bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of methadone as a β-arrestin-biased μ-opioid receptor agonist
Authors: Doi Seira , Mori Tomohisa , Uzawa Naoki , Arima Takamichi , Takahashi Tomoyuki , Uchida Masashi , Yawata Ayaka , Narita Michiko , Uezono Yasuhito , Suzuki Tsutomu , Narita Minoru 
Published: June 2016

Background Methadone is a unique µ-opioid receptor agonist. Although several researchers have insisted that the pharmacological effects of methadone are mediated through the blockade of NMDA receptor, the underlying mechanism by which methadone exerts its distinct pharmacological effects compared to those of other µ-opioid receptor agonists is still controversial. In the present study, we further investigated the pharmacological profile of methadone compared to those of fentanyl and morphine as measured mainly by the discriminative stimulus effect and in vitro assays for NMDA receptor binding, µ-opioid receptor-internalization, and µ-opioid receptor-mediated β-arrestin recruitment. Results We found that fentanyl substituted for the discriminative stimulus effects of methadone, whereas a relatively high dose of morphine was required to substitute for the discriminative stimulus effects of methadone in rats. Under these conditions, the non-competitive NMDA receptor antagonist MK-801 did not substitute for the discriminative stimulus effects of methadone. In association with its discriminative stimulus effect, methadone failed to displace the receptor binding of MK801 using mouse brain membrane. Methadone and fentanyl, but not morphine, induced potent µ-opioid receptor internalization accompanied by the strong recruitment of β-arrestin-2 in µ-opioid receptor-overexpressing cells. Conclusions These results suggest that methadone may, at least partly, produce its pharmacological effect as a β-arrestin-biased µ-opioid receptor agonist, similar to fentanyl, and NMDA receptor blockade is not the main contributor to the pharmacological profile of methadone.
Time for change? A national audit on bereavement care in intensive care units
Authors: Berry M , Brink E , Metaxa V 
Published: June 2016

Introduction Bereaved ICU family members frequently experience anxiety, depression and post-traumatic stress disorder, which have been associated with significantly impaired quality of life. Recognising that their needs extend beyond the support provided by their friends and family, the Intensive Care Society had published in 1998 recommendations around bereavement care. Objective The aim of the present national audit was to compare bereavement services in England against the nine recommendations set out by the Intensive Care Society guidelines. Methods A telephone audit was carried out in all adult ICUs in England. Results A total of 144 NHS Trusts (179 ICUs) met the inclusion criteria and 113 responses were collected (78% of Trusts, 63% of individual ICUs). Although most ICUs provided administrative information (96% had an information booklet), training (53%), auditing (19%) and adequate facilities (27%) did not meet the recommended standards. Conclusion Bereavement care is underdeveloped in English ICUs. This important but underreported topic should be prioritised in the critical care research agenda.
Making connections and promoting the profession: Social media use by World Federation of Occupational Therapists member organisations
Authors: Hamilton Anita L , Burwash Susan C , Penman Merrolee , Jacobs Karen , Hook Angela , Bodell Sarah , Ledgerd Ritchard , Pattison Marilyn 
Published: June 2016

Background World Federation of Occupational Therapists (WFOT) member organisations comprise 77 national occupational therapy organisations across the world. Each national organisation interacts with its members and the public using diverse methods. Increasingly, national organisations are broadening their communication methods. Objective The objective of this study was to examine if and how occupational therapy organisations are using social media for communication, and if so, the types of concerns or barriers they experience and what role they anticipate social media might play in the near future. Methods An online survey was developed; 57 of 77 WFOT member organisations responded. Findings This study identified that WFOT national organisations are using social media, to varying degrees, with or without an individual formally assigned to manage social media. Respondents reported that they used social media to: communicate with members, promote the organisation and promote the profession. Commonly expressed needs included assistance with guidelines for ethical social media use, developing technical expertise, and recognition of limits of time and competing priorities. Recommendations arising from this research are at the global, national, local and individual levels and incorporate active dissemination and pure diffusion approaches. Taking steps to increase the use of social media could indirectly impact occupational therapy practice through enhancing organisations’ abilities to support practitioners to enhance their practice. Limitations and recommendations for further research Although 57% of WFOT member organisations returned usable responses, there may be some additional perspectives that were not captured. It would be helpful to contact non-responding organisations to explore their social media use and plans. Further research could examine how future initiatives put in place by WFOT impact social media use by member organisations.
Exergames for the corporate wellness program in Singapore: An investigation of employees’ acceptance via watching Kinect video
Authors: Li Jinhui , Theng Yin-Leng , Cheong Wei Lun , Hoo Yi Fei , Ngo My Dung 
Published: June 2016

