindac sulfone (SSo), failed to inhibit 5-LO. Mechanistic analysis demonstrated that SSi directly suppresses 5-LO with an IC(50) of 20 muM. Together, these findings may provide a novel molecular basis to explain the COX-independent pharmacological effects of sulindac under therapy.

  8. Clinical Relevance of Autoantibodies in Patients with Autoimmune Bullous Dermatosis

    Directory of Open Access Journals (Sweden)

    Lilla Mihályi

    2012-01-01

    Full Text Available The authors present their experience related to the diagnosis, treatment, and followup of 431 patients with bullous pemphigoid, 14 patients with juvenile bullous pemphigoid, and 273 patients with pemphigus. The detection of autoantibodies plays an outstanding role in the diagnosis and differential diagnosis. Paraneoplastic pemphigoid is suggested to be a distinct entity from the group of bullous pemphigoid in view of the linear C3 deposits along the basement membrane of the perilesional skin and the “ladder” configuration of autoantibodies demonstrated by western blot analysis. It is proposed that IgA pemphigoid should be differentiated from the linear IgA dermatoses. Immunosuppressive therapy is recommended in which the maintenance dose of corticosteroid is administered every second day, thereby reducing the side effects of the corticosteroids. Following the detection of IgA antibodies (IgA pemphigoid, linear IgA bullous dermatosis, and IgA pemphigus, diamino diphenyl sulfone (dapsone therapy is preferred alone or in combination. The clinical relevance of autoantibodies in patients with autoimmune bullous dermatosis is stressed.

  9. Epileptic neuronal networks: methods of identification and clinical relevance.

    Science.gov (United States)

    Stefan, Hermann; Lopes da Silva, Fernando H

    2013-01-01

    The main objective of this paper is to examine evidence for the concept that epileptic activity should be envisaged in terms of functional connectivity and dynamics of neuronal networks. Basic concepts regarding structure and dynamics of neuronal networks are briefly described. Particular attention is given to approaches that are derived, or related, to the concept of causality, as formulated by Granger. Linear and non-linear methodologies aiming at characterizing the dynamics of neuronal networks applied to EEG/MEG and combined EEG/fMRI signals in epilepsy are critically reviewed. The relevance of functional dynamical analysis of neuronal networks with respect to clinical queries in focal cortical dysplasias, temporal lobe epilepsies, and "generalized" epilepsies is emphasized. In the light of the concepts of epileptic neuronal networks, and recent experimental findings, the dichotomic classification in focal and generalized epilepsy is re-evaluated. It is proposed that so-called "generalized epilepsies," such as absence seizures, are actually fast spreading epilepsies, the onset of which can be tracked down to particular neuronal networks using appropriate network analysis. Finally new approaches to delineate epileptogenic networks are discussed.

  10. Clinical Psychologists' Judgments of the Scientific Merit and Clinical-Relevance of Psychotherapy Outcome Research.

    Science.gov (United States)

    Cohen, Lawrence H.

    1979-01-01

    Result of this study indicated psychologists' judgments of scientific merit were influenced by patient assignment and follow-up but not by therapists' experience. Judgments of clinical relevance were influenced by patient population, the findings' applicability, and nature of therapy. Psychologists were more critical of methodology of studies…

  11. Update on Eosinophilic Meningoencephalitis and Its Clinical Relevance

    Science.gov (United States)

    Graeff-Teixeira, Carlos; da Silva, Ana Cristina Arámburu; Yoshimura, Kentaro

    2009-01-01

    Summary: Eosinophilic meningoencephalitis is caused by a variety of helminthic infections. These worm-specific infections are named after the causative worm genera, the most common being angiostrongyliasis, gnathostomiasis, toxocariasis, cysticercosis, schistosomiasis, baylisascariasis, and paragonimiasis. Worm parasites enter an organism through ingestion of contaminated water or an intermediate host and can eventually affect the central nervous system (CNS). These infections are potentially serious events leading to sequelae or death, and diagnosis depends on currently limited molecular methods. Identification of parasites in fluids and tissues is rarely possible, while images and clinical examinations do not lead to a definitive diagnosis. Treatment usually requires the concomitant administration of corticoids and anthelminthic drugs, yet new compounds and their extensive and detailed clinical evaluation are much needed. Eosinophilia in fluids may be detected in other infectious and noninfectious conditions, such as neoplastic disease, drug use, and prosthesis reactions. Thus, distinctive identification of eosinophils in fluids is a necessary component in the etiologic diagnosis of CNS infections. PMID:19366917

  12. Retrieving clinically relevant diabetic retinopathy images using a multi-class multiple-instance framework

    Science.gov (United States)

    Chandakkar, Parag S.; Venkatesan, Ragav; Li, Baoxin

    2013-02-01

    Diabetic retinopathy (DR) is a vision-threatening complication from diabetes mellitus, a medical condition that is rising globally. Unfortunately, many patients are unaware of this complication because of absence of symptoms. Regular screening of DR is necessary to detect the condition for timely treatment. Content-based image retrieval, using archived and diagnosed fundus (retinal) camera DR images can improve screening efficiency of DR. This content-based image retrieval study focuses on two DR clinical findings, microaneurysm and neovascularization, which are clinical signs of non-proliferative and proliferative diabetic retinopathy. The authors propose a multi-class multiple-instance image retrieval framework which deploys a modified color correlogram and statistics of steerable Gaussian Filter responses, for retrieving clinically relevant images from a database of DR fundus image database.

  13. Imaging of a clinically relevant stroke model: glucose hypermetabolism revisited.

    Science.gov (United States)

    Arnberg, Fabian; Grafström, Jonas; Lundberg, Johan; Nikkhou-Aski, Sahar; Little, Philip; Damberg, Peter; Mitsios, Nicholas; Mulder, Jan; Lu, Li; Söderman, Michael; Stone-Elander, Sharon; Holmin, Staffan

    2015-03-01

    Ischemic stroke has been shown to cause hypermetabolism of glucose in the ischemic penumbra. Experimental and clinical data indicate that infarct-related systemic hyperglycemia is a potential therapeutic target in acute stroke. However, clinical studies aiming for glucose control in acute stroke have neither improved functional outcome nor reduced mortality. Thus, further studies on glucose metabolism in the ischemic brain are warranted. We used a rat model of stroke that preserves collateral flow. The animals were analyzed by [2-(18)F]-2-fluoro-2-deoxy-d-glucose positron emission tomography or magnetic resonance imaging during 90-minute occlusion of the middle cerebral artery and during 60 minutes after reperfusion. Results were correlated to magnetic resonance imaging of cerebral blood flow, diffusion of water, lactate formation, and histological data on cell death and blood-brain barrier breakdown. We detected an increased [2-(18)F]-2-fluoro-2-deoxy-d-glucose uptake within ischemic regions succumbing to infarction and in the peri-infarct region. Magnetic resonance imaging revealed impairment of blood flow to ischemic levels in the infarct and a reduction of cerebral blood flow in the peri-infarct region. Magnetic resonance spectroscopy revealed lactate in the ischemic region and absence of lactate in the peri-infarct region. Immunohistochemical analyses revealed apoptosis and blood-brain barrier breakdown within the infarct. The increased uptake of [2-(18)F]-2-fluoro-2-deoxy-d-glucose in cerebral ischemia most likely reflects hypermetabolism of glucose meeting increased energy needs of ischemic and hypoperfused brain tissue, and it occurs under both anaerobic and aerobic conditions measured by local lactate production. Infarct-related systemic hyperglycemia could serve to facilitate glucose supply to the ischemic brain. Glycemic control by insulin treatment could negatively influence this mechanism. © 2015 American Heart Association, Inc.

  14. Nocebo phenomena in medicine: their relevance in everyday clinical practice.

    Science.gov (United States)

    Häuser, Winfried; Hansen, Ernil; Enck, Paul

    2012-06-01

    Nocebo phenomena are common in clinical practice and have recently become a popular topic of research and discussion among basic scientists, clinicians, and ethicists. We selectively searched the PubMed database for articles published up to December 2011 that contained the key words "nocebo" or "nocebo effect." By definition, a nocebo effect is the induction of a symptom perceived as negative by sham treatment and/or by the suggestion of negative expectations. A nocebo response is a negative symptom induced by the patient's own negative expectations and/or by negative suggestions from clinical staff in the absence of any treatment. The underlying mechanisms include learning by Pavlovian conditioning and reaction to expectations induced by verbal information or suggestion. Nocebo responses may come about through unintentional negative suggestion on the part of physicians and nurses. Information about possible complications and negative expectations on the patient's part increases the likelihood of adverse effects. Adverse events under treatment with medications sometimes come about by a nocebo effect. Physicians face an ethical dilemma, as they are required not just to inform patients of the potential complications of treatment, but also to minimize the likelihood of these complications, i.e., to avoid inducing them through the potential nocebo effect of thorough patient information. Possible ways out of the dilemma include emphasizing the fact that the proposed treatment is usually well tolerated, or else getting the patient's permission to inform less than fully about its possible side effects. Communication training in medical school, residency training, and continuing medical education would be desirable so that physicians can better exploit the power of words to patients' benefit, rather than their detriment.

  15. Hyperthermic radiosensitization : mode of action and clinical relevance

    NARCIS (Netherlands)

    Kampinga, HH; Dikomey, E

    2001-01-01

    Purpose: To provide an update on the recent knowledge about the molecular mechanisms of thermal radiosensitization and its possible relevance to thermoradiotherapy. Summary: Hyperthermia is probably the most potent cellular radiosensitizer known to date. Heat interacts with radiation and potentiates

  16. Vegetation relevés and soil measurements in the Netherlands: the Ecological Conditions Database (EC)

    NARCIS (Netherlands)

    Wamelink, G.W.W.; Adrichem, van M.H.C.; Dobben, van H.F.; Frissel, J.Y.; Held, den M.E.; Joosten, V.; Malinowska, A.H.; Slim, P.A.; Wegman, R.M.A.

    2012-01-01

    Since its establishment around 1990, the Ecological Conditions Database (EC; GIVD ID EU-00-006) has been accumulating vegetation relevés from the Netherlands, each accompanied by at least one abiotic soil measurement (e.g. pH or nutrient availability). On 1-1-2010, the database contained 8,229 relev

  17. Evidence-Based Clinical Significance in Health Care: Toward an Inferential Analysis of Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Mahsa Dousti

    2011-09-01

    Full Text Available Evidence-based dental practice requires the developmment and evaluation of protocols that en-sure translational effectiveness: that is, the efficient incorporation of the best available efficacy and effec-tiveness findings in specific clinical dentistry settings and environments. Evidence-based dentistry predi-cates the synthesis of research for obtaining the best available evidence in a validated, stringent, systematic and unbiased fashion. Research synthesis is now established as a science in its own right, precisely because it adheres to the scientific process that is driven by a research question and a hypothesis, follows through clearly defined methodology and design, yielding quantifiable data that are analyzed statistically, and from which stringent statistical inferences are drawn. The conclusions from the protocol of research synthesis define the best available evidence, which is used in the process of evidence-based revision of clinical practice guidelines. One important hurdle of the process of applying research synthesis in evidence-based dentistry lies in the fact that the statistical inferences produced by research must be translated into clinical relevance. Here, we present a model to circumvent this limitation by means of text analysis/mining protocols, which could lead the path toward a novel, valid and reliable ap-proach for the inferential analysis of clinical relevance.

  18. Clinically applied medical ethnography: relevance to cultural competence in patient care.

    Science.gov (United States)

    Engebretson, Joan

    2011-06-01

    Medical anthropology provides an excellent resource for nursing research that is relevant to clinical nursing. By expanding the understanding of ethnographic research beyond ethnicity, nurses can conduct research that explores patient's constructions and explanatory models of health and healing and how they make meaning out of chronic conditions and negotiate daily life. These findings can have applicability to culturally competent care at both the organizational or systems level, as well as in the patient/provider encounter. Individual patient care can be improved by applying ethnographic research findings to build provider expertise and then using a cultural negotiation process for individualized patient care.

  19. Carbon dioxide production during cardiopulmonary bypass: pathophysiology, measure and clinical relevance.

    Science.gov (United States)

    Ranucci, Marco; Carboni, Giovanni; Cotza, Mauro; de Somer, Filip

    2017-01-01

    Carbon dioxide production during cardiopulmonary bypass derives from both the aerobic metabolism and the buffering of lactic acid produced by tissues under anaerobic conditions. Therefore, carbon dioxide removal monitoring is an important measure of the adequacy of perfusion and oxygen delivery. However, routine monitoring of carbon dioxide removal is not widely applied. The present article reviews the main physiological and pathophysiological sources of carbon dioxide, the available techniques to assess carbon dioxide production and removal and the clinically relevant applications of carbon dioxide-related variables as markers of the adequacy of perfusion during cardiopulmonary bypass.

  20. Decaying relevance of clinical data towards future decisions in data-driven inpatient clinical order sets.

    Science.gov (United States)

    Chen, Jonathan H; Alagappan, Muthuraman; Goldstein, Mary K; Asch, Steven M; Altman, Russ B

    2017-06-01

    Determine how varying longitudinal historical training data can impact prediction of future clinical decisions. Estimate the "decay rate" of clinical data source relevance. We trained a clinical order recommender system, analogous to Netflix or Amazon's "Customers who bought A also bought B..." product recommenders, based on a tertiary academic hospital's structured electronic health record data. We used this system to predict future (2013) admission orders based on different subsets of historical training data (2009 through 2012), relative to existing human-authored order sets. Predicting future (2013) inpatient orders is more accurate with models trained on just one month of recent (2012) data than with 12 months of older (2009) data (ROC AUC 0.91 vs. 0.88, precision 27% vs. 22%, recall 52% vs. 43%, all P<10(-10)). Algorithmically learned models from even the older (2009) data was still more effective than existing human-authored order sets (ROC AUC 0.81, precision 16% recall 35%). Training with more longitudinal data (2009-2012) was no better than using only the most recent (2012) data, unless applying a decaying weighting scheme with a "half-life" of data relevance about 4 months. Clinical practice patterns (automatically) learned from electronic health record data can vary substantially across years. Gold standards for clinical decision support are elusive moving targets, reinforcing the need for automated methods that can adapt to evolving information. Prioritizing small amounts of recent data is more effective than using larger amounts of older data towards future clinical predictions. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. [The clinical relevance of opioid-induced hyperalgesia remains unresolved].

    Science.gov (United States)

    Sørensen, Jakob; Sjøgren, Per

    2011-03-28

    Opioids are widely used as analgesics in chronic pain of malignant as well as non-malignant origin. During opioid treatment, pain is occasionally worsened. This could be due to progression of the disease or tolerance or opioid-induced hyperalgesia (OIH). The present article summarizes the preclinical and clinical data in support of the existence of OIH. Further, possible mechanisms and potential treatments are outlined. We conclude that only a few clinical studies on OIH are available. However, a growing body of experimental data supports the presence of OIH in clinical settings. Diagnostic tools for assessment of OIH have yet to be developed.

  2. Teachers' Perceptions of Their Working Conditions: How Predictive of Policy-Relevant Outcomes? Working Paper 33

    Science.gov (United States)

    Ladd, Helen F.

    2009-01-01

    This quantitative study uses data from North Carolina to examine the extent to which survey based perceptions of working conditions are predictive of policy-relevant outcomes, independent of other school characteristics such as the demographic mix of the school's students. Working conditions emerge as highly predictive of teachers' stated…

  3. Opioid-induced hyperalgesia: clinically relevant or extraneous research phenomenon?

    Science.gov (United States)

    Tompkins, D Andrew; Campbell, Claudia M

    2011-04-01

    Opioids have become the unequivocal therapy of choice in treating many varieties of chronic pain. With the increased prescription of opioids, some unintended consequences have occurred. After prolonged opioid exposure, opioid-induced hyperalgesia (OIH), the paradoxical effect that opioid therapy may in fact enhance or aggravate preexisting pain, may occur. Over the past several decades, an increasing number of laboratory and clinical reports have suggested lowered pain thresholds and heightened atypical pain unrelated to the original perceived pain sensations as hallmarks of OIH. However, not all evidence supports the clinical importance of OIH, and some question whether the phenomenon exists at all. Here, we present a nonexhaustive, brief review of the recent literature. OIH will be reviewed in terms of preclinical and clinical evidence for and against its existence; recommendations for clinical evaluation and intervention also will be discussed.

  4. Clinical relevance of host immunity in breast cancer: from TILs to the clinic.

    Science.gov (United States)

    Savas, Peter; Salgado, Roberto; Denkert, Carsten; Sotiriou, Christos; Darcy, Phillip K; Smyth, Mark J; Loi, Sherene

    2016-04-01

    The clinical relevance of the host immune system in breast cancer has long been unexplored. Studies developed over the past decade have highlighted the biological heterogeneity of breast cancer, prompting researchers to investigate whether the role of the immune system in this malignancy is similar across different molecular subtypes of the disease. The presence of high levels of lymphocytic infiltration has been consistently associated with a more-favourable prognosis in patients with early stage triple-negative and HER2-positive breast cancer. These infiltrates seem to reflect favourable host antitumour immune responses, suggesting that immune activation is important for improving survival outcomes. In this Review, we discuss the composition of the immune infiltrates observed in breast cancers, as well as data supporting the clinical relevance of host antitumour immunity, as represented by lymphocytic infiltration, and how this biomarker could be used in the clinical setting. We also discuss the rationale for enhancing immunity in breast cancer, including early data on the efficacy of T-cell checkpoint inhibition in this setting.

  5. A Comparison of Management Conditions in Japan's Dental Clinics and Medical Clinics

    Directory of Open Access Journals (Sweden)

    Koichi Kawabuchi

    2015-08-01

    Full Text Available In recent years, national medical expenditures have continued to increase in Japan, and have now reached 39 trillion yen. In contrast, dental clinic expenditures have been slow to grow over the past few years, totaling 2.7132 trillion yen. At the same time, the number of dentists continues to increase, with a total of 102,551 dentists in 2012, surpassing the 100,544 physicians at medical clinics. Objective: Given this, we compared management conditions at dental clinics and medical clinics over time to determine whether management conditions of dental clinics are really as harsh as often claimed. Methods: we used the relevant data provided in the Central Social Insurance Medical Council's Survey on Economic Conditions in Health Care for statistics, which depicts management conditions at clinics, and analyzed the causes. Results: Annual fluctuations in the revenue/expense gap (revenue less expense show that the gap for dentists far undercut that for physicians at medical clinics. The main reason for this decline in revenue is that the number of dental patients declined more that the unit price rose compared to the medical clinic. Conclusion: We determined that management conditions are harsh for dental clinics.DOI: 10.14693/jdi.v22i2.507

  6. Clinical relevance of drug-drug interactions - A structured assessment procedure

    NARCIS (Netherlands)

    van Roon, EN; Flikweert, S; le Comte, M; Langendijk, PNJ; Kwee-Zuiderwijk, WJM; Smits, P; Brouwers, JRBJ

    2005-01-01

    Introduction: Computerised drug interaction surveillance systems (CIS) may be helpful in detecting clinically significant drug interactions. Experience with CIS C, reveals that they often yield alerts with questionable clinical significance, fail to provide relevant information on risk factors for t

  7. Clinical relevance of drug-drug interactions : a structured assessment procedure.

    NARCIS (Netherlands)

    Roon, E.N. van; Flikweert, S.; Comte, M. le; Langendijk, P.N.; Kwee-Zuiderwijk, W.J.; Smits, P.; Brouwers, J.R.B.J.

    2005-01-01

    INTRODUCTION: Computerised drug interaction surveillance systems (CIS) may be helpful in detecting clinically significant drug interactions. Experience with CIS reveals that they often yield alerts with questionable clinical significance, fail to provide relevant information on risk factors for the

  8. Reported insulin pump temperature fluctuations lack clinical relevance

    Directory of Open Access Journals (Sweden)

    Dokken BB

    2017-02-01

    Full Text Available Betsy B Dokken, Michael Rosinko Tandem Diabetes Care, Inc., San Diego, CA, USAIn their recent paper, Vereshchetin et al1 suggested that the heat generated by the Tandem Diabetes Care, Inc. (San Diego, CA, USA t:slim® Insulin Pump during battery charging is high enough to degrade insulin. There are several reasons that the arguments made in this paper are not relevant to patient use of the t:slim Insulin Pump.View original paper by Vereshchetin et al.

  9. Anomalous course of the extensor pollicis longus: clinical relevance.

    Science.gov (United States)

    Rubin, Guy; Wolovelsky, Alejandro; Rinott, Micha; Rozen, Nimrod

    2011-11-01

    The extensor pollicis longus (EPL) is a consistent structure with rare anomalies, the most common being a group of different tendon duplications passing through the fourth compartment without symptoms. The second form comprises anomalies in the course of the EPL having significant clinical importance due to the predisposition for creating tenosynovitis of the EPL mimicking other types of tendon tenosynovitis. Clinical symptoms of radial dorsal wrist pain mimicking intersection syndrome or de-Quervain disease with the "absent snuff box" sign should raise suspicions for an anomaly in the course of the EPL.

  10. Pharmacogenetics in Cardiovascular Disease is there clinical relevance?

    NARCIS (Netherlands)

    Maitland-Van Der Zee, A.

    2014-01-01

    • Objectives: To give an up-to-date overview of the research in pharmacogenetics of cardiovascular disease, and the clinical implications of this research. • Methods: In this lecture I will focus on these groups cardiovascular drugs where many pharmacogenetics studies have been performed (including

  11. Biomolecular features of clinical relevance in breast cancer

    NARCIS (Netherlands)

    Daidone, M.G.; Paradiso, A.; Gion, M.; Harbeck, N.; Sweep, C.G.J.; Schmitt, M.

    2004-01-01

    Breast cancer is a heterogeneous disease and its consequent complexity is a major challenge for physicians and biologists. Notwithstanding its potential curability due to the availability of treatment modalities which are effective in the presence of favourable clinical or pathobiological features,

  12. Assessment of relevant fungal species in clinical solid wastes.

    Science.gov (United States)

    Noman, Efaq Ali; Al-Gheethi, A A; Rahman, Nik Norulaini Nik Ab; Nagao, H; Ab Kadir, M O

    2016-10-01

    The study aimed to determine the fungal diversity in clinical waste samples from a healthcare facility in Penang Malaysia. Different fungi species were detected in 83.75 % of the 92 clinical waste samples that were screened from different sections of the healthcare facility. One hundred fifty fungal isolates comprising of 8 genera and 36 species were obtained. They were purified by using single spore isolation technique. Subsequently, the isolates were identified by phenotypic method based on morphological and culture characteristics on different culture media. Among all fungal isolates, Aspergillus spp. in section Nigri 10.2 %, Aspergillus niger 9.5 %, Aspergillus fumigatus 8.8 %, Penicillium. simplicissium 8 %, Aspergillus tubingensis 7.3 %, Aspergillus terreus var. terreus 6.6 %, Penicillium waksmanii 5.9 % and Curvularia lunata 6.5 % were the most frequent. Among five sections of the Wellness Centre, the clinical wastes collected from the diagnostic labs of haematology section had the highest numbers of fungal species (29 species). Glove wastes had the highest numbers of fungal species (19 species) among 17 types of clinical wastes screened. Among all fungal species, Aspergillus spp. exhibited higher growth at 37 °C than at 28 °C, indicating the potential of these opportunistic fungi to cause diseases in human. These results indicated the potential of hospital wastes as reservoirs for fungal species.

  13. Clinical relevance of negative initial angiogram in spontaneous subarachnoid hemorrhage.

    Science.gov (United States)

    Moscovici, Samuel; Fraifeld, Shifra; Ramirez-de-Noriega, Fernando; Rosenthal, Guy; Leker, Ronen R; Itshayek, Eyal; Cohen, José E

    2013-03-01

    We aimed to compare the presentation, management, and clinical course in patients with perimesencephalic and nonperimesencephalic (aneurysmal) bleeding patterns on noncontrast CT, but negative initial 4-vessel digital subtraction angiography (DSA). We retrospectively reviewed clinical and imaging data for 280 patients presenting with spontaneous SAH admitted between 2005 and 2011. We identified 56 patients (20%) with SAH diagnosed on high resolution head CT performed within 48 hours of admission, and negative initial DSA, and divided them into perimesencephalic and non-perimesencephalic groups based on hemorrhage patterns. Patients with traumatic subarachnoid bleeding and those with initial positive DSA were excluded from this analysis. Perimesencephalic SAH was seen in 25 patients (45%); non-perimesencephalic bleeding patterns were seen in 31 (55%). All patients with perimesencephalic SAH presented with Hunt and Hess (HH) I, versus 45% HH I and 55% HH II-IV in those with non-perimecenphalic SAH. All patients with perimesencephalic SAH achieved modified Rankin score (mRS) 0 at discharge and 6-month follow-up, compared with 45% mRS 0 at discharge and 68% at 6-month follow-up in non-perimesencephalic SAH. Patients with perimesencephalic SAH presented a uniformly uncomplicated clinical course. Among non-perimesencephalic SAH patients there were 19 neurological/neurosurgical and 10 medical complications, two small aneurysms diagnosed at follow-up DSA, and one death. In this series, perimesencephalic SAH was associated with good clinical grades, consistently negative initial and follow-up angiograms, and an excellent prognosis. In contrast, non-perimesencephalic SAH was associated with a worse clinical presentation, higher complication rates, higher rates of true aneurysm detection on follow-up angiogram, and a poorer outcome.

  14. Developing independent investigators for clinical research relevant for Africa

    LENUS (Irish Health Repository)

    Manabe, Yukari C

    2011-12-29

    Abstract Sustainable research capacity building requires training individuals at multiple levels within a supportive institutional infrastructure to develop a critical mass of independent researchers. At many African medical institutions, a PhD is important for academic promotion and is, therefore, an important focal area for capacity building programs. We examine the training at the Infectious Diseases Institute (IDI) as a model for in-country training based on systems capacity building and attention to the academic environment. PhD training in Africa should provide a strong research foundation for individuals to perform independent, original research and to mentor others. Training the next generation of researchers within excellent indigenous academic centers of excellence with strong institutional infrastructure will empower trainees to ask regionally relevant research questions that will benefit Africans.

  15. Framework conditions facilitating paediatric clinical research

    Directory of Open Access Journals (Sweden)

    Alfarez Deborah

    2011-02-01

    Full Text Available Abstract The use of unlicensed and "off-label" medicines in children is widespread. Between 50-80% of the medicines currently administered to children have neither been tested nor authorized for their use in the paediatric population which represents approximately 25% of the whole European population. On 26 January 2007, entered into force the European Regulation of Paediatric Medicines. It aims at the quality of research into medicines for children but without subjecting the paediatric population to unnecessary clinical trial. This article addresses ethical and legal issues arising from the regulation and makes recommendations for the framework conditions facilitating the development of clinical research with children.

  16. Hepatitis E Virus Mutations: Functional and Clinical Relevance

    OpenAIRE

    Hoang van Tong; Nghiem Xuan Hoan; Bo Wang; Heiner Wedemeyer; C.-Thomas Bock; Velavan, Thirumalaisamy P.

    2016-01-01

    Highlights • HEV causes acute hepatitis and recently comes into focus because of persistent infection in immunocompromised patients. • HEV variability can be associated with clinical pathogenesis and transmission dynamics. • Mutations in the HEV genome can influence HEV physiology and virus-host interaction. • HEV mutations and variability are likely associated with fulminant hepatic failure and chronic hepatitis E. • The Y1320H and G1634R/K mutations in the RdRp domain contribute to antivira...

  17. [Clinical research IV. Relevancy of the statistical test chosen].

    Science.gov (United States)

    Talavera, Juan O; Rivas-Ruiz, Rodolfo

    2011-01-01

    When we look at the difference between two therapies or the association of a risk factor or prognostic indicator with its outcome, we need to evaluate the accuracy of the result. This assessment is based on a judgment that uses information about the study design and statistical management of the information. This paper specifically mentions the relevance of the statistical test selected. Statistical tests are chosen mainly from two characteristics: the objective of the study and type of variables. The objective can be divided into three test groups: a) those in which you want to show differences between groups or inside a group before and after a maneuver, b) those that seek to show the relationship (correlation) between variables, and c) those that aim to predict an outcome. The types of variables are divided in two: quantitative (continuous and discontinuous) and qualitative (ordinal and dichotomous). For example, if we seek to demonstrate differences in age (quantitative variable) among patients with systemic lupus erythematosus (SLE) with and without neurological disease (two groups), the appropriate test is the "Student t test for independent samples." But if the comparison is about the frequency of females (binomial variable), then the appropriate statistical test is the χ(2).

  18. Taxonomy, Epidemiology, and Clinical Relevance of the Genus Arcobacter

    Science.gov (United States)

    Collado, Luis; Figueras, Maria José

    2011-01-01

    Summary: The genus Arcobacter, defined almost 20 years ago from members of the genus Campylobacter, has become increasingly important because its members are being considered emergent enteropathogens and/or potential zoonotic agents. Over recent years information that is relevant for microbiologists, especially those working in the medical and veterinary fields and in the food safety sector, has accumulated. Recently, the genus has been enlarged with several new species. The complete genomes of Arcobacter butzleri and Arcobacter nitrofigilis are available, with the former revealing diverse pathways characteristic of free-living microbes and virulence genes homologous to those of Campylobacter. The first multilocus sequence typing analysis showed a great diversity of sequence types, with no association with specific hosts or geographical regions. Advances in detection and identification techniques, mostly based on molecular methods, have been made. These microbes have been associated with water outbreaks and with indicators of fecal pollution, with food products and water as the suspected routes of transmission. This review updates this knowledge and provides the most recent data on the taxonomy, species diversity, methods of detection, and identification of these microbes as well as on their virulence potential and implication in human and animal diseases. PMID:21233511

  19. Clinical relevance of KIRs in hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2010-01-01

    Full Text Available Introduction Natural Killer cells (NK cells represent the subset of peripheral lymphocytes that play critical role in the innate immune response to virus-infected and tumor transformed cells. Lysis of NK sensitived target cells could be mediated independently of antigen stimulation, and unlike cytotoxic T-lymphocytes, they do not require peptide presentation by the major histocompatibility complex (MHC molecules. NK cell cytotoxic activity is controlled by considerable number of cell surface Killer cell Immunoglobulin like Receptors (KIRs, which can exist in both inhibitory and activating isoforms. The inhibitory KIRs are mostly specific for HLA class I ligands and I HLA class like molecules, while the specificity of activating receptors is regarded to lectine-like superfamily. The role of NK cells in allogeneic haematopoietic stem cell transplantation (HSCT: NK cells are the first lymphocyte subset that reconstitute the peripheral blood following allogeneic HSCT. By selecting donors mismatched for relevant HLA ligands in the context of recipients KIR genotype, multiple roles for alloreactive donor NK cells have been demonstrated, in diminishing Graft vs. Host Disease (GvHD through selective killing of recipient dendritic cells, prevention of graft rejection by killing recipient T cells and participation in Graft vs. Leukaemia (GvL effect through destruction of residual host tumor cells. Conclusion Investigation of KIRs heterogenity play an important role in the field of HSCT, because it is useful for the early diagnosis of post transplant complications and can serve as a predictive risk factor for GvHD development.

  20. Taxonomy, epidemiology, and clinical relevance of the genus Arcobacter.

    Science.gov (United States)

    Collado, Luis; Figueras, Maria José

    2011-01-01

    The genus Arcobacter, defined almost 20 years ago from members of the genus Campylobacter, has become increasingly important because its members are being considered emergent enteropathogens and/or potential zoonotic agents. Over recent years information that is relevant for microbiologists, especially those working in the medical and veterinary fields and in the food safety sector, has accumulated. Recently, the genus has been enlarged with several new species. The complete genomes of Arcobacter butzleri and Arcobacter nitrofigilis are available, with the former revealing diverse pathways characteristic of free-living microbes and virulence genes homologous to those of Campylobacter. The first multilocus sequence typing analysis showed a great diversity of sequence types, with no association with specific hosts or geographical regions. Advances in detection and identification techniques, mostly based on molecular methods, have been made. These microbes have been associated with water outbreaks and with indicators of fecal pollution, with food products and water as the suspected routes of transmission. This review updates this knowledge and provides the most recent data on the taxonomy, species diversity, methods of detection, and identification of these microbes as well as on their virulence potential and implication in human and animal diseases.

  1. Functional and clinical relevance of chondroitin sulfate proteoglycan 4.

    Science.gov (United States)

    Campoli, Michael; Ferrone, Soldano; Wang, Xinhui

    2010-01-01

    The lack of effective conventional therapies for the treatment of advanced stage melanoma has stimulated interest in the development of novel strategies for the management of patients with malignant melanoma. Among them, immunotherapy has attracted much attention because of the potential role played by immunological events in the clinical course of melanoma. For many years, T cell-based immunotherapy has been emphasized in part because of the disappointing results of the monoclonal antibody (mAb)-based clinical trials conducted in the early 1980s and in part because of the postulated major role played by T cells in tumor growth control. More recently, mAb-based therapies have gained in popularity given their clinical and commercial success for a variety of malignant diseases. As a result, there has been increased interest in identifying and characterizing antibody-defined melanoma antigens. Among them, the chondroitin sulfate proteoglycan 4 (CSPG4), also known as high molecular weight-melanoma associated antigen (HMW-MAA) or melanoma chondroitin sulfate proteoglycan (MCSP), has attracted much attention in recent years because of the growing experimental evidence that it fulfills two requirements for immunotherapy to be therapeutically effective: (1) targeting of cancer stem cells (CSC) and (2) development of combinatorial therapies to counteract the escape mechanisms driven by the genetic instability of tumor cells. With this in mind, in this chapter, we have reviewed recent information related to the distribution of CSPG4 on various types of tumors, including CSC, its expression on pericytes in the tumor microenvironment, its recognition by T cells, its role in cell biology as well as the potential mechanisms underlying the ability of CSPG4-specific immunity to control malignant cell growth.

  2. Relevance of guideline-based ICD indications to clinical practice.

    Science.gov (United States)

    Al-Jefairi, Nora; Burri, Haran

    2014-01-01

    The implantable cardioverter-defibrillator (ICD) has established itself as life-saving therapy in patients at risk for sudden cardiac death. Remarkable technological advances have made ICDs easier and safer to implant, with improved therapeutic and diagnostic functions and reduced morbidity. Guidelines on ICD indications have been proposed by American and European scientific societies since a number of years, based upon trials and expert opinion. In the context of variable economic and political constraints, it is questionable whether these guidelines may be applied to all settings. This review discusses the guideline-based indications, critically examines their applicability to clinical practice, and discusses alternatives to ICD therapy.

  3. Thyroid Autoantibodies in Pregnancy: Their Role, Regulation and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Francis S. Balucan

    2013-01-01

    Full Text Available Autoantibodies to thyroglobulin and thyroid peroxidase are common in the euthyroid population and are considered secondary responses and indicative of thyroid inflammation. By contrast, autoantibodies to the TSH receptor are unique to patients with Graves' disease and to some patients with Hashimoto's thyroiditis. Both types of thyroid antibodies are useful clinical markers of autoimmune thyroid disease and are profoundly influenced by the immune suppression of pregnancy and the resulting loss of such suppression in the postpartum period. Here, we review these three types of thyroid antibodies and their antigens and how they relate to pregnancy itself, obstetric and neonatal outcomes, and the postpartum.

  4. Clinical Practice Guidelines for Convulsive Condition Management

    Directory of Open Access Journals (Sweden)

    Victor Rene Navarro Machado

    2009-03-01

    Full Text Available Clinical Practice Guidelines for Convulsive Condition Management. It has been redefined as the occurrence of two or more successive convulsions without conscience recuperation between them; or the occurrence of convulsive uninterrupted activity for more than 5 minutes, including focal crisis. This document includes a review and update of conceptual, etiological and classification aspects for diagnosis and treatment, stressing the various therapy trends. It includes assessment guidelines focused on the most important aspects to be accomplished.

  5. A Clinically Relevant Frailty Index for Aging Rats.

    Science.gov (United States)

    Miller, Marshall G; Thangthaeng, Nopporn; Shukitt-Hale, Barbara

    2017-07-01

    Frailty is a clinical syndrome that is increasingly prevalent during aging. Frailty involves the confluence of reduced strength, speed, physical activity, and endurance and is associated with adverse health outcomes. The present study adapts existing clinical and preclinical indices of frailty to the Fischer (F344) rat. Male F344 rats (n = 133; 17 mo) completed a battery of behavioral tasks, including forelimb wire suspension (strength), rotarod (speed), open field (physical activity), and inclined screen (endurance). Rats that performed poorly (lowest quintile) on two tasks were considered mildly frail (17.29%, n = 23), and rats that performed poorly on 3-4 tasks were considered frail (2.26%, n = 3). Logistic regression of 100-day survival revealed that mildly frail rats were 3.8 times and frail rats were 27.5 times more likely to die during that period than nonfrail rats (p = .038; 95% confidence interval: 2.030, 372.564). The selected criterion tests, cutoff points, and index provide a potential tool for identifying frailty in aged F344 rats, which is consistent with existing frailty indices for humans and mice. Published by Oxford University Press on behalf of The Gerontological Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  6. [Opioid-induced hyperalgesia. Pathophysiology and clinical relevance].

    Science.gov (United States)

    Koppert, W

    2004-05-01

    Opioids are the drugs of choice for the treatment of moderate to severe acute and chronic pain. However, clinical evidence suggests that opioids can elicit increased sensitivity to noxious stimuli suggesting that administration of opioids can activate both pain inhibitory and pain facilitatory systems. Acute receptor desensitization via uncoupling of the receptor from G-proteins, up-regulation of the cAMP pathway, activation of the N-methyl-D-aspartate (NMDA) receptor system, as well as descending facilitation, have been proposed as potential mechanisms underlying opioid-induced hyperalgesia. Numerous reports exist demonstrating that opioid-induced hyperalgesia is observed both in animal and human experimental models. Brief exposures to micro-receptor agonists induce long-lasting hyperalgesic effects for days, which might by reflected by clinical observations that large doses of intraoperative micro-receptor agonists increased postoperative pain and morphine consumption. Furthermore, the prolonged use of opioids in patients often requires increasing doses and may be accompanied by the development of abnormal pain. Successful strategies that may decrease or prevent opioid-induced hyperalgesia include the concomitant administration of drugs like NMDA-antagonists, alpha(2)-agonists, or non-steroidal anti-inflammatory drugs (NSAIDs), opioid rotation or combinations of opioids with different receptor selectivity.

  7. Clinical relevance of molecular diagnosis in pet allergy.

    Science.gov (United States)

    Uriarte, S A; Sastre, J

    2016-07-01

    We describe the pattern of sensitisation to pet IgE components and its association with clinical symptoms. Hundred and fifty nine consecutive patients with rhinitis/asthma sensitised to dog, cat, and horse were recruited. Specific IgE to whole extracts and to pet recombinant allergens were performed. Only 5% of patients were monosensitised to animal allergens. Specific IgE to Can f 1 was significantly associated with persistent rhinitis, Can f 2 with asthma diagnosis, Can f 3 with moderate/severe rhinitis (M/S-R) and asthma diagnosis (AD), and Can f 5 with persistent and M/S-R. Positive IgE to Fel d 2 was significantly associated with M/S-R and AD, Equ c 1 with M/S-R and Equ c 3 with persistent rhinitis, AD and severe asthma. Sensitisation to ≥2 molecules or to pet albumins was associated with more severe respiratory symptoms. Molecular diagnosis in patients with pet allergy may also help clinicians to predict clinical symptoms and their severity.

  8. Remote ischemic conditioning: Current clinical perspectives.

    Science.gov (United States)

    Le Page, Sophie; Prunier, Fabrice

    2015-08-01

    Remote ischemic conditioning (RIC) constitutes a promising method in which a tissue or organ is exposed to intermittent ischemia/reperfusion periods enabling it to provide protection to a distant target organ. RIC has been tested in various clinical settings through its simple application by means of intermittent inflation of a blood pressure cuff placed on a limb, primarily evaluating its potential abilities to decrease myocardial injury biomarkers. Its use on other organs, such as the kidneys or brain, has recently been a topic of research. To date, no study has yet been powerful enough to reach a conclusion on the potential benefit of RIC on clinical outcomes. The future role of RIC in the clinical arena could be clarified by the large phase III trials currently underway targeting major outcomes as primary endpoints.

  9. [Research training in nutrition: relevance for medical clinical pratice].

    Science.gov (United States)

    Coronha, Ana Lúcia; Lourenço, Cláudia; Ferreira, Marlene; Reis, Nélia; Almeida, Raquel; Boléo-Tomé, Carolina; Monteiro-Grillo, Isabel; Camilo, Maria Ermelinda; Ravasco, Paula

    2011-01-01

    In oncology, early and individualized nutritional intervention for each patient is essential to improve nutritional intake and status, to reduce morbidity during treatment, enhance tolerance to treatment and improve Quality of Life. For medical students to evaluate nutritional risk and status, analyse the prevalence of undernutrition in a population of patients with diverse types of tumours. We aimed to identify difficulties regarding the use of the MUST tool (Malnutrition Universal Screening Tool) for nutritional risk by the students. This study included 35 cancer patients consecutively referenced for Radiotherapy (RT) in the Radiotherapy Department of the University Hospital of Santa Maria. Nutritional risk was evaluated by MUST; nutritional status by Patient Generated-Subjective Global Assessment (PG-SGA) validated and specific for oncology. Students identified 13 patients (36%) at moderate/high risk of undernutrition. According to PG-SGA, 31,5% (11/35) of patients presented moderate or severe undernutrition, of which 77% of patients needed individualized nutritional counselling. Students successfully detected undernourished patients using these specific methods. Risk of undernutrition and undernutrition are common in oncology, therefore indicating the critical need to educate all health professionals for risk screening and for the relevance of nutritional intervention in the multidisciplinary context. MUST is a simple and quick tool, that demonstrated to be adequate when applied by medical students, well accepted by these health professionals and effectively used. Nutritional risk evaluation can and must be performed by health professionals such as the medical team, as long as they are involved in patient's treatment. Our methodology may be used as a model allowing for early guidance to individualized intervention, human resources' optimization and education for the importance of nutrition care.

  10. Juvenile idiopathic arthritis: clinically relevant imaging in diagnosis and monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Southwood, Tauny [Birmingham Children' s Hospital NHS Foundation Trust, Department of Rheumatology, Birmingham (United Kingdom)

    2008-06-15

    The role of plain radiographs in monitoring the disease process in JIA is being increasingly superseded by MRI. The use of ultrasound by clinicians is contentious, but has the potential to corroborate and supplement the clinical impression of individual joint inflammation and it can be very useful for localising intra-articular treatment at the bedside. There are exciting developments in MRS technology which may eventually allow in vivo evaluation of the acute inflammatory process, measurement of early responses to treatment and detection of residual inflammation. The aim of this article is to describe a clinician's view of the current role of imaging in the diagnosis and monitoring of JIA. (orig.)

  11. [Bacterial genomics and metagenomics: clinical applications and medical relevance].

    Science.gov (United States)

    Diene, S M; Bertelli, C; Pillonel, T; Schrenzel, J; Greub, G

    2014-11-12

    New sequencing technologies provide in a short time and at low cost high amount of genomic sequences useful for applications such as: a) development of diagnostic PCRs and/or serological tests; b) detection of virulence factors (virulome) or genes/SNPs associated with resistance to antibiotics (resistome) and c) investigation of transmission and dissemination of bacterial pathogens. Thus, bacterial genomics of medical importance is useful to clinical microbiologists, to infectious diseases specialists as well as to epidemiologists. Determining the microbial composition of a sample by metagenomics is another application of new sequencing technologies, useful to understand the impact of bacteria on various non-infectious diseases such as obesity, asthma, or diabetes. Genomics and metagenomics will likely become a specialized diagnostic analysis.

  12. Evidence of clinically relevant efficacy for dietary supplements and nutraceuticals.

    Science.gov (United States)

    Cicero, Arrigo F G; Borghi, Claudio

    2013-06-01

    Beyond the well-known effects on blood pressure (BP) of the DASH and the Mediterranean diets, a large number of studies have investigated the possible a BP-lowering effect from different dietary supplements and nutraceuticals, mostly antioxidant agents with a high tolerability and safety profile. In particular, a relatively large body of evidence support the use of potassium, L-arginine, vitamin C, cocoa flavonoids, coenzyme Q10, controlled-release melatonin, and aged garlic extract. However there is a need for data about the long-term safety of a large part of these products. Moreover, further clinical research is advisable to identify between the available active nutraceuticals and those with the best cost-effectiveness and risk-benefit ratio for widespread use in a general population with low added cardiovascular risk related to uncomplicated hypertension.

  13. Computational Design of Short Pulse Laser Driven Iron Opacity Measurements at Stellar-Relevant Conditions

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Madison E. [Univ. of Florida, Gainesville, FL (United States)

    2017-05-20

    Opacity is a critical parameter in the simulation of radiation transport in systems such as inertial con nement fusion capsules and stars. The resolution of current disagreements between solar models and helioseismological observations would bene t from experimental validation of theoretical opacity models. Overall, short pulse laser heated iron experiments reaching stellar-relevant conditions have been designed with consideration of minimizing tamper emission and optical depth effects while meeting plasma condition and x-ray emission goals.

  14. Complementary feeding: clinically relevant factors affecting timing and composition.

    Science.gov (United States)

    Krebs, Nancy F; Hambidge, K Michael

    2007-02-01

    Exclusive breastfeeding for the first 6 mo of life followed by optimal complementary feeding are critical public health measures for reducing and preventing morbidity and mortality in young children. Clinical factors, such as birth weight, prematurity, and illness, that affect the iron and zinc requirements of younger infants are discussed. Maternal diet and nutritional status do not have a strong effect on the mineral content of human milk, but physiologic changes in milk and the infants' status determine the dependence of the infant on complementary foods in addition to human milk to meet iron and zinc requirements after 6 mo. The nature of zinc absorption, which is suitably characterized by saturation response modeling, dictates that plant-based diets, which are low in zinc, are associated with low absolute daily absorbed zinc, which is inadequate to meet requirements. Foods with a higher zinc content, such as meats, are much more likely to be sufficient to meet dietary requirements. Current plant-based complementary feeding patterns for older fully breastfed infants in both developed and developing countries pose a risk of zinc deficiency. The strong rationale for the potential benefits of providing meat as an early complementary food, and the examples of successful intervention programs, provide potent incentives to pursue broader implementation programs, with concurrent rigorous evaluation of both efficacy and effectiveness.

  15. The Emergence of Clinically Relevant Babesiosis in Southwestern Wisconsin.

    Science.gov (United States)

    Kowalski, Todd J; Jobe, Dean A; Dolan, Emily C; Kessler, Anne; Lovrich, Steven D; Callister, Steven M

    2015-08-01

    To determine the frequency and characteristics of babesiosis cases, and to assess the impact of the introduction of a tick-borne infection diagnostic panel on babesiosis diagnosis in the region surrounding La Crosse, Wisconsin, where babesiosis in non-travelers was previously rare. In the spring of 2013, we conducted a point-in-time survey of Ixodes scopuloris ticks for the presence of Babesia microti. We also conducted a retrospective study of all babesiosis cases diagnosed in our health system between January 1, 2004, and November 1, 2013. Finally, we compared the number of babesiosis cases diagnosed during the study period before and after the June 1, 2012, introduction of a tick-borne infection diagnostic panel in our organization. Babesia microti was present in 5% of ticks surveyed in our region. Twenty-two cases. of babesiosis were diagnosed in our organization during the study period-19 since 2010. The tick-borne infection diagnostic panel was used widely by clinicians, with an attendant increase in babesiosis diagnoses. Babesiosis should be considered endemic in southwestern Wisconsin, and testing should be considered for patients with compatible clinical and laboratory features.

  16. Clinically relevant drug interactions between anticancer drugs and psychotropic agents.

    Science.gov (United States)

    Yap, K Y-L; Tay, W L; Chui, W K; Chan, A

    2011-01-01

    Drug interactions are commonly seen in the treatment of cancer patients. Psychotropics are often indicated for these patients since they may also suffer from pre-existing psychological disorders or experience insomnia and anxiety associated with cancer therapy. Thus, the risk of anticancer drug (ACD)-psychotropic drug-drug interactions (DDIs) is high. Drug interactions were compiled from the British National Formulary (53rd edn), Lexi-Comp's Drug Information Handbook (15th edn), Micromedex (v5.1), Hansten & Horn's Drug Interactions (2000) and Drug Interaction Facts (2008 edn). Product information of the individual drugs, as well as documented literature on ACD-psychotropic interactions from PubMed and other databases was also incorporated. This paper identifies clinically important ACD-psychotropic DDIs that are frequently observed. Pharmacokinetic DDIs were observed for tyrosine kinase inhibitors, corticosteroids and antimicrotubule agents due to their inhibitory or inductive effects on cytochrome P450 isoenzymes. Pharmacodynamic DDIs were identified for thalidomide with central nervous system depressants, procarbazine with antidepressants, myelosuppressive ACDs with clozapine and anthracyclines with QT-prolonging psychotropics. Clinicians should be vigilant when psychotropics are prescribed concurrently with ACDs. Close monitoring of plasma drug levels should be carried out to avoid toxicity in the patient, as well as to ensure adequate chemotherapeutic and psychotropic coverage.

  17. GA(2)LEN skin test study II: clinical relevance of inhalant allergen sensitizations in Europe

    DEFF Research Database (Denmark)

    Burbach, G J; Heinzerling, L M; Edenharter, G

    2009-01-01

    BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance...... was used to determine the clinical relevance of sensitizations against the 18 most frequent inhalant allergens in Europe. The study population consisted of patients referred to one of the 17 allergy centres in 14 European countries (n = 3034, median age = 33 years). The aim of the study was to assess...... the clinical relevance of positive skin prick test reactions against inhalant allergens considering the predominating type of symptoms in a pan-European population of patients presenting with suspected allergic disease. METHODS: Clinical relevance of skin prick tests was recorded with regard to patient history...

  18. Thyroid-Stimulating Hormone Receptor Antibodies in Pregnancy: Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Ines Bucci

    2017-06-01

    Full Text Available Graves’ disease is the most common cause of thyrotoxicosis in women of childbearing age. Approximately 1% of pregnant women been treated before, or are being treated during pregnancy for Graves’ hyperthyroidism. In pregnancy, as in not pregnant state, thyroid-stimulating hormone (TSH receptor (TSHR antibodies (TRAbs are the pathogenetic hallmark of Graves’ disease. TRAbs are heterogeneous for molecular and functional properties and are subdivided into activating (TSAbs, blocking (TBAbs, or neutral (N-TRAbs depending on their effect on TSHR. The typical clinical features of Graves’ disease (goiter, hyperthyroidism, ophthalmopathy, dermopathy occur when TSAbs predominate. Graves’ disease shows some peculiarities in pregnancy. The TRAbs disturb the maternal as well as the fetal thyroid function given their ability to cross the placental barrier. The pregnancy-related immunosuppression reduces the levels of TRAbs in most cases although they persist in women with active disease as well as in women who received definitive therapy (radioiodine or surgery before pregnancy. Changes of functional properties from stimulating to blocking the TSHR could occur during gestation. Drug therapy is the treatment of choice for hyperthyroidism during gestation. Antithyroid drugs also cross the placenta and therefore decrease both the maternal and the fetal thyroid hormone production. The management of Graves’ disease in pregnancy should be aimed at maintaining euthyroidism in the mother as well as in the fetus. Maternal and fetal thyroid dysfunction (hyperthyroidism as well as hypothyroidism are in fact associated with several morbidities. Monitoring of the maternal thyroid function, TRAbs measurement, and fetal surveillance are the mainstay for the management of Graves’ disease in pregnancy. This review summarizes the biochemical, immunological, and therapeutic aspects of Graves’ disease in pregnancy focusing on the role of the TRAbs in maternal and

  19. Human tibial torsion - Morphometric assessment and clinical relevance

    Directory of Open Access Journals (Sweden)

    Swati Gandhi

    2014-02-01

    Full Text Available Background: Tibial torsion is an important anatomical parameter in clinical practice and displays variability among individuals. These variations are extremely significant in view of alignment guides such as those related to rotational landmarks of tibia in total knee arthroplasty. Further, precise knowledge and information pertaining to angle of tibial torsion also helps in correction of traumatic malunion or congenital maltorsion of tibia. Methods: The present study was carried out to determine the angle of tibial torsion in 100 adult dry tibia bones in the Department of Anatomy, Government Medical College, Amritsar. The study group comprised 50 males and 50 females with equal number of right- and left-sided bones. The measurements were meticulously recorded and the data were subjected to statistical analysis. The results were analyzed and discussed in the light of existing literature. Results: On the right side, it was found to be 29.84° ± 4.86°° (range = 22.00° -38.00° in males and 28.92° ± 5.10°° (range = 15.00°-38.00° in females. On the left side, it was found to be 28.00° ± 4.94°° (range = 20.00°-40.00°° in males and 28.12° ± 4.28°° (range = 20.00°-37.00°° in females. Conclusion: The present study is an endeavor to provide baseline data with reference to the angle of tibial torsion in the Indian population. The results of the study assume special importance in view of the technical advancements in reconstructive surgical procedures in orthopedic practice.

  20. Spectrum of clinically relevant Exophiala species in the United States.

    Science.gov (United States)

    Zeng, J S; Sutton, D A; Fothergill, A W; Rinaldi, M G; Harrak, M J; de Hoog, G S

    2007-11-01

    Numerous members of the genus Exophiala are potential agents of human and animal mycoses. The majority of these infections are cutaneous and superficial, but also fatal systemic infections are known. We re-identified 188 clinical isolates from the United States, which had a preliminary morphological identification of Exophiala species, by sequencing internal transcribed spacer (ITS) region of the rRNA. Molecular identifications of the strains were as follows, in order of frequency: 55 E. dermatitidis (29.3%), 37 E. xenobiotica (19.7%), 35 E. oligosperma (18.6%), 13 E. lecanii-corni (6.9%), 12 E. phaeomuriformis (6.4%), 7 E. jeanselmei (3.7%), 7 E. bergeri (3.7%), 6 E. mesophila (3.2%), 5 E. spinifera (2.7%), 3 Exophiala sp. 1 (1.6%), 3 E. attenuata (1.6%), 3 Phialophora europaea (1.3%), 1 E. heteromorpha (0.5%), and 1 Exophiala sp. 2 (0.5%) strains. Exophiala strains were repeatedly isolated from deep infections (39.9%) involving lung, pleural fluid, sputum, digestive organs (stomach, intestines, bile), heart, brain, spleen, bone marrow, blood, dialysis fluid, lymph node, joint, breast, middle ear, throat, and intraocular tissues. About 38.3% of the Exophiala spp. strains were agents of cutaneous infections including skin, mucous membranes, nail, and corneal epithelium lesions. The other strains caused superficial infections (0.5%, including hair) or subcutaneous infection (12.0%, including paranasal sinusitis, mycetoma, and subcutaneous cyst). The systemic infections were preponderantly caused by E. dermatitidis, E. oligosperma, E. phaeomuriformis, E. xenobiotica, and E. lecanii-corni. Strains of E. bergeri, E. spinifera, E. jeanselmei, E. mesophila, and E. attenuata mainly induced cutaneous and subcutaneous infections. Since relatively few unknown ITS motifs were encountered, we suppose that the list of opportunistic Exophiala species in temperate climates is nearing completion, but a number of species still have to be described.

  1. Nutritional status of children with clinical conditions.

    Science.gov (United States)

    Murphy, Alexia J; Hill, Rebecca J; Buntain, Helen; White, Melinda; Brookes, Denise; Davies, Peter S W

    2017-06-01

    Nutritional status is an important consideration in many pediatric clinical conditions. This paper aimed to examine and compare the nutritional status, represented by body cell mass (BCM), of children with cancer, Crohn's disease (CD), cystic fibrosis (CF) and anorexia nervosa (AN). Anthropometry was measured and BCM was calculated from whole body potassium-40 counting in 259 children being treated for clinical conditions (n = 66 cancer; n = 59 AN; n = 75 CF; n = 59 CD) and 108 healthy children. BCM was adjusted for height (BCMI) and expressed as a Z-score relative to laboratory reference data. The CD (-0.80 ± 1.61; p = 0.0001) and AN (-1.13 ± 0.99; p = 0.0001) groups had significantly lower BMI Z-score than the healthy control (0.13 ± 0.75), cancer (0.50 ± 1.40) and CF groups (-0.09 ± 0.95). The cancer (-1.16 ± 1.60; p = 0.0001), CD (-1.13 ± 1.36; p = 0.0001) and AN (-0.97 ± 1.18; p = 0.0001) groups had significantly reduced BCM compared to the healthy control (0.07 ± 0.93) and CF group (0.31 ± 1.08). According to BCMI Z-score, 42.4% of patients with cancer, 41.7% of the patients with CD, 27.1% of patients with AN, and 4.0% of patients with CF were considered malnourished. This study demonstrates that children undergoing treatment for clinical conditions may have alterations in BCM, independent of BMI. Children with cancer, CD and AN all had a high prevalence of malnutrition. Assessment of body composition, not just body size, is vital to understand nutritional status in children with clinical conditions. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  2. Triple Helical Recognition of RNA Using 2-Aminopyridine-Modified PNA at Physiologically Relevant Conditions**

    Science.gov (United States)

    Zengeya, Thomas; Gupta, Pankaj

    2013-01-01

    Peptide nucleic acids containing thymidine and 2-aminopyridine (M) nucleobases formed stable and sequence selective triple helices with double stranded RNA at physiologically relevant conditions. The M-modified PNA displayed unique RNA selectivity by having two orders of magnitude higher affinity for the double stranded RNAs than for the same DNA sequences. Preliminary results suggested that nucleobase-modified PNA could bind and recognize double helical precursors of microRNAs. PMID:23125029

  3. Triple Helical Recognition of RNA Using 2-Aminopyridine-Modified PNA at Physiologically Relevant Conditions**

    OpenAIRE

    Zengeya, Thomas; Gupta, Pankaj; Rozners, Eriks

    2012-01-01

    Peptide nucleic acids containing thymidine and 2-aminopyridine (M) nucleobases formed stable and sequence selective triple helices with double stranded RNA at physiologically relevant conditions. The M-modified PNA displayed unique RNA selectivity by having two orders of magnitude higher affinity for the double stranded RNAs than for the same DNA sequences. Preliminary results suggested that nucleobase-modified PNA could bind and recognize double helical precursors of microRNAs.

  4. Triple-helical recognition of RNA using 2-aminopyridine-modified PNA at physiologically relevant conditions.

    Science.gov (United States)

    Zengeya, Thomas; Gupta, Pankaj; Rozners, Eriks

    2012-12-07

    Peptide nucleic acids containing thymidine and 2-aminopyridine (M) nucleobases form stable and sequence-selective triple helices with double-stranded RNA at physiologically relevant conditions. The M-modified PNA showed unique RNA selectivity by having two orders of magnitude higher affinity for the double-stranded RNAs than for the same DNA sequences. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Periodontal conditions in vegetarians: a clinical study.

    Science.gov (United States)

    Staufenbiel, I; Weinspach, K; Förster, G; Geurtsen, W; Günay, H

    2013-08-01

    Investigations about possible correlations between vegetarian diet and periodontal conditions are rare and characterized by small case numbers. The aim of this clinical study was to investigate the influence of a vegetarian diet on periodontal parameters with an appropriate sample size. A total of 200 patients, 100 vegetarians and 100 non-vegetarians, were included in the study. All patients were examined including a full mouth assessment of the periodontal and dental conditions. In addition, a questionnaire was handed out to ask for patients' oral hygiene habits and level of education. For statistical analysis the Mann-Whitney Test (χ(2) for analysis of the questionnaire) was applied (level of significance: Pvegetarians versus 41.72 years non-vegetarians). Vegetarians had significantly lower probing pocket depths (P=0.039), bleeding on probing (P=0.001), periodontal screening index (P=0.012), a better hygiene index (Pvegetarians. Furthermore, vegetarians had a higher level of education (PVegetarians revealed better periodontal conditions (less inflammation signs, less periodontal damage and a better dental home care). However, it should be considered that vegetarians are not only avoiding meat in their nutrition but are also characterized by an overall healthier life style.

  6. Measuring agreement between rating interpretations and binary clinical interpretations of images: a simulation study of methods for quantifying the clinical relevance of an observer performance paradigm

    Science.gov (United States)

    Chakraborty, Dev P.

    2012-05-01

    Laboratory receiver operating characteristic (ROC) studies, that are often used to evaluate medical imaging systems, differ from ‘live’ clinical interpretations in several respects which could compromise their clinical relevance. The aim was to develop methodology for quantifying the clinical relevance of a laboratory ROC study. A simulator was developed to generate ROC ratings data and binary clinical interpretations classified as correct or incorrect for a common set of images interpreted under clinical and laboratory conditions. The area under the trapezoidal ROC curve (AUC) was used as the laboratory figure-of-merit and the fraction of correct clinical decisions as the clinical figure-of-merit. Conventional agreement measures (Pearson, Spearman, Kendall and kappa) between the bootstrap-induced fluctuations of the two figures of merit were estimated. A jackknife pseudovalue transformation applied to the figures of merit was also investigated as a way to capture agreement existing at the individual image level that could be lost at the figure-of-merit level. It is shown that the pseudovalues define a relevance-ROC curve. The area under this curve (rAUC) measures the ability of the laboratory figure-of-merit-based pseudovalues to correctly classify incorrect versus correct clinical interpretations. Therefore, rAUC is a measure of the clinical relevance of an ROC study. The conventional measures and rAUC were compared under varying simulator conditions. It was found that design details of the ROC study, namely the number of bins, the difficulty level of the images, the ratio of disease-present to disease-absent images and the unavoidable difference between laboratory and clinical performance levels, can lead to serious underestimation of the agreement as indicated by conventional agreement measures, even for perfectly correlated data, while rAUC showed high agreement and was relatively immune to these details. At the same time rAUC was sensitive to factors such

  7. Isolation, speciation, and antibiogram of clinically relevant non-diphtherial Corynebacteria (Diphtheroids

    Directory of Open Access Journals (Sweden)

    B S Reddy

    2012-01-01

    Full Text Available Purpose: Coryneform or the non-diphtherial Corynebacterium species largely remains a neglected group with the traditional consideration of these organisms as contaminants. This concept, however, is slowly changing in the light of recent observations. This study has been done to find out the species distribution and antibiogram of various members of the clinically relevant Coryneform group, isolated from various clinical materials. Materials and Methods: One hundred and fourteen non-duplicate isolates of diphtheroids from various clinical isolates were selected for the study. The isolates were identified to the species level by using a battery of tests; and antimicrobial susceptibility was tested by using a combination of Clinical and Laboratory Standards Institute (CLSI and the British Society for Antimicrobial Chemotherapy (BSAC guidelines, in the absence of definitive CLSI guidelines. Results: Corynebacterium amycolatum was the predominant species (35.9% in our series followed by the CDC Group G organisms (15.7%. Each of the remaining 19 species comprised of less than 10% of the isolates. More than half the total isolates were resistant to the penicillins, erythromycin, and clindamycin; while excellent activity (all the strains being susceptible was shown by vancomycin, linezolid, and tigecycline. Chloramphenicol and tetracycline also had good activity in inhibiting more than 80% of the isolates. Multiply drug resistance was exhibited by all the species. Conclusion: This study was an attempt to establish the clinical significance of coryneform organisms. The high level of resistance shown by this group to some of the common antibacterial agents highlights the importance of processing these isolates in select conditions to guide the clinicians towards an appropriate therapy.

  8. Detection and clinical relevance of early disseminated breast cancer cells depend on their cytokeratin expression pattern

    NARCIS (Netherlands)

    Effenberger, Katharina E.; Borgen, Elin; Eulenburg, Christine Zu; Bartkowiak, Kai; Grosser, Andrea; Synnestvedt, Marit; Kaaresen, Rolf; Brandt, Burkhard; Nesland, Jahn M.; Pantel, Klaus; Naume, Bjorn

    2011-01-01

    The factors determining the clinical relevance of disseminated tumor cells (DTC) in breast cancer patients are largely unknown. Here we compared the specificity and clinical performance of two antibodies frequently used for DTC detection. Reactivities of antibodies A45-B/B3 (A45) and AE1/AE3 (AE) fo

  9. Modeling processes in the acquisition of fears: vicarious electrodermal conditioning to fear-relevant stimuli.

    Science.gov (United States)

    Hygge, S; Ohman, A

    1978-03-01

    Fear-relevant (snakes, spiders, and rats) and fear-irrelevant (flowers, mushrooms, and berries) pictures were compared as conditioned and instigating stimuli in a vicarious classical conditioning paradigm with skin conductance responses as the dependent variable. A female confederate model and subject watched the pictures side by side. A female stimulus presentations, the experimenter interrupted to investigate alleged overreactions of the model to one of the stimulus classes. The model then vividly described a phobia for this object, which was to serve as a vicarious instigating stimulus. The experiment continued for a few conditioning trials, and then the experimenter announced that the disturbing stimulus would be omitted before the second part of the experiment. There was no effect of stimulus content on vicariously instigated responses, although significant overall instigation was observed. However, the responses to the stimulus that was paired with the model's phobic stimulus, that is, the vicariously conditioned responses, failed to extinguish during the second part of the experiment when it was fear-relevant but extinguished immediately when it was fear-irrelevant.

