Chronic pain associated with the Chikungunya Fever: long lasting burden of an acute illness

<p>Abstract</p> <p>Background</p> <p>Chikungunya virus (CHIKV) is responsible for major epidemics worldwide. Autochthonous cases were recently reported in several European countries. Acute infection is thought to be monophasic. However reports on chronic pain related to CHIKV infection have been made. In particular, the fact that many of these patients do not respond well to usual analgesics suggests that the nature of chronic pain may be not only nociceptive but also neuropathic. Neuropathic pain syndromes require specific treatment and the identification of neuropathic characteristics (NC) in a pain syndrome is a major step towards pain control.</p> <p>Methods</p> <p>We carried out a cross-sectional study at the end of the major two-wave outbreak lasting 17 months in Réunion Island. We assessed pain in 106 patients seeking general practitioners with confirmed infection with the CHIK virus, and evaluated its impact on quality of life (QoL).</p> <p>Results</p> <p>The mean intensity of pain on the visual-analogical scale (VAS) was 5.8 ± 2.1, and its mean duration was 89 ± 2 days. Fifty-six patients fulfilled the definition of chronic pain. Pain had NC in 18.9% according to the DN4 questionnaire. Conversely, about two thirds (65%) of patients with NC had chronic pain. The average pain intensity was similar between patients with or without NC (6.0 ± 1.7 vs 6.1 ± 2.0). However, the total score of the Short Form-McGill Pain Questionnaire (SF-MPQ)(15.5 ± 5.2 vs 11.6 ± 5.2; p < 0.01) and both the affective (18.8 ± 6.2 vs 13.4 ± 6.7; p < 0.01) and sensory subscores (34.3 ± 10.7 vs 25.0 ± 9.9; p < 0.01) were significantly higher in patients with NC. The mean pain interference in life activities calculated from the Brief Pain Inventory (BPI) was significantly higher in patients with chronic pain than in patients without it (6.8 ± 1.9 vs 5.9 ± 1.9, p < 0.05). This score was also significantly higher in patients with NC than in those without such a feature (7.2 ± 1.5 vs 6.1 ± 1.9, p < 0.05).</p> <p>Conclusions</p> <p>There exists a specific chronic pain condition associated to CHIKV. Pain with NC seems to be associated with more aggressive clinical picture, more intense impact in QoL and more challenging pharmacological treatment.</p

Fluorine-induced improvement of structural and optical properties of CdTe thin films for solar cell efficiency enhancement

CdTe thin films of different thicknesses were electrodeposited and annealed in air after different chemical treatments to study the effects of thickness and the different chemical treatments on these films for photovoltaic applications. The thicknesses of the samples range from 1.1 μm to 2.1 μm and the annealing process was carried out after prior CdCl2 treatment and CdCl2+CdF2 treatment as well as without any chemical treatment. Detailed optical and structural characterisation of the as-deposited and annealed CdTe thin films using UV-Vis spectrophotometry and x-ray diffraction reveal that incorporating fluorine in the well-known CdCl2 treatment of CdTe produces remarkable improvement in the optical and structural properties of the materials. This CdCl2+CdF2 treatment produced solar cell with efficiency of 8.3% compared to CdCl2 treatment, with efficiency of 3.3%. The results reveal an alternative method of post-deposition chemical treatment of CdTe which can lead to the production of CdTe-based solar cells with enhanced photovoltaic conversion efficiencies compared to the use of only CdCl2. Keywords: CdTe; CdCl2

Set optimization - a rather short introduction

Recent developments in set optimization are surveyed and extended including various set relations as well as fundamental constructions of a convex analysis for set- and vector-valued functions, and duality for set optimization problems. Extensive sections with bibliographical comments summarize the state of the art. Applications to vector optimization and financial risk measures are discussed along with algorithmic approaches to set optimization problems

Distinct Roles for Dectin-1 and TLR4 in the Pathogenesis of Aspergillus fumigatus Keratitis

