bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatty Acid Synthase Inhibition by Amentoflavone Suppresses HER2/neu (erbB2) Oncogene in SKBR3 Human Breast Cancer Cells
Authors: Lee Jin Sun , Sul Ji Young , Park Jun Beom , Lee Myung Sun , Cha Eun Young , Song In Sang , Kim Je Ryong , Chang Eil Sung
Published: July 2012

Fatty acid synthase (FASN) is a potential therapeutic target for treatment of cancer and obesity, and is highly elevated in 30% of HER2‐overexpressing breast cancers. Considerable interest has developed in searching for novel FASN inhibitors as therapeutic agents in treatment of HER2‐overexpressing breast cancers. Amentoflavone was found to be effective in suppressing FASN expression in HER2‐positive SKBR3 cells. Pharmacological inhibition of FASN by amentoflavone specifically down‐regulated HER2 protein and mRNA, and caused an up‐regulation of PEA3, a transcriptional repressor of HER2. In addition, pharmacological blockade of FASN by amentoflavone preferentially decreased cell viability and induced cell death in SKBR3 cells. Palmitate reduced the cytotoxic effect of amentoflavone, as the percentage of viable cells was increased after the addition of exogenous palmitate. Amentoflavone‐induced FASN inhibition inhibited the translocation of SREBP‐1 in SKBR3 cells. Amentoflavone inhibited phosphorylation of AKT, mTOR, and JNK. The use of pharmacological inhibitors revealed that the modulation of AKT, mTOR, and JNK phosphorylation required synergistic amentoflavone‐induced FASN inhibition and HER2 activation in SKBR3 cells. These results suggest that amentoflavone modulated FASN expression by regulation of HER2‐pathways, and induced cell death to enhance chemopreventive or chemotherapeutic activity in HER2‐positive breast cancers. Copyright © 2012 John Wiley & Sons, Ltd.
Positive molecular ions and ion‐neutral complexes in the gas phase: Structure and stability of C2H4O2+· and C2H4O22+ isomers
Authors: Fantuzzi F. , Baptista L. , Rocha A. B. , Boechat‐Roberty H. M.
Published: July 2012

The structure and stability of several C2H4O2+· and C2H4O22+ isomers were studied by quantum chemical methods in an attempt to elucidate their most stable molecular arrangements and infer their contribution to the ion chemistry of astrophysical environments. The geometry optimizations were performed at B3LYP/6‐311G** and MP2/6‐311G** level. Single‐point calculations at equilibrium geometries were performed at left eigenstate completely renormalized coupled cluster method, CR‐CCL(2,3). Ninety minimum structures for the ions at the MP2 level were found: 38 related to C2H4O2+·, 33 to C2H4O22+, and 19 to ion‐neutral complexes. The more stable C2H4O2+· isomers have enolic structures, in agreement with the McLafferty rearrangement mechanism of straight chain aliphatic acids. In contrast, the most stable C2H4O22+ isomer has an acyclic OCCO nonplanar linear chain structure, with terminal +OH2 and CO+ linkages. In addition, acetic acid and methyl formate analogue structures were found only for the monopositive ion, with higher energies though. Both global minima are significantly different from the more stable neutral isomers and, therefore, could not be found in a geometry optimization procedure starting from the neutral structures. Dissociative recombination reaction pathways of C2H4O2+· and its application to the formation of astrophysical neutral molecules are also discussed. © 2012 Wiley Periodicals, Inc.
Robust reliable control for systems with random actuator fault and probabilistic nonlinearity with new characters
Authors: Wong W.K. , Tian Engang , Yue Dong , Au R.W.M.
Published: July 2012

In this study, the reliable control for time‐varying systems with random actuator faults and probabilistic nonlinearities is investigated. The system under consideration has the following main features: (1) nonlinearities with new characters. The probability information of nonlinearities belonging to different varying bounds is used; (2) its multi‐actuators are subject to various possible faults/failures, and failure rates can vary in some measure; and (3) there are uncertainties in the plant model parameters. Covering these features, a comprehensive model is developed for uncertain time‐varying delay systems. By employing the Lyapunov functional method, free‐weighting matrix method, and the linear matrix inequality technique, we can obtain several delay‐distribution‐dependent sufficient conditions to ensure the exponentially mean square stability of the system. Those conditions are characterized in terms of linear matrix inequalities, and the reliable controller feedback gain can be solved by the standard numerical software. A simulation example is presented to show the effectiveness and applicability of the results. Copyright © 2012 John Wiley & Sons, Ltd.
FISH ASSEMBLAGES IN NON‐REGULATED AND REGULATED RIVERS FROM PERMANENT AND TEMPORARY IBERIAN SYSTEMS
Authors: Alexandre C. M. , Ferreira T. F. , Almeida P. R.
Published: July 2012

