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About 10% of Europe's surface area is prone to rapid flooding of rivers confined in valleys. The devastating potential of such floods is exacerbated by the deficits of existing gauging networks, including low station densities and recording frequencies, and lack of information beyond stage height. Here, we use seismic data of the July 2021 Ahrtal flood, Germany, to extract information to complement sparse hydrometric data, and to reconstruct the rapid evolution of this fatal event. We show that a seismic station can deliver essential flood metrics such as magnitude, propagation velocity and debris transport rate. These seismic products provide high resolution insight to the non‐linear flood behavior. We argue that an approach combining distributed low‐cost seismometers with existing seismic stations, can provide important real time data on future catastrophic floods and associated hazards in upland catchments, offering precious response time also in currently ungauged landscapes. Plain Language Summary: Rapidly evolving floods are a major hazard for 10% of European landscapes. They are hard to adequately detect and describe by the classic gauge station scheme, but seismic sensors provide a valuable alternative to this difficulty. A seismometer can sense a flood like the devastating one that hit the Ahr valley, Germany, in July 2021 up to 1.5 km away. The seismic footprint of the flood allows to provide information on flood magnitude, velocity and trajectory at sub‐minute resolution and at near real time. We show how this new approach can be utilized for future flood protection. Key Points: Seismic sensing of valley confined floods improves classic detection approachesNear‐real time information on flood magnitude, trajectory, and velocityGate keeper seismometer networks can improve flood risk management in Europe [ABSTRACT FROM AUTHOR]

This paper introduces a generative model for 3D surfaces based on a representation of shapes with mean curvature and metric, which are invariant under rigid transformation. Hence, compared with existing 3D machine learning frameworks, our model substantially reduces the influence of translation and rotation. In addition, the local structure of shapes will be more precisely captured, since the curvature is explicitly encoded in our model. Specifically, every surface is first conformally mapped to a canonical domain, such as a unit disk or a unit sphere. Then, it is represented by two functions: the mean curvature half‐density and the vertex density, over this canonical domain. Assuming that input shapes follow a certain distribution in a latent space, we use the variational autoencoder to learn the latent space representation. After the learning, we can generate variations of shapes by randomly sampling the distribution in the latent space. Surfaces with triangular meshes can be reconstructed from the generated data by applying isotropic remeshing and spin transformation, which is given by Dirac equation. We demonstrate the effectiveness of our model on datasets of man‐made and biological shapes and compare the results with other methods. [ABSTRACT FROM AUTHOR]

Hepatitis C virus ( HCV) is a human hepatotropic virus, but many hepatoma cell lines are not permissive to this virus. In a previous study, we observed that SNU-182, SNU-398 and SNU-449 hepatoma cell lines were nonpermissive to HCV. To understand the nonpermissivity, we evaluated the ability of each cell line to support the different steps of HCV life cycle (entry, replication and production of infectious particles). Using retroviral pseudoparticles pseudotyped with HCV envelope proteins and recombinant HCV produced in cell culture, we observed that low level or absence of claudin-1 (CLDN1) expression limited the viral entry process in SNU-182 and SNU-398 cells, respectively. Our results also showed that supplementation of the three cell lines with miR-122 partly restored the replication of a JFH1 HCV replicon. Finally, we observed that expression of apolipoprotein E (ApoE) was very low or undetectable in the three cell lines and that its ectopic expression permits the production of infectious viral particles in SNU-182 and SNU-398 cells but not in SNU-449 cells. Nevertheless, the supplementation of SNU-182, SNU-398 and SNU-449 cells with CLDN1, miR-122 and ApoE was not sufficient to render these cells as permissive as HuH-7 cells. Thus, these cell lines could serve as cell culture models for functional studies on the role of CLDN1, miR-122 and ApoE in HCV life cycle but also for the identification of new restriction and/or dependency host factors essential for HCV infection. [ABSTRACT FROM AUTHOR]

Intravascular imaging provides new insights into the condition of vessel walls. This is crucial for cerebrovascular diseases including stroke and cerebral aneurysms, where it may present an important factor for indication of therapy. In this work, we provide new information of cerebral artery walls by combining ex vivo optical coherence tomography (OCT) imaging with histology data sets. To overcome the obstacles of deflated and collapsed vessels due to the missing blood pressure, the lack of co-alignment as well as the geometrical shape deformations due to catheter probing, we developed the new image processing method virtual inflation. We locally sample the vessel wall thickness based on the (deflated) vessel lumen border instead of the vessel's centerline. Our method is embedded in a multi-view framework where correspondences between OCT and histology can be highlighted via brushing and linking yielding OCT signal characteristics of the cerebral artery wall and its pathologies. Finally, we enrich the data views with a hierarchical clustering representation which is linked via virtual inflation and further supports the deduction of vessel wall pathologies. [ABSTRACT FROM AUTHOR]

