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The precise regulation of microRNA (miRNA) biogenesis is crucial for plant development, which requires core microprocessors and many fine tuners to coordinate their miRNA processing activity/specificity in fluctuating cellular environments. During de-etiolation, light triggers a dramatic accumulation of core microprocessors and primary miRNAs (pri-miRNAs) but decreases pri-miRNA processing activity, resulting in relatively constant miRNA levels. The mechanisms underlying these seemingly contradictory regulatory changes remain unclear. In this study, we identified forkhead-associated domain 2 (FHA2) as a light-stabilized suppressor of miRNA biogenesis. We found that FHA2 deficiency increased the level of mature miRNAs, accompanied by a reduction in pri-miRNAs and target mRNAs. Biochemical assays showed that FHA2 associates with the core microprocessors DCL1, HYL1, and SE, forming a complex to suppress their pri-miRNA processing activity. Further analyses revealed that FHA2 promotes HYL1 binding but inhibits the binding of DCL1-PAZ-RNase-RNA-binding domains (DCL1-PRR) to miRNAs, whereas FHA2 does not directly bind to these RNAs. Interestingly, we found that FHA2 protein is unstable in the dark but stabilized by light during de-etiolation. Consistently, disruption of FHA led to defects in light-triggered changes in miRNA expression and reduced the survival rate of de-etiolated seedlings after prolonged light deprivation. Collectively, these data suggest that FHA2 is a novel light-stabilized suppressor of miRNA biogenesis and plays a role in fine-tuning miRNA processing during de-etiolation., (Copyright © 2021 The Author. Published by Elsevier Inc. All rights reserved.)

Introduction: Anorexia nervosa (AN) is a psychiatric disorder with a high mortality and unknown etiology, and effective treatment is lacking. For decades, cannabis has been known to cause physical effects on the human body, including increasing appetite, which may be beneficial in the treatment of AN., Objective: To systematically review the literature for evidence of an effect of cannabinoids on (1) weight gain, and (2) other outcomes, in AN., Method: A systematic review was done using three databases Embase, PubMed and Psychinfo. The review was registered in PROSPERO with ID number CRD42019141293 and was done according to PRISMA guidelines., Results: There were 1288 studies identified and after thorough review and exclusion of copies, 4 studies met the inclusion criteria. Three studies used the same AN population and utilized data from one original study, leaving only two original studies. Both of these were Randomized Controlled Trials that explored the effects of delta-9-tetrahydrocannabinol (Δ9-THC) or dronabinol in AN, whereof one study was properly designed and powered and showed a weight increase of an added 1 kg over 4 weeks over placebo., Discussion and Conclusion: There are few studies and the level of evidence is low. The only properly designed, low bias and highly powered study found a weight increasing effect of dronabinol in AN, while the other, using Δ9-THC at a high dose, found no effect and where the dose may have counteracted the weight gaining effects due to adverse events. More research on cannabinoids in anorexia nervosa is warranted, especially its effects on psychopathology., Level of Evidence: Level I, systematic review.

Our sensory systems provide complementary information about the multimodal objects and events that are the target of perception in everyday life. Professional musicians' specialization in the auditory domain is reflected in the morphology of their brains, which has distinctive characteristics, particularly in areas related to auditory and audio-motor activity. Here, we combined diffusion tensor imaging (DTI) with a behavioral measure of visually induced gain in pitch discrimination, and we used measures of cortical thickness (CT) correlations to assess how auditory specialization and musical expertise are reflected in the structural architecture of white and grey matter relevant to audiovisual processing. Across all participants (n = 45), we found a correlation (p < 0.001) between reliance on visual cues in pitch discrimination and the fractional anisotropy (FA) in the left inferior fronto-occipital fasciculus (IFOF), a structure connecting visual and auditory brain areas. Group analyses also revealed greater cortical thickness correlation between visual and auditory areas in non-musicians (n = 28) compared to musicians (n = 17), possibly reflecting musicians' auditory specialization (FDR < 10%). Our results corroborate and expand current knowledge of functional specialization with a specific focus on audition, and highlight the fact that perception is essentially multimodal while uni-sensory processing is a specialized task.

Since cheese is poor in energy for bacterial growth, it is believed that non-starter lactic acid bacteria growth and flavour development are supported by the nutrients from lysis of the starter culture. This study was performed to investigate the dynamics of interaction between starter and non-starter strains from cheese. A starter culture lysate was prepared by enzymatic digestion and tested as a growth substrate for Lactobacillus sp. strains. The two starter culture strains of Lactococcus lactis were also tested on the starter-lysate. All seventeen strains were individually inoculated at the level of 5.0 log 10 cfu mL -1 in M17 broth, with or without 10% starter-lysate, and incubated at 30 °C for 140 h. The optical density 600 nm was modelled with the primary log-transformed Logistic model with delay and lag phase duration, maximum specific growth rate as well as maximum population density obtained. Biphasic growth was mainly observed when the strains were able to utilize the starter-lysate as an energy source. To deal with the lack-of-fit related to the biphasic growth, the observed data points of the curve were divided after graphic evaluation and according to deviation of the residuals from the range ±0.05. Modelling was then performed in two phases by applying the same primary Logistic model in each of the two parts of the growth curve. Values of root-mean-square error and graphic evaluation indicated the good fitting of the data with the suggested approach. The growth of the two Lactococcus lactis strains was not affected by the starter-lysate. However, thirteen of the non-starter strains had their growth rates increased. The increase was greatest for Lactobacillus rhamnosus KU-LbR1, which reached maximum optical densities of 0.23 and 0.58 in the absence and the presence of starter-lysate, respectively. No effect of the starter-lysate was shown for the growth of Lactobacillus curvatus strains. The extend of the growth of non-starter strains on the starter-lysate was shown to be species and strain dependent., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Smart manufacturing, tailored by the 4th industrial revolution and forces like innovation, competition, and changing demands, lies behind the concurrent evolution (also known as co-evolution) of products, processes and production systems. Manufacturing companies need to adapt to ever-changing environments by simultaneously reforming and regenerating their product, process, and system models as well as goals and strategies to stay competitive. However, the ever-increasing complexity and ever-shortening lifecycles of product, process and system domains challenge manufacturing organization's conventional approaches to analysing and formalizing models and processes as well as management, maintenance and simulation of product and system life cycles. The digital twin-based virtual factory (VF) concept, as an integrated simulation model of a factory including its subsystems, is promising for supporting manufacturing organizations in adapting to dynamic and complex environments. In this paper, we present the demonstration and evaluation of previously introduced digital twin-based VF concept to support modelling, simulation and evaluation of complex manufacturing systems while employing multi-user collaborative virtual reality (VR) learning/training scenarios. The concept is demonstrated and evaluated using two different wind turbine manufacturing cases, including a wind blade manufacturing plant and a nacelle assembly line. Thirteen industry experts who have diverse backgrounds and expertise were interviewed after their participation in a demonstration. We present the experts' discussions and arguments to evaluate the DT-based VF concept based on four dimensions, namely, dynamic, open, cognitive, and holistic systems. The semi-structured conversational interview results show that the DT-based VF stands out by having the potential to support concurrent engineering by virtual collaboration. Moreover, DT-based VF is promising for decreasing physical builds and saving time by virtual prototyping (VP)., Competing Interests: Conflict of interestNo potential conflict of interest was reported by the authors and the stakeholders., (© The Author(s), under exclusive licence to Springer-Verlag London Ltd. part of Springer Nature 2021.)

