Suppressed immune profile in children with combined type 1 diabetes and celiac disease.

Children diagnosed with a combination of type 1 diabetes (T1D) and celiac disease (CD) show a dysregulated T helper type 1 (Th1)/Th17 response. Besides the cellular involvement, several soluble immune markers are involved in the autoimmune process of both T1D and CD. Only few studies have examined the peripheral pattern of different cytokines, chemokines and acute-phase proteins (APP) in children with combined T1D and CD. To our knowledge, no studies have evaluated the serum levels of adipocytokines and matrix metalloproteinases (MMPs) in this context. The purpose of the present study was to acquire more knowledge and to gain deeper understanding regarding the peripheral immunoregulatory milieu in children with both T1D and CD. The study included children diagnosed with both T1D and CD (n = 18), children with T1D (n = 27) or CD (n = 16) and reference children (n = 42). Sera were collected and analysis of 28 immune markers (cytokines, chemokines, APPs, adipocytokines and MMPs) was performed using the Luminex technique. The major findings showed that children with a double diagnosis had lower serum levels of interleukin (IL)-22, monocyte chemoattractant protein (MIP)-1α, monocyte chemoattractant protein (MCP)-1, procalcitonin, fibrinogen, visfatin and matrix metalloproteinase (MMP)-2. These results indicate a suppressed immune profile in children with combined T1D and CD, including Th17 cytokines, chemokines, APPs, adipocytokines and MMPs. We conclude that, besides cytokines and chemokines, other immune markers, e.g. APPs, adipocytokines and MMPs, are of importance for further investigations to elucidate the heterogeneous immune processes present in patients diagnosed with T1D in combination with CD.

Evaluating the evidence for non-monotonic dose-response relationships: A systematic literature review and (re-)analysis of in vivo toxicity data in the area of food safety.

This study aims to evaluate the evidence for the existence of non-monotonic dose-responses (NMDRs) of substances in the area of food safety. This review was performed following the systematic review methodology with the aim to identify in vivo studies published between January 2002 and February 2015 containing evidence for potential NMDRs. Inclusion and reliability criteria were defined and used to select relevant and reliable studies. A set of six checkpoints was developed to establish the likelihood that the data retrieved contained evidence for NMDR. In this review, 49 in vivo studies were identified as relevant and reliable, of which 42 were used for dose-response analysis. These studies contained 179 in vivo dose-response datasets with at least five dose groups (and a control group) as fewer doses cannot provide evidence for NMDR. These datasets were extracted and analyzed using the PROAST software package. The resulting dose-response relationships were evaluated for possible evidence of NMDRs by applying the six checkpoints. In total, 10 out of the 179 in vivo datasets fulfilled all six checkpoints. While these datasets could be considered as providing evidence for NMDR, replicated studies would still be needed to check if the results can be reproduced to rule out that the non-monotonicity was caused by incidental anomalies in that specific study. This approach, combining a systematic review with a set of checkpoints, is new and appears useful for future evaluations of the dose response datasets regarding evidence of non-monotonicity.

Oral prednisolone for 4 days does not increase exercise tolerance in men with COPD.

One of the primary objectives in management of chronic obstructive pulmonary disease (COPD) is preventing decrease in lung function and reducing the annual number of acute exacerbations of COPD (AECOPD). An oral course of systemic corticosteroids is a commonly used treatment in AECOPD. We hypothesize that this treatment also increases exercise performance and decreases muscle fatigue. In a randomized double-blinded, parallel, placebo-controlled trial, we investigated 14 men (8 on prednisolone 37.5 mg vs. 6 on placebo) with severe and very severe COPD. For 5 consecutive days, the patients performed a submaximal endurance test measuring time to exhaustion (TTE, primary endpoint), spirometry, maximal inspiratory and expiratory pressure and maximal isometric contraction of the quadriceps femoris muscle (maximum voluntary contraction (MVC)). At visits 2, 3 and 4, a fatigue protocol was carried out after 40 minutes of cycling at 40% of maximal effort. No differences between groups were found for TTE, lung function or maximal inspiratory or expiratory pressure, however, patients on prednisolone showed significant increased MVC: median 5.15 [3.35; 9.15] against placebo: -2 [-5.57; 3.95] ( p = 0.03). This finding indicates an impact of corticosteroids on muscle groups being exposed to submaximal endurance.

