Arteriovenous oscillometric plethysmography for fistula functional testing.

The aim of the presented prospective observational study was to evaluate the effect of fistula flow on peripheral wave morphology and pulse wave velocity by means of the oscillometric Vicorder®-device with the purpose of fistula surveillance. METHODS: Digitized and normalized curves of 53 haemodialysis patients at the fistula and non-fistula arm were analyzed. Slope parameters and the areas under the curve of characteristic sections of pulse waves as well as the power spectrum of the pulse waves and their first and second derivatives were computed. Furthermore, the amplitude of volumetric change (AMP) was assessed. Duplex-sonography served as a reference method. RESULTS: In the comprehensive set of novel pulse wave parameters significant inter-arm differences were demonstrated and a significant delay of the systolic maximum at the fistula arm in comparison to the non-fistula arm (204 ± 3.4 versus 162 ± 5.3 ms, p<0.001) was proven. Unexpectedly, pulse wave velocity apparently did not differ between both arms (7.85 versus 8.05 m/sec at the fistula/non-fistula side, p=0.942). The inter-arm differences of the slope parameters were more pronounced in forearm than in upper arm fistulas. Finally, we showed that the inter-arm difference of AMP correlated with volume-flow (r= 0.326 with p=0.017). CONCLUSION: Pulse waves as assessed by oscillometric pulse wave analysis have distinct features at fistula and non-fistula arms. This is due to enhanced arteriovenous flow, i.e. in both the brachial artery and the fistula vein. The analysis of those alterations has the potential to assess fistula function.

Functional recovery of secondary tropical forests.

One-third of all Neotropical forests are secondary forests that regrow naturally after agricultural use through secondary succession. We need to understand better how and why succession varies across environmental gradients and broad geographic scales. Here, we analyze functional recovery using community data on seven plant characteristics (traits) of 1,016 forest plots from 30 chronosequence sites across the Neotropics. By analyzing communities in terms of their traits, we enhance understanding of the mechanisms of succession, assess ecosystem recovery, and use these insights to propose successful forest restoration strategies. Wet and dry forests diverged markedly for several traits that increase growth rate in wet forests but come at the expense of reduced drought tolerance, delay, or avoidance, which is important in seasonally dry forests. Dry and wet forests showed different successional pathways for several traits. In dry forests, species turnover is driven by drought tolerance traits that are important early in succession and in wet forests by shade tolerance traits that are important later in succession. In both forests, deciduous and compound-leaved trees decreased with forest age, probably because microclimatic conditions became less hot and dry. Our results suggest that climatic water availability drives functional recovery by influencing the start and trajectory of succession, resulting in a convergence of community trait values with forest age when vegetation cover builds up. Within plots, the range in functional trait values increased with age. Based on the observed successional trait changes, we indicate the consequences for carbon and nutrient cycling and propose an ecologically sound strategy to improve forest restoration success.

Performance of two-dimensional shear wave elastography and transient elastography compared to liver biopsy for staging of liver fibrosis.

BACKGROUND: Staging of liver fibrosis traditionally relied on liver histology; however, transient elastography (TE) and more recently two-dimensional shear wave elastography (2D-SWE) evolved to noninvasive alternatives. Hence, we evaluated the diagnostic accuracy of 2D-SWE assessed by the Canon Aplio i800 ultrasound system using liver biopsy as reference and compared the performance to TE. METHODS: In total, 108 adult patients with chronic liver disease undergoing liver biopsy, 2D-SWE and TE were enrolled prospectively at the University Hospital Zurich. Diagnostic accuracies were evaluated using the area under the receiver operating characteristic (AUROC) analysis, and optimal cut-off values by Youden's index. RESULTS: Diagnostic accuracy of 2D-SWE was good for significant (≥F2; AUROC 85.2%, 95% confidence interval (95%CI):76.2-91.2%) as well as severe fibrosis (≥F3; AUROC 86.8%, 95%CI: 78.1-92.4%) and excellent for cirrhosis (AUROC 95.6%, 95%CI: 89.9-98.1%), compared to histology. TE performed equally well (significant fibrosis: 87.5%, 95%CI: 77.7-93.3%; severe fibrosis: 89.7%, 95%CI: 82.0-94.3%; cirrhosis: 96%, 95%CI: 90.4-98.4%), and accuracy was not statistically different to 2D-SWE. 2D-SWE optimal cut-off values were 6.5, 9.8 and 13.1 kPa for significant fibrosis, severe fibrosis and cirrhosis, respectively. CONCLUSIONS: Performance of 2D-SWE was good to excellent and well comparable with TE, supporting the application of this 2D-SWE system in the diagnostic workup of chronic liver disease.

