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Background: Single-site carcinoma of unknown primary (CUP) is recognised as a distinct favourable subtype in the European Society of Medical Oncology (ESMO) classification. There is broad consensus that these patients are candidates for local ablative treatment strategies with surgery and/or radiotherapy, but data on their outcomes are scarce., Patients and Methods: In this study, we have addressed the prospects of cure and prognostic factors in a retrospective cohort of 63 patients who were eligible for local treatment at our centre., Results: Median event-free (EFS) and overall survival (OS) were 15.6 months and 52.5 months, respectively. Of 61 patients who received local treatment, 20 (32.8%) remained event-free over a median follow-up of 28 months. Baseline clinical parameters including affected organ, number, volume and histology of metastases had no significant impact on prognosis, whereas deleterious TP53 mutations and DNA copy number loss emerged as independent adverse risk factors with respect to EFS. Surgical treatment was associated with improved OS as compared to radiation-based therapy., Conclusion: Our study advocates to pursue localised treatment with surgery and/or radiotherapy whenever feasible and implies that genetic parameters might additionally determine the clinical course of single-site CUP patients., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: VE: advisory board and lecture fees from AstraZeneca and Thermo Fisher. AS: Advisory Board and/or Speaker's Bureau: AIGnostics, Astra Zeneca, Bayer, BMS, Illumina, Janssen, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda, Thermo Fisher; Research Grants: Bayer, BMS, Chugai, Incyte. AK and TB work as study oncologists for the CUPISCO trial which is sponsored by Roche and have received reimbursement for study-related travels as well as remuneration for their work as study oncologists for the benefit of their employer. AK has also received research funding from BMS. The remaining authors have no conflict of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Niobium-alumina aggregate fractions with particle sizes up to 3150 µm were produced by crushing pre-synthesised fine-grained composites. Phase separation with niobium enrichment in the aggregate class 45-500 µm was revealed by XRD/Rietveld analysis. To reduce the amount of carbon-based impurities, no organic additives were used for the castable mixtures, which resulted in water demands of approximately 27 vol.% for the fine- and coarse-grained castables. As a consequence, open porosities of 18% and 30% were determined for the fine- and coarse-grained composites, respectively. Due to increased porosity, the modulus of rupture at room temperature decreased from 52 MPa for the fine-grained composite to 11 MPa for the coarse-grained one. However, even the compressive yield strength decreased from 49 MPa to 18 MPa at 1300 °C for the fine-grained to the coarse-grained composite, the latter showed still plasticity with a strain up to 5%. The electrical conductivity of fine-grained composite samples was in the range between 40 and 60 S /cm, which is fifteen magnitudes above the values of pure corundum.

The purpose of this article was to explore how individuals' position in a socioeconomic hierarchy is related to health behaviours that are related to socioeconomic disparities in health. We identified research which shows that: (a) low socioeconomic status (SES) is associated with living in harsh environments, (b) harsh environments are related to increased levels of stress and inflammation, (c) stress and inflammation impact neural systems involved in self-control by sensitising the impulsive system and desensitising the reflective system, (d) the effects are inflated valuations of small immediate rewards and deflated valuations of larger delayed rewards, (e) these effects are observed as increased delay discounting, and (f) delay discounting is positively associated with practicing more unhealthy behaviours. The results are discussed within an adaptive evolutionary framework which lays out how the stress response system, and its interaction with the immune system and brain systems for decision-making and behaviours, provides the biopsychological mechanisms and regulatory shifts that make widespread conditional adaptability possible. Consequences for policy work, interventions, and future research are discussed., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A recent meta-analysis has questioned the relevance of attention bias modification (ABM) for depression outcomes. However, there might be patient characteristics not yet accounted for, that are relevant to the outcome. In the context of personalized treatment, the lack of moderator studies have limited the potential for matching ABM-treatment to individual patient characteristics. Subjects (N = 301) were randomly assigned 1:1 to receive either active or placebo Attention Bias Modification (ABM) twice daily for 14 days in a double-blind design (placebo n = 148; ABM n = 153). The outcome was change in symptoms based on the Hamilton Depression Rating Scale (HDRS). Moderator variables were self-reported depression (Beck Depression Inventory-II; BDI-II), anxiety (Beck Anxiety Inventory; BAI) and attentional bias (AB) assessed at baseline. This trial was registered with ClinicalTrials.gov, number NCT02658682. Only BAI (p for interaction = .01, Bootstrap 95% CI [0.046, 0.337]) moderated the effects of ABM on change in clinician rated depressive symptoms. Interactions were significant for BAI scores ≥8. The relative effect of the intervention increased with the highest symptom load. ABM was not effective in patients with the lowest symptom load. Future research should validate this finding and continue investigating moderators of the ABM-intervention to further enhance personalization of treatment to individual symptom characteristics., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: To date, the guidelines for surgical repair of hiatal hernias do not contain any clear recommendations on the hiatoplasty technique with regard to the use of a mesh or to the type of fundoplication (Nissen vs. Toupet). This present 10-years analysis of data from the Herniamed Registry aims to investigate these questions. Methods: Data on 17,328 elective hiatal hernia repairs were entered into the Herniamed Registry between 01.01.2010 and 31.12.2019. 96.4% of all repairs were completed by laparoscopic technique. One-year follow-up was available for 11,280 of 13,859 (81.4%) patients operated during the years 2010-2018. The explorative Fisher's exact test was used for statistical calculation of significant differences with an alpha = 5%. Since the annual number of cases in the Herniamed Registry in the years 2010-2012 was still relatively low, to identify significant differences the years 2013 and 2019 were compared. Results: The use of mesh hiatoplasty for axial and recurrent hiatal hernias remained stable over the years from 2013 to 2019 at 20 and 45%, respectively. In the same period the use of mesh hiatoplasty for paraesophageal hiatal hernia slightly, but significantly, increased from 33.0 to 38.9%. The proportion of Nissen and Toupet fundoplications for axial hiatal hernia repair dropped from 90.2% in 2013 to 74.0% in 2019 in favor of "other techniques" at 20.9%. For the paraesophageal hiatal hernias (types II-IV) the proportion of Nissen and Toupet fundoplications was 68.1% in 2013 and 66.0% in 2019. The paraesophageal hiatal hernia repairs included a proportion of gastropexy procedures of 21.7% in 2013 and 18.7% in 2019. The recurrent hiatal hernia repairs also included a proportion of gastropexies 12.8% in 2013 and 15.1% in 2019, Nissen and Toupet fundoplications of 72.7 and 62.7%, respectively, and "other techniques" of 14.5 and 22.2%, respectively. No changes were seen in the postoperative complication and recurrence rates. Conclusion: Clear trends are seen in hiatal hernia repair. The use of meshes has only slightly increased in paraesophageal hiatal hernia repairs. The use of alternative techniques has resulted in a reduction in the use of the "classic" Nissen and Toupet fundoplication surgical techniques., (Copyright © 2020 Köckerling, Zarras, Adolf, Kraft, Jacob, Weyhe and Schug-Pass.)