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) CC398 has emerged in humans throughout Europe and the USA during the last decade and is associated with the spread of LA-MRSA CC398 in production animals. In this study, we investigated the risk of subsequent hospitalization with an S. aureus-related diagnosis and death within the first 2 years after MRSA diagnosis. The study included 7,521 carriers of MRSA, an age-matched reference population of 376,041 individuals and 7,607 patients infected with MRSA. Hazard ratios (HR) for hospitalization with an S. aureus-related diagnosis were 4.09 (95% CI: 2.78-6.00) and for death 1.21 (95% CI: 0.80-1.83) in LA-MRSA CC398 carriers compared with the reference population. Comparing carriers of LA-MRSA CC398 and non-CC398 MRSA, HR for hospitalization was 0.61 (95% CI: 0.37-0.99) and death 0.25 (95% CI: 0.16-0.40), respectively. Patients initially diagnosed with LA-MRSA CC398 or non-CC398 MRSA infection differed from MRSA carriers in terms of older age, higher Charlson comorbidity index score and longer hospital stays. HR for subsequent hospitalization and death was similar regardless having infection with LA-MRSA CC398 or non-CC398 MRSA at the time of MRSA diagnosis. We established that MRSA CC398 carriers have a lower risk of hospitalization and death up to 2 years after MRSA diagnosis than non-CC398 MRSA carriers do. In contrast, MRSA carriage, regardless the MRSA strain is a burden in terms of hospitalization and death when compared to the background reference population. Further, we established that there are no differences in risk of subsequent hospitalization and death in patients initially diagnosed with MRSA CC398 or non-CC398 MRSA infection. We suggest that public health surveillance of MRSA clearly needs to distinguish between carriage and infection as well as strain type before any inference from number of cases to disease burden is made., (© 2020 Wiley-VCH GmbH.)

Type 1 diabetes (T1D) is largely considered an autoimmune disease leading to the destruction of insulin-producing pancreatic β cells. Further, patients with T1D have 3-4-fold increased risk of developing micro- and macrovascular complications. However, the contribution of immune-related factors contributing to these diabetes complications are poorly understood. Individuals with long-term T1D who do not progress to vascular complications offer a great potential to evaluate end-organ protection. The aim of the present study was to investigate the association of inflammatory protein levels with vascular complications (retinopathy, nephropathy, cardiovascular disease) in individuals with long-term T1D compared to individuals who rapidly progressed to complications. We studied a panel of inflammatory markers in plasma of patients with long-term T1D with (n = 81 and 26) and without (n = 313 and 25) vascular complications from two cross-sectional Scandinavian cohorts (PROLONG and DIALONG) using Luminex technology. A subset of PROLONG individuals (n = 61) was screened for circulating immune cells using multicolor flow cytometry. We found that elevated plasma levels of soluble interleukin-2 receptor alpha (sIL-2R) were positively associated with the complication phenotype. Risk carriers of polymorphisms in the IL2RA and PTPN2 gene region had elevated plasma levels of sIL-2R. In addition, cell surface marker analysis revealed a shift from naïve to effector T cells in T1D individuals with vascular complications as compared to those without. In contrast, no difference between the groups was observed either in IL-2R cell surface expression or in regulatory T cell population size. In conclusion, our data indicates that IL2RA and PTPN2 gene variants might increase the risk of developing vascular complications in people with T1D, by affecting sIL-2R plasma levels and potentially lowering T cell responsiveness. Thus, elevated sIL-2R plasma levels may serve as a biomarker in monitoring the risk for developing diabetic complications and thereby improve patient care., (Copyright © 2020 Keindl, Fedotkina, du Plessis, Jain, Bergum, Mygind Jensen, Laustrup Møller, Falhammar, Nyström, Catrina, Jörneskog, Groop, Eliasson, Eliasson, Brismar, Nilsson, Berg, Appel and Lyssenko.)

Antiviral strategies to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here, we demonstrate that the NRF2 antioxidant gene expression pathway is suppressed in biopsies obtained from COVID-19 patients. Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a cellular antiviral program that potently inhibits replication of SARS-CoV2 across cell lines. The inhibitory effect of 4-OI and DMF extends to the replication of several other pathogenic viruses including Herpes Simplex Virus-1 and-2, Vaccinia virus, and Zika virus through a type I interferon (IFN)-independent mechanism. In addition, 4-OI and DMF limit host inflammatory responses to SARS-CoV2 infection associated with airway COVID-19 pathology. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and in suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2.

This review summarises the knowledge of abdominal ectopic pregnancy (AEP), which is a rare condition with higher morbidity and mortalilty than other types of ectopic pregnancies. The condition can be primary, if the pregnancy implants directly on to an abdominal site, or it can be secondary after a tubar abortion. AEP differs from tubal pregnancies by a normal level of human chorionic gonadotropin and rare vaginal bleeding, which causes a diagnostic delay. In an early pregnancy the treatment is laparoscopic removal, but in second and third trimester pregnancies laparotomy is preferred, if possible preceded by MRI for mapping of vascular involvement and location of placenta.

This study was performed to investigate the presence of histamine forming bacteria in commercially available cheeses as well as to evaluate the histamine forming potential using in vitro models. Five long-time-ripened cheeses made from different milk types were analysed for histamine producing bacterial isolates. The ability of the isolates to produce histamine was tested by incubation at 37 °C for five days in a restricted media with a pH indicator. Changes in the amino-compound profile were investigated using ultra performance liquid chromatography. Only eight of 106 isolates were able to produce compounds raising the pH and seven of those were confirmed to be histamine producers. Despite the fact that all isolates were obtained from the same vintage Danish Gouda cheese, made from raw cow milk, the amino-compound profile as well as the response to different environmental conditions diverged between the isolates. Rep-PCR and 16S rRNA gene sequencing was used to further characterize the isolates. Pediococcus pentosaceus was for the first time reported to be a histamine producer in cheese. The presence of the histidine decarboxylase gene (hdcA) was confirmed by PCR amplification of the histidine decarboxylase gene in four of the isolates. The results indicate that evaluating the presence and concentration of histamine is not only a relevant parameter to evaluate quality and safety, but is also an important tool to classify histamine producers in cheese., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with comorbidity and decreased quality of life. The current treatment of PsA is non-steroid anti-inflammatory drugs or in more severe cases disease modifying antirheumatic drugs such as methotrexate or leflunomide, but these agents are often inadequately effective. Biologic tumour necrosis factor (TNF)-inhibitors are effective in the treatment of PsA. However, many patients lose efficacy or have an insufficient response to TNF-inhibitors. Biologic agents targeting interleukin-17A have shown encouraging clinical results.