Biotic homogenization and differentiation of plant communities in tropical and subtropical forests.

Anthropogenic impacts on biodiversity can lead to biotic homogenization (BH) and biotic differentiation (BD). BH is a process of increasing similarity in community composition (including taxonomic, functional, and phylogenetic components), whereas BD is a process of decreasing similarity over space and time. Here, we conducted a systematic review of BH and BD in plant communities in tropical and subtropical forests to identify trends and knowledge gaps. Our bibliometric search in the Web of Science returned 1989 papers, of which 151 matched our criteria and were included in the analysis. The Neotropical region had the largest number of articles, and Brazil was the most represented country with 92 studies. Regarding the type of change, homogenization was more frequent than differentiation (noted in 69.6% of publications). The taxonomic diversity component was measured more often than functional and phylogenetic diversity components. Most studies (75.6%) assessed homogenization and differentiation based on a single observation in time; as opposed to few studies that monitored plant community over multiple years. Forest fragmentation was cited as the main determinant of homogenization and differentiation processes (57.2% of articles). Our results highlight the importance of evaluating community composition over time and more than taxonomic components (i.e., functional and phylogenetic) to advance understanding of homogenization and differentiation. Both processes were scale dependent and not mutually exclusive. As such, future research should consider differentiation as a potential transition phase to homogenization and that potential differences in both processes may depend on the spatial and temporal scale adopted. Understanding the complexity and causes of homogenization and differentiation is essential for biodiversity conservation in a world increasingly affected by anthropogenic disturbances.

Los impactos antropogénicos sobre la biodiversidad pueden resultar en la homogenización y diferenciación biótica. La homogenización biótica consiste en una creciente similitud de la composición comunitaria (incluidos los componentes taxonómicos, funcionales y filogenéticos), mientras que la diferenciación biótica conlleva la disminución en similitudes a lo largo del tiempo y el espacio. En este trabajo realizamos una revisión sistemática de la homogenización y diferenciación biótica en las comunidades vegetales en los bosques tropicales y subtropicales para identificar tendencias y vacíos de conocimiento. Nuestra búsqueda bibliométrica en Web of Science produjo 1989 artículos, de los cuales 151 cumplieron con nuestros criterios y fueron incluidos en el análisis. La región neotropical tuvo el mayor número de artículos y Brasil fue el país más representado con 92 estudios. Con respecto al tipo de cambio, la homogenización fue más frecuente que la diferenciación (reportada en 69.6% de las publicaciones). El componente de diversidad taxonómica se midió más veces que los componentes de diversidad funcional y filogenética. La mayoría de los estudios (75.6%) examinó la homogenización y la diferenciación con base en una sola observación en el tiempo; unos cuantos estudios sí monitorearon las comunidades vegetales a través de varios años. Se citó a la fragmentación del bosque como el principal determinante de los procesos de homogenización y diferenciación (57.2% de los artículos). Nuestros resultados resaltan la importancia de la evaluación de la composición de la comunidad a través del tiempo y más allá de los componentes taxonómicos para propiciar el entendimiento de la homogenización y la diferenciación. Ambos procesos dependieron de la escala y no se excluyeron mutuamente. Por lo tanto, las siguientes investigaciones deberían considerar a la diferenciación como una fase potencial de transición hacia la homogenización y que las posibles diferencias en ambos procesos podrían depender de la escala espacial y temporal aplicada. Son esenciales el entendimiento de la complejidad y las causas de la homogenización y la diferenciación para la conservación de la biodiversidad en un planeta que cada vez se ve más afectado por las perturbaciones antropogénicas.

Oscillometric pulse wave analysis for detecting low flow arteriovenous fistula.