Assessment of plasma endostatin to predict acute kidney injury in critically ill patients.

BACKGROUND: We evaluated whether plasma endostatin predicts acute kidney injury (AKI), need for renal replacement therapy (RRT), or death. METHODS: Prospective, observational, multicenter study from 1 September 2011 to 1 February 2012 with data from 17 intensive care units (ICUs) in Finland. RESULTS: A total of 1112 patients were analyzed. We measured plasma endostatin within 2 h of ICU admission. Early AKI (KDIGO stage within 12 h of ICU admission) was found in 20% of the cohort, and 18% developed late AKI (KDIGO criteria > 12 h from ICU admission). Median (IQR) admission endostatin was higher in the early AKI group, 29 (19.1, 41.9) ng/ml as compared to 22.4 (16.1, 30.1) ng/ml for the late AKI group, and 18 (14.0, 23.6) ng/ml for non-AKI patients (P < 0.001). Endostatin level increased with increasing KDIGO stage. Significantly higher endostatin levels were found in patients with sepsis as compared to those without. Predictive properties for AKI, RRT, and mortality were low with corresponding areas under the receiver operating characteristic curve (AUC) of 0.62, 0.67, and 0.59. Sensitivity analyses among patients with chronic kidney disease or sepsis did not improve the predictive ability of endostatin. Adding endostatin to a clinical AKI prediction model (illness severity score, urine output, and age) insignificantly changed the AUC from 0.67 to 0.70 (P = 0.14). CONCLUSIONS: Endostatin increases with AKI severity but has limited value as a predictor of AKI, RRT and 90-day mortality in patients admitted to ICU. Moreover, endostatin does not improve AKI risk prediction when added to a clinical risk model.

Improving the mix of institutional and community care for older people with dementia: an application of the balance of care approach in eight European countries.

OBJECTIVES: To examine whether the mix of community and institutional long-term care (ILTC) for people with dementia (PwD) in Europe could be improved; assess the economic consequences of providing alternative services for particular groups of ILTC entrants and explore the transnational application of the 'Balance of Care' (BoC) approach. METHOD: A BoC study was undertaken in Estonia, Finland, France, Germany, the Netherlands, Spain, Sweden, and the UK as part of the RightTimePlaceCare project. Drawing on information about 2014 PwD on the margins of ILTC admission, this strategic planning framework identified people whose needs could be met in more than one setting, and compared the relative costs of the possible alternatives. RESULTS: The findings suggest a noteworthy minority of ILTC entrants could be more appropriately supported in the community if enhanced services were available. This would not necessarily require innovative services, but more standard care (including personal and day care), assuming quality was ensured. Potential cost savings were identified in all countries, but community care was not always cheaper than ILTC and the ability to release resources varied between nations. CONCLUSIONS: This is believed to be the first transnational application of the BoC approach, and demonstrates its potential to provide a consistent approach to planning across different health and social care systems. Better comparative information is needed on the number of ILTC entrants with dementia, unit costs and outcomes. Nevertheless, the findings offer important evidence on the appropriateness of current provision, and the opportunity to learn from different countries' experience.

ß2-adrenergic stimulation enhances Ca2+ release and contractile properties of skeletal muscles, and counteracts exercise-induced reductions in Na+-K+-ATPase Vmax in trained men.