  10. Responder analyses and the assessment of a clinically relevant treatment effect

    Directory of Open Access Journals (Sweden)

    Jiang Qi

    2007-10-01

    Full Text Available Abstract Ideally, a clinical trial should be able to demonstrate not only a statistically significant improvement in the primary efficacy endpoint, but also that the magnitude of the effect is clinically relevant. One proposed approach to address this question is a responder analysis, in which a continuous primary efficacy measure is dichotomized into "responders" and "non-responders." In this paper we discuss various weaknesses with this approach, including a potentially large cost in statistical efficiency, as well as its failure to achieve its main goal. We propose an approach in which the assessments of statistical significance and clinical relevance are separated.

  11. Detection of Adriamycin-DNA adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations.

    Science.gov (United States)

    Coldwell, Kate E; Cutts, Suzanne M; Ognibene, Ted J; Henderson, Paul T; Phillips, Don R

    2008-09-01

    Limited sensitivity of existing assays has prevented investigation of whether Adriamycin-DNA adducts are involved in the anti-tumour potential of Adriamycin. Previous detection has achieved a sensitivity of a few Adriamycin-DNA adducts/10(4) bp DNA, but has required the use of supra-clinical drug concentrations. This work sought to measure Adriamycin-DNA adducts at sub-micromolar doses using accelerator mass spectrometry (AMS), a technique with origins in geochemistry for radiocarbon dating. We have used conditions previously validated (by less sensitive decay counting) to extract [(14)C]Adriamycin-DNA adducts from cells and adapted the methodology to AMS detection. Here we show the first direct evidence of Adriamycin-DNA adducts at clinically-relevant Adriamycin concentrations. [(14)C]Adriamycin treatment (25 nM) resulted in 4.4 +/- 1.0 adducts/10(7) bp ( approximately 1300 adducts/cell) in MCF-7 breast cancer cells, representing the best sensitivity and precision reported to date for the covalent binding of Adriamycin to DNA. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin-DNA adduct detection and revealed adduct formation within an hour of drug treatment. This method has been shown to be highly reproducible for the measurement of Adriamycin-DNA adducts in tumour cells in culture and can now be applied to the detection of these adducts in human tissues.

  12. Measuring agreement between ratings interpretations and binary clinical interpretations of images: a simulation study of methods for quantifying the clinical relevance of an observer performance paradigm

    Science.gov (United States)

    Chakraborty, Dev P.

    2012-01-01

    Laboratory receiver operating characteristic (ROC) studies, that are often used to evaluate medical imaging systems, differ from “live” clinical interpretations in several respects which could compromise their clinical relevance. The aim was to develop methodology for quantifying the clinical relevance of a laboratory ROC study. A simulator was developed to generate ROC ratings data and binary clinical interpretations classified as correct or incorrect for a common set of images interpreted under clinical and laboratory conditions. The area under the trapezoidal ROC curve was used as the laboratory figure-of-merit and the fraction of correct clinical decisions as the clinical figure-of-merit. Conventional agreement measures (Pearson, Spearman, Kendall and kappa) between the bootstrap-induced fluctuations of the two figures-of-merit were estimated. A jackknife pseudovalue transformation applied to the figures-of-merit was also investigated as a way to capture agreement existing at the individual image level that could be lost at the figure-of-merit level. It is shown that the pseudovalues define a relevance ROC curve the area under which (rAUC) measures the ability of the laboratory figure-of-merit based pseudovalues to correctly classify incorrect vs. correct clinical interpretations, and is a measure of the clinical relevance of an ROC study. The conventional measures and rAUC were compared under varying simulator conditions. It was found that design details of the ROC study, namely the number of bins, the difficulty level of the images, the ratio of disease-present to disease-absent images, and the unavoidable difference between laboratory and clinical performance levels, can seriously underestimate the agreement as indicated by conventional agreement measures, even for perfectly correlated data, while rAUC showed high agreement and was relatively immune to these details. At the same time rAUC was sensitive to factors such as intrinsic correlation between the

  13. Robotic Visual Tracking of Relevant Cues in Underwater Environments with Poor Visibility Conditions

    Directory of Open Access Journals (Sweden)

    Alejandro Maldonado-Ramírez

    2016-01-01

    Full Text Available Using visual sensors for detecting regions of interest in underwater environments is fundamental for many robotic applications. Particularly, for an autonomous exploration task, an underwater vehicle must be guided towards features that are of interest. If the relevant features can be seen from the distance, then smooth control movements of the vehicle are feasible in order to position itself close enough with the final goal of gathering visual quality images. However, it is a challenging task for a robotic system to achieve stable tracking of the same regions since marine environments are unstructured and highly dynamic and usually have poor visibility. In this paper, a framework that robustly detects and tracks regions of interest in real time is presented. We use the chromatic channels of a perceptual uniform color space to detect relevant regions and adapt a visual attention scheme to underwater scenes. For the tracking, we associate with each relevant point superpixel descriptors which are invariant to changes in illumination and shape. The field experiment results have demonstrated that our approach is robust when tested on different visibility conditions and depths in underwater explorations.

  14. Renewal of conditioned responding to food cues in rats: Sex differences and relevance of estradiol.

    Science.gov (United States)

    Anderson, Lauren C; Petrovich, Gorica D

    2015-11-01

    Cues associated with food can stimulate food anticipation, procurement, and consumption, independently of hunger. These and other behaviors driven by learned cues are persistent and can reappear after extinction, because the original learned associations continue to exist. Renewal, or reinstatement, of extinguished conditioned behavior may explain the inability to change maladaptive eating habits driven by food cues, similar to the mechanisms of drug use relapse. Here, we investigated sex differences in context-induced renewal of responding to food cues, and the role of estradiol in females in a Pavlovian conditioning preparation. We compared adult male and female rats because there is evidence for sex differences in learning and memory and in the control of feeding. Context-induced renewal involves conditioning and extinction in different contexts and the renewal of conditioned behavior is induced by return to the conditioning context ("ABA renewal"; experimental groups). Control groups remain in the same context during conditioning, extinction, and test. In Experiment 1, male and female rats were trained to associate a tone with food pellets during acquisition, and after extinction with tone only presentations, were tested for renewal of responding to the tone. Learning was assessed through the expression of the conditioned response, which included approach and activity directed at food receptacle (food cup behavior). Males and females learned the acquisition and extinction of tone-food associations similarly, but there were sex differences during renewal of the conditioned responses to the food cue. Males showed robust renewal of responding, while renewal in intact females was inconsistent. Males in the experimental group had significantly higher food cup behavior compared to males in the control group, while females in both groups showed similar levels of food cup behavior during the tone. In Experiment 2, we examined a potential role of estradiol in renewal

  15. Reduced chemistry for a gasoline surrogate valid at engine-relevant conditions

    CERN Document Server

    Niemeyer, Kyle E

    2014-01-01

    A detailed mechanism for the four-component gasoline surrogate developed by Lawrence Livermore National Laboratory has shown good agreement with experiments in engine-relevant conditions. However, with 1388 species and 5933 reversible reactions, this detailed mechanism is far too large to use in practical engine simulations. Therefore, reduction of the detailed mechanism was performed using a multi-stage approach consisting of the DRGEPSA method, unimportant reaction elimination, isomer lumping, and analytic QSS reduction based on CSP analysis. A new greedy sensitivity analysis algorithm was developed and demonstrated to be capable of removing more species for the same error limit compared to the conventional sensitivity analysis used in DRG-based skeletal reduction methods. Using this new greedy algorithm, several skeletal and reduced mechanisms were developed at varying levels of complexity and for different target condition ranges. The final skeletal and reduced mechanisms consisted of 213 and 148 species,...

  16. Intraductal papillary mucinous neoplasms of the pancreas: reporting clinically relevant features.

    Science.gov (United States)

    Del Chiaro, Marco; Verbeke, Caroline

    2016-11-22

    Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can exhibit a wide spectrum of macroscopic and microscopic appearances. This not only causes occasional difficulties for the reporting pathologist in distinguishing these tumours from other lesions, but is also relevant clinically. As evidence accumulates, it becomes clear that multiple macroscopic and histological features of these neoplasms are relevant to the risk for malignant transformation and, consequently, of prime importance for clinical patient management. The need for detailed reporting is therefore increasing. This review discusses the panoply of gross and microscopic features of IPMN as well as the recommendations from recent consensus meetings regarding the pathology reporting on this tumour entity.

  17. Assessment of college students' awareness and knowledge about conditions relevant to metabolic syndrome.

    Science.gov (United States)

    Yahia, Najat; Brown, Carrie; Rapley, Melyssa; Chung, Mei

    2014-01-01

    Despite the increasing prevalence of metabolic syndrome among young adults, little is known about the awareness level of college students about this condition. The purpose of this study was to assess students' level of awareness and knowledge about conditions relevant to metabolic syndrome (MetS). A self-reported online questionnaire was administered to 243 students attending Central Michigan University. Questions were divided into seven conditions: diabetes, adiposity, hypertension, high serum cholesterol, arteriosclerosis, stroke, and myocardial infarction. Students' responses were scored and interpreted as follows: poor knowledge if ≤50% of students answered the question correctly; fair knowledge if between 51-80% of students answered the question correctly; and good knowledge if between 81-100% of students answered the question correctly. Anthropometric measurements including height, weight, waist circumference, percentage body fat, and visceral fat score were measured. Fisher's exact test was used to test the differences in students' responses. A p value difference. More than 80% of students correctly identified symptoms and complications of diabetes, hypertension, arteriosclerosis, myocardial infarction and stroke, and 92% identified adiposity as a risk factor for heart disease. There were few false beliefs held by students on questionnaire items. For example, 58% of male students falsely believed that individuals with diabetes may only eat special kinds of sweets compared to 39% of females (p Science major, and year in school were found to be positively associated with more knowledge. The findings in this study suggest that students' knowledge about conditions relevant to metabolic syndrome can be improved. In this essence, raising awareness about MetS based on students' pre-existing knowledge is essential to enhance students' wellness.

  18. Feature Selection by Merging Sequential Bidirectional Search into Relevance Vector Machine in Condition Monitoring

    Institute of Scientific and Technical Information of China (English)

    ZHANG Kui; DONG Yu; BALL Andrew

    2015-01-01

    For more accurate fault detection and diagnosis, there is an increasing trend to use a large number of sensors and to collect data at high frequency. This inevitably produces large-scale data and causes difficulties in fault classification. Actually, the classification methods are simply intractable when applied to high-dimensional condition monitoring data. In order to solve the problem, engineers have to resort to complicated feature extraction methods to reduce the dimensionality of data. However, the features transformed by the methods cannot be understood by the engineers due to a loss of the original engineering meaning. In this paper, other forms of dimensionality reduction technique(feature selection methods) are employed to identify machinery condition, based only on frequency spectrum data. Feature selection methods are usually divided into three main types: filter, wrapper and embedded methods. Most studies are mainly focused on the first two types, whilst the development and application of the embedded feature selection methods are very limited. This paper attempts to explore a novel embedded method. The method is formed by merging a sequential bidirectional search algorithm into scale parameters tuning within a kernel function in the relevance vector machine. To demonstrate the potential for applying the method to machinery fault diagnosis, the method is implemented to rolling bearing experimental data. The results obtained by using the method are consistent with the theoretical interpretation, proving that this algorithm has important engineering significance in revealing the correlation between the faults and relevant frequency features. The proposed method is a theoretical extension of relevance vector machine, and provides an effective solution to detect the fault-related frequency components with high efficiency.

  19. Feature selection by merging sequential bidirectional search into relevance vector machine in condition monitoring

    Science.gov (United States)

    Zhang, Kui; Dong, Yu; Ball, Andrew

    2015-11-01

    For more accurate fault detection and diagnosis, there is an increasing trend to use a large number of sensors and to collect data at high frequency. This inevitably produces large-scale data and causes difficulties in fault classification. Actually, the classification methods are simply intractable when applied to high-dimensional condition monitoring data. In order to solve the problem, engineers have to resort to complicated feature extraction methods to reduce the dimensionality of data. However, the features transformed by the methods cannot be understood by the engineers due to a loss of the original engineering meaning. In this paper, other forms of dimensionality reduction technique(feature selection methods) are employed to identify machinery condition, based only on frequency spectrum data. Feature selection methods are usually divided into three main types: filter, wrapper and embedded methods. Most studies are mainly focused on the first two types, whilst the development and application of the embedded feature selection methods are very limited. This paper attempts to explore a novel embedded method. The method is formed by merging a sequential bidirectional search algorithm into scale parameters tuning within a kernel function in the relevance vector machine. To demonstrate the potential for applying the method to machinery fault diagnosis, the method is implemented to rolling bearing experimental data. The results obtained by using the method are consistent with the theoretical interpretation, proving that this algorithm has important engineering significance in revealing the correlation between the faults and relevant frequency features. The proposed method is a theoretical extension of relevance vector machine, and provides an effective solution to detect the fault-related frequency components with high efficiency.

  20. Clinical relevance is associated with allergen-specific wheal size in skin prick testing

    DEFF Research Database (Denmark)

    Haahtela, T.; Burbach, G. J.; Bachert, C.

    2014-01-01

    BackgroundWithin a large prospective study, the Global Asthma and Allergy European Network (GA(2)LEN) has collected skin prick test (SPT) data throughout Europe to make recommendations for SPT in clinical settings. ObjectiveTo improve clinical interpretation of SPT results for inhalant allergens...... SPT reactions had a smaller risk of sensitizations being clinically relevant compared with adults. The 80% PPV varied from 3 to 10mm depending on the allergen. ConclusionThese reading keys' for 18 inhalant allergens can help interpret SPT results with respect to their clinical significance. A SPT form...

  1. Clinically relevant transmitted drug resistance to first line antiretroviral drugs and implications for recommendations.

    Directory of Open Access Journals (Sweden)

    Susana Monge

    Full Text Available BACKGROUND: The aim was to analyse trends in clinically relevant resistance to first-line antiretroviral drugs in Spain, applying the Stanford algorithm, and to compare these results with reported Transmitted Drug Resistance (TDR defined by the 2009 update of the WHO SDRM list. METHODS: We analysed 2781 sequences from ARV naive patients of the CoRIS cohort (Spain between 2007-2011. Using the Stanford algorithm "Low-level resistance", "Intermediate resistance" and "High-level resistance" categories were considered as "Resistant". RESULTS: 70% of the TDR found using the WHO list were relevant for first-line treatment according to the Stanford algorithm. A total of 188 patients showed clinically relevant resistance to first-line ARVs [6.8% (95%Confidence Interval: 5.8-7.7], and 221 harbored TDR using the WHO list [7.9% (6.9-9.0]. Differences were due to a lower prevalence in clinically relevant resistance for NRTIs [2.3% (1.8-2.9 vs. 3.6% (2.9-4.3 by the WHO list] and PIs [0.8% (0.4-1.1 vs. 1.7% (1.2-2.2], while it was higher for NNRTIs [4.6% (3.8-5.3 vs. 3.7% (3.0-4.7]. While TDR remained stable throughout the study period, clinically relevant resistance to first line drugs showed a significant trend to a decline (p = 0.02. CONCLUSIONS: Prevalence of clinically relevant resistance to first line ARVs in Spain is decreasing, and lower than the one expected looking at TDR using the WHO list. Resistance to first-line PIs falls below 1%, so the recommendation of screening for TDR in the protease gene should be questioned in our setting. Cost-effectiveness studies need to be carried out to inform evidence-based recommendations.

  2. Growth kinetics of coliform bacteria under conditions relevant to drinking water distribution systems.

    Science.gov (United States)

    Camper, A K; McFeters, G A; Characklis, W G; Jones, W L

    1991-08-01

    The growth of environmental and clinical coliform bacteria under conditions typical of drinking water distribution systems was examined. Four coliforms (Klebsiella pneumoniae, Escherichia coli, Enterobacter aerogenes, and Enterobacter cloacae) were isolated from an operating drinking water system for study; an enterotoxigenic E. coli strain and clinical isolates of K. pneumoniae and E. coli were also used. All but one of the coliforms tested were capable of growth in unsupplemented mineral salts medium; the environmental isolates had greater specific growth rates than did the clinical isolates. This trend was maintained when the organisms were grown with low levels (less than 1 mg liter-1) of yeast extract. The environmental K. pneumoniae isolate had a greater yield, higher specific growth rates, and a lower Ks value than the other organisms. The environmental E. coli and the enterotoxigenic E. coli strains had comparable yield, growth rate, and Ks values to those of the environmental K. pneumoniae strain, and all three showed significantly more successful growth than the clinical isolates. The environmental coliforms also grew well at low temperatures on low concentrations of yeast extract. Unsupplemented distribution water from the collaborating utility supported the growth of the environmental isolates. Growth of the K. pneumoniae water isolate was stimulated by the addition of autoclaved biofilm but not by tubercle material. These findings indicate that growth of environmental coliforms is possible under the conditions found in operating municipal drinking water systems and that these bacteria could be used in tests to determine assimilable organic carbon in potable water.

  3. Clinical relevance of "bulging eyes" for the differential diagnosis of spinocerebellar ataxias

    OpenAIRE

    Adriana Moro; Renato Puppi Munhoz; Walter Oleschko Arruda; Salmo Raskin; Hélio Afonso Ghizoni Teive

    2013-01-01

    Objective To investigate the relevance of the clinical finding of bulging eyes (BE) in a large Brazilian cohort of spinocerebellar ataxias (SCA), to assess its importance in clinical differential diagnosis among SCA. Methods Three hundred sixty-nine patients from 168 Brazilian families with SCA were assessed with neurological examination and molecular genetic testing. BE was characterized by the presence of eyelid retraction. Genetically ascertained SCA3 was detected in 167 patients, SCA10 ...

  4. Silica desiccant packets for storage and transport of Streptococcus pneumoniae and other clinically relevant species.

    Directory of Open Access Journals (Sweden)

    Casey L Pell

    Full Text Available Bacterial isolates are often transported between laboratories for research and diagnostic purposes. Silica desiccant packets (SDPs, which are inexpensive and do not require freezing, were evaluated for storage and recovery of bacterial isolates. Conditions such as inoculum size, swab type and temperature of storage were investigated using ten Streptococcus pneumoniae isolates. The optimized protocol was then tested using 49 additional S. pneumoniae isolates representing 40 serogroups. Overall, S. pneumoniae growth was considered satisfactory (>100 colony forming units for 98/109 (89.9% and 20/20 (100% swabs after 14 days at room temperature or 28 days at 4° C, respectively. Storage in SDPs did not impact on the ability of S. pneumoniae isolates to be subsequently serotyped. When the survival of nine other clinically relevant bacterial species was tested, seven were viable after 28 days at room temperature, the exceptions being Neisseria gonorrhoeae and Haemophilus influenzae. SDPs are suitable for transport and short-term storage of bacterial species including S. pneumoniae.

  5. Comparative transcriptional analysis of clinically relevant heat stress response in Clostridium difficile strain 630.

    Directory of Open Access Journals (Sweden)

    Nigel G Ternan

    Full Text Available Clostridium difficile is considered to be one of the most important causes of health care-associated infections worldwide. In order to understand more fully the adaptive response of the organism to stressful conditions, we examined transcriptional changes resulting from a clinically relevant heat stress (41 °C versus 37 °C in C. difficile strain 630 and identified 341 differentially expressed genes encompassing multiple cellular functional categories. While the transcriptome was relatively resilient to the applied heat stress, we noted upregulation of classical heat shock genes including the groEL and dnaK operons in addition to other stress-responsive genes. Interestingly, the flagellin gene (fliC was downregulated, yet genes encoding the cell-wall associated flagellar components were upregulated suggesting that while motility may be reduced, adherence--to mucus or epithelial cells--could be enhanced during infection. We also observed that a number of phage associated genes were downregulated, as were genes associated with the conjugative transposon Tn5397 including a group II intron, thus highlighting a potential decrease in retromobility during heat stress. These data suggest that maintenance of lysogeny and genome wide stabilisation of mobile elements could be a global response to heat stress in this pathogen.

  6. Analysis of clinically relevant mechanical and thermal characteristics of titanium foam spinal implants during drilling.

    Science.gov (United States)

    Ito, Kiyoshi; Horiuchi, Tetsuyoshi; Murata, Takahiro; Hongo, Kazuhiro

    2015-09-01

    Although high biocompatibility promotes the use of titanium (Ti) alloy in spinal implants, this material shows high stiffness, which is an issue for removal by drilling. The recently developed, porous Ti foam implants, which have shown enhanced osteoformation, may overcome this flaw. Thus, this study aimed to compare the mechanical and thermal characteristics of Ti-foam (80 % porosity) and conventional Ti alloy (0 % porosity) implants drilled in clinically relevant conditions. Mechanical properties were analyzed by measuring axial and torque forces using a pressure sensor with a drill of 2.5-mm diameter at a rotation frequency of 20 Hz. Thermography was used to evaluate the heat generated by a diamond burr attached to a high-speed (80,000 rpm) drill. The torque and axial strengths of Ti foam (13.63 ± 1.43 and 82.60 ± 7.78 N, respectively) were significantly lower (P = 0.001) than those of Ti alloy (73.58 ± 13.60 and 850.72 ± 146.99 N, respectively). Furthermore, irrigation reduced the area of local heating for Ti foam to 56-82 % of that for Ti alloy, indicating lower thermal conductivity. These data suggest that the use of Ti foam implants may be advantageous in cases with a probability of implant drilling in the future.

  7. Extracellular membrane vesicles in blood products-biology and clinical relevance

    Directory of Open Access Journals (Sweden)

    Emilija Krstova Krajnc

    2016-01-01

    Full Text Available Extracellular membrane vesicles are fragments shed from plasma membranes off all cell types that are undergoing apoptosis or are being subjected to various types of stimulation or stress.  Even in the process of programmed cell death (apoptosis, cell fall apart of varying size vesicles. They expose phosphatidylserine (PS on the outer leaflet of their membrane, and bear surface membrane antigens reflecting their cellular origin. Extracellular membrane vesicles have been isolated from many types of biological fluids, including serum, cerebrospinal fluid, urine, saliva, tears and conditioned culture medium. Flow cytometry is one of the many different methodological approaches that have been used to analyze EMVs. The method attempts to characterize the EMVs cellular origin, size, population, number, and structure. EMVs are present and accumulate in blood products (erythrocytes, platelets as well as in fresh frozen plasma during storage. The aim of this review is to highlight the importance of extracellular vesicles as a cell-to-cell communication system and the role in the pathogenesis of different diseases. Special emphasis will be given to the implication of extracellular membrane vesicles in blood products and their clinical relevance. Although our understanding of the role of  EMVs in disease is far from comprehensive, they display promise as biomarkers for different diseases in the future and also as a marker of quality and safety in the quality control of blood products.

  8. Clinical relevance of pharmacological and physiological data in intrathecal baclofen therapy

    NARCIS (Netherlands)

    Heetla, Herre W; Staal, Michael; Proost, Johannes H; van Laar, Teus

    2014-01-01

    Objective: To review all pharmacological and physiological data available on intrathecal baclofen (ITB) therapy and to evaluate its use in clinical practice and future research. Data Sources: PubMed was searched for relevant anatomic, physiological, and pharmacological data available on ITB. Study S

  9. Less than meets the eye: reappraising the clinical relevance of attentional bias in addiction.

    NARCIS (Netherlands)

    Christiansen, P.; Schoenmakers, T.M.; Field, M.

    2015-01-01

    Recent years have seen an explosion of interest in attentional bias in addiction, particularly its clinical relevance. Specifically, numerous articles claimed to demonstrate either that (1) attentional bias measured in treatment settings could predict subsequent relapse to substance use, or (2) dire

  10. Preterm piglets are a clinically relevant model of pediatric GI disease

    Science.gov (United States)

    The goal of our research is to establish how nutritional support, enteral versus parenteral, affects gut function and susceptibility to disease in early development. We and others have used the neonatal pig to establish unique models of clinically relevant problems in pediatric gastroenterology, esp...

  11. Clinical relevance of studies on the accuracy of visual inspection for detecting caries lesions

    DEFF Research Database (Denmark)

    Gimenez, Thais; Piovesan, Chaiana; Braga, Mariana M

    2015-01-01

    the clinical relevance and methodological quality of studies on the accuracy of visual inspection for assessing caries lesions. Two independent reviewers searched several databases through July 2013 to identify papers/articles published in English. Other sources were checked to identify unpublished literature...

  12. A Bridge between Two Cultures: Uncovering the Chemistry Concepts Relevant to the Nursing Clinical Practice

    Science.gov (United States)

    Brown, Corina E.; Henry, Melissa L. M.; Barbera, Jack; Hyslop, Richard M.

    2012-01-01

    This study focused on the undergraduate course that covers basic topics in general, organic, and biological (GOB) chemistry at a mid-sized state university in the western United States. The central objective of the research was to identify the main topics of GOB chemistry relevant to the clinical practice of nursing. The collection of data was…

  13. Psychometric properties and clinical relevance of the Adolescent Sleep Hygiene Scale in Dutch adolescents

    NARCIS (Netherlands)

    de Bruin, E.J.; van Kampen, R.K.A.; van Kooten, T.; Meijer, A.M.

    2014-01-01

    Objective: This study investigated reliability, validity, and clinical relevance of the Adolescent Sleep Hygiene Scale (ASHS) in Dutch adolescents. Methods: The Dutch translation of the ASHS was administered to 186 normal-sleeping adolescents and 112 adolescents with insomnia. Their sleep variables

  14. Clinically relevant QTc prolongation due to overridden drug-drug interaction alerts: A retrospective cohort study

    NARCIS (Netherlands)

    I.H. van der Sijs (Heleen); R. Kowlesar (Ravi); A.P.J. Klootwijk (Peter); S.P. Nelwan (Stefan); A.G. Vulto (Arnold); T. van Gelder (Teun)

    2009-01-01

    textabstractAIMS: To investigate whether, in patients in whom drug-drug interaction (DDI) alerts on QTc prolongation were overridden, the physician had requested an electrocardiogram (ECG), and if these ECGs showed clinically relevant QTc prolongation. METHODS: For all patients with overridden DDI a

  15. Psychometric properties and clinical relevance of the Adolescent Sleep Hygiene Scale in Dutch adolescents

    NARCIS (Netherlands)

    de Bruin, E.J.; van Kampen, R.K.A.; van Kooten, T.; Meijer, A.M.

    2014-01-01

    Objective: This study investigated reliability, validity, and clinical relevance of the Adolescent Sleep Hygiene Scale (ASHS) in Dutch adolescents. Methods: The Dutch translation of the ASHS was administered to 186 normal-sleeping adolescents and 112 adolescents with insomnia. Their sleep variables

  16. Clinically relevant incidental cardiovascular findings in CT examinations; Klinisch relevante kardiovaskulaere Zufallsbefunde bei CT-Untersuchungen

    Energy Technology Data Exchange (ETDEWEB)

    Voigt, P.; Fahnert, J.; Kahn, T.; Surov, A. [Universitaetsklinikum Leipzig, Klinik fuer Diagnostische und Interventionelle Radiologie, Leipzig (Germany); Schramm, D.; Bach, A.G. [Universitaetsklinikum Halle (Saale), Klinik fuer Radiologie, Halle (Germany)

    2017-04-15

    Incidental cardiovascular findings are a frequent phenomenon in computed tomography (CT) examinations. As the result of a dedicated PubMed search this article gives a systemic overview of the current literature on the most important incidental cardiovascular findings, their prevalence and clinical relevance. The majority of incidental cardiovascular findings are of only low clinical relevance; however, highly relevant incidental findings, such as aortic aneurysms, thromboses and thromboembolic events can also occasionally be found, especially in oncology patients. The scans from every CT examination should also be investigated for incidental findings as they can be of decisive importance for the further clinical management of patients, depending on their clinical relevance. (orig.) [German] Inzidentelle kardiovaskulaere Befunde sind ein haeufiges Phaenomen bei CT-Untersuchungen. Mit dieser Arbeit soll nach gezielter PubMed-Recherche ein systematischer Literaturueberblick ueber die wichtigsten kardiovaskulaeren Zufallsbefunde sowie deren Haeufigkeit und klinische Relevanz gegeben werden. Die Mehrzahl der inzidentellen kardiovaskulaeren Befunde sind klinisch nur von untergeordneter Bedeutung, allerdings werden immer wieder auch hochgradig relevante Zufallsbefunde wie beispielsweise Aortenaneurysmata oder - gerade bei onkologischen Patienten - Thrombosen und thrombembolische Ereignisse detektiert. Jede CT-Untersuchung sollte gezielt nach inzidentellen Befunden durchsucht werden, da diese je nach klinischer Relevanz von entscheidender Bedeutung fuer das weitere klinische Management des Patienten sein koennen. (orig.)

  17. There's an App for That? Highlighting the Difficulty in Finding Clinically Relevant Smartphone Applications.

    Science.gov (United States)

    Wiechmann, Warren; Kwan, Daniel; Bokarius, Andrew; Toohey, Shannon L

    2016-03-01

    The use of personal mobile devices in the medical field has grown quickly, and a large proportion of physicians use their mobile devices as an immediate resource for clinical decision-making, prescription information and other medical information. The iTunes App Store (Apple, Inc.) contains approximately 20,000 apps in its "Medical" category, providing a robust repository of resources for clinicians; however, this represents only 2% of the entire App Store. The App Store does not have strict criteria for identifying content specific to practicing physicians, making the identification of clinically relevant content difficult. The objective of this study is to quantify the characteristics of existing medical applications in the iTunes App Store that could be used by emergency physicians, residents, or medical students. We found applications related to emergency medicine (EM) by searching the iTunes App Store for 21 terms representing core content areas of EM, such as "emergency medicine," "critical care," "orthopedics," and "procedures." Two physicians independently reviewed descriptions of these applications in the App Store and categorized each as the following: Clinically Relevant, Book/Published Source, Non-English, Study Tools, or Not Relevant. A third physician reviewer resolved disagreements about categorization. Descriptive statistics were calculated. We found a total of 7,699 apps from the 21 search terms, of which 17.8% were clinical, 9.6% were based on a book or published source, 1.6% were non-English, 0.7% were clinically relevant patient education resources, and 4.8% were study tools. Most significantly, 64.9% were considered not relevant to medical professionals. Clinically relevant apps make up approximately 6.9% of the App Store's "Medical" Category and 0.1% of the overall App Store. Clinically relevant apps represent only a small percentage (6.9%) of the total App volume within the Medical section of the App Store. Without a structured search

  18. There’s an App for That? Highlighting the Difficulty in Finding Clinically Relevant Smartphone Applications

    Directory of Open Access Journals (Sweden)

    Warren Wiechmann, MD, MBA

    2016-03-01

    Full Text Available Introduction: The use of personal mobile devices in the medical field has grown quickly, and a large proportion of physicians use their mobile devices as an immediate resource for clinical decisionmaking, prescription information and other medical information. The iTunes App Store (Apple, Inc. contains approximately 20,000 apps in its “Medical” category, providing a robust repository of resources for clinicians; however, this represents only 2% of the entire App Store. The App Store does not have strict criteria for identifying content specific to practicing physicians, making the identification of clinically relevant content difficult. The objective of this study is to quantify the characteristics of existing medical applications in the iTunes App Store that could be used by emergency physicians, residents, or medical students. Methods: We found applications related to emergency medicine (EM by searching the iTunes App Store for 21 terms representing core content areas of EM, such as “emergency medicine,” “critical care,” “orthopedics,” and “procedures.” Two physicians independently reviewed descriptions of these applications in the App Store and categorized each as the following: Clinically Relevant, Book/ Published Source, Non-English, Study Tools, or Not Relevant. A third physician reviewer resolved disagreements about categorization. Descriptive statistics were calculated. Results: We found a total of 7,699 apps from the 21 search terms, of which 17.8% were clinical, 9.6% were based on a book or published source, 1.6% were non-English, 0.7% were clinically relevant patient education resources, and 4.8% were study tools. Most significantly, 64.9% were considered not relevant to medical professionals. Clinically relevant apps make up approximately 6.9% of the App Store’s “Medical” Category and 0.1% of the overall App Store. Conclusion: Clinically relevant apps represent only a small percentage (6.9% of the total App

  19. Identifying genes relevant to specific biological conditions in time course microarray experiments.

    Science.gov (United States)

    Singh, Nitesh Kumar; Repsilber, Dirk; Liebscher, Volkmar; Taher, Leila; Fuellen, Georg

    2013-01-01

    Microarrays have been useful in understanding various biological processes by allowing the simultaneous study of the expression of thousands of genes. However, the analysis of microarray data is a challenging task. One of the key problems in microarray analysis is the classification of unknown expression profiles. Specifically, the often large number of non-informative genes on the microarray adversely affects the performance and efficiency of classification algorithms. Furthermore, the skewed ratio of sample to variable poses a risk of overfitting. Thus, in this context, feature selection methods become crucial to select relevant genes and, hence, improve classification accuracy. In this study, we investigated feature selection methods based on gene expression profiles and protein interactions. We found that in our setup, the addition of protein interaction information did not contribute to any significant improvement of the classification results. Furthermore, we developed a novel feature selection method that relies exclusively on observed gene expression changes in microarray experiments, which we call "relative Signal-to-Noise ratio" (rSNR). More precisely, the rSNR ranks genes based on their specificity to an experimental condition, by comparing intrinsic variation, i.e. variation in gene expression within an experimental condition, with extrinsic variation, i.e. variation in gene expression across experimental conditions. Genes with low variation within an experimental condition of interest and high variation across experimental conditions are ranked higher, and help in improving classification accuracy. We compared different feature selection methods on two time-series microarray datasets and one static microarray dataset. We found that the rSNR performed generally better than the other methods.

  20. Provision of water by halite deliquescence for Nostoc commune biofilms under Mars relevant surface conditions

    Science.gov (United States)

    Jänchen, Jochen; Feyh, Nina; Szewzyk, Ulrich; de Vera, Jean-Pierre P.

    2016-04-01

    Motivated by findings of new mineral related water sources for organisms under extremely dry conditions on Earth we studied in an interdisciplinary approach the water sorption behaviour of halite, soil component and terrestrial Nostoc commune biofilm under Mars relevant environmental conditions. Physicochemical methods served for the determination of water sorption equilibrium data and survival of heterotrophic bacteria in biofilm samples with different water contents was assured by recultivation. Deliquescence of halite provides liquid water at temperatures <273 K and may serve as water source on Mars during the morning stabilized by the CO2 atmosphere for a few hours. The protecting biofilm of N. commune is rather hygroscopic and tends to store water at lower humidity values. Survival tests showed that a large proportion of the Alphaproteobacteria dominated microbiota associated to N. commune is very desiccation tolerant and water uptake from saturated NaCl solutions (either by direct uptake of brine or adsorption of humidity) did not enhance recultivability in long-time desiccated samples. Still, a minor part can grow under highly saline conditions. However, the salinity level, although unfavourable for the host organism, might be for parts of the heterotrophic microbiota no serious hindrance for growing in salty Mars-like environments.

  1. Development of an inspection robot under iter relevant vacuum and temperature conditions

    Energy Technology Data Exchange (ETDEWEB)

    Hatchressian, J-C; Bruno, V; Gargiulo, L; Bayetti, P; Cordier, J-J; Samaille, F [Association Euratom-CEA, DSM/Departement de Recherche sur la Fusion Controlee, CEA Cadarache, F-13108 Saint Paul-Lez-Durance Cedex (France); Keller, D; Perrot, Y; Friconneau, J-P [CEA, LIST, Service de Robotique Interactive, 18 route du Panorama, BP6, Fontenay aux Roses F-92265 France (France); Palmer, J D [EFDA-CSU Max-Planck-Institut fuer Plasma Physik Boltzmannstr.2, D-85748 Garching Germany (Germany)

    2008-03-15

    Robotic operations are one of the major maintenance challenges for ITER and future fusion reactors. In vessel inspection operations without loss of conditioning could be very mandatory. Within this framework, the aim of the Articulated Inspection Arm (AIA) project is to demonstrate the feasibility of a multi-purpose in-vessel Remote Handling inspection system. It is a long reach, composed of 5 segments with in all 8 degrees of freedom, limited payload carrier (up to 10kg) and a total range of 8m. The project is currently developed by the CEA within the European work program. Some tests will validate chosen concepts for operations under ITER relevant vacuum and temperature conditions. The presence of magnetic fields, radiation and neutron beams will not be considered. This paper deals with the choices of the materials to minimize the out-gassing under vacuum and high temperature during conditioning, the implantation of the electronics which are enclosed in boxes with special gaskets, the design of the first embedded process which is a viewing system.

  2. Usefulness of an Implantable Loop Recorder to Detect Clinically Relevant Arrhythmias in Patients With Advanced Fabry Cardiomyopathy.

    Science.gov (United States)

    Weidemann, Frank; Maier, Sebastian K G; Störk, Stefan; Brunner, Thomas; Liu, Dan; Hu, Kai; Seydelmann, Nora; Schneider, Andreas; Becher, Jan; Canan-Kühl, Sima; Blaschke, Daniela; Bijnens, Bart; Ertl, Georg; Wanner, Christoph; Nordbeck, Peter

    2016-07-15

    Patients with genetic cardiomyopathy that involves myocardial hypertrophy often develop clinically relevant arrhythmias that increase the risk of sudden death. Consequently, guidelines for medical device therapy were established for hypertrophic cardiomyopathy, but not for conditions with only anecdotal evidence of arrhythmias, like Fabry cardiomyopathy. Patients with Fabry cardiomyopathy progressively develop myocardial fibrosis, and sudden cardiac death occurs regularly. Because 24-hour Holter electrocardiograms (ECGs) might not detect clinically important arrhythmias, we tested an implanted loop recorder for continuous heart rhythm surveillance and determined its impact on therapy. This prospective study included 16 patients (12 men) with advanced Fabry cardiomyopathy, relevant hypertrophy, and replacement fibrosis in "loco typico." No patients previously exhibited clinically relevant arrhythmias on Holter ECGs. Patients received an implantable loop recorder and were prospectively followed with telemedicine for a median of 1.2 years (range 0.3 to 2.0 years). The primary end point was a clinically meaningful event, which required a therapy change, captured with the loop recorder. Patients submitted data regularly (14 ± 11 times per month). During follow-up, 21 events were detected (including 4 asystole, i.e., ECG pauses ≥3 seconds) and 7 bradycardia events; 5 episodes of intermittent atrial fibrillation (>3 minutes) and 5 episodes of ventricular tachycardia (3 sustained and 2 nonsustained). Subsequently, as defined in the primary end point, 15 events leaded to a change of therapy. These patients required therapy with a pacemaker or cardioverter-defibrillator implantation and/or anticoagulation therapy for atrial fibrillation. In conclusion, clinically relevant arrhythmias that require further device and/or medical therapy are often missed with Holter ECGs in patients with advanced stage Fabry cardiomyopathy, but they can be detected by telemonitoring with

  3. New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis

    Directory of Open Access Journals (Sweden)

    Dass Crispin R

    2010-06-01

    Full Text Available Abstract Background Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy. Methods Two human chondrosarcoma cell lines, JJ012 and FS090, were evaluated for proliferation, colony formation, invasion, angiogenesis and osteoclastogenesis. Cell lines were also investigated for VEGF, MMP-2, MMP-9, and RECK expression. JJ012 and FS090 were injected separately into the mouse tibia intramedullary canal or tibial periosteum. Animal limbs were measured, and x-rayed for evidence of tumour take and progression. Tibias and lungs were harvested to determine the presence of tumour and lung metastases. Results JJ012 demonstrated significantly higher proliferative capacity, invasion, and colony formation in collagen I gel. JJ012 conditioned medium stimulated endothelial tube formation and osteoclastogenesis with a greater potency than FS090 conditioned medium, perhaps related to the effects of VEGF and MMP-9. In vivo, tumours formed in intratibial and periosteal groups injected with JJ012, however no mice injected with FS090 developed tumours. JJ012 periosteal tumours grew to 3 times the non-injected limb size by 7 weeks, whereas intratibial injected limbs required 10 weeks to achieve a similar tumour size. Sectioned tumour tissue demonstrated features of grade III chondrosarcoma. All JJ012 periosteal tumours (5/5 resulted in lung micro-metastases, while only 2/4 JJ012 intratibial tumours demonstrated metastases. Conclusions The established JJ012 models replicate the site, morphology, and many behavioural characteristics of human chondrosarcoma. Local tumour invasion of bone and spontaneous lung metastasis offer valuable assessment tools to test the potential of novel agents for future chondrosarcoma therapy.

  4. Predicting clinical relevance of grapefruit-drug interactions: a complicated process.

    Science.gov (United States)

    Bailey, D G

    2017-04-01

    Grapefruit juice interacts with a number of drugs. This commentary provides feedback on a previously proposed approach for predicting clinically relevant interactions with grapefruit juice based on the average inherent oral bioavailability (F) and magnitude of increase in bioavailability with other CYP3A inhibitors of the drug. Additional factors such as variability of the magnitude of the pharmacokinetic interaction among individuals, product monograph cautionary statements and vulnerability of the patient population should be considered. A flow diagram is provided that should improve prediction of the pharmacokinetic interaction and clinical relevance for affected drugs and that recommends different courses of action for patient management. Forecasting the clinical importance of a particular drug interaction with grapefruit can be improved through consideration of additional readily available drug regulatory information. © 2016 John Wiley & Sons Ltd.

  5. 42 CFR 493.1225 - Condition: Clinical cytogenetics.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Clinical cytogenetics. 493.1225 Section... Testing § 493.1225 Condition: Clinical cytogenetics. If the laboratory provides services in the specialty of Clinical cytogenetics, the laboratory must meet the requirements specified in §§ 493.1230...

  6. Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community.

    Science.gov (United States)

    Driver, Vickie R; Gould, Lisa J; Dotson, Peggy; Gibbons, Gary W; Li, William W; Ennis, William J; Kirsner, Robert S; Eaglstein, William H; Bolton, Laura L; Carter, Marissa J

    2017-05-01

    Wounds that exhibit delayed healing add extraordinary clinical, economic, and personal burdens to patients, as well as to increasing financial costs to health systems. New interventions designed to ease such burdens for patients with cancer, renal, or ophthalmologic conditions are often cleared for approval by the U.S. Food and Drug Administration (FDA) using multiple endpoints but the requirement of complete healing as a primary endpoint for wound products impedes FDA clearance of interventions that can provide other clinical or patient-centered benefits for persons with wounds. A multidisciplinary group of wound experts undertook an initiative, in collaboration with the FDA, to identify and content validate supporting FDA criteria for qualifying wound endpoints relevant to clinical practice (CP) and patient-centered outcomes (PCO) as primary outcomes in clinical trials. As part of the initiative, a research study was conducted involving 628 multidisciplinary expert wound clinicians and researchers from 4 different groups: the interdisciplinary core advisory team; attendees of the Spring 2015 Symposium on Advanced Wound Care (SAWC); clinicians employed by a national network of specialty clinics focused on comprehensive wound care; and Association for the Advancement of Wound Care (AAWC) and Wound Healing Society (WHS) members who had not previously completed the survey. The online survey assessed 28 literature-based wound care endpoints for their relevance and importance to clinical practice and clinical research. Fifteen of the endpoints were evaluated for their relevance to improving quality of life. Twenty-two endpoints had content validity indexes (CVI) ≥ 0.75, and 15 were selected as meriting potential inclusion as additional endpoints for FDA approval of future wound care interventions. This study represents an important first step in identifying and validating new measurable wound care endpoints for clinical research and practice and for regulatory

  7. Polymicrobial infections involving clinically relevant Gram-negative bacteria and fungi.

    Science.gov (United States)

    Dhamgaye, Sanjiveeni; Qu, Yue; Peleg, Anton Y

    2016-12-01

    Interactions between fungi and bacteria and their relevance to human health and disease have recently attracted increased attention in biomedical fields. Emerging evidence shows that bacteria and fungi can have synergistic or antagonistic interactions, each with important implications for human colonization and disease. It is now appreciated that some of these interactions may be strategic and helps promote the survival of one or both microorganisms within the host. This review will shed light on clinically relevant interactions between fungi and Gram-negative bacteria. Mechanism of interaction, host immune responses, and preventive measures will also be reviewed. © 2016 John Wiley & Sons Ltd.

  8. Investigating the non-classical boundary conditions relevant to strain gradient theories

    Science.gov (United States)

    Jafari, Akbar; Ezzati, Meysam

    2017-02-01

    In the present study, two classes of non-classical constitutive equations consisting of the first and the second order strain gradients theories (FSG and SSG) were applied in order to develop the governing equations of static and free vibrational behavior of beam structures. The governing equations in orders of six and eight were constructed for FSG and SSG theories, respectively. Therefore, higher order or in other words non-classical boundary conditions (HOBCs or NCBCs) came into play in addition to the classical ones (CBCs). Some explanations were presented about the concept of the non-classical boundary conditions. Analytical and finite element (FE) approaches were employed to solve the governing equations. The analytical solutions were utilized in validation and convergence study of FE results. Comparisons were made with the relevant data reported in the open literature; however, to the best of the authors' knowledge, few references have been published on SSG theory and HOBCs. In the numerical studies, the effects of applying different combinations of CBCs and HOBCs to the static and free vibration behaviors of the beam were investigated. Moreover, the impacts of non-classical elastic constants and the beam size on its behavior were also studied.

  9. Neutron imaging of diabatic two-phase flows relevant to air conditioning

    Energy Technology Data Exchange (ETDEWEB)

    Geoghegan, Patrick J [ORNL; Sharma, Vishaldeep [ORNL

    2017-01-01

    The design of the evaporator of an air conditioning system relies heavily on heat transfer coefficients and pressure drop correlations that predominantly involve an estimate of the changing void fraction and the underlying two-phase flow regime. These correlations dictate whether the resulting heat exchanger is oversized or not and the amount of refrigerant charge necessary to operate. The latter is particularly important when dealing with flammable or high GWP refrigerants. Traditional techniques to measure the void fraction and visualize the flow are either invasive to the flow or occur downstream of the evaporator, where some of the flow distribution will have changed. Neutron imaging has the potential to visualize two-phase flow in-situ where an aluminium heat exchanger structure becomes essentially transparent to the penetrating neutrons. The subatomic particles are attenuated by the passing refrigerant flow. The resulting image may be directly related to the void fraction and the overall picture provides a clear insight into the flow regime present. This work presents neutron images of the refrigerant Isopentane as it passes through the flow channels of an aluminium evaporator at flowrates relevant to air conditioning. The flow in a 4mm square macro channel is compared to that in a 250 m by 750 m rectangular microchannel in terms of void fraction and regime. All neutron imaging experiments were conducted at the High Flux Isotope Reactor, an Oak Ridge National Laboratory facility

  10. Stability of silver nanoparticles: agglomeration and oxidation in biological relevant conditions

    Science.gov (United States)

    Valenti, Laura E.; Giacomelli, Carla E.

    2017-05-01

    Silver nanoparticles (Ag-NP) are the most used nanomaterial in consumer products due to the intrinsic antimicrobial capacity of silver. However, Ag-NP may be also harmful to algae, aquatic species, mammalian cells, and higher plants because both Ag+ and nanoparticles are responsible of cell damages. The oxidative dissolution of Ag-NP would proceed to completion under oxic conditions, but the rate and extent of the dissolution depend on several factors. This work correlates the effect of the capping agent (albumin and citrate) with the stability of Ag-NP towards agglomeration in simulated body fluid (SBF) and oxidation in the presence of ROS species (H2O2). Capping provides colloidal stability only through electrostatic means, whereas albumin acts as bulky ligands giving steric and electrostatic repulsion, inhibiting the agglomeration in SBF. However, citrate capping protects Ag-NP from dissolution to a major extent than albumin does because of its reducing power. Moreover, citrate in solution minimizes the oxidation of albumin-coated Ag-NP even after long incubation times. H2O2-induced dissolution proceeds to completion with Ag-NP incubated in SBF, while incubation in citrate leads to an incomplete oxidation. In short, albumin is an excellent capping agent to minimize Ag-NP agglomeration whereas citrate provides a mild-reductive medium that prevents dissolution in biological relevant media as well as in the presence of ROS species. These results provide insight into how the surface properties and media composition affect the release of Ag+ from Ag-NP, related to the cell toxicity and relevant to the storage and lifetime of silver-containing nanomaterials.

  11. Accelerating process and catalyst development in reforming reactions with high throughput technologies under industrially relevant conditions

    Energy Technology Data Exchange (ETDEWEB)

    Schunk, S.A.; Bollmann, G.; Froescher, A.; Kaiser, H.; Lange de Oliveira, A.; Roussiere, T.; Wasserschaff, G. [hte Aktiengesellschaft, Heidelberg (Germany); Domke, I. [BASF SE, Ludwigshafen (Germany)

    2010-12-30

    The generation of hydrogen via reforming of a variety of carbon containing feed-stocks in the presence of water is up to date one of the most versatile technologies for the production of hydrogen and syngas. Although these reforming technologies are in principle well established, understood and commercialized, there are still a number of technological challenges that are not solved up to a satisfactorily degree and there is a constant demand for appropriate answers to the challenges posed. High throughput experimentation can be a valuable tool in helping accelerate the development of suitable solutions on the catalyst and process development side. In order to be able to generate test data that are close or identical to process relevant conditions, hte has developed a new technology portfolio of test technologies named Stage-IV technology. In contrast to earlier developments which address more small scale testing on the basis of catalyst volumes of 1ml up to 10 ml under isothermal conditions, our new technology portfolio offers the advantage of test volumes at sub-pilot scale also realizing reactor dimensions close to technical applications. This does not only ensure a good mimic of the hydrodynamic conditions of the technical scale, but also allows a fingerprinting of features like temperature gradients in the catalyst bed which play a large role for catalyst performance. Apart from catalyst tests with granulates when screening for optimized catalyst compositions, the units are designed to accommodate tests with shaped catalysts. In order to demonstrate how these technologies can accelerate catalyst and process development we have chosen technically challenging application examples: (I) Pre-reforming and reforming of methane based feeds which accelerate coking and catalyst deactivation. Higher reaction pressures, high CO{sub 2} contents in the feedgas (which occur typically in sources like bio-gas or certain types of natural gas), the presence of higher alkanes

  12. Putting the Pieces Together: Clinically Relevant Genetic and Genomic Resources for Hospitalists and Neonatologists.

    Science.gov (United States)

    Miller, Rebecca; Khromykh, Alina; Babcock, Holly; Jenevein, Callie; Solomon, Benjamin D

    2017-02-01

    Genetic conditions are individually rare but are common in aggregate, and they often present in the neonatal and early pediatric periods. These conditions are often severe, can be difficult to diagnose and manage, and may heavily affect patients, families, health care systems, and society. Because of recent technological advances, the availability and uptake of genetic and genomic testing are increasing rapidly. However, there is a dearth of trained geneticists and genetic counselors to help guide and explain these conditions and relevant tests. To help hospitalists, neonatologists, and related practitioners navigate this complex and evolving field, we have compiled a list of free (mostly Web-based) resources relevant to the diagnosis and management of genetic conditions and related disorders. These resources, which we describe individually, can be useful for nongeneticist clinicians, and some also include material that can be used to explain concepts and conditions to patients or families. The resources presented are divided into the following categories (which overlap): general information, databases of genetic conditions, resources that can help generate differential diagnoses, databases of genetic testing laboratories (to help with logistics of ordering tests), information on newborn screening, and other resources. We also include a separate list of helpful textbooks and manuals. We conclude with 2 examples describing how some of these resources would be used by a pediatric hospitalist or neonatologist during the inpatient management of a child with a suspected genetic condition. Copyright © 2017 by the American Academy of Pediatrics.

  13. Biomarkers for Early Detection of Clinically Relevant Prostate Cancer: A Multi-Institutional Validation Trial

    Science.gov (United States)

    2015-10-01

    biomarkers to determine the presence of or progression to aggressive disease. ( Lead site: FHCRC) Milestone 2. Execute collaboration agreement with...panel of four-kallikrein plasma-based markers to determine the presence of or progression to clinically relevant prostate cancer. ( Lead site: FHCRC... Lead site: FHCRC) Milestone 10. Urine specimens identified for analysis. Due 12/30/2014 COMPLETED Milestone 11. PCA3 and TMPRSS2:ERG validation

  14. Clinical Relevant Fatigue in Women with Breast Cancer: Prevalence and Associated Factors

    OpenAIRE

    Lamino, Daniela de Araujo; Sra Cibele, Cibele Andruciolli de Mattos Pimenta; Sra Patricia, Patricia Emilia Braga; Sra Dalete, Dalete Delalibera Corrêa de Faria Mota

    2014-01-01

    Introduction: Fatigue is a common symptom in patients with cancer. Objective: Toexamine the prevalence and independent predictors of fatigue in women with breastcancer. Material and Method: A cross-sectional study with a nonrandom sample of163 patients in outpatient follow-up. Fatigue was assessed by the Piper Fatigue Scale.Results: Clinical relevant fatigue (score ≥ 4) was present in 31.9% of the sample andthe average intensity was 6 (SD = 1.3).Pain and depression were factors independentlya...

  15. The Role and Clinical Relevance of Disseminated Tumor Cells in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Malgorzata Banys

    2014-01-01

    Full Text Available Tumor cell dissemination is a common phenomenon observed in most cancers of epithelial origin. One-third of breast cancer patients present with disseminated tumor cells (DTCs in bone marrow at time of diagnosis; these patients, as well as patients with persistent DTCs, have significantly worse clinical outcome than DTC-negative patients. Since DTC phenotype may differ from the primary tumor with regard to ER and HER2 status, reevaluation of predictive markers on DTCs may optimize treatment choices. In the present review, we report on the clinical relevance of DTC detection in breast cancer.

  16. Clinically Relevant Physical Benefits of Exercise Interventions in Breast Cancer Survivors.

    Science.gov (United States)

    Kirkham, Amy A; Bland, Kelcey A; Sayyari, Sarah; Campbell, Kristin L; Davis, Margot K

    2016-02-01

    Evidence is currently limited for the effect of exercise on breast cancer clinical outcomes. However, several of the reported physical benefits of exercise, including peak oxygen consumption, functional capacity, muscle strength and lean mass, cardiovascular risk factors, and bone health, have established associations with disability, cardiovascular disease risk, morbidity, and mortality. This review will summarize the clinically relevant physical benefits of exercise interventions in breast cancer survivors and discuss recommendations for achieving these benefits. It will also describe potential differences in intervention delivery that may impact outcomes and, lastly, describe current physical activity guidelines for cancer survivors.

  17. The Role and Clinical Relevance of Disseminated Tumor Cells in Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Banys, Malgorzata, E-mail: maggybanys@yahoo.de [Department of Obstetrics and Gynecology, University of Duesseldorf, Duesseldorf D-40225 (Germany); Department of Obstetrics and Gynecology, Marienkrankenhaus Hamburg, Hamburg D-22087 (Germany); Krawczyk, Natalia; Fehm, Tanja [Department of Obstetrics and Gynecology, University of Duesseldorf, Duesseldorf D-40225 (Germany)

    2014-01-15

    Tumor cell dissemination is a common phenomenon observed in most cancers of epithelial origin. One-third of breast cancer patients present with disseminated tumor cells (DTCs) in bone marrow at time of diagnosis; these patients, as well as patients with persistent DTCs, have significantly worse clinical outcome than DTC-negative patients. Since DTC phenotype may differ from the primary tumor with regard to ER and HER2 status, reevaluation of predictive markers on DTCs may optimize treatment choices. In the present review, we report on the clinical relevance of DTC detection in breast cancer.

  18. Targeted testing with diethylthiourea often reveals clinically relevant allergic contact dermatitis caused by neoprene rubber

    DEFF Research Database (Denmark)

    Dall, Anne B-H; Andersen, Klaus Ejner; Mortz, Charlotte G

    2012-01-01

    Background. Diethylthiourea is widely used in the rubber industry, particularly in neoprene rubber, and may cause allergic contact dermatitis. However, as thiourea allergens are not part of the European baseline series, the diagnosis of allergic contact dermatitis caused by thiourea compounds......, and positive reactions were found in 15% (13/88). Thus, 15% (37/239) had positive patch test reactions to diethylthiourea, all with current clinical relevance and all strong. Conclusion. Clinical suspicion of neoprene rubber allergy and subsequent aimed patch testing with diethylthiourea give a high yield...

  19. Minimal residual disease detection in mantle cell lymphoma: technical aspects and clinical relevance.

    Science.gov (United States)

    Pott, Christiane

    2011-07-01

    The prognostic impact of minimal residual disease (MRD) has been demonstrated for several hematologic malignancies. While in acute lymphoblastic leukemias MRD assessment by polymerase chain reaction (PCR)-based methods has been established as an important tool for clinical risk assessment and is part of clinical management, data demonstrating a prognostic value of MRD in mantle cell lymphoma (MCL) were sparse and results from randomized trials have been published only recently. In the present review technical aspects of different MRD detection methods are discussed, as well as the prognostic relevance of MRD in the context of clinical trials in patients with MCL. Furthermore, recommendations are given for workflow and useful implication of MRD in future clinical trials design.

  20. Using mixed methods to identify and answer clinically relevant research questions.

    Science.gov (United States)

    Shneerson, Catherine L; Gale, Nicola K

    2015-06-01

    The need for mixed methods research in answering health care questions is becoming increasingly recognized because of the complexity of factors that affect health outcomes. In this article, we argue for the value of using a qualitatively driven mixed method approach for identifying and answering clinically relevant research questions. This argument is illustrated by findings from a study on the self-management practices of cancer survivors and the exploration of one particular clinically relevant finding about higher uptake of self-management in cancer survivors who had received chemotherapy treatment compared with those who have not. A cross-sectional study generated findings that formed the basis for the qualitative study, by informing the purposive sampling strategy and generating new qualitative research questions. Using a quantitative research component to supplement a qualitative study can enhance the generalizability and clinical relevance of the findings and produce detailed, contextualized, and rich answers to research questions that would be unachievable through quantitative or qualitative methods alone.

  1. A direct numerical simulation of cool-flame affected autoignition in diesel engine-relevant conditions

    Energy Technology Data Exchange (ETDEWEB)

    Krisman, Alexander; Hawkes, Evatt Robert.; Talei, Mohsen; Bhagatwala, Ankit; Chen, Jacqueline H.

    2016-11-11

    In diesel engines, combustion is initiated by a two-staged autoignition that includes both low- and high-temperature chemistry. The location and timing of both stages of autoignition are important parameters that influence the development and stabilisation of the flame. In this study, a two-dimensional direct numerical simulation (DNS) is conducted to provide a fully resolved description of ignition at diesel engine-relevant conditions. The DNS is performed at a pressure of 40 atmospheres and at an ambient temperature of 900 K using dimethyl ether (DME) as the fuel, with a 30 species reduced chemical mechanism. At these conditions, similar to diesel fuel, DME exhibits two-stage ignition. The focus of this study is on the behaviour of the low-temperature chemistry (LTC) and the way in which it influences the high-temperature ignition. The results show that the LTC develops as a “spotty” first-stage autoignition in lean regions which transitions to a diffusively supported cool-flame and then propagates up the local mixture fraction gradient towards richer regions. The cool-flame speed is much faster than can be attributed to spatial gradients in first-stage ignition delay time in homogeneous reactors. The cool-flame causes a shortening of the second-stage ignition delay times compared to a homogeneous reactor and the shortening becomes more pronounced at richer mixtures. Multiple high-temperature ignition kernels are observed over a range of rich mixtures that are much richer than the homogeneous most reactive mixture and most kernels form much earlier than suggested by the homogeneous ignition delay time of the corresponding local mixture. Altogether, the results suggest that LTC can strongly influence both the timing and location in composition space of the high-temperature ignition.

  2. Manufacturing and testing in reactor relevant conditions of brazed plasma facing components of the ITER divertor

    Energy Technology Data Exchange (ETDEWEB)

    Bisio, M. [Ansaldo Ricerche s.p.a., C.so Perrone 25, I-16152 Genova (Italy); Branca, V. [Ansaldo Ricerche s.p.a., C.so Perrone 25, I-16152 Genova (Italy); Marco, M. Di [FN s.p.a., ss 35 bis dei Giovi km 15, I-15062 Bosco Marengo (Albania) (Italy); Federici, A. [Ansaldo Ricerche s.p.a., C.so Perrone 25, I-16152 Genova (Italy); Grattarola, M. [Ansaldo Ricerche s.p.a., C.so Perrone 25, I-16152 Genova (Italy)]. E-mail: grattarola@ansaldo.it; Gualco, G. [Ansaldo Ricerche s.p.a., C.so Perrone 25, I-16152 Genova (Italy); Guarnone, P. [Ansaldo Ricerche s.p.a., C.so Perrone 25, I-16152 Genova (Italy); Luconi, U. [Ansaldo Ricerche s.p.a., C.so Perrone 25, I-16152 Genova (Italy); Merola, M. [EFDA, Boltzmanstr. 2, D-85748 Garching (Germany); Ozzano, C. [Ansaldo Ricerche s.p.a., C.so Perrone 25, I-16152 Genova (Italy); Pasquale, G. [FN s.p.a., ss 35 bis dei Giovi km 15, I-15062 Bosco Marengo (AL) (Italy); Poggi, P. [Ansaldo Ricerche s.p.a., C.so Perrone 25, I-16152 Genova (Italy); Rizzo, S. [Ansaldo Ricerche s.p.a., C.so Perrone 25, I-16152 Genova (Italy); Varone, F. [Ansaldo Ricerche s.p.a., C.so Perrone 25, I-16152 Genova (Italy)

    2005-11-15

    A fabrication route based on brazing technology has been developed for the realization of the high heat flux components for the ITER vertical target and Dome-Liner. The divertor vertical target is armoured with carbon fiber reinforced carbon and tungsten in the lower straight part and in the upper curved part, respectively. The armour material is joined to heat sinks made of precipitation hardened copper-chromium-zirconium alloy. The plasma facing units of the dome component are based on a tungsten flat tile design with hypervapotron cooling. An innovative brazing technique based on the addition of carbon fibers to the active brazing alloy, developed by Ansaldo Ricerche for applications in the field of the energy production, has been used for the carbon fiber composite to copper joint to reduce residual stresses. The tungsten-copper joint has been realized by direct casting. A proper brazing thermal cycle has been studied to guarantee the required mechanical properties of the precipitation hardened alloy after brazing. The fabrication route of plasma facing components for the ITER vertical target and dome based on the brazing technology has been proved by means of thermal fatigue tests performed on mock-ups in reactor relevant conditions.

  3. Stability of Fe-oxide nanoparticles coated with natural organic matter under relevant environmental conditions.

    Science.gov (United States)

    Chekli, L; Phuntsho, S; Tijing, L D; Zhou, J L; Kim, J-H; Shon, H K

    2014-01-01

    Manufactured nanoparticles (MNPs) are increasingly released into the environment and thus research on their fate and behaviour in complex environmental samples is urgently needed. The fate of MNPs in the aquatic environment will mainly depend on the physico-chemical characteristics of the medium. The presence and concentration of natural organic matter (NOM) will play a significant role on the stability of MNPs by either decreasing or exacerbating the aggregation phenomenon. In this study, we firstly investigated the effect of NOM concentration on the aggregation behaviour of manufactured Fe-oxide nanoparticles. Then, the stability of the coated nanoparticles was assessed under relevant environmental conditions. Flow field-flow fractionation, an emerging method which is gaining popularity in the field of nanotechnology, has been employed and results have been compared to another size-measurement technique to provide increased confidence in the outcomes. Results showed enhanced stability when the nanoparticles are coated with NOM, which was due to electrosteric stabilisation. However, the presence of divalent cations, even at low concentration (i.e. less than 1 mM) was found to induce aggregation of NOM-coated nanoparticles via bridging mechanisms between NOM and Ca(2+).