The effects of river regulation on the hydrological cycle of a river and on the respective fish assemblage may differ according to dam operation purpose and type of river analysed. To assess the spatial and temporal variation of fish assemblages and their response to the hydrological changes caused by two different types of flow regulation, we selected three sampling sites in four rivers with different levels of regulation, two in a permanent river system and another two on a temporary one, which we sampled in four different annual seasons. In the permanent system, hydroelectrical regulation decreased hydrological variability, which affected fluvial specialist species, benefitting the generalist ones, and created a more homogeneous community that presented less intra‐annual variation. In the temporary system, agricultural regulation caused an inversion of the hydrological cycle, maintaining a moderate flow volume throughout the drought period that benefited the introduced, generalist and more tolerant species. Monthly volume was recognized, in a temporal scale, as the most important hydrological feature for assemblages’ structure, predicting the intra‐annual variation of several ecological guilds. This study provides important considerations for dam management and riverine ecosystems conservation. Copyright © 2012 John Wiley & Sons, Ltd.
Application of artificial bee colony for intrusion detection systems
Authors: Aldwairi Monther , Khamayseh Yaser , Al‐Masri Mohammad
Published: July 2012

The demand for better intrusion detection systems, especially anomaly intrusion detection, increases daily, as new attacks arise and Internet speeds increase. The criterion for a good intrusion detection system is to detect emerging attacks with high accuracy at line rates. Existing systems suffer from high false positives and negatives, and are unable to handle increasing traffic rates. This paper applies artificial bee colony for anomaly‐based intrusion detection systems. In addition, it uses two feature selection techniques to reduce the amount of data used for detection and classification. KDD Cup 99 dataset was used to evaluate the proposed algorithm. Experimental results show that artificial bee colony achieves average accuracy rate of 97.5% for known attacks and 93.2% overall for known and unknown attacks. The new algorithm outperforms all methods reported in the literature. Copyright © 2012 John Wiley & Sons, Ltd.
Boosting for detection of gene–environment interactions
Authors: Pashova H. , LeBlanc M. , Kooperberg C.
Published: July 2012

In genetic association studies, it is typically thought that genetic variants and environmental variables jointly will explain more of the inheritance of a phenotype than either of these two components separately. Traditional methods to identify gene–environment interactions typically consider only one measured environmental variable at a time. However, in practice, multiple environmental factors may each be imprecise surrogates for the underlying physiological process that actually interacts with the genetic factors. In this paper, we develop a variant ofL2boosting that is specifically designed to identify combinations of environmental variables that jointly modify the effect of a gene on a phenotype. Because the effect modifiers might have a small signal compared with the main effects, working in a space that is orthogonal to the main predictors allows us to focus on the interaction space. In a simulation study that investigates some plausible underlying model assumptions, our method outperforms the least absolute shrinkage and selection and Akaike Information Criterion and Bayesian Information Criterion model selection procedures as having the lowest test error. In an example for the Women's Health Initiative‐Population Architecture using Genomics and Epidemiology study, the dedicated boosting method was able to pick out two single‐nucleotide polymorphisms for which effect modification appears present. The performance was evaluated on an independent test set, and the results are promising. Copyright © 2012 John Wiley & Sons, Ltd.
Analysis of high‐throughput screening assays using cluster enrichment
Authors: Pu Minya , Hayashi Tomoko , Cottam Howard , Mulvaney Joseph , Arkin Michelle , Corr Maripat , Carson Dennis , Messer Karen
Published: July 2012

In this paper, we describe the implementation and evaluation of a cluster‐based enrichment strategy to call hits from a high‐throughput screen using a typical cell‐based assay of 160,000 chemical compounds. Our focus is on statistical properties of the prospective design choices throughout the analysis, including how to choose the number of clusters for optimal power, the choice of test statistic, the significance thresholds for clusters and the activity threshold for candidate hits, how to rank selected hits for carry‐forward to the confirmation screen, and how to identify confirmed hits in a data‐driven manner. Whereas previously the literature has focused on choice of test statistic or chemical descriptors, our studies suggest that cluster size is the more important design choice. We recommend clusters to be ranked by enrichment odds ratio, not by p‐value. Our conceptually simple test statistic is seen to identify the same set of hits as more complex scoring methods proposed in the literature do. We prospectively confirm that such a cluster‐based approach can outperform the naive top X approach and estimate that we improved confirmation rates by about 31.5% from 813 using the top X approach to 1187 using our cluster‐based method. Copyright © 2012 John Wiley & Sons, Ltd.
Substrate Templating upon Self‐Assembly of Hydrogen‐Bonded Molecular Networks on an Insulating Surface
Authors: Rahe Philipp , Nimmrich Markus , Kühnle Angelika
Published: July 2012

Molecular self‐assembly on insulating surfaces, despite being highly relvant to many applications, generally suffers from the weak molecule–surface interactions present on dielectric surfaces, especially when benchmarked against metallic substrates. Therefore, to fully exploit the potential of molecular self‐assembly, increasing the influence of the substrate constitutes an essential prerequisite. Upon deposition of terephthalic acid and trimesic acid onto the natural cleavage plane of calcite, extended hydrogen‐bonded networks are formed, which wet the substrate. The observed structural complexity matches the variety realized on metal surfaces. A detailed analysis of the molecular structures observed on calcite reveals a significant influence of the underlying substrate, clearly indicating a substantial templating effect of the surface on the resulting molecular networks. This work demonstrates that choosing suitable molecule/substrate systems allows for tuning the balance between intermolecular and molecule–surface interactions even in the case of typically weakly interacting insulating surfaces. This study, thus, provides a strategy for deliberately exploiting substrate templating to increase the structural variety in molecular self‐assembly on a bulk insulator at room temperature.
A suggested new bacteriophage genus: “Viunalikevirus”
Authors: Adriaenssens Evelien M. , Ackermann Hans-Wolfgang , Anany Hany , Blasdel Bob , Connerton Ian F. , Goulding David , Griffiths Mansel W. , Hooton Steven P. , Kutter Elizabeth M. , Kropinski Andrew M. , Lee Ju-Hoon , Maes Martine , Pickard Derek , Ryu Sangryeol , Sepehrizadeh Zargham , Shahrbabak S. Sabouri , Toribio Ana L. , Lavigne Rob
Published: July 2012