Background and Objective Matrix metalloproteinase-8 ( MMP-8) is involved in a wide range of pathologies including periodontitis and cardiovascular diseases ( CVD). The association between periodontitis and CVD has been repeatedly recognized. The aim of the study was to analyze to what extent circulating active MMP-8 ( aMMP-8) is associated with periodontal disease status and oral fluid aMMP-8 levels in otherwise healthy subjects. Material and Methods In a cross-sectional study, aMMP-8 was measured in serum of 59 volunteers, comprising 19 periodontally healthy subjects, 20 patients with gingivitis as well as 20 with periodontitis. All study subjects were characterized regarding aMMP-8 concentrations in different oral fluids as well as clinically and microbiologically with respect to periodontal disease. aMMP-8 levels in gingival crevicular fluid were measured using the enzyme-linked immunosorbent assay. Saliva enzyme levels as well as circulating aMMP-8 were determined by a time-resolved immunofluorometric assay. Both methods utilized the same monoclonal antibodies. Correlation and regression analyses were performed to study the potential association between serum aMMP-8 and oral parameters. Results Oral aMMP-8 levels were significantly higher in patients with periodontitis compared to periodontally healthy or gingivitis subjects. Highest serum aMMP-8 concentration was also found in the periodontitis group. The serum levels correlated significantly with oral aMMP-8 as well as with clinical parameters in a dose-dependent manner. These results were confirmed in a multivariate regression analysis. After adjusting for potential confounders, saliva aMMP-8 concentrations as well as periodontitis severity were significant predictors of serum aMMP-8. Conclusion The associations between circulating aMMP-8 and oral aMMP-8 as well as periodontal findings in a dose-dependent manner may contribute to linking periodontal disease with increased CVDsusceptibility. [ABSTRACT FROM AUTHOR]

Five Iron Age ceramic lamps from a tomb at the site of Sahab in the south-eastern part of central Jordan were analysed using gas chromatography - mass spectrometry (GC-MS). The results of this study provide data on the type of fuel used in three of these lamps. The study proposes that animal fat, possibly of ruminant origin, was used in three Early Iron Age II lamps. The material used in the other two Iron Age I lamps could not be determined due to the absence of diagnostic biomarkers. The data obtained from the lamps can be put in conjunction with the archaeological evidence on the availability of domestic animals and, most probably, use of their products at the site of Sahab during the Iron Age. [ABSTRACT FROM AUTHOR]

Background and Objectives Severe periodontitis affects about 10% of the world population. In addition, associations between periodontitis and systemic diseases exist. Therefore, the diagnosis should be made quickly and at an early stage. Matrix metalloproteinase-8 (MMP-8) is the most prominent collagenase found in inflamed periodontal tissues. Its active form (aMMP-8) is increasingly used as a diagnostic biomarker. Aim of the present study is to evaluate the diagnostic accuracy of a novel aMMP-8 point-of-care (POC) test in comparison to the standard laboratory test to diagnose the disease rapidly and reliably. Material and Methods In a prospective, mono-center, double-blinded, case-control study, participants with healthy gums ( n = 35), gingivitis ( n = 60) and periodontitis ( n = 35) were investigated before and after therapy. Beside clinical variables for plaque and inflammation, aMMP-8 concentrations were determined in oral rinsing specimens by the enzyme-linked immunosorbent assay (ELISA) and by POC. Positive and negative percent agreements with their exact one-sided lower 95% confidence limits were calculated. Results Of 130 participants, 111 finished the study. Overall, positive percent agreements were 75.8% (57.7-88.9) before treatment and 73.7% (56.9-86.6) after treatment. Negative percent agreements were 92.8% (85.7-97.0) before and 93.3% (85.1-97.8) after treatment. Positive test results (POC and ELISA) ranged from 5.7% to 8.6% in healthy patients, 25.0-29.8% in patients with gingivitis and 40.0-48.1% in patients with periodontitis. Patients who had positive aMMP-8 test results (POC) showed higher scores for plaque and inflammation. Conclusions The novel POC test to detect aMMP-8 has proved to agree strongly with the standard method, ELISA. The test can be recommended to screen patients at risk for periodontitis in dental offices, at the general practitioner and at specialists for associated diseases. [ABSTRACT FROM AUTHOR]

Background: Injection of the noxious peptide Bv8 has previously been shown to induce a biphasic thermal hyperalgesia in rodents, the first peak presumably due to peripheral sensitization. This hypothesis has never been directly confirmed. We have assessed whether Bv8 can indeed sensitize peripheral nerve fibres in the mouse to heat.Methods: We used recordings from single cutaneous fibres, cutaneous calcitonin gene-related peptide (CGRP) release and immunostaining in nerves and plantar skin to evaluate the Bv8 effects on cutaneous nerves.Results: Application of Bv8 at nanomolar concentrations (30-310 nmol/L) to skin preparations significantly increased the heat-induced discharge, the heat-induced afterdischarge and reduced threshold temperature of single unmyelinated polymodal fibres. Furthermore, application of Bv8 to hind-paw skin flaps or trigeminal ganglia significantly elevated their heat-induced CGRP release. Capsaicin-induced and to a lesser extent also KCl-induced CGRP releases were also augmented after Bv8 treatment. Immunohistochemistry revealed co-localization of prokineticin 2 (Bv8 ortholog in rodents) and CGRP in both plantar skin and nerve tissues. These results confirm that Bv8 sensitizes cutaneous nerve endings to heat, partly, although not exclusively through TRPV1 activation.Conclusion: Our results thus support the hypothesis that the first hyperalgesic phase to follow Bv8 injection to hind paws of intact animals is due to peripheral sensitization of nociceptors. WHAT DOES THIS STUDY ADD?: Our data provide mechanistic insights into the effect Bv8 application exerts on afferent nerve endings and into the concomitant development of thermal hyperalgesia. [ABSTRACT FROM AUTHOR]

Background: Tooth extractions lead to morphological changes of the alveolar ridge. For oral rehabilitation sufficient bone volume of the alveolar ridge is required. This clinical study compared the ability of Bio-Oss® Collagen to autogenous bone to preserve bone volume after tooth extraction.Methods: A total of 17 patients with 20 extraction sites were examined. After extraction, 10 sockets were each filled with either autogenous bone or Bio-Oss® Collagen and covered with a resorbable membrane. The width of the alveolar ridge was measured postoperatively, and after 4 and 6 months respectively. Prior to implant insertion, a bone biopsy was taken from the grafted sites and evaluated histologically.Results: The width of the alveolar ridge in the Bio-Oss® Collagen group decreased about 5.33 ± 6.62% after 4 months and 9.45 ± 10.51% after 6 months. The reduction in the group augmented with autogenous bone was 14.31 ± 21.41% after 4 months and 19.17 ± 8.38% after 6 months. No statistically significant differences were observed. The histological examination showed comparable area fractions of total bone in both groups (Bio-Oss® Collagen: 59.99 ± 24.23%; autogenous bone: 61.55 ± 25.13%; p = 1.0).Conclusions: The present study demonstrated that autogenous bone and Bio-Oss® Collagen are suitable for ridge preservation. However, both techniques could not entirely prevent tissue volume loss. [ABSTRACT FROM AUTHOR]