  4. Turbulent dispersivity under conditions relevant to airborne disease transmission between laboratory animals

    Science.gov (United States)

    Halloran, Siobhan; Ristenpart, William

    2013-11-01

    Virologists and other researchers who test pathogens for airborne disease transmissibility often place a test animal downstream from an inoculated animal and later determine whether the test animal became infected. Despite the crucial role of the airflow in pathogen transmission between the animals, to date the infectious disease community has paid little attention to the effect of airspeed or turbulent intensity on the probability of transmission. Here we present measurements of the turbulent dispersivity under conditions relevant to experimental tests of airborne disease transmissibility between laboratory animals. We used time lapse photography to visualize the downstream transport and turbulent dispersion of smoke particulates released from a point source downstream of an axial fan, thus mimicking the release and transport of expiratory aerosols exhaled by an inoculated animal. We show that for fan-generated turbulence the plume width is invariant with the mean airspeed and, close to the point source, increases linearly with downstream position. Importantly, the turbulent dispersivity is insensitive to the presence of meshes placed downstream from the point source, indicating that the fan length scale dictates the turbulent intensity and corresponding dispersivity.

  5. Clinically relevant known and candidate genes for obesity and their overlap with human infertility and reproduction.

    Science.gov (United States)

    Butler, Merlin G; McGuire, Austen; Manzardo, Ann M

    2015-04-01

    Obesity is a growing public health concern now reaching epidemic status worldwide for children and adults due to multiple problems impacting on energy intake and expenditure with influences on human reproduction and infertility. A positive family history and genetic factors are known to play a role in obesity by influencing eating behavior, weight and level of physical activity and also contributing to human reproduction and infertility. Recent advances in genetic technology have led to discoveries of new susceptibility genes for obesity and causation of infertility. The goal of our study was to provide an update of clinically relevant candidate and known genes for obesity and infertility using high resolution chromosome ideograms with gene symbols and tabular form. We used computer-based internet websites including PubMed to search for combinations of key words such as obesity, body mass index, infertility, reproduction, azoospermia, endometriosis, diminished ovarian reserve, estrogen along with genetics, gene mutations or variants to identify evidence for development of a master list of recognized obesity genes in humans and those involved with infertility and reproduction. Gene symbols for known and candidate genes for obesity were plotted on high resolution chromosome ideograms at the 850 band level. Both infertility and obesity genes were listed separately in alphabetical order in tabular form and those highlighted when involved with both conditions. By searching the medical literature and computer generated websites for key words, we found documented evidence for 370 genes playing a role in obesity and 153 genes for human reproduction or infertility. The obesity genes primarily affected common pathways in lipid metabolism, deposition or transport, eating behavior and food selection, physical activity or energy expenditure. Twenty-one of the obesity genes were also associated with human infertility and reproduction. Gene symbols were plotted on high resolution

  6. NT-ProBNP levels in saliva and its clinical relevance to heart failure.

    Directory of Open Access Journals (Sweden)

    Jared Yong Yang Foo

    Full Text Available BACKGROUND: Current blood based diagnostic assays to detect heart failure (HF have large intra-individual and inter-individual variations which have made it difficult to determine whether the changes in the analyte levels reflect an actual change in disease activity. Human saliva mirrors the body's health and well being and ∼20% of proteins that are present in blood are also found in saliva. Saliva has numerous advantages over blood as a diagnostic fluid which allows for a non-invasive, simple, and safe sample collection. The aim of our study was to develop an immunoassay to detect NT-proBNP in saliva and to determine if there is a correlation with blood levels. METHODS: Saliva samples were collected from healthy volunteers (n = 40 who had no underlying heart conditions and HF patients (n = 45 at rest. Samples were stored at -80°C until analysis. A customised homogeneous sandwich AlphaLISA((R immunoassay was used to quantify NT-proBNP levels in saliva. RESULTS: Our NT-proBNP immunoassay was validated against a commercial Roche assay on plasma samples collected from HF patients (n = 37 and the correlation was r(2 = 0.78 (p<0.01, y = 1.705× +1910.8. The median salivary NT-proBNP levels in the healthy and HF participants were <16 pg/mL and 76.8 pg/mL, respectively. The salivary NT-proBNP immunoassay showed a clinical sensitivity of 82.2% and specificity of 100%, positive predictive value of 100% and negative predictive value of 83.3%, with an overall diagnostic accuracy of 90.6%. CONCLUSION: We have firstly demonstrated that NT-proBNP can be detected in saliva and that the levels were higher in heart failure patients compared with healthy control subjects. Further studies will be needed to demonstrate the clinical relevance of salivary NT-proBNP in unselected, previously undiagnosed populations.

  7. High Prevalence and Clinical Relevance of Genes Affected by Chromosomal Breaks in Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Evert van den Broek

    Full Text Available Cancer is caused by somatic DNA alterations such as gene point mutations, DNA copy number aberrations (CNA and structural variants (SVs. Genome-wide analyses of SVs in large sample series with well-documented clinical information are still scarce. Consequently, the impact of SVs on carcinogenesis and patient outcome remains poorly understood. This study aimed to perform a systematic analysis of genes that are affected by CNA-associated chromosomal breaks in colorectal cancer (CRC and to determine the clinical relevance of recurrent breakpoint genes.Primary CRC samples of patients with metastatic disease from CAIRO and CAIRO2 clinical trials were previously characterized by array-comparative genomic hybridization. These data were now used to determine the prevalence of CNA-associated chromosomal breaks within genes across 352 CRC samples. In addition, mutation status of the commonly affected APC, TP53, KRAS, PIK3CA, FBXW7, SMAD4, BRAF and NRAS genes was determined for 204 CRC samples by targeted massive parallel sequencing. Clinical relevance was assessed upon stratification of patients based on gene mutations and gene breakpoints that were observed in >3% of CRC cases.In total, 748 genes were identified that were recurrently affected by chromosomal breaks (FDR 3% of cases, indicating that prevalence of gene breakpoints is comparable to the prevalence of well-known gene point mutations. Patient stratification based on gene breakpoints and point mutations revealed one CRC subtype with very poor prognosis.We conclude that CNA-associated chromosomal breaks within genes represent a highly prevalent and clinically relevant subset of SVs in CRC.

  8. Clinical relevance of comorbidity in anxiety disorders : A report from the Netherlands Study of Depression and Anxiety (NESDA)

    NARCIS (Netherlands)

    Hofmeijer-Sevink, Mieke Klein; Batelaan, Neeltje M.; van Megen, Harold J. G. M.; Penninx, Brenda W.; Cath, Danielle C.; van den Hout, Marcel A.; van Balkom, Anton J. L. M.

    Background: To study the clinical relevance of type of comorbidity and number of comorbid disorders in anxiety disorders. Four groups were compared according to sociodemographic-, vulnerability- and clinical factors: single anxiety disorder, anxiety-anxiety comorbidity, anxiety-depressive

  9. Clinical relevance of comorbidity in anxiety disorders : A report from the Netherlands Study of Depression and Anxiety (NESDA)

    NARCIS (Netherlands)

    Hofmeijer-Sevink, Mieke Klein; Batelaan, Neeltje M.; van Megen, Harold J. G. M.; Penninx, Brenda W.; Cath, Danielle C.; van den Hout, Marcel A.; van Balkom, Anton J. L. M.

    2012-01-01

    Background: To study the clinical relevance of type of comorbidity and number of comorbid disorders in anxiety disorders. Four groups were compared according to sociodemographic-, vulnerability- and clinical factors: single anxiety disorder, anxiety-anxiety comorbidity, anxiety-depressive comorbidit

  10. Clinical relevance of comorbidity in anxiety disorders : A report from the Netherlands Study of Depression and Anxiety (NESDA)

    NARCIS (Netherlands)

    Hofmeijer-Sevink, Mieke Klein; Batelaan, Neeltje M.; van Megen, Harold J. G. M.; Penninx, Brenda W.; Cath, Danielle C.; van den Hout, Marcel A.; van Balkom, Anton J. L. M.

    2012-01-01

    Background: To study the clinical relevance of type of comorbidity and number of comorbid disorders in anxiety disorders. Four groups were compared according to sociodemographic-, vulnerability- and clinical factors: single anxiety disorder, anxiety-anxiety comorbidity, anxiety-depressive comorbidit

  11. Developing students' clinical reasoning skills: correlates of perceived relevance of two teaching and learning approaches.

    Science.gov (United States)

    Postma, T C; White, J G

    2017-02-01

    'Relevance' is a key concept in adult learning. Hence, this study sought to examine students' perceptions of relevance of the teaching and learning in relation to different instructional designs employed in a Comprehensive Patient Care (CPC) course that aims to develop integrated clinical reasoning skills. Third to fifth year students (2009-2011) were asked to anonymously rate the relevance of the instructional design (RELID) they participated in by means of visual analogue scales at the School of Dentistry, University of Pretoria. They were also asked to rate their perceptions of the alignment between teaching and learning and outcomes (ATLO), assessments' contribution to learning (ACL), course organisation (CO) and teacher competence (TC). RELID served as the outcome measure in stepwise linear regression analyses. ATLO, ACL, CO, TC and the instructional design (case-based learning (CBL = 1) and the combination of discipline-based and lecture-based teaching in CPC (DB-LBT = 0)) served as the co-variables for each of the years of study. The analyses showed positive correlations between RELID and ATLO and between RELID and ACL for all the years of study. RELID was associated with TC in year three and four and CO was associated with RELID in year four and five. CBL outperformed DB-LBT in terms of perceived relevance of the teaching and learning. The results suggest that students' perceptions of the relevance of the instructional design may be enhanced when outcomes, teaching, learning and assessment are constructively aligned during the development of clinical reasoning skills. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Spray ignition measurements in a constant volume combustion vessel under engine-relevant conditions

    Science.gov (United States)

    Ramesh, Varun

    Pressure-based and optical diagnostics for ignition delay (ID) measurement of a diesel spray from a multi-hole nozzle were investigated in a constant volume combustion vessel (CVCV) at conditions similar to those in a conventional diesel engine at the start of injection (SOI). It was first hypothesized that compared to an engine, the shorter ID in a CVCV was caused by NO, a byproduct of premixed combustion. The presence of a significant concentration of NO+NO2 was confirmed experimentally and by using a multi-zone model of premixed combustion. Experiments measuring the effect of NO on ID were performed at conditions relevant to a conventional diesel engine. Depending on the temperature regime and the nature of the fuel, NO addition was found to advance or retard ignition. Constant volume ignition simulations were capable of describing the observed trends; the magnitudes were different due to the physical processes involved in spray ignition, not modeled in the current study. The results of the study showed that ID is sensitive to low NO concentrations (<100 PPM) in the low-temperature regime. A second source of uncertainty in pressure-based ID measurement is the systematic error associated with the correction used to account for the speed of sound. Simultaneous measurements of volumetric OH chemiluminescence (OHC) and pressure during spray ignition found the OHC to closely resemble the pressure-based heat release rate for the full combustion duration. The start of OHC was always found to be shorter than the pressure-based ID for all fuels and conditions tested by 100 ms. Experiments were also conducted measuring the location and timing of high-temperature ignition and the steady-state lift-off length by high-speed imaging of OHC during spray ignition. The delay period calculated using the measured ignition location and the bulk average speed of sound was in agreement with the delay between OHC and the pressure-based ID. Results of the study show that start of OHC

  13. Limited clinical relevance of mitochondrial DNA mutation and gene expression analyses in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Rachinger Andrea

    2008-10-01

    Full Text Available Abstract Background In recent years, numerous studies have investigated somatic mutations in mitochondrial DNA in various tumours. The observed high mutation rates might reflect mitochondrial deregulation; consequently, mutation analyses could be clinically relevant. The purpose of this study was to determine if mutations in the mitochondrial D-loop region and/or the level of mitochondrial gene expression could influence the clinical course of human ovarian carcinomas. Methods We sequenced a 1320-base-pair DNA fragment of the mitochondrial genome (position 16,000-750 in 54 cancer samples and in 44 corresponding germline control samples. In addition, six transcripts (MT-ATP6, MT-CO1, MT-CYB, MT-ND1, MT-ND6, and MT-RNR1 were quantified in 62 cancer tissues by real-time RT-PCR. Results Somatic mutations in the D-loop sequence were found in 57% of ovarian cancers. Univariate analysis showed no association between mitochondrial DNA mutation status or mitochondrial gene expression and any of the examined clinicopathologic parameters. A multivariate logistic regression model revealed that the expression of the mitochondrial gene RNR1 might be used as a predictor of tumour sensitivity to chemotherapy. Conclusion In contrast to many previously published papers, our study indicates rather limited clinical relevance of mitochondrial molecular analyses in ovarian carcinomas. These discrepancies in the clinical utility of mitochondrial molecular tests in ovarian cancer require additional large, well-designed validation studies.

  14. The Clinical and Socio-Economic Relevance of Increased IPMN Detection Rates and Management Choices.

    Science.gov (United States)

    Budde, Christoph; Beyer, Georg; Kühn, Jens-Peter; Lerch, Markus M; Mayerle, Julia

    2015-02-01

    Increased usage of computed tomography and magnetic resonance imaging has led to a large increase in identified pancreatic cysts of up to 25% in population-based studies. The clinical and economic relevance of identifying so many cystic lesions has not been established. Compared to other organs such as liver or kidney, dysontogenetic pancreatic cysts are rare. Pancreatic cysts comprise a variety of benign, premalignant or malignant lesions; however, precise diagnosis before resection has an accuracy of only 80%. The focus of recent research was the malignant potential of intraductal papillary mucinous neoplasms (IPMN) with the aim of establishing clinical pathways addressing risk of malignancy, age and comorbidity, treatment-related morbidity and mortality as well as cost-effectiveness of treatment and surveillance. The focus of this review is to analyze the clinical and socio-economic relevance as well as the cost-benefit relation for IPMNs. For analysis, the following MESH terms were used to identify original articles, reviews, and guidelines in PubMed: ('intraductal papillary mucinous neoplasm' OR 'pancreatic cysts') and (incidence OR relevance OR socio-economic OR economic OR cost-effectiveness OR cost-benefit). The retrieved publications were reviewed with a focus on clinical and socio-economic relevance in relation to the increasing incidence of IPMN. Addressing the increasing prevalence of pancreatic cystic lesions, recent consensus guidelines suggested criteria for risk stratification according to 'worrisome features' and 'high-risk stigmata'. Recent prospective cohort studies evaluated whether these can be applied in clinical practice. Evaluation of three different clinical scenarios with regard to costs and quality-adjusted life years suggested a better effectiveness of surveillance after initial risk stratification by endoscopic ultrasound-guided fine-needle aspiration with cyst fluid analysis compared with immediate resection or follow-up without

  15. Clinical relevance of antigen spreading pattern induced by CHP-MAGE-A4 cancer vaccination.

    Science.gov (United States)

    Miyauchi, Kengo; Tsuchikawa, Takahiro; Wada, Masataka; Abiko, Takehiro; Kyogoku, Noriaki; Shichinohe, Toshiaki; Miyahara, Yoshihiro; Kageyama, Shinichi; Ikeda, Hiroaki; Shiku, Hiroshi; Hirano, Satoshi

    2016-05-01

    To investigate the antigen spreading pattern in the CHP-MAGE-A4-vaccinated patients and analyze the clinical relevance of antigen spreading pattern as a surrogate marker of patient survival. 12 patients who had been injected with 300 μg of CHP-MAGE-A4 and 0.5 Klinische Einheit of OK-432 in more than five vaccinations were analyzed. Increases in the anti-MAGE-A4-specific antibody response were observed in eight patients (66.7%), compared with six patients (50%) for anti-NY-ESO-1 and five patients (41.7%) for anti-MAGE-A3 after five vaccinations. We identified frequent antigen spreading following MAGE-A4 vaccinations without associations with the clinical response or patient prognosis. Antigen spreading pattern might reflect tumor shrinkage as a response to treatment and treatment history (clinical trial registration number: UMIN000001999).

  16. A clinically relevant mouse model of canine osteosarcoma with spontaneous metastasis.

    Science.gov (United States)

    Chaffee, Beth K; Allen, Matthew J

    2013-01-01

    Many patients with osteosarcoma (OS) will succumb to distant metastasis, often involving the lungs. Effective therapies for treating lung metastases depend on the availability of a clinically relevant pre-clinical model. Mice were surgically implanted with OS tumor fragments. The time course of primary tumor growth and subsequent spread to the lung were determined. Following development of a lytic and proliferative primary bone lesion, tumor metastasized to the lung in the majority of mice. There was no evidence of tumor at three weeks, but 10 out of 11 mice ultimately developed secondary OS in the lung within 12 weeks. Implantation of OS tumor fragments leads to the development of primary bone tumors and secondary lung metastases, recapitulating the clinical behavior of OS. This model offers an advantage over cell suspension injection models by precluding initial seeding of the lung with tumor cells.

  17. Clinical relevance of sensitization to lupine in peanut-sensitized adults.

    Science.gov (United States)

    Peeters, K A B M; Koppelman, S J; Penninks, A H; Lebens, A; Bruijnzeel-Koomen, C A F M; Hefle, S L; Taylor, S L; van Hoffen, E; Knulst, A C

    2009-04-01

    The use of lupine in food has been increasing during the last decade and allergic reactions to lupine have been reported, especially in peanut-allergic patients. The frequency and the degree of cross-reactivity to other legumes are not known. The aim of the study was to investigate the frequency of sensitization to lupine, and in addition to pea and soy, and its clinical relevance, in peanut-sensitized patients. Furthermore, to determine the eliciting dose (ED) for lupine using double-blind placebo-controlled food challenges (DBPCFC). Thirty-nine unselected peanut-sensitized patients were evaluated by skin prick tests (SPT) and ImmunoCAP to lupine, pea, and soy. Clinical reactivity was measured by DBPCFC for lupine, and by history for pea and soy. Eighty-two percent of the study population was sensitized to lupine, 55% to pea, and 87% to soy. Clinically relevant sensitization to lupine, pea, or soy occurred in 35%, 29%, and 33% respectively of the study population. None of the patients was aware of the use of lupine in food. The lowest ED for lupine, inducing mild subjective symptoms, was 0.5 mg, and the no observed adverse effect level (NOAEL) was 0.1 mg. No predictive factors for lupine allergy were found. In peanut-sensitized patients, clinically relevant sensitization to either lupine or to pea or soy occurs frequently. The ED for lupine is low (0.5 mg), which is only fivefold higher than for peanut. Patients are not aware of lupine allergy and the presence of lupine in food, indicating that education is important to build awareness.

  18. NO2 uptake under practically relevant conditions on BaO/Pt(111)

    Energy Technology Data Exchange (ETDEWEB)

    Mudiyanselage, Kumudu; Szanyi, János

    2012-02-01

    The formation of nitrites and nitrates (Ba(NOx)2) under practically relevant conditions (PNO2 up to 1.0 Torr and T = 500 K) and their thermal decomposition on BaO (>20 monolayer equivalent (MLE))/Pt(1 1 1) were studied using temperature programmed desorption (TPD), infrared reflection absorption (IRA), and Xray photoelectron (XP) spectroscopies. The exposure of BaO to 1.0 × 10-8 Torr NO2 at 500 K leads to the formation of a Ba(NOx)2 layer with small, disordered crystalline nitrate clusters. Under these conditions (PNO2 = 1.0 × 10-8 Torr and T = 500 K) only the top portion of the BaO layer converts to Ba(NOx)2 and the nitrites in this Ba(NOx)2 layer stay without converting completely to nitrates even after 100 min of NO2 exposure. In the thermal decomposition of Ba(NOx)2, first nitrites decompose, releasing NO and then the decomposition of nitrates occurs via two pathways releasing NO2 and NO + O2. At 500 K and PNO2 ≥ 1.0 × 10-7 Torr, first NO2 reacts with BaO to form small disordered crystalline Ba(NO3)2 particles and then these particles agglomerate to form large, well-ordered (bulk-like) crystalline nitrates as the NO2 exposure increases. The thermal decomposition of these well-ordered, bulk-like crystalline nitrate aggregates occurs in two steps releasing NO2 and NO + O2 in each step in two different temperature regions. NO2 pressure ≥1.0 × 10-5 Torr is required for the complete oxidation of initially formed nitrites to nitrates and the full nitration of the BaO layer at 500 K sample temperature. We gratefully acknowledge the US Department of Energy (DOE), Office of Basic Energy Sciences, Division of Chemical Sciences for the support of this work. The research described in this paper was performed at the Environmental Molecular Sciences Laboratory (EMSL), a national scientific user facility sponsored by the DOE Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory (PNNL). PNNL is operated for the US DOE by

  19. Balancing Clinical and Pathologic Relevence in the Machine Learning Diagnosis of Epilepsy.

    Science.gov (United States)

    Kerr, Wesley T; Cho, Andrew Y; Anderson, Ariana; Douglas, Pamela K; Lau, Edward P; Hwang, Eric S; Raman, Kaavya R; Trefler, Aaron; Cohen, Mark S; Nguyen, Stefan T; Reddy, Navya M; Silverman, Daniel H

    2013-06-01

    The application of machine learning to epilepsy can be used both to develop clinically useful computer-aided diagnostic tools, and to reveal pathologically relevant insights into the disease. Such studies most frequently use neurologically normal patients as the control group to maximize the pathologic insight yielded from the model. This practice yields potentially inflated accuracy because the groups are quite dissimilar. A few manuscripts, however, opt to mimic the clinical comparison of epilepsy to non-epileptic seizures, an approach we believe to be more clinically realistic. In this manuscript, we describe the relative merits of each control group. We demonstrate that in our clinical quality FDG-PET database the performance achieved was similar using each control group. Based on these results, we find that the choice of control group likely does not hinder the reported performance. We argue that clinically applicable computer-aided diagnostic tools for epilepsy must directly address the clinical challenge of distinguishing patients with epilepsy from those with non-epileptic seizures.

  20. Detection of clinically relevant exonic copy-number changes by array CGH.

    Science.gov (United States)

    Boone, Philip M; Bacino, Carlos A; Shaw, Chad A; Eng, Patricia A; Hixson, Patricia M; Pursley, Amber N; Kang, Sung-Hae L; Yang, Yaping; Wiszniewska, Joanna; Nowakowska, Beata A; del Gaudio, Daniela; Xia, Zhilian; Simpson-Patel, Gayle; Immken, LaDonna L; Gibson, James B; Tsai, Anne C-H; Bowers, Jennifer A; Reimschisel, Tyler E; Schaaf, Christian P; Potocki, Lorraine; Scaglia, Fernando; Gambin, Tomasz; Sykulski, Maciej; Bartnik, Magdalena; Derwinska, Katarzyna; Wisniowiecka-Kowalnik, Barbara; Lalani, Seema R; Probst, Frank J; Bi, Weimin; Beaudet, Arthur L; Patel, Ankita; Lupski, James R; Cheung, Sau Wai; Stankiewicz, Pawel

    2010-12-01

    Array comparative genomic hybridization (aCGH) is a powerful tool for the molecular elucidation and diagnosis of disorders resulting from genomic copy-number variation (CNV). However, intragenic deletions or duplications--those including genomic intervals of a size smaller than a gene--have remained beyond the detection limit of most clinical aCGH analyses. Increasing array probe number improves genomic resolution, although higher cost may limit implementation, and enhanced detection of benign CNV can confound clinical interpretation. We designed an array with exonic coverage of selected disease and candidate genes and used it clinically to identify losses or gains throughout the genome involving at least one exon and as small as several hundred base pairs in size. In some patients, the detected copy-number change occurs within a gene known to be causative of the observed clinical phenotype, demonstrating the ability of this array to detect clinically relevant CNVs with subkilobase resolution. In summary, we demonstrate the utility of a custom-designed, exon-targeted oligonucleotide array to detect intragenic copy-number changes in patients with various clinical phenotypes.

  1. Evidence-based practice for the busy nurse practitioner: part one: relevance to clinical practice and clinical inquiry process.

    Science.gov (United States)

    Facchiano, Lynda; Snyder, Charlene Hoffman

    2012-10-01

    Evidence-based practice (EBP) continues to gain momentum within health care. The purpose of this four-part EBP series is to provide an introductory overview of the EBP process, emphasizing EBP steps one through three, in order to assist nurse practitioners (NPs) in building EBP skills that can be integrated into clinical practice. The relevance of EBP to the NP's clinical practice, an introduction to the EBP process steps, and clinical inquiry process begin the series. Scientific literature review, gray literature, and online evidence-based practice databases and resources. EBP has become increasingly important to NPs, yet there is evidence suggesting it is not being fully implemented in clinical practice. EBP is one way to keep the busy NP's knowledge up to date, enhance clinical judgment, and augment the existing provider-client decision-making process. The principles of EBP have become the cornerstone strategy for NPs to translate research findings into clinical practice. Practicing in an ever-changing healthcare environment, NPs have a responsibility to provide their clients with the best available evidence, while incorporating that evidence into the provider-client decision-making process. ©2012 The Author(s) Journal compilation ©2012 American Academy of Nurse Practitioners.

  2. MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant?

    Directory of Open Access Journals (Sweden)

    Rafael eDe La Torre

    2012-11-01

    Full Text Available In vitro human studies show that the metabolism of most amphetamine-like psychostimulants is regulated by the polymorphic cytochrome P450 isozyme CYP2D6. Two compounds, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA, were selected as archetypes to discuss the translation and clinical significance of in vitro to in vivo findings. Both compounds were chosen based on their differential interaction with CYP2D6 and their high abuse prevalence in society. Methamphetamine behaves as both a weak substrate and competitive inhibitor of CYP2D6, while MDMA acts as a high affinity substrate and potent mechanism-based inhibitor (MBI of the enzyme. The MBI behavior of MDMA on CYP2D6 implies that subjects, irrespective of their genotype/phenotype, are phenocopied to the poor metabolizer phenotype. The fraction of metabolic clearance regulated by CYP2D6 for both drugs is substantially lower than expected from in vitro studies. Other isoenzymes of cytochrome P450 and a relevant contribution of renal excretion play a part in their clearance. These facts tune down the potential contribution of CYP2D6 polymorphism in the clinical outcomes of both substances. Globally, the clinical relevance of CYP2D6 polymorphism is lower than that predicted by in vitro studies.

  3. Considerations of Environmentally Relevant Test Conditions for Improved Evaluation of Ecological Hazards of Engineered Nanomaterials

    Science.gov (United States)

    Engineered nanomaterials (ENMs) are increasingly entering the environment with uncertain consequences including potential ecological effects. Various research communities view differently whether ecotoxicological testing of ENMs should be conducted using environmentally relevant ...

  4. Clinical relevance of metronidazole and peripheral neuropathy: a systematic review of the literature.

    Science.gov (United States)

    Goolsby, Tiffany A; Jakeman, Bernadette; Gaynes, Robert P

    2017-09-05

    The objective of this paper was to review and evaluate the literature on metronidazole-associated peripheral neuropathy and determine the relevance in clinical practice. MEDLINE/PubMed, EBSCO, and Google Scholar were searched through February 2017 using the search terms metronidazole and peripheral neuropathy, or polyneuropathy, or paresthesia, or neurotoxicity. Relevant case reports, retrospective studies, surveys, and review articles were included. Bibliographies of all relevant articles were reviewed for additional sources. Overall, metronidazole is generally well tolerated but serious neurotoxicity, including peripheral neuropathy, has been reported. The overall incidence of peripheral neuropathy associated with metronidazole is unknown. Our review found 36 case reports (40 unique patients) of metronidazole-associated peripheral neuropathy with the majority of cases receiving >42 total grams (>4 weeks) of therapy (31 out of 40). In addition, we reviewed 13 clinical studies and found varying rates of peripheral neuropathy from 0-50%. Within these clinical studies, we found a higher incidence of peripheral neuropathy in patients receiving >42 total grams (>4 weeks) of metronidazole compared to those patients receiving ≤ 42 total grams (17.9% vs 1.7%). Nearly all patients had complete resolution of symptoms. In conclusion, peripheral neuropathy is exceedingly rare in patients who receive ≤ 42 total grams of metronidazole. Patients who receive larger total doses may be at higher risk of peripheral neuropathy but most patients have resolution of symptoms after discontinuing therapy. Antimicrobial stewardship programs may consider use of antibiotic combinations that include metronidazole over broad-spectrum alternatives when treating with ≤42 grams of the drug (≤4 weeks). Copyright © 2017. Published by Elsevier B.V.

  5. Metabolic acidosis in renal transplantation: neglected but of potential clinical relevance.

    Science.gov (United States)

    Messa, Pier Giorgio; Alfieri, Carlo; Vettoretti, Simone

    2016-05-01

    Chronic metabolic acidosis (CMA) is a common complication of the more advanced stages of chronic kidney diseases (CKD), and is associated with morbidity and mortality of CKD patients and possibly with the progression of renal disease. Nevertheless, there is limited evidence or information on the prevalence, the potential causal factors, the clinical impact and the effects of correction of CMA in kidney transplant recipients. In this review, we briefly look at the more relevant, though scanty, studies which have, over time, addressed the above-mentioned points, with the hope that in the future the interest of transplant nephrologists and surgeons will grow towards this unreasonably neglected issue.

  6. Nonmotor Symptoms in Parkinson’s Disease in 2012: Relevant Clinical Aspects

    Directory of Open Access Journals (Sweden)

    Anne Marie Bonnet

    2012-01-01

    Full Text Available Nonmotor symptoms (NMSs of Parkinson’s disease (PD are common, but they are often underrecognized in clinical practice, because of the lack of spontaneous complaints by the patients, and partly because of the absence of systematic questioning by the consulting physician. However, valid specific instruments for identification and assessment of these symptoms are available in 2012. The administration of the self-completed screening tool, NMSQuest, associated with questioning during the consultation, improves the diagnosis of NMSs. NMSs play a large role in degradation of quality of life. More relevant NMSs are described in this review, mood disorders, impulse control disorders, cognitive deficits, hallucinations, pain, sleep disorders, and dysautonomia.

  7. Promoting culturally competent chronic pain management using the clinically relevant continuum model.

    Science.gov (United States)

    Monsivais, Diane B

    2011-06-01

    This article reviews the culture of biomedicine and current practices in pain management education, which often merge to create a hostile environment for effective chronic pain care. Areas of cultural tensions in chronic pain frequently involve the struggle to achieve credibility regarding one's complaints of pain (or being believed that the pain is real) and complying with pain medication protocols. The clinically relevant continuum model is presented as a framework allowing providers to approach care from an evidence-based, culturally appropriate (patient centered) perspective that takes into account the highest level of evidence available, provider expertise, and patient preferences and values. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes

    Directory of Open Access Journals (Sweden)

    Hillebrands Jan-Luuk

    2008-10-01

    Full Text Available Abstract Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs.

  9. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes.

    Science.gov (United States)

    Meerwaldt, Robbert; Links, Thera; Zeebregts, Clark; Tio, Rene; Hillebrands, Jan-Luuk; Smit, Andries

    2008-10-07

    Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs.

  10. Clinically relevant safety issues associated with St. John's wort product labels

    Directory of Open Access Journals (Sweden)

    Rutledge Jennifer C

    2008-07-01

    Full Text Available Abstract Background St. John's wort (SJW, used to treat depression, is popular in the USA, Canada, and parts of Europe. However, there are documented interactions between SJW and prescription medications including warfarin, cyclosporine, indinavir, and oral contraceptives. One source of information about these safety considerations is the product label. The aim of this study was to evaluate the clinically relevant safety information included on labeling in a nationally representative sample of SJW products from the USA. Methods Eight clinically relevant safety issues were identified: drug interactions (SJW-HIV medications, SJW-immunosupressants, SJW-oral contraceptives, and SJW-warfarin, contraindications (bipolar disorder, therapeutic duplication (antidepressants, and general considerations (phototoxicity and advice to consult a healthcare professional (HCP. A list of SJW products was identified to assess their labels. Percentages and totals were used to present findings. Results Of the seventy-four products evaluated, no product label provided information for all 8 evaluation criteria. Three products (4.1% provided information on 7 of the 8 criteria. Four products provided no safety information whatsoever. Percentage of products with label information was: SJW-HIV (8.1%, SJW-immunosupressants (5.4%, SJW-OCPs (8.1%, SJW-warfarin (5.4%, bipolar (1.4%, antidepressants (23.0%, phototoxicity (51.4%, and consult HCP (87.8%. Other safety-related information on labels included warnings about pregnancy (74.3%, lactation (64.9%, discontinue if adverse reaction (23.0%, and not for use in patients under 18 years old (13.5%. The average number of a priori safety issues included on a product label was 1.91 (range 0–8 for 23.9% completeness. Conclusion The vast majority of SJW products fail to adequately address clinically relevant safety issues on their labeling. A few products do provide an acceptable amount of information on clinically relevant safety

  11. In Vitro Studies of the Activity of Dithiocarbamate Organoruthenium Complexes against Clinically Relevant Fungal Pathogens

    Directory of Open Access Journals (Sweden)

    Claudio L. Donnici

    2014-04-01

    Full Text Available The in vitro antifungal activity of nine dirutheniumpentadithiocarbamate complexes C1–C9 was investigated and assessed for its activity against four different fungal species with clinical interest and related to invasive fungal infections (IFIs, such as Candida spp. [C. albicans (two clinical isolates, C. glabrata, C. krusei, C. parapsolisis, C. tropicalis, C.dubliniensis (six clinical isolates], Paracoccidioides brasiliensis (seven clinical isolates, Cryptococcus neoformans and Sporothrix schenckii. All synthesized complexes C1–C9 and also the free ligands L1–L9 were submitted to in vitro tests against those fungi and the results are very promising, since some of the obtained MIC (minimal inhibitory concentration values were very low (from 10−6 mol mL−1 to 10−8 mol mL−1 against all investigated clinically relevant fungal pathogens, except for C. glabrata, that the MIC values are close to the ones obtained for fluconazole, the standard antifungal agent tested. Preliminary structure-activity relations (SAR might be suggested and a strong influence from steric and lipophilic parameters in the antifungal activity can be noticed. Cytotoxicity assays (IC50 showed that the complexes are not as toxic (IC50 values are much higher—30 to 200 fold—than MIC values. These ruthenium complexes are very promising lead compounds for novel antifungal drug development, especially in IFIs, one of most harmful emerging infection diseases (EIDs.

  12. Development of Microcomputer Methods for Analysis and Simulation of Clinical Pharmacokinetic Data Relevant to New Drug Development.

    Science.gov (United States)

    1985-08-02

    applications of new microcomputer graphics techonology to the analysis and interpretation of clinical pharmacological data. This involves continuing...COF AD DEVELOPMENT OF MICROCOMPUTER METHODS FOR ANALYSIS AND SIMULATION OF CLINICAL PHARMACOKINETIC DATA RELEVANT TO NEW DRUG DEVELOPMENT ANNUAL/FINAL...Simulation of Clinical Pharmacokinetic Data ERING ORG. TU Relevant to New Drug Development 6. PERFORMiNG ORG. REPORT NUMBER 7. AUTHOR(*) 5. CONTRACT OR

  13. Clinical empathy and narrative competence: the relevance of reading talmudic legends as literary fiction.

    Science.gov (United States)

    Davidson, John H

    2015-04-01

    The "curative potential" in almost any clinical setting depends on a caregiver establishing and maintaining an empathic connection with patients so as to achieve "narrative competence" in discerning and acting in accord with their preferences and best interests. The "narrative medicine" model of shared "close reading of literature and reflective writing" among clinicians as a means of fostering a capacity for clinical empathy has gained validation with recent empirical studies demonstrating the enhancement of theory of mind (ToM), broadly conceived as empathy, in readers of literary fiction. Talmudic legends, like that of Rabbi Judah's death, are under-appreciated, relevant sources of literary fiction for these efforts. The limitations of narrative medicine are readily counterbalanced by simultaneously practiced attention to traditional bioethical principles, including-especially-beneficence, non-maleficence, and autonomy.

  14. Stem cell therapy for joint problems using the horse as a clinically relevant animal model

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Betts, Dean H.

    2007-01-01

    of the developmental biology of synovial joints and their pathologies. Before human clinical trials are undertaken, stem cell-based therapies for non-life-threatening disorders should be evaluated for their safety and efficacy using animal models of spontaneous disease and not solely by the existing laboratory models...... of experimentally induced lesions. The horse lends itself as a good animal model of spontaneous joint disorders that are clinically relevant to similar human disorders. Equine stem cell and tissue engineering studies may be financially feasible to principal investigators and small biotechnology companies......Research into articular cartilage is a surprisingly recent endeavour and much remains to be learned about the normal development of the synovial joint and its components that interplay in osteoarthritis and focal cartilage defects. Stem cell research is likely to contribute to the understanding...

  15. Clinical Empathy and Narrative Competence: The Relevance of Reading Talmudic Legends as Literary Fiction

    Directory of Open Access Journals (Sweden)

    John H. Davidson

    2015-04-01

    Full Text Available The “curative potential” in almost any clinical setting depends on a caregiver establishing and maintaining an empathic connection with patients so as to achieve “narrative competence” in discerning and acting in accord with their preferences and best interests. The “narrative medicine” model of shared “close reading of literature and reflective writing” among clinicians as a means of fostering a capacity for clinical empathy has gained validation with recent empirical studies demonstrating the enhancement of theory of mind (ToM, broadly conceived as empathy, in readers of literary fiction. Talmudic legends, like that of Rabbi Judah’s death, are under-appreciated, relevant sources of literary fiction for these efforts. The limitations of narrative medicine are readily counterbalanced by simultaneously practiced attention to traditional bioethical principles, including—especially—beneficence, non-maleficence, and autonomy.

  16. Less than meets the eye: reappraising the clinical relevance of attentional bias in addiction.

    Science.gov (United States)

    Christiansen, Paul; Schoenmakers, Tim M; Field, Matt

    2015-05-01

    Recent years have seen an explosion of interest in attentional bias in addiction, particularly its clinical relevance. Specifically, numerous articles claimed to demonstrate either that (1) attentional bias measured in treatment settings could predict subsequent relapse to substance use, or (2) direct modification of attentional bias reduced substance use and improved treatment outcomes. In this paper, we critically evaluate empirical studies that investigated these issues. We show that the evidence regarding both of these claims is decidedly mixed, and that many of the studies that appear to yield positive findings have serious methodological and statistical limitations. We contend that the available literature suggests that attentional bias for drug cues fluctuates within individuals because it is an output of the underlying motivational state at that moment in time, but there is no convincing evidence that it exerts a causal influence on substance use. Future research should make use of experience sampling methodology to characterise the clinical significance of fluctuations in attentional bias over time.

  17. Clinical relevance of cluster analysis in phenotyping allergic rhinitis in a real-life study.

    Science.gov (United States)

    Bousquet, Philippe Jean; Devillier, Philippe; Tadmouri, Abir; Mesbah, Kamal; Demoly, Pascal; Bousquet, Jean

    2015-01-01

    Disease stratification, using phenotypic characterization performed either by hypothesis- or data-driven methods, was developed to improve clinical decisions. However, cluster analysis has not been used for allergic rhinitis. To define clusters in allergic rhinitis and to compare them with ARIA (Allergic Rhinitis and Its Impact on Asthma), a hypothesis-driven approach. A French observational prospective multicenter study (EVEIL: Echelle visuelle analogique dans la rhinite allergique) was carried out on 990 patients consulting general practitioners for allergic rhinitis and treated as per clinical practice. In this study, changes in symptom scores, visual analogue scales and quality of life were measured at baseline and after 14 days of treatment. A post hoc analysis was performed to identify clusters of patients with allergic rhinitis – using Ward's hierarchical method – and to define their clinical relevance at baseline and after 14 days of treatment. The cluster approach was compared to the ARIA approach. Patients were clustered into 4 phenotypes which partly followed the ARIA classes. These phenotypes differed in their disease severity including symptoms and quality of life. Physicians in real-life practice prescribed medication regardless of the phenotype and severity, with the exception of patients with ocular symptoms. Prescribed treatments were comparable in hypothesis- and data-driven analyses. The prevalence of uncontrolled patients during treatment was similar in the 4 clusters, but was significantly different according to the ARIA classes. Cluster analysis using demographic and clinical parameters only does not appear to add relevant information for disease stratification in allergic rhinitis. © 2015 S. Karger AG, Basel.

  18. Antibiofilm Activity of the Brown Alga Halidrys siliquosa against Clinically Relevant Human Pathogens

    Directory of Open Access Journals (Sweden)

    Alessandro Busetti

    2015-06-01

    Full Text Available The marine brown alga Halidrys siliquosa is known to produce compounds with antifouling activity against several marine bacteria. The aim of this study was to evaluate the antimicrobial and antibiofilm activity of organic extracts obtained from the marine brown alga H. siliquosa against a focused panel of clinically relevant human pathogens commonly associated with biofilm-related infections. The partially fractionated methanolic extract obtained from H. siliquosa collected along the shores of Co. Donegal; Ireland; displayed antimicrobial activity against bacteria of the genus Staphylococcus; Streptococcus; Enterococcus; Pseudomonas; Stenotrophomonas; and Chromobacterium with MIC and MBC values ranging from 0.0391 to 5 mg/mL. Biofilms of S. aureus MRSA were found to be susceptible to the algal methanolic extract with MBEC values ranging from 1.25 mg/mL to 5 mg/mL respectively. Confocal laser scanning microscopy using LIVE/DEAD staining confirmed the antimicrobial nature of the antibiofilm activity observed using the MBEC assay. A bioassay-guided fractionation method was developed yielding 10 active fractions from which to perform purification and structural elucidation of clinically-relevant antibiofilm compounds.

  19. Nicotine at clinically relevant concentrations affects atrial inward rectifier potassium current sensitive to acetylcholine.

    Science.gov (United States)

    Bébarová, Markéta; Matejovič, Peter; Švecová, Olga; Kula, Roman; Šimurdová, Milena; Šimurda, Jiří

    2017-02-03

    Nicotine abuse is associated with variety of diseases including arrhythmias, most often atrial fibrillation (AF). Altered inward rectifier potassium currents including acetylcholine-sensitive current I K(Ach) are known to be related to AF pathogenesis. Since relevant data are missing, we aimed to investigate I K(Ach) changes at clinically relevant concentrations of nicotine. Experiments were performed by the whole cell patch clamp technique at 23 ± 1 °C on isolated rat atrial myocytes. Nicotine was applied at following concentrations: 4, 40 and 400 nM; ethanol at 20 mM (∼0.09%). Nicotine at 40 and 400 nM significantly activated constitutively active component of I K(Ach) with the maximum effect at 40 nM (an increase by ∼100%); similar effect was observed at -110 and -50 mV. Changes at 4 nM nicotine were negligible on average. Coapplication of 40 nM nicotine and 20 mM ethanol (which is also known to activate this current) did not show cumulative effect. In the case of acetylcholine-induced component of I K(Ach), a dual effect of nicotine and its correlation with the current magnitude in control were apparent: the current was increased by nicotine in the cells showing small current in control and vice versa. The effect of 40 and 400 nM nicotine on acetylcholine-induced component of I K(Ach) was significantly different at -110 and -50 mV. We conclude that nicotine at clinically relevant concentrations significantly increased constitutively active component of I K(Ach) and showed a dual effect on its acetylcholine-induced component, similarly as ethanol. Synchronous application of nicotine and ethanol did not cause additive effect.

  20. Colonization, pathogenicity, host susceptibility, and therapeutics for Staphylococcus aureus: what is the clinical relevance?

    Science.gov (United States)

    Tong, Steven Y C; Chen, Luke F; Fowler, Vance G

    2012-03-01

    Staphylococcus aureus is a human commensal that can also cause a broad spectrum of clinical disease. Factors associated with clinical disease are myriad and dynamic and include pathogen virulence, antimicrobial resistance, and host susceptibility. Additionally, infection control measures aimed at the environmental niches of S. aureus and therapeutic advances continue to impact upon the incidence and outcomes of staphylococcal infections. This review article focuses on the clinical relevance of advances in our understanding of staphylococcal colonization, virulence, host susceptibility, and therapeutics. Over the past decade key developments have arisen. First, rates of nosocomial methicillin-resistant S. aureus (MRSA) infections have significantly declined in many countries. Second, we have made great strides in our understanding of the molecular pathogenesis of S. aureus in general and community-associated MRSA in particular. Third, host risk factors for invasive staphylococcal infections, such as advancing age, increasing numbers of invasive medical interventions, and a growing proportion of patients with healthcare contact, remain dynamic. Finally, several new antimicrobial agents active against MRSA have become available for clinical use. Humans and S. aureus co-exist, and the dynamic interface between host, pathogen, and our attempts to influence these interactions will continue to rapidly change. Although progress has been made in the past decade, we are likely to face further surprises such as the recent waves of community-associated MRSA.

  1. The p3 event-related potential as an index ofmotivational relevance a conditioning experiment

    NARCIS (Netherlands)

    I.H.A. Franken (Ingmar); J.W. van Strien (Jan); B.R. Bocanegra (Bruno); J. Huijding (Jorg)

    2011-01-01

    textabstractWatching motivationally relevant pictures modulates two types of event-related brain potentials (ERPs), the early posterior negativity (EPN) and the P3. Several studies show that the EPN and P3 to emotional stimuli are enhanced as compared to neutral stimuli. The goal of the present stud

  2. Chemical erosion of different carbon composites under ITER-relevant plasma conditions

    NARCIS (Netherlands)

    Westerhout, J.; Borodin, D.; Al, R.S.; Brezinsek, S.; Hoen, Mhjt; Kirschner, A.; Lisgo, S.; van der Meiden, H. J.; Philipps, V.; van de Pol, M.J.; Shumack, A. E.; De Temmerman, G.; Vijvers, W. A. J.; Wright, G. M.; Cardozo, N. J. L.; Rapp, J.; van Rooij, G. J.

    2009-01-01

    We have studied the chemical erosion of different carbon composites in Pilot-PSI at ITER-relevant hydrogen plasma fluxes (similar to 10(24) m(-2) s(-1)) and low electron temperatures (T-e similar to 1 eV). Optical emission spectroscopy on the CH A-X band was used to characterize the chemical

  3. Psychiatric disorders in children and adolescents presenting with unexplained chronic pain: what is the prevalence and clinical relevancy?

    NARCIS (Netherlands)

    Knook, L.M.; Konijnenberg, A.Y.; Hoeven, J. van der; Kimpen, J.L.L.; Buitelaar, J.K.; Engeland, H. van; Graeff-Meeder, E.R. de

    2011-01-01

    The prevalence of psychiatric disorders among children with unexplained chronic pain (UCP) is high in unselected populations and pain clinics, yet the clinical relevance of these disorders in children referred for unexplained pain is not known. This study assessed the prevalence of clinically releva

  4. Psychiatric disorders in children and adolescents presenting with unexplained chronic pain: what is the prevalence and clinical relevancy?

    NARCIS (Netherlands)

    Knook, L.M.; Konijnenberg, A.Y.; Hoeven, J. van der; Kimpen, J.L.L.; Buitelaar, J.K.; Engeland, H. van; Graeff-Meeder, E.R. de

    2011-01-01

    The prevalence of psychiatric disorders among children with unexplained chronic pain (UCP) is high in unselected populations and pain clinics, yet the clinical relevance of these disorders in children referred for unexplained pain is not known. This study assessed the prevalence of clinically

  5. Modeling Relevant to Safe Operations of U.S. Navy Vessels in Arctic Conditions: Physical Modeling of Ice Loads

    Science.gov (United States)

    2016-06-01

    Modeling Relevant to Safe Operations of U.S. Navy Vessels in Arctic Conditions.” The program manager was Dr. Paul Hess in Code 331, Structural...of Ice–Structure Interaction. Engineering Fracture Mechanics 68:1923–60. Jordaan, I. J., M. A. Maes, P. W. Brown, and I. P. Hermans . 1993

  6. Relevance of BFRs and thermal conditions on the formation pathways of brominated and brominated-chlorinated dibenzodioxins and dibenzofurans.

    Science.gov (United States)

    Weber, Roland; Kuch, Bertram

    2003-09-01

    The widespread use of brominated flame-retarded products in the last two decades has resulted in an increasing presence of bromine in thermal processes such as waste combustion and accidental fires. Brominated and brominated-chlorinated dibenzodioxins and dibenzofurans (PBDDs/PBDFs, PXDDs/PXDFs) are micropollutants of concern arising from such processes. The present review aims to evaluate the relevance of these compound classes in actual thermal processes. Four categories of thermal processes are discussed in this respect according to their potential for PBDD/PBDF and PXDD/PXDF generation: thermal stress, pyrolysis/gasification, insufficient combustion conditions and controlled combustion conditions. Under thermal stress situations, as they may occur in production or recycling processes, PBDDs/PBDFs precursors like polybrominated diphenylethers (PBDE) can have a relevant potential for PBDD/PBDF formation via a simple elimination. Under insufficient combustion conditions as they are present in, e.g. accidental fires and uncontrolled burning as well as gasification/pyrolysis processes, considerable amounts of PBDDs/PBDFs can be formed from BFRs, preferably via the precursor pathway. In contrast, under controlled combustion conditions, BFRs and PBDDs/PBDFs can be destroyed with high efficiency. The relevance of de novo synthesis of PXDDs/PXDFs is discussed for this condition. Providing a basis for the understanding of PXDD/PXDF formation in actual thermal processes, the present paper also summarises the formation pathways of brominated and brominated-chlorinated PXDDs/PXDFs from brominated flame retardants (BFRs) investigated during laboratory thermolysis experiments. Relevant mechanistic steps for PBDD/PBDF formation from brominated precursors are discussed including elimination reactions, condensation steps and debromination/hydrogenation reactions. In addition, chlorination/bromination and halogen exchange reactions are briefly discussed with respect for their

  7. Clinically relevant magnetic resonance imaging (MRI findings in elite swimmers’ shoulders

    Directory of Open Access Journals (Sweden)

    Arno Celliers

    2017-01-01

    Full Text Available Background: Shoulder pain is the most common and well-documented site of musculoskeletal pain in elite swimmers. Structural abnormalities on magnetic resonance imaging (MRI of elite swimmers’ symptomatic shoulders are common. Little has been documented about the association between MRI findings in the asymptomatic shoulder versus the symptomatic shoulder.Objective: To assess clinically relevant MRI findings in the shoulders of symptomatic and asymptomatic elite swimmers.Method: Twenty (aged 16–23 years elite swimmers completed questionnaires on their swimming training, pain and shoulder function. MRI of both shoulders (n = 40 were performed and all swimmers were given a standardised clinical shoulder examination. Results: Both shoulders of 11 male and 9 female elite swimmers (n = 40 were examined. Eleven of the 40 shoulders were clinically symptomatic and 29 were asymptomatic. The most common clinical finding in both the symptomatic and asymptomatic shoulders was impingement during internal rotation, with impingement in 54.5% of the symptomatic shoulders and in 31.0% of the asymptomatic shoulders. The most common MRI findings in the symptomatic and asymptomatic shoulders were supraspinatus tendinosis (45.5% vs. 20.7%, subacromial subdeltoid fluid (45.5% vs. 34.5%, increased signal in the AC Joint (45.5% vs. 37.9% and AC joint arthrosis (36.4% vs. 34.5%. Thirty-nine (97.5% of the shoulders showed abnormal MRI features.Conclusion: MRI findings in the symptomatic and asymptomatic shoulders of young elite swimmers are similar and care should be taken when reporting shoulder MRIs in these athletes. Asymptomatic shoulders demonstrate manifold MRI abnormalities that may be radiologically significant but appear not to be clinically significant.

  8. Clinical Relevance of RUNX1 and CBFB Alterations in Acute Myeloid Leukemia and Other Hematological Disorders.

    Science.gov (United States)

    Metzeler, Klaus H; Bloomfield, Clara D

    2017-01-01

    The translocation t(8;21), leading to a fusion between the RUNX1 gene and the RUNX1T1 locus, was the first chromosomal translocation identified in cancer. Since the first description of this balanced rearrangement in a patient with acute myeloid leukemia (AML) in 1973, RUNX1 translocations and point mutations have been found in various myeloid and lymphoid neoplasms. In this chapter, we summarize the currently available data on the clinical relevance of core binding factor gene alterations in hematological disorders. In the first section, we discuss the prognostic implications of the core binding factor translocations RUNX1-RUNX1T1 and CBFB-MYH11 in AML patients. We provide an overview of the cooperating genetic events in patients with CBF-rearranged AML and their clinical implications, and review current treatment approaches for CBF AML and the utility of minimal residual disease monitoring. In the next sections, we summarize the available data on rare RUNX1 rearrangements in various hematologic neoplasms and the role of RUNX1 translocations in therapy-related myeloid neoplasia. The final three sections of the chapter cover the spectrum and clinical significance of RUNX1 point mutations in AML and myelodysplastic syndromes, in familial platelet disorder with associated myeloid malignancy, and in acute lymphoblastic leukemia.

  9. Polanyi's tacit knowing and the relevance of epistemology to clinical medicine.

    Science.gov (United States)

    Henry, Stephen G

    2010-04-01

    Most clinicians take for granted a simple, reductionist understanding of medical knowledge that is at odds with how they actually practice medicine; routine medical decisions incorporate more complicated kinds of information than most standard accounts of medical reasoning suggest. A better understanding of the structure and function of knowledge in medicine can lead to practical improvements in clinical medicine. This understanding requires some familiarity with epistemology, the study of knowledge and its structure, in medicine. Michael Polanyi's theory of tacit knowing is advanced as the basis for developing a more accurate understanding of medical knowledge. Tacit knowing, which explores the taken-for-granted background knowledge that underlies all human knowing, is explained in detail with a focus on its relevance for clinical medicine. The implications of recognizing tacit knowing in medicine and medical decisions are discussed. These include the ability to explain the importance of the clinical encounter in medical practice, mechanisms for analysing patient and doctor as persons, and the need for humility given the uncertainty that the tacit dimension injects into all medical decisions. This more robust medical epistemology allows clinicians to better articulate the nature and importance of patient-centred care, to avoid pitfalls inherent in reductionist approaches to medical knowledge, and to think more clearly about the relationships between medicine and health care at the individual and population levels.

  10. Mutation databases for inherited renal disease: are they complete, accurate, clinically relevant, and freely available?

    Science.gov (United States)

    Savige, Judy; Dagher, Hayat; Povey, Sue

    2014-07-01

    This study examined whether gene-specific DNA variant databases for inherited diseases of the kidney fulfilled the Human Variome Project recommendations of being complete, accurate, clinically relevant and freely available. A recent review identified 60 inherited renal diseases caused by mutations in 132 genes. The disease name, MIM number, gene name, together with "mutation" or "database," were used to identify web-based databases. Fifty-nine diseases (98%) due to mutations in 128 genes had a variant database. Altogether there were 349 databases (a median of 3 per gene, range 0-6), but no gene had two databases with the same number of variants, and 165 (50%) databases included fewer than 10 variants. About half the databases (180, 54%) had been updated in the previous year. Few (77, 23%) were curated by "experts" but these included nine of the 11 with the most variants. Even fewer databases (41, 12%) included clinical features apart from the name of the associated disease. Most (223, 67%) could be accessed without charge, including those for 50 genes (40%) with the maximum number of variants. Future efforts should focus on encouraging experts to collaborate on a single database for each gene affected in inherited renal disease, including both unpublished variants, and clinical phenotypes. © 2014 WILEY PERIODICALS, INC.

  11. Clinical relevance of "bulging eyes" for the differential diagnosis of spinocerebellar ataxias

    Directory of Open Access Journals (Sweden)

    Adriana Moro

    2013-07-01

    Full Text Available Objective To investigate the relevance of the clinical finding of bulging eyes (BE in a large Brazilian cohort of spinocerebellar ataxias (SCA, to assess its importance in clinical differential diagnosis among SCA. Methods Three hundred sixty-nine patients from 168 Brazilian families with SCA were assessed with neurological examination and molecular genetic testing. BE was characterized by the presence of eyelid retraction. Genetically ascertained SCA3 was detected in 167 patients, SCA10 in 68 patients, SCA2 in 20, SCA1 in 9, SCA7 in 6, and SCA6 in 3 patients. Results BE was detected in 123 patients with SCA (33.3%, namely 109 of the 167 SCA3 patients (65.3% and in 5 of the others SCA patients (1 SCA10 patient, 2 SCA1 patients and 2 SCA2 patients. Conclusion BE was detected in the majority of patients with SCA3 (65.3% and could be used with a clinical tool for the differential diagnosis of SCA.

  12. Elevated Fear Conditioning to Socially Relevant Unconditioned Stimuli in Social Anxiety Disorder

    National Research Council Canada - National Science Library

    Pine, Daniel S; Grillon, Christian; Biggs, Arter L; Johnson, Linda L; Levenson, Jessica; Lissek, Shmuel; Ameli, Rezvan

    2008-01-01

    Objective: Though conditioned fear has long been acknowledged as an important etiologic mechanism in social anxiety disorder, past psychophysiological experiments have found no differences in general...

  13. What efficacy measures are clinically relevant and should be used in Cochrane Reviews of acute migraine trials?

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer

    2015-01-01

    : The following EMs were used: pain free at two hours (30%), headache relief at two hours (60%), sustained pain free for 24 hours (19%) and sustained headache relief for 24 hours (39%). These EMs were also used in four other Cochrane reviews of acute migraine treatment. Of these EMs sustained headache relief...... for 24 h is not judged clinically relevant. CONCLUSION: Pain free and sustained pain free are clinically relevant, but the responses are rather low, demonstrating that there is a need for improvement of acute drug treatment in migraine.......BACKGROUND: Cochrane Reviews are methodologically of high quality but the clinical relevance of analysed efficacy measures (EMs) should also be assessed. METHODS: The clinical relevance of EMs used in one systematic Cochrane review of oral zolmitriptan for migraine headache was evaluated. RESULTS...

  14. Markers of oxidant stress that are clinically relevant in aging and age-related disease.

    Science.gov (United States)

    Jacob, Kimberly D; Noren Hooten, Nicole; Trzeciak, Andrzej R; Evans, Michele K

    2013-03-01

    Despite the long held hypothesis that oxidant stress results in accumulated oxidative damage to cellular macromolecules and subsequently to aging and age-related chronic disease, it has been difficult to consistently define and specifically identify markers of oxidant stress that are consistently and directly linked to age and disease status. Inflammation because it is also linked to oxidant stress, aging, and chronic disease also plays an important role in understanding the clinical implications of oxidant stress and relevant markers. Much attention has focused on identifying specific markers of oxidative stress and inflammation that could be measured in easily accessible tissues and fluids (lymphocytes, plasma, serum). The purpose of this review is to discuss markers of oxidant stress used in the field as biomarkers of aging and age-related diseases, highlighting differences observed by race when data is available. We highlight DNA, RNA, protein, and lipid oxidation as measures of oxidative stress, as well as other well-characterized markers of oxidative damage and inflammation and discuss their strengths and limitations. We present the current state of the literature reporting use of these markers in studies of human cohorts in relation to age and age-related disease and also with a special emphasis on differences observed by race when relevant. Published by Elsevier Ireland Ltd.

  15. Hypersensitivities for acetaldehyde and other agents among cancer cells null for clinically relevant Fanconi anemia genes.

    Science.gov (United States)

    Ghosh, Soma; Sur, Surojit; Yerram, Sashidhar R; Rago, Carlo; Bhunia, Anil K; Hossain, M Zulfiquer; Paun, Bogdan C; Ren, Yunzhao R; Iacobuzio-Donahue, Christine A; Azad, Nilofer A; Kern, Scott E

    2014-01-01

    Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, including the engineering of new PALB2/FANCN-null cancer cells by homologous recombination. A characteristic matching of FANCC-null, FANCG-null, BRCA2/FANCD1-null, and PALB2/FANCN-null phenotypes was confirmed by uniform tumor regression on single-dose cross-linker therapy in mice and by shared chemical hypersensitivities to various inter-strand cross-linking agents and γ-radiation in vitro. Some compounds, however, had contrasting magnitudes of sensitivity; a strikingly high (19- to 22-fold) hypersensitivity was seen among PALB2-null and BRCA2-null cells for the ethanol metabolite, acetaldehyde, associated with widespread chromosomal breakage at a concentration not producing breaks in parental cells. Because FANC-defective cancer cells can share or differ in their chemical sensitivities, patterns of selective hypersensitivity hold implications for the evolutionary understanding of this pathway. Clinical decisions for cancer-relevant prevention and management of FANC-mutation carriers could be modified by expanded studies of high-magnitude sensitivities.

  16. Assessing Hospital Physicians' Acceptance of Clinical Information Systems: A Review of the Relevant Literature

    Directory of Open Access Journals (Sweden)

    Bram Pynoo

    2013-06-01

    Full Text Available In view of the tremendous potential benefits of clinical information systems (CIS for the quality of patient care; it is hard to understand why not every CIS is embraced by its targeted users, the physicians. The aim of this study is to propose a framework for assessing hospital physicians' CIS-acceptance that can serve as a guidance for future research into this area. Hereto, a review of the relevant literature was performed in the ISI Web-of-Science database. Eleven studies were withheld from an initial dataset of 797 articles. Results show that just as in business settings, there are four core groups of variables that influence physicians' acceptance of a CIS: its usefulness and ease of use, social norms, and factors in the working environment that facilitate use of the CIS (such as providing computers/workstations, compatibility between the new and existing system.... We also identified some additional variables as predictors of CIS-acceptance.

  17. Undersized annuloplasty for functional mitral regurgitation: is it responsible for clinically relevant mitral stenosis during exercise?

    Science.gov (United States)

    Grimaldi, Antonio; De Bonis, Michele; Pappalardo, Federico; Taramasso, Maurizio; Verzini, Alessandro; Calabrese, Maria Chiara; Maisano, Francesco; Alfieri, Ottavio

    2012-07-01

    The study aim was to assess if an undersized mitral annuloplasty for functional mitral regurgitation (FMR) in dilated cardiomyopathy can determine a clinically relevant mitral stenosis during exercise. Both, rest and stress echocardiography were performed in 12 patients submitted to an undersized ring annuloplasty for FMR in dilated cardiomyopathy. The mean ring size was 27 +/- 1.3 mm. All patients were in NYHA functional classes I-II, were in stable sinus rhythm, and without significant residual mitral regurgitation (grade stroke volume (63 +/- 15 versus 77 +/- 14 ml, p FMR. Stress echocardiography represents a valuable tool to assess an appropriate cardiac response to exercise and to detect a significant exercise-induced pulmonary hypertension after undersized annuloplasty ring surgery.

  18. In Vivo Photoacoustic and Fluorescence Cystography Using Clinically Relevant Dual Modal Indocyanine Green

    Directory of Open Access Journals (Sweden)

    Sungjo Park

    2014-10-01

    Full Text Available Conventional X-ray-based cystography uses radio-opaque materials, but this method uses harmful ionizing radiation and is not sensitive. In this study, we demonstrate nonionizing and noninvasive photoacoustic (PA and fluorescence (FL cystography using clinically relevant indocyanine green (ICG in vivo. After transurethral injection of ICG into rats through a catheter, their bladders were photoacoustically and fluorescently visualized. A deeply positioned bladder below the skin surface (i.e., ~1.5–5 mm was clearly visible in the PA and FL image using a laser pulse energy of less than 2 mJ/cm2 (1/15 of the safety limit. Then, the in vivo imaging results were validated through in situ studies. Our results suggest that dual modal cystography can provide a nonionizing and noninvasive imaging tool for bladder mapping.

  19. Transitional cardiovascular physiology and comprehensive hemodynamic monitoring in the neonate: relevance to research and clinical care.

    Science.gov (United States)

    Azhibekov, Timur; Noori, Shahab; Soleymani, Sadaf; Seri, Istvan

    2014-02-01

    A thorough understanding of developmental cardiovascular physiology is essential for early recognition of cardiovascular compromise, selective screening of at-risk groups of neonates, and individualized management using pathophysiology-targeted interventions. Although we have gained a better understanding of the physiology and pathophysiology of postnatal cardiovascular transition over the past decade with the use of sophisticated methods to study neonatal hemodynamics, most aspects of neonatal hemodynamics remain incompletely understood. In addition, targeted therapeutic interventions of neonatal hemodynamic compromise have not been shown to improve mortality and clinically relevant outcomes. However, the recent development of comprehensive hemodynamic monitoring systems capable of non-invasive, continuous and simultaneous bedside assessment of cardiac output, organ blood flow, microcirculation, and tissue oxygen delivery has made sophisticated analysis of the obtained physiologic data possible and has created new research opportunities with the potential of direct implications to patient care.

  20. Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench

    Directory of Open Access Journals (Sweden)

    Patricia I Diaz

    2014-07-01

    Full Text Available High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases.