Purpose: The aim of this study was to compare the deviation of the implant position after placement in single maxillary incisor post-extraction sockets between fully and partially guided surgery., Materials and Methods: Twenty-four patients with a failing maxillary incisor were randomly allocated into two groups: the partially guided surgery (PGS, n = 12) group or fully guided surgery (FGS, n = 12) group. Clinical analyses, intra-oral scans, and computed tomography scans (CT) were initially performed to define the virtual positioning of the implants and fabrication of the 3D printed surgical guides. A narrow, 3.5 × 16 mm implant was placed in each socket. In this moment, the insertion torque (IT) was assessed and resonance frequency analysis (RFA) was performed. All patients received an immediate provisional without occlusal contacts. Another CT scan was performed after the procedures to compare the implant position with the virtually planned position., Results: Significant deviations occurred at the implant apex, according to the global and facial-palatal analyses, in comparison to its cervical position. The PGS group also presented a larger deviation in the MD position. No statistical differences between the groups were detected, however, there was a tendency of lower angular deviation in the PGS group., Conclusions: While there was a slight deviation from the virtually planned position of the implant to the actual position and a tendency of lower angular deviation in the PGS group, there was no difference among groups regarding its position and primary stability. (UNT: 1111-1214-2812 - http://www.ensaiosclinicos.gov.br/rg/RBR-4tmcrk/)., (© 2020 Wiley Periodicals LLC.)

Cannabis is the most frequently used recreational drug worldwide. Moreover, the use of cannabinoids for medical purposes is also constantly growing and medical cannabis products are legalised by an increasing number of countries. First clinical reports have shown enhanced requirements for propofol and analgesics used for general anesthesia and perioperative pain management in cannabis users. Therefore, this article discusses the potential impact of medical or recreational cannabis use on patients with regard to the recent literature. Besides the significantly increased requirement for propofol and fentanyl during anesthesia and for postoperative analgesia, a higher risk for tachycardia, pulmonary and cardiovascular complications was observed. With respect to these data, the authors recommend asking patients pre-operatively about recreational or medical cannabis use or cannabinoid-based medication.

Vegetation state is largely driven by climate and the complexity of involved processes leads to non-linear interactions over multiple time-scales. Recently, the role of temporally lagged dependencies, so-called memory effects, has been emphasized and studied using data-driven methods, relying on a vast amount of Earth observation and climate data. However, the employed models are often not able to represent the highly non-linear processes and do not represent time explicitly. Thus, data-driven study of vegetation dynamics demands new approaches that are able to model complex sequences. The success of Recurrent Neural Networks (RNNs) in other disciplines dealing with sequential data, such as Natural Language Processing, suggests adoption of this method for Earth system sciences. Here, we used a Long Short-Term Memory (LSTM) architecture to fit a global model for Normalized Difference Vegetation Index (NDVI), a proxy for vegetation state, by using climate time-series and static variables representing soil properties and land cover as predictor variables. Furthermore, a set of permutation experiments was performed with the objective to identify memory effects and to better understand the scales on which they act under different environmental conditions. This was done by comparing models that have limited access to temporal context, which was achieved through sequence permutation during model training. We performed a cross-validation with spatio-temporal blocking to deal with the auto-correlation present in the data and to increase the generalizability of the findings. With a full temporal model, global NDVI was predicted with R 2 of 0.943 and RMSE of 0.056. The temporal model explained 14% more variance than the non-memory model on global level. The strongest differences were found in arid and semiarid regions, where the improvement was up to 25%. Our results show that memory effects matter on global scale, with the strongest effects occurring in sub-tropical and transitional water-driven biomes., (Copyright © 2019 Kraft, Jung, Körner, Requena Mesa, Cortés and Reichstein.)

Social stress and inflammatory processes are strong regulators of one another. Considerable evidence shows that social threats trigger inflammatory responses that increase infection susceptibility in both humans and animals, while infectious disease triggers inflammation that in turn regulates social behaviours. However, no previous study has examined whether young children's popularity and their rate of infectious disease are associated. We investigated the longitudinal bidirectional links between children's popularity status as perceived by peers, and parent reports of a variety of infectious diseases that are common in early childhood (i.e. common cold as well as eye, ear, throat, lung and gastric infections). We used data from the 'Matter of the First Friendship Study' (MOFF), a longitudinal prospective multi-informant study, following 579 Norwegian pre-schoolers (292 girls, median age at baseline = six years) with annual assessments over a period of three years. Social network analysis was used to estimate each child's level of popularity. Cross-lagged autoregressive analyses revealed negative dose-response relations between children's popularity scores and subsequent infection (b = -0.18, CI = -0.29, -0.06, and b = -0.13, CI = -0.23, -0.03). In conclusion, the results suggest that children who are unpopular in early childhood are at increased risk of contracting infection the following year., Competing Interests: The authors have declared that no competing interests exist.

Background: Following treatment, many depressed patients have significant residual symptoms. However, large randomised controlled trials (RCT) in this population are lacking. When Attention bias modification training (ABM) leads to more positive emotional biases, associated changes in clinical symptoms have been reported. A broader and more transparent picture of the true advantage of ABM based on larger and more stringent clinical trials have been requested. The current study evaluates the early effect of two weeks ABM training on blinded clinician-rated and self-reported residual symptoms, and whether changes towards more positive attentional biases (AB) would be associated with symptom reduction., Method: A total of 321 patients with a history of depression were included in a preregistered randomized controlled double-blinded trial. Patients were randomised to an emotional ABM paradigm over fourteen days or a closely matched control condition. Symptoms based on the Hamilton Rating Scale for Depression (HRSD) and Beck Depression Inventory II (BDI-II) were obtained at baseline and after ABM training., Results: ABM training led to significantly greater decrease in clinician-rated symptoms of depression as compared to the control condition. No differences between ABM and placebo were found for self-reported symptoms. ABM induced a change of AB towards relatively more positive stimuli for participants that also showed greater symptom reduction., Conclusion: The current study demonstrates that ABM produces early changes in blinded clinician-rated depressive symptoms and that changes in AB is linked to changes in symptoms. ABM may have practical potential in the treatment of residual depression., Trial Registration: ClinicalTrials.gov ID: NCT02658682 (retrospectively registered in January 2016).

Mangroves are ecosystems located in the transition zone between land and sea, characterized by periodic flooding that confer to its unique characteristics. Little is known about the transformation of nutrients that occur during the organic matter degradation in this system. In this study, we monitor the nitrogen transformations in soils from three mangroves with distinct levels of contamination using labeled 15NO3-. We also screened the mangroves metagenomes for the presence of genes that encode enzymes involved in denitrification (nirS, nirK, nosZ, norB and narG), anaerobic oxidation of ammonia (anammox) (hh, hao and hzo) and dissimilatory nitrate reduction to ammonium (DNRA) (nrfA). The transformations of 15NO3- indicated the balance of denitrification over anammox and DNRA in all three mangroves, with lower rates of processes in the mangrove affected by oil contamination. The metagenomic analysis detected 56 sequences related to denitrification, 19 with anammox and 6 with DNRA. Genes related with denitrification were phylogenetically distributed among several groups of bacteria (mainly Gammaproteobacteria). Anammox and DNRA related sequences were affiliated with Planctomycetes and Gammaproteobacteria, respectively. Thus, metagenomic and functional approaches supported the description of denitrification, anammox and DNRA rates in mangrove soils, and identified the major bacterial groups involved in these processes.