Background: When a child is diagnosed with autism, parents are faced with the task of choosing from many different intervention options. To find information about the options available, parents turn to a number of different sources. This study explores parents' (n = 23) intervention decisionmaking processes and information preferences following the diagnosis of ASD for their child. Methods: Qualitative thematic analysis of verbatim transcripts from interviews and focus groups involving parents of children with an autism diagnosis was undertaken. Results: Analysis of the results revealed that there are concurrent emotional and pragmatic intervention 'journeys' undertaken by parents post diagnosis, which encompass the primary themes of: (1) information sources used, (2) parents' information preferences and (3) factors influencing intervention decision making. Parents described a journey from the point of diagnosis that involved seeking information on ASD interventions from multiple sources, with the Internet being the primary source. They were overwhelmed by the sheer volume of information available, and their preferences for information varied according to their stage in the journey post diagnosis. Parents had a 'trial and error' approach to choosing ASD interventions, with confidence increasing as they became more familiar with their child's condition, and had opportunities to explore numerous information sources about their child's diagnosis. While confidence increased over time, consideration of the effectiveness or evidence supporting interventions remained largely absent throughout the journey. Conclusion: This study highlights the need for parents of children with ASD to be supported to make informed intervention decisions, particularly with consideration for research evidence. [ABSTRACT FROM AUTHOR]

During the last years, two new cardiovascular drug classes, namely inhibitors of DPP IV or neprilysin, have been developed. In both cases, there is clinical evidence for their potential to induce angioedema as known already from blockers of the renin-angiotensin-aldosterone system ( RAAS). The majority of angioedema induced by DPP IV inhibitors occurs during concomitant treatment with ACEi and is therefore likely mediated by overactivation of bradykinin type 2 receptors (B2). In striking contrast, the molecular pathways causing angioedema induced by neprilysin inhibitors, that is, sacubitril, are unclear, although a contribution of bradykinin appears likely. Nevertheless, there is no clinical evidence suggesting that inhibition of B2 might relieve the symptoms and/or prevent invasive treatment including coniotomy or tracheotomy in angioedema caused by these drugs. Therefore, the risk of angioedema should always be considered, especially in ambulatory care situations where patients have no rapid access to intensive care. [ABSTRACT FROM AUTHOR]

Aim Intact surface active agent (surfactant) composed of surfactant-associated proteins ( SPs) and lipids is necessary for respiration and prevents alveoli from collapsing. CD26, a transmembrane glycoprotein exerting dipeptidyl peptidase activity ( DPP4), highly expressed in lung parenchyma, is involved in inflammatory processes. A pharmacological inhibition of DPP4 influenced not only the inflammation but also elevated the SPs. Thus, DPP4 inhibitors may be a novel drug for treatment of diseases with surfactant deficiency. Therefore, we tested firstly the hypothesis that DPP4 inhibitors increase the expression of SPs in healthy rats. Methods SP mRNA and protein expression were determined different times after nebulization of aerosolized DPP4 inhibitors [L-isoleucine-thiazolidide (L-Ile-Thia), L-valine-pyrrolidide (L-Val-Pyrr)], budesonide, saline or stereoisomers. Results Compared with negative controls (1) L-Ile-Thia as well as budesonide led to a significant higher and L-Val-Pyrr had the tendency to a significant higher expression of SP-A mRNA 6 h after nebulization, (2) the expression of SP-D mRNA increased significantly 6 h after nebulization with L-Ile-Thia and 3 and 6 h after nebulization with Val-pyrr, (3) SP-B mRNA levels showed significantly higher values 3 and 6 h after nebulization with L-Val-Pyrr, (4) protein levels of SP-A, SP-B and SP-C were elevated significantly 6 h after nebulization with L-Val-Pyrr as well as with budesonide, and (5) phospholipids were also increased in response to DPP4 inhibition; the minimal surface tension was comparable. Conclusion DPP4 inhibition influence differently the expression of surfactant proteins in healthy rats and may be suitable to elevate surfactant synthesis in different diseases accompanied with surfactant deficiencies. [ABSTRACT FROM AUTHOR]

At 18 months, children engage in a variety of social behaviors that reflect their nascent ability to understand the intentions of other people (e.g. joint attention, empathy, cooperation and self-recognition). Although numerous contextual factors have been shown to predict social cognition in young children, the genetic underpinnings of social-cognitive traits has been understudied in this age group. Owing to the known effects of oxytocin on adult social cognition and psychopathology, this study hypothesized that variability in the oxytocin receptor gene ( OXTR) would be associated with social cognition in children at 18 months. Participants consisted of 350 children (182 males; 168 females) who were part of an ongoing longitudinal study that aimed to assess environmental and genetic contributions to children's cognitive and socio-emotional functioning. At 18 months, social cognition was measured using previously validated and developmentally sensitive tasks assessing children's joint attention, empathy, cooperation and self-recognition. Five potentially functional OXTR variants were genotyped: rs1042778, rs2254298, rs11131149, rs237897 and rs237899. A family-based association design was used to control for population admixture and stratification, and additional non-genomic covariates were controlled. Results showed that variability in rs11131149 was significantly associated with social cognition ( P = 0.009), with more copies of the major allele related to higher social cognition, and more copies of the minor (risk) allele associated with lower social cognition. A haplotype consisting of rs11131149-rs2254298 was also associated with social cognition ( P = 0.020). Implications for normative and pathological development are discussed, and key areas for future research are proposed. [ABSTRACT FROM AUTHOR]

