Development of the ASQoL: a quality of life instrument specific to ankylosing spondylitis

Background: Although disease-specific health status measures are available for ankylosing spondylitis (AS), no instrument exists for assessing quality of life (QoL) in the condition. Objective: To produce an AS-specific QoL measure that would be relevant and acceptable to respondents, valid, and reliable. Methods: The ASQoL employs the needs-based model of QoL and was developed in parallel in the UK and the Netherlands (NL). Content was derived from interviews with patients in each country. Face and content validity were assessed through patient field test interviews (UK and NL). A postal survey in the UK produced a more efficient version of the ASQoL, which was tested for scaling properties, reliability, internal consistency, and validity in a further postal survey in each country. Results: A 41 item questionnaire was derived from interview transcripts. Field testing interviews confirmed acceptability. Rasch analysis of data from the first survey (n=121) produced a 26 item questionnaire. Rasch analysis of data from the second survey (UK: n=164; NL: n=154) showed some item misfit, but showed that items formed a hierarchical order and were stable over time. Problematic items were removed giving an 18 item scale. Both language versions had excellent internal consistency (α=0.89–0.91), test-retest reliability (r(s)=0.92 UK and r(s)=0.91 NL), and validity. Conclusions: The ASQoL provides a valuable tool for assessing the impact of interventions for AS and for evaluating models of service delivery. It is well accepted by patients, taking about four minutes to complete, and has excellent scaling and psychometric properties

Signatures of anthocyanin metabolites identified in humans inhibit biomarkers of vascular inflammation in human endothelial cells

Scope The physiological relevance of contemporary cell culture studies is often perplexing, given the use of unmetabolized phytochemicals at supraphysiological concentrations. We investigated the activity of physiologically relevant anthocyanin metabolite signatures, derived from a previous pharmacokinetics study of 500 mg 13C5-cyanidin-3-glucoside in 8 healthy participants, on soluble vascular adhesion molecule-1 (VCAM-1) and interleukin-6 (IL-6) in human endothelial cells. Methods and results Signatures of peak metabolites (previously identified at 1, 6 and 24 h post-bolus) were reproduced using pure standards and effects were investigated across concentrations ten-fold lower and higher than observed mean (<5 μM) serum levels. Tumor necrosis factor-α (TNF-α)-stimulated VCAM-1 was reduced in response to all treatments, with maximal effects observed for the 6 h and 24 h profiles. Profiles tested at ten-fold below mean serum concentrations (0.19-0.44 μM) remained active. IL-6 was reduced in response to 1, 6 and 24 h profiles, with maximal effects observed for 6 h and 24 h profiles at concentrations above 2 μM. Protein responses were reflected by reductions in VCAM-1 and IL-6 mRNA, however there was no effect on phosphorylated NFκB-p65 expression. Conclusion Signatures of anthocyanin metabolites following dietary consumption reduce VCAM-1 and IL-6 production, providing evidence of physiologically relevant biological activity

The anti-inflammatory effects of prostaglandin E 2 on human lung macrophages are mediated by the EP 4 receptor

Background and purpose: Prostaglandin E2 (PGE2) has been shown to inhibit cytokine generation from human lung macrophages. However, the EP receptor that mediates this beneficial anti-inflammatory effect of PGE2 has not been elucidated definitively. The aim of this study was to identify the EP receptor by which PGE2 inhibits cytokine generation from human lung macrophages. This was determined by using recently-developed EP receptor ligands. Experimental approach: The effects of PGE2 and EP-selective agonists on lipopolysaccharide (LPS) induced tumour necrosis factor-α (TNFα) and interleukin-6 (IL-6) generation from macrophages were evaluated. The effects of EP2-selective (PF-04852946, PF-04418948) and EP4-selective (L-161,982, CJ-042794) antagonists on PGE2 responses were studied. The expression of EP receptor subtypes by human lung macrophages was determined by RT-PCR. Key results: PGE2 inhibited LPS-induced and Streptococcus pneumoniae-induced cytokine generation from human lung macrophages. Analysis of mRNA levels indicated that macrophages expressed EP2 and EP4 receptors. L-902,688 (EP4-selective agonist) was considerably more potent than butaprost (EP2-selective agonist) as an inhibitor of TNFα generation from macrophages. EP2-selective antagonists had marginal effects on the PGE2 inhibition of TNFα generation whereas EP4-selective antagonists caused rightward shifts in the PGE2 concentration-response curves. Conclusions and implications: These studies demonstrate that the EP4 receptor is the principal receptor that mediates the anti-inflammatory effects of PGE2 on human lung macrophages. This suggests that EP4 agonists could be effective anti-inflammatory agents in human lung disease