  1. Skin autofluorescence, a non-invasive marker of advanced glycation end products: clinical relevance and limitations.

    Science.gov (United States)

    Da Moura Semedo, Cidila; Webb, M'Balu; Waller, Helen; Khunti, Kamlesh; Davies, Melanie

    2017-01-31

    Advanced glycation end products (AGEs) are protein-bound compounds derived from glycaemic and oxidative stress that contain fluorescent properties, which can be non-invasively measured as skin autofluorescence (SAF) by the AGE Reader. SAF has been demonstrated to be a biomarker of cumulative skin AGEs and potentially may be a better predictor for the development of chronic complications and mortality in diabetes than glycated haemoglobin A1c. However, there are several confounding factors that should be assessed prior to its broader application: these include presence of other fluorescent compounds in the skin that might be measured (eg, fluorophores), skin pigmentation and use of skin creams. The aim of this article is to provide a theoretical background of this newly developed method, evaluate its clinical relevance and discuss the potential confounding factors that need further analysis.

  2. New Insights into the Surgical Management of Tetralogy of Fallot: Physiological Fundamentals and Clinical Relevance.

    Science.gov (United States)

    Bove, Thierry; François, Katrien; De Wolf, Daniel

    2015-01-01

    The surgical treatment of tetralogy of Fallot can be considered as a success story in the history of congenital heart diseases. Since the early outcome is no longer the main issue, the focus moved to the late sequelae of TOF repair, i.e. the pulmonary insufficiency and the secondary adaptation of the right ventricle. This review provides recent insights into the pathophysiological alterations of the right ventricle in relation to the reconstruction of the right ventricular outflow tract after repair of tetralogy of Fallot. Its clinical relevance is documented by addressing the policy changes regarding the optimal management at the time of surgical repair as well as properly defining criteria and timing for late pulmonary valve implantation.

  3. Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench.

    Science.gov (United States)

    Diaz, Patricia I; Strausbaugh, Linda D; Dongari-Bagtzoglou, Anna

    2014-01-01

    High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases.

  4. Clinical relevance of the ROC and free-response paradigms for comparing imaging system efficacies.

    Science.gov (United States)

    Chakraborty, D P

    2010-01-01

    Observer performance studies are widely used to assess medical imaging systems. Unlike technical/engineering measurements observer performance include the entire imaging chain and the radiologist. However, the widely used receiver operating characteristic (ROC) method ignores lesion localisation information. The free-response ROC (FROC) method uses the location information to appropriately reward or penalise correct or incorrect localisations, respectively. This paper describes a method for improving the clinical relevance of FROC studies. The method consists of assigning appropriate risk values to the different lesions that may be present on a single image. A high-risk lesion is one that is critical to detect and act upon, and is assigned a higher risk value than a low-risk lesion, one that is relatively innocuous. Instead of simply counting the number of lesions that are detected, as is done in conventional FROC analysis, a risk-weighted count is used. This has the advantage of rewarding detections of high-risk lesions commensurately more than detections of lower risk lesions. Simulations were used to demonstrate that the new method, termed case-based analysis, results in a higher figure of merit for an expert who detects more high-risk lesions than a naive observer who detects more low-risk lesions, even though both detect the same total number of lesions. Conventional free-response analysis is unable to distinguish between the two types of observers. This paper also comments on the issue of clinical relevance of ROC analysis vs. FROC for tasks that involve lesion localisation.

  5. Expression, regulation and clinical relevance of the ATPase inhibitory factor 1 in human cancers

    Science.gov (United States)

    Sánchez-Aragó, M; Formentini, L; Martínez-Reyes, I; García-Bermudez, J; Santacatterina, F; Sánchez-Cenizo, L; Willers, I M; Aldea, M; Nájera, L; Juarránz, Á; López, E C; Clofent, J; Navarro, C; Espinosa, E; Cuezva, J M

    2013-01-01

    Recent findings in colon cancer cells indicate that inhibition of the mitochondrial H+-adenosine triphosphate (ATP) synthase by the ATPase inhibitory factor 1 (IF1) promotes aerobic glycolysis and a reactive oxygen species (ROS)-mediated signal that enhances proliferation and cell survival. Herein, we have studied the expression, biological relevance, mechanism of regulation and potential clinical impact of IF1 in some prevalent human carcinomas. We show that IF1 is highly overexpressed in most (>90%) of the colon (n=64), lung (n=30), breast (n=129) and ovarian (n=10) carcinomas studied as assessed by different approaches in independent cohorts of cancer patients. The expression of IF1 in the corresponding normal tissues is negligible. By contrast, the endometrium, stomach and kidney show high expression of IF1 in the normal tissue revealing subtle differences by carcinogenesis. The overexpression of IF1 also promotes the activation of aerobic glycolysis and a concurrent ROS signal in mitochondria of the lung, breast and ovarian cancer cells mimicking the activity of oligomycin. IF1-mediated ROS signaling activates cell-type specific adaptive responses aimed at preventing death in these cell lines. Remarkably, regulation of IF1 expression in the colon, lung, breast and ovarian carcinomas is exerted at post-transcriptional levels. We demonstrate that IF1 is a short-lived protein (t1/2 ∼100 min) strongly implicating translation and/or protein stabilization as main drivers of metabolic reprogramming and cell survival in these human cancers. Analysis of tumor expression of IF1 in cohorts of breast and colon cancer patients revealed its relevance as a predictive marker for clinical outcome, emphasizing the high potential of IF1 as therapeutic target. PMID:23608753

  6. Per-beam, planar IMRT QA passing rates do not predict clinically relevant patient dose errors

    Energy Technology Data Exchange (ETDEWEB)

    Nelms, Benjamin E.; Zhen Heming; Tome, Wolfgang A. [Canis Lupus LLC and Department of Human Oncology, University of Wisconsin, Merrimac, Wisconsin 53561 (United States); Department of Medical Physics, University of Wisconsin, Madison, Wisconsin 53705 (United States); Departments of Human Oncology, Medical Physics, and Biomedical Engineering, University of Wisconsin, Madison, Wisconsin 53792 (United States)

    2011-02-15

    Purpose: The purpose of this work is to determine the statistical correlation between per-beam, planar IMRT QA passing rates and several clinically relevant, anatomy-based dose errors for per-patient IMRT QA. The intent is to assess the predictive power of a common conventional IMRT QA performance metric, the Gamma passing rate per beam. Methods: Ninety-six unique data sets were created by inducing four types of dose errors in 24 clinical head and neck IMRT plans, each planned with 6 MV Varian 120-leaf MLC linear accelerators using a commercial treatment planning system and step-and-shoot delivery. The error-free beams/plans were used as ''simulated measurements'' (for generating the IMRT QA dose planes and the anatomy dose metrics) to compare to the corresponding data calculated by the error-induced plans. The degree of the induced errors was tuned to mimic IMRT QA passing rates that are commonly achieved using conventional methods. Results: Analysis of clinical metrics (parotid mean doses, spinal cord max and D1cc, CTV D95, and larynx mean) vs IMRT QA Gamma analysis (3%/3 mm, 2/2, 1/1) showed that in all cases, there were only weak to moderate correlations (range of Pearson's r-values: -0.295 to 0.653). Moreover, the moderate correlations actually had positive Pearson's r-values (i.e., clinically relevant metric differences increased with increasing IMRT QA passing rate), indicating that some of the largest anatomy-based dose differences occurred in the cases of high IMRT QA passing rates, which may be called ''false negatives.'' The results also show numerous instances of false positives or cases where low IMRT QA passing rates do not imply large errors in anatomy dose metrics. In none of the cases was there correlation consistent with high predictive power of planar IMRT passing rates, i.e., in none of the cases did high IMRT QA Gamma passing rates predict low errors in anatomy dose metrics or vice versa

  7. Clinical relevance of studies on the accuracy of visual inspection for detecting caries lesions: a systematic review.

    Science.gov (United States)

    Gimenez, Thais; Piovesan, Chaiana; Braga, Mariana M; Raggio, Daniela P; Deery, Chris; Ricketts, David N; Ekstrand, Kim R; Mendes, Fausto Medeiros

    2015-01-01

    Although visual inspection is the most commonly used method for caries detection, and consequently the most investigated, studies have not been concerned about the clinical relevance of this procedure. Therefore, we conducted a systematic review in order to perform a critical evaluation considering the clinical relevance and methodological quality of studies on the accuracy of visual inspection for assessing caries lesions. Two independent reviewers searched several databases through July 2013 to identify papers/articles published in English. Other sources were checked to identify unpublished literature. The eligible studies were those which (1) assessed the accuracy of the visual method for detecting caries lesions on occlusal, approximal or smooth surfaces, in primary or permanent teeth, (2) used a reference standard, and (3) reported data about sample size and accuracy of the methods. Aspects related to clinical relevance and the methodological quality of the studies were evaluated. 96 of the 5,578 articles initially identified met the inclusion criteria. In general, most studies failed in considering some clinically relevant aspects: only 1 included study validated activity status of lesions, no study considered its prognosis, 79 studies did not consider a clinically relevant outcome, and only 1 evaluated a patient-centred outcome. Concerning methodological quality, the majority of the studies presented a high risk of bias in sample selection. In conclusion, studies on the accuracy of the visual method for caries detection should consider clinically relevant outcomes besides accuracy; moreover, they should be conducted with higher methodological quality, mainly regarding sample selection.

  8. Incidental Dose to Pelvic Nodes in Bladder-Only Radiotherapy: Is It Clinically Relevant?

    Science.gov (United States)

    Lewis, Shirley; Murthy, Vedang; Mahantshetty, Umesh; Shrivastava, Shyam Kishore

    2017-06-01

    Although there is a strong biological rationale to electively treat the pelvic nodes during bladder preservation, its clinical benefit is uncertain. This may be explained by the incidental dose received by the nodal regions when treating the bladder alone. This study was conducted to investigate the doses received by the different pelvic nodal regions when the bladder alone is treated by standard conformal radiotherapy. The computed tomography data sets of 20 patients with node-negative muscle-invasive bladder cancer treated in a bladder preservation protocol were studied. Patients were originally treated with conformal radiotherapy to the bladder alone. Replanning was done with additional delineation of the pelvic nodal regions namely common iliac (upper and lower), presacral, internal iliac, obturator, and external iliac. Dose volume parameters such as Dmean, Dmax, D100%, D66%, D33%, V40, and V50 to each of the nodal regions were estimated for all patients. The obturator nodes received the highest dose among all nodal regions. The mean dose received by obturator, external iliac, and internal iliac regions was 59, 45, and 36 Gy, respectively. The dose received by these 3 regions in the full bladder state was 63, 52, and 47 Gy, respectively. The dose received by all other pelvic nodal regions was low and not clinically relevant. The incidental dose received by obturator and external iliac nodes is clinically significant in bladder-only radiation, possibly enough to influence micrometastatic disease. This may be a reason for the lack of clear benefit seen with nodal irradiation in bladder cancer. Advances in Knowledge: This study highlights that the incidental dose received by obturator and external iliac nodes is clinically significant in bladder-only radiation. The obturator nodes received the highest dose among all nodal regions with mean dose of 59 Gy.

  9. Clinical relevance of "withdrawal therapy" as a form of hormonal manipulation for breast cancer

    Directory of Open Access Journals (Sweden)

    Robertson John FR

    2011-09-01

    Full Text Available Abstract Background It has been shown in in-vitro experiments that "withdrawal" of tamoxifen inhibits growth of tumor cells. However, evidence is scarce when this is extrapolated into clinical context. We report our experience to verify the clinical relevance of "withdrawal therapy". Methods Breast cancer patients since 1998 who fulfilled the following criteria were selected from the departmental database and the case-notes were retrospectively reviewed: (1 estrogen receptor positive, operable primary breast cancer in elderly (age > 70 years, locally advanced or metastatic breast cancer; (2 disease deemed suitable for treatment by hormonal manipulation; (3 disease assessable by UICC criteria; (4 received "withdrawal" from a prior endocrine agent as a form of therapy; (5 on "withdrawal therapy" for ≥ 6 months unless they progressed prior. Results Seventeen patients with median age of 84.3 (53.7-92.5 had "withdrawal therapy" as second to tenth line of treatment following prior endocrine therapy using tamoxifen (n = 10, an aromatase inhibitor (n = 5, megestrol acetate (n = 1 or fulvestrant (n = 1. Ten patients (58.8% had clinical benefit (CB (complete response/partial response/stable disease ≥ 6 months with a median duration of Clinical Benefit (DoCB of 10+ (7-27 months. Two patients remain on "withdrawal therapy" at the time of analysis. Conclusion "Withdrawal therapy" appears to produce sustained CB in a significant proportion of patients. This applies not only to "withdrawal" from tamoxifen, but also from other categories of endocrine agents. "Withdrawal" from endocrine therapy is, therefore, a viable intercalating option between endocrine agents to minimise resistance and provide additional line of therapy. It should be considered as part of the sequencing of endocrine therapy.

  10. Miniature Swine as a Clinically Relevant Model of Graft-Versus-Host Disease.

    Science.gov (United States)

    Duran-Struuck, Raimon; Huang, Christene A; Orf, Katherine; Bronson, Roderick T; Sachs, David H; Spitzer, Thomas R

    2015-10-01

    Miniature swine provide a preclinical model of hematopoietic cell transplantation (HCT) for studies of graft-versus-host disease. HCT between MHC-matched or -mismatched pigs can be performed to mimic clinical scenarios with outcomes that closely resemble those observed in human HCT recipients. With myeloablative conditioning, HCT across MHC barriers is typically fatal, with pigs developing severe (grade III or IV) GVHD involving the gastrointestinal tract, liver, and skin. Unlike rodent models, miniature swine provide an opportunity to perform extended longitudinal studies on individual animals, because multiple tissue biopsies can be harvested without the need for euthanasia. In addition, we have developed a swine GVHD scoring system that parallels that used in the human clinical setting. Given the similarities of GVHD in pigs and humans, we hope that the use of this scoring system facilitates clinical and scientific discourse between the laboratory and the clinic. We anticipate that results of swine studies will support the development of new strategies to improve the identification and treatment of GVHD in clinical HCT scenarios.

  11. Plant Growth and Morphogenesis under Different Gravity Conditions: Relevance to Plant Life in Space.

    Science.gov (United States)

    Hoson, Takayuki

    2014-05-16

    The growth and morphogenesis of plants are entirely dependent on the gravitational acceleration of earth. Under microgravity conditions in space, these processes are greatly modified. Recent space experiments, in combination with ground-based studies, have shown that elongation growth is stimulated and lateral expansion suppressed in various shoot organs and roots under microgravity conditions. Plant organs also show automorphogenesis in space, which consists of altered growth direction and spontaneous curvature in the dorsiventral (back and front) directions. Changes in cell wall properties are responsible for these modifications of growth and morphogenesis under microgravity conditions. Plants live in space with interesting new sizes and forms.

  12. Plant Growth and Morphogenesis under Different Gravity Conditions: Relevance to Plant Life in Space

    Directory of Open Access Journals (Sweden)

    Takayuki Hoson

    2014-05-01

    Full Text Available The growth and morphogenesis of plants are entirely dependent on the gravitational acceleration of earth. Under microgravity conditions in space, these processes are greatly modified. Recent space experiments, in combination with ground-based studies, have shown that elongation growth is stimulated and lateral expansion suppressed in various shoot organs and roots under microgravity conditions. Plant organs also show automorphogenesis in space, which consists of altered growth direction and spontaneous curvature in the dorsiventral (back and front directions. Changes in cell wall properties are responsible for these modifications of growth and morphogenesis under microgravity conditions. Plants live in space with interesting new sizes and forms.

  13. Flow properties of dental impression materials by means of a modified sharkfin test at clinically relevant times after mixing

    OpenAIRE

    Saker, Odie

    2008-01-01

    Objectives: The aim of this study was: (1) To determine the relevant processing times for clinical practice. (2) To analyze the flow properties of several elastomeric impression materials depending on these clinically measured times by means of the modified sharkfin test. Methods and materials: (1) Clinical trial: The processing times of 86 clinical cases were measured by the same person. The impressions were taken by 14 different clinicians with the one-step technique (Impregum-Penta as...

  14. Renewal effect on conditioning and its clinical implications

    Directory of Open Access Journals (Sweden)

    Lopez Seal, María Florencia

    2010-06-01

    Full Text Available Renewal effect refers to the reappearance of a conditioned response by a context change between extinction and testing. This phenomenon holds relevance at a theoretical level since it shows that, in extinction, learning does not go under. Also at an applied level, because psychological treatments that relay on extinction processes are done generally at a different context than that where they are put to test and therefore the response can reappear due to the renewal effect. This article reviews the procedures among which the effects of both classic and instrumental conditioning were studied as well as those treatments that prevent them from occurring

  15. The Relevance of Value Net Integrator and Shared Infrastructure Business Models in Managing Chronic Conditions

    Directory of Open Access Journals (Sweden)

    Susan Lambert

    2005-11-01

    Full Text Available There is widespread support for chronic condition management (CCM programs that require a multi-disciplinary, care-team approach. Implementation of such programs represents a paradigm shift in primary care service delivery and has significant resource implications for the general practice. Integral to the widespread uptake of care-team based CCM is information collection, storage and dissemination amongst the care-team members. This paper looks to ebusiness models for assistance in understanding the requirements of general practitioners (GPs in providing multi-disciplinary team care to patients with chronic conditions. The role required of GPs in chronic condition management is compared to that of a value net integrator. The essential characteristics of value net integrators are identified and compared to those of GPs providing multi-disciplinary team care to patients with chronic conditions. It is further suggested that a shared infrastructure is required.

  16. A framework for crafting clinical practice guidelines that are relevant to the care and management of people with multimorbidity.

    Science.gov (United States)

    Uhlig, Katrin; Leff, Bruce; Kent, David; Dy, Sydney; Brunnhuber, Klara; Burgers, Jako S; Greenfield, Sheldon; Guyatt, Gordon; High, Kevin; Leipzig, Rosanne; Mulrow, Cynthia; Schmader, Kenneth; Schunemann, Holger; Walter, Louise C; Woodcock, James; Boyd, Cynthia M

    2014-04-01

    Many patients of all ages have multiple conditions, yet clinicians often lack explicit guidance on how to approach clinical decision-making for such people. Most recommendations from clinical practice guidelines (CPGs) focus on the management of single diseases, and may be harmful or impractical for patients with multimorbidity. A major barrier to the development of guidance for people with multimorbidity stems from the fact that the evidence underlying CPGs derives from studies predominantly focused on the management of a single disease. In this paper, the investigators from the Improving Guidelines for Multimorbid Patients Study Group present consensus-based recommendations for guideline developers to make guidelines more useful for the care of people with multimorbidity. In an iterative process informed by review of key literature and experience, we drafted a list of issues and possible approaches for addressing important coexisting conditions in each step of the guideline development process, with a focus on considering relevant interactions between the conditions, their treatments and their outcomes. The recommended approaches address consideration of coexisting conditions at all major steps in CPG development, from nominating and scoping the topic, commissioning the work group, refining key questions, ranking importance of outcomes, conducting systematic reviews, assessing quality of evidence and applicability, summarizing benefits and harms, to formulating recommendations and grading their strength. The list of issues and recommendations was reviewed and refined iteratively by stakeholders. This framework acknowledges the challenges faced by CPG developers who must make complex judgments in the absence of high-quality or direct evidence. These recommendations require validation through implementation, evaluation and refinement.

  17. Fractal structures of single-walled carbon nanotubes in biologically relevant conditions: role of chirality vs. media conditions.

    Science.gov (United States)

    Khan, Iftheker A; Aich, Nirupam; Afrooz, A R M Nabiul; Flora, Joseph R V; Schierz, P Ariette; Ferguson, P Lee; Sabo-Attwood, Tara; Saleh, Navid B

    2013-11-01

    Aggregate structure of covalently functionalized chiral specific semiconducting single-walled carbon nanotubes (SWNTs) was systematically studied employing static light scattering (SLS). Fractal dimensions (Df) of two specific chirality SWNTs-SG65 and SG76 with (6, 5) and (7, 6) chiral enrichments-were measured under four biological exposure media conditions, namely: Dulbecco's Modified Eagle Medium (DMEM), Minimum Essential Medium (MEM), Roswell Park Memorial Institute (RPMI) 1640 medium, and 0.9% saline solution. The SWNTs exhibited chiral dependence on Df with SG65 showing more fractal or loosely bound aggregate structures, i.e., lower Df values (range of 2.24±0.03 to 2.64±0.05), compared to the SG76 sample (range of 2.58±0.13 to 2.90±0.08). All the Df values reported are highly reproducible, measured from multiple SLS runs and estimated with 'random block-effects' statistical analysis that yielded all p values to be fractal aggregates. Moreover, presence of fetal bovine serum (FBS) and bovine serum albumin (BSA), used to mimic the in vitro cell culture condition, reduced the Df values, i.e., created more fractal structures. Steric hindrance to aggregation was identified as the key mechanism for creating the fractal structures. Also, increase in FBS concentration from 1% to 10% resulted in increasingly lower Df values.

  18. Pavlovian conditioning with sexually relevant UCS: which is the necessary UCR?

    Science.gov (United States)

    Chu, Xi; Ågmo, Anders

    2012-10-01

    In Experiment 1, four groups of male rats were subjected to Pavlovian conditioning of an approach response. In one group the reinforcer was one mount with a sexually receptive female and in another group it was one intromission. A third group was deprived of food for 8 h before every session and a fourth group was deprived for 16 h. These latter groups received a 94 mg food pellet as reinforcement. The conditional stimulus (CS)+ and CS- were different lights. Rats reinforced with mount, intromission, or food after 16 h of deprivation learned to approach the CS+ more than the CS-. There was no difference in performance between the groups making one mount and one intromission. Rats deprived of food for 8 h failed to discriminate between the CS+ and the CS-. The results obtained with food reinforcement show that performance in the conditioning procedure depends on the level of motivation, which should be the case in any valid procedure. In Experiment 2 we determined whether access to female odor, exposure to an inaccessible female, one mount, and one intromission could reinforce classical conditioning. Only mount and intromission were efficient. These data show that the earliest event in the sequence of sexual behaviors that can promote conditioning is mounting. The fact that mount and intromission are equally efficient for reinforcing Pavlovian conditioning shows that the somatic and visceral responses associated with these behavior patterns rather than sensory feedback from the genitals are crucial.

  19. Quality of dementia clinical guidelines and relevance to the care of older people with comorbidity: evidence from the literature

    Directory of Open Access Journals (Sweden)

    Damiani G

    2014-08-01

    Full Text Available Gianfranco Damiani, Giulia Silvestrini, Lucrezia Trozzi, Donatella Maci, Lanfranco Iodice, Walter Ricciardi Department of Public Health, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli, Rome, Italy Purpose: The aim of this paper was to explore the applicability of dementia clinical guidelines (CGs to older patients, to patients with one or several comorbidities, and to both targets in order to evaluate if an association between the applicability and quality of the CGs exists.Materials and methods: A systematic search strategy conducted on electronic databases identified CGs on diagnosis and treatment of dementia published from 2000 to 2013. In addition, websites of organizations devoted to the treatment and awareness of dementia were searched. The quality of evidence was assessed using the Appraisal of Guidelines Research and Evaluation (AGREE instrument. Two investigators independently scored the relevance of the CGs by means of a specific tool. Descriptive and inferential analyses were performed (Mann–Whitney test, 0.05 α-level.Results: Twenty-two CGs met our inclusion criteria. On average, the quality of the CGs was higher than 70% in three of six domains measured by the AGREE tool. The domains with lower mean scores (less than 50% were “Applicability” and “Editorial independence”. Considering applicability to older patients, 20 CGs (91% addressed issues of treatment for older patients, five of them (23% classified older patients by age, and 13 CGs (60% addressed issues of comorbidity. Only seven (32% discussed the quality of evidence for patients with multiple comorbid conditions. Thirteen CGs (60% reported recommendations for patients with at least one comorbid condition, while seven of them (32% reported on several comorbid conditions. No statistically significant association between CG quality and relevance to care of older people with or without comorbidity was found (P>0.05.Conclusion: This study showed that

  20. Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use.

    Science.gov (United States)

    Taylor, Charles P; Traynelis, Stephen F; Siffert, Joao; Pope, Laura E; Matsumoto, Rae R

    2016-08-01

    Dextromethorphan (DM) has been used for more than 50years as an over-the-counter antitussive. Studies have revealed a complex pharmacology of DM with mechanisms beyond blockade of N-methyl-d-aspartate (NMDA) receptors and inhibition of glutamate excitotoxicity, likely contributing to its pharmacological activity and clinical potential. DM is rapidly metabolized to dextrorphan, which has hampered the exploration of DM therapy separate from its metabolites. Coadministration of DM with a low dose of quinidine inhibits DM metabolism, yields greater bioavailability and enables more specific testing of the therapeutic properties of DM apart from its metabolites. The development of the drug combination DM hydrobromide and quinidine sulfate (DM/Q), with subsequent approval by the US Food and Drug Administration for pseudobulbar affect, led to renewed interest in understanding DM pharmacology. This review summarizes the interactions of DM with brain receptors and transporters and also considers its metabolic and pharmacokinetic properties. To assess the potential clinical relevance of these interactions, we provide an analysis comparing DM activity from in vitro functional assays with the estimated free drug DM concentrations in the brain following oral DM/Q administration. The findings suggest that DM/Q likely inhibits serotonin and norepinephrine reuptake and also blocks NMDA receptors with rapid kinetics. Use of DM/Q may also antagonize nicotinic acetylcholine receptors, particularly those composed of α3β4 subunits, and cause agonist activity at sigma-1 receptors.

  1. Relevance of anatomy to medical education and clinical practice: perspectives of medical students, clinicians, and educators.

    Science.gov (United States)

    Sbayeh, Amgad; Qaedi Choo, Mohammad A; Quane, Kathleen A; Finucane, Paul; McGrath, Deirdre; O'Flynn, Siun; O'Mahony, Siobhain M; O'Tuathaigh, Colm M P

    2016-12-01

    Against a backdrop of ever-changing diagnostic and treatment modalities, stakeholder perceptions (medical students, clinicians, anatomy educators) are crucial for the design of an anatomy curriculum which fulfils the criteria required for safe medical practice. This study compared perceptions of students, practising clinicians, and anatomy educators with respect to the relevance of anatomy education to medicine. A quantitative survey was administered to undergraduate entry (n = 352) and graduate entry students (n = 219) at two Irish medical schools, recently graduated Irish clinicians (n = 146), and anatomy educators based in Irish and British medical schools (n = 30). Areas addressed included the association of anatomy with medical education and clinical practice, mode of instruction, and curriculum duration. Graduate-entry students were less likely to associate anatomy with the development of professionalism, teamwork skills, or improved awareness of ethics in medicine. Clinicians highlighted the challenge of tailoring anatomy education to increase student readiness to function effectively in a clinical role. Anatomy educators indicated dissatisfaction with the time available for anatomy within medical curricula, and were equivocal about whether curriculum content should be responsive to societal feedback. The group differences identified in the current study highlight areas and requirements which medical education curriculum developers should be sensitive to when designing anatomy courses.

  2. Relevance of cellular to clinical electrophysiology in interpreting antiarrhythmic drug action.

    Science.gov (United States)

    Vaughan Williams, E M

    1989-12-01

    The usefulness of cellular electrophysiologic techniques in elucidating the fundamental actions of antiarrhythmic drugs is contrasted with their apparent lack of relevance to the selection of drugs for the treatment of particular arrhythmias. Clinical electrophysiologists employ different techniques, but their results may be explained in terms of cellular drug actions. The varying clinical effects of class IA, IB and IC agents are due to differences in the speed of their attachment to, and detachment from, sodium channels. The role of sympathetic activity in arrhythmogenesis is complex, but again readily explicable in terms of the electrophysiologic cellular actions of stimulation of the individual types of adrenoceptors (alpha 1, alpha 2, beta 1 and beta 2) and the distribution of these receptors, and of the longterm effects of sympathetic deprivation, either by antisympathetic drugs (class II) or by sympathetic denervation. Delayed repolarization (e.g., by class III drugs or prolonged beta blockade) is antiarrhythmic because it is homogeneous, despite the incidental prolongation of QT. If, however, QT is prolonged by heterogeneity of conduction or repolarization, or by partial sympathetic denervation (long QT syndrome or post myocardial infarction), this indicates increased risk of arrhythmia. Finally, the efficacy of calcium antagonists (class IV) in supraventricular arrhythmias is attributable to the cellular electrophysiologic characteristics of sinoatrial and atrioventricular nodal and transitional elements.

  3. Analysis of Clinically Relevant Factors for Pulmonary Hypertension in Maintenance Hemodialysis Patients

    Science.gov (United States)

    Shen, Shen; Sun, Qianmei

    2015-01-01

    Background Pulmonary hypertension (PH) is common in patients with maintenance hemodialysis (MHD) and is associated with high mortality. This study analyzed clinically relevant factors for pulmonary hypertension in MHD patients and the effect of serum pentraxin3 (PTX3) in the pathogenesis of PH to provide the basis for early diagnosis and treatment of MHD patients with PH. Material/Methods This study included 60 MHD patients (group A) and 30 healthy controls (group B). Group A was further divided into PH and non-PH groups. Clinical characteristics, auxiliary examination results and serum PTX3 level of the PH and non-PH groups were compared. Binary logistic regression was used to assess the risk factors for PH in MHD patients. ROC curve was applied to evaluate the diagnostic value of PTX3 in PH. Results The incidence rate of PH in MHD patients was 50%, and most presented as mild to moderate. Compared with the non-PH group, patients in PH group presented significantly longer atrial diameter, right ventricular diameter and main pulmonary artery diameter (PMHD patients. AUC of PTX3 was 0.721 (95%CI: 0.590–0.851, P=0.003). Conclusions The prevalence of PH was higher in MHD patients and mostly presented as mild to moderate. Such patients often developed heart structural changes and cardiac ultrasound was highly recommended. Serum PTX3 level was significantly elevated and could be used as a marker of PH in MHD patients. PMID:26706606

  4. Warfarin accelerates ectopic mineralization in Abcc6(-/-) mice: clinical relevance to pseudoxanthoma elasticum.

    Science.gov (United States)

    Li, Qiaoli; Guo, Haitao; Chou, David W; Harrington, Dominic J; Schurgers, Leon J; Terry, Sharon F; Uitto, Jouni

    2013-04-01

    Pseudoxanthoma elasticum (PXE) is a multisystem ectopic mineralization disorder caused by mutations in the ABCC6 gene. Warfarin, a commonly used anticoagulant, is associated with increased mineralization of the arterial blood vessels and cardiac valves. We hypothesized that warfarin may accelerate ectopic tissue mineralization in PXE, with clinical consequences. To test this hypothesis, we developed a model in which Abcc6(-/-) mice, which recapitulate features of PXE, were fed a diet supplemented with warfarin and vitamin K1. Warfarin action was confirmed by significantly increased serum levels of oxidized vitamin K. For mice placed on a warfarin-containing diet, quantitative chemical and morphometric analyses revealed massive accumulation of mineral deposits in a number of tissues. Mice fed a warfarin-containing diet were also shown to have abundant uncarboxylated form of matrix Gla protein, which allowed progressive tissue mineralization to ensue. To explore the clinical relevance of these findings, 1747 patients with PXE from the approximately 4000 patients in the PXE International database were surveyed about the use of warfarin. Of the 539 respondents, 2.6% reported past or present use of warfarin. Based on the prevalence of PXE (approximately 1:50,000), thousands of patients with PXE worldwide may be at risk for worsening of PXE as a result of warfarin therapy.

  5. Clinical Relevance of Androgen Receptor Splice Variants in Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Maughan, Benjamin L; Antonarakis, Emmanuel S

    2015-12-01

    Metastatic castration-resistant prostate cancer (mCRPC) currently benefits from a wealth of treatment options, yet still remains lethal in the vast majority of patients. It is becoming increasingly understood that this disease entity continues to evolve over time, acquiring additional and diverse resistance mechanisms with each subsequent therapy used. This dynamic relationship between treatment pressure and disease resistance can be challenging for the managing clinician. The recent discovery of alternate splice variants of the androgen receptor (AR) is one potential mechanism of escape in mCRPC, and recognizing this resistance mechanism might be important for optimal treatment selection for our patients. AR-V7 appears to be the most relevant AR splice variant, and early clinical data suggest that it is a negative prognostic marker in mCRPC. Emerging evidence also suggests that detection of AR-V7 may be associated with resistance to novel hormonal therapy (abiraterone and enzalutamide) but may be compatible with sensitivity to taxane chemotherapy (docetaxel and cabazitaxel). Adding to this complexity is the observation that AR-V7 is a dynamic marker whose status may change across time and depending on selective pressures induced by different therapies. Finally, it is possible that AR-V7 may represent a therapeutic target in mCRPC if drugs can be designed that degrade or inhibit AR splice variants or block their transcriptional activity. Several such agents (including galeterone, EPI-506, and bromodomain/BET inhibitors) are now in clinical development.

  6. Serology and clinical relevance of Corynebacterium pseudotuberculosis in native Korean goats (Capra hircus coreanae).

    Science.gov (United States)

    Jung, Byeong Yeal; Lee, Seung-Hun; Kim, Ha-Young; Byun, Jae-Won; Shin, Dong-Ho; Kim, Daekeun; Kwak, Dongmi

    2015-04-01

    This study was conducted to assess the seroprevalence and clinical relevance of Corynebacterium pseudotuberculosis, which is the causative agent of caseous lymphadenitis (CLA), in native Korean goats (Capra hircus coreanae). A total of 466 native Korean goats from 40 herds (11 to 12 samples per herd) were randomly selected throughout the nation and evaluated by direct palpation, bacterial isolation, ELISA, and PCR. In serological examinations, 267 (57.3 %) of the goats tested were positive against C. pseudotuberculosis. When seroprevalence was analyzed according to age, region, and season, statistically significant differences were observed in relation to all three parameters (P < 0.05). For clinical examination, the superficial lymph nodes of all goats were palpated to diagnose CLA. Pus samples taken from superficial abscesses were used for bacterial isolation. Among the 466 goats tested, 34 (7.3 %) were presumptively diagnosed with CLA, and C. pseudotuberculosis was isolated from 24 goats (70.6 % of goats with CLA lesions) whose infections were confirmed by PCR. Considering the high seroprevalence and bacterial isolation rate from most of the superficial CLA lesions, it is suspected that many internal CLA lesions exist in this goat population. These results suggest that C. pseudotuberculosis infection is widespread in native Korean goats, and appropriate control programs need to be established.

  7. Clinical relevance of Corylus pollen in Poznań, western Poland.

    Science.gov (United States)

    Grewling, Lukasz; Jenerowicz, Dorota; Nowak, Małgorzata; Polańska, Adriana; Jackowiak, Bogdan; Czarnecka-Operacz, Magdalena; Smith, Matt

    2014-01-01

    In Central Europe, hazel (Corylus sp.) pollen is considered to be an important aeroallergen in early spring. This study examines hazel pollen levels in Poznań, western Poland, and the clinical relevance of this aeroallergen in the city. Corylus pollen data (1996-2010) were obtained by volumetric spore trap located near the centre of Poznań. Clinical data (2006-2010), i.e. skin prick test (SPT) and allergen-specific IgE measurements (asIgE), were supplied by the Allergy Diseases Diagnostic Centre in Poznań. Mean diurnal hazel pollen concentrations peaked around 14:00-16:00 when mean bi-hourly pollen concentrations were ~60 P m(-3). Onset of the hazel pollen season varied up to 87 days annually, and was significantly (r=-0.647; pHazel pollen has a detrimental effect on the allergic population of Poznań, with more than half of those sensitised to hazel pollen allergens showing symptoms of atopic dermatitis. Hazel pollen concentrations reach levels recognized as being able to induce allergy symptoms, especially in the afternoon and early evening when many people are returning home from work. The cross-reactivity with other members of the Fagales order also increases the allergenic potential of hazel pollen.

  8. MR assessment of the repaired rotator cuff: prevalence, size, location, and clinical relevance of tendon rerupture

    Energy Technology Data Exchange (ETDEWEB)

    Mellado, J.M. [Hospital Reina Sofia de Tudela, Servicio de Radiodiagnostico, Tudela, Navarra (Spain); Calmet, J.; Ballabriga, J.; Gine, J. [Hospital Universitari de Tarragona Joan XXIII, Servei de Cirurgia Ortopedica i Traumatologia, Tarragona (Spain); Olona, M. [Hospital Universitari de Tarragona Joan XXIII, Servei de Medicina Preventiva i Epidemiologia, Tarragona (Spain); Camins, A. [Hospital Universitari de Tarragona Joan XXIII, Institut de Diagnostic per la Imatge, Tarragona (Spain); Perez del Palomar, L. [Hospital Ernest Lluch, Servicio de Radiologia, Calatayud, Zaragoza (Spain)

    2006-10-15

    The objectives of this study were to use magnetic resonance (MR) imaging to evaluate the prevalence, size, location, and clinical relevance of tendon rerupture following complete repair of full-thickness rotator cuff tear (RCT). A total of 78 surgically proven full-thickness rotator cuff tears in 74 patients were retrospectively included in the study. Clinical assessment was performed using the University of California at Los Angeles score. Postoperative MR imaging was evaluated to determine prevalence, size, and location of tendon rerupture. At a mean 48.4 months' follow-up, 62 shoulders (79.5%) had favorable outcomes and 45 shoulders (57.6%) showed rerupture on MR imaging studies. Reruptures were significantly more prevalent among patients with intermediate-to-bad outcomes (81.3%), with surgically demonstrated two-tendon tears (78.9%) or three-tendon tears (100%), and with preoperative fatty degeneration of the supraspinatus muscle greater than 1 (91.6%). Reruptures were also significantly larger in those subgroups. Complete repair of RCT of all sizes may have favorable outcomes in a significant proportion of patients in spite of a high prevalence of reruptures. Preoperative tear size and degree of muscle fatty degeneration influence the prevalence and rerupture size. After repair of supraspinatus tears, reruptures tend to invade the posterior aspect of the tendon. (orig.)

  9. Quality of care at retail clinics for 3 common conditions.

    Science.gov (United States)

    Shrank, William H; Krumme, Alexis A; Tong, Angela Y; Spettell, Claire M; Matlin, Olga S; Sussman, Andrew; Brennan, Troyen A; Choudhry, Niteesh K

    2014-10-01

    Evaluation of quality of care across retail clinics in a geographically diverse population has not been undertaken to date. We sought to evaluate and compare the quality of care for otitis media, pharyngitis, and urinary tract infection received in retail medical clinics in CVS pharmacies ("MinuteClinics" [MCs]), ambulatory care facilities (ACFs), and emergency departments (EDs). We used 14 measures constructed from RAND Corporation's Quality Assurance Tools and guidelines from the American Academy of Pediatrics, the American Academy of Family Physicians, and the Infectious Diseases Society of America. Our cohort was drawn from Aetna medical and prescription claims, 2009-2012. Members were matched on visit date, condition, and propensity score. Generalized estimating equations were used to compare quality across clinic type, overall, and by index condition. We matched 75,886 episodes of care, of which 20,153 were eligible for at least 1 quality measure. MCs performed better than EDs and ACFs in 7 measures. In a multivariable model, MCs performed better than ACFs and EDs across all quality measures ([OR 0.42; 95% CI, 0.40-0.45; P < .0001; ACF vs MC] [OR 0.29; 95% CI, 0.27-0.31; P < .0001; ED vs MC]). Results for each condition were significant at P < .0001. Quality of care for these conditions based on widely accepted objective measures was superior in MinuteClinics compared with ACFs and EDs.

  10. Vasopressin in preeclampsia: a novel very early human pregnancy biomarker and clinically relevant mouse model.

    Science.gov (United States)

    Santillan, Mark K; Santillan, Donna A; Scroggins, Sabrina M; Min, James Y; Sandgren, Jeremy A; Pearson, Nicole A; Leslie, Kimberly K; Hunter, Stephen K; Zamba, Gideon K D; Gibson-Corley, Katherine N; Grobe, Justin L

    2014-10-01

    Preeclampsia, a cardiovascular disorder of late pregnancy, is characterized as a low-renin hypertensive state relative to normotensive pregnancy. Because other nonpregnant low-renin hypertensive disorders often exhibit and are occasionally dependent on elevated arginine vasopressin (AVP) secretion, we hypothesized a possible use for plasma AVP measurements in the prediction of preeclampsia. Copeptin is an inert prosegment of AVP that is secreted in a 1:1 molar ratio and exhibits a substantially longer biological half-life compared with AVP, rendering it a clinically useful biomarker of AVP secretion. Copeptin was measured throughout pregnancy in maternal plasma from preeclamptic and control women. Maternal plasma copeptin was significantly higher throughout preeclamptic pregnancies versus control pregnancies. While controlling for clinically significant confounders (age, body mass index, chronic essential hypertension, twin gestation, diabetes mellitus, and history of preeclampsia) using multivariate regression, the association of higher copeptin concentration and the development of preeclampsia remained significant. Receiver operating characteristic analyses reveal that as early as the sixth week of gestation, elevated maternal plasma copeptin concentration is a highly significant predictor of preeclampsia throughout pregnancy. Finally, chronic infusion of AVP during pregnancy (24 ng per hour) is sufficient to phenocopy preeclampsia in C57BL/6J mice, causing pregnancy-specific hypertension, renal glomerular endotheliosis, proteinuria, and intrauterine growth restriction. These data implicate AVP release as a novel predictive biomarker for preeclampsia very early in pregnancy, identify chronic AVP infusion as a novel and clinically relevant model of preeclampsia in mice, and are consistent with a potential causative role for AVP in preeclampsia in humans. © 2014 American Heart Association, Inc.

  11. Relevance of pharmacokinetic and pharmacodynamic modeling to clinical care of critically ill patients.

    Science.gov (United States)

    Bulitta, Jurgen B; Landersdorfer, Cornelia B; Forrest, Alan; Brown, Silvia V; Neely, Michael N; Tsuji, Brian T; Louie, Arnold

    2011-12-01

    Efficacious therapy is of utmost importance to save lives and prevent bacterial resistance in critically ill patients. This review summarizes pharmacokinetic (PK) and pharmacodynamic (PD) modeling methods to optimize clinical care of critically ill patients in empiric and individualized therapy. While these methods apply to all therapeutic areas, we focus on antibiotics to highlight important applications, as emergence of resistance is a significant problem. Nonparametric and parametric population PK modeling, multiple-model dosage design, Monte Carlo simulations, and Bayesian adaptive feedback control are the methods of choice to optimize therapy. Population PK can estimate between patient variability and account for potentially increased clearances and large volumes of distribution in critically ill patients. Once patient- specific PK data become available, target concentration intervention and adaptive feedback control algorithms can most precisely achieve target goals such as clinical cure of an infection or resistance prevention in stable and unstable patients with rapidly changing PK parameters. Many bacterial resistance mechanisms cause PK/PD targets for resistance prevention to be usually several-fold higher than targets for near-maximal killing. In vitro infection models such as the hollow fiber and one-compartment infection models allow one to study antibiotic-induced bacterial killing and emergence of resistance of mono- and combination therapies over clinically relevant treatment durations. Mechanism-based (and empirical) PK/PD modeling can incorporate effects of the immune system and allow one to design innovative dosage regimens and prospective validation studies. Mechanism-based modeling holds great promise to optimize mono- and combination therapy of anti-infectives and drugs from other therapeutic areas for critically ill patients.

  12. New insights of an old defense system: structure, function, and clinical relevance of the complement system.

    Science.gov (United States)

    Ehrnthaller, Christian; Ignatius, Anita; Gebhard, Florian; Huber-Lang, Markus

    2011-01-01

    The complement system was discovered a century ago as a potent defense cascade of innate immunity. After its first description, continuous experimental and clinical research was performed, and three canonical pathways of activation were established. Upon activation by traumatic or surgical tissue damage, complement reveals beneficial functions of pathogen and danger defense by sensing and clearing injured cells. However, the latest research efforts have provided a more distinct insight into the complement system and its clinical subsequences. Complement has been shown to play a significant role in the pathogenesis of various inflammatory processes such as sepsis, multiorgan dysfunction, ischemia/reperfusion, cardiovascular diseases and many others. The three well-known activation pathways of the complement system have been challenged by newer findings that demonstrate direct production of central complement effectors (for example, C5a) by serine proteases of the coagulation cascade. In particular, thrombin is capable of producing C5a, which not only plays a decisive role on pathogens and infected/damaged tissues, but also acts systemically. In the case of uncontrolled complement activation, "friendly fire" is generated, resulting in the destruction of healthy host tissue. Therefore, the traditional research that focuses on a mainly positive-acting cascade has now shifted to the negative effects and how tissue damage originated by the activation of the complement can be contained. In a translational approach including structure-function relations of this ancient defense system, this review provides new insights of complement-mediated clinical relevant diseases and the development of complement modulation strategies and current research aspects.

  13. Toluene biodegradation rates in unsaturated soil systems versus liquid batches and their relevance to field conditions

    NARCIS (Netherlands)

    Picone, S.; Grotenhuis, J.T.C.; Gaans, van P.; Valstar, J.; Langenhoff, A.A.M.; Rijnaarts, H.

    2013-01-01

    Contaminant biodegradation in unsaturated soils may reduce the risks of vapor intrusion. However, the reported rates show large variability and are often derived from slurry experiments that are not representative of unsaturated conditions. Here, different laboratory setups are used to derive the

  14. Toluene biodegradation rates in unsaturated soil systems versus liquid batches and their relevance to field conditions

    NARCIS (Netherlands)

    Picone, S.; Grotenhuis, J.T.C.; Gaans, van P.; Valstar, J.; Langenhoff, A.A.M.; Rijnaarts, H.

    2013-01-01

    Contaminant biodegradation in unsaturated soils may reduce the risks of vapor intrusion. However, the reported rates show large variability and are often derived from slurry experiments that are not representative of unsaturated conditions. Here, different laboratory setups are used to derive the bi

  15. Assessing the Risk Relevance of Accounting Variables in Diverse Economic conditions

    NARCIS (Netherlands)

    Brimble, M.; Hodgson, A.

    2005-01-01

    This paper examines the association between accounting information and systematic (beta) risk. We extend previous research by using an updated data set, a range of risk measures that adjust for different market and time-varying conditions, and by examining whether the long-run association has change

  16. The inter-examiner reliability of standardized manual palpation for the identification of clinically relevant myofascial triggerpoints

    DEFF Research Database (Denmark)

    Myburgh, Corrie; Lauridsen, Henrik Hein; Larsen, Anders Holsgaard

    A clinical diagnosis of Myofascial Pain Syndrome (MPS) requires manual palpation for the identification of at least one clinically relevant trigger point (TP). However, few comparable, high quality studies exist regarding the robustness of TP examination. Our aim was to determine the inter...

  17. Does the choice of display system influence perception and visibility of clinically relevant features in digital pathology images?

    Science.gov (United States)

    Kimpe, Tom; Rostang, Johan; Avanaki, Ali; Espig, Kathryn; Xthona, Albert; Cocuranu, Ioan; Parwani, Anil V.; Pantanowitz, Liron

    2014-03-01

    Digital pathology systems typically consist of a slide scanner, processing software, visualization software, and finally a workstation with display for visualization of the digital slide images. This paper studies whether digital pathology images can look different when presenting them on different display systems, and whether these visual differences can result in different perceived contrast of clinically relevant features. By analyzing a set of four digital pathology images of different subspecialties on three different display systems, it was concluded that pathology images look different when visualized on different display systems. The importance of these visual differences is elucidated when they are located in areas of the digital slide that contain clinically relevant features. Based on a calculation of dE2000 differences between background and clinically relevant features, it was clear that perceived contrast of clinically relevant features is influenced by the choice of display system. Furthermore, it seems that the specific calibration target chosen for the display system has an important effect on the perceived contrast of clinically relevant features. Preliminary results suggest that calibrating to DICOM GSDF calibration performed slightly worse than sRGB, while a new experimental calibration target CSDF performed better than both DICOM GSDF and sRGB. This result is promising as it suggests that further research work could lead to better definition of an optimized calibration target for digital pathology images resulting in a positive effect on clinical performance.

  18. Photooxidation of the Antimicrobial, Nonribosomal Peptide Bacitracin A by Singlet Oxygen under Environmentally Relevant Conditions.

    Science.gov (United States)

    Lundeen, Rachel A; Chu, Chiheng; Sander, Michael; McNeill, Kristopher

    2016-08-16

    Bacitracin is a mixture of nonribosomal peptides (NRPs) that is extensively used as an antibiotic in both human and veterinary medicine. Despite its widespread use over the past six decades, very few studies have addressed the environmental fate of bacitracin and zinc-bacitracin complexes. In this study, the photochemical transformation of bacitracin components (i.e., cyclic dodecapeptides) in the aquatic environment was investigated. A high resolution mass spectrometry (HRMS)-based approach enabled monitoring of the photochemical degradation kinetics of individual bacitracin components, investigation of the relative contribution of reactive oxygen species (e.g., singlet oxygen, (1)O2) in dissolved organic matter-sensitized photoreactions, and identification of oxidative modifications in bacitracin photoproducts. The results of this study support the hypothesis that indirect photochemical oxidation of the histidine (His) residue by (1)O2 is a major degradation pathway for bacitracin A, the most potent congener of the mixture. Furthermore, the photooxidation rate of bacitracin A with (1)O2 decreased upon bacitracin A coordination with Zn(2+), demonstrating that the photochemistry of metal-bound His is different from that of metal-free His. Overall, these results provide insight into the fate of bacitracin components in the aquatic environment and highlight the potential of utilizing this HRMS-based methodology to study transformations of other environmentally relevant NRPs.

  19. Validation of a CFD Methodology for Variable Speed Power Turbine Relevant Conditions

    Science.gov (United States)

    Ameri, Ali A.; Giel, Paul W.; McVetta, Ashlie B.

    2013-01-01

    Analysis tools are needed to investigate aerodynamic performance of Variable-Speed Power Turbines (VSPT) for rotorcraft applications. The VSPT operates at low Reynolds numbers (transitional flow) and over a wide range of incidence. Previously, the capability of a published three-equation turbulence model to predict accurately the transition location for three-dimensional heat transfer problems was assessed. In this paper, the results of a post-diction exercise using a three-dimensional flow in a transonic linear cascade comprising VSPT blading are presented. The measured blade pressure distributions and exit total pressure and flow angles for two incidence angles corresponding to cruise (i = 5.8deg) and takeoff (i = -36.7deg) were used for this study. For the higher loading condition of cruise and the negative incidence condition of takeoff, overall agreement with data may be considered satisfactory but areas of needed improvement are also indicated.

  20. Characterization of ion fluxes and heat fluxes for PMI relevant conditions on Proto-MPEX

    Science.gov (United States)

    Beers, Clyde; Shaw, Guinevere; Biewer, Theodore; Rapp, Juergen

    2016-10-01

    Plasma characterization, in particular, particle flux and electron and ion temperature distributions nearest to an exposed target, are critical to quantifying Plasma Surface Interaction (PSI). In the Proto-Material Plasma Exposure eXperiment (Proto-MPEX), the ion fluxes and heat fluxes are derived from double Langmuir Probes (DLP) and Thomson Scattering in front of the target assuming Bohm conditions at the sheath entrance. Power fluxes derived from ne and Te measurements are compared to heat fluxes measured with IR thermography. The comparison will allow conclusions on the sheath heat transmission coefficient to be made experimentally. Different experimental conditions (low and high density plasmas (0.5 - 6 x 1019 m-3) with different magnetic configuration are compared. This work was supported by the U.S. D.O.E. contract DE-AC05-00OR22725.

  1. Monitoring the condition of the Canadian forest environment: The relevance of the concept of 'ecological indicators'.

    Science.gov (United States)

    Kimmins, J P

    1990-11-01

    The Canadian forest environment is characterized by high spatial and temporal variability, especially in the west. Our forests vary according to climate, landform, and surficial geology, and according to the type, intensity, extent of, and the time since the last disturbance. Most Canadian forests have had a history of repeated acute, episodic disturbance from fire, insects, wind, diseases and/or logging, with a frequency of disturbance varying from a few decades to many centuries. These sources of variability have resulted in a complex and continually changing mosaic of forest conditions and stages of successional development.Monitoring the 'quality' of this dynamic forested landscape mosaic is extremely difficult, and in most cases the concept of a relatively simple index of forest ecosystem quality or condition (i.e. an 'ecological indicator') is probably inappropriate. Such ecological indicators are better suited for monitoring chronic anthropogenically induced disturbances that are continuous in their effect (e.g. 'acid rain', heavy metal pollution, air pollution, and the 'greenhouse effect') in ecosystems that, in the absence of such chronic disturbance, exhibit very slow directional change (e.g. lakes, higher order streams and rivers). Monitoring the effects of a chronic anthropogenic disturbance to forest ecosystems to determine if it is resulting in a sustained, directional alteration of environmental 'quality' will require a definition of the expected pattern of episodic disturbance and recovery therefrom (i.e. patterns of secondary succession in the absence of the chronic disturbance). Only when we have such a 'temporal fingerprint' of forest ecosystem condition for 'normal' patterns of disturbance and recovery can we determine if the ecosystem condition is being degraded by chronic human-induced alteration of the environment. Thus, degradation is assessed in terms of deviations from the expected temporal pattern of conditions rather than in terms of an

  2. Pneumomediastinum and the aortic nipple: the clinical relevance of the left superior intercostal vein.

    Science.gov (United States)

    Walters, Andy; Cassidy, Lindsey; Muhleman, Mitchel; Peterson, Ashley; Blaak, Christa; Loukas, Marios

    2014-07-01

    This article discusses the appearance of the "aortic nipple" in chest radiography, and reviews the embryology and anatomy of the left superior intercostal vein which causes the appearance of an "aortic nipple." This radiological sign is useful in differentiating certain thoracic pathologies, such as pneumomediastinum, pneumopericardium, and medial pneumothorax. Pneumomediastinum is an encompassing term describing the presence of air in the mediastinum, and may arise from a wide range of pathological conditions. Despite the well-described imaging of pneumomediastinum, it is sometimes difficult to differentiate from other conditions such as pneumopericardium and medial pneumothorax. A separate finding, "aortic nipple" is the radiographic term used to describe the lateral nipple-like projection from the aortic knob present in a small number of individuals. The aortic nipple corresponds to the end-on appearance of the left superior intercostal vein coursing around the aortic knob, and may be mistaken radiologically for lymphadenopathy or a neoplasm. Despite their relative independence, the aortic nipple is defined by new contours in cases of pneumomediastinum, taking on an "inverted aortic nipple" appearance. In this position, the inverted aortic nipple may facilitate radiographic discrimination of pneumomediastinum from similar conditions. This study aims to review the common clinical and radiographic features of both pneumomediastinum and the aortic nipple. The radiologic appearance of the aortic nipple occurring in unison with pneumomediastinum, and its potential role as a tool in the differentiation of pneumomediastinum from similarly presenting conditions will also be described. Copyright © 2013 Wiley Periodicals, Inc.

  3. Effects of Initial Conditions on Compressible Mixing in Supernova-Relevant Laboratory Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Miles, A R; Edwards, M; Greenough, J

    2004-04-30

    In core-collapse supernovae, strong blast waves drive interfaces susceptible to Rayleigh-Taylor (RT), Richtmyer-Meshkov (RM), and Kelvin-Helmholtz (KH) instabilities. In addition, perturbation growth can result from material expansion in large-scale velocity gradients behind the shock front. Laser-driven experiments are designed to produce a strongly shocked interface whose evolution is a scaled version of the unstable hydrogen-helium interface in core-collapse supernovae such as SN 1987A. The ultimate goal of this research is to develop an understanding of the effect of hydrodynamic instabilities and the resulting transition to turbulence on supernovae observables that remain as yet unexplained. In this paper, we summarize recent results from our computational study of unstable systems driven by high Mach number shock and blast waves. For planar multimode systems, compressibility effects preclude the emergence of a regime of self-similar instability growth independent of the initial conditions (IC's) by allowing for memory of the initial conditions to be retained in the mix-width at all times. With higher-dimensional blast waves, divergence restores the properties necessary for establishment of the self-similar state, but achieving it requires very high initial characteristic mode number and high Mach number for the incident blast wave. Initial conditions predicted by some recent stellar calculations are incompatible with self-similarity.

  4. Assessing the Behavior of Typically Lithophile Elements Under Highly Reducing Conditions Relevant to the Planet Mercury

    Science.gov (United States)

    Rowland, Rick, II; Vander Kaaden, Kathleen E.; McCubbin, Francis M.; Danielson, Lisa R.

    2017-01-01

    With the data returned from the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) mission, there are now numerous constraints on the physical and chemical properties of Mercury, including its surface composition (e.g., Evans et al. 2012; Nittler et al. 201 l; Peplowski et al. 2012; Weider et al. 2012). The high Sand low FeO contents observed from MESSENGER on the planet's surface suggests a low oxygen fugacity of the present planetary materials. Estimates of the oxygen fugacity for Mercurian magmas are approximately 3- 7 log units below the Iron-Wiistite (Fe-FeO) oxygen buffer (McCubbin et al. 2012; Zolotov et al. 2013), several orders of magnitude more reducing than other terrestrial bodies we have data from such as the Earth, Moon, or Mars (Herd 2008; Sharp, McCubbin, and Shearer 2013; Wadhwa 2008). Most of our understanding of elemental partitioning behavior comes from observations made on terrestrial rocks, but Mercury's oxygen fugacity is far outside the conditions of those samples. With limited oxygen available, lithophile elements may instead exhibit chalcophile, halophile, or siderophile behaviors. Furthermore, very few natural samples of rocks that formed under reducing conditions are available in our collections (e.g., enstatite chondrites, achondrites, aubrites). The goal of this study is to conduct experiments at high pressure and temperature conditions to determine the elemental partitioning behavior of typically lithophile elements as a function of decreasing oxygen fugacity.

  5. Prevalence and clinical relevance of helminth co-infections among tuberculosis patients in urban Tanzania

    Science.gov (United States)

    Hella, Jerry; Said, Khadija; Kamwela, Lujeko; Sasamalo, Mohamed; Maroa, Thomas; Chiryamkubi, Magreth; Mhalu, Grace; Schindler, Christian; Reither, Klaus; Knopp, Stefanie; Utzinger, Jürg; Gagneux, Sébastien; Fenner, Lukas

    2017-01-01

    Background Helminth infections can negatively affect the immunologic host control, which may increase the risk of progression from latent Mycobacterium tuberculosis infection to tuberculosis (TB) disease and alter the clinical presentation of TB. We assessed the prevalence and determined the clinical relevance of helminth co-infection among TB patients and household contact controls in urban Tanzania. Methodology Between November 2013 and October 2015, we enrolled adult (≥18 years) sputum smear-positive TB patients and household contact controls without TB during an ongoing TB cohort study in Dar es Salaam, Tanzania. We used Baermann, FLOTAC, Kato-Katz, point-of-care circulating cathodic antigen, and urine filtration to diagnose helminth infections. Multivariable logistic regression models with and without random effects for households were used to assess for associations between helminth infection and TB. Principal findings A total of 597 TB patients and 375 household contact controls were included. The median age was 33 years and 60.2% (585/972) were men. The prevalence of any helminth infection among TB patients was 31.8% (190/597) and 25.9% (97/375) among controls. Strongyloides stercoralis was the predominant helminth species (16.6%, 161), followed by hookworm (9.0%, 87) and Schistosoma mansoni (5.7%, 55). An infection with any helminth was not associated with TB (adjusted odds ratio (aOR) 1.26, 95% confidence interval (CI): 0.88–1.80, p = 0.22), but S. mansoni infection was (aOR 2.15, 95% CI: 1.03–4.45, p = 0.040). Moreover, S. mansoni infection was associated with lower sputum bacterial load (aOR 2.63, 95% CI: 1.38–5.26, p = 0.004) and tended to have fewer lung cavitations (aOR 0.41, 95% CI: 0.12–1.16, p = 0.088). Conclusions/Significance S. mansoni infection was an independent risk factor for active TB and altered the clinical presentation in TB patients. These findings suggest a role for schistosomiasis in modulating the pathogenesis of human TB

  6. [EDNOS is an eating disorder of clinical relevance, on a par with anorexia and bulimia nervosa].

    Science.gov (United States)

    Dingemans, A E; van Furth, E F

    2015-01-01

    The category 'eating disorder 'not otherwise specified'' (EDNOS) in DSM-IV is restricted to eating disorders of clinical severity that do not completely fulfil the criteria for anorexia and bulimia nervosa. The EDNOS category is, by definition, often regarded as a a residual category and in principle designed to incorporate a small group of patients with atypical characteristics. Health insurance companies argue that the treatment of patients diagnosed with EDNOS should not be treated in mental health institutions and therefore should not get their treatment costs reimbursed by the insurance companies. The most important argument of the insurance companies is that patients in the EDNOS category do not display serious psychiatric symptoms. The aim of this paper is to show that EDNOS is an eating disorder category of clinical relevance. The article provides a critical overview of literature on EDNOS which studies the prevalence, severity and course of the disorder. We also discuss to what extent the fifth version of dsm solves the problems relating to this residual category. We reviewed the literature. The classification given in DSM-IV is not an accurate reflection of clinical reality. Half of the patients presenting with an eating disorder and seeking treatment do meet the criteria for EDNOS. The duration and the severity of eating disorder psychopathology, the presence of comorbidity, the mortality, and the use of the mental health care services by individuals with an eating disorder appear to be very similar in EDNOS patients and in patients with anorexia and bulimia nervosa. Eating disorder classifications can be regarded as snapshots taken throughout the course of an illness. Over of the years patients can be afflicted with various subtypes of an eating disorder. DSM-5 places fewer patients in the EDNOS category that did DSM-IV. In the latest version of dsm, namely DSM-5, the number of patients with an eating disorder classified as EDNOS has declined. There

  7. Potentially pathogenic Escherichia coli can form a biofilm under conditions relevant to the food production chain.

    Science.gov (United States)

    Nesse, Live L; Sekse, Camilla; Berg, Kristin; Johannesen, Karianne C S; Solheim, Heidi; Vestby, Lene K; Urdahl, Anne Margrete

    2014-04-01

    The biofilm-producing abilities of potentially human-pathogenic serotypes of Escherichia coli from the ovine reservoir were studied at different temperatures and on different surfaces. A possible influence of the hydrophobicity of the bacterial cells, as well as the presence of two virulence factors, the Shiga toxin-encoding (Stx) bacteriophage and the eae gene, was also studied. A total of 99 E. coli isolates of serotypes O26:H11, O103:H2, and O103:H25 isolated from sheep feces were included. The results show that isolates of all three E. coli serotypes investigated can produce biofilm on stainless steel, glass, and polystyrene at 12, 20, and 37°C. There was a good general correlation between the results obtained on the different surfaces. E. coli O103:H2 isolates produced much more biofilm than those of the other two serotypes at all three temperatures. In addition, isolates of serotype O26:H11 produced more biofilm than those of O103:H25 at 37°C. The hydrophobicity of the isolates varied between serotypes and was also influenced by temperature. The results strongly indicated that hydrophobicity influenced the attachment of the bacteria rather than their ability to form biofilm once attached. Isolates with the eae gene produced less biofilm at 37°C than isolates without this gene. The presence of a Stx bacteriophage did not influence biofilm production. In conclusion, our results show that potentially human-pathogenic E. coli from the ovine reservoir can form biofilm on various surfaces and at several temperatures relevant for food production and handling.

  8. Clinical Practice Guidelines for Transfusion of Patients in Critical Condition.

    Directory of Open Access Journals (Sweden)

    Rafael Alejandro Gómez Baute

    2009-03-01

    Full Text Available Clinical Practice Guidelines for Transfusion of Patients in Critical Condition. We stress transfusion criteria (blood cells, platelets, granulocyte concentrations, plasma and cryoprecipitate, doses, diagnosis and treatment of post-transfusion reactions. It includes assessment guidelines focused on the most important aspects to be accomplished.

  9. Particle swarm optimization of neural network CAD systems with clinically relevant objectives

    Science.gov (United States)

    Habas, Piotr A.; Zurada, Jacek M.; Elmaghraby, Adel S.; Tourassi, Georgia D.

    2007-03-01

    Neural networks (NN) are typically developed to minimize the squared difference between the network's output and the target value for a set of training patterns; namely the mean squared error (MSE). However, lower MSE does not necessarily translate into a clinically more useful decision model. The purpose of this study was to investigate the particle swarm optimization (PSO) algorithm as an alternative way of NN optimization with clinically relevant objective functions (e.g., ROC and partial ROC area indices). The PSO algorithm was evaluated with respect to a NN-based CAD system developed to discriminate mammographic regions of interest (ROIs) that contained masses from normal regions based on 8 computer-extracted morphology-oriented features. Neural networks were represented as points (particle locations) in a D-dimensional search/optimization space where each dimension corresponded to one adaptable NN parameter. The study database of 1,337 ROIs (681 with masses, 656 normal) was split into two subsets to implement two-fold cross-validation sampling scheme. Neural networks were optimized with the PSO algorithm and the following objective functions (1) MSE, (2) ROC area index AUC, and (3) partial ROC area indices TPFAUC with TPF=0.90 and TPF=0.98. For comparison, performance of neural networks of the same architecture trained with the traditional backpropagation algorithm was also evaluated. Overall, the study showed that when the PSO algorithm optimized network parameters using a particular training objective, the NN test performance was superior with respect to the corresponding performance index. This was particularly true for the partial ROC area indices where statistically significant improvements were observed.