Aim and Background: To elucidate the effects on the results of student evaluation after the revision of pediatric communication training. Students repeatedly rated communication training as moderate, and indicated an insufficient level of preparedness with regard to the medical background of the cases used. Also, tutoring was often perceived as unbalanced between medical and communicative issues associated with the tutor's profession-who was either a resident or a psychologist. In addition, peer role-play was frequently criticized for being used in a case featuring cultural and language barriers., Methods: Communication training was extensively remodeled. A blended learning concept was introduced with virtual patients in preparation for case-specific medical content, peer role-play was combined with standardized parents, and team teaching by residents and psychologists was introduced to strike a balance in discussions between medical and communicative matters. During the following term, the faculty's standardized evaluation was used to elicit overall rating and particular curricular changes of the communication training; overall ratings were compared to earlier evaluation results. In addition, teaching analysis polls (TAP) were conducted to obtain direct feedback from students about their perceptions of the remodeled training., Results: The overall rating of the communication training did not improve after course revision. Items on specific changes implemented in the training received only moderate ratings. In contrast, direct feedback through TAP revealed significant learning effects perceived through the blended approach, peer role-play and standardized parents, and team teaching. However, students made requests to shorten the training duration and expressed controversial opinions on the use of peer role-play and standardized parents., Conclusions: Despite large efforts to improve teaching, evaluation results do not necessarily meet educators' expectations. If evaluations are more likely to measure acceptance alone among students, improvements in teaching might not be fully communicated to medical educators., (Copyright © 2018. Published by Elsevier GmbH.)

Theory on indirect genetic effects (IGEs) indicates that variation in the genetic composition of social groups can generate GxG epistasis that may promote the evolution of stable polymorphisms. Using a livebearing fish with a genetic polymorphism in coloration and associated behavioral differences, we tested whether genotypes of social partners interacted with focal individual genotypes to influence growth and condition over 16 weeks of development. We found that IGEs had a significant influence on patterns of feeding, regardless of focal fish genotype. There was no influence of social environment on juvenile length, but there was significant GxG epistasis for body condition. Each focal juvenile was in better condition when its own genotype was not present in adult social partners. These data are consistent with negative frequency-dependent selection in which each morph performs better when it is rare. Neither variation in feeding nor activity-related behaviors explained variation in body condition, suggesting that GxG epistasis for condition was caused by physiological differences between the two genotypes. These findings indicate that GxG epistasis in a given polymorphism can generate fitness landscapes that contribute to the maintenance of that polymorphism and to maintenance of genetic variation for additional fitness-related traits., (© 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.)

Introduction: Comparison of elective laparoscopic repair of axial vs paraesophageal hiatal hernias reveals relevant differences in both the patient collectives and the complexity of the procedures., Materials and Methods: The present uni- and multivariable analysis of data from the Herniamed Registry compares the outcome for 2047 (67.3%) (type I) axial with 996 (32.7%) (types II-IV) paraesophageal primary hiatal hernias following laparoscopic repair., Results: Compared with the patients with axial hiatal hernias, patients with paraesophageal hiatal hernia were nine years older, had a higher ASA score (ASA III/IV: 34.8 vs 13.7%; p < 0.001), and more often at least one risk factor (38.8 vs 21.4%; p < 0.001). This led in the univariable analysis to significantly more general postoperative complications (6.0 vs 3.0%; p < 0.001). Reflecting the greater complexity of the procedures used for laparoscopic repair of paraesophageal hiatal hernias, significantly higher intraoperative organ injury rates (3.7 vs 2.3%; p = 0.033) and higher postoperative complication-related reoperation rates (2.1 vs 1.1%; p = 0.032) were identified. Univariable analysis did not reveal any significant differences in the recurrence and pain rates on one-year follow-up. Multivariable analysis did not find any evidence that the use of a mesh had a significant influence on the recurrence rate., Conclusion: Surgical repair of paraesophageal hiatal hernia calls for an experienced surgeon as well as for corresponding intensive medicine competence because of the higher risks of general and surgical postoperative complications.

Mitochondrial damage is often overlooked in acute lung injury (ALI), yet most of the lung's physiological processes, such as airway tone, mucociliary clearance, ventilation-perfusion (Va/Q) matching, and immune surveillance require aerobic energy provision. Because the cell's mitochondrial quality control (QC) process regulates the elimination and replacement of damaged mitochondria to maintain cell survival, we serially evaluated mitochondrial biogenesis and mitophagy in the alveolar regions of mice in a validated Staphylococcus aureus pneumonia model. We report that apart from cell lysis by direct contact with microbes, modest epithelial cell death was detected despite significant mitochondrial damage. Cell death by TdT-mediated dUTP nick-end labeling staining occurred on days 1 and 2 postinoculation: apoptosis shown by caspase-3 cleavage was present on days 1 and 2, while necroptosis shown by increased levels of phospho- mixed lineage kinase domain-like protein (MLKL) and receptor-interacting serine/threonine-protein kinase 1 (RIPK1) was present on day 1 Cell death in alveolar type I (AT 1 ) cells assessed by bronchoalveolar lavage fluid receptor for advanced glycation end points (RAGE) levels was high, yet AT 2 cell death was limited while both mitochondrial biogenesis and mitophagy were induced. These mitochondrial QC mechanisms were evaluated mainly in AT 2 cells by localizing increases in citrate synthase content, increases in nuclear mitochondrial biogenesis regulators nuclear respiratory factor-1 (NRF-1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and increases in light chain 3B protein (LC3-I)/LC3II ratios. Concomitant changes in p62, Pink 1, and Parkin protein levels indicated activation of mitophagy. By confocal microscopy, mitochondrial biogenesis and mitophagy were often observed on day 1 within the same AT 2 cells. These findings imply that mitochondrial QC activation in pneumonia-damaged AT 2 cells promotes cell survival in support of alveolar function., (Copyright © 2017 the American Physiological Society.)

Dysfunctional metacognitive beliefs ("metacognitions") and executive control are important factors in mental disorders such as depression and anxiety, but the relationship between these concepts has not been studied systematically. We examined whether there is an association between metacognitions and executive control and hypothesized that decreased executive control statistically predicts increased levels of metacognitions. Two hundred and ninety-nine individuals recruited from the general population and outpatient psychiatric clinics completed the Metacognitions Questionnaire-30 and three subtests from the Cambridge Neuropsychological Test Automated Battery corresponding to the three-component model of executive functions. Controlling for current depression and anxiety symptoms, decreased ability to shift between mental sets was associated with increased negative beliefs about the uncontrollability and danger of worry and beliefs about the need to control thoughts. The results suggest a basic association between metacognitions and executive control. Individual differences in executive control could prove important in the personalization of metacognitive therapy.