Objective This study aimed to explore the acceptance of exergames in a work environment and investigate influencing factors through examining a conceptual model. Methods After viewing a short video on playing exergames, sixty recruited working adults scored items associated with perceived usefulness, perceived ease of use, attitude toward use, and intention to use. Confirmatory factor analysis was carried out to test the measurement model, followed by structural equation modeling to estimate the path coefficients. Results The conceptual model was generally supported, with most of the path coefficients being statistically significant. Employees who perceived a higher level of ease of use toward exergames are more likely to have higher perceived usefulness and attitude toward use; higher perceived usefulness and attitude toward use further increases employees’ intention of use for the exergames. Conclusion Findings emphasized the importance of usability in affecting employees’ acceptance of exergames, thereby implying that designers should balance hedonic and utilitarian considerations in game design.
The Influence of University Activities on Multicultural Teams
Authors: Syring Nadine 
Published: June 2016

An increasing relevance of organizational cross-border relationships, and thereby of Europeanization, globalization, and internationalization, has led to the importance of intercultural competence. To develop this competence among their students, most educational institutions have entered into international partnerships and offer international projects accompanied by intercultural curricula. This article concentrates on the influence of these activities in higher education concerning the success of multicultural student teams. The teams analyzed here consist of students from three different nations working on a joint project. Due to the cultural differences, conflicts can be anticipated (Hofstede, Hofstede & Minkov, 2010; Rohn, 2006) and intercultural competence to overcome those conflicts is needed ( Hiller, 2010 ). To reflect the effect of activities strengthening intercultural competence, four university coefficients were allocated to each team based on the theory of, inter alia, Bennett (2011) and Führing (1996) . In a survey, the students assessed at the end of the project how well they felt supported by the different activities and how comfortable they felt within their respective team. Out of this assessment, team success factors were evaluated. It was expected that a positive correlation between the assessment of activities and the team success factors would result. Interestingly, the sample used does not show this relationship. This article is based on a comprehensive and interdisciplinary study of literature as well as on empirical research. The main result of the research shows the changing importance of activities to strengthen intercultural competence based on the difference between students’ competence from international universities. Accordingly, it might be a basis on which to restructure programs teaching intercultural competence in higher education.
Inducible epithelial resistance protects mice against leukemia-associated pneumonia
Authors: Leiva-Juárez Miguel M. , Ware Hayden H. , Kulkarni Vikram V. , Zweidler-McKay Patrick A. , Tuvim Michael J. , Evans Scott E. 
Published: June 2016

Key PointsSurvival of acute myelogenous leukemia is frequently limited by pneumonia, due to disease- and therapy-associated immune defects. Inducible epithelial resistance protects neutropenic, leukemic mice against lethal pneumonia without impacting AML cell proliferation.
Hydrogen peroxide in exhaled air: a source of error, a paradox and its resolution
Authors: Peters Stefan , Kronseder Angelika , Karrasch Stefan , Neff Petra A. , Haaks Matz , Koczulla Andreas R. , Reinhold Petra , Nowak Dennis , Jörres Rudolf A. 
Published: June 2016

