bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical learning of visual transitions in monkey inferotemporal cortex
Authors: Meyer Travis , Olson Carl R.
Published: November 2011

One of the most fundamental functions of the brain is to predict upcoming events on the basis of the recent past. A closely related function is to signal when a prediction has been violated. The identity of the brain regions that mediate these functions is not known. We set out to determine whether they are implemented at the level of single neurons in the visual system. We gave monkeys prolonged exposure to pairs of images presented in fixed sequence so that each leading image became a strong predictor for the corresponding trailing image. We then monitored the responses of neurons in the inferotemporal cortex to image sequences that obeyed or violated the transitional rules imposed during training. Inferotemporal neurons exhibited a transitional surprise effect, responding much more strongly to unpredicted transitions than to predicted transitions. Thus, neurons even in the visual system make experience-based predictions and react when they fail.
Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation
Authors: Rovira Meritxell , Huang Wei , Yusuff Shamila , Shim Joong Sup , Ferrante Anthony A. , Liu Jun O. , Parsons Michael J.
Published: November 2011

Pancreatic β-cells are an essential source of insulin and their destruction because of autoimmunity causes type I diabetes. We conducted a chemical screen to identify compounds that would induce the differentiation of insulin-producing β-cells in vivo. To do this screen, we brought together the use of transgenic zebrafish as a model of β-cell differentiation, a unique multiwell plate that allows easy visualization of lateral views of swimming larval fish and a library of clinical drugs. We identified six hits that can induce precocious differentiation of secondary islets in larval zebrafish. Three of these six hits were known drugs with a considerable background of published data on mechanism of action. Using pharmacological approaches, we have identified and characterized two unique pathways in β-cell differentiation in the zebrafish, including down-regulation of GTP production and retinoic acid biosynthesis.
Wnt signaling and a Smad pathway blockade direct the differentiation of human pluripotent stem cells to multipotent neural crest cells
Authors: Menendez Laura , Yatskievych Tatiana A. , Antin Parker B. , Dalton Stephen
Published: November 2011

Neural crest stem cells can be isolated from differentiated cultures of human pluripotent stem cells, but the process is inefficient and requires cell sorting to obtain a highly enriched population. No specific method for directed differentiation of human pluripotent cells toward neural crest stem cells has yet been reported. This severely restricts the utility of these cells as a model for disease and development and for more applied purposes such as cell therapy and tissue engineering. In this report, we use small-molecule compounds in a single-step method for the efficient generation of self-renewing neural crest-like stem cells in chemically defined media. This approach is accomplished directly from human pluripotent cells without the need for coculture on feeder layers or cell sorting to obtain a highly enriched population. Critical to this approach is the activation of canonical Wnt signaling and concurrent suppression of the Activin A/Nodal pathway. Over 12–14 d, pluripotent cells are efficiently specified along the neuroectoderm lineage toward p75
+
Hnk1
+
Ap2
+
neural crest-like cells with little or no contamination by Pax6
+
neural progenitors. This cell population can be clonally amplified and maintained for >25 passages (>100 d) while retaining the capacity to differentiate into peripheral neurons, smooth muscle cells, and mesenchymal precursor cells. Neural crest-like stem cell-derived mesenchymal precursors have the capacity for differentiation into osteocytes, chondrocytes, and adipocytes. In sum, we have developed methods for the efficient generation of self-renewing neural crest stem cells that greatly enhance their potential utility in disease modeling and regenerative medicine.
Constitutive exposure of phosphatidylserine on viable cells
Authors: Segawa Katsumori , Suzuki Jun , Nagata Shigekazu
Published: November 2011

Apoptotic cells are quickly recognized and engulfed by phagocytes to prevent the release of noxious materials from dying cells. Phosphatidylserine (PS) exposed on the surface of apoptotic cells is a proposed “eat-me” signal for the phagocytes. Transmembrane protein 16F (TMEM16F), a membrane protein with eight transmembrane segments, has the Ca-dependent phospholipid scramblase activity. Here we show that when lymphoma cells were transformed with a constitutively active form of TMEM16F, they exposed a high level of PS that was comparable to that observed on apoptotic cells. The PS-exposing cells were morphologically normal and grew normally. They efficiently responded to interleukin 3 and underwent apoptosis upon treatment with Fas ligand. The viable PS-exposing cells bound to peritoneal macrophages at 4 °C, but not at 25 °C. Accordingly, these cells were not engulfed by macrophages. When apoptotic cells were injected i.v. into mice, they were phagocytosed by CD11c
+
CD8
+
dendritic cells (DCs) in the spleen, but the PS-exposing living cells were not phagocytosed by these DCs. Furthermore, when PS-exposing lymphoma cells were transplanted s.c. into nude mice, they generated tumors as efficiently as parental lymphoma cells that did not expose PS. These results indicated that PS exposure alone is not sufficient to be recognized by macrophages as an eat-me signal.
Acrosome-reacted mouse spermatozoa recovered from the perivitelline space can fertilize other eggs
Authors: Inoue Naokazu , Satouh Yuhkoh , Ikawa Masahito , Okabe Masaru , Yanagimachi Ryuzo
Published: November 2011

