In vitro elution characteristics of gentamicin- and teicoplanin-loaded CMW1 and Palacos R bone cement.

PURPOSE: To compare the in vitro elution characteristics of CMW1 and Palacos R bone cement loaded with gentamicin, teicoplanin, or in combination. METHODS: Four bone cement discs were prepared for each cement type. Disc 1 contained no antibiotics; disc 2 contained 0.5 g gentamicin; disc 3 contained 2 g teicoplanin; disc 4 contained 0.5 g gentamicin and 2 g teicoplanin. Elution studies were conducted using a fluorescence polarisation immunoassay technique and performed at intervals of 6 weeks. RESULTS: For CMW1, gentamicin and teicoplanin elution levels in combination discs were higher than those in the single antibiotic discs (p < 0.001 & p < 0.06). For Palacos R, gentamicin elution levels in combination discs were higher than those in the single antibiotic discs (p < 0.001), but teicoplanin elution levels in combination discs were lesser than that from the single antibiotic discs (p < 0.02). In single and combination discs, gentamicin elution levels in Palacos R were higher than those in CMW1 (p < 0.001 & p < 0.001). Palacos R eluted more teicoplanin than CMW1, except in combined disc with gentamicin, when less teicoplanin was eluted. CONCLUSION: Antibiotic elution is higher in Palacos R than CMW1. Antibiotic combination in both cement types has the synergistic effect of increasing antibiotic elution, except for teicoplanin from Palacos R. When high elution of gentamicin is required, Palacos R is preferable. When high elution of teicoplanin is required, Palacos R with only teicoplanin is superior to CMW1.

Evidence of Air Trapping During Ex Vivo Lung Perfusion: A Swine Experimental Lung Imaging and Mechanics Study.

Ex vivo lung perfusion (EVLP) allows the ventilation and perfusion of lungs to evaluate their viability for transplantation. The aim of this study is to compare the mechanical, morphologic and functional properties of lungs during EVLP with values obtained in vivo to guide a safe mechanical ventilation strategy. Lungs from 5 healthy pigs were studied in vivo and during 4 hours of EVLP. Lung compliance, airway resistance, gas exchange, and hemodynamic parameters were collected at positive end-expiratory pressure (PEEP) of 5 cm H2O. Computed tomography was performed at PEEP 0, PEEP 5, and total lung capacity (TLC). Lung pressure-volume (PV) curves were performed from PEEP 0 to TLC. Lung compliance decreased during EVLP (53 ± 5 mL/cm H2O vs 29 ± 7 mL/cm H2O, P < .05), and the PV curve showed a lower inflection point. Gas content (528 ± 118 mL vs 892 ± 402 mL at PEEP 0) and airway resistance (25 ± 5 vs 44 ± 9 cmH2O/L∗s-1, P < .05) were higher during EVLP. Alveolar dead space (5% ± 2% vs 17% ± 6%, P < .05) and intrapulmonary shunt (9% ± 2% vs 28% ± 13%, P < .05) increased ex vivo compared to in vivo, while the partial pressure of oxygen to inspired oxygen fraction ratio (PO2/FiO2) did not differ (468 ± 52 mm Hg vs 536 ± 14 mm Hg). In conclusion, during EVLP lungs show signs of air trapping and bronchoconstriction, resulting in low compliance and increased alveolar dead space. Intrapulmonary shunt is high despite oxygenation levels acceptable for transplantation.

Fungal Planet description sheets: 868-950.

