Enhanced Anandamide Plasma Levels in Patients with Complex Regional Pain Syndrome following Traumatic Injury: A Preliminary Report

The complex regional pain syndrome (CRPS) is a disabling neuropathic pain condition that may develop following injuries of the extremities. The pathogenesis of this syndrome is not clear; however, it includes complex interactions between the nervous and the immune system resulting in chronic inflammation, pain and trophic changes. This interaction may be mediated by chronic stress which is thought to activate the endogenous cannabinoid (endocannabinoid) system (ECS). We conducted an open, prospective, comparative clinical study to determine plasma level of the endocannabinoid anandamide by high-performance liquid chromatography and a tandem mass spectrometry system in 10 patients with CRPS type I versus 10 age- and sex-matched healthy controls. As compared to healthy controls, CRPS patients showed significantly higher plasma concentrations of anandamide. These results indicate that the peripheral ECS is activated in CRPS. Further studies are warranted to evaluate the role of the ECS in the limitation of inflammation and pain. Copyright (C) 2009 S. Karger AG, Base

Climate change impacts in agricultural communities in rural areas of coastal bangladesh: A tale of many stories

This paper identifies and analyses climate change impacts, their cascading consequences and the livelihood implications of these impacts on smallholder agricultural communities of coastal Bangladesh. Six physically and socio-economically vulnerable communities of south-western coastal regions were studied. Primary data was collected through focus group discussions, a seasonal calendar, and historical transect analysis. Three orders of impacts of climate change on smallholder farmers are identified and described. The first order impacts involve increasing erosion of the capacity of local communities to mitigate vulnerability to climate change impacts. This situation led to the second order impacts, which significantly transformed the agricultural landscape and production patterns. The cumulative effects of the first and second order impacts sparked the third order impacts in the form of worsening community livelihood assets and conditions. The findings of this paper can contribute to the formulation of sustainable adaptation policies and programs to manage the vulnerability of local communities to climate change impacts in the country effectively

Noncommutative Inspired Black Holes in Extra Dimensions

In a recent string theory motivated paper, Nicolini, Smailagic and Spallucci (NSS) presented an interesting model for a noncommutative inspired, Schwarzschild-like black hole solution in 4-dimensions. The essential effect of having noncommutative co-ordinates in this approach is to smear out matter distributions on a scale associated with the turn-on of noncommutativity which was taken to be near the 4-d Planck mass. In particular, NSS took this smearing to be essentially Gaussian. This energy scale is sufficiently large that in 4-d such effects may remain invisible indefinitely. Extra dimensional models which attempt to address the gauge hierarchy problem, however, allow for the possibility that the effective fundamental scale may not be far from $\sim$ 1 TeV, an energy regime that will soon be probed by experiments at both the LHC and ILC. In this paper we generalize the NSS model to the case where flat, toroidally compactified extra dimensions are accessible at the Terascale and examine the resulting modifications in black hole properties due to the existence of noncommutativity. We show that while many of the noncommutativity-induced black hole features found in 4-d by NSS persist, in some cases there can be significant modifications due the presence of extra dimensions. We also demonstrate that the essential features of this approach are not particularly sensitive to the Gaussian nature of the smearing employed by NSS.Comment: 30 pages, 12 figures; slight text modifications and references adde

Troubles musculo-squelettiques : rôles des médecins-conseils et relations interprofessionnelles

INTRODUCTION: Musculoskeletal disorders (MSD) were responsible for 9.7 million days of sick leave in 2010 in France. They are also a leading cause of occupational exclusion. The objective was to study the role of medical advisers (Mas) in the care of patients with MSD and their interactions with general practitioners (GPs) and occupational health physicians (OPs). METHODS: We performed a qualitative study with semi-structured interviews with medical advisers from the Brittany region. Semistructured interviews were double-coded and were submitted to thematic analysis. RESULTS: Nine interviews were conducted with MAs from the general regime, agricultural regime, and independent workers regime. MAs described an increase in MSD, especially with complex forms. They explained that their activity was not limited to control, but that they also had an important role in limiting occupational exclusion. It is important to anticipate difficulties related to return to work in this setting. They reported contrasted but necessary relations with GPs who are at the centre of care. Return to work may require negotiation with OPs. CONCLUSION: Relations between MAs and GPs are partly based on control of prescriptions, which can create a climate of suspicion. Emphasizing the fight against occupational exclusion can provide new light on the role of MAs. Improving relations between MAs and GPs can be achieved by a better understanding of their respective roles

Towards an orientation of higher education in the post Rio+20 process: How is the game changing?