Background Two transient receptor potential ( TRP) channels, TRPV1 and TRPA1, have been physiologically studied with regard to noxious heat transduction. Evidence argues against these channels as sole transducers of noxious heat or cold, respectively. Moreover, in submammalian species the TRPA1 orthologue shows heat sensitivity. Methods In vitro, single-fibre and compound action potential recordings from C-fibres as well as measurements of stimulated cutaneous CGRP release are combined with behavioural experiments to assess heat responsiveness in wild type mice, TRPA1 and TRPV1 as well as double-null mutants. Results Heat thresholds of cutaneous C-mechano-heat sensitive fibres were significantly higher in TRPA1−/− (43 ° C) than +/+ (40 ° C) mice, and averaged heat responses were clearly weaker, whereas TRPV1−/− showed normal heat thresholds and responses (up to 46 ° C). Compound action potential recordings revealed much less activity-dependent slowing of conduction velocity upon noxious heat stimulation in TRPA1−/− and a delayed deficit in TRPV1−/− in comparison to controls. Heat-induced calcitonin gene-related peptide release was reduced in TRPV1−/− but not TRPA1−/− animals. Paw withdrawal latencies to radiant heat were significantly elevated in TRPA1−/−, more so in TRPV1−/− animals. In general, double-null mutants were similar to TRPV1−/− except for the single-fibre heat responses which appeared as weak as in TRPA1−/−. Conclusions Our results indicate that in addition to TRPV1, TRPA1 plays a role in heat nociception, in particular in definition of the heat threshold, and might therefore serve as a therapeutic target in acute inflammatory pain. [ABSTRACT FROM AUTHOR]

Background The For Angioedema Subcutaneous Treatment ( FAST)-2, a phase III, double-blind, randomized, multicenter, placebo-controlled study (ClinicalTrials.gov identifier: NCT00500656), established the efficacy and safety of single injections of icatibant, a bradykinin B2 receptor antagonist, in the treatment of hereditary angioedema ( HAE) attacks. Here, we evaluate the efficacy and safety of repeated treatment with icatibant in adult patients experiencing HAE attacks during the FAST-2 open-label extension ( OLE) phase. Methods Patients completing the controlled phase were eligible to participate in the OLE phase and receive open-label icatibant (30 mg subcutaneously) for the treatment of cutaneous, abdominal, and/or laryngeal HAE attack(s) severe enough to warrant treatment. Time to onset of symptom relief was calculated for each attack. Descriptive analyses (median, 95% CIs) were performed for all attacks; post hoc analyses were conducted in patients with at least five icatibant-treated attacks throughout the FAST-2 OLE phase. Safety was also monitored. Results Fifty-four patients received icatibant for 374 attacks (176 cutaneous, 168 abdominal, and 30 laryngeal). For cutaneous and/or abdominal attacks (attacks 2-5), the median times to onset of symptom relief ranged between 2.0 and 2.5 h. For all laryngeal attacks, the median times to regression (start of improvement) of symptoms ranged between 0.3 and 4.0 h. Post hoc analyses showed that the overall median time to onset of symptom relief was 2.0 h. Overall, 89.8% of attacks resolved with a single icatibant injection. No drug-related serious adverse events were reported. Conclusions These findings have demonstrated the efficacy and safety of repeated icatibant treatment for HAE attacks. [ABSTRACT FROM AUTHOR]

ABSTRACT This contribution presents results of the chemical coupling reaction between the poly(tetrafluoroethylene) (PTFE) micropowder and oils. For the preparation of such dispersions, the reaction between the perfluoroalkyl(peroxy) radicals, which are generated by irradiation of PTFE in presence of oxygen, and the olefinic unsaturated groups of the oils was used. The modified and charged PTFE micropowder particles prevent the agglomeration by repulsion and therefore also the sedimentation. Processes of structural formation in the dispersions were studied by rheological characterisation and observed into dependence of the PTFE concentration and the chosen kind of PTFE. The tribological characterisation should explore the influence of the chemical coupling reaction between PTFE and oil in the dispersions. In addition, the tribological effect of the dispersions as an additive in a synthetic lubricant was investigated. The results obtained were discussed from rheological and tribological point of view taking into account the effect of the chemical coupling in dependence of the oils used and the chosen PTFE type. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Kraft-Neumärker M, Lorenz K, Koch R, Hoffmann T, Mäntylä P, Sorsa T, Netuschil L. Full-mouth profile of active MMP-8 in periodontitis patients. J Periodont Res 2012; 47: 121-128. © 2011 John Wiley & Sons A/S Background and Objective: MMP-8 in gingival crevicular fluid is considered as a protease with high destructive potential because of its ability to degrade collagen in periodontitis-affected patients. The aim of this study was to investigate whether there was a relationship between clinical diagnostic parameters and the concentration of active MMP-8 (aMMP-8) in gingival crevicular fluid in a site-level full-mouth analysis. Based on these data, the prognostic value of aMMP-8 levels in relation to pocket depth may be evaluated. Material and Methods: Clinical measurements of pocket depth, bleeding on probing (BOP), plaque index (PlI) and gingival index (GI), as well as samples of gingival crevicular fluid, were obtained from four sites of each tooth of nine healthy female patients with chronic generalized periodontitis. The aMMP-8 concentration in gingival crevicular fluid was quantified by ELISA using specific monoclonal antibodies. Multiple linear regression models for the single measures of aMMP-8 and pocket depth were calculated with GI and BOP as additional variables. Results: Between 92 and 112 recordings were obtained for each parameter in each patient. Mean values of between 31.5 and 88.8% were calculated for pocket depths of ≥ 4 mm. Mean pocket depths ranged from 3.11 to 4.73 mm, the mean BOP values ranged from 34.0 to 96.7% and the mean full-mouth gingival crevicular fluid aMMP-8 concentration ranged from 3.2 to 23.7 ng/mL. Conclusion: In this sample of female periodontitis patients, a broad range of intra-individual and interindividual aMMP-8 values was found. Although the explained variance was rather weak, a statistically significant relationship between aMMP-8 and pocket depth was proven. [ABSTRACT FROM AUTHOR]