Novel species of fungi described in this study include those from various countries as follows: Australia, Chaetomella pseudocircinoseta and Coniella pseudodiospyri on Eucalyptus microcorys leaves, Cladophialophora eucalypti, Teratosphaeria dunnii and Vermiculariopsiella dunnii on Eucalyptus dunnii leaves, Cylindrium grande and Hypsotheca eucalyptorum on Eucalyptus grandis leaves, Elsinoe salignae on Eucalyptus saligna leaves, Marasmius lebeliae on litter of regenerating subtropical rainforest, Phialoseptomonium eucalypti (incl. Phialoseptomonium gen. nov.) on Eucalyptus grandis × camaldulensis leaves, Phlogicylindrium pawpawense on Eucalyptus tereticornis leaves, Phyllosticta longicauda as an endophyte from healthy Eustrephus latifolius leaves, Pseudosydowia eucalyptorum on Eucalyptus sp. leaves, Saitozyma wallum on Banksia aemula leaves, Teratosphaeria henryi on Corymbia henryi leaves. Brazil, Aspergillus bezerrae, Backusella azygospora, Mariannaea terricola and Talaromyces pernambucoensis from soil, Calonectria matogrossensis on Eucalyptus urophylla leaves, Calvatia brasiliensis on soil, Carcinomyces nordestinensis on Bromelia antiacantha leaves, Dendryphiella stromaticola on small branches of an unidentified plant, Nigrospora brasiliensis on Nopalea cochenillifera leaves, Penicillium alagoense as a leaf endophyte on a Miconia sp., Podosordaria nigrobrunnea on dung, Spegazzinia bromeliacearum as a leaf endophyte on Tilandsia catimbauensis, Xylobolus brasiliensis on decaying wood. Bulgaria, Kazachstania molopis from the gut of the beetle Molops piceus. Croatia, Mollisia endocrystallina from a fallen decorticated Picea abies tree trunk. Ecuador, Hygrocybe rodomaculata on soil. Hungary, Alfoldia vorosii (incl. Alfoldia gen. nov.) from Juniperus communis roots, Kiskunsagia ubrizsyi (incl. Kiskunsagia gen. nov.) from Fumana procumbens roots. India, Aureobasidium tremulum as laboratory contaminant, Leucosporidium himalayensis and Naganishia indica from windblown dust on glaciers. Italy, Neodevriesia cycadicola on Cycas sp. leaves, Pseudocercospora pseudomyrticola on Myrtus communis leaves, Ramularia pistaciae on Pistacia lentiscus leaves, Neognomoniopsis quercina (incl. Neognomoniopsis gen. nov.) on Quercus ilex leaves. Japan, Diaporthe fructicola on Passiflora edulis × P. edulis f. flavicarpa fruit, Entoloma nipponicum on leaf litter in a mixed Cryptomeria japonica and Acer spp. forest. Macedonia, Astraeus macedonicus on soil. Malaysia, Fusicladium eucalyptigenum on Eucalyptus sp. twigs, Neoacrodontiella eucalypti (incl. Neoacrodontiella gen. nov.) on Eucalyptus urophylla leaves. Mozambique, Meliola gorongosensis on dead Philenoptera violacea leaflets. Nepal, Coniochaeta dendrobiicola from Dendriobium lognicornu roots. New Zealand, Neodevriesia sexualis and Thozetella neonivea on Archontophoenix cunninghamiana leaves. Norway, Calophoma sandfjordenica from a piece of board on a rocky shoreline, Clavaria parvispora on soil, Didymella finnmarkica from a piece of Pinus sylvestris driftwood. Poland, Sugiyamaella trypani from soil. Portugal, Colletotrichum feijoicola from Acca sellowiana. Russia, Crepidotus tobolensis on Populus tremula debris, Entoloma ekaterinae, Entoloma erhardii and Suillus gastroflavus on soil, Nakazawaea ambrosiae from the galleries of Ips typographus under the bark of Picea abies. Slovenia, Pluteus ludwigii on twigs of broadleaved trees. South Africa, Anungitiomyces stellenboschiensis (incl. Anungitiomyces gen. nov.) and Niesslia stellenboschiana on Eucalyptus sp. leaves, Beltraniella pseudoportoricensis on Podocarpus falcatus leaf litter, Corynespora encephalarti on Encephalartos sp. leaves, Cytospora pavettae on Pavetta revoluta leaves, Helminthosporium erythrinicola on Erythrina humeana leaves, Helminthosporium syzygii on a Syzygium sp. bark canker, Libertasomyces aloeticus on Aloe sp. leaves, Penicillium lunae from Musa sp. fruit, Phyllosticta lauridiae on Lauridia tetragona leaves, Pseudotruncatella bolusanthi (incl. Pseudotruncatellaceae fam. nov.) and Dactylella bolusanthi on Bolusanthus speciosus leaves. Spain, Apenidiella foetida on submerged plant debris, Inocybe grammatoides on Quercus ilex subsp. ilex forest humus, Ossicaulis salomii on soil, Phialemonium guarroi from soil. Thailand, Pantospora chromolaenae on Chromolaena odorata leaves. Ukraine, Cadophora helianthi from Helianthus annuus stems. USA, Boletus pseudopinophilus on soil under slash pine, Botryotrichum foricae, Penicillium americanum and Penicillium minnesotense from air. Vietnam, Lycoperdon vietnamense on soil. Morphological and culture characteristics are supported by DNA barcodes.

