Chronic pain clinics aim to improve challenging conditions, and although numerous studies have evaluated specific aspects of therapies and outcomes in this context, data concerning service impact on ...outcome measures in a general pain population are sparse. In addition, current trends in commissioning increasingly warrant services to provide evidence for their effectiveness. While a plethora of outcome measures, such as pain-intensity or improvement scores, exist for this purpose, it remains surprisingly unclear which one to use. It also remains uncertain what variables predict treatment success.
This cross-sectional study was conducted to evaluate clinic performance employing different tools (pain scores, pain categories, responder analysis, subjective improvement, satisfaction), and to determine predictors of outcome measures.
Patients attending scheduled clinic follow-up appointments were approached. They were asked to complete the modified short-form Brief Pain Inventory (BPI-SF) that also included assessments for satisfaction and subjective improvement. Comparisons were made with BPI-SF responses that were completed by each patient on admission. Nonparametric tests were employed to evaluate service impact and to determine predictors for outcome.
Data of 118 patients were analyzed. There was considerable variation in impact of pain clinics depending on the outcome measure employed. While median pain scores did not differ between admission and follow-up, scores improved individually in 30% of cases, such that more patients had mild pain on follow-up than on admission (relative risk 2.7). Furthermore, while only 41% reported at least moderate subjective improvement after admission to the service, the majority (83%) were satisfied with the service. Positive treatment responses were predicted by "number of painful regions" and "changes in mood", whereas subjective improvement was predicted by "helpfulness of treatments".
Depending on the outcome measure employed, pain clinics showed varying degrees of impact on patients' pain experiences. This calls into question the current practice of using nonstandardized outcome reporting for evaluation of service performances.
Gene expression patterns can provide vital clues to the pathogenesis of neoplastic diseases. We investigated the expression of 950 genes in Hodgkin's disease (HD) by analyzing differential mRNA ...expression using microarrays. In two independent microarray experiments, the HD-derived cell lines L428 and KMH2 were compared with an Epstein-Barr virus (EBV)-immortalized lymphoblastoid B cell line, LCL-GK. Interleukin (IL)-13 and IL-5 were found to be highly expressed in the HD-derived cell lines. Examination of IL-13 and IL-5 expression by Northern blot analysis and enzyme-linked immunosorbent assay confirmed these results and revealed the expression of IL-13 in a third HD-derived cell line, HDLM2. Control LCL and EBV-negative non-Hodgkin lymphoma-derived cell lines did not express IL-13. In situ hybridization of lymph node tissue from HD patients showed that elevated levels of IL-13 were specifically expressed by Hodgkin/Reed-Sternberg (H/RS) tumor cells. Treatment of a HD-derived cell line with a neutralizing antibody to IL-13 resulted in a dose-dependent inhibition of H/RS cell proliferation. These data suggest that H/RS cells produce IL-13 and that IL-13 plays an important role in the stimulation of H/RS cell growth, possibly by an autocrine mechanism. Modulation of the IL-13 signaling pathway may be a logical objective for future therapeutic strategies.
The performance of solar-thermal conversion systems can be improved by incorporation of nanocarbon-stabilized microencapsulated phase change materials (MPCMs). The geometry of MPCMs in the ...microcapsules plays an important role for improving their heating efficiency and reliability. Yet few efforts have been made to critically examine the formation mechanism of different geometries and their effect on MPCMs-shell interaction. Herein, through changing the cooling rate of original emulsions, we acquire MPCMs within the nanocarbon microcapsules with a hollow structure of MPCMs (h-MPCMs) or solid PCM core particles (s-MPCMs). X-ray photoelectron spectroscopy and atomic force microscopy reveals that the capsule shell of the h-MPCMs is enriched with nanocarbons and has a greater MPCMs-shell interaction compared to s-MPCMs. This results in the h-MPCMs being more stable and having greater heat diffusivity within and above the phase transition range than the s-MPCMs do. The geometry-dependent heating efficiency and system stability may have important and general implications for the fundamental understanding of microencapsulation and wider breadth of heating generating systems.
The immediate-early gene Nur77, which encodes an orphan nuclear receptor, is rapidly induced by various stress stimuli, including tumor necrosis factor (TNF). Nur77 has been implicated in mediating ...apoptosis, particularly in T cells and tumor cells. We report here that Nur77 can play a role in antagonizing apoptosis in TNF signaling. Nur77 expression is strongly induced by TNF. Interestingly, unlike most antiapoptotic molecules, this induced expression of Nur77 is largely independent of NF-κ B. Ectopic expression of Nur77 can protect wild-type, TRAF2-/-, and RelA-/-cells from apoptosis induced by TNF, whereas expression of a dominant-negative form of Nur77 (DN-Nur77) accelerates TNF-mediated cell death in the mutant cells. In mouse embryonic fibroblasts, Nur77 remains in the nucleus in response to TNF and is not translocated to the mitochondria, where it was reported to mediate apoptosis. Our results suggest that Nur77 is a survival effector protein in the context of TNF-mediated signaling.
We used DNA microarray screening to identify Ckap2 (cytoskeleton associated protein 2) as a novel p53 target gene in a mouse erythroleukemia cell line. DNA damage induces human and mouse CKAP2 ...expression in a p53-dependent manner and p53 activates the Ckap2 promoter. Overexpressed Ckap2 colocalizes with and stabilizes microtubules. In p53-null cells, overexpression of Ckap2 induces tetraploidy with aberrant centrosome numbers, suggesting disturbed mitosis and cytokinesis. In p53-competent cells, Ckap2 does not induce tetraploidy but activates p53-mediated cell cycle arrest and apoptosis. Our data suggest the existence of a functional positive feedback loop in which Ckap2 activates the G1 tetraploidy checkpoint and prevents aneuploidy.