The aim of the present study was to examine the effect of ß2-adrenergic stimulation on skeletal muscle contractile properties, sarcoplasmic reticulum (SR) rates of Ca(2+) release and uptake, and Na(+)-K(+)-ATPase activity before and after fatiguing exercise in trained men. The study consisted of two experiments (EXP1, n = 10 males, EXP2, n = 20 males), where ß2-adrenoceptor agonist (terbutaline) or placebo was randomly administered in double-blinded crossover designs. In EXP1, maximal voluntary isometric contraction (MVC) of m. quadriceps was measured, followed by exercise to fatigue at 120% of maximal oxygen uptake (V̇O2, max ). A muscle biopsy was taken after MVC (non-fatigue) and at time of fatigue. In EXP2, contractile properties of m. quadriceps were measured with electrical stimulations before (non-fatigue) and after two fatiguing 45 s sprints. Non-fatigued MVCs were 6 ± 3 and 6 ± 2% higher (P < 0.05) with terbutaline than placebo in EXP1 and EXP2, respectively. Furthermore, peak twitch force was 11 ± 7% higher (P < 0.01) with terbutaline than placebo at non-fatigue. After sprints, MVC declined (P < 0.05) to the same levels with terbutaline as placebo, whereas peak twitch force was lower (P < 0.05) and half-relaxation time was prolonged (P < 0.05) with terbutaline. Rates of SR Ca(2+) release and uptake at 400 nm [Ca(2+)] were 15 ± 5 and 14 ± 5% (P < 0.05) higher, respectively, with terbutaline than placebo at non-fatigue, but declined (P < 0.05) to similar levels at time of fatigue. Na(+)-K(+)-ATPase activity was unaffected by terbutaline compared with placebo at non-fatigue, but terbutaline counteracted exercise-induced reductions in maximum rate of activity (Vmax) at time of fatigue. In conclusion, increased contractile force induced by ß2-adrenergic stimulation is associated with enhanced rate of Ca(2+) release in humans. While ß2-adrenergic stimulation elicits positive inotropic and lusitropic effects on non-fatigued m. quadriceps, these effects are blunted when muscles fatigue.

B cell lymphoma and myeloma in murine Gaucher's disease.

Multiple myeloma and B cell lymphoma are leading causes of death in Gaucher's disease but the nature of the stimulus driving the often noted clonal expansion of immunoglobulin-secreting B cells and cognate lymphoid malignancy is unknown. We investigated the long-term development of B cell malignancies in an authentic model of non-neuronopathic Gaucher's disease in mice: selective deficiency of ß-glucocerebrosidase in haematopoietic cells [Gba(tm1Karl/tm1Karl)Tg(Mx1-cre)1Cgn/0, with excision of exons 9-11 of the murine GBA1 gene, is induced by poly[I:C]. Mice with Gaucher's disease showed visceral storage of ß-glucosylceramide and greatly elevated plasma ß-glucosylsphingosine [median 57.9 (range 19.8-159) nm; n = 39] compared with control mice from the same strain [median 0.56 (range 0.04-1.38) nm; n = 29] (p < 0.0001). Sporadic fatal B cell lymphomas developed in 11 of 21 GD mice (6-24 months) but only two of eight control animals developed tumours by age 24 months. Unexpectedly, most mice with overt lymphoma had absent or few Gaucher cells but local inflammatory macrophages were present. Eleven of 39 of Gaucher mice developed monoclonal gammopathy, but in the control group only one animal of 25 had clonal immunoglobulin abnormalities. Seven of 10 of the B cell lymphomas were found to secrete a monoclonal paraprotein and the lymphomas stained intensely for pan-B cell markers; reactive T lymphocytes were also present in tumour tissue. In the Gaucher mouse strain, it was notable that, as in patients with this disease, CD138(+) plasma cells frequently surrounded splenic macrophages engorged with glycosphingolipid. Our strain of mice, with inducible deficiency of ß-glucocerebrosidase in haematopoietic cells and a high frequency of sporadic lethal B cell malignancies, faithfully recapitulates human Gaucher's disease: it serves as a tractable model to investigate the putative role of bioactive sphingolipids in the control of B cell proliferation and the pathogenesis of myelomatosis-the most prevalent human cancer associated with this disorder.

Solvent-induced luminescence quenching: static and time-resolved X-ray absorption spectroscopy of a copper(I) phenanthroline complex.