Survey of dental diseases in Crioulo breed horses reared in an extensive farming system / Levantamento de afecções dentárias em equinos da raça Crioula mantidos em sistema de criação extensivo

The present study aimed to identify and quantify dental diseases in Crioulo horses reared exclusively under extensive farming conditions. In total, 254 Crioulo horses were evaluated, that were reared exclusively in native pastures with predominantly Eragrostis plana (Annoni grass). The animals were divided into three groups according to age: three to five years (G1), six to 12 years (G2), and 13 to 26 years (G3). In total, 46.1% of the animals in G1, 63.8% in G2, and 82.3% in G3 had two or more incisor disorders; 37.5% in G1, 52.5% in G2 and 45.5% in G3 had two or more disease findings in the canines; and 28.9% in G1, 35.4% in G2, and 64.7% in G3 had four or more disease findings in the second, third, and fourth premolars and molars. However, dental calculus was observed in 90.5% of G2 animals, whereas in G3, the occurrence rate of excessive enamel points and calculus was 82.4%. Although all of the horses studied were reared in an extensive farming system, dental changes were very common in the Crioulo breed reared under these management conditions.(AU)

O presente estudo teve por objetivo identificar e quantificar as afecções odontológicas de equinos da raça Crioula criados exclusivamente em regime extensivo. No total, foram avaliados 254 cavalos Crioulos, criados em pastagens nativas com predominância de Eragrostis plana (capim-annoni). Os animais foram divididos em três grupos, de acordo com a idade: de três a cinco anos (G1), seis a 12 anos (G2 ) e 13 a 26 anos (G3). No total, 46,1% dos animais do G1, 63,8% do G2 e 82,3% do G3 apresentaram dois ou mais transtornos incisivos; 37,5% do G1, 52,5% do G2 e 45,5% do G3 tiveram duas ou mais alterações nos caninos; 28,9% do G1, 35,4% do G2 e 64,7% do G3 mostraram quatro ou mais distúrbios no segundo, terceiro e quarto pré-molares e molares. Contudo, cálculo dentário foi observado em 90,5% dos animais do G2, enquanto no G3, a taxa de ocorrência de pontas excessivas de esmalte dentário e cálculo foi de 82,4%. Concluiu-se que, apesar de todos os equinos estudados serem mantidos em sistema extensivo, as afecções dentárias mostraram-se muito comuns na raça Crioula sob estas condições de manejo.(AU)

d-α-tocopherol nanoemulsions: Size properties, rheological behavior, surface tension, osmolarity and cytotoxicity.

The aim of this study was the assessment of the physicochemical stability of d-α-tocopherol formulated in medium chain triglyceride nanoemulsions, stabilized with Tween®80 and Lipoid®S75 as surfactant and co-surfactant, respectively. d-α-tocopherol was selected as active ingredient because of its well-recognized interesting anti-oxidant properties (such as radical scavenger) for food and pharmaceutical industries. A series of nanoemulsions of mean droplet size below 90 nm (polydispersity index < 0.15) have been produced by high-pressure homogenization, and their surface electrical charge (zeta potential), pH, surface tension, osmolarity, and rheological behavior, were characterized as a function of the d-α-tocopherol loading. In vitro studies in Caco-2 cell lines confirmed the safety profile of the developed nanoemulsions with percentage of cell viability above 90% for all formulations.

What I wish I'd learned at dental school.