Histochemical screening of 30 Rosaceae genera representing all classic subfamilies demonstrated flavan-3-ols (catechins) as general secondary metabolites in roots of Rosaceae. Semi-quantitative LC-MS analyses confirmed the presence of catechin, epicatechin and various dimeric flavan-3-ols (also representing higher polymeric proanthocyanidins) as prominent polyphenols in root tips of Fragaria (strawberry), Malus (apple), Rosa (rose), Pyrus (pear) and Prunus (plum). Distinct patterns of flavan-3-ol distribution at the cellular level were found in strawberry ( Fragaria × ananassa) and apple ( Malus × domestica) root tips. The calyptras (root caps) showed the most prominent flavan-3-ol staining for these two genera. Border cells of Fragaria and Malus, as first demonstrated here for Rosaceae, were also found to contain flavan-3-ols. Transcript analyses with cDNA demonstrated root expression of known flavonoid genes expressed in the respective fruits and leaves. Primarily, this proves in situ biosynthesis of flavan-3-ols in these roots. Knowledge of the distinct cellular distribution patterns and their in situ biosynthesis in roots provides a basis for analysis of the functional roles of Rosaceae root flavan-3-ols. [ABSTRACT FROM AUTHOR]

Background and Purpose: Clinical results of osanetant and talnetant (selective-NK₃ antagonists) indicate that blocking the NK₃ receptor could be beneficial for the treatment of schizophrenia. The objective of this study was to characterize the in vitro and in vivo properties of a novel dual NK₁/NK₃ antagonist, RO4583298 (2-phenyl-N-(pyridin-3-yl)-N-methylisobutyramide derivative).Experimental Approach: RO4583298 in vitro pharmacology was investigated using radioligand binding ([³H]-SP, [³H]-osanetant, [³H]-senktide), [³H]-inositol-phosphate accumulation Schild analysis (SP- or [MePhe⁷]-NKB-induced) and electrophysiological studies in guinea-pig substantia nigra pars compacta (SNpc). The in vivo activity of RO4583298 was assessed using reversal of GR73632-induced foot tapping in gerbils (GFT; NK₁) and senktide-induced tail whips in mice (MTW; NK₃).Key Results: RO4583298 has a high-affinity for NK₁ (human and gerbil) and NK₃ (human, cynomolgus monkey, gerbil and guinea-pig) receptors and behaves as a pseudo-irreversible antagonist. Unusually it binds with high-affinity to mouse and rat NK₃, yet with a partial non-competitive mode of antagonism. In guinea-pig SNpc, RO4583298 inhibited the senktide-induced potentiation of spontaneous activity of dopaminergic neurones with an apparent non-competitive mechanism of action. RO4583298 (p.o.) robustly blocked the GFT response, and inhibited the MTW.Conclusions and Implications: RO4583298 is a high-affinity, non-competitive, long-acting in vivo NK₁/NK₃ antagonist; hence providing a useful in vitro and in vivo pharmacological tool to investigate the roles of NK₁ and NK₃ receptors in psychiatric disorders. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To compare three different methods of falls reporting and examine the characteristics of the data missing from the hospital incident reporting system. DESIGN: Fourteen-month prospective observational study nested within a randomized controlled trial. SETTING: Rehabilitation, stroke, medical, surgical, and orthopedic wards in Perth and Brisbane, Australia. PARTICIPANTS: Fallers (n=153) who were part of a larger trial (1,206 participants, mean age 75.1±11.0). MEASUREMENTS: Three falls events reporting measures: participants' self-report of fall events, fall events reported in participants' case notes, and falls events reported through the hospital reporting systems. RESULTS: The three reporting systems identified 245 falls events in total. Participants' case notes captured 226 (92.2%) falls events, hospital incident reporting systems captured 185 (75.5%) falls events, and participant self-report captured 147 (60.2%) falls events. Falls events were significantly less likely to be recorded in hospital reporting systems when a participant sustained a subsequent fall, ( P=.01) or when the fall occurred in the morning shift ( P=.01) or afternoon shift ( P=.01). CONCLUSION: Falls data missing from hospital incident report systems are not missing completely at random and therefore will introduce bias in some analyses if the factor investigated is related to whether the data is missing. Multimodal approaches to collecting falls data are preferable to relying on a single source alone. [ABSTRACT FROM AUTHOR]