Many investigators maintain that spermatozoa that have initiated the acrosome reaction (AR) before reaching the surface of the egg's zona pellucida (ZP) are unable to bind and penetrate the ZP. A recent study has revealed that most fertilizing mouse spermatozoa initiate the AR before contacting the ZP. We found that acrosome-reacted spermatozoa collected from the perivitelline space of
Cd9
-null mice (whose egg plasma membranes are incapable of fusing with spermatozoa) were able to pass through both the cumulus and ZP of WT mouse eggs and produced live offspring. This means that the spermatozoa we used had the ability to pass through the ZP at least twice. Apparently, some spermatozoa that had undergone the AR long before contact with the ZP remained capable of crossing the ZP and fertilizing eggs. Thus, the concept that acrosome-reacted spermatozoa are unable to bind to the ZP and have lost their fertilizing capacity must be reconsidered.
Two processes support visual recognition memory in rhesus monkeys
Authors: Guderian Sebastian , Brigham Danielle , Mishkin Mortimer
Published: November 2011

A large body of evidence in humans suggests that recognition memory can be supported by both recollection and familiarity. Recollection-based recognition is characterized by the retrieval of contextual information about the episode in which an item was previously encountered, whereas familiarity-based recognition is characterized instead by knowledge only that the item had been encountered previously in the absence of any context. To date, it is unknown whether monkeys rely on similar mnemonic processes to perform recognition memory tasks. Here, we present evidence from the analysis of receiver operating characteristics, suggesting that visual recognition memory in rhesus monkeys also can be supported by two separate processes and that these processes have features considered to be characteristic of recollection and familiarity. Thus, the present study provides converging evidence across species for a dual process model of recognition memory and opens up the possibility of studying the neural mechanisms of recognition memory in nonhuman primates on tasks that are highly similar to the ones used in humans.
POST, partner of stromal interaction molecule 1 (STIM1), targets STIM1 to multiple transporters
Authors: Krapivinsky Grigory , Krapivinsky Luba , Stotz Stephanie C. , Manasian Yunona , Clapham David E.
Published: November 2011

Specialized proteins in the plasma membrane, endoplasmic reticulum (ER), and mitochondria tightly regulate intracellular calcium. A unique mechanism called store-operated calcium entry is activated when ER calcium is depleted, serving to restore intra-ER calcium levels. An ER calcium sensor, stromal interaction molecule 1 (STIM1), translocates within the ER membrane upon store depletion to the juxtaplasma membrane domain, where it interacts with intracellular domains of a highly calcium-selective plasma membrane ion channel, Orai1. STIM1 gates Orai1, allowing calcium to enter the cytoplasm, where it repletes the ER store via calcium-ATPases pumps. Here, we performed affinity purification of Orai1 from Jurkat cells to identify partner of STIM1 (POST), a 10-transmembrane–spanning segment protein of unknown function. The protein is located in the plasma membrane and ER. POST-Orai1 binding is store depletion-independent. On store depletion, the protein binds STIM1 and moves within the ER to localize near the cell membrane. This protein, TMEM20 (POST), does not affect store-operated calcium entry but does reduce plasma membrane Ca
2+
pump activity. Store depletion promotes STIM1–POST complex binding to smooth ER and plasma membrane Ca
2+
ATPases (SERCAs and PMCAs, respectively), Na/K-ATPase, as well as to the nuclear transporters, importins-β and exportins.
Evi1 is essential for hematopoietic stem cell self-renewal, and its expression marks hematopoietic cells with long-term multilineage repopulating activity
Authors: Kataoka Keisuke , Sato Tomohiko , Yoshimi Akihide , Goyama Susumu , Tsuruta Takako , Kobayashi Hiroshi , Shimabe Munetake , Arai Shunya , Nakagawa Masahiro , Imai Yoichi , Kumano Keiki , Kumagai Katsuyoshi , Kubota Naoto , Kadowaki Takashi , Kurokawa Mineo
Published: November 2011

Ecotropic viral integration site 1 (Evi1), a transcription factor of the SET/PR domain protein family, is essential for the maintenance of hematopoietic stem cells (HSCs) in mice and is overexpressed in several myeloid malignancies. Here, we generate reporter mice in which an internal ribosome entry site (IRES)-GFP cassette is knocked-in to the Evi1 locus. Using these mice, we find that Evi1 is predominantly expressed in long-term HSCs (LT-HSCs) in adult bone marrow, and in the hematopoietic stem/progenitor fraction in the aorta-gonad-mesonephros, placenta, and fetal liver of embryos. In both fetal and adult hematopoietic systems, Evi1 expression marks cells with long-term multilineage repopulating activity. When combined with conventional HSC surface markers, sorting according to Evi1 expression markedly enhances purification of cells with HSC activity. Evi1 heterozygosity leads to marked impairment of the self-renewal capacity of LT-HSCs, whereas overexpression of Evi1 suppresses differentiation and boosts self-renewal activity. Reintroduction of Evi1, but not Mds1-Evi1, rescues the HSC defects caused by Evi1 heterozygosity. Thus, in addition to documenting a specific relationship between Evi1 expression and HSC self-renewal activity, these findings highlight the utility of Evi1-IRES-GFP reporter mice for the identification and sorting of functional HSCs.
Dendritic cells induce antigen-specific regulatory T cells that prevent graft versus host disease and persist in mice
Authors: Sela Uri , Olds Peter , Park Andrew , Schlesinger Sarah J. , Steinman Ralph M.
Published: November 2011

