COX-2 expression mediated by calcium-TonEBP signaling axis under hyperosmotic conditions serves osmoprotective function in nucleus pulposus cells.

The nucleus pulposus (NP) of intervertebral discs experiences dynamic changes in tissue osmolarity because of diurnal loading of the spine. TonEBP/NFAT5 is a transcription factor that is critical in osmoregulation as well as survival of NP cells in the hyperosmotic milieu. The goal of this study was to investigate whether cyclooxygenase-2 (COX-2) expression is osmoresponsive and dependent on TonEBP, and whether it serves an osmoprotective role. NP cells up-regulated COX-2 expression in hyperosmotic media. The induction of COX-2 depended on elevation of intracellular calcium levels and p38 MAPK pathway, but independent of calcineurin signaling as well as MEK/ERK and JNK pathways. Under hyperosmotic conditions, both COX-2 mRNA stability and its proximal promoter activity were increased. The proximal COX-2 promoter (-1840/+123 bp) contained predicted binding sites for TonEBP, AP-1, NF-κB, and C/EBP-β. While COX-2 promoter activity was positively regulated by both AP-1 and NF-κB, AP-1 had no effect and NF-κB negatively regulated COX-2 protein levels under hyperosmotic conditions. On the other hand, TonEBP was necessary for both COX-2 promoter activity and protein up-regulation in response to hyperosmotic stimuli

METABOLIC EFFECTS OF SULFONYLUREAS IN NORMAL MEN and IN VARIOUS TYPES OF DIABETIC PATIENTS

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73037/1/j.1749-6632.1957.tb54592.x.pd

State-of-the-art in product service-systems

A Product Service-System (PSS) is an integrated combination of products and services. This western concept embraces a service-led competitive strategy, environmental sustainability, and the basis to differentiate from competitors who simply offer lower priced products. This paper aims to report the state-of-the-art of PSS research by presenting a clinical review of literature currently available on this topic. The literature is classified and the major outcomes of each study are addressed and analysed. On this basis, this paper defines the PSS concept, reports on its origin and features, gives examples of applications along with potential benefits and barriers to adoption, summarises available tools and methodologies, and identifies future research challenges

"Oh! What a tangled web we weave": Englishness, communicative leisure, identity work and the cultural web of the English folk morris dance scene

In this paper, we consider the relationship between Englishness and the English folk morris dance scene, considering how the latter draws from and reinforces the former. Englishness is considered within the context of the cultural web; a tool more often applied to business management but linked to a sociological viewpoint here. By doing so, we draw the connections between this structured business model and the cultural identity of Englishness. Then, we use the framework of the cultural web and theories of leisure, culture and identity to understand how morris dancers see their role as dancers and ‘communicative leisure’ agents in consciously defending Englishness, English traditions and inventions, the practices and traditions of folk and morris, and the various symbolic communities they inhabit. We argue that most morris dancers in our research become and maintain their leisured identities as dancers because they are attracted to the idea of tradition – even if that tradition is invented and open to change

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Low-temperature alteration and magnetic changes of variably altered pillow basalts

Pillow basalt fragments from the East Pacific Rise, dredged during the Phoenix expedition, often show discoloured rims due to alteration. A suite of nine pillow basalts with such discoloured rims and ranging in age between 200 and 820 ka has been characterized in terms of their Fe–Ti-oxide mineralogy and rock magnetic properties. These large pillow fragments show relatively unaltered grey interiors, surrounded by darker, concentric halos, which vary in thickness as measured from glassy pillow rims and surfaces caused by large cracks penetrating into the original pillow interior. The discoloured zones are characterized by precipitation of abundant secondary minerals, such as Fe 3+ -rich clays that filled vesicle spaces. Fe–Ti oxides in subsamples from discoloured rims and grey interiors have been investigated with electron microscopy and rock magnetic techniques. The subsamples come from traverses that are parallel to the outer glassy pillow rims, allowing us to study the low-temperature alteration effects and rock magnetic properties without having to take variable grain size into account. Not surprisingly, titanomaghemites in discoloured rims are, in a general sense, oxidized to a higher degree ( z typically >0.55) than those in the relatively unaltered grey interior ( z typically 0.6 within 200 000 yr. The difference between the oxidation states of titanomaghemite within the grey pillow interior and the discoloured rims gradually diminishes with increasing age, so that for samples with ages of 800 ka the oxidation state of titanomaghemites in the grey interior approaches that of the discoloured rim. Our study demonstrates that visible discolouration of pillow basalts is not a suitable proxy for z . Because average Ti content can vary from sample to sample, Curie temperatures are also inaccurate proxies for z . If one wants to study possible correlations between z and rock magnetic parameters, the best technique is to determine z for each subsample by using transmission electron microscopy (TEM), electron microprobe, MÖssbauer or similar techniques. In agreement with many (but not all) previous observations on natural samples, we find that bulk coercivity ( H c ) , and high-field susceptibility (Χ hf ) increase, whereas low-field susceptibility (Χ l f ) , natural remanent magnetization intensity and saturation magnetization ( M s ) generally decrease with increasing oxidation state.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73443/1/j.1365-246X.2005.02819.x.pd

Golimumab induction and maintenance for moderate to severe ulcerative colitis: results from GO-COLITIS (Golimumab: a Phase 4, UK, open label, single arm study on its utilization and impact in ulcerative Colitis)