Aim: We assessed the prevalence and extent of periodontitis in Germany. Furthermore, region- and gender-specific differences in periodontal disease prevalence were evaluated. Material and Methods: The fourth German Dental Health Survey is a national cross-sectional survey conducted in 2005. Nine hundred and twenty-five adults (35-44 years) and 1040 seniors (65-74 years) were examined. The survey comprised social- and health-related interviews and dental examinations. Probing depth (PD) and clinical attachment loss (CAL) were assessed at three sites at 12 index teeth. Results: Prevalence of CAL3 mm was found in 95.0% in adults and 99.2% in seniors with 68.7% and 91.4% of teeth being affected, respectively. PD4 mm was prevalent in 76.9% and 87.7% in both age groups, respectively. According to the CDC definition considering mesiobuccal and distolingual sites, prevalence of periodontitis was 70.9% and 87.4% in both age cohorts, with one-fourth and one-half presenting severe forms, respectively. Periodontal prevalence was significantly higher in male subjects and East German subjects. Conclusions: Periodontitis was highly prevalent in German adults. To reduce periodontal burden, treatment of periodontal diseases and continuous maintenance should become an integral part in dental practice. Furthermore, health recommendations should be implemented at the community, professional, and individual level. [ABSTRACT FROM AUTHOR]

Aim: We aimed to assess the association of different genotypes with increased aggressive periodontitis susceptibility by studying functional relevant variants in the pathogen-recognition receptor Toll-like receptor 4 (TLR4) and variants in the promoter region of the pro-inflammatory cytokine interleukin-18 (IL-18). Material and Methods: One hundred and eleven patients with aggressive periodontitis and 80 periodontally healthy controls were genotyped for four functional variants in the TLR4 gene (c.896A>G and c.1196C>T) and in the IL-18 promoter (c.-368G>C and c.-838C>A). The genotype and allele frequencies, as well as the frequency of combined genotypes were compared between study groups. Results: There were no statistical differences in genotype and allele frequencies within the four variants between the groups. All study subjects were further classified into carriers and non-carriers of at least one variant of both genes. The logistic regression analysis adjusted for gender and smoking showed no association between carrier status of at least one variant of both genes and periodontal status (OR=1.41, 95% CI: 0.43-4.70). Conclusions: Our results reject the hypothesis that functionally relevant IL-18 and TLR4 gene mutations have a major effect on aggressive periodontitis susceptibility alone or in combination. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Comparison of the outcomes of a combination of an enamel matrix derivative and a synthetic bone graft (EMD/SBC) with EMD alone in wide intra-bony defects. MATERIAL AND METHODS: Seventy-three patients with chronic periodontitis were recruited in five centres in Germany. All patients had one wide intra-bony defect of >/=4 mm. Surgical procedures involved microsurgical technique and the modified papilla preservation flap. After debridement, defects were randomly assigned to EMD/SBC (test) or EMD (control). Assessments at baseline and after 6 months included bone sounding, attachment levels, probing pocket depths, bleeding on probing and recessions. Early wound-healing, adverse effects and patients' perceptions were also recorded. RESULTS: Both treatment modalities led to significant clinical improvements. Change in bone fill 6 months after surgery was 2.0 mm (+/- 2.1) in the test group and 2.1 mm (+/- 1.2) in the control group. A gain in clinical attachment of 1.3 mm (+/- 1.8) in the test group and 1.8 mm (+/- 1.6) in the control group was observed. One week after surgery, primary closure was maintained in 95% of the test sites and 100% of the control sites. No differences in patients' perceptions were found. CONCLUSION: The results of the present study showed similar clinical outcomes following both treatment modalities. [ABSTRACT FROM AUTHOR]

AIM: The autosomal-recessive Papillon-Lefèvre syndrome (PLS) is characterized by severe aggressive periodontitis, combined with palmoplantar hyperkeratosis, and is caused by mutations in the Cathepsin C (CTSC) gene. This study aimed to identify CTSC mutations in different PLS phenotypes, including atypical forms and isolated pre-pubertal aggressive periodontitis (PAP). MATERIAL AND METHODS: Thirteen families with different phenotypes were analysed by direct sequencing of the entire coding region and the regulatory regions of CTSC. The function of novel mutations was tested with enzyme activity measurements. RESULTS: In 11 of 13 families, 12 different pathogenic CTSC mutations were found in 10 typical PLS patients, three atypical cases and one PAP patient. Out of four novel mutations, three result in protein truncation and are thus considered to be pathogenic. The homozygous c.854C>T nucleotide exchange (p.P285L) was associated with an almost complete loss of enzyme activity. The observed phenotypic heterogeneity could not be associated with specific genotypes. CONCLUSIONS: The phenotypic variability of the PLS associated with an identical genetic background may reflect the influence of additional genetic or environmental factors on disease characteristics. CTSC mutation analyses should be considered for differential diagnosis in all children suffering from severe aggressive periodontitis. [ABSTRACT FROM AUTHOR]