Foxp3+ regulatory T cells (T reg cells) effectively suppress immunity, but it is not determined if antigen-induced T reg cells (iT reg cells) are able to persist under conditions of inflammation and to stably express the transcription factor Foxp3. We used spleen cells to stimulate the mixed leukocyte reaction (MLR) in the presence of transforming growth factor β (TGF-β) and retinoic acid. We found that the CD11chigh dendritic cell fraction was the most potent at inducing high numbers of alloreactive Foxp3+ cells. The induced CD4+CD25+Foxp3+ cells appeared after extensive proliferation. When purified from the MLR, iT reg cells suppressed both primary and secondary MLR in vitro in an antigen-specific manner. After transfer into allogeneic mice, iT reg cells persisted for 6 mo and prevented graft versus host disease (GVHD) caused by co-transferred CD45RBhi T cells. Similar findings were made when iT reg cells were transferred after onset of GVHD. The CNS2 intronic sequence of the Foxp3 gene in the persisting iT reg cells was as demethylated as the corresponding sequence of naturally occurring T reg cells. These results indicate that induced Foxp3+ T reg cells, after proliferating and differentiating into antigen-specific suppressive T cells, can persist for long periods while suppressing a powerful inflammatory disease.
Type I interferon negatively controls plasmacytoid dendritic cell numbers in vivo
Authors: Swiecki Melissa , Wang Yaming , Vermi William , Gilfillan Susan , Schreiber Robert D. , Colonna Marco
Published: November 2011

Plasmacytoid dendritic cells (pDCs) specialize in the secretion of type I interferons (IFN-I) and thus are considered critical mediators of antiviral responses. We recently reported that pDCs have a very early but limited and transient capacity to curtail viral infections. Additionally, pDC numbers are not sustained in human infections caused by Hepatitis B or C viruses (HBV and HCV) and HIV. Thus, the numbers and/or function of pDCs appear to be regulated during the course of viral infection. In this study, we show that splenic pDCs are reduced in vivo during several systemic viral infections and after administration of synthetic toll-like receptor ligands. We demonstrate that IFN-I, regardless of the source, contributes to this decline and mediates pDC death via the intrinsic apoptosis pathway. These findings demonstrate a feedback control mechanism by which IFN-I modulates pDC numbers, thus fine-tuning systemic IFN-I response to viruses. IFN-I–mediated control of pDCs may explain the loss of pDCs during human infections caused by HBV, HCV, or HIV and has important therapeutic implications for settings in which IFN-I is used to treat infections and autoimmune diseases.
IGSF4 is a novel TCR ζ-chain–interacting protein that enhances TCR-mediated signaling
Authors: Kim Hye-Ran , Jeon Byeong-Hun , Lee Hyun-Su , Im Sin-Hyeog , Araki Masatake , Araki Kimi , Yamamura Ken-ichi , Choi Suck-Chei , Park Do-Sim , Jun Chang-Duk
Published: November 2011

Immunoglobulin superfamily member 4 (IGSF4) is a known ligand of CRTAM, a receptor expressed in activated NKT and CD8+ T cells, but its function in T cell immunity has not been elucidated. In this study, we show that IGSF4 directly interacts with the T cell receptor (TCR) ζ-chain and enhances TCR signaling by enhancing ζ-chain phosphorylation. Ectopic overexpression of IGSF4 enhances TCR-mediated T cell activation. In contrast, IGSF4 knockdown shows a dramatic decrease in markers associated with T cell activation compared with those in control small interfering RNA. The transmembrane domain is essential for TCR ζ-chain association and clustering to the immunological synapse, and the ectodomain is associated with T cell interaction with antigen-presenting cells (APCs). IGSF4-deficient mice have impaired TCR-mediated thymocyte selection and maturation. Furthermore, these mice reveal attenuated effector T cell functions accompanied by defective TCR signaling. Collectively, the results indicate that IGSF4 plays a central role in T cell functioning by dual independent mechanisms, control of TCR signaling and control of T cell–APC interaction.
Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic–pituitary–adrenal axis
Authors: Braun Theodore P. , Zhu Xinxia , Szumowski Marek , Scott Gregory D. , Grossberg Aaron J. , Levasseur Peter R. , Graham Kathryn , Khan Sheehan , Damaraju Sambasivarao , Colmers William F. , Baracos Vickie E. , Marks Daniel L.
Published: November 2011

Skeletal muscle catabolism is a co-morbidity of many chronic diseases and is the result of systemic inflammation. Although direct inflammatory cytokine action on muscle promotes atrophy, nonmuscle sites of action for inflammatory mediators are less well described. We demonstrate that central nervous system (CNS)–delimited interleukin 1β (IL-1β) signaling alone can evoke a catabolic program in muscle, rapidly inducing atrophy. This effect is dependent on hypothalamic–pituitary–adrenal (HPA) axis activation, as CNS IL-1β–induced atrophy is abrogated by adrenalectomy. Furthermore, we identified a glucocorticoid-responsive gene expression pattern conserved in models of acute and chronic inflammatory muscle atrophy. In contrast with studies suggesting that the direct action of inflammatory cytokines on muscle is sufficient to induce catabolism, adrenalectomy also blocks the atrophy program in response to systemic inflammation, demonstrating that glucocorticoids are requisite for this process. Additionally, circulating levels of glucocorticoids equivalent to those produced under inflammatory conditions are sufficient to cause profound muscle wasting. Together, these data suggest that a significant component of inflammation-induced muscle catabolism occurs indirectly via a relay in the CNS.
Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor κB–mediated pathogenic pathways
Authors: Swarup Vivek , Phaneuf Daniel , Dupré Nicolas , Petri Susanne , Strong Michael , Kriz Jasna , Julien Jean-Pierre
Published: November 2011