  10. Clinical relevance of [i]Corylus[/i] pollen in Poznań, western Poland

    Directory of Open Access Journals (Sweden)

    Łukasz Grewling

    2014-03-01

    Full Text Available Background. In Central Europe, hazel ([i]Corylus[/i] sp. pollen is considered to be an important aeroallergen in early spring. Objective. This study examines hazel pollen levels in Poznań, western Poland, and the clinical relevance of this aeroallergen in the city. Methods. [i]Corylus[/i] pollen data (1996–2010 were obtained by volumetric spore trap located near the centre of Poznań. Clinical data (2006–2010, i.e. skin prick test (SPT and allergen-specific IgE measurements (asIgE, were supplied by the Allergy Diseases Diagnostic Centre in Poznań. Results. Mean diurnal hazel pollen concentrations peaked around 14:00–16:00 when mean bi-hourly pollen concentrations were ~60 P m-3. Onset of the hazel pollen season varied up to 87 days annually, and was significantly (r=–0.647; p<0.01 related to mean maximum temperature during late December. SPT data revealed that ~11% of allergy patients had positive skin reactions to [i]Corylus[/i] pollen allergens, and most of these (94.4% reacted to pollen allergens from other members of the Betulaceae family – alder or birch. Of those sensitized, 53% suffered from atopic dermatitis. Of patients examined for serum asIgE, 26.0% had asIgE measurements in classes 5 and 6. Conclusions. Hazel pollen has a detrimental effect on the allergic population of Poznań, with more than half of those sensitised to hazel pollen allergens showing symptoms of atopic dermatitis. Hazel pollen concentrations reach levels recognized as being able to induce allergy symptoms, especially in the afternoon and early evening when many people are returning home from work. The cross-reactivity with other members of the Fagales order also increases the allergenic potential of hazel pollen.

  11. Headache and psychiatric comorbidity: historical context, clinical implications, and research relevance.

    Science.gov (United States)

    Lake, Alvin E; Rains, Jeanetta C; Penzien, Donald B; Lipchik, Gay L

    2005-05-01

    The comorbidity of headache and psychiatric disorders is a well-recognized clinical phenomenon warranting further systematic research. Affective disorders occur with at least three-fold greater frequency among migraineurs than among the general population, and the prevalence increases in clinical populations, especially with chronic daily headache. When present, psychiatric comorbidity complicates headache management and portends a poorer prognosis for headache treatment. However, the relationship between headache and psychopathology has historically been misunderstood, and measures of psychopathology have not always met the standard of formal Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria. In some cases, headache has been inappropriately attributed to psychological or psychiatric features, based on anecdotal observations. The challenge for future studies is to employ research methods and designs that accurately identify and classify the subset of headache patients with psychiatric disorders, evaluate their impact on headache symptoms and treatment, and identify optimal behavioral and pharmacologic treatment strategies. This article offers methodological considerations and recommendations for future research including: (i) ascribing dual-International Classification of Headache Disorders, 2nd ed. (ICHD-2) headache and DSM-IV psychiatric diagnoses according to reliable and valid diagnostic criteria, (ii) differentiating subclinical levels of depression and anxiety from major psychiatric disorders, (iii) encouraging validation studies of the recently published ICHD-2 diagnoses for "headache attributed to psychiatric disorder," (iv) expanding epidemiological research to address the range of DSM-IV Axis I and II psychiatric diagnoses among various headache populations, (v) identifying relevant psychiatric and behavioral mediator/moderator variables, and (vi) developing empirically based screening and treatment algorithms.

  12. Circulating tumor cells: clinically relevant molecular access based on a novel CTC flow cell.

    Directory of Open Access Journals (Sweden)

    Jessamine P Winer-Jones

    the way for clinically relevant genetic profiling of CTCs.

  13. Assessment and clinical relevance of non-fasting and postprandial triglycerides: an expert panel statement.

    Science.gov (United States)

    Kolovou, Genovefa D; Mikhailidis, Dimitri P; Kovar, Jan; Lairon, Dennis; Nordestgaard, Børge G; Ooi, Teik Chye; Perez-Martinez, Pablo; Bilianou, Helen; Anagnostopoulou, Katherine; Panotopoulos, George

    2011-05-01

    An Expert Panel group of scientists and clinicians met to consider several aspects related to non-fasting and postprandial triglycerides (TGs) and their role as risk factors for cardiovascular disease (CVD). In this context, we review recent epidemiological studies relevant to elevated non-fasting TGs as a risk factor for CVD and provide a suggested classification of non-fasting TG concentration. Secondly, we sought to describe methodologies to evaluate postprandial TG using a fat tolerance test (FTT) in the clinic. Thirdly, we discuss the role of non-fasting lipids in the treatment of postprandial hyperlipemia. Finally, we provide a series of clinical recommendations relating to non-fasting TGs based on the consensus of the Expert Panel: 1). Elevated non-fasting TGs are a risk factor for CVD. 2). The desirable non-fasting TG concentration is fast and should consist of 75 g of fat, 25 g of carbohydrates and 10 g of protein. 4). A single TG measurement 4 h after a FTT meal provides a good evaluation of the postprandial TG response. 5). Preferably, subjects with non-fasting TG levels of 1-2 mmol/l (89-180 mg/dl) should be tested with a FTT. 6). TG concentration ≤ 2.5 mmol/l (220 mg/dl) at any time after a FTT meal should be considered as a desirable postprandial TG response. 7). A higher and undesirable postprandial TG response could be treated by aggressive lifestyle modification (including nutritional supplementation) and/or TG lowering drugs like statins, fibrates and nicotinic acid.

  14. Social and clinically-relevant cardiovascular risk factors in Asian Americans adults: NHANES 2011-2014.

    Science.gov (United States)

    Echeverria, Sandra E; Mustafa, Mehnaz; Pentakota, Sir Ram; Kim, Soyeon; Hastings, Katherine; Amadi, Chioma; Palaniappan, Latha

    2017-02-17

    Little evidence exists examining cardiovascular risk factors among Asian Americans and how social determinants such as nativity status and education pattern risk in the United States (U.S.) context. We used the 2011-2014 National Health and Nutrition Examination Survey, which purposely oversampled Asian Americans from 2011 to 2014, and examined prevalence of Type II diabetes, smoking and obesity for Asian Americans (n=1363) and non-Latino Whites (n=4121). We classified Asian Americans as U.S. or foreign-born and by years in the U.S. Obesity status was based on standard body mass index (BMI) cut points of ≥30kg/m(2) and Asian-specific cut points (BMI≥25kg/m(2)) that may be more clinically relevant for this population. We fit separate logistic regression models for each outcome using complex survey design methods and tested for the joint effect of race, nativity and education on each outcome.Diabetes and obesity prevalence (applying Asian-specific BMI cut points) were higher among Asian Americans when compared to non-Latino Whites but smoking prevalence was lower. These patterns remained in fully adjusted models and showed small increases with longer duration in the U.S. Joint effects models showed higher odds of prevalent Type II diabetes and obesity (Asian-specific) for foreign-born Asians, regardless of years in the U.S. and education, when compared to non-Latino Whites with high education. Smoking models showed significant interaction effects between race and education for non-Latino Whites only. Our study supports the premise that social as well as clinical factors should be considered when developing health initiatives for Asian Americans.

  15. Auxin polar transport in arabidopsis under simulated microgravity conditions - relevance to growth and development

    Science.gov (United States)

    Miyamoto, K.; Oka, M.; Yamamoto, R.; Masuda, Y.; Hoson, T.; Kamisaka, S.; Ueda, J.

    1999-01-01

    Activity of auxin polar transport in inflorescence axes of Arabidopsis thaliana grown under simulated microgravity conditions was studied in relation to the growth and development. Seeds were germinated and allowed to grow on an agar medium in test tubes on a horizontal clinostat. Horizontal clinostat rotation substantially reduced the growth of inflorescence axes and the productivity of seeds of Arabidopsis thaliana (ecotypes Landsberg erecta and Columbia), although it little affected seed germination, development of rosette leaves and flowering. The activity of auxin polar transport in inflorescence axes decreased when Arabidopsis plants were grown on a horizontal clinostat from germination stage, being ca. 60% of 1 g control. On the other hand, the auxin polar transport in inflorescence axes of Arabidopsis grown in 1 g conditions was not affected when the segments were exposed to various gravistimuli, including 3-dimensional clinorotation, during transport experiments. Pin-formed mutant of Arabidopsis, having a unique structure of the inflorescence axis with no flower and extremely low levels of the activity of auxin polar transport in inflorescence axes and endogenous auxin, did not continue its vegetative growth under clinostat rotation. These facts suggest that the development of the system of auxin polar transport in Arabidopsis is affected by microgravity, resulting in the inhibition of growth and development, especially during reproductive growth.

  16. Using magnetically responsive tea waste to remove lead in waters under environmentally relevant conditions.

    Science.gov (United States)

    Yeo, Siang Yee; Choi, Siwon; Dien, Vivian; Sow-Peh, Yoke Keow; Qi, Genggeng; Hatton, T Alan; Doyle, Patrick S; Thio, Beng Joo Reginald

    2013-01-01

    We report the use of a simple yet highly effective magnetite-waste tea composite to remove lead(II) (Pb(2+)) ions from water. Magnetite-waste tea composites were dispersed in four different types of water-deionized (DI), artificial rainwater, artificial groundwater and artificial freshwater-that mimic actual environmental conditions. The water samples had varying initial concentrations (0.16-5.55 ppm) of Pb(2+) ions and were mixed with the magnetite-waste tea composite for at least 24 hours to allow adsorption of the Pb(2+) ions to reach equilibrium. The magnetite-waste tea composites were stable in all the water samples for at least 3 months and could be easily removed from the aqueous media via the use of permanent magnets. We detected no significant leaching of iron (Fe) ions into the water from the magnetite-waste tea composites. The percentage of Pb adsorbed onto the magnetite-waste tea composite ranged from ∼70% to 100%; the composites were as effective as activated carbon (AC) in removing the Pb(2+) ions from water, depending on the initial Pb concentration. Our prepared magnetite-waste tea composites show promise as a green, inexpensive and highly effective sorbent for removal of Pb in water under environmentally realistic conditions.

  17. Using Magnetically Responsive Tea Waste to Remove Lead in Waters under Environmentally Relevant Conditions

    KAUST Repository

    Yeo, Siang Yee

    2013-06-20

    We report the use of a simple yet highly effective magnetite-waste tea composite to remove lead(II) (Pb2+) ions from water. Magnetite-waste tea composites were dispersed in four different types of water–deionized (DI), artificial rainwater, artificial groundwater and artificial freshwater–that mimic actual environmental conditions. The water samples had varying initial concentrations (0.16–5.55 ppm) of Pb2+ ions and were mixed with the magnetite-waste tea composite for at least 24 hours to allow adsorption of the Pb2+ ions to reach equilibrium. The magnetite-waste tea composites were stable in all the water samples for at least 3 months and could be easily removed from the aqueous media via the use of permanent magnets. We detected no significant leaching of iron (Fe) ions into the water from the magnetite-waste tea composites. The percentage of Pb adsorbed onto the magnetite-waste tea composite ranged from ~70% to 100%; the composites were as effective as activated carbon (AC) in removing the Pb2+ ions from water, depending on the initial Pb concentration. Our prepared magnetite-waste tea composites show promise as a green, inexpensive and highly effective sorbent for removal of Pb in water under environmentally realistic conditions.

  18. Coupling Between Turbulent Boundary Layer and Radiative Heat Transfer Under Engine-Relevant Conditions

    Science.gov (United States)

    Sircar, A.; Paul, C.; Ferreyro, S.; Imren, A.; Haworth, D. C.; Roy, S.; Ge, W.; Modest, M. F.

    2016-11-01

    The lack of accurate submodels for in-cylinder radiation and heat transfer has been identified as a key shortcoming in developing truly predictive CFD models that can be used to develop combustion systems for advanced high-efficiency, low-emissions engines. Recent measurements of wall layers in engines show discrepancies of up to 100% with respect to standard CFD boundary-layer models. And recent analysis of in-cylinder radiation based on recent spectral property databases and high-fidelity radiative transfer equation (RTE) solvers has shown that at operating conditions typical of heavy-duty CI engines, radiative emission can be as high as 40% of the wall heat losses, that molecular gas radiation can be more important than soot radiation, and that a significant fraction of the emitted radiation can be reabsorbed before reaching the walls. That is, radiation changes the in-cylinder temperature distribution, which in turn affects combustion and emissions. The goal of this research is to develop models that explicitly account for the potentially strong coupling between radiative and turbulent boundary layer heat transfer. For example, for optically thick conditions, a simple diffusion model might be formulated in terms of an absorption-coefficient-dependent turbulent Prandtl number. NSF, DOE.

  19. Experimental and Numerical Models of Complex Clinical Scenarios; Strategies to Improve Relevance and Reproducibility of Joint Replacement Research.

    Science.gov (United States)

    Bechtold, Joan E; Swider, Pascal; Goreham-Voss, Curtis; Soballe, Kjeld

    2016-02-01

    , material, and surgical features to influence implant-bone healing, using a selection of results from two decades of coordinated experimental and numerical work and (b) discuss limitations of such models and the implications for research reproducibility. Focusing model conditions toward the clinical scenario to be studied, and limiting conclusions to the conditions of a particular model can increase clinical relevance and research reproducibility.

  20. 3D Culture as a Clinically Relevant Model for Personalized Medicine.

    Science.gov (United States)

    Fong, Eliza Li Shan; Toh, Tan Boon; Yu, Hanry; Chow, Edward Kai-Hua

    2017-03-01

    Advances in understanding many of the fundamental mechanisms of cancer progression have led to the development of molecular targeted therapies. While molecular targeted therapeutics continue to improve the outcome for cancer patients, tumor heterogeneity among patients, as well as intratumoral heterogeneity, limits the efficacy of these drugs to specific patient subtypes, as well as contributes to relapse. Thus, there is a need for a more personalized approach toward drug development and diagnosis that takes into account the diversity of cancer patients, as well as the complex milieu of tumor cells within a single patient. Three-dimensional (3D) culture systems paired with patient-derived xenografts or patient-derived organoids may provide a more clinically relevant system to address issues presented by personalized or precision medical approaches. In this review, we cover the current methods available for applying 3D culture systems toward personalized cancer research and drug development, as well as key challenges that must be addressed in order to fully realize the potential of 3D patient-derived culture systems for cancer drug development. Greater implementation of 3D patient-derived culture systems in the cancer research field should accelerate the development of truly personalized medical therapies for cancer patients.

  1. Clinically-relevant chemotherapy interactions with complementary and alternative medicines in patients with cancer.

    Science.gov (United States)

    Yap, Kevin Yi-Lwern; See, Cheng Shang; Chan, Alexandre

    2010-01-01

    Complementary and alternative medicines (CAMs), in particular herbal medicines, are commonly used by cancer patients in conjunction with chemotherapy treatment for their anticancer properties and supportive care. However, the effects of many of these herbs are not well-documented due to limited studies done on them. Severe herb-drug interactions (HDIs) have been recorded in some cases, and failure to recognize these harmful HDIs can lead to dire consequences in cancer patients. This study discusses clinically-relevant interactions between anticancer drugs (ACDs) and herbs classified into 7 categories: cancer treatment and prevention, immune-system-related, alopecia, nausea and vomiting, peripheral neuropathy and pain, inflammation, and fatigue. Some promising patents which contain these herbs and thus may manifest these interactions are also presented in this article. Pharmacokinetic interactions involved mainly induction or inhibition of the cytochrome P450 isozymes and p-glycoprotein, while pharmacodynamic interactions were related to increased risks of central nervous system-related effects, hepatotoxicity and bleeding, among others. Clinicians should be vigilant when treating cancer patients who take CAMs with concurrent chemotherapy since they face a high risk of HDIs. These HDIs can be minimized or avoided by selecting herb-drug pairs which are less likely to interact. Furthermore, close monitoring of pharmacological effects and plasma drug levels should be carried out to avoid toxicity and ensure adequate chemotherapeutic coverage in patients with cancer.

  2. Clinical relevancy and risks of potential drug–drug interactions in intensive therapy

    Science.gov (United States)

    Rodrigues, Aline Teotonio; Stahlschmidt, Rebeca; Granja, Silvia; Falcão, Antonio Luis Eiras; Moriel, Patricia; Mazzola, Priscila Gava

    2014-01-01

    Purpose Evaluate the potential Drug–Drug Interactions (pDDI) found in prescription orders of adult Intensive Care Unit (ICU) of a Brazilian public health system hospital; quantify and qualify the pDDI regarding their severity and risks to the critical patient, using the database from Micromedex®. Methods Prospective study (January–December of 2011) collecting and evaluating 369 prescription orders (convenient sampling), one per patient. Results During the study 1844 pDDIs were identified and distributed in 405 pairs (medication A × medication B combination). There was an average of 5.00 ± 5.06 pDDIs per prescription order, the most prevalent being moderate and important interactions, present in 74% and 67% of prescription orders, respectively. In total, there were 9 contraindicated, 129 important and 204 moderate pDDIs. Among them 52 had as management recommendation to “avoid concomitant use” or “suspension of medication”, while 306 had as recommendation “continuous and adequate monitoring”. Conclusion The high number of pDDIs found in the study combined with the evaluation of the clinical relevancy of the most frequent pDDIs in the ICU shows that moderate and important interactions are highly incident. As the majority of them demand monitoring and adequate management, being aware of these interactions is major information for the safe and individualized risk management. PMID:27134536

  3. Immune Memory and Exhaustion: Clinically Relevant Lessons from the LCMV Model.

    Science.gov (United States)

    Zehn, D; Wherry, E J

    2015-01-01

    The development of dysfunctional or exhausted T cells is characteristic of immune responses to chronic viral infections and cancer. Exhausted T cells are defined by reduced effector function, sustained upregulation of multiple inhibitory receptors, an altered transcriptional program and perturbations of normal memory development and homeostasis. This review focuses on (a) illustrating milestone discoveries that led to our present understanding of T cell exhaustion, (b) summarizing recent developments in the field, and (c) identifying new challenges for translational research. Exhausted T cells are now recognized as key therapeutic targets in human infections and cancer. Much of our knowledge of the clinically relevant process of exhaustion derives from studies in the mouse model of Lymphocytic choriomeningitis virus (LCMV) infection. Studies using this model have formed the foundation for our understanding of human T cell memory and exhaustion. We will use this example to discuss recent advances in our understanding of T cell exhaustion and illustrate the value of integrated mouse and human studies and will emphasize the benefits of bi-directional mouse-to-human and human-to-mouse research approaches.

  4. Clinical relevance of infections with zoonotic and human oral species of Campylobacter.

    Science.gov (United States)

    Lee, Soomin; Lee, Jeeyeon; Ha, Jimyeong; Choi, Yukyung; Kim, Sejeong; Lee, Heeyoung; Yoon, Yohan; Choi, Kyoung-Hee

    2016-07-01

    Genus Campylobacter has been recognized as a causative bacterial agent of animal and human diseases. Human Campylobacter infections have caused more concern. Campylobacters can be classified into two groups in terms of their original host: zoonotic and human oral species. The major zoonotic species are Campylobacter jejuni and Campylobacter coli, which mostly reside in the intestines of avian species and are transmitted to humans via consumption of contaminated poultry products, thus causing human gastroenteritis and other diseases as sequelae. The other campylobacters, human oral species, include C. concisus, C. showae, C. gracilis, C. ureolyticus, C. curvus, and C. rectus. These species are isolated from the oral cavity, natural colonization site, but have potential clinical relevance in the periodontal region to varying extent. Two species, C. jejuni and C. coli, are believed to be mainly associated with intestinal diseases, but recent studies suggested that oral Campylobacter species also play a significant role in intestinal diseases. This review offers an outline of the two Campylobacter groups (zoonotic and human oral), their virulence traits, and the associated illnesses including gastroenteritis.

  5. Polymorphisms in drug-metabolizing enzymes: What is their clinical relevance and why do they exist?

    Energy Technology Data Exchange (ETDEWEB)

    Nebert, D.W. [Univ. of Cincinnati Medical Center, OH (United States)

    1997-02-01

    The beautiful report by Sachse in this issue of the journal represents the culmination of 2 decades of increasingly exciting work on the {open_quotes}debrisoquine oxidation polymorphism,{close_quotes} one of dozens of pharmacogenetic or ecogenetic polymorphisms that have been shown to have an important impact on innumerable clinical diseases. Pharmacogenetics is the study of the hereditary basis of the differences in responses to drugs. Ecogenetics is the broader field of interindividual differences in response to all environmental chemical and physical agents (e.g., heavy metals, insecticides, compounds formed during combustion, and UV radiation). It is now clear that each of us has his or her own {open_quotes}individual fingerprint{close_quotes} of unique alleles encoding the so-called drug-metabolizing enzymes (DMEs) and the receptors that regulate these enzymes. In this invited editorial, I first introduce the current thinking in the field of DME (and DME-receptor) research and how DMEs have evolved from animal-plant interactions. I then describe the debrisoquine oxidation polymorphism, as well as two other relevant DME polymorphisms; show the relationship between these polymorphisms and human disease; provide examples of synergistic effects caused by the combination of two DME polymorphisms; and discuss the ethical considerations of such research. Last, I speculate on why these allelic frequencies of the DME genes might exist in human populations in the first place. 35 refs.

  6. Clinical relevance of oxidative stress and sperm chromatin damage in male infertility: an evidence based analysis

    Directory of Open Access Journals (Sweden)

    Marcello Cocuzza

    2007-10-01

    Full Text Available Oxidative stress (OS in the reproductive tract is now a real entity and concern due to the potential harmful effects of high levels of reactive oxygen species (ROS on sperm number, motility, quality, and function including damage to sperm nuclear DNA. Evaluation of OS related damage to non-functional sperm is highly relevant as intracytoplasmic sperm injection (ICSI technique, an effective therapy for severe male factor infertility, bypasses the majority of reproductive tract deficiencies. Despite the controversial findings in the existing literature, there is now enough evidence to show that sperm DNA damage is detrimental to reproductive outcomes. In addition, spermatozoa of infertile men are suggested to carry more DNA damage than do the spermatozoa from fertile men. Besides impairment of fertility such damage is likely to increase the transmission of genetic diseases during the assisted reproductive procedures. Standardization of protocols to assess reactive oxygen species and DNA damage is very important in introducing these tests in such clinical practice. Thus evaluation of seminal ROS levels and extent of sperm DNA damage especially in an infertile male may help develop new therapeutic strategies and improve success of assisted reproductive techniques (ART.

  7. Quantitative Aortic Distensibility Measurement Using CT in Patients with Abdominal Aortic Aneurysm: Reproducibility and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Yunfei Zha

    2017-01-01

    Full Text Available Purpose. To investigate the reproducibility of aortic distensibility (D measurement using CT and assess its clinical relevance in patients with infrarenal abdominal aortic aneurysm (AAA. Methods. 54 patients with infrarenal abdominal aortic aneurysm were studied to determine their distensibility by using 64-MDCT. Aortic cross-sectional area changes were determined at two positions of the aorta, immediately below the lowest renal artery (level 1. and at the level of its maximal diameter (level 2. by semiautomatic segmentation. Measurement reproducibility was assessed using intraclass correlation coefficient (ICC and Bland-Altman analyses. Stepwise multiple regression analysis was performed to assess linear associations between aortic D and anthropometric and biochemical parameters. Results. A mean distensibility of Dlevel  1.=(1.05±0.22×10-5  Pa-1 and Dlevel  2.=(0.49±0.18×10-5  Pa-1 was found. ICC proved excellent consistency between readers over two locations: 0.92 for intraobserver and 0.89 for interobserver difference in level 1. and 0.85 and 0.79 in level 2. Multivariate analysis of all these variables showed sac distensibility to be independently related (R2=0.68 to BMI, diastolic blood pressure, and AAA diameter. Conclusions. Aortic distensibility measurement in patients with AAA demonstrated high inter- and intraobserver agreement and may be valuable when choosing the optimal dimensions graft for AAA before endovascular aneurysm repair.

  8. Protein abundance of clinically relevant multidrug transporters along the entire length of the human intestine.

    Science.gov (United States)

    Drozdzik, Marek; Gröer, Christian; Penski, Jette; Lapczuk, Joanna; Ostrowski, Marek; Lai, Yurong; Prasad, Bhagwat; Unadkat, Jashvant D; Siegmund, Werner; Oswald, Stefan

    2014-10-01

    Intestinal transporters are crucial determinants in the oral absorption of many drugs. We therefore studied the mRNA expression (N = 33) and absolute protein content (N = 10) of clinically relevant transporters in healthy epithelium of the duodenum, the proximal and distal jejunum and ileum, and the ascending, transversal, descending, and sigmoidal colon of six organ donors (24-54 years). In the small intestine, the abundance of nearly all studied proteins ranged between 0.2 and 1.6 pmol/mg with the exception of those of OCT3 (intestinal segment. ABCB1, ABCG2, PEPT1, and ASBT were significantly more abundant in jejunum and ileum than in colon. In contrast to this, the level of expression of ABCC2, ABCC3, and OCT3 was found to be highest in colon. Site-dependent differences in the levels of gene and protein expression were observed for ABCB1 and ASBT. Significant correlations between mRNA and protein levels have been found for ABCG2, ASBT, OCT3, and PEPT1 in the small intestine. Our data provide further physiological pieces of the puzzle required to predict intestinal drug absorption in humans.

  9. Misdiagnosis of tuberculosis and the clinical relevance of non-tuberculous mycobacteria in Zambia

    Institute of Scientific and Technical Information of China (English)

    Patricia CAM Buijtels; Michael D Iseman; Shelagh Parkinson; Cas S de Graaff; Henri A Verbrugh; Pieter LC Petit; Dick van Soolingen

    2010-01-01

    Objective:To determine the accuracy of TB diagnosis of TB in Zambia in the era of increasing HIV prevalence. Methods: Sputum of the clinically diagnosed TB cases was additionally subjected to liquid culture and molecular identification. This study distinguished between TB cases confirmed by positive Mycobacterium tuberculosis (M. tuberculosis) cultures and mycobacterial disease caused by non-tuberculous mycobacteria (NTM). Results: Only 49%of the 173 presumptively diagnosed TB cases was M. tuberculosis cultured, while in 13%(22) cases, a combination of M. tuberculosis and NTM was found. In 18%of the patients only NTM were cultured. In 28%, no mycobacteria was cultivable. HIV positive status was correlated with the isolation of NTM (P<0.05). Conclusions:The diagnosis of tuberculosis based on symptoms, sputum smear and/or chest X-ray leads to significant numbers of false-positive TB cases in Zambia, most likely due to the increased prevalence of HIV. The role of NTM in tuberculosis-like disease also seems relevant to the false diagnosis of TB in Zambia.

  10. Fungal Contaminants in Drinking Water Regulation? A Tale of Ecology, Exposure, Purification and Clinical Relevance

    Science.gov (United States)

    Novak Babič, Monika; Gunde-Cimerman, Nina; Vargha, Márta; Tischner, Zsófia; Magyar, Donát; Veríssimo, Cristina; Sabino, Raquel; Viegas, Carla; Meyer, Wieland; Brandão, João

    2017-01-01

    Microbiological drinking water safety is traditionally monitored mainly by bacterial parameters that indicate faecal contamination. These parameters correlate with gastro-intestinal illness, despite the fact that viral agents, resulting from faecal contamination, are usually the cause. This leaves behind microbes that can cause illness other than gastro-intestinal and several emerging pathogens, disregarding non-endemic microbial contaminants and those with recent pathogenic activity reported. This white paper focuses on one group of contaminants known to cause allergies, opportunistic infections and intoxications: Fungi. It presents a review on their occurrence, ecology and physiology. Additionally, factors contributing to their presence in water distribution systems, as well as their effect on water quality are discussed. Presence of opportunistic and pathogenic fungi in drinking water can pose a health risk to consumers due to daily contact with water, via several exposure points, such as drinking and showering. The clinical relevance and influence on human health of the most common fungal contaminants in drinking water is discussed. Our goal with this paper is to place fungal contaminants on the roadmap of evidence based and emerging threats for drinking water quality safety regulations.

  11. Occult hepatitis B virus infection: A complex entity with relevant clinical implications

    Institute of Scientific and Technical Information of China (English)

    Juan Ramon Larrubia

    2011-01-01

    Occult hepatitis B virus (HBV) infection is a world-wide entity, following the geographical distribution of detectable hepatitis B. This entity is defined as the persistence of viral genomes in the liver tissue and in some instances also in the serum, associated to negative HBV surface antigen serology. The molecular basis of the occult infection is related to the life cycle of HBV, which produces a covalently closed circular DNA that persists in the cell nuclei as an episome, and serves as a template for gene transcription. The mechanism responsible for the HBsAg negative status in occult HBV carriers is a strong suppression of viral replication, probably due to the host's immune response, co-infection with other infectious agents and epigenetic factors. There is emerging evidence of the potential clinical relevance of occult HBV infection, since this could be involved in occult HBV transmission through orthotopic liver transplant and blood transfusion, reactivation of HBV infection during immunosuppression, impairing chronic liver disease outcome and acting as a risk factor for hepatocellular carcinoma. Therefore it is important to bear in mind this entity in cryptogenetic liver diseases, hepatitis C virus/HIV infected patients and immunosupressed individuals.It is also necessary to increase our knowledge in this fascinating field to define better strategies to diagnose and treat this infection.

  12. Dose-dependent cytotoxicity of clinically relevant cobalt nanoparticles and ions on macrophages in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Young-Min; Xia Zhidao; Glyn-Jones, Sion; Beard, David; Gill, Harinderjit S; Murray, David W, E-mail: young-min.kwon@ndos.ox.ac.u [Nuffield Department of Orthopaedic Surgery, University of Oxford, Oxford OX3 7LD (United Kingdom)

    2009-04-15

    Despite the satisfactory short-term implant survivorship of metal-on-metal hip resurfacing arthroplasty, periprosthetic soft-tissue masses such as pseudotumours are being increasingly reported. Cytotoxic effects of cobalt or chromium have been suggested to play a role in its aetiology. The aim of this study was to investigate the effects of clinically relevant metal nanoparticles and ions on the viability of macrophages in vitro. A RAW 264.7 murine macrophage cell line was cultured in the presence of either: (1) cobalt, chromium and titanium nanoparticles sized 30-35 nm; or (2) cobalt sulphate and chromium chloride. Two methods were used to quantify cell viability: Alamar Blue assay and Live/Dead assay. The cytotoxicity was observed only with cobalt. Cobalt nanoparticles and ions demonstrated dose-dependent cytotoxic effects on macrophages in vitro: the cytotoxic concentrations of nanoparticles and ions were 1 x 10{sup 12} particles ml{sup -1} and 1000 {mu}M, respectively. The high concentration of cobalt nanoparticles required for cytotoxicity of macrophages in vitro suggests that increased production of cobalt nanoparticles in vivo, due to excessive MoM implant wear, may lead to local adverse biological effects. Therefore, cytotoxicity of high concentrations of metal nanoparticles phagocytosed by macrophages located in the periprosthetic tissues may be an important factor in pathogenesis of pseudotumours.

  13. A clinically relevant model of perinatal global ischemic brain damage in rats.

    Science.gov (United States)

    Yang, Ting; Zhuang, Lei; Terrando, Niccolò; Wu, Xinmin; Jonhson, Mark R; Maze, Mervyn; Ma, Daqing

    2011-04-06

    We have designed a clinically relevant model of perinatal asphyxia providing intrapartum hypoxia in rats. On gestation day 22 SD rats were anesthetized and the uterine horns were exteriorized and placed in a water bath at 37°C for up to 20min. After this, pups were delivered from the uterus and manually stimulated to initiate breathing in an incubator at 37°C for 1 h in air. Brains were harvested and stained with cresyl violet, caspase-3, and TUNEL to detect morphological and apoptotic changes on postnatal days (PND) 1, 3, and 7. Separate cohorts were maintained until PND 50 and tested for learning and memory using Morris water maze (WM). Survival rate was decreased with longer hypoxic time, and 100% mortality was noted when hypoxia time was beyond 18min. Apoptosis was increased with the duration of hypoxia with neuronal loss and cell shrinkage in the CA1 of hippocampus. The time taken for the juveniles to locate the hidden platform during WM was increased in animals subjected to hypoxia. These data demonstrate that perinatal ischemic injury leads to neuronal death in the hippocampus and long-lasting cognitive dysfunction. This model mimics hypoxic ischemic encephalopathy in humans and may be appropriate for investigating therapeutic interventions. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Severe neuromuscular denervation of clinically relevant muscles in a mouse model of spinal muscular atrophy.

    Science.gov (United States)

    Ling, Karen K Y; Gibbs, Rebecca M; Feng, Zhihua; Ko, Chien-Ping

    2012-01-01

    Spinal muscular atrophy (SMA), a motoneuron disease caused by a deficiency of the survival of motor neuron (SMN) protein, is characterized by motoneuron loss and muscle weakness. It remains unclear whether widespread loss of neuromuscular junctions (NMJs) is involved in SMA pathogenesis. We undertook a systematic examination of NMJ innervation patterns in >20 muscles in the SMNΔ7 SMA mouse model. We found that severe denervation (<50% fully innervated endplates) occurs selectively in many vulnerable axial muscles and several appendicular muscles at the disease end stage. Since these vulnerable muscles were located throughout the body and were comprised of varying muscle fiber types, it is unlikely that muscle location or fiber type determines susceptibility to denervation. Furthermore, we found a similar extent of neurofilament accumulation at NMJs in both vulnerable and resistant muscles before the onset of denervation, suggesting that neurofilament accumulation does not predict subsequent NMJ denervation. Since vulnerable muscles were initially innervated, but later denervated, loss of innervation in SMA may be attributed to defects in synapse maintenance. Finally, we found that denervation was amendable by trichostatin A (TSA) treatment, which increased innervation in clinically relevant muscles in TSA-treated SMNΔ7 mice. Our findings suggest that neuromuscular denervation in vulnerable muscles is a widespread pathology in SMA, and can serve as a preparation for elucidating the biological basis of synapse loss, and for evaluating therapeutic efficacy.

  15. On thermionic emission from plasma-facing components in tokamak-relevant conditions

    Science.gov (United States)

    Komm, M.; Ratynskaia, S.; Tolias, P.; Cavalier, J.; Dejarnac, R.; Gunn, J. P.; Podolnik, A.

    2017-09-01

    The first results of particle-in-cell simulations of the electrostatic sheath and magnetic pre-sheath of thermionically emitting planar tungsten surfaces in fusion plasmas are presented. Plasma conditions during edge localized modes (ELMs) and during inter-ELM periods have been considered for various inclinations of the magnetic field and for selected surface temperatures. All runs have been performed under two assumptions for the sheath potential drop; fixed or floating. The primary focus lies on the evaluation of the escaping thermionic current and the quantification of the suppression due to the combined effects of space-charge and Larmor gyration. When applicable, the results are compared with the predictions of analytical models. The heat balance in the presence of thermionic emission as well as the contribution of the escaping thermionic current to surface cooling are also investigated. Regimes are identified where emission needs to be considered in the energy budget.

  16. Experiment on laser interaction with a planar target for conditions relevant to shock ignition

    Science.gov (United States)

    Maheut, Y.; Antonelli, L.; Atzeni, S.; Badziak, J.; Baffigi, F.; Batani, D.; Cecchetti, C.; Chodukowski, T.; Consoli, F.; Cristoforetti, G.; De Angelis, R.; Folpini, G.; Gizzi, L. A.; Kalinowska, Z.; Kucharik, M.; Köster, P.; Krousky, E.; Labate, L.; Levato, T.; Liska, R.; Malka, G.; Marocchino, A.; Nicolaï, P.; O'Dell, T.; Parys, P.; Pisarczyk, T.; Rączka, P.; Renner, O.; Rhee, Y. J.; Ribeyre, X.; Richetta, M.; Rosinski, M.; Ryć, L.; Skala, J.; Schiavi, A.; Schurtz, G.; Smid, M.; Spindloe, C.; Ullschmied, J.; Wolowski, J.; Zaraś, A.

    2014-05-01

    We report the experiment conducted on the Prague Asterix Laser System (PALS) laser facility dedicated to make a parametric study of the laser-plasma interaction under the physical conditions corresponding to shock ignition thermonuclear fusion reactions. Two laser beams have been used: the auxiliary beam, for preplasma creation on the surface of a plastic foil, and the main beam to launch a strong shock. The ablation pressure is inferred from the volume of the crater in the Cu layer situated behind the plastic foil and by shock breakout chronometry. The population of fast electrons is analyzed by Kα emission spectroscopy and imaging. The preplasma is characterized by three-frame interferometry, x-ray spectroscopy and ion diagnostics. The numerical simulations constrained with the measured data gave a maximum pressure in the plastic layer of about 90 Mbar.

  17. Tungsten melt layer erosion due to J x B force under conditions relevant to ITER ELMs

    Energy Technology Data Exchange (ETDEWEB)

    Garkusha, I.E. [Institute of Plasma Physics of the NSC KIPT, Akademicheskaya 1, 61108 Kharkov (Ukraine)]. E-mail: garkusha@ipp.kharkov.ua; Bazylev, B.N. [Forschungszentrum Karlsruhe, IHM, 76021 Karlsruhe (Germany); Bandura, A.N. [Institute of Plasma Physics of the NSC KIPT, Akademicheskaya 1, 61108 Kharkov (Ukraine); Byrka, O.V. [Institute of Plasma Physics of the NSC KIPT, Akademicheskaya 1, 61108 Kharkov (Ukraine); Chebotarev, V.V. [Institute of Plasma Physics of the NSC KIPT, Akademicheskaya 1, 61108 Kharkov (Ukraine); Landman, I.S. [Forschungszentrum Karlsruhe, IHM, 76021 Karlsruhe (Germany); Kulik, N.V. [Institute of Plasma Physics of the NSC KIPT, Akademicheskaya 1, 61108 Kharkov (Ukraine); Makhlaj, V.A. [Institute of Plasma Physics of the NSC KIPT, Akademicheskaya 1, 61108 Kharkov (Ukraine); Petrov, Yu.V. [Institute of Plasma Physics of the NSC KIPT, Akademicheskaya 1, 61108 Kharkov (Ukraine); Solyakov, D.G. [Institute of Plasma Physics of the NSC KIPT, Akademicheskaya 1, 61108 Kharkov (Ukraine); Tereshin, V.I. [Institute of Plasma Physics of the NSC KIPT, Akademicheskaya 1, 61108 Kharkov (Ukraine)

    2007-06-15

    The behavior of tungsten under repetitive hydrogen plasma impacts causing surface melting in conditions of an applied J x B force of up to 20 MN/m{sup 3} is studied with the plasma accelerator QSPA Kh-50. Tungsten samples of EU trademark have been exposed to up to 100 pulses simulating ITER ELMs of the energy load 0.7 MJ/m{sup 2} and the duration 0.25 ms. An electric current J flows across the magnetic field B of 1.4 T, and the resulting J x B force produces a displacement of the melt with formation of an erosion crater and an inclination of the surface profile along the force. Surface morphology and the damage by surface cracks are discussed. Comparisons of experimental results with numerical simulations of the code MEMOS-1.5D are presented.

  18. Relevance of the EMG/grip relationship in isometric anisotonic conditions.

    Science.gov (United States)

    Claudon, Laurent

    2003-01-01

    The aim of the present study was to develop a relationship to evaluate grip force using the electromyogram (EMG) in isometric anisotonic conditions. The EMGs of the flexor digitorum superficialis (FDS) and the extensor digitorum (ED) were recorded in 3 flexion-extension positions of the wrist (30 degrees flexion, 30 degrees extension, and 60 degrees extension) associated with 3 positions of the forearm (70 degrees pronation, prono-supination, and 70 degrees supination). For each position, the participants had to follow linear ramp targets (2 rates of increase and decrease) displayed on an oscilloscope. The results show the best fit is a quadratic type force-EMG relationship. Some aspects such as the rate of force variation and the forearm and wrist positions are then discussed along with the limitations of the relationship.

  19. Assessing the Behavior of Typically Lithophile Elements Under Highly Reducing Conditions Relevant to the Planet Mercury

    Science.gov (United States)

    Rowland, Rick, II; Vander Kaaden, Kathleen E.; McCubbin, Francis M.; Danielson, Lisa R.

    2017-01-01

    With the data returned from the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) mission, there are now numerous constraints on the physical and chemical properties of Mercury, including its surface composition. The high Sand low FeO contents observed from MESSENGER suggest a low oxygen fugacity of the present materials on the planet's surface. Most of our understanding of elemental partitioning behavior comes from observations made on terrestrial rocks, but Mercury's oxygen fugacity is far outside the conditions of those samples, estimated at approximately 3-7 log units below the Iron-Wtistite (lW) oxygen buffer, several orders of magnitude more reducing than other terrestrial bodies we have data from. With limited oxygen available, lithophile elements may instead exhibit chalcophile, halophile, or siderophile behaviors. Furthermore, very few natural samples of rocks that formed under reducing conditions (e.g., enstatite chondrites, achondrites, aubrites) are available in our collections for examination of this change in geochemical affinity. Our goal is to determine the elemental partitioning behavior of typically lithophile elements at lower oxygen fugacity as a function of temperature and pressure. Experiments were conducted at I GPa in a 13 mm QUICKpress piston cylinder and at 4 GPa in an 880-ton multianvil press, at temperatures up to 1850degC. The composition of starting materials for the experiments were designed so the final run products contained metal, silicate melt, and sulfide melt phases. Oxygen fugacity was controlled in the experiments by adding silicon metal to the samples, in order to utilize the Si-Si02 buffer, which is approximately 5 log units more reducing than the IW buffer at our temperatures of interest. The target silicate melt composition was diopside (CaMgSi206) because measured surface compositions indicate partial melting of a pyroxene-rich mantle. The results of our experiments will aid in our understanding of

  20. Formation of stable uranium(VI) colloidal nanoparticles in conditions relevant to radioactive waste disposal.

    Science.gov (United States)

    Bots, Pieter; Morris, Katherine; Hibberd, Rosemary; Law, Gareth T W; Mosselmans, J Frederick W; Brown, Andy P; Doutch, James; Smith, Andrew J; Shaw, Samuel

    2014-12-09

    The favored pathway for disposal of higher activity radioactive wastes is via deep geological disposal. Many geological disposal facility designs include cement in their engineering design. Over the long term, interaction of groundwater with the cement and waste will form a plume of a hyperalkaline leachate (pH 10-13), and the behavior of radionuclides needs to be constrained under these extreme conditions to minimize the environmental hazard from the wastes. For uranium, a key component of many radioactive wastes, thermodynamic modeling predicts that, at high pH, U(VI) solubility will be very low (nM or lower) and controlled by equilibrium with solid phase alkali and alkaline-earth uranates. However, the formation of U(VI) colloids could potentially enhance the mobility of U(VI) under these conditions, and characterizing the potential for formation and medium-term stability of U(VI) colloids is important in underpinning our understanding of U behavior in waste disposal. Reflecting this, we applied conventional geochemical and microscopy techniques combined with synchrotron based in situ and ex situ X-ray techniques (small-angle X-ray scattering and X-ray adsorption spectroscopy (XAS)) to characterize colloidal U(VI) nanoparticles in a synthetic cement leachate (pH > 13) containing 4.2-252 μM U(VI). The results show that in cement leachates with 42 μM U(VI), colloids formed within hours and remained stable for several years. The colloids consisted of 1.5-1.8 nm nanoparticles with a proportion forming 20-60 nm aggregates. Using XAS and electron microscopy, we were able to determine that the colloidal nanoparticles had a clarkeite (sodium-uranate)-type crystallographic structure. The presented results have clear and hitherto unrecognized implications for the mobility of U(VI) in cementitious environments, in particular those associated with the geological disposal of nuclear waste.

  1. Biosafety evaluations of well-dispersed mesoporous silica nanoparticles: towards in vivo-relevant conditions

    Science.gov (United States)

    Liu, Tsang-Pai; Wu, Si-Han; Chen, Yi-Ping; Chou, Chih-Ming; Chen, Chien-Tsu

    2015-04-01

    This study aimed to investigate how mesoporous silica nanoparticles (MSNs), especially focussing on their surface functional groups, interacted with Raw 264.7 macrophages, as well as with zebrafish embryos. Upon introducing nanoparticles into a biological milieu, adsorption of proteins and biomolecules onto the nanoparticle surface usually progresses rapidly. Nanoparticles bound with proteins can result in physiological and pathological changes, but the mechanisms remain to be elucidated. In order to evaluate how protein corona affected MSNs and the subsequent cellular immune responses, we experimented in both serum and serum-deprived conditions. Our findings indicated that the level of p-p38 was significantly elevated by the positively charged MSNs, whereas negatively charged MSNs resulted in marked ROS production. Most significantly, our experiments demonstrated that the presence of protein efficiently mitigated the potential nano-hazard. On the other hand, strongly positively charged MSNs caused 94% of the zebrafish embryos to die. In that case, the toxicity caused by the quaternary ammonium ligands on the surface of those nanoparticles was exerted in a dose-dependent manner. In summary, these fundamental studies here provide valuable insights into the design of better biocompatible nanomaterials in the future.This study aimed to investigate how mesoporous silica nanoparticles (MSNs), especially focussing on their surface functional groups, interacted with Raw 264.7 macrophages, as well as with zebrafish embryos. Upon introducing nanoparticles into a biological milieu, adsorption of proteins and biomolecules onto the nanoparticle surface usually progresses rapidly. Nanoparticles bound with proteins can result in physiological and pathological changes, but the mechanisms remain to be elucidated. In order to evaluate how protein corona affected MSNs and the subsequent cellular immune responses, we experimented in both serum and serum-deprived conditions. Our

  2. Locating relevant patient information in electronic health record data using representations of clinical concepts and database structures.

    Science.gov (United States)

    Pan, Xuequn; Cimino, James J

    2014-01-01

    Clinicians and clinical researchers often seek information in electronic health records (EHRs) that are relevant to some concept of interest, such as a disease or finding. The heterogeneous nature of EHRs can complicate retrieval, risking incomplete results. We frame this problem as the presence of two gaps: 1) a gap between clinical concepts and their representations in EHR data and 2) a gap between data representations and their locations within EHR data structures. We bridge these gaps with a knowledge structure that comprises relationships among clinical concepts (including concepts of interest and concepts that may be instantiated in EHR data) and relationships between clinical concepts and the database structures. We make use of available knowledge resources to develop a reproducible, scalable process for creating a knowledge base that can support automated query expansion from a clinical concept to all relevant EHR data.

  3. Iron and Nickel spectral opacity calculations in conditions relevant for pulsating stellar envelopes and experiments

    Directory of Open Access Journals (Sweden)

    Gilles D.

    2013-11-01

    Full Text Available Seismology of stars is strongly developing. To address this question we have formed an international collaboration, OPAC, to perform specific experimental measurements, compare opacity calculations, and improve the opacity calculations in stellar codes [1]. We consider the following opacity codes: SCO, CASSANDRA, STA, OPAS, LEDCOP, OP, SCO-RCG. Their comparison has shown large differences for Fe and Ni in equivalent conditions of envelopes of type II supernova precursors, temperatures between 15 and 40 eV and densities of a few mg/cm3 [2–4]. LEDCOP, OPAS, SCO-RCG structure codes and STA give similar results and differ from OP ones for the lower temperatures and for spectral interval values [3]. In this work we discuss the role of Configuration Interaction (CI and the influence of the number of used configurations. We present and include in the opacity code comparisons new HULLAC-v9 calculations [5, 6] that include full CI. To illustrate the importance of this effect we compare different CI approximations (modes available in HULLAC-v9 [7]. These results are compared to previous predictions and to experimental data. Differences with OP results are discussed.

  4. Iron and Nickel spectral opacity calculations in conditions relevant for pulsating stellar envelopes and experiments

    CERN Document Server

    Gilles, D; Busquet, M; Thais, F; Loisel, G; Piau, L; Ducret, J E; Blenski, T; Blancard, C; Cossé, P; Faussurier, G; Gilleron, F; Pain, J C; Porcherot, Q; Guzik, J A; Kilcrease, D P; Magee, N H; Harris, J; Bastiani-Ceccotti, S; Delahaye, F; Zeippen, C J

    2012-01-01

    Seismology of stars is strongly developing. To address this question we have formed an international collaboration OPAC to perform specific experimental measurements, compare opacity calculations and improve the opacity calculations in the stellar codes [1]. We consider the following opacity codes: SCO, CASSANDRA, STA, OPAS, LEDCOP, OP, SCO-RCG. Their comparison has shown large differences for Fe and Ni in equivalent conditions of envelopes of type II supernova precursors, temperatures between 15 and 40 eV and densities of a few mg/cm3 [2, 3, 4]. LEDCOP, OPAS, SCO-RCG structure codes and STA give similar results and differ from OP ones for the lower temperatures and for spectral interval values [3]. In this work we discuss the role of Configuration Interaction (CI) and the influence of the number of used configurations. We present and include in the opacity code comparisons new HULLAC-v9 calculations [5, 6] that include full CI. To illustrate the importance of this effect we compare different CI approximation...

  5. Clinical relevance of antiphospholipid antibodies in systemic sclerosis: A systematic review and meta-analysis.

    Science.gov (United States)

    Merashli, Mira; Alves, Jose'Delgado; Ames, Paul R J

    2017-04-01

    To evaluate the clinical relevance of antiphospholipid antibodies (aPL) in systemic sclerosis (SSc). A systematic search of EMBASE and PubMed databases from January 1983 to July 2016 was carried out according to PRISMA guidelines whereas Peto׳s odds ratio (OR) for rare events was used for the meta-analysis. The pooled prevalence of participants positive for IgG and IgM anticardiolipin (aCL) antibodies was higher in SSc than controls (12.8% vs 1.6% and 7.8% vs 0.6%; p < 0.0001 for both) as was that of IgG and IgM anti-beta-2-glycoprotein-I antibodies (aβ2GPI) (6.1% vs 0.58%, p < 0.0001; 3.5% vs 0.3%, p = 0.001). The pooled prevalence of pulmonary arterial hypertension (PAH) was more common in SSc positive than negative patients for aCL (IgG/IgM combined) (26.5% vs 10.9%, p < 0.0001) whereas the pooled prevalence of renal disease (RD) was more common in IgG aCL positive than negative patients (36.3% vs 10.9%, p = 0.02). The pooled prevalence of thrombosis was higher in IgG aCL, IgM aCL, and IgM aβ2GPI positive than negative SSc patients (12.6% vs 1.4%, p < 0.0001), (15.1% vs 2.7%, p = 0.002) and (15% vs 0.78%, p = 0.009), respectively. The pooled prevalence of digital infarction/ischemia (DI) was higher in IgG aCL and IgM positive than negative SSc (52.8% vs 39.8%, p = 0.002) and (68.1% vs 29%, p = 0.07). A strong relationship exists between aCL and aβ2GPI of IgG/IgM isotype and SSc; patients positive for these antibodies are more likely to suffer from PAH, RD, thrombosis, and DI. However, data expressed as frequency of aPL positive patients rather than average antibody titers preclude further insight into the relevance of these assumptions. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. The conditions and course of clinically induced phonological change.

    Science.gov (United States)

    Gierut, J A

    1992-10-01

    This two-part study continued the evaluation of minimal pair treatment in phonological change (Gierut, 1989, 1990, 1991a; Gierut & Neumann, 1992). Three linguistic variables relevant to change were experimentally manipulated within an alternating treatments design to determine specifically the interplay of a maximal number of feature distinctions, feature class, and relationship of treated phonemes to a child's grammar in inducing sound change. The conditions of treatment that were shown to facilitate optimal phonological change in previous research were again experimentally replicated. Specifically, minimal pairs comparing two phonemes previously unknown to a child that also differed by maximal and major class features were found to be the preferred context motivating change. Important individual differences emerged and underscored the role of a child's pretreatment grammar in phonological change. These differences contributed to descriptions of possible courses of change followed by children with phonological disorders and bear upon the predictability of change and the effectiveness of treatments that may condition change.

  7. Clinical conditions and memory complaints in outpatient elderly

    Directory of Open Access Journals (Sweden)

    Regina Miksian Magaldi

    Full Text Available Abstract Memory complaints are common in elderly, and may be associated with many clinical problems. Objective: To identify clinical conditions and possible factors related to memory complaints in elderly outpatients presenting at a tertiary unit. Methods: Patients with memory complaints and normal cognitive screening tests were submitted to clinical and laboratorial testing. Radiological evaluation was performed as needed for diagnosis. Results: One hundred and seventy-seven subjects were initially evaluated, 12 were excluded because of poor and inconsistent memory complaints. Of the remainder, seventeen had criteria for dementia diagnosis. Ninety-two (55.4% had one or more comorbid conditions possibly related to their complaints. Major depression was present in 26.0%. Sixteen patients (9.6% had vitamin B12 deficiency, 8 were in use of inappropriate medications, and 7 (4.2% had hypothyroidism. Other conditions diagnosed were: generalized anxiety disorder, obstructive sleep apnea syndrome, hyperparathyroidism, normal pressure hydrocephalus. Three patients had severe hearing loss (in 22 with hearing complaints; one had severe visual impairment (in 22 with visual complaints. Conclusions: Comprehensive evaluation was able to identify treatable conditions possibly related to memory complaints.

  8. The materials irradiation experiment for testing plasma facing materials at fusion relevant conditions

    Science.gov (United States)

    Garrison, L. M.; Zenobia, S. J.; Egle, B. J.; Kulcinski, G. L.; Santarius, J. F.

    2016-08-01

    The Materials Irradiation Experiment (MITE-E) was constructed at the University of Wisconsin-Madison Inertial Electrostatic Confinement Laboratory to test materials for potential use as plasma-facing materials (PFMs) in fusion reactors. PFMs in fusion reactors will be bombarded with x-rays, neutrons, and ions of hydrogen and helium. More needs to be understood about the interactions between the plasma and the materials to validate their use for fusion reactors. The MITE-E simulates some of the fusion reactor conditions by holding samples at temperatures up to 1000 °C while irradiating them with helium or deuterium ions with energies from 10 to 150 keV. The ion gun can irradiate the samples with ion currents of 20 μA-500 μA; the typical current used is 72 μA, which is an average flux of 9 × 1014 ions/(cm2 s). The ion gun uses electrostatic lenses to extract and shape the ion beam. A variable power (1-20 W), steady-state, Nd:YAG laser provides additional heating to maintain a constant sample temperature during irradiations. The ion beam current reaching the sample is directly measured and monitored in real-time during irradiations. The ion beam profile has been investigated using a copper sample sputtering experiment. The MITE-E has successfully been used to irradiate polycrystalline and single crystal tungsten samples with helium ions and will continue to be a source of important data for plasma interactions with materials.

  9. Dynamic outgassing of deuterium, helium and nitrogen from plasma-facing materials under DEMO relevant conditions

    Science.gov (United States)

    Möller, S.; Matveev, D.; Martynova, Y.; Unterberg, B.; Rasinski, M.; Wegener, T.; Kreter, A.; Linsmeier, Ch.

    2017-01-01

    In confined plasma magnetic fusion devices significant amounts of the hydrogen isotopes used for the fusion reaction can be stored in the plasma-facing materials by implantation. The desorption of this retained hydrogen was seen to follow a t α law with α  ≈  -0.7 in tokamaks. For a pulsed fusion reactor this outgassing can define the inter-pulse waiting time. This work presents new experimental data on the dynamic outgassing in ITER grade tungsten exposed under the well-defined conditions of PSI-2 to pure and mixed D2 plasmas. A peak ion flux of 1022 D+ m-2 s is applied for up to 6 h at sample temperatures of up to 900 K. Pure D2 and mixed D2  +  He, D2  +  N2 and D2  +  He  +  N2 plasmas are applied to the sample at 68 V bias. The D2, He, N outgassing at 293 K and 580 k are observed via in-vacuo quadrupole mass spectrometry covering the range of 40 s-200 000 s after exposure. The outgassing decay follows a single power law with exponents α  =  -0.7  to  -1.1 at 293 K, but at 580 K a drop from α  =  -0.25 to  -2.35 is found. For DEMO a pump-down time to 0.5 mPa in the order of 1-5 h can be expected. The outgassing is in all cases dominated by D2.

  10. Investigating the laser heating of underdense plasmas at conditions relevant to MagLIF

    Science.gov (United States)

    Harvey-Thompson, Adam

    2015-11-01

    The magnetized Liner Inertial Fusion (MagLIF) scheme has achieved thermonuclear fusion yields on Sandia's Z Facility by imploding a cylindrical liner filled with D2 fuel that is preheated with a multi-kJ laser and pre-magnetized with an axial field Bz = 10 T. The challenge of fuel preheating in MagLIF is to deposit several kJ's of energy into an underdense (ne/ncritMagLIF. In particular, magnetization of the preheated plasma suppresses electron thermal conduction, which can modify laser energy coupling. Providing an experimental dataset in this regime is essential to not only understand the dynamics of a MagLIF implosion and stagnation, but also to validate magnetized transport models and better understand the physics of laser propagation in magnetized plasmas. In this talk, we present data and analysis of several experiments conducted at OMEGA-EP and at Z to investigate laser propagation and plasma heating in underdense D2 plasmas under a range of conditions, including densities (ne = 0.05-0.1 nc) and magnetization parmaters (ωceτe ~ 0-10). The results show differences in the electron temperature of the heated plasma and the velocity of the laser burn wave with and without an applied magnetic field. We will show comparisons of these experimental results to 2D and 3D HYDRA simulations, which show that the effect of the magnetic field on the electron thermal conduction needs to be taken into account when modeling laser preheat. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the National Nuclear Security Administration under Contract No. DE-AC04-94AL85000.

  11. A clinical report of Type III dens invaginatus: relevant aspects of a combined therapeutic approach.

    Science.gov (United States)

    Silva E Souza, Patricia de Almeida Rodrigues; de Almeida, Bruno Vila Nova; Tartari, Talita; Alves, Ana Claudia Braga Amoras; Tuji, Farbicio Mesquita; Silva E Souza, Mario Honorato

    2013-01-01

    Dens invaginatus is a developmental abnormality that alters dental morphology; as a result, treating this condition is a challenge for endodontic practices. This article describes how a combination of nonsurgical and surgical therapies was utilized to treat a maxillary central incisor with Type III dens invaginatus and vital pulp. The treatment plan included using computed tomography (CT) for a detailed analysis of the dental anatomy and periapical area, endodontic and surgical procedures, and a 4-year follow-up period that included periodic clinical and radiographic examinations. The follow-up examinations revealed a regression of the apical lesion and no other signs or symptoms. Based on the present case report, the authors concluded that this combination of surgical and nonsurgical approaches was effective and that CT is a valuable auxiliary tool for the study of dental anatomy.

  12. Modeling the Relationship between Vibration Features and Condition Parameters Using Relevance Vector Machines for Health Monitoring of Rolling Element Bearings under Varying Operation Conditions

    Directory of Open Access Journals (Sweden)

    Lei Hu

    2015-01-01

    Full Text Available Rotational speed and load usually change when rotating machinery works. Both this kind of changing operational conditions and machine fault could make the mechanical vibration characteristics change. Therefore, effective health monitoring method for rotating machinery must be able to adjust during the change of operational conditions. This paper presents an adaptive threshold model for the health monitoring of bearings under changing operational conditions. Relevance vector machines (RVMs are used for regression of the relationships between the adaptive parameters of the threshold model and the statistical characteristics of vibration features. The adaptive threshold model is constructed based on these relationships. The health status of bearings can be indicated via detecting whether vibration features exceed the adaptive threshold. This method is validated on bearings running at changing speeds. The monitoring results show that this method is effective as long as the rotational speed is higher than a relative small value.

  13. Cost-effective multiplexing before capture allows screening of 25 000 clinically relevant SNPs in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Wesolowska, Agata; Dalgaard, M. D.; Borst, L.;

    2011-01-01

    a model disease for exploring the impact of genetic variation due to well-characterized cytogenetics, drug response pathways and precise monitoring of minimal residual disease. Here, we have selected clinically relevant genes and SNPs through literature screening, and on the basis of associations with key...... designed a cost-effective, high-throughput capture assay of â¼25â000 clinically relevant SNPs, and demonstrated that multiple samples can be tagged and pooled before genome capture in targeted enrichment with a sufficient sequencing depth for genotyping. This multiplexed, targeted sequencing method allows...

  14. Sequence selective recognition of double-stranded RNA at physiologically relevant conditions using PNA-peptide conjugates.

    Science.gov (United States)

    Muse, Oluwatoyosi; Zengeya, Thomas; Mwaura, Juddy; Hnedzko, Dziyana; McGee, Dennis W; Grewer, Christof T; Rozners, Eriks

    2013-08-16

    Conjugation of short peptide nucleic acids (PNA) with tetralysine peptides strongly enhanced triple helical binding to RNA at physiologically relevant conditions. The PNA hexamers and heptamers carrying cationic nucleobase and tetralysine modifications displayed high binding affinity for complementary double-stranded RNA without compromising sequence selectivity. The PNA-peptide conjugates had unique preference for binding double-stranded RNA, while having little, if any, affinity for double-stranded DNA. The cationic PNAs were efficiently taken up by HEK293 cells, whereas little uptake was observed for unmodified PNA.

  15. Anatomical masking of pressure footprints based on the Oxford Foot Model: validation and clinical relevance.

    Science.gov (United States)

    Giacomozzi, Claudia; Stebbins, Julie A

    2017-03-01

    Plantar pressure analysis is widely used in the assessment of foot function. In order to assess regional loading, a mask is applied to the footprint to sub-divide it into regions of interest (ROIs). The most common masking method is based on geometric features of the footprint (GM). Footprint masking based on anatomical landmarks of the foot has been implemented more recently, and involves the integration of a 3D motion capture system, plantar pressure measurement device, and a multi-segment foot model. However, thorough validation of anatomical masking (AM) using pathological footprints has not yet been presented. In the present study, an AM method based on the Oxford Foot Model (OFM) was compared to an equivalent GM. Pressure footprints from 20 young healthy subjects (HG) and 20 patients with clubfoot (CF) were anatomically divided into 5 ROIs using a subset of the OFM markers. The same foot regions were also identified by using a standard GM method. Comparisons of intra-subject coefficient of variation (CV) showed that the OFM-based AM was at least as reliable as the GM for all investigated pressure parameters in all foot regions. Clinical relevance of AM was investigated by comparing footprints from HG and CF groups. Contact time, maximum force, force-time integral and contact area proved to be sensitive parameters that were able to distinguish HG and CF groups, using both AM and GM methods However, the AM method revealed statistically significant differences between groups in 75% of measured variables, compared to 62% using a standard GM method, indicating that the AM method is more sensitive for revealing differences between groups. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Human Y chromosome microdeletion analysis by PCR multiplex protocols identifying only clinically relevant AZF microdeletions.

    Science.gov (United States)

    Vogt, Peter H; Bender, Ulrike

    2013-01-01

    PCR multiplex assays are the method of choice for quickly revealing genomic microdeletions in the large repetitive genomic sequence blocks on the long arm of the human Y chromosome. They harbor the Azoospermia Factor (AZF) genes, which cause male infertility when functionally disrupted. These protein encoding Y genes are expressed exclusively or predominantly during male germ cell development, i.e., at different phases of human spermatogenesis. They are located in three distinct genomic sequence regions designated AZFa, AZFb, and AZFc, respectively. Complete deletion of an AZF region, also called "classical" AZF microdeletion, is always associated with male infertility and a distinct testicular pathology. Partial AZF deletions including single AZF Y genes can cause the same testicular pathology as the corresponding complete deletion (e.g., DDX3Y gene deletions in AZFa), or might not be associated with male infertility at all (e.g., some BPY2, CDY1, DAZ gene deletions in AZFc). We therefore propose that a PCR multiplex assay aimed to reduce only those AZF microdeletions causing a specific testicular pathology-thus relevant for clinical applications. It only includes Sequence Tagged Site (STS) deletion markers inside the exon structures of the Y genes known to be expressed in male germ cells and located in the three AZF regions. They were integrated in a robust standard protocol for four PCR multiplex mixtures which also include the basic principles of quality control according to the strict guidelines of the European Molecular Genetics Quality Network (EMQN: http://www.emqn.org). In case all Y genes of one AZF region are deleted the molecular extension of this AZF microdeletion is diagnosed to be yes or no comparable to that of the "classical" AZF microdeletion by an additional PCR multiplex assay analyzing the putative AZF breakpoint borderlines.