Angioedema is an underestimated clinical problem. Many cases are nonallergic reactions, e.g. bradykinin-induced angioedema caused by genetic defects and angiotensin-converting enzyme (ACE) inhibitors. This difference is crucial for successful therapy, in particular when complete emergency care is not available. Five important forms of nonallergic angioedema can be distinguished: hereditary (HAE), acquired (AAE), renin-angiotensin-aldosterone system (RAAS)-blocker-induced (RAE), pseudoallergic angioedema (PAE) and idiopathic angioedema (IAE). Some angioedema are present in the larynx and may cause death. A vast majority of nonallergic angioedema are RAE, particularly those caused by ACE inhibitors. It appears important to emphasize that in patients with complete intolerance to RAAS-blockers, cessation of RAAS-blockers is likely to be associated with increased cardiovascular risk. Currently, there is no published algorithm for diagnosis and treatment. Angioedema is usually treated by a conservative clinical approach using artificial ventilation, glucocorticoids and antihistamines. Today, a plasma pool C1-esterase inhibitor (C1-INH) concentrate is the therapy of choice in HAE. The current pharmacotherapy of nonallergic angioedema is not satisfactory, thus requiring the identification of effective agents in clinical trials. Recently, several new drugs were developed: a recombinant C1-INH, a kallikrein inhibitor (ecallantide) and a specific bradykinin-B2-receptor antagonist (icatibant). According to currently available reports, these drugs may improve the treatment of kinin-induced angioedema. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The CARD15 gene encodes a protein that acts as an intracellular receptor of bacterial products, thus playing an important role in the innate immune response. Recently, CARD15 gene variants have been identified as a cause of increased susceptibility to Crohn's disease. The present study aimed to examine a potential association of CARD15 gene variants with aggressive periodontitis susceptibility. MATERIAL AND METHODS: The three main known CARD15 gene variants (p.R702W, p.G908R, and p.L1007fsX1008) were analysed by direct sequencing of exon 4, 8, and 11 of the gene in a total of 86 generalized aggressive periodontitis patients in comparison with 67 healthy controls. RESULTS: The mutant allele frequencies of the CARD15 variants were low in the generalized aggressive periodontitis group as well as in the control group and not significantly different (R702W: 3.5% versus 5.2%; G908R: 1.7% versus 1.5%; L1007fsX1008: 5.2% versus 4.5%). Two rare variants (A755V and R791Q), previously described only in patients with other inflammatory diseases, were observed in three patients having aggressive periodontitis but not in controls. CONCLUSIONS: Unlike in Crohn's disease, our results did not show an association between the three main CARD15 mutations and aggressive periodontitis. The role of rare variants remains unclear. [ABSTRACT FROM AUTHOR]

In a well-established murine abortion model, stress is thought to trigger fetal rejection by inducing a proinflammatory immune response via substance P (SP), being tumour necrosis factor (TNF)-α-producing CD8+ T cells involved. Interestingly, the SP metabolite SP5-11 also binds to SP receptors and mediates SP-like effects on immune cells at sites of inflammation. No data were available regarding the effects of SP5-11 on pregnancy outcome in the CBA/J × DBA/2J abortion-prone combination. We investigated the influence of SP5-11 in contrast to stress or SP on the abortion rate and the cytokine production by lymphocytes as well as on the levels of CD8+ T cells. Stress and SP boosted the abortion rate and increased the percentage of type 1 [TNF-α, interferon-γ, interleukin (IL)-12] and type 2 (IL-4 and IL-10) cytokine-producing lymphocytes in blood and decidua, predominantly CD8+ T cells. Interestingly, SP5-11 did not significantly affect the abortion rate or cytokine production in the decidua, while increasing the Th1 and Th2 cytokine production systemically. Our data suggest that stress and SP induce abortion by augmenting the local levels of TNF-α, which seems therefore to be a potent trigger of miscarriage. On the contrary, the SP metabolite SP5-11 only affects the systemic cytokine production without boosting the abortion rate in this experimental model. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Online databases can support the implementation of evidence-based practice by providing easy access to research. OTseeker (http://www.otseeker.com), an electronic evidence database, was introduced in 2003 to assist occupational therapists to locate and interpret research. OBJECTIVES: This study explored Australian occupational therapists' use and perceptions of OTseeker and its impact on their knowledge and practice. METHODS: A postal survey questionnaire was distributed to two samples: (i) a proportionate random sample of 400 occupational therapists from all states and territories of Australia, and (ii) a random sample of occupational therapists working in 95 facilities in two Australian states (Queensland and New South Wales). RESULTS: The questionnaire was completed by 213 participants. While most participants (85.9%) had heard of OTseeker, only 103 (56.6%) had accessed it, with lack of time being the main reason for non-use. Of the 103 participants who had accessed OTseeker, 68.9% had done so infrequently, 63.1% agreed that it had increased their knowledge and 13.6% had changed their practice after accessing information on OTseeker. CONCLUSION: Despite OTseeker being developed to provide occupational therapists with easy access to research, lack of time was the main reason why over half of the participants in this study had not accessed it. This exploratory research suggests, however, that there is potential for the database to influence occupational therapists' knowledge and practice about treatment efficacy through access to the research literature. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that periodontal disease may be an important risk factor for preterm low birth weight. However, the link between periodontal health status of pregnant women and preterm low birth weight is contentious, as recent studies found no association between periodontitis and pregnancy outcome. The aim of this study was to investigate this potential link in a German Caucasian population. Fifty-nine pregnant women with a high risk for a preterm low birth weight infant (suffering from preterm contractions, cases, group 1) as well as 42 control women with no preterm contractions during pregnancy and having an infant appropriate for date and weight (≥ 37 weeks gestation, ≥ 2500 g, group 2) were examined. Clinical periodontal status was recorded on a full mouth basis. Subgingival plaque samples were taken and periodontal pathogens were identified by polymerase chain reaction. Additionally, interleukin-1β level in gingival crevicular fluid was analysed. The mean percentage of sites showing moderate to advanced attachment loss (≥ 3 mm) was low in all study groups (group 1: 9.9 ± 11.2%; group 2: 10.6 ± 14.1%, respectively). No significant differences between the groups in any aspects of the studied periodontitis parameters could be detected. Using a logistic regression model controlling for known preterm low birth weight risk factors, no periodontitis-associated factors increased risk for preterm contractions or preterm low birth weight. The odds ratio (OR) was 1.19 for preterm contractions, the 95% confidence interval (CI) 0.46; 3.11 and 0.73 for preterm low birth weight; 95% CI: 0.13; 4.19, respectively. In this population, periodontitis was not a detectable risk factor for preterm low birth weight in pregnant women. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of long-term treatment with the dipeptidyl peptidase inhibitor P32/98 and its combination with rosiglitazone on blood glucose control and islet of Langerhans histology in male Zucker diabetic fatty (ZDF) rats, when treatment begins before or after the development of overt diabetes.ZDF rats were treated with P32/98 from the age of 9, 12 or 15 weeks. Rosiglitazone maleate was given to a separate group from the age of 13 weeks. P32/98 was given to all of these rosiglitazone-treated rats from 16 weeks of age. Rosiglitazone maleate was also given from 16 weeks of age to half the rats that were given P32/98 from 9 weeks of age. The compounds were given by oral gavage until the rats were 14 weeks old and then in the diet. The experiment was terminated at the age of 20–21 weeks. Blood glucose, plasma insulin and oral glucose tolerance were measured at intervals; islet histology was assessed terminally.P32/98 improved glucose tolerance after both single and multiple doses when treatment started at 9 weeks of age, also after the third week of treatment when treatment began at 12 or 15 weeks of age. P32/98 reduced daytime blood glucose when treatment began at 12 weeks. Treatment with rosiglitazone increased food intake and body weight, and after 2 weeks, reduced daytime blood glucose, water intake and the area under the glucose tolerance curve. A single dose of P32/98 markedly improved glucose tolerance in rosiglitazone-treated rats. When treatment had begun at 9 weeks of age, P32/98 stimulated insulin secretion in some glucose tolerance tests. Neither P32/98 nor rosiglitazone affected pancreatic insulin content, nor did they have clear effects on islet histology.P32/98 elicited a sustained improvement in glucose tolerance in both prediabetic and diabetic ZDF rats. The effects of P32/98 on glucose and insulin were similar to those of rosiglitazone, and in contrast to rosiglitazone, P32/98 did not increase food intake or body weight. However, neither compound was especially effective at improving diabetes in ZDF rats when treatment began at 9, 12 or 15 (P32/98) or 13 (rosiglitazone) weeks of age. [ABSTRACT FROM AUTHOR]

