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Nonsteroidal anti-inflammatory drugs produce their analgesic and adverse effects through interaction with cyclooxygenase in a variety of tissues. The authors evaluated the therapeutic potential of administering a sustained-release formulation of flurbiprofen into a surgical wound following oral surgery to produce analgesia at the site of injury while minimizing exposure to potential targets for toxicity. Subjects (N = 98) received 1 of 8 treatments: flurbiprofen in a microparticle formulation in doses of 3.125 mg, 6.25 mg, 12.5 mg, 25 mg, or 50 mg; PO flurbiprofen 25 mg or 50 mg; or placebo. The flurbiprofen microparticle formulation or matching placebo was placed into the extraction sites at the end of surgery (removal of 2 lower impacted third molars). The sum of the pain visual analog scale over the 6-hour observation period demonstrated significantly less pain (P < .05) for flurbiprofen microparticle in comparison with placebo. Fewer subjects remedicated in the flurbiprofen microparticle drug groups, primarily for the 12.5-mg and higher doses. The incidence of adverse effects and local complications did not differ across groups. These data suggest that direct administration of flurbiprofen in a microparticle formulation at a site of tissue injury delays the onset and lowers the intensity of postoperative pain at lower doses than usually administered orally. [ABSTRACT FROM AUTHOR]

Contrast-enhanced intra-vascular ultrasound (CE-IVUS) imaging could provide clinicians a valuable tool to assess cardiovascular risk and guide the choice of therapeutic strategies. In this technical note, we evaluated the feasibility of combining subharmonic and ultraharmonic imaging to improve the performance of CE-IVUS. Vessel phantoms perfused with phospholipid-shelled ultrasound contrast agents were visualized using subharmonic, ultraharmonic and combined CE-IVUS modes with commercial peripheral and coronary imaging catheters. Flow channels as small as 0.8 mm and 0.5 mm were imaged at 12-MHz and 30-MHz transmit frequencies, respectively. Subharmonic and ultraharmonic imaging modes achieved a contrast-to-tissue ratio (CTR) up to 18.1 ± 1.8 dB and 19.6 ± 1.9 dB at 12-MHz, and 8.8 ± 1.8 and 12.5 ± 1.1 dB at 30-MHz transmit frequencies, respectively. Combining these modes improved the CTR to 32.5 ± 3.0 dB and 25.0 ± 1.6 dB at 12-MHz and 30-MHz transmit frequencies. These results underscore the potential of combined-mode CE-IVUS imaging. Furthermore, the demonstration of this approach with commercial catheters may serve as a first step toward the clinical translation of CE-IVUS., (Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Within agricultural watersheds suspended sediment-discharge hysteresis during storm events is commonly used to indicate dominant sediment sources and pathways. However, availability of high-resolution data, qualitative metrics, longevity of records, and simultaneous multiwatershed analyses has limited the efficacy of hysteresis as a sediment management tool. This two year study utilizes a quantitative hysteresis index from high-resolution suspended sediment and discharge data to assess fluctuations in sediment source location, delivery mechanisms and export efficiency in three intensively farmed watersheds during events over time. Flow-weighted event sediment export was further considered using multivariate techniques to delineate rainfall, stream hydrology, and antecedent moisture controls on sediment origins. Watersheds with low permeability (moderately- or poorly drained soils) with good surface hydrological connectivity, therefore, had contrasting hysteresis due to source location (hillslope versus channel bank). The well-drained watershed with reduced connectivity exported less sediment but, when watershed connectivity was established, the largest event sediment load of all watersheds occurred. Event sediment export was elevated in arable watersheds when low groundcover was coupled with high connectivity, whereas in the grassland watershed, export was attributed to wetter weather only. Hysteresis analysis successfully indicated contrasting seasonality, connectivity and source availability and is a useful tool to identify watershed specific sediment management practices.