Succession of redox processes is sometimes assumed to define a basic microbial community structure for ecosystems with oxygen gradients. In this paradigm, aerobic respiration, denitrification, fermentation and sulfate reduction proceed in a thermodynamically determined order, known as the 'redox tower'. Here, we investigated whether redox sorting of microbial processes explains microbial community structure at low-oxygen concentrations. We subjected a diverse microbial community sampled from a coastal marine sediment to 100 days of tidal cycling in a laboratory chemostat. Oxygen gradients (both in space and time) led to the assembly of a microbial community dominated by populations that each performed aerobic and anaerobic metabolism in parallel. This was shown by metagenomics, transcriptomics, proteomics and stable isotope incubations. Effective oxygen consumption combined with the formation of microaggregates sustained the activity of oxygen-sensitive anaerobic enzymes, leading to braiding of unsorted redox processes, within and between populations. Analyses of available metagenomic data sets indicated that the same ecological strategies might also be successful in some natural ecosystems.

Introduction: For open and endoscopic inguinal hernia surgery, it has been demonstrated that low-volume surgeons with fewer than 25 and 30 procedures, respectively, per year are associated with significantly more recurrences than high-volume surgeons with 25 and 30 or more procedures, respectively, per year. This paper now explores the relationship between the caseload and the outcome based on the data from the Herniamed Registry., Patients and Methods: The prospective data of patients in the Herniamed Registry were analyzed using the inclusion criteria minimum age of 16 years, male patient, primary unilateral inguinal hernia, TEP or TAPP techniques and availability of data on 1-year follow-up. In total, 16,290 patients were enrolled between September 1, 2009, and February 1, 2014. Of the participating surgeons, 466 (87.6 %) had carried out fewer than 25 endoscopic/laparoscopic operations (low-volume surgeons) and 66 (12.4 %) surgeons 25 or more operations (high-volume surgeons) per year., Results: Univariable (1.03 vs. 0.73 %; p = 0.047) and multivariable analysis [OR 1.494 (1.065-2.115); p = 0.023] revealed that low-volume surgeons had a significantly higher recurrence rate compared with the high-volume surgeons, although that difference was small. Multivariable analysis also showed that pain on exertion was negatively affected by a lower caseload <25 [OR 1.191 (1.062-1.337); p = 0.003]. While here, too, the difference was small, the fact that in that group there was a greater proportion of patients with small hernia defect sizes may have also played a role since the risk in that group was higher. In this analysis, no evidence was found that pain at rest [OR 1.052 (0.903-1.226); p = 0.516] or chronic pain requiring treatment [OR 1.108 (0.903-1.361); p = 0.326] were influenced by the surgeon volume. As confirmed by previously published studies, the data in the Herniamed Registry also demonstrated that the endoscopic/laparoscopic inguinal hernia surgery caseload impacted the outcome. However, given the overall high-quality level the differences between a "low-volume" surgeon and a "high-volume" surgeon were small. That was due to the use of a standardized technique, structured training as well as continuous supervision of trainees and surgeons with low annual caseload., Competing Interests: Compliance with ethical standards Disclosures R. Bittner, B. Kraft, M. Hukauf, A. Kuthe, C. Schug-Pass have no conflicts of interest or financial ties to disclose.

Background: A tight regulation of the Wnt-signaling network, activated by 19 Wnt molecules and numerous receptors and co-receptors, is required for the establishment of a complex organism. Different branches of this Wnt-signaling network, including the canonical Wnt/β-catenin and the non-canonical Wnt/PCP, Wnt/Ror2 and Wnt/Ca(2+) pathways, are assigned to distinct developmental processes and are triggered by certain ligand/receptor complexes. The Wnt-signaling molecules are closely related and it is still on debate whether the information for activating a specific branch is encoded by specific sequence motifs within a particular Wnt protein. The model organism Xenopus offers tools to distinguish between Wnt-signaling molecules activating distinct branches of the network., Results: We created chimeric Wnt8a/Wnt11 molecules and could demonstrate that the C-terminal part (containing the BS2) of Wnt8a is responsible for secondary axis formation. Chimeric Wnt11/Wnt5a molecules revealed that the N-terminus with the elements PS3-1 and PS3-2 defines Wnt11 specificity, while elements PS3-1, PS3-2 and PS3-3 are required for Wnt5a specificity. Furthermore, we used Xenopus dorsal marginal zone explants to identify non-canonical Wnt target genes regulated by the Wnt5a branch and the Wnt11 branch. We found that pbk was specifically regulated by Wnt5a and rab11fip5 by Wnt11. Overexpression of these target genes phenocopied the overexpression of their regulators, confirming the distinct roles of Wnt11 and Wnt5a triggered signaling pathways. Furthermore, knock-down of pbk was able to restore convergent extension movements in Wnt5a morphants., Conclusions: The N-terminal part of non-canonical Wnt proteins decides whether the Wnt5a or the Wnt11 branch of the Wnt-signaling network gets activated. The different non-canonical Wnt branches not only regulate cellular behavior, but, surprisingly, also regulate the expression of different target genes. One of these target genes, pbk, seems to be the relevant target gene executing Wnt5a-mediated regulation of convergent extension movements.

Objective: For ultrasound, a wide variation is often observed among the number and sequence of images acquired for a particular examination type. Scanner-based protocols are preset pathways in the ultrasound machine that guide a sonographer through the required study images. These protocols can streamline image acquisition by improving consistency and efficiency of ultrasound examinations. This study evaluated whether implementation of scanner-based protocol-driven ultrasound improves efficiency by decreasing the scanning duration and number of images acquired., Materials and Methods: Retrospective evaluation of 437 carotid Doppler examinations, 395 complete abdominal ultrasound examinations with Doppler imaging, and 413 bilateral lower extremity venous Doppler examinations for deep venous thrombosis (DVT) performed by five sonographers before and after implementation of scanner-based protocol-driven ultrasound was performed. The scanning duration and number of images acquired for each study were recorded. Statistical analysis compared the scanning duration and number of images acquired before and after implementation of protocol-driven ultrasound. A p value of < 0.05 was considered significant., Results: A significant decrease in scanning duration occurred for both carotid Doppler ultrasound examinations (decrease by 12.4% [2.7 minutes], p < 0.0001) and complete abdominal ultrasound examinations with Doppler imaging (decrease by 7.5% [2.0 minutes], p = 0.0054) after implementation of protocol-driven ultrasound. The decrease in scanning duration was not significant for lower extremity DVT Doppler examinations (p = 0.4192). In addition, there was a significant decrease in the overall number of images obtained for all three types of studies., Conclusion: Scanner-based protocol-driven ultrasound is an effective method that streamlines image acquisition and significantly improves efficiency in an ultrasound department while ensuring consistency and adherence to accreditation guidelines.