Aspergillus species are a major worldwide cause of corneal ulcers, resulting in visual impairment and blindness in immunocompetent individuals. To enhance our understanding of the pathogenesis of Aspergillus keratitis, we developed a murine model in which red fluorescent protein (RFP)-expressing A. fumigatus (Af293.1RFP) conidia are injected into the corneal stroma, and disease progression and fungal survival are tracked over time. Using Mafia mice in which c-fms expressing macrophages and dendritic cells can be induced to undergo apoptosis, we demonstrated that the presence of resident corneal macrophages is essential for production of IL-1β and CXCL1/KC, and for recruitment of neutrophils and mononuclear cells into the corneal stroma. We found that β-glucan was highly expressed on germinating conidia and hyphae in the cornea stroma, and that both Dectin-1 and phospho-Syk were up-regulated in infected corneas. Additionally, we show that infected Dectin-1−/− corneas have impaired IL-1β and CXCL1/KC production, resulting in diminished cellular infiltration and fungal clearance compared with control mice, especially during infection with clinical isolates expressing high β-glucan. In contrast to Dectin 1−/− mice, cellular infiltration into infected TLR2−/−, TLR4−/−, and MD-2−/− mice corneas was unimpaired, indicating no role for these receptors in cell recruitment; however, fungal killing was significantly reduced in TLR4−/− mice, but not TLR2−/− or MD-2−/− mice. We also found that TRIF−/− and TIRAP−/− mice exhibited no fungal-killing defects, but that MyD88−/− and IL-1R1−/− mice were unable to regulate fungal growth. In conclusion, these data are consistent with a model in which β-glucan on A.fumigatus germinating conidia activates Dectin-1 on corneal macrophages to produce IL-1β, and CXCL1, which together with IL-1R1/MyD88-dependent activation, results in recruitment of neutrophils to the corneal stroma and TLR4-dependent fungal killing

Distinct Roles for Dectin-1 and TLR4 in the Pathogenesis of Aspergillus fumigatus Keratitis

Aspergillus species are a major worldwide cause of corneal ulcers, resulting in visual impairment and blindness in immunocompetent individuals. To enhance our understanding of the pathogenesis of Aspergillus keratitis, we developed a murine model in which red fluorescent protein (RFP)-expressing A. fumigatus (Af293.1RFP) conidia are injected into the corneal stroma, and disease progression and fungal survival are tracked over time. Using Mafia mice in which c-fms expressing macrophages and dendritic cells can be induced to undergo apoptosis, we demonstrated that the presence of resident corneal macrophages is essential for production of IL-1β and CXCL1/KC, and for recruitment of neutrophils and mononuclear cells into the corneal stroma. We found that β-glucan was highly expressed on germinating conidia and hyphae in the cornea stroma, and that both Dectin-1 and phospho-Syk were up-regulated in infected corneas. Additionally, we show that infected Dectin-1−/− corneas have impaired IL-1β and CXCL1/KC production, resulting in diminished cellular infiltration and fungal clearance compared with control mice, especially during infection with clinical isolates expressing high β-glucan. In contrast to Dectin 1−/− mice, cellular infiltration into infected TLR2−/−, TLR4−/−, and MD-2−/− mice corneas was unimpaired, indicating no role for these receptors in cell recruitment; however, fungal killing was significantly reduced in TLR4−/− mice, but not TLR2−/− or MD-2−/− mice. We also found that TRIF−/− and TIRAP−/− mice exhibited no fungal-killing defects, but that MyD88−/− and IL-1R1−/− mice were unable to regulate fungal growth. In conclusion, these data are consistent with a model in which β-glucan on A.fumigatus germinating conidia activates Dectin-1 on corneal macrophages to produce IL-1β, and CXCL1, which together with IL-1R1/MyD88-dependent activation, results in recruitment of neutrophils to the corneal stroma and TLR4-dependent fungal killing

Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Development of this roadmap received support from Cancer Research UK and the Engineering and Physical Sciences Research Council (grant references A/15267, A/16463, A/16464, A/16465, A/16466 and A/18097), the EORTC Cancer Research Fund, and the Innovative Medicines Initiative Joint Undertaking (grant agreement number 115151), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution

Generalized Nash equilibrium problems, bilevel programming and mpec

The book discusses three classes of problems: the generalized Nash equilibrium problems, the bilevel problems and the mathematical programming with equilibrium constraints (MPEC). These problems interact through their mathematical analysis as well as their applications. The primary aim of the book is to present the modern tool of variational analysis and optimization, which are used to analyze these three classes of problems. All contributing authors are respected academicians, scientists and researchers from around the globe. These contributions are based on the lectures delivered by experts at CIMPA School, held at the University of Delhi, India, from 25 November–6 December 2013, and peer-reviewed by international experts. The book contains five chapters. Chapter 1 deals with nonsmooth, nonconvex bilevel optimization problems whose feasible set is described by using the graph of the solution set mapping of a parametric optimization problem. Chapter 2 describes a constraint qualification to MPECs considered as an application of calmness concept of multifunctions and is used to derive M-stationarity conditions for MPEC. Chapter 3 discusses the first- and second-order optimality conditions derived for a special case of a bilevel optimization problem in which the constraint set of the lower level problem is described as a general compact convex set. Chapter 4 concentrates the results of the modelization and analysis of deregulated electricity markets with a focus on auctions and mechanism design. Chapter 5 focuses on optimization approaches called reflection methods for protein conformation determination within the framework of matrix completion. The last chapter (Chap. 6) deals with the single-valuedness of quasimonotone maps by using the concept of single-directionality with a special focus on the case of the normal operator of lower semi-continuous quasiconvex functions

Comparison of Dexamethasone Implant and Anti-VEGF Agents in the Treatment of Naive Diabetic Macular Oedema: A Prospective Cohort Study

Introduction: Diabetic Retinopathy (DR) is one of the common microvascular complications of diabetes. In patients with DR, the most frequent cause of vision loss is Diabetic Macular oedema (DME). In the present era, anti-Vascular Endothelial Growth Factor (anti-VEGF) agents are the mainstay of treatment for managing DME. A majority of patients show a good response to multiple doses of these agents administered by a pro re nata regimen at regularly spaced fixed intervals. However, the tendency of DME to become chronic and resistant to these agents, as well as the burden of repeated injections, necessitates considering alternative treatment options with similar or better efficacy. As steroids can address these drawbacks of anti-VEGF treatment, the present study compared the efficacy of anti-VEGF agents with dexamethasone implant in the treatment of naïve DME. Aim: To compare the effectiveness of dexamethasone implant with anti-VEGF agents in the treatment of naïve DME. Materials and Methods: A prospective cohort study was conducted in the Department of Ophthalmology at Kalinga Institute of Medical Sciences and Pradyumna Bal Memorial Hospital, Bhubaneswar, Odisha, India from September 2020 to September 2022. A total of 100 eyes with DME, newly diagnosed patients aged 18 years and above, without other macular oedema-causing diseases, were included. A total of 50 eyes in each group were treated with an anti-VEGF agent (Group A) or dexamethasone implant (Group B), and Best Corrected Visual Acuity (BCVA) and Central Foveal Thickness (CFT) were monitored for six months. For statistical analysis, paired t-test and independent t-test were used for within-group and inter-group analysis, respectively. A p-value <0.05 was considered statistically significant. Results: In both groups, post-treatment BCVA showed marked improvement, but there was no significant difference in mean BCVA between the groups (p=0.89) at six months. However, the mean CFT showed significant improvement in Group B at six months. In Group A, the mean CFT reduced from 441.87±54.48 μm to 257.83±25.73 μm, and in Group B, the mean CFT reduced from 464±109.44 μm to 207±22.51 μm at six months (p<0.0001). Adverse events like cataracts and glaucoma were seen in patients treated with the dexamethasone implant and were managed by cataract surgery and topical anti-glaucoma medications, respectively. Conclusion: Dexamethasone implant and anti-VEGF agents are equally effective in improving visual acuity; however, dexamethasone stands superior in reducing macular thickness. Needing fewer injections while treating with a dexamethasone implant improves compliance. The progression of cataract remains a major side-effect with the dexamethasone implant, which is not a concern when treating DME in pseudophakic eye