Background Much concern appears to exist as to the scope and content of contemporary dental school programmes, with the oft-cited criticism being made that dental graduates are 'no longer as good as they used to be'.Aim The aim of this project was to survey the views of dentists - both new graduates and more established practitioners - on aspects of their own dental school training they felt had been deficient as well as commenting on what aspects of dental school education they would like to see improved/enhanced in current times.Methods An invitation to complete an Internet-based questionnaire was emailed to the Fellows and Members of the Faculty of General Dental Practice (UK). Topics in the questionnaire included the respondent's own dental education history, how well they felt their dental school training had covered certain clinical and non-clinical topics; and their opinions on areas they felt should be included in contemporary dental school programmes.Results Six hundred and forty-nine responses were received from 3,348 emailed invitations (response rate = 19.4%). Sixty-one percent (395) of respondents were qualified for 10 years or more. Among clinical skills and techniques, a majority of respondents reported they felt they had not had sufficient teaching/training in dental school in surgical endodontics (76%), conscious sedation (72%), root surface debridement (71%), fixed orthodontic appliances (68%), porcelain veneers (63%), implants (56%) and posterior composites (53%). If designing a new dental school programme, the most common topics respondents would seek to include/increase were business and practice management (21%), communication skills (including patient management and leadership skills) (10%), and increased clinical time and experience (8%).Conclusions The findings of this project are of interest and relevance to those working with student dentists and young dental practitioners. A greater emphasis is needed on the teaching of certain non-clinical subjects such as business and communication skills, while within clinical subjects there is need to refine and expand teaching in identified areas such as exodontia and endodontics.

Genetic variability in isolates of Chromobacterium violaceum from pulmonary secretion, water, and soil.

Chromobacterium violaceum is a free-living Gram-negative bacillus usually found in the water and soil in tropical regions, which causes infections in humans. Chromobacteriosis is characterized by rapid dissemination and high mortality. The aim of this study was to detect the genetic variability among C. violaceum type strain ATCC 12472, and seven isolates from the environment and one from a pulmonary secretion from a chromobacteriosis patient from Ilhéus, Bahia. The molecular characterization of all samples was performed by polymerase chain reaction (PCR) sequencing and 16S rDNA analysis. Primers specific for two ATCC 12472 pathogenicity genes, hilA and yscD, as well as random amplified polymorphic DNA (RAPD), were used for PCR amplification and comparative sequencing of the products. For a more specific approach, the PCR products of 16S rDNA were digested with restriction enzymes. Seven of the samples, including type-strain ATCC 12472, were amplified by the hilA primers; these were subsequently sequenced. Gene yscD was amplified only in type-strain ATCC 12472. MspI and AluI digestion revealed 16S rDNA polymorphisms. This data allowed the generation of a dendogram for each analysis. The isolates of C. violaceum have variability in random genomic regions demonstrated by RAPD. Also, these isolates have variability in pathogenicity genes, as demonstrated by sequencing and restriction enzyme digestion.

Tramadol hydrochloride: pharmacokinetics, pharmacodynamics, adverse side effects, co-administration of drugs and new drug delivery systems.

Tramadol hydrochloride (TrHC) is a synthetic analgesic drug exhibiting opioid and non-opioid properties, acting mainly on the central nervous system. It has been mostly used to treat pain, although its use to treat anxiety and depression has also been documented. These properties arise from the fact that they inhibit serotonin (5-HT) reuptake augmenting 5-HT concentration on the synaptic cleft. Despite this, TrHC has also been described to have several side effects which are mainly due to its fast metabolization and excretion which in turn requires multiple doses per day. To surpass this limitation, new pharmaceutical formulations are being developed intending the protection, target and sustained delivery as well as a reduction on daily dose aiming a reduction on the side effects. In the present work we have revised the efficacy, safety, biological and adverse effects of TrHC, and the added value of developing a novel drug delivery system for topical administration.

Tailored excisional treatment for high-grade haemorrhoidal disease.