Nutrient concentration relationships between the fourth petiole and upper-stem of potato plants

Successfully evaluating the nutritional status of a crop during growth and development is dependent upon sampling an identifiable plant part. Consistently sampling a petiole of the same maturity in potatoes (Solanum tuberosum L.) is difficult. We evaluated the nutrient relationships between the upper-stem and the fourth petiole from Russet Burbank plants in field studies having N, P, K, Zn or Mn variables. The upper-stem was obtained by excising the stem below the sixth leaf and removing all leaves and the terminal meristem. Petole NO3-N, P, K, Zn and Mn concentrations were from deficient to sufficient. The NO 3-N, P and K concentrations were similar in the fourth petiole and upper-stem, while the Zn concentration was 40% higher in the upper-stem. Calcium, Mg and Mn concentrations were lower in the upper-stem than in the fourth petiole. Copper and S relationships were not adequately defined. The fourth petiole's NO 3-N, P and K diagnostic concentrations now used to monitor plant nutrient status can also be used for upper-stem samples. Zinc diagnostic concentrations should be increased, while Ca, Mg and Mn concentrations should be adjusted downward in the upper-tem. Additional data are needed to refine the Ca and Mg relationships, and to establish relationships for Cu, S and other essential nutrients. A significant advantage of using the upper-stem is the elimination of the petiole selection problem when sampling

The "physical process" version of the first law and the generalized second law for charged and rotating black holes

We investigate both the ``physical process'' version of the first law and the second law of black hole thermodynamics for charged and rotating black holes. We begin by deriving general formulas for the first order variation in ADM mass and angular momentum for linear perturbations off a stationary, electrovac background in terms of the perturbed non-electromagnetic stress-energy, $\delta T_{ab}$, and the perturbed charge current density, $\delta j^a$. Using these formulas, we prove the "physical process version" of the first law for charged, stationary black holes. We then investigate the generalized second law of thermodynamics (GSL) for charged, stationary black holes for processes in which a box containing charged matter is lowered toward the black hole and then released (at which point the box and its contents fall into the black hole and/or thermalize with the ``thermal atmosphere'' surrounding the black hole). Assuming that the thermal atmosphere admits a local, thermodynamic description with respect to observers following orbits of the horizon Killing field, and assuming that the combined black hole/thermal atmosphere system is in a state of maximum entropy at fixed mass, angular momentum, and charge, we show that the total generalized entropy cannot decrease during the lowering process or in the ``release process''. Consequently, the GSL always holds in such processes. No entropy bounds on matter are assumed to hold in any of our arguments.Comment: 35 pages; 1 eps figur

Cost Containment Through Disability Prevention: Preliminary Results of a Health Promotion Workshop for People with Physical Disabilities

The Disability Prevention Project at the University of Montana and the University of Kansas has developed and evaluated an eight week workshop and self-help manual that targets the prevention and management of secondary conditions among adults with spinal cord injuries. The preliminary results of this intervention are very encouraging

Novel codon-optimized mini-intronic plasmid for efficient, inexpensive, and xeno-free induction of pluripotency