Angiogenesis is considered integral to the reparative process after ischemic injury. The α v β₃ integrin is a critical modulator of angiogenesis and highly expressed in activated endothelial cells. 68 Ga-NODAGA-E[(cRGDyK)]₂ (RGD) is a positron-emission-tomography (PET) ligand targeted towards α v β₃ integrin. The aim was to present data for the uptake of RGD and correlate it with histology and to further illustrate the differences in angiogenesis due to porcine adipose-derived mesenchymal stromal cell (pASC) or saline treatment in minipigs after induction of myocardial infarction (MI). Three minipigs were treated with direct intra-myocardial injection of pASCs and two minipigs with saline. MI was confirmed by 82 Rubidium ( 82 Rb) dipyridamole stress PET. Mean Standardized Uptake Values (SUV mean ) of RGD were higher in the infarct compared to non-infarct area one week and one month after MI in both pASC-treated (SUV mean : 1.23 vs. 0.88 and 1.02 vs. 0.86, p < 0.05 for both) and non-pASC-treated minipigs (SUV mean : 1.44 vs. 1.07 and 1.26 vs. 1.04, p < 0.05 for both). However, there was no difference in RGD uptake, ejection fractions, coronary flow reserves or capillary density in histology between the two groups. In summary, indications of angiogenesis were present in the infarcted myocardium. However, no differences between pASC-treated and non-pASC-treated minipigs could be demonstrated., Competing Interests: T.R., B.F., J.K., M.B.-L., J.M., T.E.C., M.J., K.P.H., C.H.M., J.P.G., P.H., A.K.: Has nothing to disclose. S.C.: Have a US patent pending on alginate hydrogel formulation.

During copy-editing, the y-axes of Fig. 2 (top) and Fig. 3 (top) were erroneously labelled mean BCG (d') in the version of the paper published as Online First. The correct label is meanCE (d').

Perception is fundamentally a multisensory experience. The principle of inverse effectiveness (PoIE) states how the multisensory gain is maximal when responses to the unisensory constituents of the stimuli are weak. It is one of the basic principles underlying multisensory processing of spatiotemporally corresponding crossmodal stimuli that are well established at behavioral as well as neural levels. It is not yet clear, however, how modality-specific stimulus features influence discrimination of subtle changes in a crossmodally corresponding feature belonging to another modality. Here, we tested the hypothesis that reliance on visual cues to pitch discrimination follow the PoIE at the interindividual level (i.e., varies with varying levels of auditory-only pitch discrimination abilities). Using an oddball pitch discrimination task, we measured the effect of varying visually perceived vertical position in participants exhibiting a wide range of pitch discrimination abilities (i.e., musicians and nonmusicians). Visual cues significantly enhanced pitch discrimination as measured by the sensitivity index d', and more so in the crossmodally congruent than incongruent condition. The magnitude of gain caused by compatible visual cues was associated with individual pitch discrimination thresholds, as predicted by the PoIE. This was not the case for the magnitude of the congruence effect, which was unrelated to individual pitch discrimination thresholds, indicating that the pitch-height association is robust to variations in auditory skills. Our findings shed light on individual differences in multisensory processing by suggesting that relevant multisensory information that crucially aids some perceivers' performance may be of less importance to others, depending on their unisensory abilities.

Background: The lack of lung transplant donors has necessitated the use of donors with a smoking history and donors of older age. We have evaluated the effects of donor smoking history and age on recipient morbidity and mortality with baseline values of pulmonary function and survival free of chronic lung allograft dysfunction (CLAD) as morbidity variables., Methods: This is a retrospective analysis of 588 consecutive lung transplant recipients and their corresponding 454 donors. Donors were divided into three groups: group 1 included smokers, group 2 nonsmokers, and group 3 had unknown smoking status; these were further divided into three age groups: group A: 0 to 39 years; group B: 40 to 54 years; and group C: ≥55 years., Results: One hundred fifty-one donors were former or actual smokers, 175 were nonsmokers, and 128 had unknown smoking histories. Baseline forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of carbon monoxide were lowest in the groups who received lungs from a smoking donor. CLAD-free survival was identical in all smoking groups, and overall survival was better both for lungs from nonsmoking donors and donors with unknown smoking status compared to lungs from smoking donors. One hundred sixty-nine donors were in age group A, 203 in B, and 82 in C. Baseline forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of carbon monoxide were lowest in the groups who received lungs from donors older than 55 years. Overall survival as well as CLAD-free survival was significantly lower with donors ≥55 years., Conclusions: Donor smoking history and older donor age impact lung function, mortality, and CLAD-free survival after transplantation. Because of a shortage of organs, extended donor criteria may be considered while taking waiting list mortality into account., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Ionotropic glutamate receptor antagonists are valuable tool compounds for studies of neurological pathways in the central nervous system. On the basis of rational ligand design, a new class of selective antagonists, represented by (2S,4R)-4-(2-carboxyphenoxy)pyrrolidine-2-carboxylic acid (1b), for cloned homomeric kainic acid receptors subtype 1 (GluK1) was attained (K i = 4 μM). In a functional assay, 1b displayed full antagonist activity with IC 50 = 6 ± 2 μM. A crystal structure was obtained of 1b when bound in the ligand binding domain of GluK1. A domain opening of 13-14° was seen compared to the structure with glutamate, consistent with 1b being an antagonist. A structure-activity relationship study showed that the chemical nature of the tethering atom (C, O, or S) linking the pyrrolidine ring and the phenyl ring plays a key role in the receptor selectivity profile and that substituents on the phenyl ring are well accommodated by the GluK1 receptor.