We present a static and picosecond X-ray absorption study at the Cu K-edge of bis(2,9-dimethyl-1,10-phenanthroline)copper(I) ([Cu(dmp)2](+); dmp = 2,9-dimethyl-1,10-phenanthroline) dissolved in acetonitrile and dichloromethane. The steady-state photoluminescence spectra in dichloromethane and acetonitrile are also presented and show a shift to longer wavelengths for the latter, which points to a stronger stabilization of the excited complex. The fine structure features of the static and transient X-ray spectra allow an unambiguous assignment of the electronic and geometric structure of the molecule in both its ground and excited (3)MLCT states. Importantly, the transient spectra are remarkably similar for both solvents, and the spectral changes can be rationalized using the optimized ground- and excited-state structures of the complex. The proposed assignment of the lifetime shortening of the excited state in donor solvents (acetonitrile) to a metal-centered exciplex is not corroborated here. Molecular dynamics simulations confirm the lack of complexation; however, in both solvents the molecules come close to the metal but undergo rapid exchange with the bulk. The shortening of the lifetime of the title complex and nine additional related complexes can be rationalized by the decrease in the (3)MLCT energy. Deviations from this trend may be explained by means of the effects of the dihedral angle between the ligand planes, the solvent, and the (3)MLCT-(1)MLCT energy gap.

Plasma neutrophil gelatinase-associated lipocalin and adverse outcome in critically ill patients with ventilatory support.

OBJECTIVE: Plasma neutrophil gelatinase-associated lipocalin (pNGAL) has been introduced as an early and sensitive biomarker of acute kidney injury (AKI), with an increased risk for renal replacement therapy (RRT) and adverse outcome in selected critically ill patient groups. Acute respiratory failure is the most common organ dysfunction in critically ill patients with an increased risk for AKI. Accordingly, we hypothesized that pNGAL would independently predict adverse outcome in a heterogeneous group of critically ill adult patients with acute respiratory failure. DESIGN AND SETTING: Prospective, multi-centre study in 25 Finnish intensive care units. PATIENTS AND METHODS: pNGAL was measured from critically ill patients with acute respiratory failure. We evaluated the predictive value of pNGAL for RRT, and hospital and 90-day mortality first separately, second in addition to the Simplified Acute Physiology Score (SAPS II), and third to RIFLE (Risk, Injury, Failure, Loss, End-Stage Renal Disease) AKI classification. Additionally, we assessed the factors associated with pNGAL by linear regression analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 369 patients. Median (interquartile range) baseline pNGAL was 169 (92-370) ng/ml. The areas under receiver operating characteristic curves of baseline pNGAL were as follows: 0.733 [95% confidence interval (CI) 0.656-0.810] for RRT, 0.627 (95% CI 0.561-0.693) for hospital, and 0.582 (95% CI 0.520-0.645) for 90-day mortality. Present infection, baseline creatinine, operative status, and pancreatitis were independently associated with baseline pNGAL. CONCLUSIONS: Baseline pNGAL gives no additional value into prediction of hospital and 90-day mortality compared with RIFLE or SAPS II, and has only moderate predictive power regarding RRT in critically ill adult patients with acute respiratory failure.

Acute kidney injury in patients with severe sepsis in Finnish Intensive Care Units.

BACKGROUND: Severe sepsis is one of the leading causes of acute kidney injury (AKI). Patients with sepsis-associated AKI demonstrate high-hospital mortality. We evaluated the incidence of severe sepsis-associated AKI and its association with outcome in intensive care units (ICUs) in Finland. METHODS: This was a predetermined sub-study of the prospective, observational, multicentre FINNAKI study conducted in 17 ICUs during 1 September 2011 and 1 February 2012. All emergency ICU admissions and elective admissions exceeding 24 hours in the ICU were screened for presence of severe sepsis and AKI up to 5 days in ICU. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria and severe sepsis according to the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) criteria. RESULTS: Of the 2901 included patients, severe sepsis was diagnosed in 918 (31.6%, 95% confidence interval [CI] 29.9-33.4%) patients. Of these 918 patients, 488 (53.2% [95% CI 49.9-56.5%]) had AKI. The 90-day mortality rate was 38.1% (95% CI 33.7-42.5%) for severe sepsis patients with AKI and 24.7% (95% CI 20.5-28.8%) for those without AKI. After adjusting for covariates, KDIGO stage 3 AKI was associated with an increased risk for 90-day mortality with an adjusted odds ratio (OR) of 1.94 (95% CI 1.28-2.94), but stages 1 and 2 were not. CONCLUSIONS: More than half of the patients with severe sepsis had AKI according to the KDIGO classification, and AKI stage 3 was independently associated with 90-day mortality.