The development of human induced pluripotent stem cell (iPSC) technology has revolutionized the regenerative medicine field. This technology provides a powerful tool for disease modeling and drug screening approaches. To circumvent the risk of random integration into the host genome caused by retroviruses, non-integrating reprogramming methods have been developed. However, these techniques are relatively inefficient or expensive. The mini-intronic plasmid (MIP) is an alternative, robust transgene expression vector for reprogramming. Here we developed a single plasmid reprogramming system which carries codon-optimized (Co) sequences of the canonical reprogramming factors (Oct4, Klf4, Sox2, and c-Myc) and short hairpin RNA against p53 ("4-in-1 CoMiP"). We have derived human and mouse iPSC lines from fibroblasts by performing a single transfection. Either independently or together with an additional vector encoding for LIN28, NANOG, and GFP, we were also able to reprogram blood-derived peripheral blood mononuclear cells (PBMCs) into iPSCs. Taken together, the CoMiP system offers a new highly efficient, integration-free, easy to use, and inexpensive methodology for reprogramming. Furthermore, the CoMIP construct is color-labeled, free of any antibiotic selection cassettes, and independent of the requirement for expression of the Epstein-Barr Virus nuclear antigen (EBNA), making it particularly beneficial for future applications in regenerative medicine

Regulated complex assembly safeguards the fidelity of Sleeping Beauty transposition

The functional relevance of the inverted repeat structure (IR/DR) in a subgroup of the Tc1/mariner superfamily of transposons has been enigmatic. In contrast to mariner transposition, where a topological filter suppresses single-ended reactions, the IR/DR orchestrates a regulatory mechanism to enforce synapsis of the transposon ends before cleavage by the transposase occurs. This ordered assembly process shepherds primary transposase binding to the inner 12DRs (where cleavage does not occur), followed by capture of the 12DR of the other transposon end. This extra layer of regulation suppresses aberrant, potentially genotoxic recombination activities, and the mobilization of internally deleted copies in the IR/DR subgroup, including Sleeping Beauty (SB). In contrast, internally deleted sequences (MITEs) are preferred substrates of mariner transposition, and this process is associated with the emergence of Hsmar1-derived miRNA genes in the human genome. Translating IR/DR regulation to in vitro evolution yielded an SB transposon version with optimized substrate recognition (pT4). The ends of SB transposons excised by a K248A excision(+)/integration(-) transposase variant are processed by hairpin resolution, representing a link between phylogenetically, and mechanistically different recombination reactions, such as V(D)J recombination and transposition. Such variants generated by random mutation might stabilize transposon-host interactions or prepare the transposon for a horizontal transfer

Evaluation of Irradiated Mandibles Using Emission Tomography, Bone Scans, and Radiography

This study compared radiographs, bone scans, and computed emission tomograms with histologic findings in irradiated mandibles of adult Rhesus monkeys. Although osteocytes were lost in the path of the beam, many vessels were partially or totally occluded, the periosteum degenerated, the marrow became fibrotic, and cancellous bone proliferated abundantly, no changes were noted with radiography, conventional bone scanning, or computed emission tomograms. These clinical methods of examination may misrepresent the true condition of irradiated bone because of inadequate sensitivity or balance among factors that control radioactive tracer uptake in bone.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68112/2/10.1177_00220345800590120201.pd

Late coronary occlusion after intracoronary brachytherapy

BACKGROUND: Intracoronary brachytherapy appears to be a promising technology to prevent restenosis. Presently, limited data are available regarding the late safety of this therapeutic modality. The aim of the study was to determine the incidence of late (>1 month) thrombosis after PTCA and radiotherapy. METHODS AND RESULTS: From April 1997 to March 1999, we successfully treated 108 patients with PTCA followed by intracoronary beta-radiation. Ninety-one patients have completed at least 2 months of clinical follow-up. Of these patients, 6.6% (6 patients) presented with sudden thrombotic events confirmed by angiography 2 to 15 months after intervention (2 balloon angioplasty and 4 stent). Some factors (overlapping stents, unhealed dissection) may have triggered the thrombosis process, but the timing of the event is extremely unusual. Therefore, the effect of radiation on delaying the healing process and maintaining a thrombogenic coronary surface is proposed as the most plausible mechanism to explain such late events. CONCLUSIONS: Late and sudden thrombosis after PTCA followed by intracoronary radiotherapy is a new phenomenon in interventional cardiology