TDP-43 (TAR DNA-binding protein 43) inclusions are a hallmark of amyotrophic lateral sclerosis (ALS). In this study, we report that TDP-43 and nuclear factor κB (NF-κB) p65 messenger RNA and protein expression is higher in spinal cords in ALS patients than healthy individuals. TDP-43 interacts with and colocalizes with p65 in glial and neuronal cells from ALS patients and mice expressing wild-type and mutant TDP-43 transgenes but not in cells from healthy individuals or nontransgenic mice. TDP-43 acted as a co-activator of p65, and glial cells expressing higher amounts of TDP-43 produced more proinflammatory cytokines and neurotoxic mediators after stimulation with lipopolysaccharide or reactive oxygen species. TDP-43 overexpression in neurons also increased their vulnerability to toxic mediators. Treatment of TDP-43 mice with Withaferin A, an inhibitor of NF-κB activity, reduced denervation in the neuromuscular junction and ALS disease symptoms. We propose that TDP-43 deregulation contributes to ALS pathogenesis in part by enhancing NF-κB activation and that NF-κB may constitute a therapeutic target for the disease.
Cl− concentration changes and desensitization of GABAA and glycine receptors
Authors: Karlsson Urban , Druzin Michael , Johansson Staffan
Published: November 2011

Desensitization of ligand-gated ion channels plays a critical role for the information transfer between neurons. The current view on γ-aminobutyric acid (GABA)A and glycine receptors includes significant rapid components of desensitization as well as cross-desensitization between the two receptor types. Here, we analyze the mechanism of apparent cross-desensitization between native GABAA and glycine receptors in rat central neurons and quantify to what extent the current decay in the presence of ligand is a result of desensitization versus changes in intracellular Cl− concentration ([Cl−]i). We show that apparent cross-desensitization of currents evoked by GABA and by glycine is caused by changes in [Cl−]i. We also show that changes in [Cl−]i are critical for the decay of current in the presence of either GABA or glycine, whereas changes in conductance often play a minor role only. Thus, the currents decayed significantly quicker than the conductances, which decayed with time constants of several seconds and in some cells did not decay below the value at peak current during 20-s agonist application. By taking the cytosolic volume into account and numerically computing the membrane currents and expected changes in [Cl−]i, we provide a theoretical framework for the observed effects. Modeling diffusional exchange of Cl− between cytosol and patch pipettes, we also show that considerable changes in [Cl−]i may be expected and cause rapidly decaying current components in conventional whole cell or outside-out patch recordings. The findings imply that a reevaluation of the desensitization properties of GABAA and glycine receptors is needed.
Expression and characterization of the bacterial mechanosensitive channel MscS in Xenopus laevis oocytes
Authors: Maksaev Grigory , Haswell Elizabeth S.
Published: November 2011

We have successfully expressed and characterized mechanosensitive channel of small conductance (MscS) from Escherichia coli in oocytes of the African clawed frog, Xenopus laevis. MscS expressed in oocytes has the same single-channel conductance and voltage dependence as the channel in its native environment. Two hallmarks of MscS activity, the presence of conducting substates at high potentials and reversible adaptation to a sustained stimulus, are also exhibited by oocyte-expressed MscS. In addition to its ease of use, the oocyte system allows the user to work with relatively large patches, which could be an advantage for the visualization of membrane deformation. Furthermore, MscS can now be compared directly to its eukaryotic homologues or to other mechanosensitive channels that are not easily studied in E. coli.
PubChem promiscuity: a web resource for gathering compound promiscuity data from PubChem
Authors: Canny Stephanie A. , Cruz Yasel , Southern Mark R. , Griffin Patrick R.
Published: November 2011

Summary: Promiscuity counts allow for a better understanding of a compound's assay activity profile and drug potential. Although PubChem contains a vast amount of compound and assay data, it currently does not have a convenient or efficient method to obtain in-depth promiscuity counts for compounds. PubChem promiscuity fills this gap. It is a Java servlet that uses NCBI Entrez (eUtils) web services to interact with PubChem and provide promiscuity counts in a variety of categories along with compound descriptors, including PAINS-based functional group detection.

Availability:  http://chemutils.florida.scripps.edu/pcpromiscuity

Contact:  southern@scripps.edu
Discovering transcription factor regulatory targets using gene expression and binding data
Authors: Maienschein-Cline Mark , Zhou Jie , White Kevin P. , Sciammas Roger , Dinner Aaron R.
Published: November 2011

Motivation: Identifying the target genes regulated by transcription factors (TFs) is the most basic step in understanding gene regulation. Recent advances in high-throughput sequencing technology, together with chromatin immunoprecipitation (ChIP), enable mapping TF binding sites genome wide, but it is not possible to infer function from binding alone. This is especially true in mammalian systems, where regulation often occurs through long-range enhancers in gene-rich neighborhoods, rather than proximal promoters, preventing straightforward assignment of a binding site to a target gene.

