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Southern African grasslands with a rich flora, shaped by fire, grazing, climate and geology, as well as playing a role in carbon sequestration, are becoming more important in conservation. Fire is often used as a management tool to improve vegetation and to protect property against uncontrolled fire. We therefore attempt to determine the effect consecutive burning has on vegetation. Paired plots along firebreaks were used to collect vegetation data using the Braun-Blanquet cover abundance scale. Soil samples were also collected to determine the impact of fire on below-ground nitrogen (N) and carbon (C) stocks and ratios. The results indicate that there is no difference between the plant communities of the firebreaks and the adjacent grassland; however, there are certain species that are favoured by firebreaks and others by the adjacent grassland. There is also no difference in diversity between the firebreaks and adjacent grassland areas. Carbon and nitrogen stocks as well as C:N ratios did not differ significantly between the firebreaks and the adjacent grassland plots although trends indicate a decline in both C and N with repeated burning. [ABSTRACT FROM AUTHOR]

We report the incorporation of an ensemble of G centers in silicon-on-insulator (SOI) microrings using ion implantation and conventional nanofabrication. The coupling between the emitters and the resonant modes of the microrings is studied using continuous-wave and time-resolved microphotoluminescence (PL) experiments. We observe the resonant modes of the microrings on PL spectra, on the wide spectral range that is covered by G center emission. By finely tuning the size of the microrings, we match their zero-phonon line at 1278 nm with a resonant mode of quality factor around 3000 and volume 7.2 (λ/n)3. The zero-phonon line intensity is enhanced by a factor of 5, both in continuous-wave and time-resolved measurements. This is attributed to the Purcell enhancement of zero-phonon spontaneous emission into the resonant mode and quantitatively understood considering the distribution of the G center dipoles. Despite the enhancement of the zero-phonon emission, we do not observe any sizeable decrease in the average lifetime of the G centers, which points at a low radiative yield (<10%). We reveal the detrimental impact of parasitic defects in heavily implanted silicon and discuss the perspectives for quantum electrodynamics experiments with individual color centers in lightly implanted SOI rings. Our results provide key information for the development of deterministic single-photon sources for integrated quantum photonics. [ABSTRACT FROM AUTHOR]

Background: Seventy per cent of patients with psychotic disorders has paranoid delusions. Paranoid delusions are associated with significant distress, hospital admission and social isolation. Cognitive-behavioural therapy for psychosis (CBTp) is the primary psychological treatment, but the median effect size is only small to medium. Virtual reality (VR) has a great potential to improve the effectiveness of CBTp. In a previous study, we found that VR based CBT (VRcbt) for paranoid delusions is superior to waiting list. As a next step, a direct comparison with CBTp is needed. The present study aims to investigate whether VRcbt is more effective and cost-effective than regular CBTp in treating paranoid delusions and improving daily life social functioning of patients with psychotic disorders. Methods: A total of 106 patients with DSM-5 diagnosis of psychotic disorder and at least moderate level of paranoid ideations will be recruited for this multicentre randomized controlled trial (RCT). Patients will be randomized to either VRcbt or standard CBTp for paranoid delusions. VRcbt consists of maximum 16 sessions in virtual social situations that trigger paranoid ideations and distress, delivered in an 8–12 week time frame. Standard CBTp also consists of maximum 16 sessions including exposure and behavioural experiments, delivered in an 8–12 week time frame. The two groups will be compared at baseline, post-treatment and six months follow-up. Primary outcome is the level of paranoid ideations in daily life social situations, measured with ecological momentary assessments (EMA) at semi-random moments ten times a day during seven days, before and after treatment. Every session, participants and therapists will rate the level of paranoid ideation and global clinical impression. Discussion: Comparison of VRcbt and CBTp will provide information about the relative (cost-) effectiveness of VRcbt for this population. VRcbt may become a preferred psychological treatment for paranoid delusions and social anxiety in patients with psychotic disorder. Trial registration: Netherlands Trial Register, NL7758. Registered on 23 May 2019. [ABSTRACT FROM AUTHOR]