Introduction: More than 20 years since the introduction of TAPP and TEP into clinical routine, there is a lack of clarity due to conflicting comparative data. Therefore, more results from registries are needed., Patients and Methods: A total of 17,587 patients were enrolled prospectively between September 1, 2009, and April 15, 2013, in the Herniamed registry. Of these patients, 10,887 (61.9%) had a TAPP and 6700 (38.1%) a TEP repair. The dependent variables were intra- and postoperative complication rates, number of reoperations as well as absolute and relative frequencies. The results of unadjusted analyses were verified via multivariable analyses., Results: Multivariable analysis verified the results of unadjusted analysis, indicating that the surgical technique did not have any significant impact, also while taking account of other factors, on occurrence of intraoperative [p = 0.1648; OR = 1.214 (0.923; 1.596)] and general postoperative complications [p = 0.0738; OR = 1.315 (0.974; 1.775)]. Postoperative surgical complications [OR = 2.323 (1.882; 2.866); p < 0.0001] were noted more often after TAPP. Furthermore, the hernia defect size [p < 0.0001; I vs III: OR = 0.439 (0.313; 0.615), II vs III: OR = 0.712 (0.582; 0.872)] or scrotal [p < 0.0001; OR = 2.170 (1.501; 3.137)] hernia and age [p = 0.0002; 10-year OR = 1.135 (1.062; 1.213)] had a significant impact on the occurrence of postoperative complications. Complications were observed more commonly for larger hernia defects and a scrotal hernia. However, the difference in the postoperative complication rate between TEP and TAPP did not result in any difference in the reoperation rate (TEP 0.82% vs TAPP 0.90%; p = 0.6165)., Conclusion: The intraoperative and general postoperative complication rates as well as the reoperation rate for complications show no significant difference between TEP and TAPP. The higher postoperative complication rate for TAPP, which could be managed conservatively, is partly explained by larger defect sizes, more scrotal hernias and older age.

Introduction: Following repair of a unilateral inguinal hernia, there is a risk of 1% per year of onset of an inguinal hernia on the other side. Comparison of bilateral with unilateral TAPP operation in a high-volume center found that morbidity and reoperation rates were only marginally higher for bilateral TAPP operation. Some authors are calling for prophylactic operation of the contralateral side., Methods: Between September 2009 and April 2013, data were entered into the Herniamed Registry on 15,176 patients who had undergone TAPP operation. Of these patients, 10,887 had been operated on because of a unilateral (71.7%) and 4289 because of a bilateral (28.3%) inguinal hernia., Results: A significant difference was noted in the rate of postoperative complications occurring within 30 days, which was 4.9% for bilateral compared with 3.9% for unilateral inguinal hernia (p = 0.009). The postoperative complications necessitated reoperation in 0.9% of patients after unilateral and in 1.9% of patients after bilateral inguinal hernia repair, thus attesting to the significantly higher risk presented by bilateral inguinal hernia repair (p = <0.001).Multivariate analysis confirmed the highly significant influence of bilateral TAPP on increased reoperation rates due to complications (p > 0.0001). The odds ratio was 2.13 (95% CI 1.58-2.86). Comparison of the results from a high-volume center with those from the Herniamed Registry showed that perioperative complication rates were markedly higher., Conclusion: Perioperative outcome of bilateral TAPP operation demonstrates significantly worse postoperative complication and reoperation rates compared with unilateral TAPP. Likewise, the results were markedly unfavorable compared with those of a high-volume center. If a bilateral hernia repair should be attempted in those patients with only a unilateral hernia, these data give the surgeon more information on how to better prepare a patient and obtain consent preoperatively.

All Staphylococcus aureus genomes contain a genomic island, which is termed νSaα and characterized by two clusters of tandem repeat sequences, i.e. the exotoxin (set) and 'lipoprotein-like' genes (lpl). Based on their structural similarities the νSaα islands have been classified as type I to IV. The genomes of highly pathogenic and particularly epidemic S. aureus strains (USA300, N315, Mu50, NCTC8325, Newman, COL, JH1 or JH9) belonging to the clonal complexes CC5 and CC8 bear a type I νSaα island. Since the contribution of the lpl gene cluster encoded in the νSaα island to virulence is unclear to date, we deleted the entire lpl gene cluster in S. aureus USA300. The results showed that the mutant was deficient in the stimulation of pro-inflammatory cytokines in human monocytes, macrophages and keratinocytes. Purified lipoprotein Lpl1 was further shown to elicit a TLR2-dependent response. Furthermore, heterologous expression of the USA300 lpl cluster in other S. aureus strains enhanced their immune stimulatory activity. Most importantly, the lpl cluster contributed to invasion of S. aureus into human keratinocytes and mouse skin and the non-invasive S. carnosus expressing the lpl gene cluster became invasive. Additionally, in a murine kidney abscess model the bacterial burden in the kidneys was higher in wild type than in mutant mice. In this infection model the lpl cluster, thus, contributes to virulence. The present report is one of the first studies addressing the role of the νSaα encoded lpl gene cluster in staphylococcal virulence. The finding that the lpl gene cluster contributes to internalization into non-professional antigen presenting cells such as keratinocytes highlights the lpl as a new cell surface component that triggers host cell invasion by S. aureus. Increased invasion in murine skin and an increased bacterial burden in a murine kidney abscess model suggest that the lpl gene cluster serves as an important virulence factor.

In healthy human skin host defense molecules such as antimicrobial peptides (AMPs) contribute to skin immune homeostasis. In patients with the congenital disease ectodermal dysplasia (ED) skin integrity is disturbed and as a result patients have recurrent skin infections. The disease is characterized by developmental abnormalities of ectodermal derivatives and absent or reduced sweating. We hypothesized that ED patients have a reduced skin immune defense because of the reduced ability to sweat. Therefore, we performed a label-free quantitative proteome analysis of wash solution of human skin from ED patients or healthy individuals. A clear-cut difference between both cohorts could be observed in cellular processes related to immunity and host defense. In line with the extensive underrepresentation of proteins of the immune system, dermcidin, a sweat-derived AMP, was reduced in its abundance in the skin secretome of ED patients. In contrast, proteins involved in metabolic/catabolic and biosynthetic processes were enriched in the skin secretome of ED patients. In summary, our proteome profiling provides insights into the actual situation of healthy versus diseased skin. The systematic reduction in immune system and defense-related proteins may contribute to the high susceptibility of ED patients to skin infections and altered skin colonization.

We opportunistically evaluated a combination of acepromazine maleate and medetomidine HCl for use in sedating Rocky Mountain elk (Cervus elaphus nelsoni) and black bears (Ursus americanus) as an alternative to scheduled drug combinations. This combination was safe and effective with limitations inherent in its sedative rather than anesthetic properties.