Results: We present EMBER (Expectation Maximization of Binding and Expression pRofiles), a method that integrates high-throughput binding data (e.g. ChIP-chip or ChIP-seq) with gene expression data (e.g. DNA microarray) via an unsupervised machine learning algorithm for inferring the gene targets of sets of TF binding sites. Genes selected are those that match overrepresented expression patterns, which can be used to provide information about multiple TF regulatory modes. We apply the method to genome-wide human breast cancer data and demonstrate that EMBER confirms a role for the TFs estrogen receptor alpha, retinoic acid receptors alpha and gamma in breast cancer development, whereas the conventional approach of assigning regulatory targets based on proximity does not. Additionally, we compare several predicted target genes from EMBER to interactions inferred previously, examine combinatorial effects of TFs on gene regulation and illustrate the ability of EMBER to discover multiple modes of regulation.

Availability: All code used for this work is available at http://dinner-group.uchicago.edu/downloads.html

Contact:  dinner@uchicago.edu

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Low levels of population genetic structure in the gilthead sea bream, Sparus aurata, along the coast of Italy
Authors: Franchini Paolo , Sola Luciana , Crosetti Donatella , Milana Valentina , Rossi Anna Rita
Published: November 2011

Franchini, P., Sola, L., Crosetti, D., Milana, V., and Rossi, A. R. 2012. Low levels of population genetic structure in the gilthead sea bream, Sparus aurata, along the coast of Italy. – ICES Journal of Marine Science, 69: 41–50. The gilthead sea bream, Sparus aurata, is a coastal, commercially important fish. Contrasting results concerning the genetic structure of the species at different geographic scales have been reported. Here, an investigation is made into the population genetic structure of S. aurata along the coast of Italy, using samples analysed previously and material from new sampling sites (12) and using different microsatellite loci (10). One sample from the eastern Atlantic and three temporal replicates from one site were also included. The presence of a weak (overall FST = 0.0072), but significant, genetic population subdivision was detected by F-statistics. Temporal replicates indicate genetic data consistency over time. Isolation by distance between the Atlantic and the coast of Italy is suggested by a Mantel test. The distributional pattern of genetic variance obtained by analysis of molecular variation reflects the geographic sampling areas, but is only partially congruent with the results obtained with fewer sites and loci. The dispersal of passive eggs/larvae by the main currents appears to contribute to shaping the gene flow. Given the intensity of sea bream aquaculture activities in Italy, the possibility that aquaculture may have partially contributed to the population genetic pattern detected cannot be excluded.
Influenza H1N1 (swine flu) vaccination: a safety surveillance feasibility study using self‐reporting of serious adverse events and pregnancy outcomes
Authors: Mackenzie Isla S. , MacDonald Thomas M. , Shakir Saad , Dryburgh Moira , Mantay Brian J. , McDonnell Patrick , Layton Deborah
Published: November 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• While the new H1N1 vaccines underwent the usual rigorous safety and efficacy testing, concerns remained that there may be unexpected side effects of the vaccines.

• The strategy for H1N1 vaccine pharmacovigilance in the UK consisted of two patient studies by the two vaccine manufacturers, 14 small scale studies supported by the National Institute of Health Research, monitoring by specialist neurologists and the MHRA.

• There were calls to investigate the feasibility of a large‐scale prospective active surveillance system for ‘near real‐time’ vaccine safety monitoring that would be complementary to the other aforementioned initiatives.

WHAT THIS STUDY ADDS

• This pilot study demonstrated that collecting ‘near real‐time’ reporting of event data from patients who experienced side effects as well as those who reported no problems after swine flu vaccination is feasible.

• The use of information technologies improves patient involvement in research as well as dramatically limiting the cost of the study.

• The online methodology facilitates rapid surveillance in response to urgent safety issues.

AIMS

During the global H1N1 influenza A (swine flu) pandemic 2009–2010, swine flu vaccines were expeditiously licensed and a mass vaccination programme for high risk groups, including pregnant women, was introduced in the UK. This pilot active safety surveillance study was performed to establish the feasibility of rapidly monitoring the new swine flu vaccines in large patient numbers receiving or offered the vaccination under normal conditions of use within a short time frame.

METHODS

A cohort design with safety data capture through modern technologies was carried out in Scotland, UK during the winter swine flu vaccination programme 2009–2010 in individuals receiving or offered the swine flu vaccination. The main outcome measures were self‐reported serious adverse events (SAEs) and pregnancy outcomes.

RESULTS

The cohort comprised 4066 people; 3754 vaccinated and 312 offered the vaccination but not vaccinated. There were 939 self‐reported events (838 different events), 53 judged to fit SAE criteria by the investigators, with nine judged as possibly, probably or definitely vaccine related. None of the seven deaths (six in vaccinees) were judged as vaccine related. One hundred and twenty‐eight women reported 130 pregnancies during the study with 117 pregnant at study start. There were reports of four miscarriages in three women and six possible congenital abnormalities in live births.