Metal–organic frameworks (MOFs) are typically crystalline microporous materials with metal ions of usually one oxidation state (although mixed-valence MOFs have been reported) and one type of ...co-ordination structure. Here, a microporous mixed-valence Cu( i , ii )-MOF featuring a unique network of distinct Cu( i ) and Cu( ii ) coordination sites is prepared by solvothermal reduction of HKUST-1. Like HKUST-1, this compound is assembled solely from Cu ions and benzene 1,3,5-tricarboxylate (BTC) ligands. The new MOF exhibits dual micropore size distribution and shows superior water stability compared to HKUST-1.
Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates interferon-induced genes and type I interferons. Recently, studies of IRF-l-deficient mice have revealed that IRF-I ...regulates the induction of molecules that play important roles in inflammation, such as inducible nitric oxide synthase (iNOS) and interleukin-l beta-converting enzyme (ICE). To study the role of IRF-1 in autoimmunity, we investigated type II collagen-induced arthritis (CIA), and experimental allergic encephalomyelitis (EAE), in mice lacking IRF-1. The incidence and severity of CIA were significantly decreased in IRF-1-/- mice compared with IRF-l +/- mice, as was the production of interferon (IFN)-gamma in lymph node cells. Both IRF-l+/- and IRF-1-/- mice exhibited mild and transient disease after adoptive transfer of a type II collagen (CII)-specific T cell line together with sera from arthritic mice, but the IRF-1-/- mice were less severely affected than the IRF-1+/- mice. In addition, the incidence of EAE in IRF-1-/- mice was decreased as compared with IRF-1 +/- mice. Reverse transcription polymerase chain reaction showed that IRF-1 mRNA was constitutively expressed in the spinal cords of IRF-1+/- mice, and was upregulated in mice with clinical EAE. Expression of iNOS was also detected in inflamed spinal cords. These results suggest that IRF-I plays a key role in promoting inflammation and autoimmunity in CIA and EAE animal models.
CD28 provides a critical costimulatory signal in Ag-specific T cell activation. Recent studies have revealed an important role for CD28 in the development of autoimmune diseases. We have examined the ...role of CD28 in collagen-induced arthritis (CIA) by inducing CIA in CD28-deficient DBA/1 mice. CD28-deficient mice never developed arthritis and showed markedly decreased levels of IgG and IgM anti-type II collagen (CII) Abs. In addition, the CD28+/- mice had similar levels of IgG1 and IgG2a anti-CII Abs, whereas in the CD28-deficient mice the level of IgG1 anti-CII Abs was decreased compared with that of IgG2a. IFN-gamma production by lymph node cells in response to CII was also reduced. CD28-deficient mice were either immunized four times with CII in CFA to augment Ag loading or given low doses of IL-12 to enhance Thl type responses. Both treatments resulted in a very low incidence of CIA development and minimal disease. CD28-deficient mice developed arthritis from injection of lymph node cells from CII-immunized wild-type mice, followed by immunization with CII in CFA. Taken together, these results indicate that costimulation of CD28 cannot be replaced by repeated activation through TCR or other costimulatory molecules. Thus, CD28 plays a critical role in both cellular and humoral immunity against CII and is indispensable for the development of CIA.
This thesis describes the synthesis and supramolecular structural directing methods of a perylene diimide derivative (PDI) for applications in aqueous metal-ion sensing and as a precursor for carbon ...nanofibres as electrode materials for supercapacitors. Perylene diimide derivatives are receiving increasing attraction due to their thermal stability and chemical inertness as well as their interesting electronic properties. Initially used as industrial grade pigments, more recent applications make use of its n-type semiconductivity which rises due to the high electron affinity of perylene dyes.In order to exploit their interesting potential applications, the initial insolubility of perylene-based molecules requires modification through substitution with primary amines (N-substitution). The soluble PDI was investigated for its susceptibility to pH-triggered self-assembly into fibres as well as fibre production through electrospinning using polyethylene glycol as a carrier polymer. Collected fibres could be carbonized at 800°C yielding carbon nanofibres (CNFs).PDI which could be dissolved in alkali aqueous conditions was sensitive to the presence of metal ions through UV-Vis absorbtion techniques. Dilute solutions of metal salts were added in microlitre-scale increments to cuvettes filled with PDI solution to record the UVVis response. PDI solutions provided a turn-off fluorescent sensor which was sensitive to the presence of metal cations within solution at low concentrations (2.5 nM) for iron (III) and copper (II) solutions. Further investigation is required into the effect of counter-ions.CNFs produced from ordered PDI molecules were assembled as an electrode for cyclic voltammetry capacitance testing. Using polyvinylidene fluoride (PVDF) as a binder in N-methyl pyrrolidone (NMP), CNFs were adhered to a carbon electrode surface and cycled in an acid, alkali, and neutral electrolyte. Brunauer Emmett Teller analysis showed microporous materials with surface areas ~300m2.g-1 and Raman spectroscopy was employed using ID/IG ratios as a measure of degree of graphetisation. Supramolecular CNFs demonstrated capacitances up to 247 F.g-1 (1 mV.s-1) while CNFs produced through electrospinning gave capacitances up to 427 F.g-1 (1 mV.s-1). Both materials demonstrated pseudocapacitive behaviour rather than that of pure electrochemical double-layer.
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