Over 50% of the world's population live within 3 km of rivers and lakes highlighting the on-going importance of freshwater resources to human health and societal well-being. Whilst covering c. 3.5% of the Earth's non-glaciated land mass, trends in the environmental quality of the world's standing waters (natural lakes and reservoirs) are poorly understood, at least in comparison with rivers, and so evaluation of their current condition and sensitivity to change are global priorities. Here it is argued that a geospatial approach harnessing existing global datasets, along with new generation remote sensing products, offers the basis to characterise trajectories of change in lake properties e.g., water quality, physical structure, hydrological regime and ecological behaviour. This approach furthermore provides the evidence base to understand the relative importance of climatic forcing and/or changing catchment processes, e.g. land cover and soil moisture data, which coupled with climate data provide the basis to model regional water balance and runoff estimates over time. Using examples derived primarily from the Danube Basin but also other parts of the World, we demonstrate the power of the approach and its utility to assess the sensitivity of lake systems to environmental change, and hence better manage these key resources in the future., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Climate change is a significant global health threat requiring concerted action to reduce greenhouse gas emissions. This study provides the first systematic attempt to quantify the carbon emissions of a national dental service., Methods: Carbon accounting combined a top-down approach using input-output analysis for indirect emissions (procurement) and a process analysis (bottom-up) approach for direct emissions (building energy, travel, waste and water). Energy and water consumption were based on meter readings, waste-related emissions from collection contracts and travel from staff and patient questionnaires. Dental companies were approached for carbon footprint data on their products., Results: The carbon footprint for the service was 1798.9 tonnes CO(2)eq per annum. Travel was the greatest source (45.1%) followed by procurement (35.9%) and building energy (18.3%). Perhaps counter-intuitively older clinics had lower footprints than newer clinics as they are less energy intensive. Extrapolating the data suggests that Scotland's NHS dental service annually generates 0.16 mega tonne (Mt)CO(2)eq (4%) of the total Scottish NHS carbon footprint., Conclusions: The lack of comprehensive data reduces the ability to effectively manage emissions. Consideration needs to be given to the impact of patient travel, staff travel and new clinic construction on the carbon footprint. Medical suppliers are encouraged to provide life cycle analysis (LCA) for dental products., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

Background: The role that nitric oxide (NO) plays in modulating pain in the periphery is unclear. We show here, the results of two independent clinical studies (microdialysis and gene expression studies) and a pilot dose finding study (glyceryl trinitrate study), to study the role of NO in the early phase of acute inflammatory pain following oral surgery. The effect of ketorolac on NO production and nitric oxide synthase (NOS) gene expression was also studied., Results: Microdialysis samples showed significantly higher levels of NO at the first 100 min compared to the last 80 minutes in the placebo treated group. In the ketorolac group, on the other hand, NO levels gradually decreased over the first 60 min but were similar to placebo over the later 100-180 min, with no significant change in NO level over time. The levels of NO were negatively correlated to pain intensity scores. Local infusion of the NO donor glyceryl trinitrate at the site of surgery, showed a small analgesic effect that did not reach statistical significance in the sample size used. While the gene expression of iNOS and eNOS were not up-regulated, 3 hours after surgery, nNOS was downregulated in both treatment groups and eNOS gene expression was significantly lower in the ketorolac group compared to the placebo group. Further, there was a positive correlation between the change in gene expression of nNOS and eNOS in the placebo group but not in the ketorolac group., Conclusion: We suggest that at this early stage of inflammatory pain in man, NO is analgesic in the periphery. Further, ketorolac down-regulates eNOS gene expression.

Background: Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B1 and B2 receptors. It is generally accepted that the B2 receptor is constitutively expressed, whereas the B1 receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels., Results: Tissue injury resulted in a significant up-regulation in the gene expression of B1 and B2 receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B1 and B2 receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B1 and B2 receptors were correlated. Following tissue injury, B1 ligands des-Arg9-BK and des-Arg10-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B1 receptor but not B2 receptor., Conclusions: These results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the early phase of inflammation and inflammatory pain. The up-regulation of B1 receptors may contribute to acute inflammatory pain through TRPV1 activation.

This article critically reviews environmental assessment (EA) practices in Sri Lanka, with a particular focus on ecology. An overview is provided of the domestic and international influences which have shaped the administrative process which is currently a two-tiered scheme. An Initial Environmental Examination (IEE) provides a preliminary screening tool, prior to the requirement for a full Environmental Impact Assessment (EIA). A comprehensive survey of Sri Lankan national archives showed that 463 EAs were completed in the period 1981-2005, with the bulk of these in the more populated Western and North Western Provinces. Two-thirds were IEE surveys, while the remaining third advanced to full EIA. A representative sample of 130 EAs (both IEEs and full EIAs) spanning a broad range of project types, scales, and environmental settings was selected to evaluate the quality of the ecological investigations within the published environmental impact statements (EISs). These were assigned into five classes of "explanatory power", on the basis of their scientific content in relation to survey, analysis, and reporting of ecological interests. Within most EISs, the ecological impact assessment (EcIA) was restricted to the lowest two categories of ecological assessment, i.e., tokenistic presentation of reconnaissance-level species lists without further analysis of the development implications for individual organisms or communities. None of the assessments reviewed provided statistically rigorous analysis, which would be required if ecological impact studies are to include quantitative and testable predictions of impact, which could then be followed up by appropriate post-impact monitoring programs. Attention to key local issues such as biodiversity or ecosystem services, which also have strong social dimensions in the developing world, was also notably underrepresented. It was thus concluded that despite the existence of a sound legislative framework in Sri Lanka, the analysis contained within EISs generally fails to convey meaningful information to the relevant stakeholders and decision makers involved in protecting ecological interests and promoting sustainable development. The introduction of strategic environmental assessment (SEA) is considered an important tool to strengthen the institutional capacity of Sri Lankan government to implement current regulations and, in particular, to combat the cumulative effects of incremental development.