Introduction: The debate on non-medical male circumcision has gaining momentum during the past few years. The objective of this systematic review was to determine if circumcision, medical indication or age at circumcision had an impact on perceived sexual function in males., Methods: Systematic searches were performed in MEDLINE and Embase. The included studies compared long-term sexual function in circumcised and non-circumcised males, before and after circumcision, or compared different ages at circumcision. The quality of the studies was assessed according to the level of evidence (Grade A-D)., Results: Database and hand searches yielded 3,677 records. Inclusion criteria were fulfilled in 38 studies including two randomised trials. Overall, the only identified differences in sexual function in circumcised males were decreased premature ejaculation and increased penile sensitivity (Grade A-B). Following non-medical circumcision, no inferior sexual function was reported (A-B). Following medical circumcision, most outcomes were comparable (B); however, problems in obtaining an orgasm were increased (C) and erectile dysfunction was reported with inconsistency (D). A younger age at circumcision seemed to cause less sexual dysfunction than circumcision later in life., Conclusions: The hypothesis of inferior male sexual function following circumcision could not be supported by the findings of this systematic review. However, further studies on medical circumcision and age at circumcision are required.

In a previous study, a model was developed to describe the transfer and survival of Salmonella during grinding of pork (Møller, C.O.A., Nauta, M.J., Christensen, B.B., Dalgaard, P., Hansen, T.B., 2012. Modelling transfer of Salmonella typhimurium DT104 during simulation of grinding of pork. Journal of Applied Microbiology 112 (1), 90-98). The robustness of this model is now evaluated by studying its performance for predicting the transfer and survival of Salmonella spp. and Listeria monocytogenes during grinding of different types of meat (pork and beef), using two different grinders, different sizes and different numbers of pieces of meats to be ground. A total of 19 grinding trials were collected. Acceptable Simulation Zone (ASZ), visual inspection of the data, Quantitative Microbiological Risk Assessment (QMRA), as well as the Total Transfer Potential (TTP) were used as approaches to evaluate model performance and to access the quality of the cross contamination model predictions. Using the ASZ approach and considering that 70% of the observed counts have to be inside a defined acceptable zone of ±0.5 log10CFU per portion, it was found that the cross contamination parameters suggested by Møller et al. (2012) were not able to describe all 19 trials. However, for each of the collected grinding trials, the transfer event was well described when fitted to the model structure proposed by Møller et al. (2012). Parameter estimates obtained by fitting observed trials performed at different conditions, such as size and number of pieces of meat to be ground, may not be applied to describe cross contamination of unlike processing. Nevertheless, the risk estimates, as well as the TTP, revealed that the risk of disease may be reduced when the grinding of meat is performed in a grinder made of stainless steel (for all surfaces in contact with the meat), using a well-sharpened knife and holding at room temperatures lower than 4°C., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A novel transparent touch sensor was fabricated with a drop-on-demand inkjet printing technique on borosilicate glass and flexible polyethylene terephthalate (PET) substrates. Conductive poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (, Pedot: PSS) and dielectric poly(methylsiloxane) were deposited on a desired area to form a capacitive touch sensor structure. The properties of the printed sensors (optical transparency, electrical resistance and touch sensing performance) were investigated with varying, Pedot: PSS printing passes. A novel transparent touch sensor fabricated with an all-inkjet-printing method is demonstrated for the first time. This process holds industrially viable potential to fabricate transparent touch sensors with an inkjet printing technique on both rigid and flexible substrates for a wide range of applications.

Herein we describe the first structure-activity relationship study of the broad-range iGluR antagonist (2S,3R)-3-(3-carboxyphenyl)pyrrolidine-2-carboxylic acid (1) by exploring the pharmacological effect of substituents in the 4, 4', or 5' positions and the bioisosteric substitution of the distal carboxylic acid for a phosphonic acid moiety. Of particular interest is a hydroxyl group in the 4' position 2a which induced a preference in binding affinity for homomeric GluK3 over GluK1 (Ki = 0.87 and 4.8 μM, respectively). Two X-ray structures of ligand binding domains were obtained: 2e in GluA2-LBD and 2f in GluK1-LBD, both at 1.9 Å resolution. Compound 2e induces a D1-D2 domain opening in GluA2-LBD of 17.3-18.8° and 2f a domain opening in GluK1-LBD of 17.0-17.5° relative to the structures with glutamate. The pyrrolidine-2-carboxylate moiety of 2e and 2f shows a similar binding mode as kainate. The 3-carboxyphenyl ring of 2e and 2f forms contacts comparable to those of the distal carboxylate in kainate.

Two α-amino acid-functionalized quinoxalines, 1a (CNG-10301) and 1b (CNG-10300), of a quinoxaline moiety coupled to an amino acid moiety were designed, synthesized, and characterized pharmacologically. While 1a displayed low affinity at native AMPA, KA, and NMDA receptors, and at homomeric GluK1,3 receptors, the affinity for GluK2 was in the midmicromolar range (Ki = 136 μM), 1b displayed low to midmicromolar range binding affinity at all the iGluRs (Ki = 9-126 μM). In functional experiments (outside-out patches excised from transfected HEK293T cells), 100 μM 1a partially blocked GluK1 (33% peak response), while GluK2 was unaffected (96% peak response). Furthermore, 1a was shown not to be an agonist at GluK1 and GluK2 at 100 μM. On the other hand, 100 μM 1b fully antagonized GluK1 (8% peak response) but only partially blocked GluK2 (33% peak response). An X-ray structure at 2.3 Å resolution of 1b in the GluK1-LBD (ligand-binding domain) disclosed an unexpected binding mode compared to the predictions made during the design phase; the quinoxaline moiety remains to act as an amino acid bioisostere, but the amino acid moiety is oriented into a new area within the GluK1 receptor. The structure of the GluK1-LBD with 1b showed a large variation in domain openings of the three molecules from 25° to 49°, demonstrating that the GluK1-LBD is capable of undergoing major domain movements.

Objective: This study aims to evaluate the diagnostic efficiency of pattern recognition by transvaginal ultrasonography (TVS) and gel infusion sonography (GIS) for identifying endometrial pathology and to compare this setup with a standard setup of endometrial sampling (ES), hysteroscopy with pattern evaluation (HY(pattern)), or magnetic resonance imaging (MRI)., Methods: This study used a prospective cohort of 174 women with postmenopausal bleeding and endometrial thickness of 5 mm or greater. Resectoscopic biopsy (hysteroscopy with biopsy) samples or hysterectomy served as reference standard. Malignant and benign endometrial patterns were evaluated with TVS, GIS and HY(pattern) were then added. The efficiency of each diagnostic strategy, including ES and MRI findings (n = 83), was compared and evaluated against the reference standard., Results: ES, TVS, GIS, and HY(pattern) had high diagnostic efficiency (area under the curve) for malignancy diagnosis (ES, 0.90; TVS, 0.88; GIS, 0.92; HY(pattern), 0.91). When insufficient samples were incorporated, ES was less efficient than the other techniques. ES was not more efficient in the subgroup of women without localized lesions than in the subgroup of women with localized lesions. MRI and HY(pattern) added limited efficiency, whereas hysteroscopy with biopsy was most efficient., Conclusions: As a first-line technique, pattern recognition on TVS, GIS, and HY(pattern) correctly identifies 9 of 10 women with malignancy and is superior to pattern recognition on ES when insufficient samples are included. Endometrial pattern evaluated with TVS and GIS is a fast and efficient first-line diagnostic tool that outperforms ES in women with or without localized lesions. Malignant patterns on TVS/GIS should warrant fast-track evaluation, whereas women with benign patterns may be selected for office or operative hysteroscopy. A fast-track diagnostic setup based on pattern recognition is presented.