Objectives: Topical drug administration is commonly applied to control oral inflammation. However, it requires sufficient drug adherence and a high degree of bioavailability. Here, we tested the hypothesis whether an ester-based core-multishell (CMS) nanocarrier is a suitable nontoxic drug-delivery system that penetrates efficiently to oral mucosal tissues, and thereby, increase the bioavailability of topically applied drugs. Material and methods: To evaluate adhesion and penetration, the fluorescence-labeled CMS 10-E-15-350 nanocarrier was applied to ex vivo porcine masticatory and lining mucosa in a Franz cell diffusion assay and to an in vitro 3D model. In gingival epithelial cells, potential cytotoxicity and proliferative effects of the nanocarrier were determined by MTT and sulphorhodamine B assays, respectively. Transepithelial electrical resistance (TEER) was measured in presence and absence of CMS 10-E-15-350 using an Endohm-12 chamber and a volt-ohm-meter. Cellular nanocarrier uptake was analyzed by laser scanning microscopy. Inflammatory responses were determined by monitoring pro-inflammatory cytokines using real-time PCR and ELISA. Results: CMS nanocarrier adhered to mucosal tissues within 5 min in an in vitro model and in ex vivo porcine tissues. The CMS nanocarrier exhibited no cytotoxic effects and induced no inflammatory responses. Furthermore, the physical barrier expressed by the TEER remained unaffected by the nanocarrier. Conclusions: CMS 10-E-15-350 adhered to the oral mucosa and adhesion increased over time which is a prerequisite for an efficient drug release. Since TEER is unaffected, CMS nanocarrier may enter the oral mucosa transcellularly. Clinical relevance: Nanocarrier technology is a novel and innovative approach for efficient topical drug delivery at the oral mucosa. [ABSTRACT FROM AUTHOR]

Thanks to their unique optical properties Ge–Sb–S–Se–Te amorphous chalcogenide materials and compounds offer tremendous opportunities of applications, in particular in near and mid-infrared range. This spectral range is for instance of high interest for photonics or optical sensors. Using co-sputtering technique of chalcogenide compound targets in a 200 mm industrial deposition tool, we show how by modifying the amorphous structure of GeSbwSxSeyTez chalcogenide thin films one can significantly tailor their linear and nonlinear optical properties. Modelling of spectroscopic ellipsometry data collected on the as-deposited chalcogenide thin films is used to evaluate their linear and nonlinear properties. Moreover, Raman and Fourier-transform infrared spectroscopies permitted to get a description of their amorphous structure. For the purpose of applications, their thermal stability upon annealing is also evaluated. We demonstrate that depending on the GeSbwSxSeyTez film composition a trade-off between a high transparency in near- or mid-infrared ranges, strong nonlinearity and good thermal stability can be found in order to use such materials for applications compatible with the standard CMOS integration processes of microelectronics and photonics. [ABSTRACT FROM AUTHOR]

Fast and label-free techniques to analyze viruses and bacteria are of crucial interest in biological and bio-medical applications. For this purpose, optofluidic systems based on the integration of photonic structures with microfluidic layers were shown to be promising tools for biological analysis, thanks to their small footprint and to their ability to manipulate objects using low powers. In this letter, we report on the optical trapping of living bacteria in a 2D silicon hollow photonic crystal cavity. This structure allows for the Gram-type differentiation of bacteria at the single cell scale, in a fast, label-free, and non-destructive way. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The United Kingdom Prospective Diabetes Study (UKPDS) study showed that glycaemic control (HbA1c) can predict vascular complications in Type 2 diabetes mellitus. The Diabetes Control and Complications Trial (DCCT) study showed that accumulation of advanced glycation end products (AGEs) from skin biopsies predicts vascular complications in Type 1 diabetes. Previously, we showed that tissue AGEs can be measured non‐invasively using skin autofluorescence (SAF). The aim of this study was to compare the predictive value of HbA1c and SAF for new macrovascular events and microvascular complications in people with Type 2 diabetes. Methods: A prospective cohort study of 563 participants, median age 64 years [interquartile range (IQR) 57–72], diabetes duration of 13 years, from five Dutch hospitals was performed. Results: After a median follow‐up of 5.1 (IQR 4.3–5.9) years, 79 (15%) participants had died and 49 (9%) were lost to follow‐up. Some 133 (26%) developed a microvascular complication and 189 (37%) a macrovascular event. Tertiles of HbA1c were significantly associated with development of microvascular complications (log rank P = 0.022), but not with macrovascular events. Tertiles of SAF were significantly associated with macrovascular events (log rank P = 0.003). Cox regression analysis showed SAF was associated with macrovascular events: crude hazard ratio (HR) 1.53 (P < 0.001) per unit increase, HR 1.28 (P = 0.03) after correction for UKPDS score. HbA1c was predictive for microvascular complications: crude HR 1.20 (P = 0.004), HR 1.20 (P = 0.004) after correction for UKPDS score. Conclusion: This study shows that tissue accumulation of AGEs, assessed by SAF, is associated with development of macrovascular events in people with Type 2 diabetes, whereas HbA1c is associated with the development of microvascular complications. [ABSTRACT FROM AUTHOR]

