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Colchicine effectiveness in symptom and inflammation modification in knee osteoarthritis (COLKOA): study protocol for a randomized controlled trial.

BACKGROUND: Despite the high prevalence and global impact of knee osteoarthritis (KOA), current treatments are palliative. No disease modifying anti-osteoarthritic drug (DMOAD) has been approved. We recently demonstrated significant involvement of uric acid and activation of the innate immune response in osteoarthritis (OA) pathology and progression, suggesting that traditional gout therapy may be beneficial for OA. We therefore assess colchicine, an existing commercially available agent for gout, for a new therapeutic application in KOA. METHODS/DESIGN: COLKOA is a double-blind, placebo-controlled, randomized trial comparing a 16-week treatment with standard daily dose oral colchicine to placebo for KOA. A total of 120 participants with symptomatic KOA will be recruited from a single center in Singapore. The primary end point is 30% improvement in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at week 16. Secondary end points include improvement in pain, physical function, and quality of life and change in serum, urine and synovial fluid biomarkers of cartilage metabolism and inflammation. A magnetic resonance imaging (MRI) substudy will be conducted in 20 participants to evaluate change in synovitis. Logistic regression will be used to compare changes between groups in an intention-to-treat analysis. DISCUSSION: The COLKOA trial is designed to evaluate whether commercially available colchicine is effective for improving signs and symptoms of KOA, and reducing synovial fluid, serum and urine inflammatory and biochemical joint degradation biomarkers. These biomarkers should provide insights into the underlying mechanism of therapeutic response. This trial will potentially provide data to support a new treatment option for KOA. TRIAL REGISTRATION: The trial has been registered at clinicaltrials.gov as NCT02176460 . Date of registration: 26 June 2014.

The photography and the motion landscape in the urban expressway

A new kind of photographic representation, called movement-image is proposed and discussed to record the visual experience of the journey through urban highways. It consists of performing long exposure photographic shots while the track is traversed, thus registering a time-panorama which includes landscape signs and inner spaces of the ways involved. This proposal is linked to the limitations of representing these expressways, if they are understood as structures of instrumental origin, where the resulting experience comes from moving at high speed through the territory. In al almost all cases the aesthetic approach or urban integration with the city and landscape are excluded. In this sense, although such structures may be an opportunity to collect, build and colonize the urban landscape, the lack of adequate representation of the phenomenon causes a difficulty in its understanding and transformation. The options for representation using photography is assumed, knowing its own particular tradition in the use of long exposures, for the expression of the mobile, and the multiple visual attention, divided or weakened.

Topical antihistamines and mast cell stabilisers for treating seasonal and perennial allergic conjunctivitis

BACKGROUND: Seasonal/perennial allergic conjunctivitis is the most common allergic conjunctivitis, usually with acute manifestations when a person is exposed to allergens and with typical signs and symptoms including itching, redness, and tearing. The clinical signs and symptoms of allergic conjunctivitis are mediated by the release of histamine by mast cells. Histamine antagonists (also called antihistamines) inhibit the action of histamine by blocking histamine H1 receptors, antagonising the vasoconstrictor, and to a lesser extent, the vasodilator effects of histamine. Mast cell stabilisers inhibit degranulation and consequently the release of histamine by interrupting the normal chain of intracellular signals. Topical treatments include eye drops with antihistamines, mast cell stabilisers, non-steroidal anti-inflammatory drugs, combinations of the previous treatments, and corticosteroids. Standard treatment is based on topical antihistamines alone or topical mast cell stabilisers alone or a combination of treatments. There is clinical uncertainty about the relative efficacy and safety of topical treatment.

OBJECTIVES: The objective of this review was to assess the effects of topical antihistamines and mast cell stabilisers, alone or in combination, for use in treating seasonal and perennial allergic conjunctivitis.

SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2014, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2014), EMBASE (January 1980 to July 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 17 July 2014. We also searched the reference lists of review articles and relevant trial reports for details of further relevant publications.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing topical antihistamine and mast cell stabilisers, alone or in combination, with placebo, no treatment or to any other antihistamine or mast cell stabiliser, or both, that examined people with seasonal or perennial allergic conjunctivitis, or both. The primary outcome was any participant-reported evaluation (by questionnaire) of severity of four main ocular symptoms: itching, irritation, watering eye (tearing), and photophobia (dislike of light), both separately and, if possible, by an overall symptom score. We considered any follow-up time between one week and one year.

DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias. Disagreements were resolved by discussion among review authors and the involvement of a third review author. We followed standard methodological approaches used by Cochrane.

MAIN RESULTS: We identified 30 trials with a total of 4344 participants randomised, with 17 different drugs or treatment comparisons. The following antihistamines and mast cell stabilisers were evaluated in at least one RCT: nedocromil sodium or sodium cromoglycate, olopatadine, ketotifen, azelastine, emedastine, levocabastine (or levocabastine), mequitazine, bepotastine besilate, combination of antazoline and tetryzoline, combination of levocabastine and pemirolast potassium. The most common comparison was azelastine versus placebo (nine studies).We observed a large variability in reporting outcomes. The quality of the studies and reporting was variable, but overall the risk of bias was low. Trials evaluated only short-term effects, with a range of treatment of one to eight weeks. Meta-analysis was only possible in one comparison (olopatadine versus ketotifen). There was some evidence to support that topical antihistamines and mast cell stabilisers reduce symptoms and signs of seasonal allergic conjunctivitis when compared with placebo. There were no reported serious adverse events related to the use of topical antihistamine and mast cell stabilisers treatment.

AUTHORS' CONCLUSIONS: It seems that all reported topical antihistamines and mast cell stabilisers reduce symptoms and signs of seasonal allergic conjunctivitis when compared with placebo in the short term. However, there is no long-term data on their efficacy. Direct comparisons of different antihistamines and mast cell stabilisers need to be interpreted with caution. Overall, topical antihistamines and mast cell stabilisers appear to be safe and well tolerated. We observed a large variability in outcomes reported. Poor quality of reporting challenged the synthesis of evidence.

Readjusting our Sporting Sites/Sight: Sportification and the Theatricality of Social Life

This paper points out the potential of using sport for the analysis of society. Cultivated human movement is a specific social and cultural subsystem (involving sport, movement culture and physical culture), yet it becomes a part of wider social discourses by extending some of its characteristics into various other spheres. This process, theorised as sportification, provides as useful concept to examine the permeation of certain phenomena from the area of sport into the social reality outside of sport. In this paper, we investigate the phenomena of sportification which we parallel with visual culture and spectatorship practices in the Renaissance era. The emphasis in our investigation is on theatricality and performativity; particularly, the superficial spectator engagement with modern sport and sporting spectacles. Unlike the significance afforded to visualisation and deeper symbolic interpretation in Renaissance art, contemporary cultural shifts have changed and challenged the ways in which the active and interacting body is positioned, politicised, symbolised and ultimately understood. We suggest here that the ways in which we view sport and sporting bodies within a (post)modern context (particularly with the confounding amalgamations of signs and symbols and emphasis on hyper-realities) has invariably become detached from sports’ profound metaphysical meanings and resonance. Subsequently, by emphasising the associations between social theatrics and the sporting complex, this paper aims to remind readers of ways that sport—as a nuanced phenomenon—can be operationalised to help us to contemplate questions about nature, society, ourselves and the complex worlds in which we live.

Lighting conditions and optical filters effects on visual performance of speleologists exposed to cave environments