Background: Acute kidney injury (AKI) after cardiac surgery is common and is associated with increased mortality. We wanted to investigate if the arterial pressure or the use of norepinephrine during cardiopulmonary bypass were associated with AKI., Methods: A retrospective analysis of patients who underwent coronary artery bypass grafting with or without concomitant procedures was conducted. AKI was defined using the RIFLE criteria. Data on arterial pressure and use of norepinephrine during cardiopulmonary bypass were entered in a binary logistic regression model to control for possible perioperative confounders., Results: A total of 623 patients were included. Mean age was 68.3 ± 9.7 years and 81% were males. AKI was observed in 198 patients (32%). Mean arterial pressure was 47 ± 6 mmHg and 45 ± 6 mmHg (P = 0.008) in the AKI and no-AKI group, respectively. Norepinephrine was used more frequently and in higher amounts, during cardiopulmonary bypass, in patients who developed AKI. These differences in arterial pressures and use of norepinephrine between the groups were not found to be significant when entered in the binary logistic regression model., Conclusion: No independent relationship between arterial pressure or use of norepinephrine and AKI was found., (© 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Risk of human papillomavirus (HPV) transmission during laser vaporisation of genital warts or loop electrode excision procedure is controversial. An oral rinse, a nasal swabs, history of HPV related diseases and data on HPV exposure were collected from 287 employees at departments of dermato-venerology and gynaecology in Denmark. A mucosal HPV type was found among 5.8% of employees with experience of laser treatment of genital warts as compared to 1.7% of those with no experience (p = 0.12). HPV prevalence was not higher in employees participating in electrosurgical treatment or cryotherapy of genital warts, or loop electrode excision procedure compared with those who did not. HPV 6 or 11 were not detected in any samples. Hand warts after the age of 24 years was more common among dermatology than among non-dermatology personnel (18% vs. 8.0%, p = 0.03). Mucosal HPV types are infrequent in the oral and nasal cavity of health care personnel, however, employees at departments of dermato-venereology are at risk of acquiring hand warts.

Objective: To propose a scoring system to predict endometrial cancer using different ultrasound image characteristics at gray-scale, with and without enhancement by gel infusion, and Doppler transvaginal sonography (TVS) and to evaluate intra- and interobserver variability in assessment of these characteristics., Method: Unenhanced TVS, Doppler examinations and gel infusion sonography (GIS) were performed prospectively in 174 consecutive postmenopausal women with endometrial thickness ≥ 5 mm. The reference standard in all women was hysteroscopy or hysterectomy with pathological evaluation of the malignancy. The presence of various ultrasound pattern characteristics indicative of endometrial malignancy and intra- and interobserver variability in their assessment were evaluated. Multivariate logistic regression was used to correlate image and clinical parameters to presence of endometrial cancer., Results: A simple Doppler flow score (which considered only presence of vascularity and not presence of single/double dominant vessel, multiple vessels, large vessels, color splash or densely packed vessels) had an area under the receiver-operating characteristics curve (AUC) of 0.83 in the prediction of endometrial cancer. Models including endometrial thickness, Doppler score and interrupted endomyometrial junction on unenhanced TVS predicted endometrial cancer with an AUC of 0.95 (95% CI, 0.92-0.99) and, with addition of irregular surface on GIS, the AUC was 0.97 (95% CI, 0.94-0.99). A risk of endometrial cancer (REC) scoring system based on body mass index, Doppler score, endometrial thickness and interrupted endomyometrial junction on unenhanced TVS and irregular surface at GIS performed very well at identifying endometrial cancer; at a REC-score of ≥ 4 the sensitivity for detection of endometrial cancer was 91% and specificity was 94%. Observers agreed in 82.3% of cases (kappa, 0.63 (0.48-0.78)) when subjective parameters were analyzed in stored videoclips., Conclusion: Our observer-dependent proposed scoring system seems to perform well in the prediction of endometrial cancer and should be tested in future studies., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Some foreign prostitutes are victims of traffiquing, do not speak Danish and are not familiar with the services offered in the Danish Health Service. The mobile health initiative localises foreign prostitutes and offers health checks and help in case of illness or pregnancy. The article reports method and findings from the first two-year period with this initiative.

Objective: Fibroblast growth factor 21 (FGF21) is a metabolic regulator of glucose and lipid metabolism. The physiological role of FGF21 is not yet fully elucidated, however, administration of FGF21 lowers blood glucose in diabetic animals. Moreover, increased levels of FGF21 are found in obese and diabetic rodents and humans compared with lean/non-diabetic controls., Methods: Adult male rhesus macaque monkeys were chronically maintained on a high-fat diet (HFD) or a standard diet (control, CTR). Plasma levels of FGF21, triglycerides and cholesterol were measured and body weight was record. Glucose-stimulated insulin secretion (GSIS) and glucose clearance was determined during an intravenous glucose tolerance test. Furthermore, expression of FGF21 and its receptors were determined in liver, pancreas, three white adipose tissues (WATs) and two skeletal muscles., Results: A cohort of the high-fat fed monkeys responded to the HFD with increasing body weight, plasma lipids, total cholesterol, GSIS and decreased glucose tolerance. These monkeys were termed HFD sensitive. Another cohort of monkeys did not become obese and maintained normal insulin sensitivity. These animals were defined as HFD resistant. Plasma FGF21 levels were significantly increased in all HFD fed monkeys compared with the CTR group. The HFD-sensitive monkeys showed a significant increase in FGF21 mRNA expression in all examined tissues compared with CTR, whereas FGF21 expression in the HFD-resistant group was only increased in the liver, pancreas and the retroperitoneal WAT. In the WAT, the co-receptor β-klotho was downregulated in the HFD-sensitive monkeys compared with the HFD-resistant group., Conclusion: This study demonstrates that HFD changes FGF21 and FGF21 receptor expression in a tissue-specific manner in rhesus monkeys; differential regulation is moreover observed between HFD-sensitive and -resistant monkeys. Monkeys that maintain normal levels of the FGF21 co-receptor β-klotho in the WAT on HFD were protected toward development of dyslipidemia and hyperglycemia.