Patients affected by high-grade haemorrhoid with a fibrous internal pile or an important external component are suitable for an excisional procedure. The aim of this study is to evaluate the outcome of different excisional treatments such as Milligan and Morgan haemorrhoidectomy, Ferguson haemorrhoidectomy and Pexy-excision carried out according to a tailored treatment on each pathological pile. All the consecutive patients that underwent an excisional procedure for high-grade haemorrhoids in two different centres were considered for the present study. From January 2010 to December 2012, 135 patients affected by high-grade haemorrhoidal disease were treated with excisional procedures. No statistically significant differences were noted regarding age, sex distribution, symptoms, Goligher grade, length of surgery, number of pathological piles treated and number of pathological piles excised for each patient between groups. The Ferguson and Pexy-excision procedures yield better results in terms of pain and healing than open haemorrhoidectomy, whereas recurrence and complications are similar after 1 year. Excisional procedures are safe and effective for the treatment of high-grade haemorrhoids mostly if performed according to a tailored project. An increase in the number of pathological piles treated corresponded to an increase in the need of analgesics regardless of the procedure performed.

Health care and patients' education in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom study.

BACKGROUND AND AIMS: The EpiCom study and inception cohort was initiated in 2010 in 31 centers from 14 Western and 8 Eastern European countries, covering a 10.1million person background population. Our aim was to investigate whether there is a difference between Eastern and Western Europe in health care and education of patients with inflammatory bowel disease (IBD). METHODS: A quality of care (QoC) questionnaire was developed in the EpiCom group consisting of 16 questions covering 5 items: time interval between the onset of symptoms and diagnosis, information, education, empathy and access to health care providers. RESULTS: Of 1,515 patients, 947 (217 east/730 west) answered the QoC questionnaire. Only 23% of all patients had knowledge about IBD before diagnosis. In Eastern Europe, significantly more patients searched out information about IBD themselves (77% vs. 68%, p<0.05), the main source was the Internet (92% vs. 88% p=0.23). In Western Europe, significantly more patients were educated by nurses (19% vs. 1%, p<0.05), while in Eastern Europe, gastroenterologists were easier to contact (80% vs. 68%, p<0.05). CONCLUSION: Health care differed significantly between Eastern and Western Europe in all items, but satisfaction rates were high in both geographic regions. Because of the low awareness and the rising incidence of IBD, general information should be the focus of patient organizations and medical societies. In Western Europe IBD nurses play a very important role in reducing the burden of patient management.

Genetic diversity of Burkholderia (Proteobacteria) species from the Caatinga and Atlantic rainforest biomes in Bahia, Brazil.

The genus Burkholderia (ß-Proteobacteria) currently comprises more than 60 species, including parasites, symbionts and free-living organisms. Several new species of Burkholderia have recently been described showing a great diversity of phenotypes. We examined the diversity of Burkholderia spp in environmental samples collected from Caatinga and Atlantic rainforest biomes of Bahia, Brazil. Legume nodules were collected from five locations, and 16S rDNA and recA genes of the isolated microorganisms were analyzed. Thirty-three contigs of 16S rRNA genes and four contigs of the recA gene related to the genus Burkholderia were obtained. The genetic dissimilarity of the strains ranged from 0 to 2.5% based on 16S rDNA analysis, indicating two main branches: one distinct branch of the dendrogram for the B. cepacia complex and another branch that rendered three major groups, partially reflecting host plants and locations. A dendrogram designed with sequences of this research and those designed with sequences of Burkholderia-type strains and the first hit BLAST had similar topologies. A dendrogram similar to that constructed by analysis of 16S rDNA was obtained using sequences of the fragment of the recA gene. The 16S rDNA sequences enabled sufficient identification of relevant similarities and groupings amongst isolates and the sequences that we obtained. Only 6 of the 33 isolates analyzed via 16S rDNA sequencing showed high similarity with the B. cepacia complex. Thus, over 3/4 of the isolates have potential for biotechnological applications.

Biomarker discovery by plasma proteomics in familial Brugada Syndrome.

