Constructing Number Field Isomorphisms from *-Isomorphisms of Certain Crossed Product C*-Algebras.

We prove that the class of crossed product C*-algebras associated with the action of the multiplicative group of a number field on its ring of finite adeles is rigid in the following explicit sense: Given any *-isomorphism between two such C*-algebras, we construct an isomorphism between the underlying number fields. As an application, we prove an analogue of the Neukirch-Uchida theorem using topological full groups, which gives a new class of discrete groups associated with number fields whose abstract isomorphism class completely characterises the number field.

Native contrast visualization and tissue characterization of myocardial radiofrequency ablation and acetic acid chemoablation lesions at 0.55 T.

PURPOSE: Low-field (0.55 T) high-performance cardiovascular magnetic resonance (CMR) is an attractive platform for CMR-guided intervention as device heating is reduced around 7.5-fold compared to 1.5 T. This work determines the feasibility of visualizing cardiac radiofrequency (RF) ablation lesions at low field CMR and explores a novel alternative method for targeted tissue destruction: acetic acid chemoablation. METHODS: N = 10 swine underwent X-ray fluoroscopy-guided RF ablation (6-7 lesions) and acetic acid chemoablation (2-3 lesions) of the left ventricle. Animals were imaged at 0.55 T with native contrast 3D-navigator gated T1-weighted T1w) CMR for lesion visualization, gated single-shot imaging to determine potential for real-time visualization of lesion formation, and T1 mapping to measure change in T1 in response to ablation. Seven animals were euthanized on ablation day and hearts imaged ex vivo. The remaining animals were imaged again in vivo at 21 days post ablation to observe lesion evolution. RESULTS: Chemoablation lesions could be visualized and displayed much higher contrast than necrotic RF ablation lesions with T1w imaging. On the day of ablation, in vivo myocardial T1 dropped by 19 ± 7% in RF ablation lesion cores, and by 40 ± 7% in chemoablation lesion cores (p < 4e-5). In high resolution ex vivo imaging, with reduced partial volume effects, lesion core T1 dropped by 18 ± 3% and 42 ± 6% for RF and chemoablation, respectively. Mean, median, and peak lesion signal-to-noise ratio (SNR) were all at least 75% higher with chemoablation. Lesion core to myocardium contrast-to-noise (CNR) was 3.8 × higher for chemoablation. Correlation between in vivo and ex vivo CMR and histology indicated that the periphery of RF ablation lesions do not exhibit changes in T1 while the entire extent of chemoablation exhibits T1 changes. Correlation of T1w enhancing lesion volumes indicated in vivo estimates of lesion volume are accurate for chemoablation but underestimate extent of necrosis for RF ablation. CONCLUSION: The visualization of coagulation necrosis from cardiac ablation is feasible using low-field high-performance CMR. Chemoablation produced a more pronounced change in lesion T1 than RF ablation, increasing SNR and CNR and thereby making it easier to visualize in both 3D navigator-gated and real-time CMR and more suitable for low-field imaging.

Learned pacing for adults with chronic pain: A randomised controlled trial feasibility study.

INTRODUCTION: Chronic pain can significantly impact on an individual's occupational performance and quality of life. Pacing is a pain management strategy regularly used in occupational therapy practice; however, evidence for its effectiveness has not been established. OBJECTIVES: To determine the feasibility of a future randomised controlled trial to investigate the effectiveness of a learned pacing intervention on occupational performance and satisfaction for adults with chronic pain. METHODS: A randomised controlled trial feasibility study was conducted with participants randomly assigned to a learned pacing intervention or a waitlist control group. The primary outcome measure was the Canadian Occupational Performance Measure. RESULTS: One hundred and twenty-eight people were screened for eligibility over 36 weeks, with 74 people invited to participate. Twelve were randomly assigned, eight to the learned pacing group and four to the control group. Those receiving the learned pacing intervention had clinically important changes in occupational performance and occupational satisfaction. Participants in the waitlist control group also had clinically important changes in occupational satisfaction. The method design was deemed feasible; however, several improvements would increase the rate of participant recruitment and reduce attrition. Recruitment from multiple sites is required to obtain an adequate sample size of 60. CONCLUSION: Undertaking a future randomised controlled trial is feasible and warranted to establish the effectiveness of a learned pacing intervention on occupational performance and satisfaction for adults with chronic pain.

Effectiveness of Pacing as a Learned Strategy for People With Chronic Pain: A Systematic Review.