  17. Molecular Mechanisms of Glutamine Synthetase Mutations that Lead to Clinically Relevant Pathologies.

    Directory of Open Access Journals (Sweden)

    Benedikt Frieg

    2016-02-01

    Full Text Available Glutamine synthetase (GS catalyzes ATP-dependent ligation of ammonia and glutamate to glutamine. Two mutations of human GS (R324C and R341C were connected to congenital glutamine deficiency with severe brain malformations resulting in neonatal death. Another GS mutation (R324S was identified in a neurologically compromised patient. However, the molecular mechanisms underlying the impairment of GS activity by these mutations have remained elusive. Molecular dynamics simulations, free energy calculations, and rigidity analyses suggest that all three mutations influence the first step of GS catalytic cycle. The R324S and R324C mutations deteriorate GS catalytic activity due to loss of direct interactions with ATP. As to R324S, indirect, water-mediated interactions reduce this effect, which may explain the suggested higher GS residual activity. The R341C mutation weakens ATP binding by destabilizing the interacting residue R340 in the apo state of GS. Additionally, the mutation is predicted to result in a significant destabilization of helix H8, which should negatively affect glutamate binding. This prediction was tested in HEK293 cells overexpressing GS by dot-blot analysis: Structural stability of H8 was impaired through mutation of amino acids interacting with R341, as indicated by a loss of masking of an epitope in the glutamate binding pocket for a monoclonal anti-GS antibody by L-methionine-S-sulfoximine; in contrast, cells transfected with wild type GS showed the masking. Our analyses reveal complex molecular effects underlying impaired GS catalytic activity in three clinically relevant mutants. Our findings could stimulate the development of ATP binding-enhancing molecules by which the R324S mutant can be repaired extrinsically.

  18. No clinically relevant interaction between sugammadex and aspirin on platelet aggregation and coagulation parameters.

    Science.gov (United States)

    de Kam, Pieter-Jan; El Galta, Rachid; Kruithof, Annelieke C; Fennema, Hein; van Lierop, Marie-José; Mihara, Katsuhiro; Burggraaf, Jacobus; Moerland, Matthijs; Peeters, Pierre; Troyer, Matthew D

    2013-12-01

    This study evaluated interaction potential between sugammadex and aspirin on platelet aggregation. This was a randomized, double-blind, placebo-controlled, four-period crossover study in 26 healthy adult males. Treatments were i.v. placebo, i.v. sugammadex 4 mg/kg, and i.v. placebo/sugammadex with oncedaily oral aspirin 75 mg. Primary objective was to assess interaction between sugammadex and aspirin on platelet aggregation using collagen-induced whole-blood aggregometry. Effects on activated partial thromboplastin time (APTT) and cutaneous bleeding time were also evaluated. Platelet aggregation and APTT were evaluated by geometric mean ratios, using area-under-effect curves 3 - 30 minutes after sugammadex/placebo dosing. Bleeding time ratio was evaluated at 5 minutes post-dosing. Non-inferiority margins were pre-specified via literature review. Type I error was controlled using a hierarchical strategy. Ratio for platelet aggregation for aspirin with sugammadex vs. aspirin alone was 1.01, with lower limit of two-sided 90% CI of 0.91(above non-inferiority margin of 0.75). Ratio for statistical interaction between sugammadex and aspirin on APTT was 1.01, with upper 90% CI of 1.04 (below non-inferiority margin of 1.50), and for sugammadex vs. placebo alone was 1.06, with an upper 90% CI of 1.07 (below non-inferiority margin of 1.50). Ratio for bleeding time for aspirin with sugammadex vs. aspirin plus placebo was 1.20, with upper 90% CI of 1.45 (below non-inferiority margin of 1.50). Sugammadex was generally well tolerated. There was no clinically relevant reduction in platelet aggregation with addition of sugammadex 4 mg/kg to aspirin. Pre-determined non-inferiority margins were not exceeded for bleeding time and APTT.

  19. Observed inter-camera variability of clinically relevant performance characteristics for Siemens Symbia gamma cameras.

    Science.gov (United States)

    Kappadath, S Cheenu; Erwin, William D; Wendt, Richard E

    2006-11-28

    We conducted an evaluation of the intercamera (i.e., between cameras) variability in clinically relevant performance characteristics for Symbia gamma cameras (Siemens Medical Solutions, Malvern, PA) based on measurements made using nine separate systems. The significance of the observed intercamera variability was determined by comparing it to the intracamera (i.e., within a single camera) variability. Measurements of performance characteristics were based on the standards of the National Electrical Manufacturers Association and reports 6, 9, 22, and 52 from the American Association of Physicists in Medicine. All measurements were performed using 99mTc (except 57Co used for extrinsic resolution) and low-energy, high-resolution collimation. Of the nine cameras, four have crystals 3/8 in. thick and five have crystals 5/8 in. thick. We evaluated intrinsic energy resolution, intrinsic and extrinsic spatial resolution, intrinsic integral and differential flood uniformity over the useful field-of-view, count rate at 20% count loss, planar sensitivity, single-photon emission computed tomography (SPECT) resolution, and SPECT integral uniformity. The intracamera variability was estimated by repeated measurements of the performance characteristics on a single system. The significance of the observed intercamera variability was evaluated using the two-tailed F distribution. The planar sensitivity of the gamma cameras tested was found be variable at the 99.8% confidence level for both the 3/8-in. and 5/8-in. crystal systems. The integral uniformity and energy resolution were found to be variable only for the 5/8-in. crystal systems at the 98% and 90% confidence level, respectively. All other performance characteristics tested exhibited no significant variability between camera systems. The measured variability reported here could perhaps be used to define nominal performance values of Symbia gamma cameras for planar and SPECT imaging.

  20. Molecular Mechanisms of Glutamine Synthetase Mutations that Lead to Clinically Relevant Pathologies.

    Science.gov (United States)

    Frieg, Benedikt; Görg, Boris; Homeyer, Nadine; Keitel, Verena; Häussinger, Dieter; Gohlke, Holger

    2016-02-01

    Glutamine synthetase (GS) catalyzes ATP-dependent ligation of ammonia and glutamate to glutamine. Two mutations of human GS (R324C and R341C) were connected to congenital glutamine deficiency with severe brain malformations resulting in neonatal death. Another GS mutation (R324S) was identified in a neurologically compromised patient. However, the molecular mechanisms underlying the impairment of GS activity by these mutations have remained elusive. Molecular dynamics simulations, free energy calculations, and rigidity analyses suggest that all three mutations influence the first step of GS catalytic cycle. The R324S and R324C mutations deteriorate GS catalytic activity due to loss of direct interactions with ATP. As to R324S, indirect, water-mediated interactions reduce this effect, which may explain the suggested higher GS residual activity. The R341C mutation weakens ATP binding by destabilizing the interacting residue R340 in the apo state of GS. Additionally, the mutation is predicted to result in a significant destabilization of helix H8, which should negatively affect glutamate binding. This prediction was tested in HEK293 cells overexpressing GS by dot-blot analysis: Structural stability of H8 was impaired through mutation of amino acids interacting with R341, as indicated by a loss of masking of an epitope in the glutamate binding pocket for a monoclonal anti-GS antibody by L-methionine-S-sulfoximine; in contrast, cells transfected with wild type GS showed the masking. Our analyses reveal complex molecular effects underlying impaired GS catalytic activity in three clinically relevant mutants. Our findings could stimulate the development of ATP binding-enhancing molecules by which the R324S mutant can be repaired extrinsically.

  1. Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer

    Directory of Open Access Journals (Sweden)

    Schillaci Roxana

    2012-02-01

    Full Text Available Abstract Background The biological relevance of nuclear ErbB-2/HER2 (NuclErbB-2 presence in breast tumors remains unexplored. In this study we assessed the clinical significance of ErbB-2 nuclear localization in primary invasive breast cancer. The reporting recommendations for tumor marker prognostic studies (REMARK guidelines were used as reference. Methods Tissue microarrays from a cohort of 273 primary invasive breast carcinomas from women living in Chile, a Latin American country, were examined for membrane (MembErbB-2 and NuclErbB-2 expression by an immunofluorescence (IF protocol we developed. ErbB-2 expression was also evaluated by immunohistochemistry (IHC with a series of antibodies. Correlation between NuclErbB-2 and MembErbB-2, and between NuclErbB-2 and clinicopathological characteristics of tumors was studied. The prognostic value of NuclErbB-2 in overall survival (OS was evaluated using Kaplan-Meier method, and Cox model was used to explore NuclErbB-2 as independent prognostic factor for OS. Results The IF protocol we developed showed significantly higher sensitivity for detection of NuclErbB-2 than IHC procedures, while its specificity and sensitivity to detect MembErbB-2 were comparable to those of IHC procedures. We found 33.6% NuclErbB-2 positivity, 14.2% MembErbB-2 overexpression by IF, and 13.0% MembErbB-2 prevalence by IHC in our cohort. We identified NuclErbB-2 positivity as a significant independent predictor of worse OS in patients with MembErbB-2 overexpression. NuclErbB-2 was also a biomarker of lower OS in tumors that overexpress MembErbB-2 and lack steroid hormone receptors. Conclusions We revealed a novel role for NuclErbB-2 as an independent prognostic factor of poor clinical outcome in MembErbB-2-positive breast tumors. Our work indicates that patients presenting NuclErbB-2 may need new therapeutic strategies involving specific blockage of ErbB-2 nuclear migration.

  2. Clinical conditions associated withintestinal strongyloidiasis in Rio de Janeiro, Brazil

    Directory of Open Access Journals (Sweden)

    Anna Caryna Cabral

    2015-06-01

    Full Text Available INTRODUCTION: Strongyloides stercoralis is a soil-transmitted helminth that produces an infection that can persist for decades. The relationships between certain clinical conditions and strongyloidiasis remains controversial. This study aims to identify the clinical conditions associated with intestinal strongyloidiasis at a reference center for infectious diseases in Rio de Janeiro, Brazil. METHODS: The clinical conditions that were assessed included HIV/AIDS, HTLV infection, cardiovascular diseases, diabetes, obstructive respiratory diseases, viral hepatitis, tuberculosis, cancer, chronic renal disease, nutritional/metabolic disorders, psychiatric conditions, rheumatic diseases and dermatologic diseases. We compared 167 S. stercoralis-positive and 133 S. stercoralis-negative patients. RESULTS: After controlling for sex (male/female OR = 2.29; 95% (CI: (1.42 - 3.70, rheumatic diseases remained significantly associated with intestinal strongyloidiasis (OR: 4.96; 95% CI: 1.34-18.37 in a multiple logistic regression model. With respect to leukocyte counts, patients with strongyloidiasis presented with significantly higher relative eosinophil (10.32% ± 7.2 vs. 4.23% ± 2.92 and monocyte (8.49% ± 7.25 vs. 5.39% ± 4.31 counts and lower segmented neutrophil (52.85% ± 15.31 vs. 61.32% ± 11.4 and lymphocyte counts (28.11% ± 9.72 vs. 30.90% ± 9.51 than S. stercoralis-negative patients. CONCLUSIONS: Strongyloidiasis should be routinely investigated in hospitalized patients with complex conditions facilitate the treatment of patients who will undergo immunosuppressive therapy. Diagnoses should be determined through the use of appropriate parasitological methods, such as the Baermann-Moraes technique.

  3. Clonal spread and interspecies transmission of clinically relevant ESBL-producing Escherichia coli of ST410--another successful pandemic clone?

    Science.gov (United States)

    Schaufler, Katharina; Semmler, Torsten; Wieler, Lothar H; Wöhrmann, Michael; Baddam, Ramani; Ahmed, Niyaz; Müller, Kerstin; Kola, Axel; Fruth, Angelika; Ewers, Christa; Guenther, Sebastian

    2016-01-01

    Clinically relevant extended-spectrum beta-lactamase (ESBL)-producing multi-resistant Escherichia coli have been on the rise for years. Initially restricted to mostly a clinical context, recent findings prove their prevalence in extraclinical settings independent of the original occurrence of antimicrobial resistance in the environment. To get further insights into the complex ecology of potentially clinically relevant ESBL-producing E. coli, 24 isolates from wild birds in Berlin, Germany, and 40 ESBL-producing human clinical E. coli isolates were comparatively analyzed. Isolates of ST410 occurred in both sample groups (six). In addition, three ESBL-producing E. coli isolates of ST410 from environmental dog feces and one clinical dog isolate were included. All 10 isolates were clonally analyzed showing almost identical macrorestriction patterns. They were chosen for whole-genome sequencing revealing that the whole-genome content of these 10 E. coli isolates showed a very high genetic similarity, differing by low numbers of single nucleotide polymorphisms only. This study gives initial evidence for a recent interspecies transmission of a new successful clone of ST410 E. coli between wildlife, humans, companion animals and the environment. The results underline the zoonotic potential of clinically relevant multi-resistant bacteria found in the environment as well as the mandatory nature of the 'One Health' approach.

  4. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network.

    Science.gov (United States)

    van de Donk, Niels W C J; Palumbo, Antonio; Johnsen, Hans Erik; Engelhardt, Monika; Gay, Francesca; Gregersen, Henrik; Hajek, Roman; Kleber, Martina; Ludwig, Heinz; Morgan, Gareth; Musto, Pellegrino; Plesner, Torben; Sezer, Orhan; Terpos, Evangelos; Waage, Anders; Zweegman, Sonja; Einsele, Hermann; Sonneveld, Pieter; Lokhorst, Henk M

    2014-06-01

    Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; light-chain monoclonal gammopathy of undetermined significance of light-chain multiple myeloma; and IgM monoclonal gammopathy of undetermined significance of Waldenström's macroglobulinemia and other lymphoproliferative disorders. Clonal burden, as determined by bone marrow plasma cell percentage or M-protein level, as well as biological characteristics, including heavy chain isotype and light chain production, are helpful in predicting risk of progression of monoclonal gammopathy of undetermined significance to symptomatic disease. Furthermore, alterations in the bone marrow microenvironment of monoclonal gammopathy of undetermined significance patients result in an increased risk of venous and arterial thrombosis, infections, osteoporosis, and bone fractures. In addition, the small clone may occasionally be responsible for severe organ damage through the production of a monoclonal protein that has autoantibody activity or deposits in tissues. These disorders are rare and often require therapy directed at eradication of the underlying plasma cell or lymphoplasmacytic clone. In this review, we provide an overview of the clinical relevance of monoclonal gammopathy of undetermined significance. We also give general recommendations of how to diagnose and manage patients with monoclonal gammopathy of undetermined significance. Copyright© Ferrata Storti Foundation.

  5. Effect of specific or random c-DNA priming on sensitivity of tyrosinase nested RT-PCR : Potential clinical relevance

    NARCIS (Netherlands)

    Calogero, A; Hospers, GAP; Timmer-Bosscha, H; Mulder, NH; Schraffordt Koops, H.

    2000-01-01

    The reverse transcriptase polymerase chain reaction (RT-PCR) can be of clinical relevance in identifying malignant melanoma cells in blood or tissues of patients at risk for disseminated melanoma. The diagnostic value of this marker however, is still controversial. The objective of this study was to

  6. Potential causative agents of acute gastroenteritis in households with preschool children : prevalence, risk factors, clinical relevance and household transmission

    NARCIS (Netherlands)

    Heusinkveld, M.; Mughini-Gras, L.; Pijnacker, R.; Vennema, H.; Scholts, R.; van Huisstede-Vlaanderen, K. W.; Kortbeek, T.; Kooistra-Smid, M.; van Pelt, W.

    2016-01-01

    Acute gastroenteritis (AGE) morbidity remains high amongst preschool children, posing a significant societal burden. Empirical data on AGE-causing agents is needed to gauge their clinical relevance and identify agent-specific targets for control. We assessed the prevalence, risk factors and associat

  7. Bottom–up protein identifications from microliter quantities of individual human tear samples. Important steps towards clinical relevance.

    Directory of Open Access Journals (Sweden)

    Peter Raus

    2015-12-01

    With 375 confidently identified proteins in the healthy adult tear, the obtained results are comprehensive and in large agreement with previously published observations on pooled samples of multiple patients. We conclude that, to a limited extent, bottom–up tear protein identifications from individual patients may have clinical relevance.

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

    NARCIS (Netherlands)

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

    2016-01-01

    OBJECTIVES: A proposed method for bridging the gap between clinically relevant epilepsy outcome measures and quality-adjusted life years is to derive utility scores for epilepsy health states. The aim of this study is to develop such a utility-function and to investigate the impact of the epilepsy o

  9. Time-driven activity-based costing in an outpatient clinic environment: development, relevance and managerial impact.

    Science.gov (United States)

    Demeere, Nathalie; Stouthuysen, Kristof; Roodhooft, Filip

    2009-10-01

    Healthcare managers are continuously urged to provide better patient services at a lower cost. To cope with these cost pressures, healthcare management needs to improve its understanding of the relevant cost drivers. Through a case study, we show how to perform a time-driven activity-based costing of five outpatient clinic's departments and provide evidence of the benefits of such an analysis.

  10. Potential causative agents of acute gastroenteritis in households with preschool children : prevalence, risk factors, clinical relevance and household transmission

    NARCIS (Netherlands)

    Heusinkveld, M.; Mughini-Gras, L.; Pijnacker, R.; Vennema, H.; Scholts, R.; van Huisstede-Vlaanderen, K. W.; Kortbeek, T.; Kooistra-Smid, M.; van Pelt, W.

    2016-01-01

    Acute gastroenteritis (AGE) morbidity remains high amongst preschool children, posing a significant societal burden. Empirical data on AGE-causing agents is needed to gauge their clinical relevance and identify agent-specific targets for control. We assessed the prevalence, risk factors and

  11. Comparative Evaluation of Etest, EUCAST, and CLSI Methods for Amphotericin B, Voriconazole, and Posaconazole against Clinically Relevant Fusarium Species

    NARCIS (Netherlands)

    Al-Hatmi, A.M.; Normand, A.C.; Ranque, S.; Piarroux, R.; Hoog, G.S. de; Meletiadis, J.; Meis, J.F.G.M.

    2017-01-01

    We compared EUCAST and CLSI methods versus Etest for antifungal susceptibility testing of 20 clinically relevant Fusarium species against amphotericin B, posaconazole, and voriconazole. The median Etest amphotericin B and posaconazole MICs were 1 dilution higher than the median EUCAST and the CLSI M

  12. Potential causative agents of acute gastroenteritis in households with preschool children : prevalence, risk factors, clinical relevance and household transmission

    NARCIS (Netherlands)

    Heusinkveld, M.; Mughini-Gras, L.; Pijnacker, R.; Vennema, H.; Scholts, R.; van Huisstede-Vlaanderen, K. W.; Kortbeek, T.; Kooistra-Smid, M.; van Pelt, W.

    2016-01-01

    Acute gastroenteritis (AGE) morbidity remains high amongst preschool children, posing a significant societal burden. Empirical data on AGE-causing agents is needed to gauge their clinical relevance and identify agent-specific targets for control. We assessed the prevalence, risk factors and associat

  13. Clinical relevance of the gap between pre-marketing trials and medical practice : the case of the cardiovascular drugs

    NARCIS (Netherlands)

    Wieringa, N F; Denig, P; de Graeff, P A; Vos, R

    2002-01-01

    OBJECTIVES/BACKGROUND: The external validity of trial results of new cardiovascular drugs is limited, because the short-term studies are performed with relatively small, highly selected populations. Using qualitative methods, we examined the clinical relevance of under-representation of subgroups of

  14. A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes

    Directory of Open Access Journals (Sweden)

    Wiebe Natasha

    2011-11-01

    Full Text Available Abstract Background The major metabolic complications of obesity and type 2 diabetes may be prevented and managed with dietary modification. The use of sweeteners that provide little or no calories may help to achieve this objective. Methods We did a systematic review and network meta-analysis of the comparative effectiveness of sweetener additives using Bayesian techniques. MEDLINE, EMBASE, CENTRAL and CAB Global were searched to January 2011. Randomized trials comparing sweeteners in obese, diabetic, and healthy populations were selected. Outcomes of interest included weight change, energy intake, lipids, glycated hemoglobin, markers of insulin resistance and glycemic response. Evidence-based items potentially indicating risk of bias were assessed. Results Of 3,666 citations, we identified 53 eligible randomized controlled trials with 1,126 participants. In diabetic participants, fructose reduced 2-hour blood glucose concentrations by 4.81 mmol/L (95% CI 3.29, 6.34 compared to glucose. Two-hour blood glucose concentration data comparing hypocaloric sweeteners to sucrose or high fructose corn syrup were inconclusive. Based on two ≤10-week trials, we found that non-caloric sweeteners reduced energy intake compared to the sucrose groups by approximately 250-500 kcal/day (95% CI 153, 806. One trial found that participants in the non-caloric sweetener group had a decrease in body mass index compared to an increase in body mass index in the sucrose group (-0.40 vs 0.50 kg/m2, and -1.00 vs 1.60 kg/m2, respectively. No randomized controlled trials showed that high fructose corn syrup or fructose increased levels of cholesterol relative to other sweeteners. Conclusions Considering the public health importance of obesity and its consequences; the clearly relevant role of diet in the pathogenesis and maintenance of obesity; and the billions of dollars spent on non-caloric sweeteners, little high-quality clinical research has been done. Studies are

  15. A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes.

    Science.gov (United States)

    Wiebe, Natasha; Padwal, Raj; Field, Catherine; Marks, Seth; Jacobs, Rene; Tonelli, Marcello

    2011-11-17

    The major metabolic complications of obesity and type 2 diabetes may be prevented and managed with dietary modification. The use of sweeteners that provide little or no calories may help to achieve this objective. We did a systematic review and network meta-analysis of the comparative effectiveness of sweetener additives using Bayesian techniques. MEDLINE, EMBASE, CENTRAL and CAB Global were searched to January 2011. Randomized trials comparing sweeteners in obese, diabetic, and healthy populations were selected. Outcomes of interest included weight change, energy intake, lipids, glycated hemoglobin, markers of insulin resistance and glycemic response. Evidence-based items potentially indicating risk of bias were assessed. Of 3,666 citations, we identified 53 eligible randomized controlled trials with 1,126 participants. In diabetic participants, fructose reduced 2-hour blood glucose concentrations by 4.81 mmol/L (95% CI 3.29, 6.34) compared to glucose. Two-hour blood glucose concentration data comparing hypocaloric sweeteners to sucrose or high fructose corn syrup were inconclusive. Based on two ≤10-week trials, we found that non-caloric sweeteners reduced energy intake compared to the sucrose groups by approximately 250-500 kcal/day (95% CI 153, 806). One trial found that participants in the non-caloric sweetener group had a decrease in body mass index compared to an increase in body mass index in the sucrose group (-0.40 vs 0.50 kg/m2, and -1.00 vs 1.60 kg/m2, respectively). No randomized controlled trials showed that high fructose corn syrup or fructose increased levels of cholesterol relative to other sweeteners. Considering the public health importance of obesity and its consequences; the clearly relevant role of diet in the pathogenesis and maintenance of obesity; and the billions of dollars spent on non-caloric sweeteners, little high-quality clinical research has been done. Studies are needed to determine the role of hypocaloric sweeteners in a wider

  16. Cortical atrophy patterns in multiple sclerosis are non-random and clinically relevant.

    Science.gov (United States)

    Steenwijk, Martijn D; Geurts, Jeroen J G; Daams, Marita; Tijms, Betty M; Wink, Alle Meije; Balk, Lisanne J; Tewarie, Prejaas K; Uitdehaag, Bernard M J; Barkhof, Frederik; Vrenken, Hugo; Pouwels, Petra J W

    2016-01-01

    Grey matter atrophy is common in multiple sclerosis. However, in contrast with other neurodegenerative diseases, it is unclear whether grey matter atrophy in multiple sclerosis is a diffuse 'global' process or develops, instead, according to distinct anatomical patterns. Using source-based morphometry we searched for anatomical patterns of co-varying cortical thickness and assessed their relationships with white matter pathology, physical disability and cognitive functioning. Magnetic resonance imaging was performed at 3 T in 208 patients with long-standing multiple sclerosis (141 females; age = 53.7 ± 9.6 years; disease duration = 20.2 ± 7.1 years) and 60 age- and sex-matched healthy controls. Spatial independent component analysis was performed on cortical thickness maps derived from 3D T1-weighted images across all subjects to identify co-varying patterns. The loadings, which reflect the presence of each cortical thickness pattern in a subject, were compared between patients with multiple sclerosis and healthy controls with generalized linear models. Stepwise linear regression analyses were used to assess whether white matter pathology was associated with these loadings and to identify the cortical thickness patterns that predict measures of physical and cognitive dysfunction. Ten cortical thickness patterns were identified, of which six had significantly lower loadings in patients with multiple sclerosis than in controls: the largest loading differences corresponded to the pattern predominantly involving the bilateral temporal pole and entorhinal cortex, and the pattern involving the bilateral posterior cingulate cortex. In patients with multiple sclerosis, overall white matter lesion load was negatively associated with the loadings of these two patterns. The final model for physical dysfunction as measured with Expanded Disability Status Scale score (adjusted R(2) = 0.297; P atrophy patterns relevant for multiple sclerosis were found. This suggests that

  17. Physiological and pathological clinical conditions and light scattering in brain

    Science.gov (United States)

    Kurata, Tsuyoshi; Iwata, Sachiko; Tsuda, Kennosuke; Kinoshita, Masahiro; Saikusa, Mamoru; Hara, Naoko; Oda, Motoki; Ohmae, Etsuko; Araki, Yuko; Sugioka, Takashi; Takashima, Sachio; Iwata, Osuke

    2016-08-01

    MRI of preterm infants at term commonly reveals subtle brain lesions such as diffuse white matter injury, which are linked with later cognitive impairments. The timing and mechanism of such injury remains unclear. The reduced scattering coefficient of near-infrared light (μs’) has been shown to correlate linearly with gestational age in neonates. To identify clinical variables associated with brain μs’, 60 preterm and full-term infants were studied within 7 days of birth. Dependence of μs’ obtained from the frontal head on clinical variables was assessed. In the univariate analysis, smaller μs’ was associated with antenatal glucocorticoid, emergency Caesarean section, requirement for mechanical ventilation, smaller gestational age, smaller body sizes, low 1- and 5-minute Apgar scores, higher cord blood pH and PO2, and higher blood HCO3‑ at the time of study. Multivariate analysis revealed that smaller gestational age, requirement for mechanical ventilation, and higher HCO3‑ at the time of study were correlated with smaller μs’. Brain μs’ depended on variables associated with physiological maturation and pathological conditions of the brain. Further longitudinal studies may help identify pathological events and clinical conditions responsible for subtle brain injury and subsequent cognitive impairments following preterm birth.

  18. Cardioprotection by remote ischemic conditioning: Mechanisms and clinical evidences

    Institute of Scientific and Technical Information of China (English)

    Alberto; Aimo; Chiara; Borrelli; Alberto; Giannoni; Luigi; Emilio; Pastormerlo; Andrea; Barison; Gianluca; Mirizzi; Michele; Emdin; Claudio; Passino

    2015-01-01

    In remote ischemic conditioning(RIC), several cycles of ischemia and reperfusion render distant organ and tissues more resistant to the ischemia-reperfusion injury. The intermittent ischemia can be applied before the ischemic insult in the target site(remote ischemic preconditioning), during the ischemic insult(remote ischemic perconditioning) or at the onset of reperfusion(remote ischemic postconditioning). The mechanisms of RIC have not been completely defined yet; however, these mechanisms must be represented by the release of humoral mediators and/or the activation of a neural reflex. RIC has been discovered in the heart, and has been arising great enthusiasm in the cardiovascular field. Its efficacy has been evaluated in many clinical trials, which provided controversial results. Our incomplete comprehension of the mechanisms underlying the RIC could be impairing the design of clinical trials and the interpretation of their results. In the present review we summarize current knowledge about RIC pathophysiology and the data about its cardioprotective efficacy.

  19. Magnetic resonance imaging of the brain in children with headache: the clinical relevance with modern acquisition techniques.

    Science.gov (United States)

    Streibert, Phillipp Fridolin; Piroth, Werner; Mansour, Michael; Haage, Patrick; Langer, Thorsten; Borusiak, Peter

    2011-12-01

    The aim of this study was to evaluate the frequency of abnormal findings in magnetic resonance imaging (MRI) in children with headache, the clinical relevance of these findings, and whether more sophisticated technologies also result in more relevant abnormal findings. The MRIs of 1004 children with age ranging from 1 to 17 years were retrospectively analyzed. Children who were investigated with established sequences (n = 419) were compared with those examined with state-of-the-art MRI acquisition technology (n = 585). In 216/1004 investigations, MRI was performed because of headache (74/216 with established sequences, 142/216 with state-of-the-art acquisition technology). In 114/216 (52.8%) patients with headache, the MRI was abnormal with relevant findings in 23/114 patients and findings without clinical relevance in 91/114 children. A higher incidence of abnormal findings than in previous reports was found but there was only limited clinical gain of information using modern sequences in children with headache.

  20. Investigation of the Minimum Conditions for Reliable Estimation of Clinically Relevant HRV Measures

    DEFF Research Database (Denmark)

    Ahrens, Esben; Sørensen, Helge Bjarup Dissing; Langberg, Henning;

    2015-01-01

    The R-peak localization error (jitter) of a heart rate variability (HRV) system has a great impact on the values of the HRV measures. Only a few studies have analyzed this subject and purely done so from the aspect of choice of sampling frequency. In this study we provide an overview of the various...... factors that comprise the jitter of a system. We propose a method inspired by the field of signal averaged electrocardiography (SAECG) that allows for a quantification of the jitter of any HRV system that records and stores the raw ECG signal. Furthermore, with this method the differences between the HRV...

  1. Initial Public Offerings: The Relevance of the Market Timing Hypothesis Under Conditions of the Czech Capital Market

    Directory of Open Access Journals (Sweden)

    Meluzín Tomáš

    2011-12-01

    Full Text Available Abstract In this article, the authors study the relevance of the market timing hypothesis of going public, which tends to explain the lower post-issue operating performance of Czech initial public offerings. The data collected under the conditions of the Czech capital market are compared with the performance of companies selected from the main European stock exchanges, when they decided to adopt the IPO strategy. Achieving the objective required an empirical survey that involved a collection of accounting data in companies that had completed an initial public offer in the Czech capital market. The data were evaluated by financial performance measures. The comparisons were made using descriptive statistical methods. The research results broaden and deepen the present understanding of the market timing hypothesis in companies going public, particularly in the Czech Republic.

  2. Animal model of PTSD based on clinically relevant features of trauma susceptibility and expression

    Directory of Open Access Journals (Sweden)

    David Diamond

    2012-09-01

    Full Text Available Rationale/statement of the problem : There is an insufficient understanding of the neurobiology of post-traumatic stress disorder (PTSD. Therefore, the development of an animal model of PTSD that takes into account clinical features of the disorder is of value toward enhancing our understanding of the mechanisms, and in the development of novel treatments, of emotional trauma. Methods : Adult male rats were administered chronic psychosocial stress composed of two 1-hour periods of inescapable exposure to a cat, in conjunction with daily unstable pair housing, over a 31 day period. The rats were then given a battery of tests, including measures of behavior (anxiety testing, startle response, cognition (predator-based fear memory and new memory testing, hormone levels (basal and evoked glucocorticoids, responses to pharmacological agents (dexamethasone and yohimbine and cardiovascular activity (blood pressure/heart rate. In addition, we measured epigenetic alterations (methylation of the brain-derived neurotrophic factor (BDNF gene. Results : Psychosocially stressed rats exhibited a PTSD-like phenotype. The stressed rats exhibited a strong fear-conditioned memory of the two cat exposures, an increase in behavioral signs of anxiety, an exaggerated startle response, increased blood pressure, greater sensitivity to yohimbine and a hippocampus-dependent memory impairment, relative to controls. In addition, stressed rats exhibited reduced basal glucocorticoid levels, greater sensitivity to dexamethasone and hypermethylation of the BDNF gene in the hippocampus. Conclusion : These findings demonstrate that intense psychosocial stress produced dramatic changes in physiology and behavior in rats which are comparable to those observed in people diagnosed with PTSD. This rat model, therefore, may enhance our understanding of the mechanisms underlying human trauma and in the development of more effective pharmacotherapy for people with PTSD.

  3. Differential Effectiveness of Clinically-Relevant Analgesics in a Rat Model of Chemotherapy-Induced Mucositis.

    Directory of Open Access Journals (Sweden)

    Alexandra L Whittaker

    Full Text Available Chemotherapy-induced intestinal mucositis is characterized by pain and a pro-inflammatory tissue response. Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the effect that analgesic administration may have on study outcomes. This study investigated different classes of analgesics with the aim of determining their analgesic effects and impact on research outcomes of interest in a rat model of mucositis. Female DA rats were allocated to 8 groups to include saline and chemotherapy controls (n = 8. Analgesics included opioid derivatives (buprenorphine; 0.05mg/kg and tramadol 12.5mg/kg and NSAID (carprofen; 15mg/kg in combination with either saline or 5-Fluorouracil (5-FU; 150mg/kg. Research outcome measures included daily clinical parameters, pain score and gut histology. Myeloperoxidase assay was performed to determine gut inflammation. At the dosages employed, all agents had an analgesic effect based on behavioural pain scores. Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001. Carprofen had no ameliorating effect on myeloperoxidase levels. None of the agents reduced the histological damage caused by 5-FU administration although tramadol tended to increase villus length even when administered to healthy animals. These data provide evidence that carprofen offers potential as an analgesic in this animal model due to its pain-relieving efficacy and minimal effect on measured parameters. This study also supports further investigation into the mechanism and utility of opioid agents in the treatment of chemotherapy-induced mucositis.

  4. Tumor-derived spheroids: Relevance to cancer stem cells and clinical applications.

    Science.gov (United States)

    Ishiguro, Tatsuya; Ohata, Hirokazu; Sato, Ai; Yamawaki, Kaoru; Enomoto, Takayuki; Okamoto, Koji

    2017-03-01

    Recently, many types of in vitro 3-D culture systems have been developed to recapitulate the in vivo growth conditions of cancer. The cancer 3-D culture methods aim to preserve the biological characteristics of original tumors better than conventional 2-D monolayer cultures, and include tumor-derived organoids, tumor-derived spheroids, organotypic multicellular spheroids, and multicellular tumor spheroids. The 3-D culture methods differ in terms of cancer cell sources, protocols for cell handling, and the required time intervals. Tumor-derived spheroids are unique because they are purposed for the enrichment of cancer stem cells (CSCs) or cells with stem cell-related characteristics. These spheroids are grown as floating spheres and have been used as surrogate systems to evaluate the CSC-related characteristics of solid tumors in vitro. Because eradication of CSCs is likely to be of clinical importance due to their association with the malignant nature of cancer cells, such as tumorigenicity or chemoresistance, the investigation of tumor-derived spheroids may provide invaluable clues to fight against cancer. Spheroid cultures have been established from cancers including glioma, breast, colon, ovary, and prostate cancers, and their biological and biochemical characteristics have been investigated by many research groups. In addition to the investigation of CSCs, tumor-derived spheroids may prove to be instrumental for a high-throughput screening platform or for the cultivation of CSC-related tumor cells found in the circulation or body fluids. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  5. Clinically relevant risk factors for suicide: Comparison between clinical group with passive suicidal ideation, active suicidal ideation and without suicidal ideation

    OpenAIRE

    Miloseva, Lence; Cuijpers, Pim; Stojcev, Saso; Niklewski, Gunter; Richter, Kneginja; Jovevska, Svetlana; Arsova, Roza; Serafimov, Aleksandar

    2015-01-01

    Introduction: In recent years, researchers and clinicians do not treat passive suicidal ideation as a clinically relevant risk factor for suicide, while underestimating the strength of this desire to die, compared with making a plan for suicide in individuals having active suicidal ideation. This research study is clinically prospective, cross-sequential, but also partly retrospective because it involves also variables from the past, such as patients’ history data (number of suicidal attempts...

  6. Two clinically relevant pressures of carbon dioxide pneumooperitoneum cause hepatic injury in a rabbit model

    Institute of Scientific and Technical Information of China (English)

    Jun Li; Ying-Hai Liu; Zhan-Yong Ye; He-Nian Liu; Shan Ou; Fu-Zhou Tian

    2011-01-01

    AIM: To observe the hepatic injury induced by carbon dioxide pneumoperitoneum (CDPP) in rabbits, compare the effffects off low- and high-pressure pneumoperitoneum, and to determine the degree off hepatic injury induced by these two clinically relevant CDPP pressures. METHODS: Thirty healthy male New Zealand rabbits weighing 3.0 to 3.5 kg were randomly divided into three groups (n = 10 ffor each group) and subjected to the ffollowing to CDPP pressures: no gas control, 10 mmHg, or 15 mmHg. Histological changes in liver tissues were observed with hematoxylin and eosin staining and transmission electron microscopy. Liver ffunction was evaluated using an automatic biochemical analyzer. Adenine nucleotide translocator (ANT) activity in liver tissue was detected with the atractyloside-inhibitor stop technique. Bax and Bcl-2 expression levels were detected by western blotting. RESULTS: Liver ffunctions in the 10 mmHg and 15 mmHg experimental groups were significantly disturbed compared with the control group. Affter CDPP, the levels off alanine transaminase and aspartate transaminase were 77.3 ± 14.5 IU/L and 60.1 ± 11.4 IU/L, respectively, in the 10 mmHg experimental group and 165.1 ± 19.4 IU/L and 103.8 ± 12.3 IU/L, respectively, in the 15 mmHg experimental group, which were all higher than those off the control group (PP < 0.05). There was no difffference in pre-albumin concentration between the 10 mmHg experimental group and the control group, but the pre-albumin level off the 15 mmHg experimental group was significantly lower than that of the control group (< 0.05). No significant differences were observed in the levels off total bilirubin or albumin among the three groups. Affter 30 and 60 min off CDPP, pH was reduced (PP < 0.05) and PPaCO2 was elevated (< 0.05) in the 10 mmHg group compared with controls, and these changes were more pronounced in the 15 mmHg group. Hematoxylin and eosin staining showed no significant change in liver morphology, except ffor mild

  7. Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues.

    Science.gov (United States)

    Tong, Mengsha; Zheng, Weicheng; Lu, Xingrong; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Cai, Hao; Li, Mengyao; Yan, Haidan; Guo, You; Chi, Pan; Guo, Zheng

    2015-12-01

    Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens.

  8. Assessment and clinical relevance of non-fasting and postprandial triglycerides

    DEFF Research Database (Denmark)

    Kolovou, Genovefa D; Mikhailidis, Dimitri P; Kovar, Jan

    2011-01-01

    An Expert Panel group of scientists and clinicians met to consider several aspects related to non-fasting and postprandial triglycerides (TGs) and their role as risk factors for cardiovascular disease (CVD). In this context, we review recent epidemiological studies relevant to elevated non-fastin...

  9. Assessment and clinical relevance of non-fasting and postprandial triglycerides

    DEFF Research Database (Denmark)

    Kolovou, Genovefa D; Mikhailidis, Dimitri P; Kovar, Jan

    2011-01-01

    An Expert Panel group of scientists and clinicians met to consider several aspects related to non-fasting and postprandial triglycerides (TGs) and their role as risk factors for cardiovascular disease (CVD). In this context, we review recent epidemiological studies relevant to elevated non...

  10. Engaging Stakeholders to Inform Clinical Practice Guidelines That Address Multiple Chronic Conditions.

    Science.gov (United States)

    Bennett, Wendy L; Robbins, Craig W; Bayliss, Elizabeth A; Wilson, Renee; Tabano, Heather; Mularski, Richard A; Chan, Wiley V; Puhan, Milo; Yu, Tsung; Leff, Bruce; Li, Tianjing; Dickersin, Kay; Glover, Carol; Maslow, Katie; Armacost, Karen; Mintz, Suzanne; Boyd, Cynthia M

    2017-08-01

    Having more than one chronic condition is common and is associated with greater health care utilization, higher medication burden and complexity of treatment. However, clinical practice guidelines (CPGs) do not routinely address the balance between harms and benefits of treatments for people with multiple chronic conditions (MCCs). To partner with the Kaiser Permanente Integrated Cardiovascular Health (ICVH) program to engage multiple stakeholders in a mixed-methods approach in order to: 1) identify two high-priority clinical questions related to MCCs, and 2) understand patients' and family caregivers' perceptions of meaningful outcomes to inform benefit/harm assessments for these two high-priority questions. These clinical questions and outcomes will be used to inform CPG recommendations for people with MCCs. DESIGN AND PARTICIPANTS: The ICVH program provided 130 topics rank-ordered by the potential for finding evidence that would change clinical recommendations regarding the topic. We used a modified Delphi method to identify and reword topics into questions relevant to people with MCCs. We used two sets of focus groups (n = 27) to elicit patient and caregiver perspectives on two important research questions and relevant patient-important outcomes on benefit/harm balance for people with MCCs. Co-investigators, patients and caregivers identified "optimal blood pressure goals" and "diabetes medication management" as important clinical topics for CPGs related to people with MCCs. Stakeholders identified a list of relevant outcomes to be addressed in future CPG development including 1) physical function and energy, 2) emotional health and well-being, 3) avoidance of treatment burden, side effects and risks, 4) interaction with providers and health care system, and 5) prevention of adverse long-term health outcomes. Through the application of a mixed-methods process, we identified the questions regarding optimal blood pressure goals and diabetes medication management

  11. Stability of the Elbow Joint: Relevant Anatomy and Clinical Implications of In Vitro Biomechanical Studies

    NARCIS (Netherlands)

    J. de Haan (Jeroen); D. Eygendaal (Denise); N.W.L. Schep (Niels); G.J. Kleinrensink (Gert Jan); W.E. Tuinebreijer (Wim); D. den Hartog (Dennis)

    2011-01-01

    textabstractAbstract: The aim of this literature review is to describe the clinical anatomy of the elbow joint based on information from in vitro biomechanical studies. The clinical consequences of this literature review are described and recommendations are given for the treatment of elbow joint di

  12. Awareness of cognitive deficits and clinical competence in mild to moderate Alzheimer's disease: their relevance in clinical practice.

    Science.gov (United States)

    Gambina, G; Bonazzi, A; Valbusa, V; Condoleo, M T; Bortolami, O; Broggio, E; Sala, F; Moretto, G; Moro, V

    2014-03-01

    Awareness of cognitive deficits and clinical competence were investigated in 79 mild to moderate Alzheimer's disease patients. Awareness was assessed by the anosognosia questionnaire for dementia, and clinical competence by specific neuropsychological tests such as trail making test-A, Babcock story recall test, semantic and phonemic verbal fluency. The findings show that 66 % of the patients were aware of memory deficits, while the 34 % were unaware. Deficit in awareness correlated with lower scores on the Mini Mental State Examination test that, in the score range from 24.51 to 30 and from 19.50 to 24.50, appeared to be a significant predictor of level of awareness. None of the AD patients had fully preserved clinical competence, only 7 patients (9 %) had partially preserved clinical competence and 72 patients (91 %) had completely lost clinical competence. All the patients with partially preserved clinical competence (9 %) were aware of their memory deficit. The study indicates that neuropsychological tests used for the assessment of executive functions are not suitable for investigating clinical competence. Therefore, additional and specific tools for the evaluation of clinical competence are necessary. Indeed, these might allow clinicians to identify AD patients who, despite their deficits in selected functions, retain their autonomy of choice as well as recognize those patients who should proceed to the nomination of a legal representative.

  13. Cork stoppers as an effective sorbent for water treatment: the removal of mercury at environmentally relevant concentrations and conditions.

    Science.gov (United States)

    Lopes, Cláudia B; Oliveira, Joana R; Rocha, Luciana S; Tavares, Daniela S; Silva, Carlos M; Silva, Susana P; Hartog, Niels; Duarte, Armando C; Pereira, E

    2014-02-01

    The technical feasibility of using stopper-derived cork as an effective biosorbent towards bivalent mercury at environmentally relevant concentrations and conditions was evaluated in this study. Only 25 mg/L of cork powder was able to achieve 94 % of mercury removal for an initial mercury concentration of 500 μg/L. It was found that under the conditions tested, the efficiency of mercury removal expressed as equilibrium removal percentage does not depend on the amount of cork or its particle size, but is very sensitive to initial metal concentration, with higher removal efficiencies at higher initial concentrations. Ion exchange was identified as one of the mechanisms involved in the sorption of Hg onto cork in the absence of ionic competition. Under ionic competition, stopper-derived cork showed to be extremely effective and selective for mercury in binary mixtures, while in complex matrices like seawater, moderate inhibition of the sorption process was observed, attributed to a change in mercury speciation. The loadings achieved are similar to the majority of literature values found for other biosorbents and for other metals, suggesting that cork stoppers can be recycled as an effective biosorbent for water treatment. However, the most interesting result is that equilibrium data show a very rare behaviour, with the isotherm presenting an almost square convex shape to the concentration axis, with an infinite slope for an Hg concentration in solution around 25 μg/L.

  14. New understanding of adolescent brain development: relevance to transitional healthcare for young people with long term conditions.

    Science.gov (United States)

    Colver, Allan; Longwell, Sarah

    2013-11-01

    Whether or not adolescence should be treated as a special period, there is now no doubt that the brain changes much during adolescence. From an evolutionary perspective, the idea of an under developed brain which is not fit for purpose until adulthood is illogical. Rather, the adolescent brain is likely to support the challenges specific to that period of life. New imaging techniques show striking changes in white and grey matter between 11 and 25 years of age, with increased connectivity between brain regions, and increased dopaminergic activity in the pre-frontal cortices, striatum and limbic system and the pathways linking them. The brain is dynamic, with some areas developing faster and becoming more dominant until other areas catch up. Plausible mechanisms link these changes to cognitive and behavioural features of adolescence. The changing brain may lead to abrupt behavioural change with attendant risks, but such a brain is flexible and can respond quickly and imaginatively. Society allows adolescent exuberance and creativity to be bounded and explored in relative safety. In healthcare settings these changes are especially relevant to young people with long term conditions as they move to young adult life; such young people need to learn to manage their health conditions with the support of their healthcare providers.

  15. Work function measurements during plasma exposition at conditions relevant in negative ion sources for the ITER neutral beam injection.

    Science.gov (United States)

    Gutser, R; Wimmer, C; Fantz, U

    2011-02-01

    Cesium seeded sources for surface generated negative hydrogen ions are major components of neutral beam injection systems in future large-scale fusion experiments such as ITER. The stability and delivered current density depend highly on the work function during vacuum and plasma phases of the ion source. One of the most important quantities that affect the source performance is the work function. A modified photocurrent method was developed to measure the temporal behavior of the work function during and after cesium evaporation. The investigation of cesium exposed Mo and MoLa samples under ITER negative hydrogen ion based neutral beam injection relevant surface and plasma conditions showed the influence of impurities which result in a fast degradation when the plasma exposure or the cesium flux onto the sample is stopped. A minimum work function close to that of bulk cesium was obtained under the influence of the plasma exposition, while a significantly higher work function was observed under ITER-like vacuum conditions.

  16. Investigation of critical inter-related factors affecting the efficacy of pulsed light for inactivating clinically relevant bacterial pathogens.

    Science.gov (United States)

    Farrell, H P; Garvey, M; Cormican, M; Laffey, J G; Rowan, N J

    2010-05-01

    To investigate critical electrical and biological factors governing the efficacy of pulsed light (PL) for the in vitro inactivation of bacteria isolated from the clinical environment. Development of this alternative PL decontamination approach is timely, as the incidence of health care-related infections remains unacceptably high. Predetermined cell numbers of clinically relevant Gram-positive and Gram-negative bacteria were inoculated separately on agar plates and were flashed with pulses of broad-spectrum light under varying operating conditions, and their inactivation measured. Significant differences in inactivation largely occurred depending on the level of the applied lamp discharge energy (range 3.2-20 J per pulse), the amount of pulsing applied (range 0-60 pulses) and the distance between light source and treatment surface (range 8-20 cm) used. Greater decontamination levels were achieved using a combination of higher lamp discharge energies, increased number of pulses and shorter distances between treatment surface and the xenon light source. Levels of microbial sensitivity also varied depending on the population type, size and age of cultures treated. Production of pigment pyocynanin and alginate slime in mucoid strains of Pseudomonas aeruginosa afforded some protection against lethal action of PL; however, this was evident only by using a combination of reduced amount of pulsing at the lower lamp discharge energies tested. A clear pattern was observed where Gram-positive bacterial pathogens were more resistant to cidal effects of PL compared to Gram negatives. While negligible photoreactivation of PL-treated bacterial strains occurred after full pulsing regimes at the different lamp discharge energies tested, some repair was evident when using a combination of reduced pulsing at the lower lamp discharge energies. Strains harbouring genes for multiple resistances to antibiotics were not significantly more resistant to PL treatments. Slight temperature

  17. Propofol at Clinically Relevant Concentrations Increases Neuronal Differentiation but Is Not Toxic to Hippocampal Neural Precursor Cells In Vitro

    Science.gov (United States)

    Sall, Jeffrey W.; Stratmann, Greg; Leong, Jason; Woodward, Elliott; Bickler, Philip E.

    2012-01-01

    Background Propofol in the early postnatal period has been shown to cause brain cell death. One proposed mechanism for cognitive dysfunction after anesthesia is alteration of neural stem cell function and neurogenesis. We examined the effect of propofol on neural precursor or stem cells (NPCs) grown in vitro. Methods Hippocampal derived NPCs from postnatal day 2 rats were exposed to propofol or to Diprivan. NPCs were then analyzed for bromodeoxyuridine incorporation to measure proliferation. Cell death was measured by lactate dehydrogenase release. Immunocytochemistry was used to evaluate the expression of neuronal and glial markers in differentiating NPCs exposed to propofol. Results Propofol dose dependently increases the release of lactate dehydrogenase from NPCs under both proliferating and differentiating conditions at supraclinical concentrations (> 7.1μM). Both Diprivan and propofol had the same effect on NPCs. Propofol mediated release of lactate dehydrogenase is not inhibited by blocking the γ-aminobutyric acid type A receptor or extracellular calcium influx and is not mediated by caspase-3/7. Direct γ-aminobutyric acid type A receptor activation did not have the same effect. In differentiating NPCs 6 h of propofol at 2.1 μM increased the number neurons but not glial cells 4 days later. Increased neuronal differentiation was not blocked by Bicuculline. Conclusions Only supraclinical concentrations of propofol or Diprivan kill NPCs in culture by a non-γ-aminobutyric acid type A, noncaspase 3 mechanism. Clinically relevant doses of propofol increase neuronal fate choice by a non-γ-aminobutyric acid type A mechanism. PMID:23001052

  18. Application of concave microwells to pancreatic tumor spheroids enabling anticancer drug evaluation in a clinically relevant drug resistance model.

    Directory of Open Access Journals (Sweden)

    Sang-Eun Yeon

    Full Text Available Intrinsic drug resistance of pancreatic ductal adenocarcinoma (PDAC warrants studies using models that are more clinically relevant for identifying novel resistance mechanisms as well as for drug development. Tumor spheroids (TS mimic in vivo tumor conditions associated with multicellular resistance and represent a promising model for efficient drug screening, however, pancreatic cancer cells often fail to form spheroids using conventional methods such as liquid overlay. This study describes the induction of TS of human pancreatic cancer cells (Panc-1, Aspc-1, Capan-2 in concave polydimethylsiloxane (PDMS microwell plates and evaluation of their usefulness as an anticancer efficacy test model. All three cell lines showed TS formation with varying degree of necrosis inside TS. Among these, Panc-1 spheroid with spherical morphology, a rather rough surface, and unique adhesion structures were successfully produced with no notable necrosis in concave microwell plates. Panc-1 TS contained growth factors or enzymes such as TGF-β1, CTGF, and MT1-MMP, and extracellular matrix proteins such as collagen type I, fibronectin, and laminin. Panc-1 cells grown as TS showed changes in stem cell populations and in expression levels of miRNAs that may play roles in chemoresistance. Visualization of drug penetration and detection of viability indicators, such as Ki-67 and MitoSOX, were optimized for TS for quantitative analysis. Water-soluble tetrazolium (MTS and acid phosphatase (APH assays were also successfully optimized. Overall, we demonstrated that concave PDMS microwell plates are a novel platform for preparation of TS of weakly aggregating cells and that Panc-1 spheroids may represent a novel three-dimensional model for anti-pancreatic cancer drug screening.

  19. Application of concave microwells to pancreatic tumor spheroids enabling anticancer drug evaluation in a clinically relevant drug resistance model.

    Science.gov (United States)

    Yeon, Sang-Eun; No, Da Yoon; Lee, Sang-Hoon; Nam, Suk Woo; Oh, Il-Hoan; Lee, Jaehwi; Kuh, Hyo-Jeong

    2013-01-01

    Intrinsic drug resistance of pancreatic ductal adenocarcinoma (PDAC) warrants studies using models that are more clinically relevant for identifying novel resistance mechanisms as well as for drug development. Tumor spheroids (TS) mimic in vivo tumor conditions associated with multicellular resistance and represent a promising model for efficient drug screening, however, pancreatic cancer cells often fail to form spheroids using conventional methods such as liquid overlay. This study describes the induction of TS of human pancreatic cancer cells (Panc-1, Aspc-1, Capan-2) in concave polydimethylsiloxane (PDMS) microwell plates and evaluation of their usefulness as an anticancer efficacy test model. All three cell lines showed TS formation with varying degree of necrosis inside TS. Among these, Panc-1 spheroid with spherical morphology, a rather rough surface, and unique adhesion structures were successfully produced with no notable necrosis in concave microwell plates. Panc-1 TS contained growth factors or enzymes such as TGF-β1, CTGF, and MT1-MMP, and extracellular matrix proteins such as collagen type I, fibronectin, and laminin. Panc-1 cells grown as TS showed changes in stem cell populations and in expression levels of miRNAs that may play roles in chemoresistance. Visualization of drug penetration and detection of viability indicators, such as Ki-67 and MitoSOX, were optimized for TS for quantitative analysis. Water-soluble tetrazolium (MTS) and acid phosphatase (APH) assays were also successfully optimized. Overall, we demonstrated that concave PDMS microwell plates are a novel platform for preparation of TS of weakly aggregating cells and that Panc-1 spheroids may represent a novel three-dimensional model for anti-pancreatic cancer drug screening.

  20. Clinically relevant HOCl concentrations reduce clot retraction rate via the inhibition of energy production in platelet mitochondria.

    Science.gov (United States)

    Misztal, T; Rusak, T; Tomasiak, M

    2014-12-01

    Using porcine blood, we examined the impact of hypochlorite, product of activated inflammatory cells, on clot retraction (CR), an important step of hemostasis. We found that, in vitro, HOCl is able to reduce CR rate and enlarge final clot size in whole blood (t.c. 100 μM), platelet-rich plasma (PRP) threshold concentration (t.c. 50 μM), and an artificial system (washed platelets and fibrinogen) (t.c. 25 nM). Combination of low HOCl and peroxynitrite concentrations resulted in synergistic inhibition of CR by these stressors. Concentrations of HOCl completely inhibiting CR failed to affect the kinetics of coagulation measured in PRP and in platelet-free plasma. Concentrations of HOCl reducing CR rate in PRP augmented production of lactate, inhibited consumption of oxygen by platelets, and decreased total adenosine triphosphate (ATP) content in PRP-derived clots. In an artificial system, concentrations of HOCl resulting in inhibition of CR (25-100 nM) reduced mitochondrial transmembrane potential and did not affect actin polymerization in thrombin-stimulated platelets. These concentrations of HOCl failed to affect the adhesion of washed platelets to fibrinogen and to evoke sustained calcium signal, thus excluding stressor action on glycoprotein IIb/IIIa receptors. Exogenously added Mg-ATP almost completely recovered HOCl-mediated retardation of CR. Concentrations of HOCl higher than those affecting CR reduced thromboelastometric variables (maximum clot firmness and α angle). We conclude that low clinically relevant HOCl concentrations may evoke the inhibition of CR via the reduction of platelet contractility resulted from malfunction of platelet mitochondria. At the inflammatory conditions, CR may be the predominant HOCl target.

  1. Opioid-induced hyperalgesia: is it clinically relevant for the treatment of pain patients?

    Science.gov (United States)

    Raffa, Robert B; Pergolizzi, Joseph V

    2013-09-01

    There is a curious and paradoxic phenomenon, reliably demonstrated in animal models, that consists of an increased sensitivity to pain that is apparently induced by the very opioid drugs used to ameliorate the pain. This phenomenon is termed "opioid-induced hyperalgesia." Whether opioid-induced hyperalgesia occurs in humans, and, if so, to what extent and consequence, is far less established. This is a critical question for attempting to treat pain. If opioid-induced hyperalgesia develops in a patient, it would masquerade as tolerance (because the clinical effectiveness of the opioid would be diminished), yet the appropriate clinical adjustment would be precisely the opposite to that of tolerance. It would be to decrease, rather than increase, the dose of opioid. We review the evidence, particularly the clinical evidence, about opioid-induced hyperalgesia and the postulated mechanisms. We conclude that given the clinical ramifications, opioid-induced hyperalgesia is one of the most understudied important aspects of opioid research.

  2. Fatigue is a frequent and clinically relevant problem in Ehlers-Danlos Syndrome.

    NARCIS (Netherlands)

    Voermans, N.C.; Knoop, H.; Kamp, N. van de; Hamel, B.C.J.; Bleijenberg, G.; Engelen, B.G.M. van

    2010-01-01

    OBJECTIVES: Ehlers-Danlos Syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Fatigue and musculoskeletal pain are associated features but have never been stud

  3. Clinical relevance and scope of accidental extracoronary findings in coronary computed tomography angiography: A cardiac versus thoracic FOV study

    Energy Technology Data Exchange (ETDEWEB)

    Aglan, Iman; Jodocy, Daniel; Hiehs, Stefan; Soegner, Peter; Frank, Renate; Haberfellner, Berhard; Klauser, Andrea; Jaschke, Werner [Department of Radiology II, Innsbruck Medical University, Innsbruck (Austria); Feuchtner, Gudrun M. [Department of Radiology II, Innsbruck Medical University, Innsbruck (Austria)], E-mail: Gudrun.Feuchtner@i-med.ac.at

    2010-04-15

    Objective: To assess the spectrum and clinical relevance of extracoronary findings in coronary CT angiography (CCTA), and to compare a small (cardiac) field of view (FOV) to a large (thoracic) FOV setting. Material and methods: 1084 consecutive patients (mean 57 years) with low-to-intermediate risk of coronary artery disease were enrolled. 542 CCTA scans were interpreted with small FOV (160-190 mm{sup 2}) encompassing the cardiac region. In another 542 CCTA (patients matched for age and gender), read-out of an additional full FOV (>320 mm{sup 2}) covering the thorax was performed. Clinical relevance of extracoronary findings was considered as either 'significant' or 'non-significant'. 'Significant' findings were subclassified as either score 1: findings necessitating immediate therapeutic actions, or score 2: findings with undoubted clinical or prognostic relevance, requiring clinical awareness, follow-up or further investigations (non-urgent). 'Non-significant' findings were assigned to either score 3: findings not requiring follow-up or further tests, or as score 4: irrelevant incidental findings. Results: Significantly more patients with extracoronary findings were identified by using a full FOV with 43.2% (234/542) compared to a small FOV with 33.6% (182/542) (p = 0.001). Similarly, a higher total number of extracoronary findings (n = 394) was found on full FOV compared to small FOV (n = 250) (p < 0.001). The detection rate of clinically significant findings was higher by using full FOV compared to small FOV (25.6% versus 15.4%) (p < 0.001), out of those 2.2% versus 1.8% of findings required immediate actions (score 1), and 23.4% versus 13.6% (p = 0.0001), respectively were of clinical relevance (non-urgent, score 2). The rate of malign findings was 0.2%, and of acute pulmonary embolism 0.1%. More lung pathologies were observed by using full FOV compared to small FOV (22% versus 7%) (p < 0.0001), and the detection rate of

  4. Understanding the breakdown of classic two-phase theory and spray atomization at engine-relevant conditions

    Science.gov (United States)

    Dahms, Rainer N.

    2016-04-01

    A generalized framework for multi-component liquid injections is presented to understand and predict the breakdown of classic two-phase theory and spray atomization at engine-relevant conditions. The analysis focuses on the thermodynamic structure and the immiscibility state of representative gas-liquid interfaces. The most modern form of Helmholtz energy mixture state equation is utilized which exhibits a unique and physically consistent behavior over the entire two-phase regime of fluid densities. It is combined with generalized models for non-linear gradient theory and for liquid injections to quantify multi-component two-phase interface structures in global thermal equilibrium. Then, the Helmholtz free energy is minimized which determines the interfacial species distribution as a consequence. This minimal free energy state is demonstrated to validate the underlying assumptions of classic two-phase theory and spray atomization. However, under certain engine-relevant conditions for which corroborating experimental data are presented, this requirement for interfacial thermal equilibrium becomes unsustainable. A rigorously derived probability density function quantifies the ability of the interface to develop internal spatial temperature gradients in the presence of significant temperature differences between injected liquid and ambient gas. Then, the interface can no longer be viewed as an isolated system at minimal free energy. Instead, the interfacial dynamics become intimately connected to those of the separated homogeneous phases. Hence, the interface transitions toward a state in local equilibrium whereupon it becomes a dense-fluid mixing layer. A new conceptual view of a transitional liquid injection process emerges from a transition time scale analysis. Close to the nozzle exit, the two-phase interface still remains largely intact and more classic two-phase processes prevail as a consequence. Further downstream, however, the transition to dense-fluid mixing

  5. Clinical relevance of cytogenetics to pediatric practice. Postnatal findings of Patau syndrome - Review of 5 cases.

    Science.gov (United States)

    Plaiasu, Vasilica; Ochiana, Diana; Motei, Gabriela; Anca, Ioana; Georgescu, Adrian

    2010-07-01

    Patau syndrome (trisomy 13) is one of the most common chromosomal anomalies clinically characterized by the presence of numerous malformations with a limited survival rate for most cases. Babies are usually identified at birth and the diagnosis is confirmed with genetic testing. In this review we outline the clinical and cytogenetic aspects of trisomy 13 and associated phenotypes for 5 cases analyzed in the last 3 years, referred to our Clinical Genetics Department. For each child cytogenetic analysis was performed to determine the genetic variant; also, the patients were investigated for other associated malformations (cardiac, cerebral, renal, ocular anomalies). All 5 cases presented multiple malformations, including some but not all signs of the classical clinical triad suggestive of Patau syndrome. The cytogenetic investigation confirmed for each case the suspected diagnosis and also indicated the specific genetic variant, this being a valuable information for the genetic counselling of the families. The application of genetic analysis can increase diagnosis and prognosis accuracy and have an impact on clinical management.

  6. Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

    Directory of Open Access Journals (Sweden)

    W. B. Mattes

    2013-01-01

    Full Text Available Addressing safety concerns such as drug-induced kidney injury (DIKI early in the drug pharmaceutical development process ensures both patient safety and efficient clinical development. We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI. To examine this approach, a study of five compounds (phenytoin, cyclosporin A, doxorubicin, captopril, and lisinopril was initiated by the Technology Evaluation Consortium under the auspices of the Drug Safety Executive Council (DSEC. The metabolite profiles for rats treated with these compounds matched established reference patterns in the MetaMap Tox metabolomics database indicative of each compound’s well-described clinical toxicities. For example, the DIKI associated with cyclosporine A and doxorubicin was correctly predicted by metabolite profiling, while no evidence for DIKI was found for phenytoin, consistent with its clinical picture. In some cases the clinical toxicity (hepatotoxicity, not generally seen in animal studies, was detected with MetaMap Tox. Thus metabolite profiling coupled with the MetaMap Tox metabolomics database offers a unique and powerful approach for augmenting safety assessment and avoiding clinical adverse events such as DIKI.

  7. In vitro activity of levofloxacin against planktonic and biofilm Stenotrophomonas maltophilia lifestyles under conditions relevant to pulmonary infection in cystic fibrosis, and relationship with SmeDEF multidrug efflux pump expression.