We suggest a bacteriophage genus, “Viunalikevirus”, as a new genus within the family Myoviridae. To date, this genus includes seven sequenced members: Salmonella phages ViI, SFP10 and ΦSH19; Escherichia phages CBA120 and PhaxI; Shigella phage phiSboM-AG3; and Dickeya phage LIMEstone1. Their shared myovirus morphology, with comparable head sizes and tail dimensions, and genome organization are considered distinguishing features. They appear to have conserved regulatory sequences, a horizontally acquired tRNA set and the probable substitution of an alternate base for thymine in the DNA. A close examination of the tail spike region in the DNA revealed four distinct tail spike proteins, an arrangement which might lead to the umbrella-like structures of the tails visible on electron micrographs. These properties set the suggested genus apart from the recently ratified subfamily Tevenvirinae, although a significant evolutionary relationship can be observed.
Pattern of carbon allocation across three different stages of stand development of a Chinese pine (Pinus tabulaeformis) forest
Authors: Cao Jixin , Wang Xiaoping , Tian Yun , Wen Zhiyong , Zha Tianshan
Published: July 2012

The pattern of carbon (C) allocation across different stages of stand development of Chinese pine (Pinus tabulaeformis) forests is poorly documented. In order to understand the effects of stand age on the C pool of the Chinese pine forest ecosystem, we have examined the above‐ and belowground C pools in three differently aged stands of Chinese pine in the northern mountains of Beijing, China, by plot‐level inventories and destructive sampling. Our results suggest that tree branch and foliage biomass should be estimated by age‐specific equations. Reasonably accurate estimates of tree stem, tree root, aboveground, and total tree biomass in a Chinese pine forest at different development stages were obtained using age‐independent allometric equations from tree diameter only. The ratio of belowground to aboveground tree biomass was relatively constant with stand aging, remaining around 21 %. The contribution of aboveground tree biomass C increased from 21 % of the total ecosystem C in a 25‐year‐old stand to 44 % in a 65‐year‐old stand, subsequently falling to 41 % in a 105‐year‐old stand, while the contribution of mineral soil C decreased from 64 % of the total ecosystem C in 25‐year‐old stand to 38 % in a 65‐year‐old stand, subsequently increasing to 41 % in a 105‐year‐old stand. The C stock of the total ecosystem and its aboveground tree, tree root, forest floor, and mineral soil components continuously increased with stand ageing, whereas the C stock of the understory showed a declining trend and contributed little to the total site C pool.
Trophic position estimates of formalin‐fixed samples with nitrogen isotopic compositions of amino acids: an application to gobiid fish (Isaza) in Lake Biwa, Japan
Authors: Ogawa Nanako O. , Chikaraishi Y. , Ohkouchi N.
Published: July 2012

To evaluate the influence of formalin‐fixation on the nitrogen isotopic composition of individual amino acids, we conducted a formalin‐fixation experiment over 62 weeks using muscle tissues of largemouth bass (Micropterus salmoides) and freshwater minnow (Zacco platypus) collected in Lake Biwa. The results indicated that the formalin‐fixation does not affect the nitrogen isotopic composition of amino acids including glutamic acid and phenylalanine from muscle protein of the fish. We applied this technique to formalin‐fixed gobiid fish “Isaza” (Gymnogobius isaza, Tanaka) specimens that had been collected from Lake Biwa through the twentieth century. The pattern of the δ15N values for these amino acids remains relatively constant, even though each amino acid exhibits a gradual increase by ~3 ‰ from 1916 to 1992. With a formula proposed by Chikaraishi et al. (Limnol Oceanogr Method 7:740–750, 2009), we estimated the temporal variations in the trophic position of Isaza in Lake Biwa. The trophic position of Isaza remained quite constant (3.2–3.3) across a major eutrophication period in 1960–1980. The estimated trophic position of Isaza fish is consistent with the stomach content analysis in the previous reports. The constant trophic position suggests that the eutrophication did not apparently affect the trophic position of Isaza fish, although Isaza's dietary preference changed from zooplankton to gammarids around 1970.
Thinking Sociologically about Religion: Implications for Faith Communities
Authors: Davie Grace
Published: July 2012

This article is the published version of the 2011 H. Paul Douglass Lecture given at the Religious Research Association meeting in Milwaukee, WI. It argues that there has been a step change in activity with regard to the social scientific work on religion in Europe in the last half decade. It sets out the evidence for this claim and the (not always positive) reasons why this had happened. It then examines the implications of this work for the faith communities of modern Europe, arguing that effective cooperation between the religious sector and the researchers who study this is the best antidote for the misconceptions about religion that currently abound in many European societies.
The Career and Work Adaptability Questionnaire (CWAQ): A first contribution to its validation
Authors: Nota Laura , Ginevra Maria Cristina , Soresi Salvatore
Published: July 2012