The aim of this study is to evaluate lighting conditions and speleologists’ visual performance using optical filters when exposed to the lighting conditions of cave environments. A crosssectional study was conducted. Twenty-three speleologists were submitted to an evaluation of visual function in a clinical lab. An examination of visual acuity, contrast sensitivity, stereoacuity and flashlight illuminance levels was also performed in 16 of the 23 speleologists at two caves deprived of natural lightning. Two organic filters (450 nm and 550 nm) were used to compare visual function with and without filters. The mean age of the speleologists was 40.65 (± 10.93) years. We detected 26.1% participants with visual impairment of which refractive error (17.4%) was the major cause. In the cave environment the majority of the speleologists used a head flashlight with a mean illuminance of 451.0 ± 305.7 lux. Binocular visual acuity (BVA) was -0.05 ± 0.15 LogMAR (20/18). BVA for distance without filter was not statistically different from BVA with 550 nm or 450 nm filters (p = 0.093). Significant improved contrast sensitivity was observed with 450 nm filters for 6 cpd (p = 0.034) and 18 cpd (p = 0.026) spatial frequencies. There were no signs and symptoms of visual pathologies related to cave exposure. Illuminance levels were adequate to the majority of the activities performed. The enhancement in contrast sensitivity with filters could potentially improve tasks related with the activities performed in the cave.

Long-Term Lamivudine Treatment of Children with Chronic Hepatitis B: Durability of Therapeutic Responses and Safety

Lamivudine has been demonstrated safe and efficacious in the short term in a large cohort of children with chronic hepatitis B (CHB), but optimal duration of treatment has not been elucidated and limited data on the safety of long-term lamivudine administration have been reported. In addition, the durability of favourable therapeutic outcomes after lamivudine therapy in children has not been well characterized. The aim of this study was to examine the safety of lamivudine and the durability of clinical responses in a group of children who received up to 3 years of treatment for CHB. One hundred and fifty-one children from centres in nine countries who had previously received lamivudine in a large prospective trial were enrolled. During the first year, children had been randomized to either lamivudine or placebo treatment. Subsequently, in a separate extension study, those who remained hepatitis B e antigen (HBeAg) positive were given lamivudine for up to 2 years and those who were HBeAg negative were observed for additional 2 years. Results of these studies have been previously reported. In this study, these children were followed for 2 additional years. Data gathered from medical record review included weight, height, signs and symptoms of hepatitis, alanine aminotransferase (ALT) levels, serologic markers, hepatitis B virus (HBV) DNA levels and serious adverse events (SAEs). Other pharmacological treatments for CHB were allowed according to the practices of individual investigators and were documented. Subjects were divided into two groups for analysis, those who had achieved virological response (VR), defined as HBeAg negative and undetectable HBV DNA by the bDNA assay by the end of the extension study at 3 years, and those who had not. In those who had achieved VR by the end of the extension study, long-term durability of HBeAg seroconversion was 82% and >90% in those who had received lamivudine for 52 weeks and at least 2 years respectively. This compares to 75% for those who had achieved seroconversion after placebo. In those who had not achieved VR by the end of the extension study, an additional 11% did so by the end of the study; they had all received lamivudine in the previous trial, and none had received further treatment during the study. Eight children lost hepatitis B surface antigen during the study and all had received lamivudine at some point during the previous trials. Evaluation of safety data revealed no SAEs related to lamivudine. There was no effect of treatment on weight or height z scores. Clinically benign ALT flares (>10 times normal) were seen in 2% of children. Favourable outcomes from lamivudine treatment of CHB in children are maintained for at least several years after completion of treatment. Up to 3 years of lamivudine treatment is safe in children.

Prevalence and clinical importance of mesenteric venous thrombosis in the swiss inflammatory bowel disease cohort.