The extracellular matrix in colorectal cancer and its metastatic settling - Alterations and biological implications.

Colorectal cancer (CRC) remains one of the most common cancers worldwide. Metastatic disease is ultimately fatal when incurable. Cancer research has evolved to take the importance of the tumour microenvironment (TME) into account. The extracellular matrix (ECM) has been viewed merely as a structural scaffold, but it is now evident that the ECM is a highly active part of the TME and affects tumour cell behaviour and metastatic capability. The ECM context and composition are linked to patient outcome and the response to surgical and oncological therapy in CRC patients and may be an area for developing novel biomarkers and targeted therapy. In this review we focus on the components of the ECM in human primary and metastatic CRC. We discuss future aspects of the ECM for targeted therapy, as a source of novel biomarkers, current knowledge of the area and important considerations when studying the ECM in human CRC.

Preoperative levosimendan infusion in combined aortic valve and coronary bypass surgery.

BACKGROUND: Cardiopulmonary bypass may have detrimental effects on intestinal function and decrease the concentrations of the active, long-acting metabolites of levosimendan, an inodilator used to improve cardiac function. The aim of this study was to evaluate the haemodynamic effects of preoperative levosimendan in patients undergoing high-risk cardiac surgery. METHODS: Twenty-four patients were randomized to receive levosimendan (12 µg bolus followed by an infusion of 0.2 µg kg(-1) min(-1)) or a placebo 24 h before surgery. The inclusion criteria were left ventricular ejection fraction (LVEF) <50% or LV hypertrophy indicated by a wall thickness of >12 mm. Haemodynamics were recorded every hour for 24 h (pulmonary artery catheter) and daily until postoperative day 4 (whole-body impedance cardiography). Doppler echocardiography with tissue Doppler imaging was used to assess systolic and diastolic cardiac function. RESULTS: The cardiac index (CI) and stroke volume index (SI) were higher in the levosimendan group (LG) for the 4 day postoperative period (P<0.05); on the fourth postoperative day, the CI was 3.0 litre m(-2) min(-1) in the LG compared with 2.4 litre m(-2) min(-1) in the control group (CG) and the SI was 30 vs 25 ml m(-2), respectively. The LVEF measured at baseline and on the fourth postoperative morning decreased in the CG, but was maintained in the LG. CONCLUSIONS: Levosimendan improved haemodynamics compared with a placebo in patients undergoing high-risk cardiac surgery. The concentrations of levosimendan's metabolites were higher compared with earlier studies using perioperative dosing.

Serum zinc in critically ill adult patients with acute respiratory failure.

BACKGROUND AND AIMS: Zinc deficiency leads to susceptibility to infections and may affect pulmonary epithelial cell integrity. Low zinc levels have also been associated with a degree of organ failure and decreased survival in critically ill children. Accordingly, the purpose of the study was to assess serum zinc in adult patients with acute respiratory failure, its association with ventilatory support time, intensive care unit (ICU) length of stay (LOS), organ dysfunction and 30-day mortality. METHODS: We included consecutive patients with acute respiratory failure during an eight-week prospective, observational multicentre study (the FINNALI-study). Acute respiratory failure was defined as a need for either non-invasive or invasive positive pressure ventilation for >6 h regardless of the underlying cause or risk factors. After informed consent, a sample for zinc measurement was drawn at 6 h after the start of treatment and analysed from 551 of these patients. RESULTS: Low serum zinc was frequent (95.8%) at the onset acute respiratory failure. The median interquartile range [IQR] was 4.7 [3.0-6.9] µmol/l. The median [IQR] serum zinc levels in non-infectious, sepsis and septic shock patients were 5.0 [3.1-7.1], 5.1 [3.5-7.3] and 3.8 [2.6-5.9] µmol/l, respectively, P<0.01. Baseline zinc levels were not associated with ventilatory support time (P=0.98) or ICU LOS (P=0.053). The area under curve in receiver operating characteristics analysis for serum zinc regarding 30-day mortality was 0.55 (95% CI 0.49-0.60). CONCLUSIONS: Serum zinc on initiation of ventilation had no predictive value for 30-day mortality, ventilatory support time or intensive care unit LOS.