Over the last decade, occupational changes have the rapidly changing job market has begun to demand that people more actively construct their professional lives and acquire career adaptability. The aim of the present study was to develop a specific, new instrument, “Career and Work Adaptability”, to assess degree of adaptability in adolescents planning their futures. We conducted three studies, the first of which aimed to formulate the instrument's items and to verify its factor structure; the second study confirmed the instrument's multidimensional structure and evaluated its discriminant validity; the third study was conducted to verify the factorial structure's across‐gender invariance and to evaluate its stability over time. Our results showed that the instrument is an effective and multidimensional instrument for accurately measuring career adaptability. Specifically, it can serve as a useful vocational guidance tool in analyzing adolescents' career adaptability.
A “Systematic” Discussion of What I Want Roger to do for us Next
Authors: Shapiro Stanley J.
Published: July 2012

This short commentary begins with a discussion of the author's mostly macromarketing-related contact with Roger Layton since 1979. It next briefly reviews Layton's stream of publications, both before and after his Deanship, on marketing systems over that same period. It closes by urging Roger to now turn his attention to providing materials and methods for use in the teaching of marketing systems.
Immunomodulatory effects of environmental endocrine disrupting chemicals
Authors: Kuo Chang‐Hung , Yang San‐Nan , Kuo Po‐Lin , Hung Chih‐Hsing
Published: July 2012

During recent decades more than 100,000 new chemicals have been introduced as common consumer products into our environment. Among these chemicals, endocrine‐disrupting chemicals (EDCs) are of particular concern owing to their toxicity in animal studies and their impacts on human health. EDCs are ubiquitous in the environment, including the air, water, and soil. The endocrine‐disrupting effect of EDCs has been found to imitate the action of steroid hormones and promote several endocrine and reproductive disorders in both animal and human studies. In the present review, we focus on the effects of EDCs on the immune system. EDCs interfere with the synthesis of cytokines, immunoglobulins, and inflammatory mediators, and they also affect the activation and survival of immune cells. The dysfunction of the immune system caused by EDCs may lead to the attenuation of immunity (immunodeficiency) against infection or hyperreactivity of immune responses (allergy and autoimmune disease). In this review, we summarize epidemiologic, animal, and cell studies to demonstrate the potential effects of EDCs on immunity, allergy, and autoimmune diseases. We also address the impact of EDCs on epigenetic regulation.
Alkylphenols—potential modulators of the allergic response
Authors: Suen Jau‐Ling , Hung Chih‐Hsin , Yu Hsin‐Su , Huang Shau‐Ku
Published: July 2012

The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene‐environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine‐disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4‐Nonylphenol (NP) and 4‐octylphenol (OP)—two major alkylphenols—have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation.
Self‐reported Walking Ability in Persons With Chronic Stroke and the Relationship With Gait Performance Tests
Authors: Brogårdh Christina , Flansbjer Ulla‐Britt , Lexell Jan
Published: July 2012

Objective

To assess self‐reported walking ability in individuals with chronic stroke and to determine the relationship with gait performance tests.

Design

Descriptive analysis of a convenience sample.

Setting

A university hospital rehabilitation medicine clinic.

Participants

Fifty ambulatory community‐dwelling poststroke individuals (mean age, 64 years [range, 44‐74 years] and mean time since stroke onset 42 months [range, 6‐101 months]).

Main Outcome Measures

The Walking Impact Scale (the Walk‐12) to assess self‐reported walking ability, and the Timed “Up & Go” test, 10‐m Comfortable Gait Speed and Fast Gait Speed tests, and 6‐Minute Walk Test to assess gait performance.

Results

A majority of the participants (94%) reported limitations in their walking ability. The most common limitations were related to standing or walking, walking speed and distance, effort, and gait quality aspects. The ability to run was reported as most affected, whereas the need for support indoors or outdoors was least affected. Significant correlations (P < .01) were found between the Walk‐12 and the 4 gait performance tests (ρ = –0.60 to 0.60).

Conclusions

Persons with chronic stroke perceive limitations in their walking ability. The relationship between the Walk‐12 and the 4 gait performance tests indicates that self‐reports and quantitative assessments are associated. Because the Walk‐12 reflects broader dimensions than the gait performance tests, it can be a complementary tool when walking ability in persons with chronic stroke is evaluated.
What determines the stock market's reaction to monetary policy statements?
Authors: Kurov Alexander
Published: July 2012

We find that information communicated through monetary policy statements has important business cycle dependent implications for stock prices. For example, during periods of economic expansion, stocks tend to respond negatively to announcements of higher rates ahead. In recessions, however, we find a strong positive reaction of stocks to seemingly similar signals of future monetary tightening. We provide evidence that the state dependence in the stock market's response is explained by information about the expected equity premium and future corporate cash flows contained in monetary policy statements. We also show state dependence in the average stock returns on days of scheduled FOMC meetings and in the impact of monetary policy statements on stock and bond return volatility.
Validation of a porcine behavioural model of UVB induced inflammatory pain
Authors: Di Giminiani Pierpaolo , Petersen Lars J. , Herskin Mette S.
Published: July 2012

Background and aim

Cutaneous inflammation induced by ultraviolet B-light (UV-B) is considered a valuable translational pain model. Until now, the development of primary hyperalgesia has been assessed predominantly in rodents, whereas porcine skin might be advantageous due to its greater homology with human skin.

The aim of the present study was to investigate porcine behavioural responses to nociceptive mechanical and thermal stimulations following UV-B inflammation.