OBJECTIVE. The purpose of this study was to evaluate the prevalence of mesenteric venous thrombosis (MVT) in the Swiss Inflammatory Bowel Disease Cohort Study and to correlate MVT with clinical outcome. MATERIALS AND METHODS. Abdominal portal phase CT was used to examine patients with inflammatory bowel disease (IBD). Two experienced abdominal radiologists retrospectively analyzed the images, focusing on the superior and inferior mesenteric vein branches and looking for signs of acute or chronic thrombosis. The location of abnormalities was registered. The presence of MVT was correlated with IBD-related radiologic signs and complications. RESULTS. The cases of 160 patients with IBD (89 women, 71 men; Crohn disease [CD], 121 patients; ulcerative colitis [UC], 39 patients; median age at diagnosis, 27 years for patients with CD, 32 years for patients with UC) were analyzed. MVT was detected in 43 patients with IBD (26.8%). One of these patients had acute MVT; 38, chronic MVT; and four, both. The prevalence of MVT did not differ between CD (35/121 [28.9%]) and UC (8/39 [20.5%]) (p = 0.303). The location of thrombosis was different between CD and UC (CD, jejunal or ileal veins only [p = 0.005]; UC, rectocolic veins only [p = 0.001]). Almost all (41/43) cases of thrombosis were peripheral. MVT in CD patients was more frequently associated with bowel wall thickening (p = 0.013), mesenteric fat hypertrophy (p = 0.005), ascites (p = 0.002), and mesenteric lymph node enlargement (p = 0.036) and was associated with higher rate of bowel stenosis (p < 0.001) and more intestinal IBD-related surgery (p = 0.016) in the outcome. Statistical analyses for patients with UC were not relevant because of the limited population (n = 8). CONCLUSION. MVT is frequently found in patients with IBD. Among patients with CD, MVT is associated with bowel stenosis and CD-related intestinal surgery.

Diagnostic et traitement des infections d'implants orthopédiques [Update on implant related infections in orthopaedic surgery. Diagnosis and treatment]

Infections associated with implants are increasingly important in modem medicine. Biofilms are the cause that these infections are more difficult to diagnose and to cure. Particularly low-grade infections are difficult to distinguish from aseptic failure, because they often present with early loosening and persisting pain. For an accurate diagnosis, clinical signs and symptoms, laboratory markers of infection, microbiology, histology and imaging examinations are needed. The treatment goal is eradication of infection and an optimal functional result. Successful treatment requires adequate surgical procedure combined with long-term antimicrobial therapy, ideally with an agent acting on biofilms.

Behavioral and psychological symptoms and cognitive decline in patients with amnestic MCI and mild AD: a two-year follow-up study.

BACKGROUND: Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and dementia. In many cases, MCI represents an early stage of developing cognitive impairment. Patients diagnosed with MCI do not meet the criteria for dementia as their general intellect and everyday activities are preserved, although minor changes in instrumental activities of daily living (ADL) may occur. However, they may exhibit significant behavioral and psychological signs and symptoms (BPS), also frequently observed in patients with Alzheimer's disease (AD). Hence, we wondered to what extent specific BPS are associated with cognitive decline in participants with MCI or AD. METHODS: Our sample consisted of 164 participants, including 46 patients with amnestic (single or multi-domain) MCI and 54 patients with AD, as well as 64 control participants without cognitive disorders. Global cognitive performance, BPS, and ADL were assessed using validated clinical methods at baseline and at two-year follow-up. RESULTS: The BPS variability over the follow-up period was more pronounced in the MCI group than in patients with AD: some BPS improve, others occur newly or worsen, while others still remain unchanged. Moreover, specific changes in BPS were associated with a rapid deterioration of the global cognitive level in MCI patients. In particular, an increase of euphoria, eating disorders, and aberrant motor behavior, as well as worsened sleep quality, predicted a decline in cognitive functioning. CONCLUSIONS: Our findings confirm a higher variability of BPS over time in the MCI group than in AD patients. Moreover, our results provide evidence of associations between specific BPS and cognitive decline in the MCI group that might suggest a risk of conversion of individuals with amnestic MCI to AD.

Sodium and potassium balance depends on αENaC expression in connecting tubule.