Corticosteroid therapy in intensive care unit patients with PCR-confirmed influenza A(H1N1) infection in Finland.

OBJECTIVE: To evaluate the incidence, treatment, and outcome of influenza A(H1N1) in Finnish intensive care units (ICUs) with special reference to corticosteroid treatment. METHODS: During the H1N1 outbreak in Finland between 11 October and 31 December 2009, we prospectively evaluated all consecutive ICU patients with high suspicion of or confirmed pandemic influenza A(H1N1) infection. We assessed severity of acute disease and daily organ dysfunction. Ventilatory support and other concomitant treatments were evaluated and recorded daily throughout the ICU stay. The primary outcome was hospital mortality. RESULTS: During the 3-month period altogether 132 ICU patients were tested polymerase chain reaction-positive for influenza A(H1N1). Of these patients, 78% needed non-invasive or invasive ventilatory support. The median (interquartile) length of ICU stay was 4 [2-12] days. Hospital mortality was 10 of 132 [8%, 95% confidence interval (CI) 3-12%]. Corticosteroids were administered to 72 (55%) patients, but rescue therapies except prone positioning were infrequently used. Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores in patients with and without corticosteroid treatment were 31 [24-36] and 6 [2-8] vs. 22 [5-30] and 3 [2-6], respectively. The crude hospital mortality was not different in patients with corticosteroid treatment compared to those without: 8 of 72 (11%, 95% CI 4-19%) vs. 2 of 60 (3%, 95% CI 0-8%) (P = 0.11). CONCLUSIONS: The majority of H1N1 patients in ICUs received ventilatory support. Corticosteroids were administered to more than half of the patients. Despite being more severely ill, patients given corticosteroids had comparable hospital outcome with patients not given corticosteroids.

Cytokine-induced Src homology 2 protein (CIS) promotes T cell receptor-mediated proliferation and prolongs survival of activated T cells.

Members of the suppressor of cytokine signaling (SOCS) family were discovered as negative regulators of cytokine signaling by inhibition of the Janus kinase-signal transducer and activator of transcription (Jak-STAT) pathway. Among them, cytokine-induced Src homology 2 (SH2) protein (CIS) was found to inhibit the interleukin 3- and erythropietin-mediated STAT5 signaling pathway. However, involvement of SOCS proteins in other signaling pathways is still unknown. This study shows that the expression of CIS is selectively induced in T cells after T cell receptor (TCR) stimulation. In transgenic mice, with selective expression of CIS in CD4 T cells, elevated CIS strongly promotes TCR-mediated proliferation and cytokine production in vitro, and superantigen-induced T cell activation in vivo. Forced expression of CIS also prolongs survival of CD4 T cells after TCR activation. Molecular events immediately downstream from the TCR are not changed in CIS-expressing CD4 T cells, but activation of mitogen-activated protein (MAP) kinase pathways by TCR stimulation is significantly enhanced. Together with the increased MAP kinase activation, a direct interaction of CIS and protein kinase Ctheta was also demonstrated. These results suggest that CIS is one of the important regulators of TCR-mediated T cell activation. The functions of CIS, enhancing TCR signaling and inhibiting cytokine signaling, may be important in the regulation of immune response and homeostasis.

HEMA reduces cell proliferation and induces apoptosis in vitro.

OBJECTIVES: Methacrylate monomers have been identified in aqueous extracts of freshly cured compomers. Both cells in the pulpal cavity and various cells of the oral mucosa can potentially be exposed to these leachables. Short-term exposure to dental monomers at relatively high concentrations induces adverse biological effects in vitro. The mechanisms involved have not been fully elucidated although involvement of various signaling pathways including ROS formation, activation of MAP-kinases and caspases has been suggested. The aim of this study was to investigate potential cellular responses following long-term exposure to relatively low and potentially more clinical relevant HEMA concentrations. METHODS: A submandibular gland cell line was exposed to HEMA (20-600 microM) for up to 72h. The impact on cell proliferation, apoptosis, and possible underlying mechanisms was assessed by flow cytometry, microscopy and western blotting. RESULTS: Exposure to HEMA (600 microM) resulted in reduced cell proliferation after 24h and increased apoptosis after 60h. Further, we observed ATM dependent phosphorylation of p53, advocating an initial DNA damage in the HEMA exposed cells. SIGNIFICANCE: In conclusion, we show that exposure to relatively low concentration of HEMA for a prolonged time result in cell death, possibly as a consequence of DNA damage.