Methods

One skin area of 4 cm2 in the flank of 16 male pigs of 55 ± 6 kg was irradiated by UV-B using 3xMED (Minimum Erythema Dose).

Changes in pain sensitivity were assessed 24 and 48 h following irradiation via delivery of mechanical (Pressure Application Measurement device) and thermal (CO2 laser) stimulations to the inflamed skin area and to an untreated control site.

Results

All animals showed higher sensitivity in the inflamed skin site 24 and 48 h following irradiation, compared to the control site (P< 0.05). Pressure withdrawal threshold decreased in the inflamed site: 231 g (148–451) against 408g (347–684) after 24 hours and 200 g (106–293) against 656g (405–902) after 48 h.

Similarly, latency to respond to the laser stimulus was lower at the inflamed site: 5 s (3–7) against 9 s (4–2) after 24h and 4 s (3–15) against 20 s (8–25) after 48 h.

One and two days after irradiation, a tendency was found for an increased cutaneous mechanical pain sensitivity compared to baseline values in the site irradiated with UV-B light (P = 0.092). Thermal sensitivity was increased within the inflamed site 24 h after irradiation with latency changing from 17s (4–25) at baseline to 5 s (3–7) at 24 h (P =0.001). At 48 h, the response latency had not decreased any further (P = 0.414).

Conclusions

Our study shows that behavioural recordings are a valid tool for the assessment of mechanical and heat sensitization following UV-B inflammation in porcine skin.
Pain sensitivity changes in chronic pain patients with and without spinal cord stimulation assessed by nociceptive withdrawal reflex thresholds and electrical pain thresholds
Authors: Biurrun Manresa J.A. , Sörensen J. , Sandell A.-C. , Andersen O.K. , Arendt-Nielsen L. , Gerdle B.
Published: July 2012

Background and aim

Previous studies have shown that patients with chronic pain had significantly lower nociceptive withdrawal reflex thresholds (NWR-T) and electrical pain thresholds (EP-T) than healthy controls. Patients with chronic pain and implanted spinal cord stimulator (SCS) system presents an opportunity to study dynamic pain sensitivity changes in a situation where patients just have been stimulated (i.e., pain-free or greatly reduced pain) and compare with the situation where patients are not stimulated (i.e., experiencing severe pain).

Methods

Seventeen volunteers with chronic neuropathic pain and a SCS implanted for pain relief participated in the experiment. Volunteers were asked to turn off the SCS and refrain from medication at least 8 h before the experiment. Electrical stimulation (train-of-five 1-ms pulses delivered at 200 Hz) was applied to the arc of the foot in order to elicit the NWR and electromyographic responses were recorded from tibialis anterior muscle. A staircase procedure was used to assess the NWR-T and a Visual-Analog-Scale (VAS) scale (range 0–10) was used to assess the EP-T. After the initial testing, the SCS was turned on, and thresholds were reassessed after 1 h. Paired t-tests were used to compare the thresholds before and after the SCS was turned on. All values are presented as mean ± SD.

Results

The NWR-T were significantly higher after the SCS was turned on (before: 16.3 ±8.1 mA; after: 19.0 ± 10.9 mA; p = 0.028). EP-T did not show any significant differences (before: 3.2 ± 1.5 mA; after: 2.9 ± 2.0 mA; p = 0.324).

Conclusion

Results showed a higher NWR-T after the SCS was turned on, which indicates a depression of spinal nociception. Moreover, the NWR-T was able to detect ongoing and relatively quick changes in pain sensitivity.
Pain prevalence in a university hospital in Iceland
Authors: Zoëga S. , Ward S. , Aspelund T. , Sveinsdóttir H. , Sigurdsson G. , Gunnarsdóttir S.
Published: July 2012

Background/aims

Despite multiple efforts to improve practice, pain is prevalent in many hospital settings causing unnecessary complications and suffering. The aim of the study was to explore the epidemiology of pain in a university hospital in Iceland.

Methods

A point prevalence study was conducted in 23 departments in medical and surgical services in a 650 bed university hospital in January 2011. Data was collected from medical charts and with a questionnaire (APS-POQ-R) assessing pain severity and quality of pain management. Participants had to be 18 years or older, hospitalized for at least 24 h, speak Icelandic, alert, and able to participate.

Results

Of the 369 participants the mean (SD) age was 67.9 (17.6) years (range 18–100) and gender proportions were equal. Response rate was 80%. Of patients in pain (scoring ≥1 on a 0–10 scale) the mean (SD) worst pain severity was 5.6 (2.5). Total pain prevalence was 80.4%, but of patients in pain 36.5% had mild (1–4) pain, 22.6% moderate (5–6) and 40.9% had severe (7–10) pain. The mean (SD) proportion of time spent in severe pain was 25.9% (27.0%). Pain was both more prevalent, [χ2(1, N= 367) = 7.05, p = 0.008] and severe [t(365) =−4.16, p = 0.000] in women compared to men. Similarly, pain was more prevalent [χ2(1, N= 368) = 9.71, p = 0.002] and severe [t(216,2) =−3.18, p = 0.002] in surgical services compared to medical. Worst pain severity was weakly negatively associated with age [r(369) =−0.23, p = 0.000]. Worst pain severity was higher in patients receiving pain medications [t(357) =−9.84, p = 0.000] and in patients using non-pharmacological methods to treat their pain [t(311.7) =−5.76, p = 0.000].