    Science.gov (United States)

    Pompilio, Arianna; Crocetta, Valentina; Verginelli, Fabio; Bonaventura, Giovanni Di

    2016-07-01

    The activity of levofloxacin against planktonic and biofilm Stenotrophomonas maltophilia cells and the role played by the multidrug efflux pump SmeDEF were evaluated under conditions relevant to the cystic fibrosis (CF) lung. MIC, MBC and MBEC of levofloxacin were assessed, against five CF strains, under 'standard' (CLSI-recommended) and 'CF-like' (pH 6.8, 5% CO2, in a synthetic CF sputum) conditions. Levofloxacin was tested against biofilms at concentrations (10, 50 and 100 μg mL(-1)) corresponding to achievable serum levels and sputum levels by aerosolisation. smeD expression was evaluated, under both conditions, in planktonic and biofilm cells by RT-PCR. The bactericidal effect of levofloxacin was decreased, in three out of five strains tested, under 'CF-like' conditions (MBC: 2-4 vs 8-16 μg mL(-1), under 'standard' and 'CF-like' conditions, respectively). Biofilm was intrinsically resistant to levofloxacin, regardless of conditions tested (MBECs ≥ 100 μg mL(-1) for all strains). Only under 'CF-like' conditions, smeD expression increased during planktonic-to-biofilm transition, and in biofilm cells compared to stationary planktonic cells. Our findings confirmed that S. maltophilia biofilm is intrinsically resistant to therapeutic concentrations of levofloxacin. Under conditions relevant to CF, smeD overexpression could contribute to levofloxacin resistance. Further studies are warranted to define the clinical relevance of our findings.

  8. A Closer Look at Seborrheic Keratoses: Patient Perspectives, Clinical Relevance, Medical Necessity, and Implications for Management.

    Science.gov (United States)

    Del Rosso, James Q

    2017-03-01

    The author sought to discover why seborrheic keratoses that are not symptomatic or clinically suspicious are not considered therapeutically important to most clinicians. The author conducted an office-based, observational study examining how the diagnosis of asymptomatic seborrheic keratoses personally affects patients and what these patients think concerning treatment. Many patients reported being bothered by the diagnosis of seborrheic keratoses, even when told it's not cancerous, and indicated an interest in its treatment. Lack of insurance coverage for the treatment of non-symptomatic seborrheic keratoses may be the primary reason clinicians do not consider seborrheic keratoses therapeutically important, as clinicians often find the discussion of "self payment" with their patients to be awkward. Furthermore, patients may not understand the implications that "lack of medical necessity" may have on their treatment options. The author describes a clinical approach that may better serve patients and clinicians through the compartmentalization of asymptomatic seborrheic keratoses treatment as a cosmetic procedure within the clinical practice model.

  9. Development and application of two independent real-time PCR assays to detect clinically relevant Mucorales species.

    Science.gov (United States)

    Springer, Jan; Goldenberger, Daniel; Schmidt, Friderike; Weisser, Maja; Wehrle-Wieland, Elisabeth; Einsele, Hermann; Frei, Reno; Löffler, Jürgen

    2016-03-01

    PCR-based detection of Mucorales species could improve diagnosis of suspected invasive fungal infection, leading to a better patient outcome. This study describes two independent probe-based real-time PCR tests for detection of clinically relevant Mucorales, targeting specific fragments of the 18S and the 28S rRNA genes. Both assays have a short turnaround time, allow fast, specific and very sensitive detection of clinically relevant Mucorales and have the potential to be used as quantitative tests. They were validated on various clinical samples (fresh and formalin-fixed paraffin-embedded specimens, mainly biopsies, n = 17). The assays should be used as add-on tools to complement standard techniques; a combined approach of both real-time PCR assays has 100 % sensitivity. Genus identification by subsequent sequencing is possible for amplicons of the 18S PCR assay. In conclusion, combination of the two independent Mucorales assays described in this study, 18S and 28S, detected all clinical samples associated with proven Mucorales infection (n = 10). Reliable and specific identification of Mucorales is a prerequisite for successful antifungal therapy as these fungi show intrinsic resistance to voriconazole and caspofungin.

  10. A new cognitive evaluation battery for Down syndrome and its relevance for clinical trials.

    Science.gov (United States)

    de Sola, Susana; de la Torre, Rafael; Sánchez-Benavides, Gonzalo; Benejam, Bessy; Cuenca-Royo, Aida; Del Hoyo, Laura; Rodríguez, Joan; Catuara-Solarz, Silvina; Sanchez-Gutierrez, Judit; Dueñas-Espin, Ivan; Hernandez, Gimena; Peña-Casanova, Jordi; Langohr, Klaus; Videla, Sebastia; Blehaut, Henry; Farre, Magi; Dierssen, Mara

    2015-01-01

    The recent prospect of pharmaceutical interventions for cognitive impairment of Down syndrome (DS) has boosted a number of clinical trials in this population. However, running the trials has raised some methodological challenges and questioned the prevailing methodology used to evaluate cognitive functioning of DS individuals. This is usually achieved by comparing DS individuals to matched healthy controls of the same mental age. We propose a new tool, the TESDAD Battery that uses comparison with age-matched typically developed adults. This is an advantageous method for probing the clinical efficacy of DS therapies, allowing the interpretation and prediction of functional outcomes in clinical trials. In our DS population the TESDAD battery permitted a quantitative assessment of cognitive defects, which indicated language dysfunction and deficits in executive function, as the most important contributors to other cognitive and adaptive behavior outcomes as predictors of functional change in DS. Concretely, auditory comprehension and functional academics showed the highest potential as end-point measures of therapeutic intervention for clinical trials: the former as a cognitive key target for therapeutic intervention, and the latter as a primary functional outcome measure of clinical efficacy. Our results also emphasize the need to explore the modulating effects of IQ, gender and age on cognitive enhancing treatments. Noticeably, women performed significantly better than men of the same age and IQ in most cognitive tests, with the most consistent differences occurring in memory and executive functioning and negative trends rarely emerged on quality of life linked to the effect of age after adjusting for IQ and gender. In sum, the TESDAD battery is a useful neurocognitive tool for probing the clinical efficacy of experimental therapies in interventional studies in the DS population suggesting that age-matched controls are advantageous for determining normalization of

  11. A new cognitive evaluation battery for Down syndrome and its relevance for clinical trials

    Directory of Open Access Journals (Sweden)

    Susana ede Sola

    2015-06-01

    Full Text Available The recent prospect of pharmaceutical interventions for cognitive impairment of Down syndrome(DS has boosted a number of clinical trials in this population. However, running the trials has raised some methodological challenges and questioned the prevailing methodology used to evaluate cognitive functioning of DS individuals. This is usually achieved by comparing DS individuals to matched healthy controls of the same mental age. We propose a new tool, the TESDAD Battery that uses comparison with age-matched typically developed adults. This is an advantageous method for probing the clinical efficacy of DS therapies, allowing the interpretation and prediction of functional outcomes in clinical trials. In our DS population the TESDAD battery permitted a quantitative assessment of cognitive defects, which indicated language dysfunction and deficits in executive function, as the most important contributors to other cognitive and adaptive behavior outcomes as predictors of functional change in DS. Concretely, auditory comprehension and functional academics showed the highest potential as end-point measures of therapeutic intervention for clinical trials: the former as a cognitive key target for therapeutic intervention, and the latter as a primary functional outcome measure of clinical efficacy. Our results also emphasize the need to explore the modulating effects of IQ, gender and age on cognitive enhancing treatments. Noticeably, women performed significantly better than men of the same age and IQ in most cognitive tests, with the most consistent differences occurring in memory and executive functioning and negative trends rarely emerged on quality of life linked to the effect of age after adjusting for IQ and gender. In sum, the TESDAD battery is a useful neurocognitive tool for probing the clinical efficacy of experimental therapies in interventional studies in the DS population suggesting that age-matched controls are advantageous for determining

  12. Investigation of coatings of natural organic matter on silver nanoparticles under environmentally relevant conditions by surface-enhanced Raman scattering.

    Science.gov (United States)

    Kühn, Melanie; Ivleva, Natalia P; Klitzke, Sondra; Niessner, Reinhard; Baumann, Thomas

    2015-12-01

    The widespread use of engineered inorganic nanoparticles (EINP) leads to a growing risk for an unintended release into the environment. Despite the good characterization of EINP in regard to their function scale and the application areas, there is still a gap of knowledge concerning their behaviour in the different environmental compartments. Due to their high surface to volume ratio, surface properties and existence or development of a coating are of high importance for their stability and transport behaviour. However, analytical methods to investigate organic coatings on nanoparticles in aqueous media are scarce. We used Raman microspectroscopy in combination with surface-enhanced Raman scattering (SERS) to investigate humic acid coatings on silver nanoparticles under environmentally relevant conditions and in real world samples. This setup is more challenging than previous mechanistic studies using SERS to characterize the humic acids in tailored settings where only one type of organic matter is present and the concentrations of the nanoparticles can be easily adjusted to the experimental needs. SERS offers the unique opportunity to work with little sample preparation directly with liquid samples, thus significantly reducing artefacts. SERS spectra of different natural organic matter brought into contact with silver nanoparticles indicate humic acid in close proximity to the nanoparticles. This coating was also present after several washing steps by centrifugation and resuspension in deionized water and after an increase in ionic strength.

  13. Modeling Laser-Plasma Interactions at Direct-Drive Ignition-Relevant Plasma Conditions at the National Ignition Facility

    Science.gov (United States)

    Solodov, A. A.; Rosenberg, M. J.; Myatt, J. F.; Epstein, R.; Seka, W.; Hohenberger, M.; Short, R. W.; Shaw, J. G.; Regan, S. P.; Froula, D. H.; Radha, P. B.; Bates, J. W.; Schmitt, A. J.; Michel, P.; Moody, J. D.; Ralph, J. E.; Turnbull, D. P.; Barrios, M. A.

    2016-10-01

    Laser-plasma interaction instabilities, such as two-plasmon decay (TPD) and stimulated Raman scattering (SRS), can be detrimental for direct-drive inertial confinement fusion because of target preheat by generated high-energy electrons. The radiation-hydrodynamics code DRACO has been used to design planar-target experiments that generate plasma and interaction conditions relevant to direct-drive-ignition designs (IL 1015 W / cm 2 , Te > 3 KeV density gradient scale lengths of Ln 600 μm) . The hot-electron temperature of 40to50keV and the fraction of laser energy converted to hot electrons of 0.5to were inferred based on comparing the simulated and experimentally observed x-ray emission when the laser intensity at the quarter-critical surface increased from 6 to 15 ×1014 W / cm 2 . The measured SRS energy was sufficient to explain the observed total energy in hot electrons. Implications for ignition-scale direct-drive experiments and hot-electron preheat mitigation using mid- Z ablators will be discussed. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

  14. Naturally occurring BRCA2 alternative mRNA splicing events in clinically relevant samples

    DEFF Research Database (Denmark)

    Fackenthal, James D; Yoshimatsu, Toshio; Zhang, Bifeng

    2016-01-01

    BACKGROUND: BRCA1 and BRCA2 are the two principal tumour suppressor genes associated with inherited high risk of breast and ovarian cancer. Genetic testing of BRCA1/2 will often reveal one or more sequence variants of uncertain clinical significance, some of which may affect normal splicing patte...

  15. High Prevalence and Clinical Relevance of Genes Affected by Chromosomal Breaks in Colorectal Cancer

    NARCIS (Netherlands)

    Broek, E. van den; Dijkstra, M.J.; Krijgsman, O.; Sie, D.; Haan, J.C.; Traets, J.J.; Wiel, M.A. van de; Nagtegaal, I.D.; Punt, C.J.A.; Carvalho, B.; Ylstra, B.; Abeln, S.; Meijer, G.A.; Fijneman, R.J.

    2015-01-01

    BACKGROUND: Cancer is caused by somatic DNA alterations such as gene point mutations, DNA copy number aberrations (CNA) and structural variants (SVs). Genome-wide analyses of SVs in large sample series with well-documented clinical information are still scarce. Consequently, the impact of SVs on

  16. The scientific and clinical relevance of studying rare genetic/neurodevelopmental disease

    NARCIS (Netherlands)

    Kleefstra, T.; Pfundt, R.P.; Brunner, H.G.; Egger, J.I.M.

    2016-01-01

    Objective: Intellectual disability (ID) with or without autism spectrum disorders (ASD), is one of the main reasons for referral to a clinical geneticist. ID has a major impact on affected individuals, their families and society. The recent advances in genetic technologies have enabled to identify d

  17. Matrix metalloproteinases in gastric inflammation and cancer : clinical relevance and prognostic impact

    NARCIS (Netherlands)

    Kubben, Francois Jozef Gerard Marie

    2007-01-01

    The studies in this thesis describe the clinical impact of several matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in H. pylori-induced gastritis and gastric cancer. In patients with H. pylori-induced gastritis, significantly increased mucosal MMP-9 levels were f

  18. Matrix metalloproteinases in gastric inflammation and cancer : clinical relevance and prognostic impact

    NARCIS (Netherlands)

    Kubben, Francois Jozef Gerard Marie

    2007-01-01

    The studies in this thesis describe the clinical impact of several matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in H. pylori-induced gastritis and gastric cancer. In patients with H. pylori-induced gastritis, significantly increased mucosal MMP-9 levels were

  19. Determination of Clinically Relevant Content for a Musculoskeletal Anatomy Curriculum for Physical Medicine and Rehabilitation Residents

    Science.gov (United States)

    Lisk, Kristina; Flannery, John F.; Loh, Eldon Y.; Richardson, Denyse; Agur, Anne M. R.; Woods, Nicole N.

    2014-01-01

    To address the need for more clinical anatomy training in residency education, many postgraduate programs have implemented structured anatomy courses into their curriculum. Consensus often does not exist on specific content and level of detail of the content that should be included in such curricula. This article describes the use of the Delphi…

  20. The neurobiological mechanisms of gamma-hydroxybutyrate dependence and withdrawal and their clinical relevance: A review

    NARCIS (Netherlands)

    Kamal, R.M.; Noorden, M.S. van; Franzek, E.; Dijkstra, B.A.G.; Loonen, A.J.M.; Jong, C.A.J. de

    2016-01-01

    Objective: gamma-Hydroxybutyrate (GHB) has gained popularity as a drug of abuse. In the Netherlands the number of patients in treatment for GHB dependence has increased sharply. Clinical presentation of GHB withdrawal can be life threatening. We aim, through this overview, to explore the neurobiolog

  1. The inter-examiner reliability of standardized manual palpation for the identification of clinically relevant myofascial triggerpoints

    DEFF Research Database (Denmark)

    Myburgh, Corrie; Lauridsen, Henrik Hein; Larsen, Anders Holsgaard

    -observer agreement of TP examination among four examiners and whether reproducibility is influenced by examiner clinical experience. Two experienced and two inexperienced clinicians each performed a standardized palpation of the upper Trapezius musculature. Each observer was asked to judge the presents...... in order to improve protocol standardization. Kappa co-efficients were calculated for all possible examiner pairings. Good agreement was noted between the experienced pairing (κ= 0.63). Moderate levels of agreement were observed among the two mixed pairings (κ=0.35 and 0.47 respectively). However, poor......A clinical diagnosis of Myofascial Pain Syndrome (MPS) requires manual palpation for the identification of at least one clinically relevant trigger point (TP). However, few comparable, high quality studies exist regarding the robustness of TP examination. Our aim was to determine the inter...

  2. Shrimp allergy beyond Tropomyosin in Italy: clinical relevance of Arginine Kinase, Sarcoplasmic calcium binding protein and Hemocyanin.

    Science.gov (United States)

    Giuffrida, M G; Villalta, D; Mistrello, G; Amato, S; Asero, R

    2014-09-01

    Little is known about the prevalence and clinical relevance of sensitization to shrimp allergens other than tropomyosin. We detected the prevalence of arginine kinase and sarcoplasmic calcium binding protein sensitization, and identified a high molecular weight allergen that is frequently recognized by Italian shrimp-allergic patients. Sera from 40 shrimp-allergic patients underwent the detection of IgE specific for arginine kinase (rPen m 2) and sarcoplasmic calcium-binding protein (rPen m 4) by ISAC 112 Microarray platform and immunoblot analysis. A high molecular weight shrimp allergen was identified by N-terminal amino acid sequencing. IgE to rPen m 2 and rPen m 4 were found in 4/40 (10%) and 6/40 (15%) sera, respectively; two sera reacted to both allergens. Clinically, 6/8 Pen m 2 and/or Pen m 4 reactors experienced severe allergies to shrimp. On immunoblot, 4/6 rPen m 4-positive sera showed IgE reactivity at about 20 kDa, whereas no rPen m 2-positive serum reacted at about 40 kDa. Nineteen (47%) sera showed IgE reactivity at molecular weights > 60 kDa. Such profile was not associated with IgE reactivity to rPen m 2 or rPen m 4. N-terminal amino acid sequencing of the high molecular weight allergen led to the identification of hemocyanin. Shrimp arginine kinase and sarcoplasmic calcium-binding protein are minor allergens sensitizing only 10%-15% of Italian shrimp-allergic patients, but are clinically relevant. Hemocyanin is a clinically relevant high molecular weight shrimp allergen possibly cross-reacting to house dust mite.

  3. Characteristics and risk factors of major and clinically relevant non-major bleeding in cancer patients receiving anticoagulant treatment for acute venous thromboembolism-the CATCH study

    NARCIS (Netherlands)

    Kamphuisen, P.W.; Lee, A.Y.Y.; Meyer, Guy; Bauersachs, R.; Janas, M.S.; Jarner, M.F.; Khorana, A.A.

    2015-01-01

    Background: Cancer patients with acute venous thromboembolism (VTE) receiving anticoagulant treatment have a substantial risk of bleeding complications. Aims: To assess the rate, site and risk factors of clinically relevant bleeding (CRB; major or clinically relevant non-major bleeding) in cancer pa

  4. HIV/AIDS Indicators for Clinical Care Quality Assessment: Relevance and Utility Assessed by Health Professionals.

    Science.gov (United States)

    Catumbela, Emanuel Castro Cassoco; Santos, Cristina; Freitas, Alberto; Costa, Carlos; Sarmento, António; Costa Pereira, Altamiro

    2016-06-01

    Introdução: Após a realização de uma revisão sistemática sobre indicadores de qualidade para avaliar os cuidados clínicos prestados a doentes com infecção VIH/ SIDA, procuramos avaliar a relevância e utilidade clínica prática desses indicadores, do ponto de vista dos médicos especialistas em doenças infecciosas, incluindo VIH/ SIDA. Material e Métodos: Este é um estudo observacional, transversal, em que foram selecionados, por conveniência, os médicos que trabalham em um Departamento de Doenças Infecciosas de um hospital central, para responder a dois questionários, com um conjunto básico de indicadores, selecionando aqueles mais relevantes e úteis para a avaliação dos cuidados clínicos para avaliação do atendimento clínico prestado aos doentes com infeção por VIH/SIDA. A escala do tipo Likert foi utilizada para classificar os indicadores. Resultados: Onze dos treze médicos preencheram os dois questionários. A partir da lista inicial de 53 indicadores de qualidade, 21 foram identificados como os mais relevantes e úteis para avaliar os cuidados clínicos prestados a doentes com infeção por VIH/SIDA. A consistência interna para a relevância clínica, em cada domínio de indicadores foi quanto à relevância clínica – sinais clínicos (p = 0,971), terapêutica (p = 0,900), prognóstico (p = 0,820) e diagnóstico (p = 0,733) e quanto à utilidade prática – diagnóstico (p = 0,934), sinais clínicos (p = 0,964), exames laboratoriais (p = 0,947), terapêutica (p = 0,583) e prognóstico (p = 0,368). Discussão: No processo de avaliação da relevância clínica e utilidade prática dos indicadores de qualidade de cuidados prestados a doentes com infeção por VIH/SIDA, descobrimos que a maioria dos médicos concorda que os indicadores dos domínios de diagnóstico, sinais e sintomas clínicos são os mais importantes para avaliar a qualidade dos cuidados clínicos prestados a doentes com infeção por VIH/SIDA. Conclusão: Este

  5. Exhaled nitric oxide measure using multiple flows in clinically relevant subgroups of COPD

    DEFF Research Database (Denmark)

    Roberts, Nassim Bazeghi; Gerds, Thomas A; Budtz-Jørgensen, Esben

    2011-01-01

    meaningful subgroups of COPD in a group of 91 COPD patients with FEV(1) 17-77% of predicted. Multiple flow rates FeNO at 10, 30, 50, 100 and 200 mL/s were measured and a two-compartment model was used to estimate the diffusion Capacity (D), alveolar NO concentration (Calv) and airway wall NO concentration...... on D and Calv. The results were the same if the advanced non-linear mixed model was substituted by more standard analysis techniques. This study questions the relevance of using FeNO as a biomarker to evaluate local inflammation in COPD and points to a need for developing novel non-invasive biomarkers...

  6. Developing optimal search strategies for retrieving clinically relevant qualitative studies in EMBASE.

    Science.gov (United States)

    Walters, Leslie A; Wilczynski, Nancy L; Haynes, R Brian

    2006-01-01

    Qualitative researchers address many issues relevant to patient health care. Their studies appear in an array of journals, making literature searching difficult. Large databases such as EMBASE provide a means of retrieving qualitative research, but these studies represent only a minuscule fraction of published articles, making electronic retrieval problematic. Little work has been done on developing search strategies for the detection of qualitative studies. The objective of this study was to develop optimal search strategies to retrieve qualitative studies in EMBASE for the 2000 publishing year. The authors conducted an analytic survey, comparing hand searches of journals with retrievals from EMBASE for candidate search terms and combinations. Search strategies reached peak sensitivities at 94.2% and peak specificities of 99.7%. Combining search terms to optimize the combination of sensitivity and specificity resulted in values over 89% for both. The authors identified search strategies with high performance for retrieving qualitative studies in EMBASE.

  7. Non-celiac gluten sensitivity: clinical relevance and recommendations for future research.

    Science.gov (United States)

    Mooney, P D; Aziz, I; Sanders, D S

    2013-11-01

    There has been increasing interest in the entity of Non-Celiac Gluten Sensitivity (NCGS) in recent years; however, it still remains a controversial topic and its pathogenesis is not well understood. Celiac Disease, in contrast, is a well-studied condition that has become increasingly recognized as a prevalent condition arising from a heightened immunological response to gluten. Wheat allergy is an IgE-mediated condition capable of causing a variety of gastrointestinal symptoms. However, the number of patients who have neither celiac disease nor wheat allergy, but appear to derive benefit from a gluten-free diet, is also increasing substantially. The use of the term NCGS as a way of describing this condition has become increasingly prevalent in recent years. In this review, we will focus on gastrointestinal manifestations of NCGS and discuss the evidence for the condition and its putative pathogenesis. We will discuss areas of controversy and areas for potential future research. © 2013 John Wiley & Sons Ltd.

  8. Plutonium chemistry under conditions relevant for WIPP performance assessment. Review of experimental results and recommendations for future work

    Energy Technology Data Exchange (ETDEWEB)

    Oversby, Virginia M.

    2000-09-30

    The Waste Isolation Pilot Plant (WIPP), located at a depth of 650 m in bedded salt at a site approximately 40 km east of Carlsbad, New Mexico, was constructed by the US Department of Energy for the disposal of transuranic wastes arising from defense-related activities. The disposal site is regulated by the US Environmental Protection Agency (EPA). During the process leading to certification of the site for initial emplacement of waste, EEG and their contractors reviewed the DOE Compliance Certification Application (CCA) and raised a number of issues. This report reviews the issues related to the chemistry of plutonium as it will affect the potential for release of radioactivity under WIPP conditions. Emphasis is placed on conditions appropriate for the Human Intrusion scenario(s), since human intrusion has the largest potential for releasing radioactivity to the environment under WIPP conditions. The most significant issues that need to be addressed in relation to plutonium chemistry under WIPP conditions are (1) the effects of heterogeneity in the repository on Pu concentrations in brines introduced under the human intrusion scenario, (2) the redox state of Pu in solution and potential for plutonium in solid phases to have a different redox state from that in the solution phase, (3) the effect of organic ligands on the solubility of Pu in WIPP-relevant brines, and (4) the effects of TRU waste characteristics in determining the solubility of Pu. These issues are reviewed with respect to the treatment they received in the DOE CCA, DOE’s response to EEG’s comments on the CCA, and EPA’s response to those comments as reflected in the final EPA rule that led to the opening of the WIPP. Experimental results obtained in DOE’s Actinide Source-Term Test Program (STTP) during the last two years are reviewed and interpreted in the light of other developments in the field of Pu solution chemistry. This analysis is used as the basis for a conceptual model for Pu

  9. Are tidal lagoons ecologically relevant to larval recruitment of small pelagic fish? An approach using nutritional condition and growth rate

    Science.gov (United States)

    Chícharo, M. A.; Amaral, A.; Faria, A.; Morais, P.; Mendes, C.; Piló, D.; Ben-Hamadou, R.; Chícharo, L.

    2012-10-01

    There are numerous studies dealing with larvae of Small Pelagic Fish (SPF), but only a few have actually addressed advanced larval phases. Temperate coastal lagoons are particularly understudied, due to the absence of standard method to capture advanced larval fish in these near shore shallow habitats. Accordingly, this study aims to describe abundances, nutritional condition and in situ growth of post-flexion (SPF) from the Ria Formosa, a tidal coastal lagoon in southern Portugal. The nutritional condition and in situ growth were determined through cohort analysis and standardized RNA:DNA ratio (sRD), complemented with feeding incidence (gut content) and fatty acids (FAs, trophic biomarkers) of postflexion larvae sampled sequentially with light traps, from spring 2005 to summer 2006. Simultaneously, environmental parameters such as water temperature, salinity, dissolved oxygen and chlorophyll a were measured. Post-larvae of SPF were captured through the year in important numbers. The dominant species were Sardina pilchardus (50.7%), Engraulis encrasicolus and Atherina presbyter (11.4%). These results are distinct from those based on adult/juvenile surveys or early planktonic phases in the Ria Formosa where clupeiformes were occasionally reported. Sardines were captured mainly in winter, spring and early summer and anchovies mainly during summer and autumn. Sand smelt, a resident species, was present throughout the year. In the early summer, the three species were present and during this period some diet overlapping occurred, the feeding incidence of the clupeiformes was very low, but atherinids always exhibited full guts reflecting the different gut morphology or indicating different life-cycle strategies. The bulk of the diet was mollusks, crustaceans and appendicularians, for sand smelts, sardines and anchovies, respectively. The results of FA analyses showed some contribution of phytoplankton to SPF in the area. All SPF exhibited higher condition (sRD) and

  10. The Colorectal cancer disease-specific transcriptome may facilitate the discovery of more biologically and clinically relevant information

    Directory of Open Access Journals (Sweden)

    Proutski Vitali

    2010-12-01

    Full Text Available Abstract Background To date, there are no clinically reliable predictive markers of response to the current treatment regimens for advanced colorectal cancer. The aim of the current study was to compare and assess the power of transcriptional profiling using a generic microarray and a disease-specific transcriptome-based microarray. We also examined the biological and clinical relevance of the disease-specific transcriptome. Methods DNA microarray profiling was carried out on isogenic sensitive and 5-FU-resistant HCT116 colorectal cancer cell lines using the Affymetrix HG-U133 Plus2.0 array and the Almac Diagnostics Colorectal cancer disease specific Research tool. In addition, DNA microarray profiling was also carried out on pre-treatment metastatic colorectal cancer biopsies using the colorectal cancer disease specific Research tool. The two microarray platforms were compared based on detection of probesets and biological information. Results The results demonstrated that the disease-specific transcriptome-based microarray was able to out-perform the generic genomic-based microarray on a number of levels including detection of transcripts and pathway analysis. In addition, the disease-specific microarray contains a high percentage of antisense transcripts and further analysis demonstrated that a number of these exist in sense:antisense pairs. Comparison between cell line models and metastatic CRC patient biopsies further demonstrated that a number of the identified sense:antisense pairs were also detected in CRC patient biopsies, suggesting potential clinical relevance. Conclusions Analysis from our in vitro and clinical experiments has demonstrated that many transcripts exist in sense:antisense pairs including IGF2BP2, which may have a direct regulatory function in the context of colorectal cancer. While the functional relevance of the antisense transcripts has been established by many studies, their functional role is currently unclear

  11. Autoimmune ear disease: clinical and diagnostic relevance in Cogan’s sydrome

    Directory of Open Access Journals (Sweden)

    Luigi Maiolino

    2017-03-01

    Full Text Available The autoimmune inner ear disease is a clinical syndrome with uncertain pathogenesis that is often associated to rapidly progressive hearing loss that, especially at the early stages of disease, may be at monoaural localization, although more often it is at binaural localization. It usually occurs as a sudden deafness, or a rapidly progressive sensorineural hearing loss. In this study a particular form of autoimmune inner ear disease is described, Cogan’s syndrome. Cogan’s syndrome is a chronic inflammatory disorder that most commonly affects young adults. Clinical hallmarks are interstitial keratitis, vestibular and auditory dysfunction. Associations between Cogan’s syndrome and systemic vasculitis, as well as aortitis, also exist. We report a case of a young woman who presented audiological and systemic characteristics attributable to Cogan’s syndrome. In the description of the case we illustrate how the appearance and evolution of the disease presented.

  12. [Basic symptoms in schizophrenia, their clinical study and relevance in research].

    Science.gov (United States)

    Miret, Salvador; Fatjó-Vilas, Mar; Peralta, Víctor; Fañanás, Lourdes

    2016-01-01

    Basic symptoms consist of subtle sub-clinical disturbances subjectively experienced by schizophrenia patients. These are mainly related to drive, affect, thinking and language, perception, memory, motor action, central vegetative functions, control of cognitive processes, and stress tolerance. Initially described by Huber, from a phenomenological approach, basic symptoms are part of the earliest features of schizophrenia, and they can evolve along the course of the disorder. Their assessment during the prodromal phase of the disease (together with ultra-high risk criteria) is one of the 2 main approaches that allow the definition of states of clinical risk for the development of psychosis. The present review provides an updated view of the concept of basic symptoms, highlighting its potential value in establishing neurobiological correlates of interest in aetiopathogenic research. Copyright © 2015 SEP y SEPB. Published by Elsevier España. All rights reserved.

  13. Phylogeny of the clinically relevant species of the emerging fungus Trichoderma and their antifungal susceptibilities.

    Science.gov (United States)

    Sandoval-Denis, Marcelo; Sutton, Deanna A; Cano-Lira, José F; Gené, Josepa; Fothergill, Annette W; Wiederhold, Nathan P; Guarro, Josep

    2014-06-01

    A set of 73 isolates of the emerging fungus Trichoderma isolated from human and animal clinical specimens were characterized morphologically and molecularly using a multilocus sequence analysis that included the internal transcribed spacer (ITS) regions of the nuclear ribosomal DNA and fragments of the translation elongation factor 1 alpha (Tef1), endochitinase CHI18-5 (Chi18-5), and actin 1 (Act1) genes. The most frequent species was Trichoderma longibrachiatum (26%), followed by Trichoderma citrinoviride (18%), the Hypocrea lixii/Trichoderma harzianum species complex (15%), the newly described species Trichoderma bissettii (12%), and Trichoderma orientale (11%). The most common anatomical sites of isolation in human clinical specimens were the respiratory tract (40%), followed by deep tissue (30%) and superficial tissues (26%), while all the animal-associated isolates were obtained from superficial tissue samples. Susceptibilities of the isolates to eight antifungal drugs in vitro showed mostly high MICs, except for voriconazole and the echinocandins.

  14. Occult hepatitis C virus infection and its relevance in clinical practice.

    Science.gov (United States)

    Pham, Tram Nq; Michalak, Tomasz I

    2011-12-01

    Hepatitis C virus (HCV) can persist in the liver, lymphoid (immune) cells, and serum of individuals long after an apparently complete therapy-induced or a spontaneous resolution of hepatitis C. This essential asymptomatic infection, called secondary occult HCV infection (OCI), usually occurs in anti-HCV antibody reactive individuals with normal liver function tests. This infection has been identified when the nucleic acid amplification assays of enhanced sensitivity were applied for the detection of HCV genome and its replication. In addition to the secondary OCI, a form of low-level HCV-RNA-positive infection of unknown etiology coinciding with moderately elevated serum liver enzymes and progressing in the absence of anti-HCV detectable by standard clinical assays has been reported. Because of its undefined origin, it can be termed cryptogenic OCI. In this review, the general characteristics of OCI, the ways of its detection and associated controversies, and the potential clinical implications of its existence will be concisely outlined.

  15. Relevance of basic research to clinical data: good answers, wrong questions!

    Science.gov (United States)

    Ben-Ari, Yehezkel; Holmes, Gregory L

    2008-01-01

    Do early seizures beget seizures later in life? Clinical data and experimental observations seem to answer that question differently, with a no and a yes, respectively, which may stem from an inadequate readout of what experimental data actually do tell us and a possible simplification of what clinical data indicate. Using specific experimental examples, it is possible to show that in the developing brain, seizures do produce long-lasting alterations of neuronal excitability, although ongoing seizures are not observed in adults. The findings suggest that the long-lasting changes in developmental programs and network activity that seizures induce do not necessarily lead to epilepsy, unless other events that remain to be identified occur.

  16. The clinical relevance of cell-based therapy for the treatment of stress urinary incontinence

    DEFF Research Database (Denmark)

    Gräs, Søren; Lose, Gunnar

    2011-01-01

    Stress urinary incontinence is a common disorder affecting the quality of life for millions of women worldwide. Effective surgical procedures involving synthetic permanent meshes exist, but significant short- and long-term complications occur. Cell-based therapy using autologous stem cells...... or progenitor cells presents an alternative approach, which aims at repairing the anatomical components of the urethral continence mechanism. In vitro expanded progenitor cells isolated from muscle biopsies have been most intensely investigated, and both preclinical trials and a few clinical trials have...... provided proof of concept for the idea. An initial enthusiasm caused by positive results from early clinical trials has been dampened by the recognition of scientific irregularities. At the same time, the safety issue for cell-based therapy has been highlighted by the appearance of new and comprehensive...

  17. Spectrometric determination of clinically relevant fatty acids in the blood serum

    Science.gov (United States)

    Kalinin, A. V.; Krasheninnikov, V. N.; Sviridov, A. P.; Titov, V. N.

    2017-01-01

    The content of fatty acid (FA) triglycerides in food and biological media is predicting traditionally using gas and liquid chromatographic methods. Named techniques aren't available for clinical labs due to their complexity. So, our objective was to develop the method and apparatus for rapid assay of a few clinically important FA as the saturated palmitic, mono unsaturated oleic and others in serum using near infrared spectrometer. As a result, the applicability of the FT spectrometer in the wavelength range of 0.9 -1.8 μ to analyze these FA in serum without sample preparation was confirmed. Besides, measurement specifications were determined and a correlations of the absorption spectra and contents of total triglycerides and cholesterol, palmitic, oleic, linoleic and arachidonic FA in serum were established

  18. Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus.

    Science.gov (United States)

    Sommese, Linda; Zullo, Alberto; Mancini, Francesco Paolo; Fabbricini, Rossella; Soricelli, Andrea; Napoli, Claudio

    2017-06-03

    Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling β-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on β-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease.

  19. Circulating tumour cells as tumour biomarkers in melanoma: detection methods and clinical relevance.

    Science.gov (United States)

    Khoja, L; Lorigan, P; Dive, C; Keilholz, U; Fusi, A

    2015-01-01

    Circulating tumour cells (CTCs) are cells of solid tumour origin detectable in the peripheral blood. Their occurrence is considered a prerequisite step for establishing distant metastases. Metastatic melanoma was the first malignancy in which CTCs were detected and numerous studies have been published on CTC detection in melanoma at various stages of disease. In spite of this, there is no general consensus as to the clinical utility of CTCs in melanoma, largely due to conflicting results from heterogeneous studies and discrepancies in methods of detection between studies. In this review, we examine the possible clinical significance of CTCs in cutaneous, mucosal and ocular melanoma, focusing on detection methods and prognostic value of CTC detection.

  20. Spectrometric determination of clinically relevant fatty acids in the blood serum

    Science.gov (United States)

    Kalinin, A. V.; Krasheninnikov, V. N.; Sviridov, A. P.; Titov, V. N.

    2016-12-01

    The content of fatty acid (FA) triglycerides in food and biological media is predicting traditionally using gas and liquid chromatographic methods. Named techniques aren't available for clinical labs due to their complexity. So, our objective was to develop the method and apparatus for rapid assay of a few clinically important FA as the saturated palmitic, mono unsaturated oleic and others in serum using near infrared spectrometer. As a result, the applicability of the FT spectrometer in the wavelength range of 0.9 -1.8 μ to analyze these FA in serum without sample preparation was confirmed. Besides, measurement specifications were determined and a correlations of the absorption spectra and contents of total triglycerides and cholesterol, palmitic, oleic, linoleic and arachidonic FA in serum were established

  1. Lack of clinical relevance in routine final subcultures of radiometrically negative BACTEC blood culture vials

    Energy Technology Data Exchange (ETDEWEB)

    Plorde, J.J.; Carlson, L.G.; Dau, M.E.

    1982-11-01

    During a 38-month period, 10,106 blood specimens were received in the laboratory for culture. These were inoculated into 26,424 vials and processed using the BACTEC radiometric detection system. Of these vials, 1,914 were eventually found to be microbiologically positive. Isolates from 836 vials were judged to be contaminants. In the remaining 1,078 vials, growth was first detected visually or radiometrically in 1,062 and by final subculture in 16. Growth from these sixteen bottles represented 12 clinically significant bacteremic episodes in as many patients. In nine of these episodes, other culture vials from the same patient were positive radiometrically. Therefore, 358 of 361 (99.2%) bacteremic episodes were detected without the benefit of routine final subcultures. The three patients whose bacteremia was missed were diagnosed clinically and placed on appropriate therapy prior to the detection of the bacteremias by final subculture.

  2. Ultrasound in sports medicine: relevance of emerging techniques to clinical care of athletes.

    Science.gov (United States)

    Yim, Eugene Sun; Corrado, Gianmichael

    2012-08-01

    The applications of ultrasound in managing the clinical care of athletes have been expanding over the past decade. This review provides an analysis of the research that has been published regarding the use of ultrasound in athletes and focuses on how these emerging techniques can impact the clinical management of athletes by sports medicine physicians. Electronic database literature searches were performed using the subject terms 'ultrasound' and 'athletes' from the years 2003 to 2012. The following databases were searched: PubMed, Web of Science, Cochrane Library, CINAHL, and SPORTDiscus™. The search produced 617 articles in total, with a predominance of articles focused on cardiac and musculoskeletal ultrasound. 266 of the studies involved application of ultrasound in evaluating the cardiovascular properties of athletes, and 151 studies involved musculoskeletal ultrasound. Other applications of ultrasound included abdominal, vascular, bone density and volume status. New techniques in echocardiography have made significant contributions to the understanding of the physiological changes that occur in the athlete's heart in response to the haemodynamic stress associated with different types of activity. The likely application of these techniques will be in managing athletes with hypertrophic cardiomyopathy, and the techniques are near ready for application into clinical practice. These techniques are highly specialized, however, and will require referral to dedicated laboratories to influence the clinical management of athletes. Investigation of aortic root pathology and pulmonary vascular haemodynamics are also emerging, but will require additional studies with larger numbers and outcomes analysis to validate their clinical utility. Some of these techniques are relatively simple, and thus hold the potential to enter clinical management in a point-of-care fashion. Musculoskeletal ultrasound has demonstrated a number of diagnostic and therapeutic techniques

  3. [Classification and staging systems for hilar cholangio-carcinoma (Klatskin tumors): clinical application and practical relevance].

    Science.gov (United States)

    Gavrilovici, V; Grecu, F; Seripcariu, V; Dragomir, Cr

    2011-01-01

    Hilar cholangiocarcinomas or Klatskin tumors have been classified in 1975 by French surgeons Henri Bismuth and Marvin B. Corlette and this remains largely used in clinical practice. The authors present the TNM classification and the changes introduced by the sixth and seventh edition of Union for International Cancer Control regarding the tumors of the proximal bile duct and describe Blumgart classification for tumors of this site. The usefulness of these systems is assessed considering the last six years experience of the service.

  4. Clinical relevance of changes in bone metabolism in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Pal; Miheller; Katalin; Lrinczy; Peter; Laszlo; Lakatos

    2010-01-01

    Low bone mineral density is an established, frequent, but often neglected complication in patients with inflammatory bowel disease (IBD). Data regarding the diagnosis, therapy and follow-up of low bone mass in IBD has been partially extrapolated from postmenopausal osteoporosis; however, the pathophysiology of bone loss is altered in young patients with IBD. Fracture, a disabling complication, is the most important clinical outcome of low bone mass. Estimation of fracture risk in IBD is difficult. Numerous ...

  5. Warfarin Accelerates Ectopic Mineralization in Abcc6−/− Mice: Clinical Relevance to Pseudoxanthoma Elasticum

    OpenAIRE

    2013-01-01

    Pseudoxanthoma elasticum (PXE) is a multisystem ectopic mineralization disorder caused by mutations in the ABCC6 gene. Warfarin, a commonly used anticoagulant, is associated with increased mineralization of the arterial blood vessels and cardiac valves. We hypothesized that warfarin may accelerate ectopic tissue mineralization in PXE, with clinical consequences. To test this hypothesis, we developed a model in which Abcc6−/− mice, which recapitulate features of PXE, were fed a diet supplement...

  6. Attentional bias modification based on visual probe task: methodological issues, results and clinical relevance

    Directory of Open Access Journals (Sweden)

    Fernanda Machado Lopes

    2015-12-01

    Full Text Available Introduction: Attentional bias, the tendency that a person has to drive or maintain attention to a specific class of stimuli, may play an important role in the etiology and persistence of mental disorders. Attentional bias modification has been studied as a form of additional treatment related to automatic processing. Objectives: This systematic literature review compared and discussed methods, evidence of success and potential clinical applications of studies about attentional bias modification (ABM using a visual probe task. Methods: The Web of Knowledge, PubMed and PsycInfo were searched using the keywords attentional bias modification, attentional bias manipulation and attentional bias training. We selected empirical studies about ABM training using a visual probe task written in English and published between 2002 and 2014. Results: Fifty-seven studies met inclusion criteria. Most (78% succeeded in training attention in the predicted direction, and in 71% results were generalized to other measures correlated with the symptoms. Conclusions: ABM has potential clinical utility, but to standardize methods and maximize applicability, future studies should include clinical samples and be based on findings of studies about its effectiveness.

  7. Ultrasonographic Findings of the Gallbladder in Patients with Acute Hepatitis A: Do They Have Clinical Relevance?

    Energy Technology Data Exchange (ETDEWEB)

    An, Ji Young; Kim, Hyoung Jung; Lee, Dong Ho; Lim, Joo Won; Ko, Young Tae; Choi, Bong Keun [Dept. of Radiology, Graduate School of Medicine, Kyung Hee University, Kyung Hee University Medical Center, Seoul (Korea, Republic of)

    2012-06-15

    To determine the association of gallbladder (GB) abnormalities on ultrasonography (US) of patients with acute hepatitis A with demographic, clinical, and biochemical factors, and with other US findings. This retrospective study was approved by our institutional review board, which waived the requirement for informed consent. We retrospectively evaluated 152 consecutive patients with acute hepatitis A who underwent US. The diagnosis of acute hepatitis A was made during acute illness by demonstrating anti- HAV of the IgM class. US images were reviewed simultaneously by two abdominal radiologists and a consensus was reached for GB wall thickening, GB collapse, lymphadenopathy, and hepatic echogenicity. The associations between demographic, clinical, biochemical, and US findings and GB wall thickening or collapse were then assessed. GB wall thickening was present in 123 (81%) and GB collapse in 96 (63%) of the 152 patients. Total bilirubin level and GB collapse differed significantly (p < 0.05) between patients with and without GB wall thickening. Gender ratio, total and peak total bilirubin level, and GB wall thickness differed significantly (p < 0.05) between patients with and without GB collapse. Multivariate analysis showed that GB wall thickening was associated with GB collapse and vice versa. GB wall thickening and GB collapse are common US abnormalities associated with each other in patients with acute hepatitis A. However, GB wall thickening or collapse is not associated with any demographic, clinical, or biochemical factors, or with other US findings, in patients with acute hepatitis A.

  8. Clinical Relevance of Coronary Fractional Flow Reserve: Art-of-state

    Institute of Scientific and Technical Information of China (English)

    Yohanes Adiputra; Shao-Liang Chen

    2015-01-01

    Objective:The objective was to delineate the current knowledge of fractional flow reserve (FFR) in terms of definition,features,clinical applications,and pitfalls of measurement of FFR.Data Sources:We searched database for primary studies published in English.The database of National Library of Medicine (NLM),MEDLINE,and PubMed up to July 2014 was used to conduct a search using the keyword term "FFR".Study Selection:The articles about the definition,features,clinical application,and pitfalls of measurement of FFR were identified,retrieved,and reviewed.Results:Coronary pressure-derived FFR rapidly assesses the hemodynamic significance of individual coronary artery lesions and can readily be performed in the catheterization laboratory.The use of FFR has been shown to effectively guide coronary revascularization procedures leading to improved patient outcomes.Conclusions:FFR is a valuable tool to determine the functional significance of coronary stenosis.It combines physiological and anatomical information,and can be followed immediately by percutaneous coronary intervention (PCI) if necessary.The technique of FFR measurement can be performed easily,rapidly,and safely in the catheterization laboratory.By systematic use of FFR in dubious stenosis and multi-vessel disease,PCI can be made an even more effective and better treatment than it is currently.The current clinical evidence for FFR should encourage cardiologists to use this tool in the catheterization laboratory.

  9. Clinical Relevance of Coronary Fractional Flow Reserve: Art-of-state.

    Science.gov (United States)

    Adiputra, Yohanes; Chen, Shao-Liang

    2015-05-20

    The objective was to delineate the current knowledge of fractional flow reserve (FFR) in terms of definition, features, clinical applications, and pitfalls of measurement of FFR. We searched database for primary studies published in English. The database of National Library of Medicine (NLM), MEDLINE, and PubMed up to July 2014 was used to conduct a search using the keyword term "FFR". The articles about the definition, features, clinical application, and pitfalls of measurement of FFR were identified, retrieved, and reviewed. Coronary pressure-derived FFR rapidly assesses the hemodynamic significance of individual coronary artery lesions and can readily be performed in the catheterization laboratory. The use of FFR has been shown to effectively guide coronary revascularization procedures leading to improved patient outcomes. FFR is a valuable tool to determine the functional significance of coronary stenosis. It combines physiological and anatomical information, and can be followed immediately by percutaneous coronary intervention (PCI) if necessary. The technique of FFR measurement can be performed easily, rapidly, and safely in the catheterization laboratory. By systematic use of FFR in dubious stenosis and multi-vessel disease, PCI can be made an even more effective and better treatment than it is currently. The current clinical evidence for FFR should encourage cardiologists to use this tool in the catheterization laboratory.

  10. Enhancing clinically-relevant shoulder function assessment using only essential movements.

    Science.gov (United States)

    Pichonnaz, C; Lécureux, E; Bassin, J-P; Duc, C; Farron, A; Aminian, K; Jolles, B M; Gleeson, N

    2015-03-01

    Kinematic functional evaluation with body-worn sensors provides discriminative and responsive scores after shoulder surgery, but the optimal movements' combination has not yet been scientifically investigated. The aim of this study was the development of a simplified shoulder function kinematic score including only essential movements. The P Score, a seven-movement kinematic score developed on 31 healthy participants and 35 patients before surgery and at 3, 6 and 12 months after shoulder surgery, served as a reference. Principal component analysis and multiple regression were used to create simplified scoring models. The candidate models were compared to the reference score. ROC curve for shoulder pathology detection and correlations with clinical questionnaires were calculated. The B-B Score (hand to the Back and hand upwards as to change a Bulb) showed no difference to the P Score in time*score interaction (P > .05) and its relation with the reference score was highly linear (R(2) > .97). Absolute value of correlations with clinical questionnaires ranged from 0.51 to 0.77. Sensitivity was 97% and specificity 94%. The B-B and reference scores are equivalent for the measurement of group responses. The validated simplified scoring model presents practical advantages that facilitate the objective evaluation of shoulder function in clinical practice.

  11. Direct oral anticoagulants and antiplatelet agents. Clinical relevance and options for laboratory testing.

    Science.gov (United States)

    Sibbing, D; Spannagl, M

    2014-01-01

    Oral anticoagulants and platelet receptor blockers are widely used in clinical practice with the aim of reducing the risk of thrombotic complications in patients with cardiovascular diseases. Their regular intake and adequate antithrombotic action is vital and this is way numerous assays have been developed for laboratory testing and monitoring of these agents. Available assays can be stratified into pharmacokinetic and pharmacodynamic assays. Such assays are increasingly used in clinical routine and their daily use is triggered by the advent of the novel direct oral anticoagulants (DOACs) as an alternative for vitamin K antagonist (VKA) treatment, which are dabigatran, rivaroxaban and apixaban, and by the advent of prasugrel or ticagrelor as an alternative for clopidogrel with regard to platelet P2Y12 receptor inhibition. In this review the most important and most commonly used laboratory assays are summarized as well as their clinical implications with the focus on DOACs as an alternative for VKAs and the different P2Y12 receptor blockers for antiplatelet treatment.

  12. Clinical relevance of post-transplant pharmacodynamic analysis of cyclosporine in renal transplantation.

    Science.gov (United States)

    Kurata, Yoko; Kuzuya, Takafumi; Miwa, Yuko; Iwasaki, Kenta; Haneda, Masataka; Amioka, Katsuo; Yamada, Kiyofumi; Watarai, Yoshihiko; Katayama, Akio; Uchida, Kazuharu; Kobayashi, Takaaki

    2014-10-01

    Although therapeutic drug monitoring based on blood concentration has been widely implemented in transplant recipients treated with immunosuppressive agents, clinical adverse events such as rejection, infection or drug-induced toxicity caused by inappropriate dosage cannot be completely controlled. Development of an effective assay for optimized immunosuppression would be desirable, which can potentially lead to personalized medicine in renal transplantation. Cyclosporine (CSA) pharmacodynamic analysis using carboxyfluorescein diacetate succinimidyl ester (CFSE)-based T cell proliferation assay was examined in 66 kidney transplant recipients before and after transplantation. Two parameters, the 50% inhibitory concentration (IC50) and the percentage of T-cell proliferation values at the lower plateau (bottom), were compared with clinical events. A significant relation in CSA pharmacodynamic parameters was observed between pre- and post-transplantation. Analysis of the association between clinical outcomes and pharmacodynamic parameters in post-transplant samples demonstrated the following findings: (i) cytomegalovirus (CMV)/varicella zoster virus (VZV) reactivation and CSA-induced nephrotoxicity were significantly associated with high sensitivity to CSA (low bottom or low IC50), (ii) acute T cell-mediated rejection (ATMR) was significantly related to low sensitivity to CSA (high bottom), and (iii) de novo human leukocyte antigen (HLA) antibody production was associated with lower bottom and IC50 values, although the elucidation of those mechanisms is still in progress. It was suggested that CSA pharmacodynamics applied at post-transplantation would be useful for optimizing immunosuppressive therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Clinically relevant pain relief with an ibuprofen-releasing foam dressing

    DEFF Research Database (Denmark)

    Fogh, Karsten; Andersen, Maibritt B; Bischoff-Mikkelsen, Morten

    2012-01-01

    ) and the corresponding number needed to treat (NNT). Wound-related parameters such as ulcer healing, ulcer area reduction, and peri-ulcer skin condition as well as adverse events were recorded during all 6 weeks of the investigation. PAR was significantly greater in the ibuprofen foam group than the comparator group (p...

  14. Latarjet procedure: evolution of the bone block and correspondent clinical relevance-a clinical and radiological study.

    Science.gov (United States)

    Vadalà, A; Lanzetti, R M; De Carli, A; Lupariello, D; Guzzini, M; Desideri, D; Ferretti, A

    2017-07-29

    The purpose of this study was to correlate the bone block graft position, its dimension, its reabsorption and its integration with clinical outcome in patients operated on for recurrent anterior shoulder instability. Twenty-four patients affected by recurrent anterior shoulder dislocation and operated on using the Latarjet procedure were enrolled in this study. At 6 and 24 months, patients were evaluated with the following scales: ROWE, WOSI, Oxford instability score, UCLA, DASH and Constant score. Patients underwent two postoperative CT scans: immediately after surgery (T0) and at 24 months post-op (T1). At 24 months, none of the 24 patients reported further episodes of dislocation. Clinically at the final follow-up, we found excellent results in all the evaluation scales. Mean reduction in bone graft from T0 to T1 was 42% of the overall volume; similarly reduction in the overall surface was 29.3%; decrease in length, width and depth was, respectively, 3.4, 2.2 and 1.0 mm; all these parameters decreased significantly (p Latarjet procedure, but they do not significantly affect the clinical and functional results.

  15. Clinical and ultrasonographic findings of some ocular conditions in sheep and goats

    Directory of Open Access Journals (Sweden)

    O. El-Tookhy

    2013-01-01

    Full Text Available This study was carried out to describe the ultrasonographic findings in relation to the clinical symptoms of some common ocular conditions in sheep and goats. Fifty animals (32 goats and 18 sheep with different ocular problems were examined. Ultrasonographic examination was performed using a B-mode ocular ultrasound unit, and the structure of the globe was evaluated at a depth of 4-6 cm. Early cases (n=35, 70% showed varying ocular conditions; hypopyon, (n=8, 16%, stromal abscesses, (n=4, 8%, and anterior uveitis (n=23, 46%. Hypopyon appeared clinically as a white or yellowish material in the anterior chamber, and ultrasonographically as a hyperechoic mass in the anterior chamber. Severe iridocyclitis was noticed in acute cases of infectious keratoconjunctivitis (IKC accompanied by blepharospasm, photophobia, excessive tearing and eyelid margin crust formation. Ultrasonographically, the pupil appeared constricted with increased hyperechoic thickening of the ciliary body. In chronic cases of IKC, corneal pigmentation (n=5, 10% and cataract (n=10, 20% were seen. Ultrasonographically the type and degree of cataract were diagnosed. The present study provides an inside view of the inner ocular structures during the course of certain eye diseases where ophthalmoscopic examination is not possible. Our findings, although preliminary, are relevant for the more complete diagnosis of certain external ocular conditions in sheep and goat herds.

  16. Targeting breast cancer through its microenvironment: current status of preclinical and clinical research in finding relevant targets.

    Science.gov (United States)

    Nienhuis, H H; Gaykema, S B M; Timmer-Bosscha, H; Jalving, M; Brouwers, A H; Lub-de Hooge, M N; van der Vegt, B; Overmoyer, B; de Vries, E G E; Schröder, C P

    2015-03-01

    It is increasingly evident that not only breast cancer cells, but also the tissue embedding these cells: the tumor microenvironment, plays an important role in tumor progression, metastasis formation and treatment sensitivity. This review focuses on the current knowledge of processes by which the microenvironment affects breast cancer, including formation of the metastatic niche, metabolic stimulation, stimulation of tumor cell migration, immune modulation, angiogenesis and matrix remodeling. The number of drugs targeting key factors in these processes is expanding, and the available clinical data is increasing. Therefore current strategies for intervention and prediction of treatment response are outlined. At present, targeting the formation of the metastatic niche and metabolic stimulation by the breast cancer microenvironment, are already showing clinical efficacy. Intervening in the stimulation of tumor cell migration and immune modulation by the microenvironment upcoming fields of great research interest. In contrast, targeting microenvironmental angiogenesis or matrix remodeling appears to be of limited clinical relevance in breast cancer treatment so far. Further research is warranted to optimize intervention strategies and develop predictive tests for the relevance of targeting involved factors within the microenvironment in order to optimally personalize breast cancer treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Relationship between oral clinical conditions and daily performances

    Directory of Open Access Journals (Sweden)

    Andréa Silveira Gomes

    2009-03-01

    Full Text Available The aim of this study was to assess the impact of oral status on the daily performances of civil servants from the Public Works and Waste Management Department of the city of Porto Alegre, located in Southern Brazil. A cross-sectional study was conducted on a representative sample composed of 276 civil servants with ages ranging from 35 to 44 years. The Oral Impacts on Daily Performances index developed was employed to measure impacts caused by oral clinical conditions. Oral examinations were performed after the interviews. Multinomial Logistic Regression Analysis was used. After adjusting for sex and educational level, the results showed that the subjects with high DMFT scores were 5.8 times (95% CI = 2.1-16.1 more likely to have high impacts on their everyday life than those with low DMFT scores. Subjects that presented some coronal caries were 4.3 times (95% CI = 1.9-9.8 more likely to have high impacts on their everyday life than those with no coronal caries. Dental status assessed through the DMFT index and coronal caries are important indicators of impacts on the everyday life of the studied population.

  18. Obesity induction in hamster that mimics the human clinical condition.

    Science.gov (United States)

    Jordania da Silva, Vivian; Dias, Sílvia Regina Costa; Maioli, Tatiani Uceli; Serafim, Luciana Ribeiro; Furtado, Luis Fernando Viana; Quintão Silva, Maria da Gloria; Faria, Ana Maria Caetano de; Rabelo, Élida Mara Leite

    2017-08-05

    Although obesity is well established in hamsters, studies using diets with high levels of simple carbohydrate associated with lipids are necessary to assess the impact of this type of food in the body. In this study a high sugar and butter diet (HSB) and high temperature were employed towards this end. Obesity was successfully induced at a temperature of 30.3°C to 30.9°C after 38 days feeding the animals an HSB diet. It was shown that although diet is important for the induction of obesity, temperature is also essential because at a temperature slightly below the one required, obesity was not induced, even when the animals were fed for a longer period (150 days).The obese clinical condition was accompanied by biochemical and hematological changes, as increased cholesterol and triglyceride levels and increased leukocyte numbers, similar to alterations observed in obese humans. Furthermore, it was demonstrated that increasing the intake of simple carbohydrates associated with lipids provided evidence of inflammation in obese animals.

  19. Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors.

    Directory of Open Access Journals (Sweden)

    Winyoo Chowanadisai

    Full Text Available The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05 (S2 Table. Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition.

  20. The relevance of cellular to clinical electrophysiology in classifying antiarrhythmic actions.

    Science.gov (United States)

    Vaughan Williams, E M

    1992-01-01

    The division of class I antiarrhythmic agents (sodium-channel blockers) into Ia, Ib, and Ic subgroups was based on clinical observations. Lidocaine, mexiletine, and tocainide (Ib) did not alter the QRS or H-V interval in sinus rhythm, but prolonged effective refractory period (ERP) in spite of some shortening of the J-T interval. Encainide, flecainide, and lorcainide (Ic) widened the QRS and prolonged H-V in sinus rhythm and at low concentration, but had little effect on the ERP or J-T. These clinical findings could be explained by fast onset/offset kinetics of Ib drugs, that when used in high concentrations, blocked most sodium channels during the action potential plateau; therefore, at the beginning of diastole, insufficient drug-free channels were available to support conduction, and the ERP was prolonged. Rapid dissociation of the drugs after repolarization insured that by the end of diastole most channels were again drug free, so that the QRS and H-V were normal. The Ic compounds were more potent, but of slow onset, so that a steady-state block of Na channels was not achieved until after many beats. Offset was also slow, so that a proportion of channels was persistently unavailable, Na current was reduced, and conduction slowed, causing widening of the QRS and lengthening of H-V. Because the remaining drug-free channels were normal, they recovered rapidly from inactivation, and the ERP was not prolonged. By clinical criteria, moricizine also must be classed as Ic, and its offset/onset kinetics are much slower than those of Ib drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. [Detection of coronary calcifications by electron beam tomography and multislice spiral CT: clinical relevance].

    Science.gov (United States)

    Achenbach, S; Schmermund, A; Erbel, R; Silber, S; Haberl, R; Moshage, W; Daniel, W G

    2003-11-01

    Coronary calcifications can be detected and quantified using electron beam tomography (EBT) or newer generation multi-slice spiral CT (MSCT) scanners. An abundance of data has been acquired by EBT. It could be shown that the amount of coronary calcium correlates to the coronary plaque burden. The detection of coronary calcium with CT imaging methods therefore provides a unique opportunity to detect and quantify coronary atherosclerosis in a subclinical stage. Consequently, the presence and amount of coronary calcium has been shown to be indicative for an increased coronary event risk in symptomatic and asymptomatic individuals. Several clinical studies found a predictive value that was superior to conventional risk factors. Clinically, the use of coronary calcification assessment may therefore be beneficial in patients who, based on traditional risk factors, seem to be at "intermediate risk" for coronary events (10-year event risk 10-20%) in order to decide on the aggressiveness of risk factor modification. The role of coronary calcium quantification to monitor the progression of disease has not been clarified yet. Large, ongoing trials will provide further data as to the relative merit of coronary calcium assessment for risk stratification and will help to more clearly define its clinical role. The relationship between coronary calcium and coronary stenoses is more complex. While the absence of coronary calcifications makes significant coronary stenoses unlikely, even large amounts of coronary calcium do not necessarily indicate the presence of coronary artery stenoses. Pronounced coronary calcifications as an isolated finding should therefore not be the motivation for invasive diagnostic procedures in the absence of other evidence of ischemic heart disease.

  2. LEFT VENTRICULAR ROTATION, TWIST AND UNTWIST: PHYSIOLOGICAL ROLE AND CLINICAL RELEVANCE

    Directory of Open Access Journals (Sweden)

    E. N. Pavlyukova

    2015-01-01

    Full Text Available The helical ventricular myocardial band of Torrent-Guasp is a new concept, which provides strong grounds for reconciliation of some important aspects in cardiovascular medicine. Oblique fiber orientation provides left ventricular rotation, which in addition to radial thickening and longitudinal shortening, is predicted as an essential component of the effective left ventricular pumping. Left ventricular rotation can be measured in clinical practice noninvasively using echocardiography and this provides new opportunities for the assessment of different aspects of left ventricular mechanical function.

  3. Clinical and Pharmacotherapeutic Relevance of the Double-Chain Domain of the Angiotensin II Type 1 Receptor Blocker Olmesartan

    OpenAIRE

    Kiya, Yoshihiro; Miura, Shin-ichiro; Fujino, Masahiro; Imaizumi, Satoshi; Karnik, Sadashiva S.; Saku, Keijiro

    2010-01-01

    We previously reported that the angiotensin II type 1 (AT1) receptor blocker (ARB) olmesartan has two important interactions to evoke inverse agonism (IA). We refer to these interactions as the “double-chain domain (DCD).” Since the clinical pharmacotherapeutic relevance of olmesartan is still unclear, we examined these effects in rats and humans. We analyzed the effects at an advanced stage of renal insufficiency in Dahl salt-sensitive hypertensive rats (Study 1). Rats were fed a high-salt d...

  4. Pyrosequencing for detection of drug resistant relevant mutation in the polymerase gene of hepatitis B virus and its clinical application

    Institute of Scientific and Technical Information of China (English)

    陈占国

    2014-01-01

    Objective To explore the accuracy and clinical application of pyrosequencing for detection of drug resistant relevant mutation in the polymerase gene of hepatitis B virus(HBV).Methods Compared with Sanger sequencing,the accuracy and sensitivity of pyrosequencing were assessed.Pyrosequencing was used to determine the serum of 1 164 patients with chronic Hepatitis B and its re-sults were analyzed.Results The sensitivity of pyrosequencing was 1×103KIU/L,the same as Sanger sequencing.But

  5. Clinical Relevance of the Advanced Microbiologic and Biochemical Investigations in Periodontal Diagnosis: A Critical Analysis

    Directory of Open Access Journals (Sweden)

    Vishakha Grover

    2014-01-01

    Full Text Available New approaches to periodontal diagnosis, including advanced microbiologic, biochemical, and genetic tests, have been shown to provide the clinician with the information not available by traditional means. The purpose of a diagnostic test is to confirm, exclude, classify, or monitor disease to guide treatment. Their clinical value depends on whether the information they provide leads to improved patient outcomes. This can be assessed by randomized trials, which compare patient outcomes from the new diagnostic test versus the old test strategy. Being nonmandatory for marketing approval, such trials are not always feasible because of large sample sizes requirements. So, many diagnostic tests enter the practice without being critically analysed for any additional benefits. Effective diagnosis is just as essential as the selection of effective treatments for the success of periodontal therapy. So, the current paper aims to focus on the practical utility of this rapidly emerging plethora of periodontal diagnostic tools, emphasizing the critical issues surrounding the clinical application of microbiologic and biochemical investigations, employed for periodontal diagnosis.