BACKGROUND: Pulse wave analysis may be useful to assess fistula function. We aimed to prospectively evaluate if convenient oscillometric devices are applicable to detect flow below 500 ml/min in a real life clinical setting. METHODS: Pulse waves were recorded ambilaterally with the vicorder® device at the brachial artery in 53 patients on haemodialysis with native fistula. Primary variables consisted of the mean slope between the systolic maximum and the diacrotic notch (Slope2), the sum of the mean slopes in the four characteristic sections of pulse waves (Slope∑) and the amplitude of relative volumetric change in the measuring cuff at the upper arm (AMP). Fistula flow was measured with the use of duplex sonography using a standardized approach. RESULTS: Parameter values above or below the median indicated measurement at the non-fistula side, with sensitivities/specificities of 0.79/0.79 (p < 0.001) for Slope 2, 0.64/0.64 (p = 0.003) for Slope∑ and 0.81/0.81 (p < 0.001) for AMP if measurements at the fistula and non-fistula arm were considered. ROC-analyses of parameter values measured at the fistula to detect low flow demonstrated AUCs (with CI) of 0.652 (0.437-0.866, p = 0.167) for Slope2, 0.732 (0.566-0.899, p = 0.006) for Slope∑ and 0.775 (0.56-0.991, p = 0.012) for AMP. The point with maximal youden's index was regarded as optimal cut-off, which corresponded to sensitivities and specificities of 0.8/0.56 for slope2, 0.86/ 0.56 for Slope∑ and 0.93/0.78 for AMP. CONCLUSION: Functional surveillance with oscillometry is a promising clinical application to detect a low fistula flow. Among all investigated pulse wave parameters AMP revealed the highest diagnostic accuracy.

Variability in Macro- and Micronutrients of 15 Rarely Researched Microalgae.

Microalgae have enormous potential for human nutrition, yet the European Commission has authorized the consumption of only eleven species. Strains of fifteen rarely researched microalgae from two kingdoms were screened regarding their nutritional profile and value for human health in two cultivation phases. Contents of protein, fiber, lipids, fatty acids, minerals, trace elements and heavy metals were determined. In the growth phase, microalgae accumulated more arginine, histidine, ornithine, pure and crude protein, Mg, Mn, Fe and Zn and less Ni, Mo and I2 compared to the stationary phase. Higher contents of total fat, C14:0, C14:1n5, C16:1n7, C20:4n6, C20:5n3 and also As were observed in microalgae from the chromista kingdom in comparison to microalgae from the plantae kingdom (p < 0.05). Conversely, the latter had higher contents of C20:0, C20:1n9 and C18:3n3 as well as Ca and Pb (p < 0.05). More precisely, Chrysotila carterae appeared to have great potential for human nutrition because of its high nutrient contents such as fibers, carotenoids, C20:6n3, Mg, Ca, Mn, Fe, Se, Zn, Ni, Mo and I2. In summary, microalgae may contribute to a large variety of nutrients, yet the contents differ between kingdoms, cultivation phases and also species.

Variability in Macro- and Micronutrients of 15 Commercially Available Microalgae Powders.

The nutrient composition of 15 commercially available microalgae powders of Arthrospira platensis, Chlorella pyrenoidosa and vulgaris, Dunaliella salina, Haematococcus pluvialis, Tetraselmis chuii, and Aphanizomenon flos-aquae was analyzed. The Dunaliella salina powders were characterized by a high content of carbohydrates, saturated fatty acids (SFAs), omega-6-polyunsaturated fatty acids (n6-PUFAs), heavy metals, and α-tocopherol, whereas the protein amounts, essential amino acids (EAAs), omega-3-PUFAs (n3-PUFAs), vitamins, and minerals were low. In the powder of Haematococcus pluvialis, ten times higher amounts of carotenoids compared to all other analyzed powders were determined, yet it was low in vitamins D and E, protein, and EAAs, and the n6/n3-PUFAs ratio was comparably high. Vitamin B12, quantified as cobalamin, was below 0.02 mg/100 g dry weight (d.w.) in all studied powders. Based on our analysis, microalgae such as Aphanizomenon and Chlorella may contribute to an adequate intake of critical nutrients such as protein with a high content of EAAs, dietary fibers, n3-PUFAs, Ca, Fe, Mg, and Zn, as well as vitamin D and E. Yet, the nutritional value of Aphanizomenon flos-aquae was slightly decreased by high contents of SFAs. The present data show that microalgae are rich in valuable nutrients, but the macro- and micronutrient profiles differ strongly between and within species.

[Balance between structured activities and individual leisure time : Perceptions of retirement by people with intellectual and mental disabilities]. / Balance zwischen strukturierten Aktivitäten und individuellen Freiräumen : Vorstellungen vom Ruhestand von Menschen mit intellektueller und psychischer Beeinträchtigung.