Conclusions

Pain was prevalent in the hospital and an unsatisfactory proportion of patients experienced moderate to severe pain. The quality of pain management in the hospital needs to be improved. Further studies are needed to test and evaluate the efficacy and effectiveness of interventions aimed at advancing pain practice in the hospital setting.
The effect of tail-docking neonate piglets on ATF-3 and NR2B immunoreactivity in coccygeal dorsal root ganglia and spinal cord dorsal horn neurons: Preliminary data
Authors: Sandercock D.A. , Monteiro A. , Scott E.M. , Nolan A.M.
Published: July 2012

Background/aims

Tail docking neonatal piglets remains a controversial animal welfare issue. Although banned in the UK, it is widely practiced in many countries as a safeguard against tail biting among pigs reared in intensive systems. Concerns exist whether tail docking can induce chronic pain in later life. This preliminary study examined the effects of partial tail amputation on activating transcription factor 3 (ATF3), a marker of peripheral nerve injury and regeneration and NMDA-glutamate receptor NR2B subunit which participates in the mediation of chronic pain.

Methods

Procedures were performed according to the ethical guidelines for the study of experimental pain in animals. Six piglets (2–3 days old) were tail-docked (a portion of the tail amputated with sterile surgical cutters), six piglets (2–3 days old) were sham-docked. Three animals from each treatment were euthanised 7 and 56 days post-amputation. Coccygeal dorsal root ganglia (DRG) and spinal cord were collected post-mortem for immunohistochemistry.

Results

ATF3 immunoreactivity (IR) was significantly increased (p <0.05) in the DRG neurons from tail-docked piglets 7 days after tail amputation, compared with sham-docked piglets. ATF3-IR was not different in sham and tail-docked piglets 56 days post amputation. NR2B-IR was significantly increased (p < 0.05) in dorsal horn neurons in tail-docked piglets compared with intact piglets 7 days after docking. There was no difference in NR2B-IR in neurons 56 days post amputation, compared with intact piglets.

Conclusions

Increased ATF3 and NR2B-IR 7 days after tail-docking suggests that injury to the peripheral nerves in the tail was sufficient to trigger neuronal regeneration and altered dorsal horn signaling respectively, however the effects of tail-docking on neuronal regeneration and nociceptive signaling were relatively short lasting. Tail-docking neonatal piglets does not cause sustained changes in ATF3, which might suggest ongoing nerve fibre damage and NR2B which might be implicated in chronic pain.
Acute behavioural responses to tail docking in piglets – Effects of increasing docking length?
Authors: Herskin Mette S. , Giminiani Pierpaolo Di , Damgaard Birthe M. , Thodberg Karen
Published: July 2012

Background and aim

Tail docking has been suggested as an animal model of neuropathy and pain based on findings of relations between the degree of neuroma formation and the docking length. We examined effects of docking length on behaviour of piglets during and 6 h after tail docking.

Methods

Piglets were tail docked 2–4 d post-partum. We used 53 piglets and four treatments: intact (I), removal of either 25 (Q), 50 (H) or 75% (T) of the tail. The piglets were kept with sow and littermates under production conditions, and docked using a gas-heated instrument. Behaviour was observed during docking and for the following 6 h.

Results

Tail docking led to behavioural changes, the magnitude of which to some extend depended on docking length. Increased docking length led to increased intra-procedural vocalization score (0, 0.6 ± 0.2, 1.4 ± 0.2 and 1.4 ± 0.2 for I, Q, H and T, respectively, P<0.001). In the initial 6h, increased docking length led to increased time spent in the heated creep area (2 ± 1%, 15 ± 6%, 18±8% and 30±6% for I, Q, H and T, respectively; P<0.05). Piglet posture was affected as well, showing that increased docking length led to decreased lying (71 ± 2%, 68 ± 2%, 61 ± 2% and 61 ± 2% for I, Q, H and T, respectively, P<0.01) and increased time spent active (24 ± 2%, 23 ± 2%, 32 ± 2% and 30 ± 3% for I, Q, H and T, respectively, P< 0.05). Pain specific behaviours such as trembling or tail flicking were registered and occurred in 5 ± 1% and 9 ± 1% of observations. However, no effects of docking length could be shown.

Conclusions

Piglets responded behaviourally to tail docking. Increasing docking length led to increased pain responses such as intra-procedural vocalizations, hiding behaviour and reduced rest, indicative of increased pain. These results confirm earlier reports suggesting that tail docking might be suitable as an animal model for neuropathy and pain.
Neuroplastic alterations in brain responses to painful visceral stimulations reflects individual neuropathic symptoms in diabetes mellitus patients
Authors: Brock Christina , Graversen Carina , Frøkjær Jens B. , Søfteland Eirik , Valeriani Massimiliano , Drewes Asbjørn M.
Published: July 2012

Background/aims

Abnormal visceral sensory function in diabetes mellitus (DM) leads to neuronal changes in the enteric, peripheral and/or central nervous system (CNS). To explore the role of diabetic autonomic neuropathy (DAN) in patients with long-standing DM, we investigated psychophysical responses and neuronal activity recorded as evoked brain potentials (EPs) and dipolar source modelling.