The concentration of hydrogen peroxide (H2O2) in exhaled air has been reported to be elevated in asthma and chronic obstructive pulmonary disease (COPD), but results are inconsistent and difficult to reproduce. As H2O2occurs in ambient air, we examined its association with exhaled H2O2in human subjects.Exhaled breath condensate (EBC) of 12 COPD patients and nine healthy control subjects was collected either with an inhalation filter (efficiency 81%) or without. Ambient air condensate (AAC) was collected in parallel and samples were analysed for H2O2. Additionally, ambient H2O2was recorded by an atmospheric measuring device (online fluorometric measurement).H2O2concentration in AAC was significantly higher (p<0.001) than in EBC. AAC variations were concordant with the data from the atmospheric measuring instrument. In both subjects' groups, the inhalation filter reduced H2O2values (p<0.01). Despite generally low levels in exhaled air, analysis by a mathematical model revealed a contribution from endogenous H2O2production.The low H2O2levels in exhaled air are explained by the reconditioning of H2O2-containing inhaled air in the airways. Inhaled H2O2may be one factor in the heterogeneity and limited reproducibility of study results. A valid determination of endogenous H2O2production requires inhalation filters.
MR microscopy of the human fetal upper extremity – a proof-of-principle study
Authors: Langner Inga , Stahnke Thomas , Stachs Oliver , Lindner Tobias , Kühn Jens-Peter , Kim Simon , Wree Andreas , Langner Soenke 
Published: June 2016

Abstract
Background
Current knowledge of the human fetal and embryonic development relies on early descriptive studies of humans and from experimental studies of laboratory animals and embryos. Taking the upper extremity as an example, this study explores the potential of magnetic resonance microscopy (MRM) for the assessment of the development of the fetal upper extremity and discusses its correlation with histological findings.

Methods
Ex vivo MRM at 7.1 T (Clin Scan, Bruker Biospin, Germany) was performed in 10 human specimens at 8 to 12 weeks of gestational age (GA). In-plane resolution was 20 μm with a slice thickness of 70 μm. MRM was followed by histological work-up of the specimens. MRM images were then correlated with conventional histology with a focus on the presence of chondrification and ossification.

Results
Ossification of the upper human extremity is detectable at 8 weeks GA in the humerus and the long bones of the forearm. There is excellent correlation for location and size of ossification between MRM and conventional histology. MRM imaging is in accordance with historical studies.

Conclusion
Ex vivo MRM for the non-invasive assessment of the embryonic and fetal development of the upper human extremity is feasible. It may provide an accurate complementary tool for the evaluation of embryological development.
Environmental cues orchestrate regional immune surveillance and protection by pulmonary CTLs
Authors: Cauley Linda S 
Published: June 2016

Abstract
Tissue-resident memory CD8 T cells (TRM) provide preemptive immunity against infections that begin in peripheral tissues by guarding the site of initial pathogen exposure. Their role in immunity to respiratory virus infection is particularly important because severe damage to the alveoli can be avoided when local populations of TRM cells reduce viral burdens and dampen the responses of effector CD8 T cells in the lungs. Although a connection between rapid immune activation and early viral control is well established, the signals that keep TRM cells poised for action in the local tissues remain poorly defined. Recent studies have shown that environmental cues influence the fate decisions of activated CTLs during memory formation. Manipulation of these signaling pathways could provide new ways to capitalize on protection from TRM cells in mucosal tissues, while reducing collateral damage and pathology during vaccination.
Dendritic cell expression of ADAM23 governs T cell proliferation and cytokine production through the α(v)β(3) integrin receptor
Authors: Elizondo D M , Andargie T E , Marshall K M , Zariwala A M , Lipscomb M W 
Published: June 2016