This study was designed to identify new factors which may contribute to angiotensin-converting-enzyme-inhibitor (ACEI)-induced angioedema.In a retrospective cohort study we examined 25 patients who used an ACEI and presented at our emergency room with acute angioedema as well as 18 patients with unknown cause of angioedema and a total of 21 patients on ACEI-therapy without previous angioedema. We measured markers of inflammation such as acute-phase proteins (C-reactive protein, fibrinogen), leukocyte count and body temperature.The mean interval between initiation of ACEI treatment and first manifestation of angioedema was 35.8 ± 5.3 months. During symptomatic angioedema, mean plasma levels of C-reactive protein and fibrinogen were significantly increased by 7.3-fold and 1.5-fold, respectively, while leukocyte count and body temperature were normal. These changes disappeared after successful treatment of angioedema and were not found in patients with angioedema of unknown cause and those receiving ACEI without having experienced angioedema.Our findings demonstrate for the first time that ACEI-induced angioedema is associated with strongly increased plasma levels of CRP. We suggest that CRP is involved in the pathophysiology of ACEI-induced angioedema. [ABSTRACT FROM AUTHOR]

This study describes the discharge destination, basic and instrumental activities of daily living (ADL), community reintegration and generic health status of people after stroke, and explored whether sociodemographic and clinical characteristics were associated with these outcomes. Participants were 51 people, with an initial stroke, admitted to an acute hospital and discharged to the community. Admission and discharge data were obtained by chart review. Follow-up status was determined by telephone interview using the Modified Barthel Index, the Assessment of Living Skills and Resources, the Reintegration to Normal Living Index, and the Short-Form Health Survey (SF-36). At follow up, 57% of participants were independent in basic ADL, 84% had a low risk of experiencing instrumental ADL difficulties, most had few concerns with community reintegration, and SF-36 physical functioning and vitality scores were lower than normative values. At follow up, poorer discharge basic ADL status was associated with poorer instrumental ADL and community reintegration status, and older participants had poorer instrumental ADL, community reintegration and physical functioning. Occupational therapists need to consider these outcomes when planning inpatient and post-discharge intervention for people after stroke. [ABSTRACT FROM AUTHOR]

Based on scientific proof, only few mouthrinse solutions can be recommended. However, it is impossible to construct an extended table that would provide precise recommendations or advices for mouthrinse utilisation related to any possible discomfort or diseases. Only reliable information on the drugs available against periodontal disease can be offered to the therapist. By evaluation of her or his individual experiences, she or he has to judge all the armamentarium she or he possesses to react in the best possible way in each specific situation. [ABSTRACT FROM AUTHOR]

In recent years, natural killer (NK) cells, as well as subpopulations of T cells, have been found to express diverse NK receptors (NKRs) for HLA class I molecules. We have characterized NKR phenotypes in lymphoproliferative disorders of NK or T-cell type. Peripheral blood of patients with lymphoproliferative disorders (n = 9) was analysed by multiparametric immunofluorescence flow cytometry with eight different antibodies against NKRs. Abnormal neoplastic cell populations from different types of NK or T-cell lymphoproliferative disorders lacked diversity in their NKR repertoires, i.e. all or none of the abnormal cells expressed individual NKRs and this expression occurred at single levels of intensity. This pattern of expression was specific for lymphoproliferative disorders as these resticted NKR repertoires were not found either in healthy donors (n = 9) or in patients with viral or autoimmune disease (n = 5). We conclude that NKRs are clonally expressed in lymphoproliferative disorders of NK or T-cell origin. NKR repertoires may represent a novel tool in diagnosing clonal disorders of NK and T-cell type. [ABSTRACT FROM AUTHOR]

The article presents a study on emission of volatile organic compounds (VOC) from ozone exposed plants. It mentions that the ozone-induced reactions of the ozone-sensitive Bel W3 plants look like the hypersensitive response found after pathogen attack. It highlights that feedback mechanisms in photooxidant formation may be caused by an increased VOC emission as a consequence of elevated ozone concentrations in the troposphere.