Mutations in α, β, or γ subunits of the epithelial sodium channel (ENaC) can downregulate ENaC activity and cause a severe salt-losing syndrome with hyperkalemia and metabolic acidosis, designated pseudohypoaldosteronism type 1 in humans. In contrast, mice with selective inactivation of αENaC in the collecting duct (CD) maintain sodium and potassium balance, suggesting that the late distal convoluted tubule (DCT2) and/or the connecting tubule (CNT) participates in sodium homeostasis. To investigate the relative importance of ENaC-mediated sodium absorption in the CNT, we used Cre-lox technology to generate mice lacking αENaC in the aquaporin 2-expressing CNT and CD. Western blot analysis of microdissected cortical CD (CCD) and CNT revealed absence of αENaC in the CCD and weak αENaC expression in the CNT. These mice exhibited a significantly higher urinary sodium excretion, a lower urine osmolality, and an increased urine volume compared with control mice. Furthermore, serum sodium was lower and potassium levels were higher in the genetically modified mice. With dietary sodium restriction, these mice experienced significant weight loss, increased urinary sodium excretion, and hyperkalemia. Plasma aldosterone levels were significantly elevated under both standard and sodium-restricted diets. In summary, αENaC expression within the CNT/CD is crucial for sodium and potassium homeostasis and causes signs and symptoms of pseudohypoaldosteronism type 1 if missing.

Representations of swinging London in 1960s British cinema : Blowup (1966), Smashing Time (1967), and Performance (1970)

This thesis explores the representation of Swinging London in three examples of 1960s British cinema: Blowup (Michelangelo Antonioni, 1966), Smashing Time (Desmond Davis, 1967) and Performance (Donald Cammell and Nicolas Roeg, 1970). It suggests that the films chronologically signify the evolution, commodification and dissolution of the Swinging London era. The thesis explores how the concept of Swinging London is both critiqued and perpetuated in each film through the use of visual tropes: the reconstruction of London as a cinematic space; the Pop photographer; the dolly; representations of music performance and fashion; the appropriation of signs and symbols associated with the visual culture of Swinging London. Using fashion, music performance, consumerism and cultural symbolism as visual narratives, each film also explores the construction of youth identity through the representation of manufactured and mediated images. Ultimately, these films reinforce Swinging London as a visual economy that circulates media images as commodities within a system of exchange. With this in view, the signs and symbols that comprise the visual culture of Swinging London are as central and significant to the cultural era as their material reality. While they attempt to destabilize prevailing representations of the era through the reproduction and exchange of such symbols, Blowup, Smashing Time, and Performance nevertheless contribute to the nostalgia for Swinging London in larger cultural memory.

Vertical R&D Sprillovers, Cooperation, Market Structure, and Innovation.

This paper studies vertical R&D spillovers between upstream and downstream firms. The model incorporates two vertically related industries, with horizontal spillovers within each industry and vertical spillovers between the two industries. Four types of R&D cooperation are studied : no cooperation, horizontal cooperation, vertical cooperation, and simultaneous horizontal and vertical cooperation. Vertical spillovers always increase R&D and welfare, while horizontal spillovers may increase or decrease them. The comparison of cooperative settings in terms of R&D shows that no setting uniformly dominates the others. Which type of cooperation yields more R&D depends on horizontal and vertical spillovers, and market structure. The ranking of cooperative structures hinges on the signs and magnitudes of three competitive externalities (vertical, horizontal, and diagonal) which capture the effect of the R&D of a firm on the profits of other firms. One of the basic results of the strategic investment literature is that cooperation between competitors increases (decreases) R&D when horizontal spillovers are high (low); the model shows that this result does not necessarily hold when vertical spillovers and vertical cooperation are taken into account. The paper proposes a theory of innovation and market structure, showing that the relation between innovation and competition depends on horizontal spillovers, vertical spillovers, and cooperative settings. The private incentives for R&D cooperation are addressed. It is found that buyers and sellers have divergent interests regarding the choice of cooperative settings and that spillovers increase the likelihood of the emergence of cooperation in a decentralized equilibrium.