CONCLUSIONS

Overall, no significant safety issues were identified. The methodology and use of modern technologies to collect safety data from large numbers of patients was successful and could be used again in similar safety studies.
Clot lysis time and the risk of myocardial infarction and ischaemic stroke in young women; results from the RATIO case–control study
Authors: Siegerink Bob , Meltzer Mirjam E. , de Groot Philip G. , Algra Ale , Lisman Ton , Rosendaal Frits R.
Published: November 2011

Reduced overall fibrinolytic capacity increases the risk of myocardial infarction (MI), as demonstrated in studies with predominantly male participants. We determined the influence of altered fibrinolysis on the risk of MI and ischaemic stroke (IS) in young women. The RATIO (Risk of Arterial Thrombosis In relation to Oral contraceptives) study is a population‐based case‐control study including young women with MI (n = 203), IS (N = 175) and 638 matched healthy controls. Fibrinolytic potential was determined with a tissue factor/tissue plasminogen activator induced clot‐lysis assay. Odds ratios (OR) adjusted for cardiovascular risk factors were obtained with logistic regression. Clot‐lysis time (CLT) was divided into tertiles based on the control group (T1–T3), with T2 as reference. Hypofibrinolysis (prolonged CLT) was associated with an increase in risk of MI (T3 vs. T2, OR 2·8; 95%confidence interval [CI] 1·7–4·7). Hyperfibrinolysis (decreased CLT) had no clear effect (T1 vs. T2, OR 1·6; 95% CI 0·9–2·9). Hypofibrinolysis did not affect the risk of IS (T3 vs. T2, OR 1·5; 95% CI 0·7–3·0), whereas hyperfibrinolysis increased this risk (T1 vs. T2, OR 4·1; 95% CI 2·1–8·0). Oral contraceptive use and smoking further increased these risks. Hypofibrinolysis increases the risk for MI in young women, a finding similar to previous studies. Counter‐intuitively, hyperfibrinolysis increased the risk of IS four‐fold, which suggests that MI and IS have different aetiologies.
Enhanced levels of CCL19 in patients with advanced acquired immune deficiency syndrome (AIDS)
Authors: Damås J K , Øktedalen O , Ueland T , Landrø L , Barstad J , Müller F , Frøland S S , Flo T H , Aukrust P
Published: November 2011

Based on the ability to recruit lymphocytes and dendritic cells to lymphoid tissue and to promote inflammation, we hypothesized a role for dysregulated CCL19 and CCL21 levels in human immunodeficiency virus (HIV)-infected patients with advanced immunodeficiency, and in particular in those with accompanying Mycobacterium avium complex (MAC) infection. The hypothesis was explored by studies in HIV-infected patients with and without MAC infection, as well as in vitro, examining the ability of proteins from MAC to promote CCL19 and CCL21 responses in peripheral blood mononuclear cells (PBMC) during highly active anti-retroviral therapy (HAART). Our main findings were: (i) raised serum levels of CCL19 in HIV-infected patients with CD4+ T cell count <50 cells/µl compared with HIV-infected patients with CD4+ T cell count >500 cells/µl and healthy controls, with particularly high levels in those with MAC infection; (ii) elevated plasma levels of CCL19 predicted a higher mortality in acquired immune deficiency syndrome (AIDS)-patients, independent of ongoing MAC infection; and (iii) marked production of CCL19 in MAC-stimulated peripheral blood mononuclear cells (PBMC) and pronounced disturbances in MAC-induced CCL19 production in PBMC from HIV patients that was partly reversed during HAART. Our findings suggest the involvement of CCL19 in AIDS patients with advanced immunodeficiency, potentially mediating both adaptive and maladaptive responses.
Phenomenological shifts for healthcare professionals after experiencing a research‐based drama on living with dementia
Authors: Jonas‐Simpson Christine , Mitchell Gail J. , Carson Jennifer , Whyte Colleen , Dupuis Sherry , Gillies Jennifer
Published: November 2011

jonas‐simpson c., mitchell g.j., carson j., whyte c., dupuis s. & gillies j. (2012) Phenomenological shifts for healthcare professionals after experiencing a research‐based drama on living with dementia. Journal of Advanced Nursing68(9), 1944–1955.

Aim.  The aim of this article is to report research findings describing phenomenological shifts, that is, changes in patterns of lived experience, for healthcare professionals who attended a performance of a research‐based drama, called I’m Still Here.

Background.  The research drama, based on six studies, was created to help change the ways persons understand, think about and relate with persons living with dementia.

Methods.  In 2006–2007, 50 healthcare professionals from various disciplines and eight nursing students participated in this study. Participants were recruited from four Canadian cities in the province of Ontario where focus groups were held before and after engaging in a live performance of I’m Still Here.

Findings.  Analysis of focus group transcripts showed shifts in patterns of lived experience for the healthcare professional participants as evident in the participants’ descriptions. The phenomenological shifts reflected a move from descriptions of ‘diminishing humanness to discerning humanness’, from ‘disengaged care/mundane relating to reflexive relating in the now’, and ‘terrifying portrayals of loss to awakening to hopeful possibility’. The shifts described herein are supported with examples from the focus group transcripts.

Conclusions.  Findings reveal the power of drama as a vibrant and meaningful means of shifting understandings, images and intended actions of healthcare professions which have the potential to affect the lived experiences, relationships and quality of life of persons with dementia.
Effect of sleep‐inducing music on sleep in persons with percutaneous transluminal coronary angiography in the cardiac care unit
Authors: Ryu Min‐Jung , Park Jeong Sook , Park Heeok
Published: November 2011

Aim and objective.  The study compared the effect of earplug‐delivered sleep‐inducing music on sleep in persons with percutaneous transluminal coronary angiography in the cardiac care unit.