Fourteen years ago, optical lattices and holographic tweezers were considered as a revolution, allowing for trapping and manipulating multiple particles at the same time using laser light. Since then, near-field optical forces have aroused tremendous interest as they enable efficient trapping of a wide range of objects, from living cells to atoms, in integrated devices. Yet, handling at will multiple objects using a guided light beam remains a challenging task for current on-chip optical trapping techniques. We demonstrate here on-chip optical trapping of dielectric microbeads and bacteria using one-dimensional optical lattices created by near-field mode beating along a few-mode silicon nanophotonic waveguide. This approach allows not only for trapping large numbers of particles in periodic trap arrays with various geometries, but also for manipulating them via diverse transport and repositioning techniques. Near-field mode-beating optical lattices may be readily implemented in lab-on-a-chip devices, addressing numerous scientific fields ranging from bio-analysis to nanoparticle processing. [ABSTRACT FROM AUTHOR]

Background and Objectives In the oral cavity, the mucosal tissues may develop a number of different pathological conditions, such as inflammatory diseases (gingivitis, periodontitis) and autoimmune disorders (eg, oral lichen planus) that require therapy. The application of topical drugs is one common therapeutic approach. However, their efficacy is limited. Dilution effects due to saliva hinder the adherence and the penetration of drug formulations. Therefore, the bioavailability of oral topical drugs is insufficient, and patients may suffer from disease over years, if not life-long. Material and Methods In the present study, we characterized core-multishell ( CMS) nanocarriers for their potential use as drug delivery systems at oral mucosal tissues. For this purpose, we prepared porcine masticatory as well as buccal mucosa and performed Franz cell diffusion experiments. Penetration of fluorescently labeled CMS nanocarriers into the mucosal tissue was analyzed using confocal laser scanning microscopy. Upon exposure to CMS nanocarriers, the metabolic and proliferative activity of gingival epithelial cells was determined by MTT and sulforhodamine B assays, respectively. Results Here, we could show that the carriers penetrate into both mucosal tissues, while particles penetrate deeper into the masticatory mucosa. Electron paramagnetic resonance spectroscopy revealed that the 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxy-labeled glucocorticoid dexamethasone loaded on to the CMS nanocarriers was released from the carriers in both mucosal tissues but with a higher efficiency in the buccal mucosa. The release from the nanocarriers is in both cases superior compared to the release from a conventional cream, which is normally used for the treatment of inflammatory conditions in the oral cavity. The CMS nanocarriers exhibited neither cytotoxic nor proliferative effects in vitro. Conclusion These findings suggested that CMS nanocarriers might be an innovative approach for topical drug delivery in the treatment of oral inflammatory diseases. [ABSTRACT FROM AUTHOR]

Photonic crystals and microcavities act as on-chip nano-optical tweezers for identification and manipulation of biological objects. Until now, optical trapping of virus and bacteria has been achieved and their presence in the vicinity of the optical resonator is deduced by the shift in the resonant wavelength. Here, we show trapping and identification of bacteria through a properly tuned silicon on insulator microcavity. Through the spatial and temporal observations of bacteria–cavity interaction, the optical identification of three different kinds of bacteria is demonstrated. [ABSTRACT FROM AUTHOR]