Marine denitrification constitutes an important part of the global nitrogen cycle and the diversity, abundance and process rates of denitrifying microorganisms have been the focus of many studies. Still, there is little insight in the ecophysiology of marine denitrifying communities. In this study, a heterotrophic denitrifying community from sediments of a marine intertidal flat active in nitrogen cycling was selected in a chemostat and monitored over a period of 50 days. The chemostat enabled the maintenance of constant and well-defined experimental conditions over the time-course of the experiment. Analysis of the microbial community composition by automated ribosomal intergenic spacer analysis (ARISA), Illumina sequencing and catalyzed reporter deposition fluorescence in situ hybridization (CARD-FISH) revealed strong dynamics in community composition over time, while overall denitrification by the enrichment culture was stable. Members of the genera Arcobacter, Pseudomonas, Pseudovibrio, Rhodobacterales and of the phylum Bacteroidetes were identified as the dominant denitrifiers. Among the fermenting organisms co-enriched with the denitrifiers was a novel archaeon affiliated with the recently proposed DPANN-superphylum. The pan-genome of populations affiliated to Pseudovibrio encoded a NirK as well as a NirS nitrite reductase, indicating the rare co-occurrence of both evolutionary unrelated nitrite reductases within coexisting subpopulations., (© 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.)

In the biogeochemical nitrogen cycle, microbial respiration processes compete for nitrate as an electron acceptor. Denitrification converts nitrate into nitrogenous gas and thus removes fixed nitrogen from the biosphere, whereas ammonification converts nitrate into ammonium, which is directly reusable by primary producers. We combined multiple parallel long-term incubations of marine microbial nitrate-respiring communities with isotope labeling and metagenomics to unravel how specific environmental conditions select for either process. Microbial generation time, supply of nitrite relative to nitrate, and the carbon/nitrogen ratio were identified as key environmental controls that determine whether nitrite will be reduced to nitrogenous gas or ammonium. Our results define the microbial ecophysiology of a biogeochemical feedback loop that is key to global change, eutrophication, and wastewater treatment., (Copyright © 2014, American Association for the Advancement of Science.)

Sandy coastal sediments are global hotspots for microbial mineralization of organic matter and denitrification. These sediments are characterized by advective porewater flow, tidal cycling and an active and complex microbial community. Metagenomic sequencing of microbial communities sampled from such sediments showed that potential sulfur oxidizing Gammaproteobacteria and members of the enigmatic BD1-5/SN-2 candidate phylum were abundant in situ (>10% and ~2% respectively). By mimicking the dynamic oxic/anoxic environmental conditions of the sediment in a laboratory chemostat, a simplified microbial community was selected from the more complex inoculum. Metagenomics, proteomics and fluorescence in situ hybridization showed that this simplified community contained both a potential sulfur oxidizing Gammaproteobacteria (at 24 ± 2% abundance) and a member of the BD1-5/SN-2 candidate phylum (at 7 ± 6% abundance). Despite the abundant supply of organic substrates to the chemostat, proteomic analysis suggested that the selected gammaproteobacterium grew partially autotrophically and performed hydrogen/formate oxidation. The enrichment of a member of the BD1-5/SN-2 candidate phylum enabled, for the first time, direct microscopic observation by fluorescent in situ hybridization and the experimental validation of the previously predicted translation of the stop codon UGA into glycine.

Xenopus cadherin-11 (Xcadherin-11) is an exceptional cadherin family member, which is predominantly expressed in cranial neural crest cells (NCCs). Apart from mediating cell-cell adhesion it promotes cranial NCC migration by initiating filopodia and lamellipodia formation. Here, we demonstrate an unexpected function of Xcadherin-11 in NCC specification by interfering with canonical Wnt/β-catenin signaling. Loss-of-function experiments, using a specific antisense morpholino oligonucleotide against Xcadherin-11, display a nuclear β-catenin localization in cranial NCCs and a broader expression domain of the proto-oncogene cyclin D1 which proceeds c-myc up-regulation. Additionally, we observe an enhanced NCC proliferation and an expansion of specific NCC genes like AP2 and Sox10. Thereby, we could allocate NCC proliferation and specification to different gene functions. To clarify which domain in Xcadherin-11 is required for early NCC development we tested different deletion mutants for their rescue ability in Xcadherin-11 morphants. We identified the cytoplasmic tail, specifically the β-catenin binding domain, to be necessary for proper NCC development. We propose that Xcadherin-11 is necessary for controlled NCC proliferation and early NCC specification in tuning the expression of the canonical Wnt/β-catenin target genes cyclin D1 and c-myc by regulating the concentration of the nuclear pool of β-catenin., (© 2013 Elsevier Inc. All rights reserved.)

Sediments of coastal upwelling areas are generally characterized by a high content of organic carbon that is mainly degraded via anaerobic microbial processes including sulfate reduction as a major terminal oxidation step. Despite the high importance of sulfate reduction in these sediments, the identity of sulfate-reducing bacteria (SRB) has remained almost unknown. Here, we applied a cultivation-based approach using selective enrichment conditions to study the diversity and distribution of active SRB in sediments along a transect perpendicular to the continental slope off the coast of Namibia (Meteor-cruise M76/1). To promote growth of the most abundant SRB, dilution series were prepared and amended with hydrogen, acetate, or a mixture of monomers representing typical substrates for SRB. Growth of SRB could be detected in the presence of all electron donors and from sediment down to 4 m depth. 16S rRNA gene-based DGGE analysis and sequencing revealed the predominance of SRB related to psychrophiles in particular to the genus Desulfofrigus, which made up 1 % of the total microbial community, accounting for an absolute abundance of up to 4.8 × 10(7)  cells mL(-1) . In general, the abundance of cultured SRB changed with depth and between the different sampling sites and correlated with the content of organic carbon as previously reported. Growth of chemolithotrophic SRB in relatively high dilution steps and the enrichment of methanogens as well as acetogens from deeper sediment point to a competition between hydrogen-utilizing microbial processes and their biogeochemical significance in deep sediment layers of the Benguela upwelling area., (© 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.)

So far, microbial physiology has dedicated itself mainly to pure cultures. In nature, cross feeding and competition are important aspects of microbial physiology and these can only be addressed by studying complete communities such as enrichment cultures. Metagenomic sequencing is a powerful tool to characterize such mixed cultures. In the analysis of metagenomic data, well established algorithms exist for the assembly of short reads into contigs and for the annotation of predicted genes. However, the binning of the assembled contigs or unassembled reads is still a major bottleneck and required to understand how the overall metabolism is partitioned over different community members. Binning consists of the clustering of contigs or reads that apparently originate from the same source population. In the present study eight metagenomic samples from the same habitat, a laboratory enrichment culture, were sequenced. Each sample contained 13-23 Mb of assembled contigs and up to eight abundant populations. Binning was attempted with existing methods but they were found to produce poor results, were slow, dependent on non-standard platforms or produced errors. A new binning procedure was developed based on multivariate statistics of tetranucleotide frequencies combined with the use of interpolated Markov models. Its performance was evaluated by comparison of the results between samples with BLAST and in comparison to existing algorithms for four publicly available metagenomes and one previously published artificial metagenome. The accuracy of the new approach was comparable or higher than existing methods. Further, it was up to a 100 times faster. It was implemented in Java Swing as a complete open source graphical binning application available for download and further development (http://sourceforge.net/projects/metawatt).