Abstract
ADAM23 is a member of the brain macrophage-derived chemokine family. Structural homology of ADAM proteins suggests their function as integrin receptors. Previous studies have linked ADAM23 as a dominant contributor to brain development and cancer metastasis. The present studies now show that ADAM23 expression on DCs partially governs antigen-presentation capacities to responder CD4+ T cells. With the use of RNAi approaches, knockdown of ADAM23 in murine BMDCs resulted in impaired T cell activation, proliferation, and cytokine production. Knockdown did not alter the maturation profile of DCs (i.e., costimulatory molecule expression or production of proinflammatory cytokines) but markedly impaired cognate T cell responses. There was a significant decrease in antigen-specific clonal expansion coupled with a global decrease in Th cytokine production. Impaired early activation and proliferation did not alter/skew the balance of Th polarization but significantly depressed total levels of IL-2, IFN-γ, IL-4, and IL-17 cytokine production in CD4+ T cells primed by ADAM23 knockdown versus control DCs. Finally, neutralizing antibodies targeting the α(v)β(3) integrin receptors resulted in similar phenotypes of impaired CD4+ T cell responses. Taken together, these studies show a novel role of ADAM23 in governing DC antigen presentation to cognate CD4+ T cells.
Timing of Preoperative Troponin Elevations and Postoperative Mortality After Noncardiac Surgery
Authors: Maile Michael D. , Jewell Elizabeth S. , Engoren Milo C. 
Published: June 2016

BACKGROUND:
Even small elevations in preoperative troponin levels have been shown to be associated with adverse outcomes. However, there are currently limited data on the relationship between troponin increase and timing of surgery.

METHODS:
We performed a single-institution, retrospective cohort study of 6030 individuals with a troponin measurement made during the 30 days preceding a noncardiac surgical procedure. Subjects with detectable troponin levels were separated into terciles based on both the magnitude of the value and the time elapsed between this value and the surgery. For those undergoing nonemergent procedures, these 9 cohorts were compared with the group of individuals with undetectable preoperative troponin levels using bivariable and multivariable logistic regression.

RESULTS:
Thirty-day mortality was 4.7% in the group with undetectable troponin levels and increased with higher concentrations, with rates of 8.9%, 12.7%, and 12.7% in the low, medium, and high tercile groups, respectively. Unadjusted risk of 30-day mortality was highest in those with the highest troponin levels and shortest duration between the measurement and surgery (odds ratio, 4.497; 95% confidence interval, 2.058–9.825). After adjusting for subject characteristics, troponin remained associated with 30-day mortality in several groups, including individuals with troponin levels in the normal range.

CONCLUSIONS:
Higher levels of preoperative cardiac troponin I were associated with higher postoperative mortality, and longer time to surgery appeared to reduce this risk for individuals with mild preoperative troponin elevations. Prospective studies are needed to determine whether delaying surgery in patients with elevated preoperative troponin levels improves postoperative outcomes.
Histaminergic Pharmacology Modulates the Analgesic and Antiedematogenic Effects of Spinally Injected Morphine
Authors: Stein Taciane , Souza-Silva Eduardo , Mascarin Lucas , Eto Carolina , Fin Franci Ellen , Tonussi Carlos Rogério 
Published: June 2016

BACKGROUND:
Histamine receptors are known to participate in spinal cord nociceptive transmission, and previous studies have suggested that histaminergic receptors are involved in the analgesic effects of morphine. Herein, we investigated the effect of intrathecal injection of histaminergic agonists and antagonists in a model of acute articular inflammation and their interaction with morphine.

METHODS:
After carrageenan injection in the right knee joint, articular incapacitation was measured hourly, for up to 6 hours, by the paw elevation time during 1-minute periods of stimulated walking. Inflammatory edema was also assessed hourly by determining an increase in articular diameter. Spinal treatments were administered 20 minutes before knee-joint carrageenan injection and were compared with the saline-treated control group.

RESULTS:
Intrathecally injected histamine increased incapacitation and articular edema, whereas the H1R antagonist, cetirizine, decreased both parameters. The H3R agonist, immepip, decreased both incapacitation and edema, but the H3R antagonist, thioperamide, increased both incapacitation and edema. Morphine inhibited both incapacitation and edema. Furthermore, combining a subeffective dose of morphine with cetirizine or immepip potentiated the analgesic and antiedematogenic effect.