Obesity, which affects 600 million adults worldwide, is a major risk factor for type 2 diabetes (T2D) and insulin resistance. Current therapies for these metabolic disorders include weight management by lifestyle intervention or bariatric surgery and pharmacological treatment with the aim of regulating blood glucose. Probably because of their short-term effectiveness, these therapies have not been able to stop the rapidly rising prevalence of T2D over the past decades, highlighting an urgent need to develop new therapeutic strategies. The role of immune cells, such as macrophages, in insulin resistance has been extensively studied. Major advances have been made to elucidate the role of adipose tissue macrophages in these pathogeneses. Recently, anti-inflammatory drugs have been suggested as an alternative treatment for T2D, and clinical trials of these agents are currently ongoing. In addition, results of previous clinical trials using antibodies against inflammatory cytokines, which showed modest effects, are now being rigorously re-evaluated. However, it is still unclear how liver macrophages [termed Kupffer cells (KCs)], which constitute the major source of macrophages in the body, contribute to the development of insulin resistance. In this review, we will discuss the present understanding of the role of liver immune cells in the development of insulin resistance. We will particularly focus on KCs, which could represent an attractive target for the treatment of metabolic diseases. [ABSTRACT FROM AUTHOR]

Two siblings were found to be affected by long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, one of which died suddenly and unexpectedly on the 3rd day of life suffering from extreme hypoketotic hypoglycaemia. The younger sibling started to have feeding problems, lowered consciousness, and liver dysfunction at the age of 5 months. Her urine contained large amounts of C6-C14 3-hydroxydicarboxylic acids and conjugated 3-hydroxyoctanoic acid, as verified by gas chromatography/mass spectrometry. Plasma long-chain acylcarnitine was increased. A clue to the diagnosis was given by the results of a phenylpropionic acid loading test. This revealed small, but significant amounts of conjugated 3-hydroxyphenylpropionic acid (phenylhydracrylic acid) in the patient's urine. Subsequently, the activity of long-chain 3-hydroxyacyl-CoA dehydrogenase was found to be deficient in cultured skin fibroblasts. Based on the findings obtained by a medium-chain triglyceride load, a diet enriched in this type of fat was prescribed. On this regimen the patient started to thrive, signs of cardiomyopathy disappeared, and her liver function normalized. [ABSTRACT FROM AUTHOR]

Objectives We investigated whether metformin can improve endothelial function and decrease inflammatory activity, and thereby decrease the risk of atherothrombotic disease. Subjects and design A randomized, placebo-controlled trial with a follow-up period of 4.3 years set in the outpatient clinics of three nonacademic hospitals (Hoogeveen, Meppel and Coevorden Hospitals, the Netherlands). A total of 390 patients with type 2 diabetes treated with insulin were included. Either metformin 850 mg or placebo (one to three times daily) was added to insulin therapy. Urinary albumin excretion and plasma levels of von Willebrand factor ( vWf), soluble vascular adhesion molecule-1 ( sVCAM-1), soluble E-selectin ( sE-selectin), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), C-reactive protein (CRP) and soluble intercellular adhesion molecule-1 ( sICAM-1) were measured at baseline and after 4, 17, 30, 43 and 52 months. Results Metformin significantly reduced levels of vWF, sVCAM-1, t-PA, PAI-1, CRP and sICAM-1, which, except for CRP, remained significant after adjustment for baseline differences in age, sex, smoking and severity of previous cardiovascular (CV) disease. No effects on urinary albumin excretion or sE-selectin were observed. The improvements in vWf and sVCAM-1 statistically explained about 34% of the reduction in the risk of CV morbidity and mortality associated with metformin treatment in this study. Conclusions Metformin is associated with improvement in some ( vWF and sVCAM-1) but not all markers of endothelial function, which may explain why it is associated with a decreased risk of CV disease in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Purpose: The goal was to provide a quantitative evaluation of the accuracy of three different fixation systems for stereotactic radiotherapy and to evaluate patients' acceptance for all fixations.Methods: A total of 16 consecutive patients with brain tumours undergoing fractionated stereotactic radiotherapy (SCRT) were enrolled after informed consent (Clinical trials.gov: NCT00181350). Fixation systems evaluated were the BrainLAB® mask, with and without custom made bite-block (fixations S and A) and a homemade neck support with bite-block (fixation B) based on the BrainLAB® frame. The sequence of measurements was evaluated in a randomized manner with a cross-over design and patients' acceptance by a questionnaire.Results: The mean three-dimensional (3D) displacement and standard deviations were 1.16 ± 0.68 mm for fixation S, 1.92 ± 1.28 and 1.70 ± 0.83 mm for fixations A and B, respectively. There was a significant improvement of the overall alignment (3D vector) when using the standard fixation instead of fixation A or B in the craniocaudal direction (p = 0.037). Rotational deviations were significantly less for the standard fixation S in relation to fixations A (p = 0.005) and B (p = 0.03). EPI imaging with off-line correction further improved reproducibility. Five out of 8 patients preferred the neck support with the bite-block.Conclusion: The mask fixation system in conjunction with a bite-block is the most accurate fixation for SCRT reducing craniocaudal and rotational movements. Patients favoured the more comfortable but less accurate neck support. To optimize the accuracy of SCRT, additional regular portal imaging is warranted. [ABSTRACT FROM AUTHOR]