BACKGROUND: The number of people with intellectual disabilities reaching retirement age has risen by more than two thirds in the last decade. OBJECTIVE: Due to the high number of retirements in this group of persons, the facilities for integration assistance are required to provide appropriate offers, both in terms of the transition to retirement and the course of retirement. METHODS: Interviews on retirement planning were conducted with aspiring pensioners from several workshops for disabled people, which were mostly located in urban areas. RESULTS: These interviews showed that people with intellectual and mental disabilities wanted a balance between structured group offers and individual privacy. Sporting and creative offers were perceived as positive. Maintaining interpersonal contact is very important for the respondents. The upcoming retirement was seen as positive by the majority of the respondents because of the associated "new freedom". Only a few worried about the financial situation in old age.

Pulse Wave Analysis and Pulse Wave Velocity for Fistula Assessment.

BACKGROUND/AIMS: Pulse wave analysis (PWA) and pulse wave velocity (PWV) provide information about arterial stiffness and elasticity, which is mainly used for cardiovascular risk stratification. In the presented prospective observational pilot study, we examined the hypothesis that radiocephalic fistula (RCF)-related changes of haemodynamics and blood vessel morphology including high as well as low flow can be seen in specific changes of pulse wave (PW) morphology. METHODS: Fifty-six patients with RCF underwent local ambilateral peripheral PWA and PWV measurement with the SphygmoCor® device. Given that the output parameters of the SphygmoCor® are not relevant for the study objectives, we defined new suitable parameters for PWA in direct proximity to fistulas and established an appropriate analysing algorithm. Duplex sonography served as reference method. RESULTS: Marked changes of peripheral PW morphology when considering interarm differences of slope and areas between the fistula and non-fistula arms were observed in the Arteria radialis, A. brachialis and arterialized Vena cephalica. The sum of the slope differences was found to correlate with an increased flow, while in patients with fistula failure no changes in PW morphology were seen. Moreover, PWV was significantly reduced in the fistula arm. CONCLUSION: Beside duplex sonography, ambilateral peripheral PWA and PWV measurements are potential new clinical applications to characterize and monitor RCF function, especially in terms of high and low flow.

Early Screening for Posttraumatic Stress Disorder in Inpatient Detoxification and Motivation Treatment: Results and Consequences.

AIMS: Posttraumatic stress disorder (PTSD) is a significant comorbidity in substance use disorders (SUDs). While most studies have addressed trauma/PTSD in abstinent patients, little is known about trauma/PTSD in early detoxification treatment. The current study therefore addresses the systematic evaluation of trauma/PTSD in early inpatient detoxification. METHODS: A cross-sectional survey was accomplished in three German-speaking clinics (n = 134) specialized in inpatient detoxification and motivation treatment. All measures are based on self-report using trauma-specific questionnaires and measures for general psychopathological burden. RESULTS: Participation rate was 60.1% and patients did not show clinically obvious psychological distress during or after assessment. DSM-IV traumatic events were reported by 66.4%. Of the total sample, 38.1% screened positive for PTSD, and 14.9% screened positive for subsyndromal PTSD. PTSD patients reported significantly more childhood adversities and significantly higher scores in depression and -general psychopathology compared to subsyndromal PTSD and SUD-only patients. CONCLUSIONS: Early and systematic evaluation of PTSD in SUD inpatient detoxification treatment is largely safe and yields important information for individual treatment. The high PTSD-rate and the high symptom load in SUD patients during inpatient detoxification treatment highlight the need for a more stringent address of trauma/PTSD in early SUD treatment.

Biodiversity and ecosystem functioning relations in European forests depend on environmental context.

The importance of biodiversity in supporting ecosystem functioning is generally well accepted. However, most evidence comes from small-scale studies, and scaling-up patterns of biodiversity-ecosystem functioning (B-EF) remains challenging, in part because the importance of environmental factors in shaping B-EF relations is poorly understood. Using a forest research platform in which 26 ecosystem functions were measured along gradients of tree species richness in six regions across Europe, we investigated the extent and the potential drivers of context dependency of B-EF relations. Despite considerable variation in species richness effects across the continent, we found a tendency for stronger B-EF relations in drier climates as well as in areas with longer growing seasons and more functionally diverse tree species. The importance of water availability in driving context dependency suggests that as water limitation increases under climate change, biodiversity may become even more important to support high levels of functioning in European forests.