The purpose of this paper is to identify and assess the implications of sustainable development for the future orientation of higher education, especially after the 2012 United Nations Conference on Sustainable Development (Rio + 20). A qualitative trend analysis is being used for this purpose, in the context of which three macro trends are combined: (1) higher education that has been developed via five periods; (2) sustainable development that has evolved through three stages; and (3) the nexus between sustainable development and higher education which has strengthened through three phases. The simultaneous analysis of the macro trends regarding their possible interactive effects (through an expert panel discussion) demonstrates that higher education and universities under the influence of sustainable development elements are entering into a new era in which the function of “higher education for sustainable development” could be interpreted as the seeds of a newly emerging mission for universities. In this regard, it is expected that the concept of “sustainable university” is likely to become more common to meet the emerging mission. Consistent with the Rio + 20 outcomes, the authors analyzed the concept of “sustainable university” and identified the fact that it is practically divided into three interrelated and complementary categories, namely social-, environmental-, and economic-oriented university in pursuit of actualizing sustainable development

Lymphocyte subsets and the role of Th1/Th2 balance in stressed chronic pain patients

Background: The complex regional pain syndrome (CRPS) and fibromyalgia (FM) are chronic pain syndromes occurring in highly stressed individuals. Despite the known connection between the nervous system and immune cells, information on distribution of lymphocyte subsets under stress and pain conditions is limited. Methods: We performed a comparative study in 15 patients with CRPS type I, 22 patients with FM and 37 age- and sex-matched healthy controls and investigated the influence of pain and stress on lymphocyte number, subpopulations and the Th1/Th2 cytokine ratio in T lymphocytes. Results: Lymphocyte numbers did not differ between groups. Quantitative analyses of lymphocyte subpopulations showed a significant reduction of cytotoxic CD8+ lymphocytes in both CRPS (p < 0.01) and FM (p < 0.05) patients as compared with healthy controls. Additionally, CRPS patients were characterized by a lower percentage of IL-2-producing T cell subpopulations reflecting a diminished Th1 response in contrast to no changes in the Th2 cytokine profile. Conclusions: Future studies are warranted to answer whether such immunological changes play a pathogenetic role in CRPS and FM or merely reflect the consequences of a pain-induced neurohumoral stress response, and whether they contribute to immunosuppression in stressed chronic pain patients. Copyright (c) 2008 S. Karger AG, Basel

Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice.

BackgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.MethodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2, Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4-/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used.ResultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.ConclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice

Multi-center dosimetric predictions to improve plan quality for brachytherapy for cervical cancer treatment

BACKGROUND AND PURPOSE: Image-guided adaptive brachytherapy (IGABT) is an important modality in the cervical cancer treatment, and plan quality is sensitive to time pressure in the workflow. Patient anatomy-based quality-assurance (QA) with overlap volume histograms (OVHs) has been demonstrated to detect suboptimal plans (outliers). This analysis quantifies the possible improvement of plans detected as outliers, and investigates its suitability as a clinical QA tool in a multi-center setting. MATERIALS AND METHODS: In previous work OVH-based models were investigated for the use of QA. In this work a total of 160 plans of 68 patients treated in accordance with the current state-of-the-art IGABT protocol from Erasmus MC (EMC) were analyzed, with a model based on 120 plans (60 patients) from UMC Utrecht (UMCU). Machine-learning models were trained to define QA thresholds, and to predict dose D2cm3 to bladder, rectum, sigmoid and small bowel with the help of OVHs of the EMC cohort. Plans out of set thresholds (outliers) were investigated and retrospectively replanned based on predicted D2cm3 values. RESULTS: Analysis of replanned plans demonstrated a median improvement of 0.62 Gy for all Organs At Risk (OARs) combined and an improvement for 96 % of all replanned plans. Outlier status was resolved for 36 % of the replanned plans. The majority of the plans that could not be replanned were reported having implantation complications or insufficient coverage due to tumor geometry. CONCLUSION: OVH-based QA models can detect suboptimal plans, including both unproblematic BT applications and suboptimal planning circumstances in general. OVH-based QA models demonstrate potential for clinical use in terms of performance and user-friendliness, and could be used for knowledge transfer between institutes. Further research is necessary to differentiate between (sub)optimal planning circumstances

Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry

<p>Abstract</p> <p>Background</p> <p>Recent genome-wide association studies have identified several genetic loci linked to coronary artery disease (CAD) and myocardial infarction (MI). The 9p21.3 locus was verified by numerous replication studies to be the first common locus for CAD and MI. In the present study, we investigated whether six single nucleotide polymorphisms (SNP) rs1333049, rs1333040, rs10757274, rs2383206, rs10757278, and rs2383207 representing the 9p21.3 locus were associated with the incidence of an acute MI in patients with the main focus on the familial aggregation of the disease.</p> <p>Methods</p> <p>The overall cohort consisted of 976 unrelated male patients presenting with an acute coronary syndrome (ACS) with ST-elevated (STEMI) as well as non-ST-elevated myocardial infarction (NSTEMI). Genotyping data of the investigated SNPs were generated and statistically analyzed in comparison to previously published findings of matchable control cohorts.</p> <p>Results</p> <p>Statistical evaluation confirmed a highly significant association of all analyzed SNP's with the occurrence of MI (p < 0.0001; OR: 1.621-2.039). When only MI patients with a positive family disposition were comprised in the analysis a much stronger association of the accordant risk alleles with incident disease was found with odds ratios up to 2.769.</p> <p>Conclusions</p> <p>The findings in the present study confirmed a strong association of the 9p21.3 locus with MI particularly in patients with a positive family history thereby, emphasizing the pathogenic relevance of this locus as a common genetic cardiovascular risk factor.</p

Transient Receptor Potential Channel Polymorphisms Are Associated with the Somatosensory Function in Neuropathic Pain Patients

Transient receptor potential channels are important mediators of thermal and mechanical stimuli and play an important role in neuropathic pain. The contribution of hereditary variants in the genes of transient receptor potential channels to neuropathic pain is unknown. We investigated the frequency of transient receptor potential ankyrin 1, transient receptor potential melastin 8 and transient receptor potential vanilloid 1 single nucleotide polymorphisms and their impact on somatosensory abnormalities in neuropathic pain patients. Within the German Research Network on Neuropathic Pain (Deutscher Forscbungsverbund Neuropathischer Schmerz) 371 neuropathic pain patients were phenotypically characterized using standardized quantitative sensory testing. Pyrosequencing was employed to determine a total of eleven single nucleotide polymorphisms in transient receptor potential channel genes of the neuropathic pain patients and a cohort of 253 German healthy volunteers. Associations of quantitative sensory testing parameters and single nucleotide polymorphisms between and within groups and subgroups, based on sensory phenotypes, were analyzed. Single nucleotide polymorphisms frequencies did not differ between both the cohorts. However, in neuropathic pain patients transient receptor potential ankyrin 1 710G>A (rs920829, E179K) was associated with the presence of paradoxical heat sensation (p = 0.03), and transient receptor potential vanilloid 1 1911A>G (rs8065080, I585V) with cold hypoalgesia (p = 0.0035). Two main subgroups characterized by preserved (1) and impaired (2) sensory function were identified. In subgroup 1 transient receptor potential vanilloid 1 1911A>G led to significantly less heat hyperalgesia, pinprick hyperalgesia and mechanical hypaesthesia (p = 0.006, p = 0.005 and p<0.001) and transient receptor potential vanilloid 1 1103C>G (rs222747, M315I) to cold hypaesthesia (p = 0.002), but there was absence of associations in subgroup 2. In this study we found no evidence that genetic variants of transient receptor potential channels are involved in the expression of neuropathic pain, but transient receptor potential channel polymorphisms contributed significantly to the somatosensory abnormalities of neuropathic pain patients