ims/hypothesis: Extracellular signal-regulated kinase (ERK) activity is increased in adipose tissue in obesity and type 2 diabetes mellitus and strong evidences suggests that it is implicated in the downregulation of insulin signalling and action in the insulin-resistant state. To determine the role of ERK1 in obesity-associated insulin resistance in vivo, we inactivated Erk1 (also known as Mapk3) in obese leptin-deficient mice ( ob/ob). Methods: Mice of genotype ob/ ob-Erk1 were obtained by crossing Erk1 mice with ob/ ob mice. Glucose tolerance and insulin sensitivity were studied in 12-week-old mice. Tissue-specific insulin sensitivity, insulin signalling, liver steatosis and adipose tissue inflammation were determined. Results: While ob/ ob-Erk1 and ob/ ob mice exhibited comparable body weight and adiposity, ob/ ob-Erk1 mice did not develop hyperglycaemia and their glucose tolerance was improved. Hyperinsulinaemic-euglycaemic clamp studies demonstrated an increase in whole-body insulin sensitivity in the ob/ ob-Erk1 mice associated with an increase in both insulin-stimulated glucose disposal in skeletal muscles and adipose tissue insulin sensitivity. This occurred in parallel with improved insulin signalling in both tissues. The ob/ ob-Erk1 mice were also partially protected against hepatic steatosis with a strong reduction in acetyl-CoA carboxylase level. These metabolic improvements were associated with reduced expression of mRNA encoding inflammatory cytokine and T lymphocyte markers in the adipose tissue. Conclusions/interpretation: Our results demonstrate that the targeting of ERK1 could partially protect obese mice against insulin resistance and liver steatosis by decreasing adipose tissue inflammation and by increasing muscle glucose uptake. Our results indicate that deregulation of the ERK1 pathway could be an important component in obesity-associated metabolic disorders. [ABSTRACT FROM AUTHOR]

Objective: Activation of extracellular signal-regulated kinase-(ERK)-1/2 by cytokines in adipocytes is involved in the alterations of adipose tissue functions participating in insulin resistance. This study aims at identifying proteins regulating ERK1/2 activity, specifically in response to inflammatory cytokines, to provide new insights into mechanisms leading to abnormal adipose tissue function.Research Design and Methods: Kinase activities were inhibited with pharmacological inhibitors or siRNA. Lipolysis was monitored through glycerol production. Gene expression in adipocytes and adipose tissue of obese mice and subjects was measured by real-time PCR.Results: IkappaB kinase-(IKK)-beta inhibition prevented mitogen-activated protein (MAP) kinase kinase (MEK)/ERK1/2 activation in response to interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha but not insulin in 3T3-L1 and human adipocytes, suggesting that IKKbeta regulated a MAP kinase kinase kinase (MAP3K) involved in ERK1/2 activation induced by inflammatory cytokines. We show that the MAP3K8 called Tpl2 was expressed in adipocytes and that IL-1beta and TNF-alpha activated Tpl2 and regulated its expression through an IKKbeta pathway. Pharmacological inhibition or silencing of Tpl2 prevented MEK/ERK1/2 activation by these cytokines but not by insulin, demonstrating its involvement in ERK1/2 activation specifically in response to inflammatory stimuli. Importantly, Tpl2 was implicated in cytokine-induced lipolysis and in insulin receptor substrate-1 serine phosphorylation. Tpl2 mRNA expression was upregulated in adipose tissue of obese mice and patients and correlated with TNF-alpha expression.Conclusions: Tpl2 is selectively involved in inflammatory cytokine-induced ERK1/2 activation in adipocytes and is implicated in their deleterious effects on adipocyte functions. The deregulated expression of Tpl2 in adipose tissue suggests that Tpl2 may be a new actor in adipose tissue dysfunction in obesity. [ABSTRACT FROM AUTHOR]