Tree species diversity affects decomposition through modified micro-environmental conditions across European forests.

Different tree species influence litter decomposition directly through species-specific litter traits, and indirectly through distinct modifications of the local decomposition environment. Whether these indirect effects on decomposition are influenced by tree species diversity is presently not clear. We addressed this question by studying the decomposition of two common substrates, cellulose paper and wood sticks, in a total of 209 forest stands of varying tree species diversity across six major forest types at the scale of Europe. Tree species richness showed a weak but positive correlation with the decomposition of cellulose but not with that of wood. Surprisingly, macroclimate had only a minor effect on cellulose decomposition and no effect on wood decomposition despite the wide range in climatic conditions among sites from Mediterranean to boreal forests. Instead, forest canopy density and stand-specific litter traits affected the decomposition of both substrates, with a particularly clear negative effect of the proportion of evergreen tree litter. Our study suggests that species richness and composition of tree canopies modify decomposition indirectly through changes in microenvironmental conditions. These canopy-induced differences in the local decomposition environment control decomposition to a greater extent than continental-scale differences in macroclimatic conditions.

Early detection of dementia in people with an intellectual disability - A German pilot study.

BACKGROUND: This study investigated the application of a newly developed neuropsychological assessment, the Wolfenbütteler Dementia Test for Individuals with Intellectual Disabilities (WDTIM) in combination with the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID). METHODS: The instruments were evaluated in a prospective 2-year follow-up study. A total of 102 people with an intellectual disability were assessed at 6-month intervals. Data were analysed using qualitative and statistical analyses. RESULTS: Four groups of individuals emerged from the analysis: (1) confirmed suspicion, (2) no suspicion, (3) questionable suspicion and (4) early suspicion. Significant differences were found between groups 1 and 2. The WDTIM could be administered to 90%-100% of all participants exhibiting mild-to-moderate intellectual disability and to 50% with severe intellectual disability . CONCLUSIONS: The WDTIM was shown to have good applicability to people with mild-to-moderate intellectual disability and to be appropriate for detecting cognitive changes. Using the two instruments in combination achieved greater accuracy in reinforcing a dementia suspicion than did using the DSQIID alone.

A Cdc42-regulated actin cytoskeleton mediates Drosophila oocyte polarization.

Polarity of the Drosophila oocyte is essential for correct development of the egg and future embryo. The Par proteins Par-6, aPKC and Bazooka are needed to maintain oocyte polarity and localize to specific domains early in oocyte development. To date, no upstream regulator or mechanism for localization of the Par proteins in the oocyte has been identified. We have analyzed the role of the small GTPase Cdc42 in oocyte polarity. We show that Cdc42 is required to maintain oocyte fate, which it achieves by mediating localization of Par proteins at distinct sites within this cell. We establish that Cdc42 localization itself is polarized to the anterolateral cortex of the oocyte and that Cdc42 is needed for maintenance of oocyte polarity throughout oogenesis. Our data show that Cdc42 ensures the integrity of the oocyte actin network and that disruption of this network with Latrunculin A phenocopies loss of Cdc42 or Par protein function in early stages of oogenesis. Finally, we show that Cdc42 and Par proteins, as well as Cdc42/Par and Arp3, interact in the context of oocyte polarity, and that loss of Par proteins reciprocally affects Cdc42 localization and the actin network. These results reveal a mutual dependence between Par proteins and Cdc42 for their localization, regulation of the actin cytoskeleton and, consequently, for the establishment of oocyte polarity. This most likely allows for the robustness in symmetry breaking in the cell.

Liposuction Preserves the Morphological Integrity of the Microvascular Network: Flow Cytometry and Confocal Microscopy Evidence in a Controlled Study.