This study was undertaken to model and predict growth of Salmonella and the dominating natural microbiota, and their interaction in ground pork. Growth of Salmonella in sterile ground pork at constant temperatures between 4 °C and 38 °C was quantified and used for developing predictive models for lag time, max. specific growth rate and max. population density. Data from literature were used to develop growth models for the natural pork microbiota. Challenge tests at temperatures from 9.4 to 24.1 °C and with Salmonella inoculated in ground pork were used for evaluation of interaction models. The existing Jameson-effect and Lotka-Volterra species interaction models and a new expanded Jameson-effect model were evaluated. F-test indicated lack-of-fit for the classical Jameson-effect model at all of the tested temperatures and at 14.1-20.2 °C this was caused by continued growth of Salmonella after the natural microbiota had reached their max. population density. The new expanded Jameson-effect model and the Lotka-Volterra model performed better and appropriately described the continued but reduced growth of Salmonella after the natural microbiota had reached their max. population density. The expanded Jameson-effect model is a new and simple species interaction model, which performed as well as the more complex Lotka-Volterra model., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the accuracy of different preoperative modalities for staging of endometrial cancer to restrict extensive surgery to patients at high risk of metastatic disease., Setting: Aarhus University Hospital., Population: 156 women referred in 2006-2011 because of atypical endometrial hyperplasia (G0) or endometrial cancer., Methods: Patients were offered preoperative transvaginal ultrasonography (TVS), magnetic resonance imaging (MRI), and hysteroscopic-directed biopsies from the uterine tumor and cervix. Final pathology of the removed uterus was the reference standard. Patients were divided into low risk (<50% myometrial invasion, and grades 0, 1, 2, and no cervical invasion) or high risk (all others)., Main Outcome Measures: Accuracy, sensitivity, specificity, positive/negative predictive value., Results: Patients were aged 32-88 years, with a mean body mass index of 29. At final pathology 81% had cancer and 19% G0 or no residual tumor; 54% were high risk. Hysteroscopy-directed biopsies had a higher accuracy (92%) than endometrial biopsy (58%) for differentiating G0 from cancer (p < 0.001); grade 3 tumor identification had similar accuracy (93 vs. 92%). Deep myometrial invasion was estimated with higher accuracy by MRI (82%) than TVS (74%) (p < 0.02). For cervical involvement, hysteroscopy-directed biopsies had higher accuracy (94%) than MRI (84%,) and TVS (80%) (p < 0.02). Accuracy for identifying high-risk women was highest (83%) using a combination of MRI and hysteroscopic-directed biopsies, compared with TVS and endometrial biopsy (72%) (p < 0.05)., Conclusion: Preoperative staging with MRI and hysteroscopy-directed biopsy can identify eight of 10 women with high risk of lymph node metastases and spare eight of 10 low-risk women extended surgery., (© 2013 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2013 Nordic Federation of Societies of Obstetrics and Gynecology.)

A new HPLC system coupled with multiple detectors - Diode array detector (DAD), fluorescence detector (FLD), electrochemical amperometric detector (ADC) and mass spectrometry detector (MSD) was developed for the characterization and differentiation of tannin-containing herbal drugs included in The European Pharmacopoeia. The HPLC separation system consisted of an Agilent ZORBAX Eclipse XDB C18 column and a gradient water and methanol as the mobile phase which was kept at a flow rate of 0.3 mL x min(-1). Four kinds of detectors were connected by a micro-splitter valve and simultaneously recorded the response of each analytical sample. Thirty-one samples from eight kinds of tannin-containing drugs were measured using this HPLC system and their signals from all detectors were comprehensively processed via principal component analysis (PCA). The statistic result demonstrates that thirty-one batches from different herbal drugs can be reasonably identified and systematically classified by their chemical fingerprints. The proposed multi-detector HPLC method aided by chemometrics not only offers a new pattern for the study of tannin-containing herbs, but also provides a useful foundation for quality control of herbal medicines.

The Danish health care system is undergoing a major reorganisation, resulting in fewer emergency departments (ED) with consultants in attendance 24/7. This questionnaire-based study evaluates the status of the reorganisation with emphasis on physician attendance and recruitment. 76% of the EDs are not staffed by consultants 24/7, 51% report difficulties in recruiting qualified personnel and 33% report problems connected to retaining them. 71% believe that a specialty in emergency medicine could help solve these problems. Danish EDs do not comply with the visions of the reorganisation plan.

Aims: The aim of this study was to develop a model to predict cross-contamination of Salmonella during grinding of pork., Methods and Results: Transfer rates of Salmonella were measured in three experiments, where between 10 and 20 kg meat was ground into 200-g portions. In each experiment, five pork slices of about 200 g per slice were inoculated with 8-9 log-units of Salmonella Typhimurium DT104 and used for building up the contamination in the grinder. Subsequently, Salmonella-free slices were ground and collected as samples of c. 200 g minced pork. Throughout the process, representative samples were quantitatively analysed for Salmonella. A model suggested by Nauta et al. (2005) predicting cross-contamination of Campylobacter in poultry processing and two modified versions of this model were tested., Conclusions: The present study observed a tailing phenomenon of transfer of Salmonella during a small-scale grinding process. It was, therefore, hypothesized that transfer occurred from two environmental matrices inside the grinder and a model was developed. The developed model satisfactorily predicted the observed concentrations of Salmonella during its cross-contamination in the grinding of up to 110 pork slices., Significance and Impact of the Study: The proposed model provides an important tool to examine the effect of cross-contamination in quantitative microbial risk assessments and might also be applied to various other food processes where cross-contamination is involved., (© 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology.)

Using insulin as a model protein for binding of oxaliplatin to proteins, various mass spectrometric approaches and techniques were compared. Several different platinum adducts were observed, e.g. addition of one or two diaminocyclohexane platinum(II) (Pt(dach)) molecules. By top-down analysis and fragmentation of the intact insulin-oxaliplatin adduct using nano-electrospray ionisation quadrupole time-of-flight mass spectrometry (nESI-Q-ToF-MS), the major binding site was assigned to histidine5 on the insulin B chain. In order to simplify the interpretation of the mass spectrum, the disulphide bridges were reduced. This led to the additional identification of cysteine6 on the A chain as a binding site along with histidine5 on the B chain. Digestion of insulin-oxaliplatin with endoproteinase Glu-C (GluC) followed by reduction led to the formation of five peptides with Pt(dach) attached. Identification of several of the binding sites was obtained using matrix-assisted laser desorption/ionization (MALDI)-ToF-ToF-MS and liquid chromatography-nESI-Q-ToF-MS. Upon comparing the top-down and bottom-up approaches, the suitability of the bottom-up approach for determining binding sites was questioned, as the release and possible re-association of Pt(dach) were demonstrated upon enzymatic digestion. The associated advantages and disadvantages of ESI and MALDI were also pointed out.