Methods

Fifteen healthy volunteers and 14 type-1 DM patients with DAN were assessed with a symptom score index characterizing upper GI abnormalities. Multi-channel (62) electroencephalography was recorded during painful electrical stimulation of the lower oesophagus. Brain activity to painful stimulations was modelled by use of Brain Electrical Source Analysis (BESA).

Results

Diabetic patients had higher stimulus intensities to evoke painful sensation (P<0.001), longer latencies of N2 and P2 components (both P<0.001), lower amplitudes of P1–N2 and N2–P2 complexes (P<0.001; P = 0.02). Inverse modelling of brain sources showed deeper bilateral insular dipolar source localization (P = 0.002). Symptom score index was negatively correlated to the depth of insular activity (P = 0.004) and positively correlated to insular dipole strength (P = 0.03).

Conclusion

DM patients show neuroplastic changes in the central nervous system. The role of abnormal insular processing may explain the development and persistence of upper GI-symptoms related to DAN. This enhanced understanding of DAN may have clinical and therapeutical implications.
Hyperalgesia in human skin and deep-tissues inside and outside of a UVB irradiated area
Authors: Vecchio Silvia Lo , Petersen Lars J. , Graven-Nielsen Thomas , Finocchietti Sara , Gazerani Parisa , Arendt-Nielsen Lars
Published: July 2012

Background/aims

The ultraviolet B (UVB) inflammatory pain model is often used to induce a steady hyperalgesic area in human skin. UVB causes a well-described erythema, developing maximal response within about 24 h. The aim of the present study was to investigate if cutaneous UVB irradiation can influence both superficial and deep-tissue mechanical pain thresholds in the site of irradiation and in the surrounding area.

Methods

An area of 3 cm × 4 cm, located on the low back of 16 healthy volunteers, was irradiated by UVB (Medlight, Germany; 3xMED: Minimal Erythema Dose). The degree of inflammation was detected by measuring superficial blood flow before and after irradiation, inside and outside the stimulated area. Applying quantitative sensory assessments, mechanical pain threshold changes were detected one day after irradiation, within and outside of the irradiated area. Sensitivity to cutaneous mechanical stimuli was assessed using pin prick and deep-tissue pressure pain thresholds were evaluated on 12 spots (4 within and 8 outside, 1.5 cm distant from the irradiated area) by a computer-controlled pressure algometer (Aalborg University, Denmark; 1.0 cm2 flat probe, 0.5 cm2 flat probe and a V-shaped probe with a contact surface of 0.03 cm2).

Results

24 h after exposure, the irradiated skin showed clear erythema with a boundary matching the irradiated area and a statistically significant increase in cutaneous blood flow (P < 0.001) compared with baseline assessment. Cutaneous pin prick pain thresholds and deep-tissue pressure pain thresholds (all probes) were significantly decreased inside and outside the irradiated area (P < 0.05).

Conclusions

Cutaneous UVB irradiation reduces mechanical pain thresholds to pin-prick and pressure stimulation which may indicate allodynic responses in both the skin and in deep-tissues. Expansion of the responses to areas outside the irradiated zone confirmed the presence of secondary hyperalgesia to mechanical stimuli.
Effect of experimental jaw muscle pain on bite force during mastication
Authors: Shimada A. , Baad-Hansen L. , Svensson P.
Published: July 2012

Background/aims

Muscular pain often impairs masticatory function in Temporomandibular disorder patients. The specific aim of this study was to investigate how the bite force during mastication is influenced by experimental muscle pain caused by infusion of glutamate into the masseter muscle.

Methods

12 healthy adults participated, after providing informed consent. Customized metal frames of the intraoral bite force sensor were manufactured for all subjects, and placed on their preferred chewing side. To induce experimental pain, a sterile solution of glutamate (0.5 M) was infused into the posterior part of the masseter muscle. Isotonic saline (0.9%) was infused as a control (randomized, cross-over design). During chewing three different kinds of test food (two different size carrots and gummy), bite force, electromyographic (EMG) activity of bilateral masseter muscle and anterior temporalis muscle were recorded. The first and last five masticatory cycles were used for analyses. The outcome parameters were as follows; Visual Analog Scale (VAS) for pain, impulse and duration from the bite force signal, duration and amplitude of EMG. Three-way ANOVAs with food (3 levels), sessions (5 levels: baseline, during glutamate, baseline 2, during isotonic saline, follow-up), cycles (2 × 5 levels) were carried out.

Results

Glutamate caused moderate levels of pain (mean VAS: 2.4 ± 0.9) whereas isotonic saline only caused low levels of pain (Mean VAS: 0.7 ± 0.5). The ANOVA of impulse data, as well as most EMG data, demonstrated a significant effect of session. Post hoc tests showed significantly higher impulse values of both the first and last five cycles in the glutamate session compared to baseline whereas the EMG activity was significantly decreased (P < 0.05).

Conclusion

Surprisingly, experimental pain induced by glutamate increased the bite force during mastication coupled with a decrease in EMG activity. This indicates a major reorganization of the motor control during painful mastication.
Cognitive modulation of experimental pain at spinal and cortical levels
Authors: Simonsen Mie Hviid , Jensen Jakob Bredal , Andersen Ole Kæseler , Petrini Laura , Egsgaard Line Lindhardt , Mørch Carsten Dahl
Published: July 2012

Background/aims

Descending modulation of the nociceptive system has proven to be pronounced in healthy humans. The descending modulation can be activated by rather distinct methods such as strong tonic painful stimulation or changes in the cognitive state. The extent of descending modulation on spinal pain processing remains unclear. Therefore, we assessed simultaneous cognitive modulation of spinal and cortical processing of experimental pain.