BACKGROUND: Liposuction is a very popular technique in plastic surgery that allows for the taking adipose tissue (AT) on large surfaces with little risk of morbidity. Although liposuction was previously shown to preserve large perforator vessels, little is known about the effects of liposuction on the microvasculature network. OBJECTIVES: The aim of this study was to analyze the effect of liposuction on the preservation of microvessels at tissue and cellular levels by flow cytometry and confocal microscopy following abdominoplasty procedure. METHODS: Percentage of endothelial cells in AT from liposuction and en bloc AT was determined by multicolor flow cytometry. Moreover, vessel density and adipocyte content were analyzed in situ in 3 different types of AT (en bloc, from liposuction, and residual AT after liposuction) by confocal microscopy. RESULTS: Flow cytometric analysis showed that en bloc AT contained 30.6% ± 12.9% and AT from liposuction 21.6% ± 9.9% of endothelial cells (CD31(pos)/CD45(neg)/CD235a(neg)/CD11b(neg)) (P = .009). Moreover, analysis of paired AT from the same patients (n = 5) confirmed a lower percentage of endothelial cells in AT from liposuction compared to en bloc AT (17.7% ± 4.5% vs 21.9% ± 3.3%, P = .031). Likewise, confocal microscopy showed that en bloc AT contained 8.2% ± 6.3%, AT from liposuction only 1.6% ± 1.0% (P < .0001), and AT after liposuction 8.9% ± 4.1% (P = .111) of CD31(pos) vessels. Conversely, adipocyte content was 39.5% ± 14.5% in the en bloc AT, 45% ± 18.4% in AT from liposuction (P = .390), and 18.8 ± 14.8% in AT after liposuction (P = .011). CONCLUSIONS: For the first time, we demonstrate that liposuction preserves the microvascular network. Indeed, a low percentage of endothelial cells was found in AT from liposuction and we confirm the persistence of microvessels in the tissue after liposuction.

IgY antibodies in human nutrition for disease prevention.

Oral administration of preformed specific antibodies is an attractive approach against infections of the digestive system in humans and animals in times of increasing antibiotic resistances. Previous studies showed a positive effect of egg yolk IgY antibodies on bacterial intoxications in animals and humans. Immunization of chickens with specific antigens offers the possibility to create various forms of antibodies. Research shows that orally applied IgY's isolated from egg yolks can passively cure or prevent diseases of the digestive system. The use of these alternative therapeutic drugs provides further advantages: (1) The production of IgY's is a non-invasive alternative to current methods; (2) The keeping of chickens is inexpensive; (3) The animals are easy to handle; (4) It avoids repetitive bleeding of laboratory animals; (5) It is also very cost effective regarding the high IgY concentration within the egg yolk. Novel targets of these antigen specific antibodies are Helicobacter pylori and also molecules involved in signaling pathways in gastric cancer. Furthermore, also dental caries causing bacteria like Streptococcus mutans or opportunistic Pseudomonas aeruginosa in cystic fibrosis patients are possible targets. Therefore, IgY's included in food for human consumption may be able to prevent or cure human diseases.

Floristic and structural patterns in South Brazilian coastal grasslands.

The natural vegetation of Southern Brazil's coastal region includes grasslands formations that are poorly considered in conservation policy, due to the lack of knowledge about these systems. This study reports results from a regional-scale survey of coastal grasslands vegetation along a 536 km gradient on southern Brazil. We sampled 16 sites along the coastal plain with 15 plots (1 m²) per site. All sites were grazed by cattle. We estimated plant species cover, vegetation height, percentage of bare soil, litter and manure, and classified species according to their growth forms. We found 221 species, 14 of them exotic and two threatened. The prostate grasses: Axonopus aff.affinis, Paspalum notatum and P. pumilumwere among the most important species. Prostrate graminoids species represented the most important vegetation cover, followed by cespitose grasses. Vegetation height, bare soil, litter and manure were similar among all areas, highlighting the homogeneity of sampling sites due to similar management. In comparison to other grasslands formations in Southern Brazil, the coastal grasslands presented rather low species richness. The presence of high values for bare soil at all sampling sites indicates the need to discuss management practices in the region, especially with regard to the intensity of livestock grazing.

Soluble polysialylated NCAM: a novel player of the innate immune system in the lung.

Posttranslational modification of the neural cell adhesion molecule (NCAM) by polysialic acid (polySia) is well studied in the nervous system and described as a dynamic modulator of plastic processes like precursor cell migration, axon fasciculation, and synaptic plasticity. Here, we describe a novel function of polysialylated NCAM (polySia-NCAM) in innate immunity of the lung. In mature lung tissue of healthy donors, polySia was exclusively attached to the transmembrane isoform NCAM-140 and located to intracellular compartments of epithelial cells. In patients with chronic obstructive pulmonary disease, however, increased polySia levels and processing of the NCAM carrier were observed. Processing of polysialylated NCAM was reproduced in a mouse model by bleomycin administration leading to an activation of the inflammasome and secretion of interleukin (IL)-1ß. As shown in a cell culture model, polySia-NCAM-140 was kept in the late trans-Golgi apparatus of lung epithelial cells and stimulation by IL-1ß or lipopolysaccharide induced metalloprotease-mediated ectodomain shedding, resulting in the secretion of soluble polySia-NCAM. Interestingly, polySia chains of secreted NCAM neutralized the cytotoxic activity of extracellular histones as well as DNA/histone-network-containing "neutrophil extracellular traps", which are formed during invasion of microorganisms. Thus, shedding of polySia-NCAM by lung epithelial cells may provide a host-protective mechanism to reduce tissue damage during inflammatory processes.