Predictive values of neurological examination, otoscopic examination and brainstem auditory evoked response (BAER) in calves with otisis media-interna

Présentement, le diagnostic d’otite moyenne-interne chez le veau est basé sur la présence de signes cliniques appropriés ainsi que les tests diagnostiques tels que la radiographie et la tomodensitométrie. L’objectif de cette étude prospective était d’évaluer les valeurs prédictives de l’examen neurologique, l’examen otoscopique et le test des potentiels auditifs évoqués (PAE) dans le diagnostic d’otite moyenne-interne chez le veau, en utilisant la tomodensitométrie comme test standard. Le deuxième objectif était de définir les valeurs de référence pour le PAE chez le veau normal et d’en décrire les anomalies chez des veaux atteints d’otite moyenne-interne. Dix-sept veaux de race Holstein entre 5-7 semaines d’âge ont été inclus. Tous les veaux ont eu un examen neurologique, un examen otoscopique et une évaluation des PAEs. Les veaux ont été tranquillisés avec de la xylazine intraveineuse (0,05-0,15mg/kg) pour la tomodensitométrie des bulles tympaniques afin d’évaluer pour la présence d’otite moyenne-interne. Selon les résultats de la tomodensitométrie, 11 des 17 veaux étaient atteints avec otite moyenne, 4 de façon unilatérale et 7 bilatéralement. Cinq ondes ont été identifiées de façon constante sur les tracés des PAEs des 6 veaux normaux. Les valeurs positives prédictives pour le PAE, l’examen neurologique et l’examen otoscopique étaient 94,7%, 91,7% et 66,7% respectivement. D’un point de vue clinique, le test le plus fiable dans le diagnostic d’otite moyenne-interne chez le veau est le PAE. Les anomalies ont été observées au PAE avant le développement des signes neurologiques chez certains veaux.

In vitro and in vivo effects of deoxynivalenol (DON) mycotoxin on porcine reproductive and respiratory syndrome virus (PRRSV) in piglets

Les récoltes de céréales sont souvent contaminées par des moisissures qui se développent pendant la récolte et l’entreposage et produisent des métabolites secondaires appelés mycotoxines. Le porc est reconnu pour être sensible au déoxynivalénol (DON). L’infection virale la plus importante chez le porc est causée par le virus du syndrome reproducteur et respiratoire porcin (VSRRP). Celui-ci provoque un syndrome grippal et des troubles de reproduction. L’objectif du présent projet était de déterminer l'effet in vitro de DON sur la réplication du VSRRP dans de lignées cellulaires permissives, MARC-145 et PAM, et déterminer in vivo l'impact de DON dans des aliments naturellement contaminés sur l’infection au VSRRP chez le porcelet. Tout d’abord, les cellules ont été incubées avec des doses croissantes de DON et ont été infectées avec du VSRRP pour évaluer la viabilité et la mortalité cellulaire, la réplication virale et l’expression de cytokines. Les résultats ont montré que les concentrations de DON de 560ng/ml et plus affectaient significativement la survie des cellules MARC-145 et PAM infectées par le VSRRP. En revanche, il y avait une augmentation significative de la viabilité et une réduction de la mortalité cellulaire à des concentrations de DON de 140 à 280 ng/ml pour les cellules PAM et de 70 à 280 ng/ml pour les cellules MARC-145 avec une réduction de l'effet cytopathique provoqué parle VSRRP. Au niveau in vivo, 30 porcelets divisés en 3 groupes de 10 porcelets et nourris pendant 2 semaines avec 3 différentes diètes naturellement ont été contaminées avec DON (0; 2,5 et 3,5 mg/kg). Les porcelets ont été subdivisés en 6 groupes, 3 groupes de 6 porcelets et ont été exposés au DON pendant 2 semaines et infectés par voie intratrachéale et intramusculaire avec le virus. Les 3 autres groupes de 4 porcelets servaient de contrôle non infectés. Les signes cliniques ont été enregistrés pendant 21 jours. La virémie a été évaluée par PCR. À la fin de l’expérimentation, les porcelets ont été euthanasiés et les lésions pulmonaires ont été évaluées. Les résultats ont montré que l’ingestion de DON à 3,5 mg/kg a augmenté l’effet du VSRRP sur la sévérité des signes cliniques, les lésions pulmonaires et la mortalité. L’ingestion de DON à 2,5 mg/kg a entrainé une augmentation de la virémie au jour 3 après l’infection mais sans impact sur les signes cliniques et les lésions pulmonaires. Mot clés: DON, VSRRP, MARC-145, PAM, effet cytopathique, cytokines, PCR