IMPORTANCE: Pacing is a key pain management strategy used by occupational therapy practitioners when working with people with chronic pain. However, there is a paucity of evidence and a lack of consensus regarding the effectiveness of pacing as a pain management strategy for people with chronic pain. OBJECTIVE: To evaluate the evidence for the effectiveness of pacing as a learned strategy for people with chronic pain. DATA SOURCES: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to undertake a systematic review. Six databases were searched in March 2016 for randomized controlled trials (RCTs). Combinations of keywords and MeSH terms were used as search terms. STUDY SELECTION AND DATA COLLECTION: We sought intervention studies that included participants using pacing as a strategy. Studies were assessed for eligibility on the basis of predetermined criteria. Of the 2,820 articles located, 7 RCTs met inclusion criteria. FINDINGS: Pacing does not reduce the severity of pain or alter psychological traits; however, it can assist in lessening joint stiffness and the interference of fatigue and in decreasing the variability of physical activity. CONCLUSIONS AND RELEVANCE: Current evidence supports the delivery of a learned pacing intervention to reduce the interference of fatigue, reduce joint stiffness, and decrease physical activity variability but does not support the use of learned pacing to reduce pain severity. Future research should investigate the effectiveness of pacing as a pain management strategy within the International Classification of Functioning, Disability and Health domains of activity and participation. WHAT THIS ARTICLE ADDS: This systematic review examines existing research on pacing as a learned intervention strategy. The findings will support the clinical reasoning of occupational therapy practitioners, to determine when a learned pacing strategy is indicated, and considerations for how it may be delivered.

Nonclinical Cardiovascular Studies of Prucalopride, a Highly Selective 5-Hydroxytryptamine 4 Receptor Agonist.

Patients with chronic constipation benefit from treatment with 5-hydroxytryptamine 4 (5-HT4) receptor agonists. However, the first-generation 5-HT4 receptor agonists cisapride and tegaserod were withdrawn from the market owing to rare cardiovascular adverse events that were not 5-HT4-receptor-related but due to the lack of selectivity of these drugs. Here we report the nonclinical cardiovascular profile of the selective 5-HT4 receptor agonist prucalopride. To assess its non-5-HT4 receptor-mediated effects on cardiovascular electrophysiological parameters, in vitro studies were performed in human ether-à-go-go-related gene-transfected cells, guinea pig ventricular myocytes and papillary muscle preparations, rabbit and dog Purkinje fibers, and the Langendorff rabbit heart. In vivo experiments were performed in a rabbit model for drug-induced proarrhythmogenesis, in anesthetized guinea pigs, and anesthetized and conscious dogs. In addition, human platelet aggregation and coronary artery contraction were studied to exclude interactions that have been suggested to mediate the cardiovascular effects of tegaserod. Effects at 5-HT4 receptors were evaluated in piglet and human atrial myocardium, and in anesthetized pigs. Finally, cardiovascular endpoints were investigated in chronic, repeated-dose toxicology studies at very high prucalopride doses in rats and dogs. No relevant effects were observed in any of the cardiovascular studies at concentrations at least 50 times the therapeutic plasma level. Only in pigs were minor and transient increases in heart rate and blood pressure noted upon first exposure to prucalopride, at plasma levels at least 10 times higher than human therapeutic plasma levels. Prucalopride may thus provide therapeutic benefit without the cardiovascular risks reported for other 5-HT4 receptor agonists.

Development and validation of the Occupational Therapy Risk Propensity Test (OT-RiPT) for drivers with disability.

BACKGROUND: Male drivers in the 16- to 19-year age group have a nine-fold increase in their crash risk compared with 25- to 34-year-olds who have a relative risk of 2.3. Crash risk in young drivers has been directly linked to risk-taking behaviour. This paper reports the development of a video risk assessment tool for use with drivers. AIM/OBJECTIVE: This paper reports on the process of validating and investigating the reliability of the Occupational Therapy Risk Propensity Test (OT-RiPT) to measure risk-taking propensity. MATERIAL AND METHODS: 20 healthy male participants were recruited. OT-RiPT scores were correlated with driving experience. Internal consistency was investigated using Cronbach's alpha. Face validity was established. The OT-RiPT and a validated driver behaviour questionnaire were administered and the results correlated to establish discriminant validity. RESULTS: There was no significant correlation between driving experience and OT-RiPT scores. Good internal consistency was established. OT-RiPT has high face validity. Discriminant validity was demonstrated. CONCLUSION AND SIGNIFICANCE: Pending further testing, OT-RiPT shows promise as a reliable and valid measure of risk-taking propensity in young drivers.