Obesity is associated with adipose tissue inflammation. The CD40 molecule, TNF receptor superfamily member 5 (CD40)/CD40 ligand (CD40L) pathway plays a role in the onset and maintenance of the inflammatory reaction, but has not been studied in human adipose tissue. Our aim was to examine CD40 expression by human adipocytes and its participation in adipose tissue inflammation. CD40 expression was investigated in human whole adipose tissue and during adipocyte differentiation by real-time PCR, Western blot and immunohistochemistry. The CD40/CD40L pathway was studied using recombinant CD40L (rCD40L) in adipocyte culture and neutralising antibodies in lymphocyte/adipocyte co-culture. CD40 mRNA levels in subcutaneous adipose tissue were higher in the adipocyte than in the stromal–vascular fraction. CD40 expression was upregulated during adipocyte differentiation. Addition of rCD40L to adipocytes induced mitogen activated protein kinase (MAPK) activation, stimulated inflammatory adipocytokine production, and decreased insulin-induced glucose transport in parallel with a downregulation of IRS1 and GLUT4 (also known as SCL2A4). rCD40L decreased the expression of lipogenic genes and increased lipolysis. CD40 mRNA levels were significantly higher in subcutaneous adipose tissue than in visceral adipose tissue of obese patients and were positively correlated with BMI, and with IL6 and leptin mRNA levels. Lymphocyte/adipocyte co-culture led to an upregulation of proinflammatory adipocytokines and a downregulation of leptin and adiponectin. Physical separation of the two cell types attenuated these effects, suggesting the involvement of a cell–cell contact. Blocking the CD40/CD40L interaction with neutralising antibodies reduced IL-6 secretion from adipocytes. Adipocyte CD40 may contribute to obesity-related inflammation and insulin resistance. T lymphocytes regulate adipocytokine production through both the release of soluble factor(s) and heterotypic contact with adipocytes involving CD40. [ABSTRACT FROM AUTHOR]

Insulin resistance is caused by numerous factors including inflammation. It is characterised by defective insulin stimulation of adipocyte and muscle glucose transport, which requires the glucose transporter GLUT4 translocation towards the plasma membrane. Defects in insulin signalling can cause insulin resistance, but alterations in GLUT4 trafficking could also play a role. Our goal was to determine whether proteins controlling GLUT4 trafficking are altered in insulin resistance linked to obesity. Using real-time RT-PCR, we searched for selected transcripts that were differentially expressed in adipose tissue and muscle in obese mice and humans. Using various adipocyte culture models and in vivo mice treatment, we searched for the involvement of TNF-α in these alterations in obesity. Sortilin mRNA and protein were downregulated in adipose tissue from obese db/db and ob/ob mice, and also in muscle. Importantly, sortilin mRNA was also decreased in morbidly obese human diabetic patients. Sortilin and TNF-α (also known as TNF) mRNA levels were inversely correlated in mice and human adipose tissues. TNF-α decreased sortilin mRNA and protein levels in cultured mouse and human adipocytes, an effect partly prevented by the peroxisome proliferator-activated receptor γ activator rosiglitazone. TNF-α also inhibited adipocyte and muscle sortilin mRNA when injected to mice. Sortilin, an essential player in adipocyte and muscle glucose metabolism through the control of GLUT4 localisation, is downregulated in obesity and TNF-α is likely to be involved in this defect. Chronic low-grade inflammation in obesity could thus contribute to insulin resistance by modulating proteins that control GLUT4 trafficking. [ABSTRACT FROM AUTHOR]