Brugada Syndrome (BS) is a polygenic inherited cardiac disease characterized by life-threatening arrhythmias and high incidence of sudden death. In this study, two-dimensional gel electrophoresis (2D-PAGE) coupled to mass spectrometry (LC-MS/MS) was used to investigate specific changes in the plasma proteome of BS patients and family members sharing the same gene mutation (SCN5AQ1118X), with the aim to identify novel disease biomarkers. Our data demonstrate that the levels of several proteins were significantly altered in BS patients compared with controls. In particular, apolipoprotein E, prothrombin, vitronectin, complement-factor H, vitamin-D-binding protein, voltage-dependent anion-selective channel protein 3 and clusterin were considerably increased in plasma sample of BS patients, whereas alpha-1-antitrypsin, fibrinogen and angiotensinogen were considerably decreased; moreover, post-translational modifications of antithrombin-III were detected in all affected individuals. On the light of these results, we hypothesize that these proteins might be considered as potential markers for the identification of disease status in BS.

Biogeographical patterns and determinants of invasion by forest pathogens in Europe.

A large database of invasive forest pathogens (IFPs) was developed to investigate the patterns and determinants of invasion in Europe. Detailed taxonomic and biological information on the invasive species was combined with country-specific data on land use, climate, and the time since invasion to identify the determinants of invasiveness, and to differentiate the class of environments which share territorial and climate features associated with a susceptibility to invasion. IFPs increased exponentially in the last four decades. Until 1919, IFPs already present moved across Europe. Then, new IFPs were introduced mainly from North America, and recently from Asia. Hybrid pathogens also appeared. Countries with a wider range of environments, higher human impact or international trade hosted more IFPs. Rainfall influenced the diffusion rates. Environmental conditions of the new and original ranges and systematic and ecological attributes affected invasiveness. Further spread of established IFPs is expected in countries that have experienced commercial isolation in the recent past. Densely populated countries with high environmental diversity may be the weakest links in attempts to prevent new arrivals. Tight coordination of actions against new arrivals is needed. Eradication seems impossible, and prevention seems the only reliable measure, although this will be difficult in the face of global mobility.

A comparative anthropometric study of the position of the mental foramen in three populations.

METHOD: The position of the mental foramen was recorded in relation to the mandibular teeth and anatomical landmarks on the mandible in 76 Chinese, 46 European and 33 Indian skulls of known or calculated age at death. One way analysis of variance (ANOVA) with Tukey's test was used to compare the means of the three groups. RESULTS: The length of Indian mandibles was significantly smaller than that of Chinese (p <0.001) and European (p <0.05), but there was no significant difference between European and Chinese mandibles (p >0.05). The distance from the symphysis menti to the mental foramen was not significant in European and Indian mandibles (p >0.05), though the latter were significantly smaller than the Chinese (p <0.001). The distance from the mental foramen to the posterior border of the ramus of the mandible was significantly larger in Chinese and European skulls compared to that of Indian (p <0.01), there being no significant difference between European and Chinese (p >0.05). There was no significant difference in the relative position of the mental foramen (distance from symphysis menti to the mental foramen divided by the length of the mandible) between the Chinese and Indian mandibles (p >0.05) but there was a significant smaller difference between the European and both Chinese and Indian (p <0.001). The modal position of the foramen in the Chinese was in line with the long axis of the second premolar, while the European and Indian between the first and second premolar. CONCLUSION: The notion that the mental foramen lies between the first and second premolars can no longer be accepted. Population differences occur and preoperative radiographs are mandatory.

Mechanisms governing the responses to anthracnose pathogen in Juglans spp.

Juglans nigra and Juglans regia are two highly economically important species for wood and fruit production that are susceptible to anthracnose caused by Gnomonia leptostyla. The identification of genotypes resistant to anthracnose could represent a valid alternative to agronomic and chemical management. In this study, we analyzed 72 walnut genotypes that showed a variety of resistance phenotypes in response to natural infection. According to the disease severity rating and microsatellite fingerprinting analysis, these genotypes were divided into three main groups: (40) J. nigra resistant, (1) J. nigra susceptible, and (31) J. regia susceptible. Data on leaf emergence rates and analysis of in vivo pathogenicity indicated that the incidence of anthracnose disease in the field might be partially conditioned by two key factors: the age and/or availability of susceptible leaves during the primary infection of fungus (avoidance by late flushing) and partial host resistance. NBS profiling approach, based on PCR amplification with an adapter primer for an adapter matching a restriction enzyme site and a degenerate primer targeting the conserved motifs present in the NBS domain of NBS-LRR genes, was applied. The results revealed the presence of a candidate marker that correlated to a reduction in anthracnose incidence in 72 walnut genotypes.