The accumulation and cytotoxicity of a 10 μmol L⁻¹ equimolar human serum albumin-cisplatin adduct (HSA-Pt) was investigated in suspension Ehrlich Ascites Tumor Cells (EATC) and adherent Ehrlich Lettré Ascites Cells (Lettré). HSA-Pt did not induce apoptosis nor was it taken up by the cells to any significant amount within 24 h incubation. The accumulation and cytotoxicity of HSA-Pt was compared to 10 μmol L⁻¹ cisplatin for which a larger accumulation and cytotoxicity were observed in EATC compared to Lettré. The experiment was performed with cell medium exchange every fourth hour as HSA-Pt and cisplatin were not stable in RPMI-1640 with 10% serum. The stability was determined using size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) and after 4 h new platinum peaks were observed. These findings indicate that before conducting cell experiments, the stability of the compound in the cell medium should be investigated especially when long exposure times are applied. Furthermore, HSA-Pt was found to be stable in Hanks Balanced Saline Solution (HBSS) and in Phosphate Buffered Saline (PBS) at pH 5.3, 6.1 and 7.4. Thus, the shift in pH when HSA-cisplatin passes from blood (pH 7.4) to tumor tissue (pH 5-6) is not capable of releasing cisplatin from HSA.

Platinum compounds are used in the treatment of cancer. We demonstrate that cisplatin-induced (10 μM) apoptosis (caspase-3 activity) is pronounced within 18 hours in non-adherent Ehrlich ascites tumour cells (EATC), whereas there is no increase in caspase-3 activity in the adherent Ehrlich Lettré ascites tumour cells (ELA). Loss of KCl and cell shrinkage are hallmarks in apoptosis and has been shown in EATC. However, we find no reduction in cell volume and only a minor loss of K(+) which is accompanied by net uptake of Na(+) following 18 hours cisplatin exposure in ELA. Glutathione and taurine have previously been demonstrated to protect cells from apoptosis. We find, however, that increase or decrease in the cellular content of glutathione and taurine has no effect on cisplatin-induced cell death in EATC and ELA. Nevertheless, knock-down of the taurine transporter TauT leads to a significant increase in apoptosis in ELA following cisplatin exposure. We find that cytosolic accumulation of cisplatin is similar in EATC and ELA. However, the nuclear accumulation and DNA-binding of cisplatin is significant lower in ELA compared to EATC. We suggest three putative reasons for the observed cisplatin insensitivity in the adherent tumor cells (ELA) compared to the non-adherent tumor cells (EATC): less nuclear cisplatin accumulation, increased TauT activity, and decreased anion and water loss., (Copyright © 2010 S. Karger AG, Basel.)

Introduction: Herbal drugs containing tannins are characterised in the European Pharmacopoeia by their tannin content analysed by the old, nonspecific, colorimetric Folin-Ciocalteu method. The result of the analysis is a single figure relating to the content of tannins, but this does not provide much information on the identity or status of the herbal drug., Objective: In the present paper methods for obtaining more detailed information of the constituents in these herbal drugs are described., Methodology: The methods developed are based on a reversed-phase gradient HPLC system coupled to DAD, fluorescence, electrochemical and MS detectors., Results: The HPLC system developed provides characteristic fingerprints of the herbal drugs when using UV detection at 250 nm. The fingerprints may be used for identification of tannin-containing herbal drugs. Methanolysis of the herbal drug generated methyl gallate and ellagic acid, which were analysed in the HPLC system. The molar ratio between methyl gallate and ellagic acid may also be used for the identification of herbal drugs., Conclusions: An HPLC system equipped with selective detectors was shown to be valuable in the identification of herbal tannin. Most promising was fingerprinting using UV detection, but methanolysis followed by HPLC also proved useful., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

Background: The inherent properties of element selectivity combined with high sensitivity and structure independent response, make inductively coupled plasma mass spectrometry (ICP-MS) an interesting alternative detection technique in drug metabolism studies., Objective: The application of online separation with ICP-MS detection in drug metabolism studies is reviewed with focus on the merits and demerits of this detection technique. The prerequisite for inclusion in this review is that the study involves a separation technique hyphenated online to the ICP-MS detection., Result/conclusion: ICP-MS detection is found to be advantageous for analysis of all drug substances detectable by ICP-MS compared to radiochemical detection. Detectable drugs are limited to halogen-, sulfur-, metal- and metalloid-containing compounds. The drawback of interference from endogenous compounds on quantitative mass balance estimations of non-metal drugs is addressed. The potential of determining the stoichiometry in metallo-drug biomolecule interactions is pointed out by presenting examples of simultaneous monitoring of metals in metallo-drugs and intrinsic ICP-MS detectable elements in biomolecules. It is concluded that ICP-MS detection is an indispensable technique in drug metabolism studies of metallo-drugs, although the applicability for traditional drugs is limited.

Objective: To examine bleeding complications and thromboembolic events in relation to timing of heparin prophylaxis after hysterectomy., Design: Nationwide prospective cohort study with 30 days post-operative follow-up within the Danish Hysterectomy Database (DHD)., Setting: All gynecological departments in Denmark (n=31)., Sample: 9,949 women who had an elective hysterectomy for benign indication between October 2003 and May 2006 and were reported to DHD (national response rate: 88-99% throughout 2004-2005)., Main Outcome Measures: Odds ratios (OR) of peri-operative bleeding complications (> or =1,000 ml bleeding during surgery or post-operative wound/vaginal-vault/intraabdominal bleeding or hematoma) and number of events of venous thromboembolism. Logistic regression analysis adjusting for: age, body mass index, alcohol, smoking, meno-/metrorrhagia, uterine weight, department volume, surgeon's experience, route and type of hysterectomy and additional surgery, and stratification on assistant's experience, peri-operative pain prophylaxis with NSAID and daily use of Acetyl Salicylic Acid (ASA)/NSAID., Results: 9,051 women (92%) received thromboprophylaxis with heparin, initiated pre-operatively in 48% and post-operatively in 52%. At least one bleeding complication was noted in 881 women (10%). Post-operative heparin administration was associated with a reduced risk of bleeding complications; OR=0.85 (95% confidence interval 0.73-0.99) compared to pre-operative administration. Excluding cases with potential impaired hemostasis at baseline, the OR was 0.78 (0.64-0.94). There was no fatal embolism. Three of seven pulmonary embolisms and one of three symptomatic deep venous thromboses occurred with the post-operative heparin administration., Conclusion: Post-operative rather than pre-operative administration of heparin prophylaxis may reduce the risk of bleeding complications after hysterectomy without apparent risk of increased thromboembolic events.