Background.  Diverse types of music have been claimed to improve sleeping elsewhere, but relatively little is known in South Korea. Most studies investigating the effect of sleep‐inducing music on sleep have involved persons with insomnia, even though many persons with cardiovascular disease in the intensive care unit suffer from sleeping problems. There is a need to investigate the effect of sleep‐inducing music on sleep disorders in persons with percutaneous transluminal coronary angiography in the cardiac care unit.

Design.  An experimental research design was used.

Methods.  Data collection was conducted in the cardiac care unit of K University Hospital in D city, from 3 September–4 October 2010. Fifty‐eight subjects participated and were randomly assigned to the experimental group (earplug‐delivered sleep‐inducing music for 52 min beginning at 10:00 pm, while wearing an eyeshield, n = 29) and the control group (no music, but earplugs and eyeshield worn, n = 29). The quantity and quality of sleep were measured using questionnaires at 7 am the next morning for each group.

Results.  Participants in the experimental group reported that the sleeping quantity and quality were significantly higher than control group (t = 3·181, p = 0·002, t = 5·269, p < 0·001, respectively).

Conclusion.  Sleep‐inducing music significantly improved sleep in patients with percutaneous transluminal coronary angiography at a cardiac care unit. Offering earplugs and playing sleep‐inducing music may be a meaningful and easily enacted nursing intervention to improve sleep for intensive care unit patients.

Relevance to clinical practice.  Nurses working at cardiac care unit can use music to improve sleeping in clients with percutaneous transluminal coronary angiography.
Predicting factors of pressure ulcers in older Thai stroke patients living in urban communities
Authors: Suttipong Chophaka , Sindhu Siriorn
Published: November 2011

Aim and objective.  To describe the contributing factors for pressure ulcer development in older Thai stroke patients in an urban community.

Background.  Pressure ulcers are a common problem signifying a source of morbidity and mortality in older stroke patients. In the past, most studies have focused on the physiological factors affecting pressure ulcer development. However, studies related to effect of stroke severity and psychosocial factors in community‐based setting have not found.

Design.  Cross‐sectional survey design.

Methods.  One hundred and sixty‐eight older stroke patients from urban communities in three districts in metropolitan Thailand were recruited for this cross sectional study. Data were collected from the Skin Assessment Tool, the Braden scale, the Canadian Neurological Scale, the Social Support Questionnaire and the Thai Geriatric Depression Scale for each patient. The results were analysed using multiple logistic regression and the chi‐square test.

Results.  Eighty older stroke patients who developed pressure ulcers (47·6%). The participants were aged between 60–93 years. Multiple logistic regression analysis was applied to calculate the odds ratio. The significant predicting factors for pressure ulcers were activity, moisture, nutrition, friction and shearing and depression. Sensory perception, mobility, severity of stroke and social support were not found to be significant predictors.

Conclusions.  Physiological factors and depression were found to be significant predicting factors for pressure ulcer development in older stroke patients living in an urban community.

Relevance to clinical practice.  To help prevent pressure ulcers in older stroke patients, the findings suggest that healthcare providers assess activity, moisture, nutrition, friction and shearing, as well as psychological assessment for depression. The results indicate that models for pressure ulcer prevention merit further investigation.
Using a nurse invented T‐Bar device in a rehabilitation program improved the range of motion for rotator cuff repair patients
Authors: Wang Ching‐Hui , Lin Pi‐Chu , Lee Yu‐Tai , Chuang Ching‐Wen , Tsay Shiow‐Luan , Chu Chan‐Yi
Published: November 2011

Aims and objectives.  This study investigates the effects on patient outcomes of using a T‐bar in rehabilitation programs in shoulder arthroscopic surgical procedure patients.

Background.  Orthopaedic nurses play an important role in facilitating restoration of patients’ range of motion shoulder function. Conventionally, nurses instruct patients to use the unaffected arm to hold the surgical arm when performing range of motion. However, patients often have difficulty performing the entire range of motion efficiently in this manner. Therefore, nurses have invented a T‐bar device to help patients perform range of motion in a rehabilitation program.

Design.  A repeated‐measure, quasi‐experimental study.

Method.  Sixty‐eight participants were recruited from four orthopaedic wards of a medical center in Taipei, Taiwan. Of the patients meeting the inclusion criteria for the study, 33 were assigned to the experimental group and 35 to the comparison group. Both groups had the same shoulder rehabilitation program including identical activities, duration and frequency, except that the experimental group used the nurse invented T‐bar device to facilitate range of motion while the comparison group used a conventional method. Data were collected when patients were admitted, five days and four weeks after the surgery. Outcome indicators were shoulder range of motion, muscle power and the American Shoulder and Elbow Society Shoulder Index. Statistical methods used for analysis included mean, standard deviation and repeated measures anova.

Results.  All the participants completed the study. Results showed a significant improvement in shoulder abduction after surgery in experimental group versus the comparison group. No significant differences were found in other outcomes.

Conclusions.  The nurse invented T‐bar device used in the rehabilitation program was effective in helping restore the abduction function of rotator cuff repair patients in our preliminary study.