Background: In addition to blocking nociceptive input from surgical sites, long-acting local anesthetics might directly modulate inflammation. In the present study, we describe the proinflammatory effects of bupivacaine on local prostaglandin E2 (PGE2) production and cyclooxygenase (COX) gene expression that increases postoperative pain in human subjects., Methods: Subjects (n = 114) undergoing extraction of impacted third molars received either 2% lidocaine or 0.5% bupivacaine before surgery and either rofecoxib 50 mg or placebo orally 90 min before surgery and for the following 48 h. Oral mucosal biopsies were taken before surgery and 48 h after surgery. After extraction, a microdialysis probe was placed at the surgical site for PGE2 and thromboxane B2 (TXB2) measurements., Results: The bupivacaine/rofecoxib group reported significantly less pain, as assessed by a visual analog scale, compared with the other three treatment groups over the first 4 h. However, the bupivacaine/placebo group reported significantly more pain at 24 h and PGE2 levels during the first 4 h were significantly higher than the other three treatment groups. Moreover, bupivacaine significantly increased COX-2 gene expression at 48 h as compared with the lidocaine/placebo group. Thromboxane levels were not significantly affected by any of the treatments, indicating that the effects seen were attributable to inhibition of COX-2, but not COX-1., Conclusions: These results suggest that bupivacaine stimulates COX-2 gene expression after tissue injury, which is associated with higher PGE2 production and pain after the local anesthetic effect dissipates.

Mangrove ecosystems in Sri Lanka are increasingly under threat from development projects, especially aquaculture. An economic assessment is presented for a relatively large (42 ha) shrimp culture development proposed for the Rekawa Lagoon system in the south of Sri Lanka, which involved an extended cost-benefit analysis of the proposal and an estimate of the "total economic value" (TEV) of a mangrove ecosystem. The analysis revealed that the internal benefits of developing the shrimp farm are higher than the internal costs in the ratio of 1.5:1. However, when the wider environmental impacts are more comprehensively evaluated, the external benefits are much lower than the external costs in a ratio that ranges between 1:6 and 1:11. In areas like Rekawa, where agriculture and fisheries are widely practiced at subsistence levels, shrimp aquaculture developments have disproportionately large impacts on traditional livelihoods and social welfare. Thus, although the analysis retains considerable uncertainties, more explicit costing of the environmental services provided by mangrove ecosystems demonstrates that low intensity, but sustainable, harvesting has far greater long-term value to local stakeholders and the wider community than large shrimp aquaculture developments.

Unlabelled: This study evaluates the sensitivity of normal subjects (N = 617; 369 women, 248 men) to experimentally induced pain including thermal stimuli and the cold pressor test to delineate individual response patterns and pain phenotypes. A subset of subjects (n = 157; 99 women and 58 men) also underwent standardized oral surgery, and the responses to clinically induced acute inflammatory pain were evaluated. A wide range of pain responses was found in both the experimental and clinical situations. The latency for withdrawal in the cold pressor test exhibited a dichotomous distribution of short and long times. Women exhibited higher responses to cold (P < .001) and thermal stimuli (P < .05) than men. Ethnicity affected pain responses to thermal stimuli ranging from 43 degrees C to 47 degrees C (P < .05) and cold stimuli (P < .001). However, neither gender nor ethnicity affected pain responses to clinically induced acute inflammatory stimuli. Cross-modality comparisons of responses within experimental pain showed strong correlations (P < .01) but weaker relationships with clinical inflammatory pain. These data suggest that the background factors and characteristics of experimental pain responses differ from those of clinical pain; therefore, experimental pain ratings alone are not sufficient to predict responses to clinically induced acute pain., Perspective: The findings of the present study suggest that investigations of pain phenotypes should take into consideration the subjects' gender and ethnicity and the pain-inducing stimuli. The predictive value of experimental pain for clinically induced pain is weak and not reliable.