  6. The trends of relevance about telling lung cancer diagnosis: social constraints, medical practice in several clinics.

    Science.gov (United States)

    Doruk, Sibel; Sevinç, Can; Sever, Fidan; Itil, Oya; Akkoçlu, Atila

    2012-01-01

    The aim of this study is to assess the opinions of relatives about telling the lung cancer diagnosis to the patient and evaluate the implementation in our hospital. A survey questionnaire was designed, and applied on nurses and physicians working in oncology care units, 4th-6th grade medical students, and relatives of cancer and non-cancer patients. Totally 347 (228 males, 119 females) participants (64 physicians, 100 nurses, 61 medical students, and 122 relatives of patients) with a mean age of 28 were enrolled in the study. 62.5% of doctors, 53.2% of nurses, 59.5% of medical students and 45.9% of relatives of lung cancer patients thought that the patient should be informed about his/her cancer diagnosis. 29.5% of the physicians told their patients about their diagnosis of cancer. Gender, age, abroad experience, academic career, speciality, and period of professional experience were not determined to have any impact on physician's opinion and clinical practices. It was determined that physicians care more about patients' right to be informed than other participating groups. Generally, although physicians agree that the diagnosis of cancer should be told to the patient, their routine clinical practices do not reflect this viewpoint.

  7. Teaching clinically relevant dental anatomy in the dental curriculum: description and assessment of an innovative module.

    Science.gov (United States)

    Obrez, Ales; Briggs, Charlotte; Buckman, James; Goldstein, Loren; Lamb, Courtney; Knight, William G

    2011-06-01

    The primary objective of the preclinical dental anatomy course in the predoctoral dental curriculum is to introduce students to cognitive and psychomotor skills related to the morphology and spatial and functional relationships of human dentition. Traditionally, didactic content for the subject is found in textbooks and course manuals and summarized by the faculty in lectures to the entire class. Psychomotor skills associated with recognition and reproduction of tooth morphology are traditionally learned by examining preserved tooth specimens and their cross-sections, combined with producing two-dimensional line drawings and carving teeth from wax blocks. These activities have little direct clinical application. In most cases, students are passive in the learning process, and assessment of student performance is unilateral and subjective. A recently revised dental anatomy module at the University of Illinois at Chicago College of Dentistry integrates independent class preparation with active small-group discussion and patient scenario-based wax-up exercises to replace missing tooth structure on manikin teeth. The goal of the revision is to shift emphasis away from decontextualized technical learning toward more active and clinically applicable learning that improves conceptual understanding while contributing to early acquisition of psychomotor skills. This article describes the rationale, components, and advantages of the revised module and presents a pre-post comparison of student learning outcomes for three class cohorts (N=203).

  8. DGIdb 2.0: mining clinically relevant drug-gene interactions.

    Science.gov (United States)

    Wagner, Alex H; Coffman, Adam C; Ainscough, Benjamin J; Spies, Nicholas C; Skidmore, Zachary L; Campbell, Katie M; Krysiak, Kilannin; Pan, Deng; McMichael, Joshua F; Eldred, James M; Walker, Jason R; Wilson, Richard K; Mardis, Elaine R; Griffith, Malachi; Griffith, Obi L

    2016-01-01

    The Drug-Gene Interaction Database (DGIdb, www.dgidb.org) is a web resource that consolidates disparate data sources describing drug-gene interactions and gene druggability. It provides an intuitive graphical user interface and a documented application programming interface (API) for querying these data. DGIdb was assembled through an extensive manual curation effort, reflecting the combined information of twenty-seven sources. For DGIdb 2.0, substantial updates have been made to increase content and improve its usefulness as a resource for mining clinically actionable drug targets. Specifically, nine new sources of drug-gene interactions have been added, including seven resources specifically focused on interactions linked to clinical trials. These additions have more than doubled the overall count of drug-gene interactions. The total number of druggable gene claims has also increased by 30%. Importantly, a majority of the unrestricted, publicly-accessible sources used in DGIdb are now automatically updated on a weekly basis, providing the most current information for these sources. Finally, a new web view and API have been developed to allow searching for interactions by drug identifiers to complement existing gene-based search functionality. With these updates, DGIdb represents a comprehensive and user friendly tool for mining the druggable genome for precision medicine hypothesis generation.

  9. Clinical Relevance of Telomere Status and Telomerase Activity in Colorectal Cancer.

    Science.gov (United States)

    Fernández-Marcelo, Tamara; Sánchez-Pernaute, Andrés; Pascua, Irene; De Juan, Carmen; Head, Jacqueline; Torres-García, Antonio-José; Iniesta, Pilar

    2016-01-01

    The role of telomeres and telomerase in colorectal cancer (CRC) is well established as the major driving force in generating chromosomal instability. However, their potential as prognostic markers remains unclear. We investigated the outcome implications of telomeres and telomerase in this tumour type. We considered telomere length (TL), ratio of telomere length in cancer to non-cancer tissue (T/N ratio), telomerase activity and TERT levels; their relation with clinical variables and their role as prognostic markers. We analyzed 132 CRCs and paired non-cancer tissues. Kaplan-Meier curves for disease-free survival were calculated for TL, T/N ratio, telomerase activity and TERT levels. Overall, tumours had shorter telomeres than non-tumour tissues (P Telomere lengths of non-tumour tissues and CRCs were positively correlated (P telomere status and clinical variables, the lowest degree of telomere shortening was shown by tumours located in the rectum (P = 0.021). Regarding prognosis studies, patients with tumours showing a mean TL telomere shortening relapsed during the follow-up period (P = 0.043). The mean TL in CRCs emerged as an independent prognostic factor in the Cox analysis (P = 0.017). Telomerase-positive activity was identified as a marker that confers a trend toward a poor prognosis. In CRC, our results support the use of telomere status as an independent prognostic factor. Telomere status may contribute to explaining the different molecular identities of this tumour type.

  10. Clinical relevance of microbleeds in acute stroke thrombolysis: Comprehensive meta-analysis.

    Science.gov (United States)

    Charidimou, Andreas; Shoamanesh, Ashkan

    2016-10-11

    We performed a systematic review and meta-analysis to assess whether the presence of cerebral microbleeds (CMBs) on pretreatment MRI of patients with acute ischemic stroke treated with IV thrombolysis is associated with increased risk of symptomatic intracerebral hemorrhage (ICH) and poor functional outcome. We searched PubMed for relevant studies and calculated pooled odds ratios (OR) for symptomatic ICH and poor (i.e., modified Rankin Scale score >2) 3- to 6-month functional outcome using random effects models with DerSimonian-Laird weights among individuals with vs without CMBs. Eight eligible studies including 2,601 stroke patients treated with IV thrombolysis were pooled in a meta-analysis. The cumulative CMBs prevalence was 24% (95% confidence interval [CI] 18%-30%). The pooled symptomatic ICH incidence was 5% (95% CI 4%-7%) among patients with CMBs and 3% (95% CI 2%-5%) in patients without CMBs. CMB presence was associated with higher risk of symptomatic ICH compared to patients without CMBs (OR 2.18; 95% CI 1.12-4.22; p = 0.021). Four studies (n = 1,665) reported data on 3- to 6-month poststroke functional outcome. The pooled incidence of poor functional outcome was 52% (95% CI 45%-59%) in patients with CMBs vs 41% (95% CI 35%-46%) in those without CMBs. Meta-analysis of these studies demonstrated OR for CMBs presence and adverse outcome to be 1.58 (95% CI 1.18-2.14; p = 0.002). CMBs are associated with greater symptomatic ICH risk and poor functional outcome in ischemic stroke patients undergoing thrombolytic therapy. In the absence of adjusted analyses and randomized evidence, this risk seems acceptable and should probably not discourage recanalization therapies in this patient population (Level B recommendation: nonrandomized Class IIa evidence). © 2016 American Academy of Neurology.

  11. Prevention of ventilator-associated pneumonia in the intensive care unit: A review of the clinically relevant recent advancements

    Directory of Open Access Journals (Sweden)

    Holly Keyt

    2014-01-01

    Full Text Available Ventilator-associated pneumonia (VAP is one of the most commonly encountered hospital-acquired infections in intensive care units and is associated with significant morbidity and high costs of care. The pathophysiology, epidemiology, treatment and prevention of VAP have been extensively studied for decades, but a clear prevention strategy has not yet emerged. In this article we will review recent literature pertaining to evidence-based VAP-prevention strategies that have resulted in clinically relevant outcomes. A multidisciplinary strategy for prevention of VAP is recommended. Those interventions that have been shown to have a clinical impact include the following: (i Non-invasive positive pressure ventilation for able patients, especially in immunocompromised patients, with acute exacerbation of chronic obstructive pulmonary disease or pulmonary oedema, (ii Sedation and weaning protocols for those patients who do require mechanical ventilation, (iii Mechanical ventilation protocols including head of bed elevation above 30 degrees and oral care, and (iv Removal of subglottic secretions. Other interventions, such as selective digestive tract decontamination, selective oropharyngeal decontamination and antimicrobial-coated endotracheal tubes, have been tested in different studies. However, the evidence for the efficacy of these measures to reduce VAP rates is not strong enough to recommend their use in clinical practice. In numerous studies, the implementation of VAP prevention bundles to clinical practice was associated with a significant reduction in VAP rates. Future research that considers clinical outcomes as primary endpoints will hopefully result in more detailed prevention strategies.

  12. Clinical relevance of precore mutations of hepatitis B virus in chronic liver disease

    Directory of Open Access Journals (Sweden)

    Chaloska-Ivanova Viktorija

    2014-07-01

    Full Text Available Introduction: Hepatitis B is one of the most frequent etiological factors for chronic liver diseases worldwide. Recent studies have suggested the important role of the genetic diversity of the virus on natural course of hepatitis B. Hepatitis B e-antigen negative type of chronic hepatitis is associated with mutations in the precore region and basic core promoter of hepatitis B viral genome. Aim of study was to identify precore mutations in viral genome of patients with chronic hepatitis B and to evaluate clinical patterns of liver disease related to this type of hepatitis B. Methods: Sixty seven patients with hepatitis B were included in the study. In order to evaluate the clinical patterns of chronic liver disease related to hepatitis B viral infection, biochemical and virological investigations were done, as well as a quantification of serum viral load. All patients underwent liver biopsy and semiquantification of necroinflammation and/or fibrosis according to Knodell scoring was done. In the group of e antigen-negative patients, molecular analysis was performed in order to identify presence of mutations in precore region of the virus. Results: Study group was divided in 25 HBeAg-positive and 42 HBeAg-negative subjects. Al anin-aminotransferase activity and level of viral load were higher in HBeAg-positive (p < 0.05, but average age and histology activity index were significantly higher in the HBeAg-negative patients (p < 0.01. Precore mutants were found in 38 of 42 patients with HBeAg-negative hepatitis (90%. Fibrosis was found in 30/38 cases with mutations. Discussion: Mutations in precore region of HBV in HBeAg-negative patients were more prevalent in older age and were associated with higher rate of fibrosis in liver tissue, meaning more advanced stage of the disease. This could be a consequence of longer duration of HBV infection or more severe clinical course of the disease. Conclusion: Our results suggest that precore mutations are

  13. Micro-separation in vitro produces clinically relevant wear of ceramic-ceramic total hip replacements

    Energy Technology Data Exchange (ETDEWEB)

    Nevelos, J.; Fisher, J. [Leeds Univ. (United Kingdom). School of Mechanical Engineering; Ingham, E. [Leeds Univ. (United Kingdom). Div. of Microbiology; Doyle, C. [Stryker Howmedica Osteonics, Newbury (United Kingdom); Streicher, R. [Stryker Howmedica Osteonics, Kilchberg (Switzerland); Nevelos, A. [Bradford Royal Infirmary, Bradford (United Kingdom)

    2001-07-01

    Typical clinical wear rates for well-positioned first generation ceramic-ceramic total hip arthroplasties (THAs) were of the order of 1-5 mm{sup 3}/year. This wear took the form of a 'stripe' of worn area on the heads with an Ra of approximately 0.1 {mu}m. As-manufactured unworn areas have an average Ra of 0.005 {mu}m Ra. This wear pattern has not been recorded following standard simulator testing with typical wear rates of less than 0.1 mm{sup 3} per million cycles. Therefore new material combinations for ceramic-ceramic total hip arthroplasty cannot be validated using standard hip simulator testing methods. However, recent fluoroscopy studies have shown that the head and cup of total hip replacements can separate during normal gait. This separation would lead to rim contact upon heel strike as shown in Figure 1. (orig.)

  14. Sperm DNA damage and its clinical relevance in assessing reproductive outcome

    Institute of Scientific and Technical Information of China (English)

    R.K.Sharma; T.Said; A.Agarwal

    2004-01-01

    The routine examination of semen, which assesses sperm concentration, percentage motility and morphology,does not identify subtle defects in sperm chromatin architecture. The focus on the genomic integrity of the male gamete has intensified recently due to the growing concern that genetic diseases may be transmitted via assisted reproductive techniques (ART). Accordingly, the intent of this review is to describe the details of the informationpertaining to mitochondfial/nuclear sperm DNA damage with an emphasis on its clinical significance and its relationship with male infertility. Assessment of sperm DNA damage appears to be a potential tool for evaluating semen samples prior to their use in ART. Testing DNA integrity may help select spermatozoa with intact DNA or with the least amount of DNA damage for use in assisted conception. In turn, this may alleviate the financial, social and emotional problems associated with failed ART attempts.

  15. [Triple therapy in cirrhotic patients and those with advanced fibrosis: relevant aspects in clinical practice].

    Science.gov (United States)

    Albillos, Agustín; Luis Calleja, José; Molina, Esther; Planas, Ramon; Romero-Gómez, Manuel; Turnes, Juan; Hernández-Guerra, Manuel

    2014-07-01

    The first-line option in the treatment of patients with advanced fibrosis and cirrhosis due to genotype 1 hepatitis C virus is currently triple therapy with boceprevir/telaprevir and pegylated interferon-ribavirin. However, certain limitations could constitute a barrier to starting treatment or achieving sustained viral response in these patients. These limitations include the patient's or physician's perception of treatment effectiveness in routine clinical practice-which can weight against the decision to start treatment-, the advanced stage of the disease with portal hypertension and comorbidity, treatment interruption due to poor adherence, and adverse effects, mainly anemia. In addition, it is now possible to identify patients who could benefit from a shorter therapeutic regimen with a similar cure rate. This review discusses these issues and their possible effect on the use of triple therapy. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  16. Gain-of-Function Research and the Relevance to Clinical Practice.

    Science.gov (United States)

    Kilianski, Andy; Nuzzo, Jennifer B; Modjarrad, Kayvon

    2016-05-01

    The ongoing moratorium on gain-of-function (GOF) research with highly pathogenic avian influenza virus, severe acute respiratory syndrome coronavirus, and Middle East respiratory syndrome coronavirus has drawn attention to the current debate on these research practices and the potential benefits and risks they present. While much of the discussion has been steered by members of the microbiology and policy communities, additional input from medical practitioners will be highly valuable toward developing a broadly inclusive policy that considers the relative value and harm of GOF research. This review attempts to serve as a primer on the topic for the clinical community by providing a historical context for GOF research, summarizing concerns about its risks, and surveying the medical products that it has yielded.

  17. A Clinically Relevant Method of Analyzing Continuous Change in Robotic Upper Extremity Chronic Stroke Rehabilitation.

    Science.gov (United States)

    Massie, Crystal L; Du, Yue; Conroy, Susan S; Krebs, H Igo; Wittenberg, George F; Bever, Christopher T; Whitall, Jill

    2016-09-01

    Robots designed for rehabilitation of the upper extremity after stroke facilitate high rates of repetition during practice of movements and record precise kinematic data, providing a method to investigate motor recovery profiles over time. To determine how motor recovery profiles during robotic interventions provide insight into improving clinical gains. A convenience sample (n = 22), from a larger randomized control trial, was taken of chronic stroke participants completing 12 sessions of arm therapy. One group received 60 minutes of robotic therapy (Robot only) and the other group received 45 minutes on the robot plus 15 minutes of translation-to-task practice (Robot + TTT). Movement time was assessed using the robot without powered assistance. Analyses (ANOVA, random coefficient modeling [RCM] with 2-term exponential function) were completed to investigate changes across the intervention, between sessions, and within a session. Significant improvement (P stroke robotic interventions. © The Author(s) 2015.

  18. Mechanistic basis and clinical relevance of the role of transforming growth factor-βin cancer

    Institute of Scientific and Technical Information of China (English)

    Run-Long Lin; Lu-Jun Zhao

    2015-01-01

    Transforming growth factor-β(TGF-β) is a key factor in cancer development and progression. TGF-βcan suppress tumorigenesis by inhibiting cell cycle progression and stimulating apoptosis in early stages of cancer progression. However, TGF-βcan modulate cancer-related processes, such as cell invasion, distant metastasis, and microenvironment modiifcation that may be used by cancer cells to their advantage in late stages. Corresponding mechanisms include angiogenesis promotion, anti-tumor immunity suppression, and epithelial-to-mesenchymal transition (EMT) induction. hTe correlation between TGF-βexpression and cancer prognosis has also been extensively investigated. Results suggest that TGF-βpathway can be targeted to treat cancer;as such, the feasibility of this treatment is investigated in clinical trials.

  19. The type I interferons: Basic concepts and clinical relevance in immune-mediated inflammatory diseases.

    Science.gov (United States)

    López de Padilla, Consuelo M; Niewold, Timothy B

    2016-01-15

    There is increasing scientific and clinical interest in elucidating the biology of type I Interferons, which began approximately 60 years ago with the concept of "viral interference", a property that reduces the ability of a virus to infect cells. Although our understanding of the multiple cellular and molecular functions of interferons has advanced significantly, much remains to be learned and type I Interferons remain an active and fascinating area of inquiry. In this review, we cover some general aspects of type I interferon genes, with emphasis on interferon-alpha, and various aspects of molecular mechanisms triggered by type I interferons and toll-like receptor signaling by the Janus activated kinase/signal transducer activation of transcription (JAK-STAT) pathway and interferon regulatory factor pathway. We will also describe the role of type I interferons in autoimmune and inflammatory diseases, and its potential use as therapeutic agent.

  20. Clinical Relevance of CHEK2 And NBN Mutations in the Macedonian Population

    Directory of Open Access Journals (Sweden)

    Maleva Kostovska I.

    2015-06-01

    Full Text Available Clinical importance of the most common CHEK2 (IVS2+1 G>A, 1100delС, I157T and del5395 and NBN (R215W and 657del5 gene mutations for breast cancer development in Macedonian breast cancer patients is unknown. We performed a case-control study including 300 Macedonian breast cancer patients and 283 Macedonian healthy controls. Genotyping was done using a fast and highly accurate single-nucleotide primer extension method for the detection of five mutations in a single reaction. The detection of the del5395 was performed using an allele-specific duplex polymerase chain reaction (PCR assay. We have found that mutations were more frequent in breast cancer patients (n = 13, 4.3% than in controls (n = 5, 1.8%, although without statistical significance. Twelve patients were heterozygous for one of the analyzed mutations, while one patient had two mutations (NBN R215W and CHEK2 I157T. The most frequent variant was I157T, found in 10 patients and four controls (p = 0.176 and was found to be associated with familial breast cancer (p = 0.041. CHEK2 1100delC and NBN 657del5 were each found in one patient and not in the control group. CHEK2 IVS2+1G>A and del5395 were not found in our cohort. Frequencies of the studied mutations are low and they are not likely to represent alleles of clinical importance in the Macedonian population.

  1. [Clinical relevance of the K-ras oncogene in colorectal cancer: experience in a Mexican population].

    Science.gov (United States)

    Cabrera-Mendoza, F; Gainza-Lagunes, S; Castañeda-Andrade, I; Castro-Zárate, A

    2014-01-01

    Colorectal cancer is frequent in the developed countries, with a cancer-specific mortality rate of 33%. Different biomarkers are associated with overall survival and the prediction of monoclonal treatment effectiveness. The presence of mutations in the K-ras oncogene alters the response to target therapy with cetuximab and could be an independent prognostic factor. To analyze the difference in survival between patients with mutated K-ras and those with K-ras wild-type status. Thirty-one clinical records were retrospectively analyzed of patients presenting with colorectal cancer that underwent K-ras sequencing through real-time polymerase chain reaction within the time frame of 2009 to 2012 at the Hospital de Alta Especialidad de Veracruz of the Instituto para la Salud y Seguridad Social de los Trabajadores del Estado (HAEV-ISSSTE). Survival analysis for patients with and without K-ras mutation was performed using the Kaplan Meier method. Contrast of covariates was performed using logarithmic transformations. No statistically significant difference was found in relation to survival in the patients with mutated K-ras vs. those with K-ras wild-type (P=.416), nor were significant differences found when analyzing the covariants and survival in the patients with mutated K-ras: ECOG scale (P=.221); age (less than, equal to or greater than 65years, P=.441); clinical stage according to the AJCC (P=.057), and primary lesion site (P=.614). No relation was found between the K-ras oncogene mutation and reduced survival, in contrast to what has been established in the international medical literature. Further studies that include both a larger number of patients and those receiving monoclonal treatment, need to be conducted. There were only 5 patients in the present study that received cetuximab, resulting in a misleading analysis. Copyright © 2013 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

  2. LUPUS NEPHRITIS COMPLICATED WITH MALIGNANT HYPERTENSION: FROM RENAL VASCULAR PATHOLOGY TO CLINICAL RELEVANCE

    Institute of Scientific and Technical Information of China (English)

    Jian-ling Tao; Hang Li; Yu Tang; Yu-bing Wen; Xue-wang Li

    2008-01-01

    Objective To investigate the clinical and pathological characteristics of lupus nephritis patients complicated with malignant hypertension.Methods We retrospectively studied 19 patients with lupus nephritis complicated with malignant hypertension who underwent renal biopsy between January 2002 and December 2006.Results Of 19 patients, 3 were men and 16 were women, with a mean age of 24. 4±7. 7 years old. All had positive antinuclear antibodies and low serum complement was found in 13 patients. All were anemic and 12 of them were thrombocytopenic. Impaired renal function was found in 17 patients with an average serum creatinine of 184. 5 ± 88.9 μmol/L. Severe intrarenai arteriolar lesion was found in all patients. Six patients had lupus vasculopathy, 11 patients had renal thrombotic microangiopathy lesion, 2 had severe arteriosclerosis. All patients received steroids and immunosuppressive drugs, 15 received angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker ( ARB ) with resultant well-controlled blood pressure. Thrombocytopenia and hemolytic anemia resolved remarkably.The renal function improved or recovered in 14 of 17 patients, and 3 developed end-stage renal disease on maintenance dialysis.Conclusions Severe intrarenal vascular lesion complicated with renal nephritis parallels clinical manifestation of malignant hypertension. Renal pathology is the key of treatment strategy emphasizing on the significance of renal vascular involvement and type. On the basis of immunosuppressive drugs and steroids to control systemic lupus activity, timely initiation of ACEI/ARB could be of benefit to blood pressure control and long term renal survival.

  3. Relationship of premenstrual syndrome and premenstrual dysphoric disorder with major depression: Relevance to clinical practice

    Directory of Open Access Journals (Sweden)

    Susanta Kumar Padhy

    2015-01-01

    Full Text Available Background: Premenstrual syndrome (PMS, premenstrual dysphoric disorder (PMDD and depressive disorder are fairly common; symptoms do overlap, often under-identified and under-emphasized, particularly in rural India. Objective: The objective was to assess the occurrence of PMS and PMDD in a sample of students and staff of a nursing college and to find their correlation with depression. Materials and Methods: A prospective cohort study; Tertiary Care Hospital in Rural India (Wardha, Maharashtra; 118 female nursing students or staff aged between 18 and 40 years, who were likely to stay within the institution for the study period. The participants were rated on Penn daily symptom report prospectively for a period of 3-month. Those who scored positive were applied diagnostic and statistical manual of mental disorders, 4 th edition, text revision (DSM-IV TR criteria for PMDD; and were applied primary care evaluation of mental disorders depression screening followed by DSM-IV TR criteria for depression. Severity of depression was measured using Hamilton Depression Rating Scale. Results: Main outcome measures were frequency and severity of depression in individuals with PMS and PMDD and their clinical and sociodemographic correlation. The age range of the sample was 18-37 years. Some PMS symptoms were observed in 67%; diagnosis of PMDD in 10%; depressive symptoms in 28% of the sample. 46.4% of those with depressive symptoms had major depression. The diagnosis of major depression was significantly associated with the severity of PMS symptoms as well as the presence of PMDD. Conclusion: Premenstrual syndrome is present in a substantial proportion of young females. Concurrent depression is increased by the severity of PMS symptoms and the presence of PMDD. Gynecologist needs to screen such subjects for depression and refer to mental-health professional early, in routine clinical practice.

  4. Relevance of Retinal Thickness Changes in the OCT Inner and Outer Rings to Predict Progression to Clinical Macular Edema

    DEFF Research Database (Denmark)

    Vujosevic, Stela; Varano, Monica; Egan, Catherine

    2015-01-01

    PURPOSE: To characterize the relevance of macular thickness changes in the inner and outer rings in the progression of macular edema in eyes/patients with diabetes type 2. METHODS: A total of 374 type 2 diabetic patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20-35) were...... included in a 12-month prospective observational study to identify retinopathy progression. Retinal thickness analyses were performed in 194 eyes/patients using Cirrus SD- OCT and 166 eyes/patients using Spectralis SD-OCT. The DRCR.net classification of subclinical and clinical macular edema was used....... A composite grading of macular edema is proposed in this study. RESULTS: A total of 317 eyes/patients completed the study. SD-OCT identified clinical macular edema in 24 eyes/patients (6.7%) and subclinical macular edema in 104 eyes/patients (28.9%) at baseline. Increased thickness of the central subfield...

  5. Multicentre study highlighting clinical relevance of new high-throughput methodologies in molecular epidemiology of Pneumocystis jirovecii pneumonia.

    Science.gov (United States)

    Esteves, F; de Sousa, B; Calderón, E J; Huang, L; Badura, R; Maltez, F; Bassat, Q; de Armas, Y; Antunes, F; Matos, O

    2016-06-01

    Pneumocystis jirovecii causes severe interstitial pneumonia (PcP) in immunosuppressed patients. This multicentre study assessed the distribution frequencies of epidemiologically relevant genetic markers of P. jirovecii in different geographic populations from Portugal, the USA, Spain, Cuba and Mozambique, and the relationship between the molecular data and the geographical and clinical information, based on a multifactorial approach. The high-throughput typing strategy for P. jirovecii characterization consisted of DNA pooling using quantitative real-time PCR followed by multiplex-PCR/single base extension. The frequencies of relevant P. jirovecii single nucleotide polymorphisms (mt85, SOD110, SOD215, DHFR312, DHPS165 and DHPS171) encoded at four loci were estimated in ten DNA pooled samples representing a total of 182 individual samples. Putative multilocus genotypes of P. jirovecii were shown to be clustered due to geographic differences but were also dependent on clinical characteristics of the populations studied. The haplotype DHFR312T/SOD110C/SOD215T was associated with severe AIDS-related PcP and high P. jirovecii burdens. The frequencies of this genetic variant of P. jirovecii were significantly higher in patients with AIDS-related PcP from Portugal and the USA than in the colonized patients from Portugal, and Spain, and children infected with P. jirovecii from Cuba or Mozambique, highlighting the importance of this haplotype, apparently associated with the severity of the disease and specific clinical groups. Patients from the USA and Mozambique showed higher rates of DHPS mutants, which may suggest the circulation of P. jirovecii organisms potentially related with trimethoprim-sulfamethoxazole resistance in those geographical regions. This report assessed the worldwide distribution of P. jirovecii haplotypes and their epidemiological impact in distinct geographic and clinical populations.

  6. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders

    DEFF Research Database (Denmark)

    van de Donk, Niels W C J; Palumbo, Antonio; Johnsen, Hans Erik

    2014-01-01

    Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; light-chain monoclonal gammopathy of undetermined significance of light-chain multiple...... myeloma; and IgM monoclonal gammopathy of undetermined significance of Waldenström's macroglobulinemia and other lymphoproliferative disorders. Clonal burden, as determined by bone marrow plasma cell percentage or M-protein level, as well as biological characteristics, including heavy chain isotype...... and light chain production, are helpful in predicting risk of progression of monoclonal gammopathy of undetermined significance to symptomatic disease. Furthermore, alterations in the bone marrow microenvironment of monoclonal gammopathy of undetermined significance patients result in an increased risk...

  7. Building a clinically relevant cognitive task: case study of the AX paradigm.

    Science.gov (United States)

    MacDonald, Angus W

    2008-07-01

    Tasks developed for basic cognitive neuroscience are often ill suited for experimental psychopathology. The development of the expectancy variant of AX continuous performance task to test theories about context processing in schizophrenia is used as an illustration of how this has been done in one research program. Four design principles are recommended: tasks should (1) have a foundation in existing literature and therefore stay as close as possible to an existing task; (2) be simple, which is frequently accomplished by paring down a task to evaluate the function of interest; (3) probe a mechanism of interest, with conditions that selectively manipulate this mechanism; and (4) have the potential to distinguish a specific deficit on the mechanism of interest from a generalized impairment. Data from a number of studies support several aspects of context-processing theory; however unpredicted results have also been reported. The development of the expectancy AX paradigm continues, and future developments that may enhance its usefulness are also described.

  8. Clinical evaluation for radiotherapy of metastatic brain tumors in lung cancer. Prognostic analyses relevant to QOL

    Energy Technology Data Exchange (ETDEWEB)

    Myojin, Miyako; Nishio, Masamichi; Mizoguchi, Fumiki; Kawashima, Kazuyuki; Mita, Noriko [Sapporo National Hospital (Japan); Fujita, Akihisa

    1998-01-01

    From 1986 through 1992, 144 patients with metastatic brain tumors of lung cancer were treated with X-ray irradiation to whole brain or a comparatively wide field of the brain. To identify the subset of patients indicated for boost therapy like a stereotactic radiotherapy, we have analyzed the treatment results concerning both survival and performance status (PS). Median survival time of the patients in good PS (0-2) was 6.7 months, which was significantly better than 2.3 months in poor PS (3-4). Complete tumor-resectability, age, steroid therapy and condition within two months after the beginning of brain irradiation, seemed to be important prognostic indicators correlated with PS by both univariate and multivariates analyses. (author)

  9. Clinical relevance of aberrant polypoid nodule scar after endoscopic submucosal dissection

    Science.gov (United States)

    Arantes, Vitor; Uedo, Noriya; Pedrosa, Moises Salgado; Tomita, Yasuhiko

    2016-01-01

    AIM To describe a series of patients with aberrant polypoid nodule scar developed after gastric endoscopic submucosal dissection (ESD), and to discuss its pathogenesis and clinical management. METHODS We reviewed retrospectively the endoscopic database of two academic institutions located in Brazil and Japan and searched for all patients that underwent ESD to manage gastric neoplasms from 2003 to 2015. The criteria for admission in the study were: (1) successful en bloc ESD procedure with R0 and curative resection confirmed histologically; (2) postoperative endoscopic examination with identification of a polypoid nodule scar (PNS) at ESD scar; (3) biopsies of the PNS with hyperplastic or regenerative tissue, reviewed by two independent experienced gastrointestinal pathologists, one from each Institution. Data were examined for patient demographics, Helicobacter pylori status, precise neoplastic lesion location in the stomach, tumor size, histopathological assessment of the ESD specimen, and postoperative information including medical management, endoscopic and histological findings, and clinical outcome. RESULTS A total of 14 patients (10 men/4 women) fulfilled the inclusion criteria and were enrolled in this study. One center contributed with 8 cases out of 60 patients (13.3%) from 2008 to 2015. The second center contributed with 6 cases (1.7%) out of 343 patients from 2003 to 2015. Postoperative endoscopic follow-up revealed similar findings in all patients: A protruded polypoid appearing nodule situated in the center of the ESD scar surrounded by convergence of folds. Biopsies samples were taken from PNS, and histological assessment revealed in all cases regenerative and hyperplastic tissue, without recurrent tumor or dysplasia. Primary neoplastic lesions were located in the antrum in 13 patients and in the angle in one patient. PNS did not develop in any patient after ESD undertaken for tumors located in the corpus, fundus or cardia. All patients have been

  10. Clinicians' emotional responses and Psychodynamic Diagnostic Manual adult personality disorders: A clinically relevant empirical investigation.

    Science.gov (United States)

    Gazzillo, Francesco; Lingiardi, Vittorio; Del Corno, Franco; Genova, Federica; Bornstein, Robert F; Gordon, Robert M; McWilliams, Nancy

    2015-06-01

    The aim of this study is to explore the relationship between level of personality organization and type of personality disorder as assessed with the categories in the Psychodynamic Diagnostic Manual (PDM; PDM Task Force, 2006) and the emotional responses of treating clinicians. We asked 148 Italian clinicians to assess 1 of their adult patients in treatment for personality disorders with the Psychodiagnostic Chart (PDC; Gordon & Bornstein, 2012) and the Personality Diagnostic Prototype (PDP; Gazzillo, Lingiardi, & Del Corno, 2012) and to complete the Therapist Response Questionnaire (TRQ; Betan, Heim, Zittel-Conklin, & Westen, 2005). The patients' level of overall personality pathology was positively associated with helpless and overwhelmed responses in clinicians and negatively associated with positive emotional responses. A parental and disengaged response was associated with the depressive, anxious, and dependent personality disorders; an exclusively parental response with the phobic personality disorder; and a parental and criticized response with narcissistic disorder. Dissociative disorder evoked a helpless and parental response in the treating clinicians whereas somatizing disorder elicited a disengaged reaction. An overwhelmed and disengaged response was associated with sadistic and masochistic personality disorders, with the latter also associated with a parental and hostile/criticized reaction; an exclusively overwhelmed response with psychopathic patients; and a helpless response with paranoid patients. Finally, patients with histrionic personality disorder evoked an overwhelmed and sexualized response in their clinicians whereas there was no specific emotional reaction associated with the schizoid and the obsessive-compulsive disorders. Clinical implications of these findings were discussed.

  11. Resistance to antibiotics of clinical relevance in the fecal microbiota of Mexican wildlife.

    Directory of Open Access Journals (Sweden)

    Jurgi Cristóbal-Azkarate

    Full Text Available There are a growing number of reports of antibiotic resistance (ATBR in bacteria living in wildlife. This is a cause for concern as ATBR in wildlife represents a potential public health threat. However, little is known about the factors that might determine the presence, abundance and dispersion of ATBR bacteria in wildlife. Here, we used culture and molecular methods to assess ATBR in bacteria in fecal samples from howler monkeys (Alouatta palliata, spider monkeys (Ateles geoffroyi, tapirs (Tapirus bairdii and felids (jaguars, Panthera onca; pumas, Puma concolor; jaguarundis, Puma yagouaroundi; and ocelots, Leopardus pardalis living freely in two regions of the Mexican state of Veracruz under different degrees of human influence. Overall, our study shows that ATBR is commonplace in bacteria isolated from wildlife in southeast Mexico. Most of the resistances were towards old and naturally occurring antibiotics, but we also observed resistances of potential clinical significance. We found that proximity to humans positively affected the presence of ATBR and that ATBR was higher in terrestrial than arboreal species. We also found evidence suggesting different terrestrial and aerial routes for the transmission of ATBR between humans and wildlife. The prevalence and potential ATBR transfer mechanisms between humans and wildlife observed in this study highlight the need for further studies to identify the factors that might determine ATBR presence, abundance and distribution.

  12. Resistance to antibiotics of clinical relevance in the fecal microbiota of Mexican wildlife.

    Science.gov (United States)

    Cristóbal-Azkarate, Jurgi; Dunn, Jacob C; Day, Jennifer M W; Amábile-Cuevas, Carlos F

    2014-01-01

    There are a growing number of reports of antibiotic resistance (ATBR) in bacteria living in wildlife. This is a cause for concern as ATBR in wildlife represents a potential public health threat. However, little is known about the factors that might determine the presence, abundance and dispersion of ATBR bacteria in wildlife. Here, we used culture and molecular methods to assess ATBR in bacteria in fecal samples from howler monkeys (Alouatta palliata), spider monkeys (Ateles geoffroyi), tapirs (Tapirus bairdii) and felids (jaguars, Panthera onca; pumas, Puma concolor; jaguarundis, Puma yagouaroundi; and ocelots, Leopardus pardalis) living freely in two regions of the Mexican state of Veracruz under different degrees of human influence. Overall, our study shows that ATBR is commonplace in bacteria isolated from wildlife in southeast Mexico. Most of the resistances were towards old and naturally occurring antibiotics, but we also observed resistances of potential clinical significance. We found that proximity to humans positively affected the presence of ATBR and that ATBR was higher in terrestrial than arboreal species. We also found evidence suggesting different terrestrial and aerial routes for the transmission of ATBR between humans and wildlife. The prevalence and potential ATBR transfer mechanisms between humans and wildlife observed in this study highlight the need for further studies to identify the factors that might determine ATBR presence, abundance and distribution.

  13. Strategy for the maximization of clinically relevant information from hepatitis C virus, RT-PCR quantification.

    LENUS (Irish Health Repository)

    Levis, J

    2012-02-03

    BACKGROUND: The increasing clinical application of viral load assays for monitoring viral infections has been an incentive for the development of standardized tests for the hepatitis C virus. OBJECTIVE: To develop a simple model for the prediction of baseline viral load in individuals infected with the hepatitis C virus. METHODOLOGY: Viral load quantification of each patient\\'s first sample was assessed by RT-PCR-ELISA using the Roche MONITOR assay in triplicate. Genotype of the infecting virus was identified by reverse line probe hybridization, using amplicons resulting from the qualitative HCV Roche AMPLICOR assay. RESULTS: Retrospective evaluation of first quantitative values suggested that 82.4% (n=168\\/204) of individuals had a viral load between 4.3 and 6.7 log(10) viral copies per ml. A few patients (3.4%; n=7\\/204) have a serum viremia less than the lower limit of the linear range of the RT-PCR assay. Subsequent, prospective evaluation of hepatitis C viral load of all new patients using a model based on the dynamic range of viral load in the retrospective group correctly predicted the dynamic range in 75.9% (n=33\\/54). CONCLUSION: The dynamic range of hepatitis C viremia extends beyond the linear range of the Roche MONITOR assay. Accurate determination of serum viremia is substantially improved by dilution of specimens prior to quantification.

  14. The clinical relevance of cerebral microbleeds in patients with cerebral ischemia and atrial fibrillation.

    Science.gov (United States)

    Haji, Shamir; Planchard, Ryan; Zubair, Adeel; Graff-Radford, Jonathan; Rydberg, Charlotte; Brown, Robert D; Flemming, Kelly D

    2016-02-01

    The clinical significance of cerebral microbleeds (CMB) in patients hospitalized with atrial fibrillation (AF) and cerebral ischemia is unclear. We aimed to determine the prevalence of CMB in this population and determine the future risk of intracerebral hemorrhage (ICH) and cerebral infarction (CI). The medical records and brain imaging of patients hospitalized with cerebral ischemia due to AF between 2008 and 2011 were reviewed. Followup was obtained through medical record review, mailed survey, and acquisition of death certificates. Prevalence was calculated from those patients with a hemosiderin-sensitive MRI sequence. Recurrent CI and ICH were calculated using Kaplan-Meier curves censored at 3 years. Among 426 patients hospitalized with cerebral ischemia due to AF, 134 had an MRI with hemosiderin-sensitive sequences. The prevalence of CMB was 27.6%. At 3 years, 90.6% of CMB-negative patients were overall stroke free (ICH and CI) compared to 78.6% CMB-positive patients (p = 0.0591). Only one patient in the CMB-positive group had an ICH distant to the CMB. There was a nonsignificant trend toward higher recurrent CI, recurrent overall stroke rate, and mortality in patients with 5 or more CMB compared to 0-4 CMB. The rate of prospective CI in patients with prior cerebral ischemia due to AF is higher than the rate of ICH in patients with CMB. Further study is warranted to assess larger numbers of patients to determine appropriate antithrombotic use in this high-risk population.

  15. Poor responsiveness to antiplatelet drugs in acute coronary syndromes: clinical relevance and management.

    Science.gov (United States)

    Reny, Jean-Luc; Bonvini, Robert F; Bonvini, John M; Roffi, Marco; Fontana, Pierre

    2012-02-01

    Cardiovascular diseases are the most common cause of mortality and morbidity in Western countries, accounting for more than 40% of total mortality. An optimal pharmacological management in these patients is of major importance and antiplatelet agents remain the cornerstone of acute coronary syndrome (ACS) therapy at hospital admission and during percutaneous coronary interventions (PCI). The recently described poor biological responses to aspirin and clopidogrel have been source of major concern, especially in era of drug eluting stent implantation. Indeed, insufficient platelet inhibition at the time of PCI has been consistently associated with an increased risk of complications and recurrence of ischemic events. Despite the lack of uniformly accepted definitions of aspirin and clopidogrel poor response, we sought to describe the current evidence and gaps in knowledge. While trials on the potential benefit of an increased antiplatelet maintenance dose after PCI have shown only marginal benefits, the strengthening of the initial antiplatelet regimens by additional loading doses of clopidogrel, by the administration of glycoprotein IIb/IIIa receptor inhibitors or phosphodiesterase inhibitors might further improve outcomes during ACS and PCI in patients with poor responsiveness to conventional dual antiplatelet therapy. Overall, tailoring the antiplatelet treatment on the basis of the individual biological response improves the short-term outcome after PCI. New and more potent antiplatelet drugs may overcome the clinical consequences of the poor response to antiplatelet agents. © 2010 Blackwell Publishing Ltd.

  16. The Power of Phase I Studies to Detect Clinical Relevant QTc Prolongation: A Resampling Simulation Study

    Directory of Open Access Journals (Sweden)

    Georg Ferber

    2015-01-01

    Full Text Available Concentration-effect (CE models applied to early clinical QT data from healthy subjects are described in the latest E14 Q&A document as promising analysis to characterise QTc prolongation. The challenges faced if one attempts to replace a TQT study by thorough ECG assessments in Phase I based on CE models are the assurance to obtain sufficient power and the establishment of a substitute for the positive control to show assay sensitivity providing protection against false negatives. To demonstrate that CE models in small studies can reliably predict the absence of an effect on QTc, we investigated the role of some key design features in the power of the analysis. Specifically, the form of the CE model, inclusion of subjects on placebo, and sparse sampling on the performance and power of this analysis were investigated. In this study, the simulations conducted by subsampling subjects from 3 different TQT studies showed that CE model with a treatment effect can be used to exclude small QTc effects. The number of placebo subjects was also shown to increase the power to detect an inactive drug preventing false positives while an effect can be underestimated if time points around tmax are missed.

  17. Do not just do it, do it right: urinary metabolomics--establishing clinically relevant baselines.

    Science.gov (United States)

    Trivedi, Drupad K; Iles, Ray K

    2014-11-01

    Metabolomics is currently being adopted as a tool to understand numerous clinical pathologies. It is essential to choose the best combination of techniques in order to optimize the information gained from the biological sample examined. For example, separation by reverse-phase liquid chromatography may be suitable for biological fluids in which lipids, proteins and small organic compounds coexist in a relatively nonpolar environment, such as serum. However, urine is a highly polar environment and metabolites are often specifically altered to render them polar suitable for normal phase/hydrophilic interaction liquid chromatography. Similarly, detectors such as high-resolution mass spectrometry (MS) may negate the need for a pre-separation but specific detection and quantification of less abundant analytes in targeted metabolomics may require concentration of the ions by methods such an ion trap MS. In addition, the inherent variability of metabolomic profiles need to be established in appropriately large sample sets of normal controls. This review aims to explore various techniques that have been tried and tested over the past decade. Consideration is given to various key drawbacks and positive alternatives published by active research groups and an optimum combination that should be used for urinary metabolomics is suggested to generate a reliable dataset for baseline studies. Copyright © 2014 John Wiley & Sons, Ltd.

  18. Heterogeneous HER2 gene amplification: impact on patient outcome and a clinically relevant definition.

    Science.gov (United States)

    Bartlett, Alastair I; Starcyznski, Jane; Robson, Tammy; Maclellan, Alex; Campbell, Fiona M; van de Velde, Cornelis J H; Hasenburg, Annette; Markopoulos, Christos; Seynaeve, Caroline; Rea, Daniel; Bartlett, John M S

    2011-08-01

    Heterogeneous expression or amplification is a challenge to HER2 diagnostics. A guideline defines heterogeneity as the presence of between 5% and 50% cells with HER2/CEP17 ratios of more than 2.20. We audited the frequency of such cells and their clinical impact in the results from 2 pathology laboratories combined with data from the TEAM [Tamoxifen vs Exemestane Adjuvant Multicentre] pathology study. HER2 reports were scanned and the percentages of amplified cells reported. Of 6,461 eligible cases, 754 (11.7%) exhibited 50% or more cells with ratios of more than 2.20, which is "amplified" by College of American Pathologists guidelines. Of the cases, 2,166 (33.5%) exhibited more than 5% but less than 50% of cells with HER2/CEP17 ratios of more than 2.20, or "heterogeneous amplification." No prognostic impact was observed when fewer than 30% of cells exhibited ratios of more than 2.20. All amplified cases with 30% to 50% of cells with ratios more than 2.20 were identified as such by United Kingdom guidelines. The percentage of tumor cells with HER2/CEP17 ratios more than 2.20 does not identify cases with heterogeneous amplification or poor outcome. A modified approach for identification of true heterogeneous amplification is suggested.

  19. Selection of diverse and clinically relevant integrase inhibitor-resistant human immunodeficiency virus type 1 mutants.

    Science.gov (United States)

    Kobayashi, Masanori; Nakahara, Koichiro; Seki, Takahiro; Miki, Shigeru; Kawauchi, Shinobu; Suyama, Akemi; Wakasa-Morimoto, Chiaki; Kodama, Makoto; Endoh, Takeshi; Oosugi, Eiichi; Matsushita, Yoshihiro; Murai, Hitoshi; Fujishita, Toshio; Yoshinaga, Tomokazu; Garvey, Edward; Foster, Scott; Underwood, Mark; Johns, Brian; Sato, Akihiko; Fujiwara, Tamio

    2008-11-01

    Resistance passage studies were conducted with five INIs (integrase inhibitors) that have been tested in clinical trials to date: a new naphthyridinone-type INI S/GSK-364735, raltegravir, elvitegravir, L-870,810 and S-1360. In establishing the passage system and starting from concentrations several fold above the EC(50) value, resistance mutations against S-1360 and related diketoacid-type compounds could be isolated from infected MT-2 cell cultures from day 14 to 28. Q148R and F121Y were the two main pathways of resistance to S/GSK-364735. Q148R/K and N155H, which were found in patients failing raltegravir treatment in Phase IIb studies, were observed during passage with raltegravir with this method. The fold resistance of 40 mutant molecular clones versus wild type virus was compared with these five INIs. The overall resistance pattern of S/GSK-364735 was similar to that of raltegravir and other INIs. However, different fold resistances of particular mutations were noted among different INIs, reflecting a potential to develop INIs with distinctly different resistant profiles.

  20. Structure-activity relationship studies on clinically relevant HIV-1 NNRTIs.

    Science.gov (United States)

    Rawal, R K; Murugesan, V; Katti, S B

    2012-01-01

    In addition to the nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs) and integrase inhibitors (INIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) have contributed significantly in the treatment of HIV-1 infections. More than 60 structurally different classes of compounds have been identified as NNRTIs, which are specifically inhibiting HIV-1 reverse transcriptase (RT). Five NNRTIs (nevirapine, delavirdine, efavirenz, etravirine and rilpivirine) have been approved by US Food and Drug Administration (FDA) for clinical use. The NNRTIs bind with a specific 'pocket' site of HIV-1 RT (allosteric site) that is closely associated with the NRTI binding site. Due to mutations of the amino acid residues surrounding the NNRTI-binding site, NNRTIs are notorious for rapidly eliciting resistance. Though, the emergence of resistant HIV strains can be circumvented if the NNRTIs are used either alone or in combination with NRTIs (AZT, 3TC, ddI, ddC, TVD or d4T) and PIs (Indinavir, nelfinavir, saquinavir, ritonavir and lopinavir etc.) as shown by both a decrease in plasma HIV-1 RNA levels and increased CD4 T-cells. Here we are going to discuss recent advances in structure activity relationship studies on nevirapine, delavirdine, efavirenz, etravirine, rilpivirine and 4-thiazolidinones (privileged scaffold) HIV-1 NNRTIs.

  1. Development of a Clinically Relevant Animal Model for the Talar Osteonecrosis in Sheep

    Directory of Open Access Journals (Sweden)

    Chao-Fan Yuan, Jun-Lin Wang, Yong-Quan Zhang, Xiao-Kang Li, Yi Li, Su-Hua Wu, Zhi-Yong Zhang, Zheng Guo

    2012-01-01

    Full Text Available There are a lot of reports and reviews about osteonecrosis of the talus (ONT, yet reports about the animal model of ONT to evaluate proper therapeutic approaches are rarely heard. In our study, a novel animal model was established. Pure ethanol was injected into the cancellous bone of sheep's talus. Macroscopic observation, X-ray, CT and histology were performed at two, four, 12 and 24 weeks postoperatively. It was revealed that the trabeculae of talar head began to change their structure after two weeks postoperatively compared to the normal talus. The ONT was obvious at the end of the fourth week, and their outstanding feature was the damage of trabeculae bone and formation of cavities. CT scans and pathological changes of the subjects all showed characteristics of the early stage of osteonecrosis, also the sections of the specimens confirmed necrosis of tali. By 12 weeks, the phenomenon of necrosis still existed but fibrous tissue proliferated prominently and bone reconstruction appeared in certain area. Most specimens (3/4 got late stage necrosis which presented as synarthrosis in X-ray and mass proliferation of fibrous tissue in histology at the end of 24 weeks. The novel animal model of ONT was successful, and it is inclined to deteriorate without any intervention. The study provides us a new way to evaluate various treatments on ONT in laboratory, which may eventually pave way to clinical applications.

  2. [Antibiotic therapy for community acquired Streptococcus pneumoniae pneumonia: clinical relevance of antibiotic resistance].

    Science.gov (United States)

    Bédos, J-P; Bruneel, F

    2006-01-01

    The emergence of Streptococcus pneumoniae strains with reduced susceptibility to beta-lactams and with multiple drug resistance has not led to major changes in recommendations for antibiotic therapy in patients with acute community-acquired pneumococcal pneumonia. Numerous factors explain the limited clinical impact of this major microbiological change. The frequency of intermediate strains is high but the frequency of resistant strains to beta-lactams is very low. There is a complex relation between the acquisition of resistance to beta-lactams and the decreased virulence of S. pneumoniae strains. The only finding in studies of humanized experimental animal models of lethal bacteremic pneumonia caused by resistance and tolerant strains was a slowing in the kinetics of beta-lactams bactericidal activity, especially for amoxicillin. Taken together, this preclinical data shows that microbiological resistance of pneumococci to beta-lactams has very little influence on a possible failure of recommanded treatment regimens for pneumococcal pneumonia. The high rate of multiple drug resistance, particularly among beta-lactam resistant strains, rules out the probabilistic use of macrolides. Conversely, fluoroquinolone (FQ) resistance remains low, inferior to 3%, and the same is true for ketolides (management in the use of these new drugs could ensure their long-term activity. The high mortality rate of hospitalized S. pneumoniae pneumonia will only be improved with a better understanding of the complex host-bacteria interactions.

  3. Endoscopic Pancreas Fluid Collection: Methods and Relevance for Clinical Care and Translational Science.

    Science.gov (United States)

    Hart, Phil A; Topazian, Mark; Raimondo, Massimo; Cruz-Monserrate, Zobeida; Fisher, William E; Lesinski, Gregory B; Steen, Hanno; Conwell, Darwin L

    2016-09-01

    Pancreatic secretions have an important role in the regulation of a normal nutritional state but can be altered owing to a variety of pathophysiological mechanisms in the context of exocrine pancreatic disease. The development of an endoscopic technique for collection of pancreatic fluid, termed endoscopic pancreatic function testing, has led to improved understanding of these alterations and is particularly helpful to characterize chronic pancreatitis. In addition, investigators have found endoscopically collected pancreatic fluid to be a valuable biofluid for the purposes of translational science. Techniques such as proteomic, cytokine, genetic mutation, DNA methylation, and microRNA analyses, among others, can be utilized to gain a better understanding of the molecular characteristics of chronic pancreatitis and other pancreatic diseases. Endoscopic collection of pancreatic fluid is safe and relatively straightforward, permitting opportunities for longitudinal analysis of these translational markers throughout the course of disease. This manuscript summarizes our current knowledge of pancreatic fluid, with an emphasis on proper techniques for sample collection and handling, its clinical utility, and preliminary observations in translational science.

  4. Changes of IL-6 and relevant cytokines in patients with hepatocellularcarcinoma and their clinical significance

    Institute of Scientific and Technical Information of China (English)

    Cai Yah Zhao; Yue Lin Li; Su Xia Liu; Zhong Jun Feng

    2000-01-01

    AIM To study the changes of IL-6,IL-2, sIL-2R and TNF ir patients with hepatocellular carcinoma(HCC)and their clinical significance.METHODS IL-6, IL-2, sIL-2R and TNF were detected by avidin-biotin-system ELISA, double-sandwichELISA respectively in 60 patients with HCC and 36 patients with liver cirrhosis (LC) and 66 healthy persons.RESULTS The levels of IL-6, sIL-2R and TNF increased, but IL-2 level was lower in patients with HCCthan that in normal controls (NC) (t test, t=8.21, 4.71, 3.87, 2.13, P<0.01 or 0.05). IL-6 level in HCCwas 10 fold higher than NC, and also much higher than LC. IL-6 level was higher in later stage than that inearlier stage. There was a positive correlation between IL-6 and sIL-2R, TNF, while no positive correlationwas found between IL-2 and IL-6, sIL-2R in HCC.CONCLUSION The remarkably higher level of IL-6 is helpful for the early diagnosis of HCC.

  5. Distinct Characteristics of Mandibular Bone Collagen Relative to Long Bone Collagen: Relevance to Clinical Dentistry

    Directory of Open Access Journals (Sweden)

    Takashi Matsuura

    2014-01-01

    Full Text Available Bone undergoes constant remodeling throughout life. The cellular and biochemical mechanisms of bone remodeling vary in a region-specific manner. There are a number of notable differences between the mandible and long bones, including developmental origin, osteogenic potential of mesenchymal stem cells, and the rate of bone turnover. Collagen, the most abundant matrix protein in bone, is responsible for determining the relative strength of particular bones. Posttranslational modifications of collagen, such as intermolecular crosslinking and lysine hydroxylation, are the most essential determinants of bone strength, although the amount of collagen is also important. In comparison to long bones, the mandible has greater collagen content, a lower amount of mature crosslinks, and a lower extent of lysine hydroxylation. The great abundance of immature crosslinks in mandibular collagen suggests that there is a lower rate of cross-link maturation. This means that mandibular collagen is relatively immature and thus more readily undergoes degradation and turnover. The greater rate of remodeling in mandibular collagen likely renders more flexibility to the bone and leaves it more suited to constant exercise. As reviewed here, it is important in clinical dentistry to understand the distinctive features of the bones of the jaw.

  6. Involvement of Oct-1 in the regulation of CDKN1A in response to clinically relevant doses of ionizing radiation.

    Science.gov (United States)

    Nenoi, Mitsuru; Daino, Kazuhiro; Nakajima, Tetsuo; Wang, Bing; Taki, Keiko; Kakimoto, Ayana

    2009-03-01

    CDKN1A is a cyclin-dependent kinase inhibitor that plays a critical role in cell cycle checkpoint regulation. It is transcriptionally induced by TP53 (p53) following exposure to ionizing radiation (IR). Induction of CDKN1A after irradiation is closely related to IR-sensitivity of tumor cells, but the underlying mechanisms remain obscure because conventional reporter gene systems respond poorly to IR unless hyperlethal doses are used. Here, we performed a promoter analysis of the CDKN1A gene following irradiation with clinically relevant doses of IR using the adeno-associated virus-mediated reporter system which we have recently shown to be highly responsive to IR. We demonstrate that there are regulatory elements at -1.1 kb, -1.4 kb, and -1.8 kb, and deletion of these elements attenuate induction of the CDKN1A gene promoter in response to 0.2-2.0 Gy of IR. EMSA and ChIP assays showed that Oct-1 binds constitutively to the elements at -1.1 kb and -1.8 kb. Functional involvement of Oct-1 was confirmed by RNA interference targeting the Oct-1 gene, which suppressed both the basal and IR-inducible components of the CDKN1A expression. Thus, our results reveal that Oct-1 is crucial to the TP53-mediated regulation of the CDKN1A gene promoter following exposure to clinically relevant doses of IR.

  7. Involvement of Oct-1 in the regulation of CDKN1A in response to clinically relevant doses of ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nenoi, M.; Nakajima, T.; Wang, B.; Taki, K.; Kakimoto, A. [Radiation Effect Mechanisms Research Group, National Institute of Radiological Sciences, 9-1, Anagawa-4-chome, Inage-ku, Chiba 263-8555 (Japan); Daino, K. [Laboratoire de Cancerologie Experimentale, Departement de Radiobiologie et Radiopathologie, Commissariat a l' Energie Atomique, 92265 Fontenay-aux-Roses Cedex (France)

    2009-07-01

    CDKN1A is a cyclin-dependent kinase inhibitor that plays a critical role in cell cycle checkpoint regulation. It is transcriptionally induced by TP53 (p53) following exposure to ionizing radiation (IR). Induction of CDKN1A after irradiation is closely related to IR-sensitivity of tumor cells, but the underlying mechanisms remain obscure because conventional reporter gene systems respond poorly to IR unless hyper-lethal doses are used. Here, we performed a promoter analysis of the CDKN1A gene following irradiation with clinically relevant doses of IR using the adeno-associated virus-mediated reporter system which we have recently shown to be highly responsive to IR. We demonstrate that there are regulatory elements at -1.1 kb, -1.4 kb, and -1.8 kb, and deletion of these elements attenuate induction of the CDKN1A gene promoter in response to 0.2-2.0 Gy of IR. EMSA and ChIP assays showed that Oct-1 binds constitutively to the elements at -1.1 kb and -1.8 kb. Functional involvement of Oct-1 was confirmed by RNA interference targeting the Oct-1 gene, which suppressed both the basal and IR-inducible components of the CDKN1A expression. Thus, our results reveal that Oct-1 is crucial to the TP53-mediated regulation of the CDKN1A gene promoter following exposure to clinically relevant doses of IR. (authors)

  8. The effects of clinically relevant doses of amphetamine and methylphenidate on signal detection and DRL in rats.

    Science.gov (United States)

    Andrzejewski, Matthew E; Spencer, Robert C; Harris, Rachel L; Feit, Elizabeth C; McKee, Brenda L; Berridge, Craig W

    2014-04-01

    Low dose amphetamine (AMPH) and methylphenidate (MPH, Ritalin(®)) are the most widely prescribed and most effective pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD). Certain low, clinically relevant doses of MPH improve sustained attention and working memory in normal rats, in contrast to higher doses that impair cognitive ability and induce locomotor activity. However, the effects of AMPH of MPH on sustained attention and behavioral inhibition remain poorly characterized. The present experiments examined the actions of AMPH (0.1 and 0.25 mg/kg) and MPH (0.5 and 1.0 mg/kg) in a rat model of 1) sustained attention, where signal and blank trials were interspersed randomly and occurred at unpredictable times, and 2) behavioral inhibition, using a differential reinforcement of low rate (DRL) schedule. In a signal detection paradigm, both 0.5 mg/kg and 1.0 mg/kg MPH and 0.25 mg/kg AMPH improve sustained attention, however neither AMPH nor MPH improve behavioral inhibition on DRL. Taken together with other recent studies, it appears that clinically-relevant doses of AMPH and MPH may preferentially improve attention-related behavior while having little effect on behavioral inhibition. These observations provide additional insight into the basic behavioral actions of low-dose psychostimulants and further suggest that the use of sustained attention tasks may be important in the development of novel pharmacological treatments for ADHD.

  9. The effects of clinically relevant doses of amphetamine and methylphenidate on signal detection and DRL in rats

    Science.gov (United States)

    Andrzejewski, Matthew E.; Spencer, Robert C.; Harris, Rachel L.; Feit, Elizabeth C.; McKee, Brenda L.; Berridge, Craig W.

    2014-01-01

    Low dose amphetamine (AMPH) and methylphenidate (MPH, Ritalin®) are the most widely prescribed and most effective pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD). Certain low, clinically relevant doses of MPH improve sustained attention and working memory in normal rats, in contrast to higher doses that impair cognitive ability and induce locomotor activity. However, the effects of AMPH of MPH on sustained attention and behavioral inhibition remain poorly characterized. The present experiments examined the actions of AMPH (0.1 and 0.25 mg/kg) and MPH (0.5 and 1.0 mg/kg) in a rat model of 1) sustained attention, where signal and blank trials were interspersed randomly and occurred at unpredictable times, and 2) behavioral inhibition, using a differential reinforcement of low rate (DRL) schedule. In a signal detection paradigm, both 0.5 mg/kg and 1.0 mg/kg MPH and 0.25 mg/kg AMPH improve sustained attention, however neither AMPH nor MPH improve behavioral inhibition on DRL. Taken together with other recent studies, it appears that clinically-relevant doses of AMPH and MPH may preferentially improve attention-related behavior while having little effect on behavioral inhibition. These observations provide additional insight into the basic behavioral actions of low-dose psychostimulants and further suggest that the use of sustained attention tasks may be important in the development of novel pharmacological treatments for ADHD. PMID:24467844

  10. The clinical relevance of Organ Procurement and Transplantation Network screening criteria for program performance review in the United States.

    Science.gov (United States)

    Salkowski, Nicholas; Wey, Andrew; Snyder, Jon J; Orlowski, Jeffrey P; Israni, Ajay K; Kasiske, Bertram L

    2016-09-01

    The Organ Procurement and Transplantation Network is charged with overseeing the quality of transplant programs in the United States. However, there has been controversy over whether too many programs are being identified as underperforming. It has also been suggested that dramatic improvements in outcomes throughout the United States have made the thresholds for determining which deceased donor transplant programs are underperforming no longer clinically relevant. The Scientific Registry of Transplant Recipients compared actual and expected 1-y graft survival for transplant programs identified as underperforming in the most recent cohort (transplants from July 1, 2012 to December 31, 2014). For most organs, actual 1-y graft survival was substantially lower for programs identified as underperforming than for programs identified as performing as expected. Differences were smallest for kidney programs: median 1-y graft survival 89.2% vs 95.4% in large-volume programs identified and not identified for Membership and Professional Standards Committee review, respectively. Median expected graft survival was only slightly lower (94.8% vs 95.1%, respectively), suggesting that identified and not identified programs tend to have similar risk tolerances. An excess of 143 grafts were lost from kidney programs identified as underperforming. Transplant programs identified as underperforming generally have reduced 1-y graft survival that stakeholders may consider clinically relevant.

  11. Clinical relevance and public health significance of hepatitis B virus genomic variations

    Institute of Scientific and Technical Information of China (English)

    Guang-Wen Cao

    2009-01-01

    Ten hepatitis B virus (HBV) genotypes (A-J) and 34 HBV subgenotypes have been identified so far. HBV genotypes and subgenotypes have distinct geographical distributions, and have been shown to differ with regard to clinical outcome, prognosis, and response to interferon treatment. Infection with subgenotype A2 is frequently associated with high viral load, resulting in acute infection via horizontal transmission. Genotypes A and B are more sensitive to interferon treatment than genotypes D and C, respectively. Genotype B is more frequent in acute hepatitis than genotype C, whereas genotype C (C2) is more frequently associated with an increased risk of hepatocellular carcinoma (HCC), mostly cirrhotic, as compared with genotype B (B2). Genotype mixture is associated with high viral load and worse outcome of HBV infection. HBV mutations in the S genes, especially amino acids substitution at position 145 (G145R), are associated with immune escape, whereas mutations in the PreS or S genes which impair HBsAg secretion could present a risk to blood safety. HBV variants harboring mutations in the viral polymerase gene that confer resistance to nucleoside analogs may be selected during antiviral therapy. Different genotypes have distinct mutation patterns in the PreS and EnhⅡ/BCP/Precore regions.PreS deletions, C1653T, T1753V, and A1762T/G1764A are associated with an increased risk of HCC. HCCassociated HBV mutants may not transmit via motherto- child transmission, and are likely generated during HBV-induced pathogenesis. Examination of HBV mutations alone or in combination and host genetic suscep susceptibility will be helpful in classifying the HBV-infected subjects who will develop HCC and need active antiviral treatments.

  12. Camptothecin targets WRN protein: mechanism and relevance in clinical breast cancer.

    Science.gov (United States)

    Shamanna, Raghavendra A; Lu, Huiming; Croteau, Deborah L; Arora, Arvind; Agarwal, Devika; Ball, Graham; Aleskandarany, Mohammed A; Ellis, Ian O; P