Methods

Painful (1.7 × pain threshold (PT)) and non-painful (0.5 × PT) electrical stimulation was applied to the sole of the foot of 9 healthy subjects. Cortical activity was recorded by EEG from the vertex and the nociceptive withdrawal reflex (NWR) was recorded from the tibialis anterior muscle. Stimulations were applied during the Spatial Attention Task, where the subject was asked to indicate the direction of arrows presented in a computer screen, and when the subjects were relaxed. The subject was asked to rate the average pain intensity after 30 stimuli. A total of 240 stimuli were applied.

Results

The amplitude of the EEG P100 (p < 0.001), P300 (p = 0.019) peaks, the pain intensity (p < 0.001) and the NWR (p < 0.05) were all significantly higher when noxious stimulation was applied than when non-noxious stimuli were applied. The spatial attention task did not significantly modulate the amplitude of the P100 (p = 0.083), the P300 (p = 0.804) peaks, and the pain intensity (p = 0.139), but the NWR were significantly lower during the Spatial Attention Task (p = 0.042).

Conclusion

The results indicated that attracting the attention of the subjects to a task of spatial discrimination evoked a descending modulation affecting nociceptive processing at the spinal level. Still pain perception and late components of the vertex EEG were not significantly altered by the spatial attention task.
Multivariate pattern analysis of evoked brain potentials by temporal matching pursuit and support vector machine
Authors: Graversen Carina , Brock Christina , Frøkjær Jens Brøndum , Dimcevski Georg , Farina Dario , Drewes Asbjørn Mohr
Published: July 2012

Background/aims

Electroencephalography (EEG) recorded as evoked brain potentials (EPs) reflects the cortical processing to an external event. This approach is often used to study the altered response to acute pain in chronic pain patients compared to healthy volunteers. However, discrimination of the responses from the study populations is a non-trivial task, which calls for improved objective methods.

Methods

To develop and validate a new methodology, we analyzed data from 16 type-1 diabetes mellitus patients and 15 age and gender matched volunteers, by means of brain activity recorded from 62 EEG channels. The EEG signals were recorded as EPs elicited by painful electrical stimulations in the oesophagus with an intensity corresponding to the individual pain detection threshold. The EPs from all channels and subjects were decomposed simultaneously by a temporal matching pursuit (TMP) algorithm with Gabor atoms.

Results

Amplitude and phase features were classified by a support vector machine (SVM) to discriminate patients from healthy volunteers. A classification performance of 93.1% (P<0.001) was obtained when applying a majority voting scheme to the 3 best performing channels (FC4, C1, and C6) and including features from 2 atoms. The most discriminative features were determined by the slope coefficients from the SVM decision rule, which identified the biomarkers as delayed latency of the first atom (N2–P2 complex) and decreased amplitude of the second atom (NI–P1 complex).

Conclusion

The combination of TMP and SVM is a novel approach to classify two study populations, which may provide a new objective tool to identify biomarkers from various chronic pain populations.
Chronic pain after breast augmentation is associated with both signs of peripheral nerve injury and central nervous mechanisms
Authors: Kaasa T. , Romundstad L. , Stubhaug A.
Published: July 2012

Background/aims

The mechanisms behind chronic postsurgical pain remains unsettled. Quantitative sensory testing and questioning sensory function may help understand mechanisms behind the transition from acute to chronic pain. The aim of this study was to assess these aspects in postsurgical patients with and without chronic postsurgical pain.

Methods

116 women, who answered a questionnaire in a four years follow-up study of pain, sensory changes and quality of life after cosmetic breast augmentation surgery [1], were invited to participate in a psychophysical study. Twenty women answered the request and filled in a questionnaire, and 12 of these women finally met for examination.

Results

Six of the 12 women had pain in the area of surgery, three were pain-free, but reported sensory changes and three reported no pain or sensory disturbances. We performed a detailed quantitative sensory examination, with a protocol adapted from Rollke et al. [2] While only 3/6 patients in the pain-free group reported hypoesthesia, an area of hypoesthesia to tactile-, heat- and cold stimuli was identified in all subjects when examined (Table 1).

Table 1

Number in each group (subjects with pain vs. subjects without pain) showing presence of sensory characteristics.

Pain (N = 6)
No pain (N = 6)

Questionnaire

Hypoesthesia
5
3

Hyperesthesia
6
3

Examination

Hypoesthesia (tactile, heat, cold)
6
6

Hypersensitivity detected
4
1

Hyperpathia to heat
5
5

Paradoxical heat sensation during cold stimulation
4
0

Allodynia, cotton
0
0

Allodynia, brush
0
1

Cold allodynia
5
1

Abnormal temporal summation
5
1

Deep pain after algometry
4
0

The most striking difference between the group reporting pain and the one not reporting pain was the presence of paradoxical heat sensation, cold allodynia, abnormal temporal summation, and the presence of deep pain during/after pressure pain threshold testing with the algometer in the group with pain.

Conclusion

Self-reported sensory changes under-estimated sensory changes. Sensory testing revealed signs of peripheral nerve injury changes in all subjects, while signs of central nervous changes were found predominantly in patients with persistent pain.