Objective: Prostanoids formed by cyclooxygenase play an important role in pain and the induction of inflammation. It is generally believed that COX-1 is constitutively expressed, whereas COX-2 is primarily inducible during inflammation. This study examined the in vivo selectivity of celecoxib, a COX-2 inhibitor, and evaluated whether estimates of selectivity that are based on in vitro and ex vivo analyses are reliable indicators of in vivo selectivity., Methods: Subjects (103 outpatients undergoing surgical removal of two impacted mandibular third molars) received either 200 mg celecoxib, 600 mg ibuprofen, or placebo 8 hours before surgery and a second dose 1 hour before surgery. After surgery, microdialysis probes were placed in the surgical sites for collection of inflammatory transudate. Samples were collected every 20 minutes and pain intensity was estimated concurrently with a visual analog scale and a categorical rating scale for up to 4 hours after surgery., Results: A significant analgesic effect (P <.01, compared with placebo) was shown for both drugs, with the efficacy of celecoxib being intermediate between ibuprofen and placebo. A similar relationship was observed for the suppression of prostaglandin E(2) (a product of both isoforms) at time points consistent with COX-2 expression (P <.001). Ibuprofen consistently suppressed thromboxane B(2) (a product of COX-1) levels at all time points (P <.05), whereas the effect of celecoxib did not differ from that of placebo., Conclusions: The suppression of products of COX-2 coincident with pain suppression and the absence of COX-1 inhibition suggest that celecoxib is a relatively selective COX-2 inhibitor in vivo.

We conducted a pilot study to evaluate the efficacy of topiramate in trigeminal neuralgia using a randomized, double-blind, placebo-controlled, two-period crossover design. Three patients were enrolled in and completed the study. All three patients responded to topiramate in this main study and entered a subsequent confirmatory study consisting of three topiramate-placebo crossovers. In the main study, topiramate reduced pain by 31%, 42%, and 64% in the three patients (p = 0.04). However, topiramate showed no effect in the confirmatory study. Given that trials of less common pain conditions are fraught with low patient recruitment rates, a multiple crossover design provides more information, which is important in conditions associated with considerable pain fluctuation. Larger trials are needed to more precisely estimate the effect of topiramate in trigeminal neuralgia.

The contribution of the sympathetic nervous system (SNS) to pain, mechanical allodynia (MA), and hyperalgesia in humans is controversial. A clearer understanding is crucial to guide therapeutic use of sympatholytic surgery, blocks, and drug treatments. In rats, capsaicin-evoked MA, and to some extent, pinprick hyperalgesia (PPH), can be blocked with alpha-adrenoreceptor antagonists. In this study, we examined the contribution of the SNS to MA and PPH in normal human subjects by blocking alpha-adrenoreceptors with intravenous phentolamine. In a double-blinded, placebo-controlled, crossover study, subjects were given IV saline or phentolamine, 1 mg/kg over 20 min. Ten minutes after the start of the infusion, subjects received 100 micrograms of intradermal capsaicin on the foot dorsum with the temperature of the injected site clamped at 36 degrees C. The temperature of the uninjected foot was used to monitor the degree of alpha-adrenoreceptor blockade produced by phentolamine. Ongoing pain and MA and PPH areas were measured every 5 min for 60 min. A significantly greater increase in temperature on the uninjected foot was seen during the phentolamine infusion compared with the saline infusion, indicating alpha-adrenergic blockade. Significantly less MA was observed with the phentolamine infusion 10-25 min after capsaicin injection than with the saline infusion. No significant differences in ongoing pain or PPH areas were seen between the two infusions at any time. Our results suggest that capsaicin-evoked MA and PPH have different mechanisms, with the SNS having a role in MA but not in PPH or ongoing pain.

Relatively little attention has been given to the long term prospect of fluvial transport processes redistributing Chernobyl-derived radiocaesium within the UK. Work undertaken within the Wye basin, central Wales, demonstrates a complex distribution of fallout at the catchment scale, with the bulk of the deposition concentrated in a narrow north-south band, situated in the west central areas of the basin, which contained in excess of 1500 Bq m(-2) of (134)Cs. Fluvial transport and redistribution of this material was demonstrated by river sampling during the winter of 1988/89, when the radiocaesium content of suspended sediment transported by the River Wye (approximately 30-50 mBq g(-1) of (137)Cs) remained 3-5 times higher than pre-Chernobyl levels. Floodplain reaches displayed variable levels of secondary contamination, dependent upon the upstream supply of radiocaesium and local morphological controls. Accordingly, the highest (134)Cs inventories within the basin (> 6000 Bq m(-2)) were associated with rapidly accreting floodplain sites. A number of these sites experienced only limited amounts of direct atmospheric fallout. The importance of fluvial redistribution as a secondary contamination mechanism is thus highlighted.