Functional outcome of staged bilateral knee replacements.

INTRODUCTION: The aim of this study was to compare the functional outcome between the first and second knee replacement in patients undergoing staged bilateral total knee arthroplasty. METHODS: We identified 64 patients who had bilateral knee replacements and had at least one year of postoperative outcome studies. Data on pain scores, walking ability, use of walking aids, range of movement, instability, muscle strength, WOMAC® (Western Ontario and McMaster Universities) scores, SF-12 (Short Form 12) scores, American Knee Society radiological scores and length of hospital stay (LOS) were recorded. The difference in data between the first and second knee was assessed. RESULTS: Groups remained statistically comparable between the first and second operation. Four outcomes showed a significant difference between the second and first knee. The mean score for postoperative walking ability was 4.83 (second knee) vs 4.51 (first knee) (p =0.03). The mean score for postoperative walking aid requirement was 5.73 (second knee) vs 5.46 (first knee) (p=0.01). The mean postoperative SF-12 score was 54.26 (second knee) vs 52.45 (first knee) (p=0.04). The mean LOS was 4.73 days (second knee) vs 6.16 days (first knee) (p =0.05). All other data comparisons were statistically insignificant. CONCLUSIONS: Patients have a reduced LOS and continue to improve after the second procedure with regards to walking ability, use of walking aids and psychological wellbeing.

General dental practitioners' knowledge of polymerisation of resin-based composite restorations and light curing unit technology.

OBJECTIVE: Clinical successful use of resin-based composite restorations (RBCs) depends on knowledge of material and light curing unit (LCU) related factors. The purpose of this study was to evaluate general dental practitioners' knowledge of polymerisation of RBCs and LCU technology. METHODS: Members of the Active Research Group of the Faculty of General Dental Practice (UK) in England, Scotland and Wales engaged in primary dental care were sent a letter introducing the study and asking for their cooperation, followed by an email containing a link to the online survey questionnaire, hosted on Surveymonkey.com. The questionnaire enquired about current LCUs, and asked a series of questions on material science. RESULTS: Sixty-six percent of the 274 members contacted responded. Fifty-seven percent used LED units, 25% quartz tungsten halogen (QTH), and 1% plasma arc (missing: 17%). Thirty percent reported having access to a radiometer. Appropriate responses regarding the degree of conversion of composite and adhesive materials were given by 32% and 23% respectively, and 22% agreed that LED and QTH LCUs had comparable efficiency in polymerising composites. Thirty-three percent were aware that RBCs eluted substances that may have adverse local or systemic consequences. Fifty-eight percent stated that if polymerisation of RBC is slowed down, polymerisation stress will be lower, and 43% said that polymerisation shrinkage will be reduced if the degree of conversion is reduced. Knowledge (measured by appropriate responses to these questions) was not related to years since qualification (r=-0.05, n=168, p=0.53). CONCLUSION: The study suggests that dentists' knowledge of curing RBC restorations and LCUs is poor. This indicates that there is a need for training and guidance in this aspect of primary dental care.

Echocardiographic values in clinically healthy adult dogue de Bordeaux dogs.

OBJECTIVES: To assess the influence of body surface area, age and gender on echocardiographic parameters and to establish echocardiographic reference values for dogue de Bordeaux dogs. METHODS: Thirty-nine healthy dogue de Bordeaux dogs of both sexes, older than one year, were recruited and 31 of these were included in the study. The classic linear regression model proved to be the best way to analyse the data. The reference limits of the echocardiographic measurements were calculated using the regression equations. The difference between the mean values of body surface area in both gender groups was evaluated by using one-way ANOVA. RESULTS: A significant correlation was seen between several echocardiographic parameters and body surface area or body surface area and age, and high coefficients of determination (R2) were found. No effect of gender was detected on echocardiographic variables, except for the thickness of the left ventricular posterior wall at end diastole. CLINICAL SIGNIFICANCE: The echocardiographic parameters related to body surface area, in the absence of correlation with other independent variables (gender and age) should be interpreted with caution because their variation could be significant for the presence of heart disease. The proposed statistical model allows estimation of echocardiographic parameters in dogue de Bordeaux dogs with different body surface areas and ages.