Implants and/or teeth: consensus statements and recommendations.

In August 23-25, 2007, the Scandinavian Society for Prosthetic Dentistry in collaboration with the Danish Society of Oral Implantology arranged a consensus conference on the topic 'Implants and/or teeth'. It was preceded by a workshop in which eight focused questions were raised and answered in eight review articles using a systematic approach. Twenty-eight academicians and clinicians discussed the eight review papers with the purpose to reach consensus on questions relevant for the topic. At the conference the consensus statements were presented as well as lectures based on the review articles. In this article the methods used at the consensus workshop are briefly described followed by the statements with comments.

Bond strength of luting materials to ceramic crowns after different surface treatments.

The aim of present study was to evaluate the effect of different pre-treatments of alumina and zirconia copings on the bond strength of different luting materials. Pull out tests was performed on 60 alumina and 80 zirconia copings. Randomly selected, copings were divided in groups of i) un-treated alumina and zirconia copings, (n=20) ii) alumina and zirconia copings sandblasted with 50 or 110 microm alumina particles respectively (n=20), iii) zirconia copings treated with monolayer of glass pearls fused to the inner surface (n=20), iv) zirconia copings treated with silanized glass pearls (n=10). Zinc phosphate, Panavia 21 and VarioLink II were used for cementation. Pull out tests were done in an Instron universal testing machine with a speed of 0.5 mm/min and fracture loads was measured in N. Untreated zirconia copings cemented with zinc phosphate showed significantly higher bond strength values compared to those with sandblasted surfaces. No difference was seen between untreated alumina copings and those with sandblasted surfaces. Sandblasting decreased bond strength of zirconia and alumina copings. Glass pearls increased bond strength of zirconia copings, which was even better after silanization. Variolink II in combination with alumina gave significantly lower bond strength.

Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) shortens the period of neutropenia after autologous bone marrow transplantation in a primate model.

The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on hematopoietic reconstitution after autologous bone marrow transplantation was evaluated in a primate model. Animals were given a continuous intravenous infusion of recombinant human GM-CSF for several days both before and after transplantation or only after the transplant procedure. Marrow ablation was accomplished by total body irradiation. In both groups of animals, the neutrophil count reached 1,000/mm3 by 8-9 d posttransplant compared with an interval of 17 and 24 d for two concurrent controls. After withdrawal of GM-CSF, neutrophil counts fell to values comparable to those observed in untreated controls. Accelerated recovery of platelet production was also observed in four of the five animals. Two additional animals were initially given GM-CSF several weeks posttransplantation because of inadequate engraftment. Prompt and sustained increases in neutrophil and platelet counts were observed. We conclude that GM-CSF may be useful in accelerating bone marrow reconstitution.

Autism spectrum traits and visual processing in young adults with very low birth weight: the Helsinki Study of Very Low Birth Weight adults.

Visual processing problems may be one underlying factor for cognitive impairments related to autism spectrum disorders (ASDs). We examined associations between ASD-traits (Autism-Spectrum Quotient) and visual processing performance (Rey-Osterrieth Complex Figure Test; Block Design task of the Wechsler Adult Intelligence Scale-III) in young adults (mean age=25.0, s.d.=2.1 years) born preterm at very low birth weight (VLBW; <1500 g) (n=101) or at term (n=104). A higher level of ASD-traits was associated with slower global visual processing speed among the preterm VLBW, but not among the term-born group (P<0.04 for interaction). Our findings suggest that the associations between ASD-traits and visual processing may be restricted to individuals born preterm, and related specifically to global, not local visual processing. Our findings point to cumulative social and neurocognitive problems in those born preterm at VLBW.