Objective: To describe the concept and early results from the Danish Hysterectomy Database (DHD)., Design: Nationwide prospective cohort., Setting: Denmark., Population: All women who had undergone an elective hysterectomy for benign indication carried out in 2004-2006., Methods: Structured data are registered prospectively by the surgeons involved in the treatment. Data is reported using the Danish National Patient Registry (LPR) and feedback is provided as clinical indicators with well-defined goals. The DHD concept includes annual plenary meetings, elaboration of national clinical guidelines and parallel causal studies., Main Outcome Measures: Completeness, data validation and department-identifiable clinical indicators (surgical volume, method of hysterectomy, use of antibiotic and thromboembolic prophylaxis, postoperative hospitalization and bleeding complications, surgical infections, reoperations, readmissions and death within 30 days postoperatively)., Results: A total of 13,425 hysterectomies were performed in Denmark from 2004 to 2006. In 2005, all gynecological departments in Denmark (n=31) were included in the database collaboration and the national response rate was 99%. Data validity was good in general (82-100% agreement and kappa=0.40-1.00) and data completeness was high (92-100% in 2006). From 2004 to 2006, two clinical guidelines were implemented, the postoperative hospitalization was stable at median 2 days, the rate of postoperative surgical infections was reduced from 4 to 2%, the rate of bleeding complications from 8 to 6%, the reoperation rate from 5 to 4%, and the readmission rate from 7 to 5%., Conclusions: Clinical performance indicators, audit meetings and nationwide collaboration are useful in monitoring and improving outcome after hysterectomy on a national level. In addition, the DHD offers scope for causal studies about perioperative management.

Background: Erythropoietin (EPO) is neuroprotective in experimental models of stroke and subarachnoid haemorrhage (SAH) and possibly in patients with thromboembolic stroke. We studied the efficacy and safety of EPO in patients with SAH., Methods: A larger scale clinical trial was planned but preliminarily terminated because of a lower than expected inclusion rate. However, 73 patients were randomised to treatment with EPO (500 IU/kg/day for three days) or placebo. The primary endpoint was Glasgow Outcome Score at six months. We further studied surrogate measures of secondary ischaemia, i.e. transcranial Doppler (TCD) flow velocity, symptomatic vasospasm, cerebral metabolism (microdialysis) and jugular venous oximetry, biochemical markers of brain damage (S-100beta and neuron specific enolase) and blood-brain barrier integrity., Findings: The limited sample size precluded our primary hypotheses being verified and refuted. However, data from this study are important for any other study of SAH and as much raw data as possible are presented and can be included in future meta analyses. On admission the proportion of patients in a poor condition was higher in the EPO group compared with the placebo group but the difference was statistically insignificant. In the EPO-treated patients the CSF concentration of EPO increased 600-fold. Except for a higher extracelullar concentration of glycerol in the EPO group probably caused by the poorer clinical condition of these patients, there were no statistically significant group differences in the primary or secondary outcome measures. EPO was well tolerated., Conclusions: Beneficial effects of EPO in patients with SAH cannot be excluded or concluded on the basis of this study and larger scale trials are warranted.

Transurethral resection of the prostate (TURP) has become the "gold standard" although there is risk of postoperative bleeding and TUR syndrome. The main advantage of photoselective vaporisation of the prostate (PVP) is minimal bleeding; however, long-term results of PVP are pending. Transvesical prostatectomy is limited today to large prostates because of the high perioperative morbidity. Transurethral microwave therapy (TUMT) has lost some of its popularity because of post treatment catherization for several weeks and reduced long-term results compared with TURP.

Prostatitis is classified according to the National Institute of Health Prostatitis Classification. The term Chronic Pelvic Pain Syndrome (CPPS) covers the symptomathology and clinical findings. The main symptoms are pain and voiding disorders. Acute bacterial prostatitis is only seen in 5% of cases. The vast majority of symptoms are found in CPPS, and urodynamic investigation is crucial in order to identify bladder neck dysfunction which occurs in a considerable number of patients.

Objective: The purpose of this study was to determine the effect of early oral bowel stimulation with osmotic laxatives on gastrointestinal function, postoperative nausea and vomiting (PONV) and pain in patients who undergo fast-track abdominal hysterectomy., Study Design: This was a double-blind, placebo-controlled study of 53 women who were assigned randomly to either laxative (magnesium oxide + disodium phosphate) or placebo that was initiated 6 hours after the operation. Primary outcome was time to first defecation; the number of vomiting episodes; nausea and pain score were assessed on a visual analogue scale., Results: Time to first postoperative defecation was a median of 45 hours in the laxative group and a median of 69 hours in the placebo group (P < .0001). There were no significant differences between groups in pain scores, PONV and the use of morphine or antiemetics. Postoperative hospitalization was a median of 1 day in the laxative group and of 2 days in the placebo group (P = .41)., Conclusion: Laxative improves recovery of gastrointestinal function after fast-track hysterectomy but has no significant effect on pain and PONV.

Objective: During recent years Conventional Coronary Artery Bypass Grafting (cCABG) and Off-Pump Coronary Bypass (OPCAB) have been compared in several randomised and non-randomised studies. Focus has been on postoperative outcome with short-term follow-up in low-risk patients and therefore little is known of the effectiveness of OPCAB in high-risk patients. Furthermore, it is unknown if a potential beneficial short-term outcome is consistent over time., Design: In 2001, 217 patients with a Euroscore > or =5 were included in an observational cohort study; 162 patients were operated by cCABG and 55 by OPCAB. Follow-up data were retrieved from the Danish national person registry. The study includes a mid-term follow-up, with a mean follow-up time of 3.97 years+/-0.32., Results: No differences in mortality between OPCAB and cCABG were found. In-hospital mortality was 5.5% in the OPCAB group vs 5.6% in the cCABG group and mid-term mortality was 21.8% in the OPCAB group vs 24.7% in the cCABG group; p = 0.71. During the follow-up period 41.5% of patients with an EF < or =35% at the time of surgery and 43.3% of patients with a Euroscore >8 died. Seven percent in the cCABG group had a perioperative AMI vs none in the OPCAB group; p < 0.05. In 74.5% cCABG's allogenic transfusions of blood components was necessary vs only 55.6% OPCAB's (p < 0.05). No significant differences in CNS complications or atrial fibrillation could be demonstrated., Conclusion: A similar outcome between OPCAB in cCABG in high-risk patients with respect to mortality was found. OPCAB seems to have a beneficial effect on morbidity. A cautious approach to patients with a combined high Euroscore and low ejection fraction should be the strategy of choice.