Activation of Toll-like receptor 5 decreases the attachment of human trophoblast cells to endometrial cells in vitro.

BACKGROUND: Embryo implantation in the uterus involves the trophoblast cells apposing and adhering to, then invading across the epithelium lining of the endometrium. However, ethical concerns regarding experimentation with primary human tissue during this period of life necessitates creation of in vitro models for understanding the basic mechanisms involved. Toll-like receptors (TLRs) play a crucial role in defence against pathogens invading the female reproductive tract. The objective of this study is to establish and optimize an in vitro model for studying human endometrial embryonic interactions and to understand the effect of TLR5 stimulation on the attachment of trophoblast cells to endometrial cells. METHODS: By using a human telomerase immortalized endometrial epithelial cell line (hTERT-EECs) and choriocarcinoma human trophoblast cells (JAr cells), an in vitro assay of human implantation was established. In order to investigate the impact of TLR5 stimulation on attachment in this assay, bacterial flagellin was applied to the endometrial and trophoblast cells. In order to block TLR5 in the endometrial and trophoblast cells, TLR5 function-blocking antibody was applied to the cells prior to flagellin treatment. RESULTS: The results demonstrated that JAr spheroids attached to hTERT-EECs in a time and concentration-dependent manner. Our results also demonstrated that treatment of endometrial cells with flagellin, suppressed the attachment of JAr spheres to the endometrial cells. Application of TLR5 function-blocking antibody significantly restored the attachment of JAr spheres to the endometrium. CONCLUSIONS: These data suggest a novel mechanism by which the presence of intrauterine infection through TLR5 activation may result in implantation failure. These data may provide a new opportunity in the management of infertility cases.

Expression and function of Toll-like receptors in human endometrial epithelial cell lines.

In mammals, Toll-like receptors (TLRs) are the principal family of innate immune pattern recognition receptors (PRRs). The main function for TLRs is the detection of molecular patterns associated with invading pathogens. We investigated TLR expression and function in three established human endometrial epithelial cell lines, including hTERT-EEC, HEC-1B and Ishikawa cells, and clarified the application of these endometrial cell lines as in vitro models for studying TLR expression and function in the female reproductive tract. TLR gene expression was examined by RT-PCR and protein localization by immunohistochemistry. Our results showed that TLR expression in these cell lines is comparable to published literature on TLR expression in primary human endometrial tissue. TLR function was investigated by the detection of IL-6 and IL-8 production by ELISA in response to TLR2, TLR3, TLR5, TLR7 and TLR9 ligands. We found that hTERT-EEC cells were responsive to TLR5 ligand and HEC-1B cells respond to TLR3 and TLR5 ligands. In contrast, Ishikawa cells respond only to PMA/I which was used as a positive control for IL-8 production. Finally, we investigated the influence of flagellin as a TLR5 stimulant on TLR5 expression in these cell lines by QPCR. Our results showed that the endometrial cell lines showed a tendency for increased TLR5 expression in response to flagellin stimulation and in hTERT-EEC cells this tendency was statistically significant. These results suggest that hTERT-EEC, HEC-1B and Ishikawa cell lines can be used as in vitro models to investigate innate immune responses of endometrial cells in the female reproductive tract.

Evolutionary and functional conservation of the DNA non-homologous end-joining protein, XLF/Cernunnos.

Non-homologous end-joining is a major pathway of DNA double-strand break repair in mammalian cells, deficiency in which confers radiosensitivity and immune deficiency at the whole organism level. A core protein complex comprising the Ku70/80 heterodimer together with a complex between DNA ligase IV and XRCC4 is conserved throughout eukaryotes and assembles at double-strand breaks to mediate ligation of broken DNA ends. In Saccharomyces cerevisiae an additional NHEJ protein, Nej1p, physically interacts with the ligase IV complex and is required in vivo for ligation of DNA double-strand breaks. Recent studies with cells derived from radiosensitive and immune-deficient patients have identified the human protein, XLF (also named Cernunnos), as a crucial NHEJ protein. Here we show that XLF and Nej1p are members of the same protein superfamily and that this family has members in diverse eukaryotes. Indeed, we show that a member of this family encoded by a previously uncharacterized open-reading frame in the Schizosaccharomyces pombe genome is required for NHEJ in this organism. Furthermore, our data reveal that XLF family proteins can bind to DNA and directly interact with the ligase IV-XRCC4 complex to promote DSB ligation. We therefore conclude that XLF family proteins interact with the ligase IV-XRCC4 complex to constitute the evolutionarily conserved enzymatic core of the NHEJ machinery.