Objective GO-COLITIS aimed to measure the effectiveness of subcutaneous golimumab in tumour necrosis factor-α antagonist–naive patients with moderate to severe ulcerative colitis (UC) despite conventional treatment. Design GO-COLITIS was an open label, single arm, phase 4 study with a pragmatic design which reflected UK clinical practice. Adult patients were eligible if diagnosed with UC ≥3 months, partial Mayo score (PMS) 4–9. Patients received subcutaneous golimumab induction (200 mg initially and 100 mg at week 2) followed at week 6 by 50 mg or 100 mg (depending on weight) every 4 weeks until week 54 with a 12-week follow-up. Efficacy was measured by PMS at baseline, week 6, 30, 54 and 66. Health-related quality of life (HRQoL; Inflammatory Bowel Disease Questionnaire (IBDQ) and EuroQol Group 5 Dimensions Health Questionnaire (EQ-5D)) was assessed at baseline, week 6 and week 54. All safety adverse events (AEs) were recorded. Results 207 patients were enrolled and 205 received golimumab (full analysis set (FAS)205). At week 6, 68.8% (95% CI 62.0% to 75.1%) and 38.5% (95% CI 31.8% to 45.6%) of patients were in response and remission, respectively, using PMS. At the end of the induction phase, 140/141 patients in clinical response continued into the maintenance phase (Maintenance FAS). Sustained clinical response through week 54 was achieved in 51/205 (24.9%) of the FAS205 population and 51/140 (36.4%) of the Maintenance FAS population. Statistically significant improvements from baseline to week 6 were observed for the IBDQ total score and for each IBDQ domain score (bowel symptoms, emotional function, systemic symptoms and social function), as well as the EQ-5D index score and associated visual analogue scale score (p<0.0001). Improvement of HRQoL was sustained through week 54. Serious AEs leading to treatment discontinuation occurred in 8.8% of patients. Conclusion In this study measuring patient-reported outcomes in patients with moderate to severe UC, golimumab induced and maintained response as measured by PMS and significantly improved quality of life measures. Trial registration number NCT02092285; 2013-004583-56

The ∼270 Ma palaeolatitude of Baltica and its significance for Pangea models

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86901/1/j.1365-246X.2011.05061.x.pd

Evidence for Exotic J^{PC}=1^{-+} Meson Production in the Reaction pi- p --> eta pi- p at 18 GeV/c

Details of the analysis of the eta pi- system studied in the reaction pi^{-} p --> eta pi^{-} p at 18 GeV/c are given. Separate analyses for the 2 gamma and pi+ pi- pi0 decay modes of the eta are presented. An amplitude analysis of the data indicates the presence of interference between the a(2)(1320)- and a J^{PC}=1^{-+} wave between 1.2 and 1.6 GeV/c^2. The phase difference between these waves shows phase motion not attributable solely to the a(2)(1320)-. The data can be fitted by interference between the a(2)(1320)- and an exotic 1^{-+} resonance with M = 1370 +-16 +50 -30} MeV/c^2 and Gamma = 385 +- 40 +65 -105 MeV/c^2. Our results are compared with those of other experiments.Comment: 50 pages of text and 34 figure

Effect of duration of postherpetic neuralgia on efficacy analyses in a multicenter, randomized, controlled study of NGX-4010, an 8% capsaicin patch evaluated for the treatment of postherpetic neuralgia

<p>Abstract</p> <p>Background</p> <p>Postherpetic neuralgia (PHN) is a painful and difficult to treat complication of acute herpes zoster. Current treatment options provide only partial relief and are often limited by poor tolerability. We evaluated the safety and efficacy of a single 60-minute application of NGX-4010, an 8% capsaicin patch, in patients with PHN.</p> <p>Methods</p> <p>This multicenter, double-blind, controlled study randomized 155 patients 2:1 to receive either NGX-4010 or a 0.04% capsaicin control patch. Patients were at least 18 years old with PHN for at least 3 months, and an average Numeric Pain Rating Scale (NPRS) score of 3 to 9. The primary efficacy endpoint was the percentage change in NPRS score from baseline to weeks 2-8.</p> <p>Results</p> <p>The mean percent reduction in "average pain for the past 24 hours" NPRS scores from baseline to weeks 2-8 was greater in the NGX-4010 group (36.5%) compared with control (29.9%) although the difference was not significant (p = 0.296). PGIC analysis demonstrated that more NGX-4010 recipients considered themselves improved (much, or very much) compared with control at weeks 8 and 12, but the differences did not reach statistical significance. Post hoc analyses of patients with PHN for at least 6 months showed significantly greater reductions in "average pain for the past 24 hours" NPRS scores from baseline to weeks 2-8 in NGX-4010 patients compared to controls (37.6% versus 23.4%; p = 0.0291). PGIC analysis in this subgroup demonstrated that significantly more NGX-4010 recipients considered themselves much or very much improved compared with control at week 12 (40% versus 20%; p = 0.0403;).</p> <p>Conclusions</p> <p>Although treatment appeared to be safe and well tolerated, a single 60-minute application of NGX-4010 failed to show efficacy in this study which included patients with PHN for less than 6 months. Large reductions in pain observed among control patients with pain for less than 6 months may have been due to spontaneous resolution of PHN, may have confounded the results of the prespecified analyses, and should be taken into account when designing PHN studies.</p> <p>Trial Registration</p> <p>NCT00068081</p