Pharmacokinetic and pharmacodynamic characterization of an oral lysophosphatidic acid type 1 receptor-selective antagonist.

Lysophosphatidic acid (LPA) is a bioactive phospholipid that signals through a family of at least six G protein-coupled receptors designated LPA1₋6. LPA type 1 receptor (LPA1) exhibits widespread tissue distribution and regulates a variety of physiological and pathological cellular functions. Here, we evaluated the in vitro pharmacology, pharmacokinetic, and pharmacodynamic properties of the LPA1-selective antagonist AM095 (sodium, {4'-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-biphenyl-4-yl}-acetate) and assessed the effects of AM095 in rodent models of lung and kidney fibrosis and dermal wound healing. In vitro, AM095 was a potent LPA1 receptor antagonist because it inhibited GTPγS binding to Chinese hamster ovary (CHO) cell membranes overexpressing recombinant human or mouse LPA1 with IC50 values of 0.98 and 0.73 µM, respectively, and exhibited no LPA1 agonism. In functional assays, AM095 inhibited LPA-driven chemotaxis of CHO cells overexpressing mouse LPA1 (IC50= 778 nM) and human A2058 melanoma cells (IC50 = 233 nM). In vivo, we demonstrated that AM095: 1) had high oral bioavailability and a moderate half-life and was well tolerated at the doses tested in rats and dogs after oral and intravenous dosing, 2) dose-dependently reduced LPA-stimulated histamine release, 3) attenuated bleomycin-induced increases in collagen, protein, and inflammatory cell infiltration in bronchalveolar lavage fluid, and 4) decreased kidney fibrosis in a mouse unilateral ureteral obstruction model. Despite its antifibrotic activity, AM095 had no effect on normal wound healing after incisional and excisional wounding in rats. These data demonstrate that AM095 is an LPA1 receptor antagonist with good oral exposure and antifibrotic activity in rodent models.

A novel, orally active LPA(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model.

BACKGROUND AND PURPOSE: The aim of this study was to assess the potential of an antagonist selective for the lysophosphatidic acid receptor, LPA(1), in treating lung fibrosis We evaluated the in vitro and in vivo pharmacological properties of the high affinity, selective, oral LPA(1)-antagonist (4'-{4-[(R)-1-(2-chloro-phenyl)-ethoxycarbonylamino]-3-methyl-isoxazol-5-yl}-biphenyl-4-yl)-acetic acid (AM966). EXPERIMENTAL APPROACH: The potency and selectivity of AM966 for LPA(1) receptors was determined in vitro by calcium flux and cell chemotaxis assays using recombinant and native cell cultures. The in vivo efficacy of AM966 to reduce tissue injury, vascular leakage, inflammation and fibrosis was assessed at several time points in the mouse bleomycin model. KEY RESULTS: AM966 was a potent antagonist of LPA(1) receptors, with selectivity for this receptor over the other LPA receptors. In vitro, AM966 inhibited LPA-stimulated intracellular calcium release (IC(50)= 17 nM) from Chinese hamster ovary cells stably expressing human LPA(1) receptors and inhibited LPA-induced chemotaxis (IC(50)= 181 nM) of human IMR-90 lung fibroblasts expressing LPA(1) receptors. AM966 demonstrated a good pharmacokinetic profile following oral dosing in mice. In the mouse, AM966 reduced lung injury, vascular leakage, inflammation and fibrosis at multiple time points following intratracheal bleomycin instillation. AM966 also decreased lactate dehydrogenase activity and tissue inhibitor of metalloproteinase-1, transforming growth factor beta1, hyaluronan and matrix metalloproteinase-7, in bronchoalveolar lavage fluid. CONCLUSIONS AND IMPLICATIONS: These findings demonstrate that AM966 is a potent, selective, orally bioavailable LPA(1) receptor antagonist that may be beneficial in treating lung injury and fibrosis, as well as other diseases that are characterized by pathological inflammation, oedema and fibrosis.