CONCLUSIONS:
Histamine seems to act at the spinal level via H1 and H3 receptors to modulate acute arthritis in rats. An H1R antagonist and H3R agonist were found to potentiate the analgesic and antiedematogenic effects of morphine, suggesting that histaminergic and opioid spinal systems may be explored for means of improving analgesia, as well as peripheral anti-inflammatory effects.
The Ropivacaine Concentration Required for Ultrasound-Guided Ilioinguinal/Iliohypogastric Nerve Block in Pediatric Patients
Authors: Yamada Kumiko , Inomata Shinichi , Tanaka Makoto 
Published: June 2016

BACKGROUND:
To the best of our knowledge, the ropivacaine concentration required for ultrasound-guided ilioinguinal and iliohypogastric nerve block (INB) has not been reported. We designed this study to examine the 50% effective concentration (EC50) of ropivacaine for ultrasound-guided INB in children anesthetized with 2% sevoflurane.

METHODS:
We studied 30 consecutive children (age range, 6 months to 11 years) ASA physical status I to II undergoing unilateral open inguinal hernia repair. General anesthesia was induced by sevoflurane and maintained with 2% end-tidal concentration of sevoflurane in air and oxygen (Fio
2 = 0.4). Ultrasound-guided INB was performed using a 3 mL ropivacaine solution. The first child received 0.3% ropivacaine, and subsequent concentrations were determined by the response of the previous patient to initial skin incision using Dixon up-and-down method. The testing interval was set at 0.1%, and the lowest concentration was 0.05% (0.05%, 0.1%, 0.2%, 0.3%, 0.4%, or 0.5%). The EC50 for INB of ropivacaine was analyzed using probit test.

RESULTS:
The concentration at which all patients showed complete block was 0.50%, according to the up-and-down method. The EC50 was 0.21% (95% confidence interval, 0.03–0.34).

CONCLUSIONS:
The EC50 of ropivacaine for ultrasound-guided INB was 0.21% (95% confidence interval, 0.03–0.34), in pediatric patients anesthetized with 2% sevoflurane.
The Posterior Transcallosal Approach to the Pineal Region and Posterior Third Ventricle: Intervenous and Paravenous Variants
Authors: Patel Prayash G. , Cohen-Gadol Aaron A. , Mercier Philippe , Boop Frederick A. , Klimo Paul 
Published: June 2016

Abstract

BACKGROUND: There are a number of surgical approaches to the posterior third ventricle and pineal region, each with its associated advantages and disadvantages.

OBJECTIVE: To present our experience with the posterior interhemispheric transcallosal approach and to analyze the indications, technique, and outcomes.

METHODS: A retrospective study was conducted to identify and analyze all children and young adults who underwent the posterior transcallosal approach from July 2010 to March 2015. Perioperative data included patient demographics, signs and symptoms on presentation, tumor characteristics (type, origin, and size), complications, and clinical and radiographic outcome at final follow-up.

RESULTS: Twenty-two patients (9 female, 13 male) were identified in 24 cases with a mean age of 10.5 years (range, 3-32 years). The most common tumor type was pineoblastoma (n = 6). Eleven patients underwent gross total resections; 11 underwent subtotal resections; and 2 tumors were biopsied. The intervenous operative corridor was used in 15 cases; the paravenous was used in 9. Of the 22 patients, 19 experienced 31 total postoperative events. There were 12 instances of contralateral weakness. Retraction-related hemiparesis was usually temporary; resection-related hemiparesis lasted longer. There were no complications related to occlusion of one or more bridging cortical veins or from thrombosis of 1 internal cerebral vein. Eight patients have died of tumor progression, and of the remaining 14 patients, only 1 patient to date has developed local progression.

CONCLUSION: The posterior interhemispheric transcallosal approach allows resection of tumors located within the pineal region, posterior third ventricle, and thalamus. New postoperative neurological deficits can occur; however, many will improve significantly or resolve completely over time.