Relevance to clinical practice.  Using a T‐bar in the rehabilitation program to improve range of motion may be considered for patients with shoulder surgery.
Symptoms and uncertainty in breast cancer survivors in Korea: differences by treatment trajectory
Authors: Kim Soo Hyun , Lee Ran , Lee Keon Suk
Published: November 2011

Aims.  The study compared the levels of symptoms and uncertainty, their associated factors, relationships between them and predictors of uncertainty by treatment trajectory among breast cancer survivors.

Background.  Little is known with regard to how uncertainty and symptoms are related to treatment trajectory among breast cancer survivors.

Design.  A cross‐sectional descriptive design was used.

Method.  A total of 252 women with breast cancer, receiving cancer therapy, or having completed their therapy were recruited from the National Cancer Center in Korea. Measurements used included symptom subscales of the European Organization of Research and Therapy for Cancer QLQ‐C30 and Breast Cancer Module BR23 and the Mishel Uncertainty in Illness Scale.

Results.  Women in treatment reported more severe symptoms and higher levels of uncertainty than women having completed treatment. During treatment, most symptoms were positively correlated with the level of uncertainty, whereas, in women who had completed treatment, only dyspnoea, insomnia, systemic therapy side effects and arm symptoms positively correlated with uncertainty. There were also differences in predictors of uncertainty by treatment trajectory. Age, marital status and pain were significant predictors of uncertainty during treatment, while monthly income, dyspnoea and insomnia were predictors of uncertainty after treatment.

Conclusions.  Among breast cancer survivors, levels of symptoms and uncertainty, associated factors, relationships between them and predictors of uncertainty differed depending on treatment trajectory.

Relevance to clinical practice.  To provide trajectory‐sensitive nursing intervention for uncertainty among breast cancer survivors, age, marital status and pain should be considered during treatment, while factors such as economic status, dyspnoea and insomnia should be taken into account after treatment.
An exploration of Singaporean parental experiences in managing school‐aged children’s postoperative pain: a descriptive qualitative approach
Authors: Lim Siew Hoon , Mackey Sandra , Liam Joanne Li Wee , He Hong‐Gu
Published: November 2011

Aims and objectives.  To enhance understanding of the experience of parents in managing their children’s postoperative pain in Singapore.

Background.  Parents play a significant role in their hospitalised child’s postoperative pain care. Their active involvement may contribute to accurate pain assessment and effective pain management for their child. However, there is a lack of in‐depth research exploring the experience of parents involved in their children’s postoperative pain management.

Design.  This study adopted a descriptive qualitative approach, which is situated in the interpretive paradigm.

Method.  Semi‐structured interviews were conducted to collect data from 14 parents whose children were hospitalised in one of the three paediatric surgical wards in a hospital in Singapore in December 2009. Thematic analysis was used to analyse the data.

Results.  Three themes were identified: ‘Actions used by parents to alleviate their child’s postoperative pain’, ‘Factors influencing parents’ management of their child’s postoperative pain’ and ‘Parents’ needs in the process of caring for their child’s postoperative pain’. Parents used a range of non‐pharmacological pain relief interventions for their child. Parental roles and expectations, bond between parent and child, support from nurses, family and own religious beliefs, as well as children’s age and maturity level were factors which promoted parental participation, whereas parents’ negative feelings, knowledge deficit and nurses’ busy schedule were hindering factors. Parents expressed needs for more involvement in their child’s care, adequate rest and information support from nurses.

Conclusions.  This study highlights the importance of involving parents in their child’s postoperative pain management. It provides evidence for health care professionals to pay attention to factors that may influence parental participation and, therefore, guide their practice.

Relevance to clinical practice.  Nurses need to provide parents with support and education to facilitate their roles and improve their child’s postoperative pain management.
Effects of denervation at ileocecal junction and ileocecal resection in dogs
Authors: Morita H. , Mochiki E. , Ogawa A. , Yanai M. , Toyomasu Y. , Tabe Y. , Ohno T. , Tsutsumi S. , Asao T. , Kuwano H.
Published: November 2011

Background  To investigate neural regulation at the ileocecal junction (ICJ) and motility changes after ileocecal resection (ICR). Previous studies showed normal basal motility at the ICJ directly by force transducers in dogs, but these observations were limited to normal contractile activity.

Methods  Continuous strain gauge recordings of stomach, terminal ileum, ileocecal sphincter (ICS), and colon were performed in dogs. The dogs were divided into four groups, namely control (CONT), extrinsic denervation at ICJ (ED), intrinsic denervation at ICJ (ID), and ICR groups. Colonic activity was recorded 2 h before a meal, in the early postprandial period (first 2 h), and in the late postprandial period (4–6 h after a meal). The meal lasted 5 min.

Key Results  Motility index was significantly increased at the ICS (P = 0.0056) and proximal colon (P = 0.0059) after feeding. However, such changes were not observed in the ED and ID groups. The amplitude of contractions at proximal colon in the interdigestive state was significantly decreased by ED. In the ID and ICR groups, the numbers of nonmigrating contractions were significantly decreased (P < 0.05), and colonic migrating motor complex (CMMC) ratio was significantly higher than that of the CONT group (P < 0.001). The dogs in these two groups had diarrhea.

Conclusions & Inferences  Gastrocolonic response at the ICJ may require both intrinsic and extrinsic innervation. When ID was performed, CMMC ratio increased. As a result, intraluminal water absorption may have decreased. ID may be one of the causes of diarrhea after ICR.