Wnt-11/planar cell polarity signaling polarizes mesodermal cells undergoing convergent extension during Xenopus laevis gastrulation. These shape changes associated with lateral intercalation behavior require a dynamic modulation of cell adhesion. In this paper, we report that Wnt-11/frizzled-7 (Fz7) controls cell adhesion by forming separate adhesion-modulating complexes (AMCs) with the paraxial protocadherin (PAPC; denoted as AMCP) and C-cadherin (denoted as AMCC) via distinct Fz7 interaction domains. When PAPC was part of a Wnt-11-Fz7 complex, its Dynamin1- and clathrin-dependent internalization was blocked. This membrane stabilization of AMCP (Fz7/PAPC) by Wnt-11 prevented C-cadherin clustering, resulting in reduced cell adhesion and modified cell sorting activity. Importantly, Wnt-11 did not influence C-cadherin internalization; instead, it promoted the formation of AMCC (Fz7/Cadherin), which competed with cis-dimerization of C-cadherin. Because PAPC and C-cadherin did not directly interact and did not form a joint complex with Fz7, we suggest that Wnt-11 triggers the formation of two distinct complexes, AMCC and AMCP, that act in parallel to reduce cell adhesion by hampering lateral clustering of C-cadherin.

3,5-Di-t-butyl catechol (DTCAT) releases Ca(2+) from rat skeletal muscle sarcoplasmic reticulum (SR) vesicles. Hence, it is a candidate for use as a substitute for halothane or caffeine in the in vitro contracture test for the diagnosis of susceptibility to malignant hyperthermia (MH). To characterize the effect of DTCAT at cell level, Ca(2+) release experiments were performed on cultured, human skeletal muscle myotubes using the fluorescent Ca(2+) indicator fura2-AM. DTCAT was also assayed in the in vitro contracture test on human skeletal muscle bundles obtained from individuals diagnosed susceptible (MHS), normal (MHN) or equivocal for halothane (MHEH) and compared to the standard test substances caffeine and halothane. DTCAT increased, in a concentration-dependent manner and with a higher efficacy as compared to caffeine, the free, intracellular Ca(2+) levels of cultured MHN and MHS skeletal muscle myotubes. This effect was similar in both types of myotubes and involved the release of Ca(2+) from SR stores as well as Ca(2+)-influx from the extracellular space. Inhibition of ryanodine receptors either with ryanodine or with ruthenium red markedly reduced DTCAT-induced increase in intracellular Ca(2+) concentration while abolishing that induced by caffeine. In MHN skeletal muscle bundles, DTCAT induced contractures with an EC(50) value of 160 ± 91 μM. However, the sensitivity of MHS or MHEH muscles to DTCAT was similar to that of MHN muscles. In conclusion, DTCAT is not suitable for the diagnosis of MH susceptibility due to its failure to discriminate between MHN and MHS muscles., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Malignant hyperthermia (MH) is a potentially lethal genetic disorder in response to volatile anesthetics and depolarizing muscle relaxants. To support the claim that a novel genetic variant causes MH, it is necessary to demonstrate that it has significant effects on the sensitivity of the ryanodine receptor (RYR1) calcium channel. In this study we focused on 2 Austrian families with strong MH disposition and new RYR1 variants., Methods: We sequenced the entire coding region of the RYR1 from 2 Austrian MH individuals. Genotype-phenotype segregation and evolutionary conservation of the variants were considered. On a functional level, Ca(2+) release experiments with fura-2-acetoxymethyl ester were performed in cultured skeletal muscle cells derived from individuals carrying the new variants and compared with control cells from nonsusceptible individuals. Caffeine, 4-chloro-m-cresole (4-CmC), and halothane were used as specific Ca(2+) releasing agents., Results: The variant p.A612P in family A segregated with an MH-susceptible phenotype and cells showed an increased sensitivity for all Ca(2+)-releasing substances tested. In family B, 2 variants (p.R2458H/p.R3348C) were identified. While p.R2458H and p.R2458H/p.R3348C segregated with an MH-susceptible diagnosis, p.R3348C alone showed an MH equivocal diagnosis. Ca(2+)-release experiments showed that exchanges of these highly conserved amino acids increased the sensitivities for the substances tested (except 4-CmC with p.R2458H and p.R3348C) when compared with the MH-negative control group., Conclusions: Our results suggest that these variants are new causative MH variants.

Cnidarians surprise by the completeness of Wnt gene subfamilies (11) expressed in an overlapping pattern along the anterior-posterior axis. While the functional conservation of canonical Wnt-signaling components in cnidarian gastrulation and organizer formation is evident, a role of Nematostella Wnts in noncanonical Wnt-signaling has not been shown so far. In Xenopus, noncanonical Wnt-5a/Ror2 and Wnt-11 (PCP) signaling are distinguishable by different morphant phenotypes. They differ in PAPC regulation, cell polarization, cell protrusion formation, and the so far not reported reorientation of the microtubules. Based on these readouts, we investigated the evolutionary conservation of Wnt-11 and Wnt-5a function in rescue experiments with Nematostella orthologs and Xenopus morphants. Our results revealed that NvWnt-5 and -11 exhibited distinct noncanonical Wnt activities by disturbing convergent extension movements. However, NvWnt-5 rescued XWnt-11 and NvWnt-11 specifically XWnt-5a depleted embryos. This unexpected 'inverse' activity suggests that specific structures in Wnt ligands are important for receptor complex recognition in Wnt-signaling. Although we can only speculate on the identity of the underlying recognition motifs, it is likely that these crucial structural features have already been established in the common ancestor of cnidarians and vertebrates and were conserved throughout metazoan evolution.

The glycolipid specific Drosophila melanogaster β1,4-N-acetylgalactosaminyltransferase B (β4GalNAcTB) depends on a zinc finger DHHC protein family member named GalNAcTB pilot (GABPI) for activity and translocation to the Golgi. The six-membrane spanning protein actually lacks the cysteine in the cytoplasmic DHHC motif, displaying DHHS instead. Here we show that the whole conserved region around the DHHS sequence, which is essential for palmitoylation in DHHC proteins, is not required for GABPI to interact with β4GalNAcTB. In contrast, the two luminal loops between transmembrane domain 3-4 and 5-6 contain conserved amino acids, which are crucial for activity. Besides the dependence on GABPI, β4GalNAcTB requires its exceptional short stem region for activity. A few hydrophobic amino acids positioned close to the transmembrane domain are essential for the interaction with GABPI. Along with its catalytic domain, β4GalNAcTB, thus, requires an area in its own stem region and two small luminal loops of GABPI as "add-on" domains. Moreover, some inactive GABPI mutants could be rescued by fusion with β4GalNAcTB, indicating their importance in direct GABPI-β4GalNAcTB interaction.