[Dextromethorphan abuse in adolescents: what can the pharmacists do?]. / Dextromethorphan-Missbrauch bei Jugendlichen: Wie kann sich der Apotheker verhalten?

In Germany, dextromethorphan (DXM) is used as OTC cough and cold medication. Overdose, however, can cause psychotropic side effects and is therefore abused among adolescents. To better control the drug by the pharmacist, a pilot was undertaken to monitor drug selling of DXM in German retail pharmacies. Over a 6-month period, pharmacies documented the request of DXM preparations. These data were compared to abuse cases of the German regulatory agency, the Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), an analysis of the 2010 annual sales statistic from the IMS OTC and information about DXM products from drug abuse websites. Especially the young DXM buyers in German retail pharmacies showed characteristics similar to those people from the BfArM abuse data file: They were male and used the DXM product Hustenstiller-ratiopharm. Hustenstiller-ratiopharm has well-directed instructions for DXM abuse in the internet. However, the 2010 annual sales statistic from the IMS OTC report identified Wick MediNait as the product with highest sales numbers whereas Hustenstiller-ratiopharm" was of less importance indicating DXM abuse is limited to a small part of the DXM user population.

Intraoperative ultrasound guidance for palpable breast cancer excision (COBALT trial): a multicentre, randomised controlled trial.

BACKGROUND: Breast-conserving surgery for palpable breast cancer is associated with tumour-involved margins in up to 41% of cases and excessively large excision volumes. Ultrasound-guided surgery has the potential to resolve both of these problems, thereby improving surgical accuracy for palpable breast cancer. We aimed to compare ultrasound-guided surgery with the standard for palpable breast cancer-palpation-guided surgery-with respect to margin status and extent of healthy breast tissue resection. METHODS: In this randomised controlled trial, patients with palpable T1-T2 invasive breast cancer were recruited from six medical centres in the Netherlands between October, 2010, and March, 2012. Eligible participants were randomly assigned to either ultrasound-guided surgery or palpation-guided surgery in a 1:1 ratio via a computer-generated random sequence and were stratified by study centre. Patients and investigators were aware of treatment assignments. Primary outcomes were surgical margin involvement, need for additional treatment, and excess healthy tissue resection (defined with a calculated resection ratio derived from excision volume and tumour diameter). Data were analysed by intention to treat. This trial is registered at http://www.TrialRegister.nl, number NTR2579. FINDINGS: 134 patients were eligible for random allocation. Two (3%) of 65 patients allocated ultrasound-guided surgery had tumour-involved margins compared with 12 (17%) of 69 who were assigned palpation-guided surgery (difference 14%, 95% CI 4-25; p=0·0093). Seven (11%) patients who received ultrasound-guided surgery and 19 (28%) of those who received palpation-guided surgery required additional treatment (17%, 3-30; p=0·015). Ultrasound-guided surgery also resulted in smaller excision volumes (38 [SD 26] vs 57 [41] cm(3); difference 19 cm(3), 95% CI 7-31; p=0·002) and a reduced calculated resection ratio (1·0 [SD 0·5] vs 1·7 [1·2]; difference 0·7, 95% CI 0·4-1·0; p=0·0001) compared with palpation-guided surgery. INTERPRETATION: Compared with palpation-guided surgery, ultrasound-guided surgery can significantly lower the proportion of tumour-involved resection margins, thus reducing the need for re-excision, mastectomy, and radiotherapy boost. By achieving optimum resection volumes, ultrasound-guided surgery reduces unnecessary resection of healthy breast tissue and could contribute to improved cosmetic results and quality of life. FUNDING: Dutch Pink Ribbon Foundation, Osinga-Kluis Foundation, Toshiba Medical Systems.