In the United States, products from chickens that were not administered antimicrobial medications during growout can contain labels stating "no antibiotics added." Here we compared microbial profiles of chicken products labeled as coming from birds raised without antimicrobial medications (N=201; NON) with chicken products carrying conventional labels (N=201; CONV). There were no differences in percentages of samples positive for Enterococcus spp. (CONV: 17.4%; NON: 21.3%) or Escherichia coli (CONV: 25.9%; NON: 22.3%). The number of samples positive for Salmonella was low in both groups, but statistically higher in the NON samples (5.0%) versus CONV samples (1.5%; p<0.05). Conversely, CONV samples contained higher concentrations of coliforms (CONV: 3.0 log(10)CFU/mL; NON: 2.5 log(10)CFU/mL; p<0.05). E. coli (N=190) and Enterococcus spp. isolates (N=113) were tested for resistance to common antimicrobials. E. coli isolates from CONV samples were more frequently resistant to at least one antimicrobial (CONV: 61.3%; NON: 41.2%; p<0.05). Enterococcus spp. isolates from both groups were equally likely to be resistant to at least one antimicrobial, but Enterococcus spp. isolates from CONV samples were more likely to be resistant to erythromycin, kanamycin, and gentamicin (p<0.05). Taken together, these data suggest that NON samples may more frequently carry Salmonella; however, E. coli and Enterococcus spp. found on CONV are more likely to be resistant to some antimicrobials.

Background: A low rate of chronic pain and maximum postoperative comfort are the main goals today in inguinal hernia repair. This four-arm randomised trial compares these parameters after laparoscopic hernia repair (TAPP) with a standard heavyweight mesh (HW), a pure middleweight polypropylene mesh (MW), a lightweight composite polypropylene mesh (LW), or a titanised lightweight mesh (TLW). The primary endpoint of the study was the incidence of chronic pain of any severity at the site of hernia repair at 1 year., Methods: A total of 600 patients with a laparoscopic inguinal hernia repair and a defect diameter of 3-5 cm were included in the trial. In all patients, a non-invasive mesh fixation technique was performed using fibrin glue. Patients were assessed for pain, foreign body sensation, and physical activities preoperatively, early postoperatively, at 4 weeks, at 6 months, and at 1 year by questionnaire, and were examined clinically. Postoperatively, seroma formation was measured by ultrasound., Results: At 1 year after TAPP, frequency of pain did not differ statistically between the four groups (depending on type of activity: between 6-8% with HW mesh, 2-4% with middleweight mesh, and 2-4.7% with both lightweight meshes); average intensity of pain was very low, at between VAS 0.4 ± 3.1 and 1.5 ± 7.8 (MW, LW, TLW) and between 1.9 ± 8.6 and 2.3 ± 9.1 (HW) depending on activity (n.s.). Early postoperatively between 31.3% (LW) and 21.3% (TLW) of the patients needed pain medication (n.s.); at 1 year this percentage had dropped to 0.3% (one HW, one MW). Foreign body sensation did not differ but impairment of physical activities (P = 0.0437) was significantly less in the MW, LW, and TLW group (6-12.7%) compared to HW (15.3%) at 4 weeks; at 1 year this percentage was between 0 and 1.3% (n.s.)., Conclusion: Compared to HW mesh, the use of MW, LW, and TLW meshes for laparoscopic hernia repair did not significantly affect rate of chronic pain, but seemed to improve early postoperative convalescence. No difference was found between middleweight pure polypropylene (MW), composite lightweight (LW), or titanised lightweight polypropylene (TLW) meshes.

Objectives: The aim of the present in vitro study was to evaluate the effects of different biomaterials used for regenerative periodontal surgery on the growth of the periodontopathogen Aggregatibacter actinomycetemcomitans., Methods: Three commercially available biomaterials of synthetic origin (hydroxyapatite/beta-tricalcium phosphate, nanostructured hydroxyapatite paste, oily calcium hydroxide suspension), a bovine-derived xenograft as well as an enamel matrix derivative (EMD) were added in different concentrations to calibrated suspensions of A. actinomycetemcomitans ATCC 43718/33384 (serotype b/c). Equal aliquots (0.1 ml) for the viability assay were taken after 5 min, 1h, 3h, 8h and 24h, plated on blood agar and incubated in an anaerobic environment for 48 h at 37°C. Viable cell counts were expressed as colony forming units (cfu)/0.1 ml., Results: The results demonstrated that none of the investigated biomaterials could inhibit the growth of A. actinomycetemcomitans serotype b. A marked growth reduction of A. actinomycetemcomitans serotype c was observed in the presence of oily calcium hydroxide suspension and nanostructured hydroxyapatite. In contrast, no significant growth inhibition could be observed in the presence of hydroxyapatite/beta-tricalcium phosphate, enamel matrix derivative and bovine-derived xenograft., Conclusions: The results of the present study suggest that none of the investigated biomaterials possesses antimicrobial properties against A. actinomycetemcomitans serotype b. Therefore, the use of these biomaterials for regenerative procedures should be weighted critically in the presence of A. actinomycetemcomitans serotype b., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Nitrate is a key node in the network of the assimilatory and respiratory nitrogen pathways. As one of the 'fixed' forms of nitrogen, nitrate plays an essential role in both nature and industry. For bacteria, it is both a nitrogen source and an electron acceptor. In agriculture and wastewater treatment, nitrate respiration by microorganisms is an important issue with respect to economics, greenhouse gas emission and public health. Several microbial processes compete for nitrate: denitrification, dissimilatory nitrate reduction to ammonium and anaerobic ammonium oxidation. In this review we provide an up to date overview of the organisms, genes and enzymes involved in nitrate respiration. We also address the molecular detection of these processes in nature. We show that despite rapid progress in the experimental and genomic analyses of pure cultures, knowledge on the mechanism of nitrate reduction in natural ecosystems is still largely lacking., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Introduction: The medical use of cannabinoids is limited mainly by their undesirable effects. With respect to acute psychotropic effects, the aim of this study is the comparison of an oral cannabis extract and low-dose diazepam in a cross-over experiment in drug-naïve healthy women., Methods: Sixteen healthy females participated in this randomized, double-blind, active comparator-controlled, single-dose, balanced 2-way cross-over study. Cannabis extract with standardised Delta (9)-tetrahydrocannabinol (THC) content (20 mg) or active placebo (5 mg diazepam) was administered orally. Subjects were assessed by self- and observer-rated visual analogue scales (VAS), the BRIEF PSYCHIATRIC RATING SCALE (BPRS) and three psychomotor tests up to 6 h after administration., Results: VAS showed significantly elevated fatigue, drowsiness, dizziness, and "feeling high" after cannabis as compared to baseline and diazepam. BPRS scores were significantly higher after cannabis intake. Only in one psychomotor test a decrease of psychomotor activity after cannabis was evident. One subject in the cannabis condition experienced severe transient psychotic symptoms., Discussion: Orally administered cannabis produced significant central depressant side-effects compared to diazepam, mostly subjective effects (VAS) but marginal effects in psychomotor performance in 15 healthy females. Regarding the medical use of cannabis, a rigorous benefit-risk analysis and an exact psychiatric assessment before and during treatment are necessary., ((c) Georg Thieme Verlag KG Stuttgart . New York.)