Background Unexplained fatigue is frequently encountered in general practice. Because of the low prior probability of underlying somatic pathology, the positive predictive value of abnormal (blood) test results is limited in such patients. Aim The study objectives were to investigate the relationship between established diagnoses and the occurrence of abnormal blood test results among patients with unexplained fatigue; to survey the effects of the postponement of test ordering on, this relationship; and to explore consultation-related determinants of abnormal test results. Design of study Cluster randomised trial. Setting General practices of 91 GPs in the Netherlands. Method GPs were randomised to immediate or postponed blood-test ordering. Patients with new unexplained fatigue were included. Limited and expanded sets of blood tests were ordered either immediately or after 4 weeks. Diagnoses during the 1-year follow-up period were extracted from medical records. Two-by-two tables were generated. To establish independent determinants of abnormal test results, a multivariate logistic regression model was used. Results Data of 325 patients were analysed (71% women; mean age 41 years). Eight per cent of patients had a somatic illness that was detectable by blood-test ordering. The number of false-positive test results increased in particular in the expanded test set. Patients rarely reconsulted after 4 weeks. Test postponement did not affect the distribution of patients over the two-by-two tables. No independent consultation-related determinants of abnormal test results were found. Conclusion Results support restricting the number of tests ordered because of the increased risk of false-positive test results from expanded test sets. Although the number of reconsulting patients was small, the data do not refute the advice to postpone blood-test ordering for medical reasons in patients with unexplained fatigue in general practice. [ABSTRACT FROM AUTHOR]

Abstract: Little is known about the role of p38MAPK in human adipocyte differentiation. Here we showed that p38MAPK activity increases during human preadipocytes differentiation. Pharmacological inhibition of p38MAPK during adipocyte differentiation of primary human preadipocytes markedly reduced triglycerides accumulation and adipocyte markers expression. Cell cycle arrest or proliferation was not affected by p38MAPK inhibition. Although induction of C/EBPβ was not altered by the p38MAPK inhibitor, its phosphorylation on Threonine188 was decreased as well as PPARγ expression. These results indicate that p38MAPK plays a positive role in human adipogenesis through regulation of C/EBPβ and PPARγ factors. [Copyright &y& Elsevier]

de Jager J, Kooy A, Lehert Ph, Bets D, Wulffelé MG, Teerlink T, Scheffer PG, Schalkwijk CG, Donker AJM, Stehouwer CDA (Bethesda General Hospital Hoogeveen, Hoogeveen, The Netherlands; University of Mons, Belgium; E. Merck Nederland B.V. Amsterdam; VU University Medical Centre, and Institute for Cardiovascular Research, Amsterdam; and University Hospital Maastricht, Maastricht; The Netherlands). Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial.J Intern Med2005;257:100–109.The UK Prospective Diabetes Study (UKPDS) showed that treatment with metformin decreases macrovascular morbidity and mortality independent of glycaemic control. We hypothesized that metformin may achieve this by improving endothelial function and chronic, low-grade inflammation. Data on this issue are scarce and we therefore tested, in the setting of a randomized, placebo-controlled trial, whether metformin can affect endothelial function and low-grade inflammation.The Hyperinsulinaemia the Outcome of its Metabolic Effects (HOME) trial is a double-blind trial, in which all patients were randomized to receive either metformin or placebo in addition to insulin therapy. At the beginning and the end of a 16-week treatment period fasting blood samples were drawn and a physical examination was carried out.The trial was conducted in the outpatient clinics of three nonacademic hospitals (Hoogeveen, Meppel and Coevorden; the Netherlands).Patients were included if they were between 30 and 80 years of age; had received a diagnosis of diabetes after the age of 25; had never had an episode of ketoacidosis; and their blood glucose-lowering treatment previously consisted of oral agents but now only consisted of either insulin (n = 345) or insulin and metformin (n = 45). We excluded pregnant women and women trying to become pregnant, patients with a Cockroft-Gault-estimated creatinine clearance<50 mL min−1, or low plasma cholinesterase (reference value<3.5 units L−1), patients with congestive heart failure (New York Heart Association class III/IV), or patients with other serious medical or psychiatric disease. A total of 745 eligible patients were approached; 390 gave informed consent and were randomized (196 metformin, 194 placebo). About 353 patients completed 16 weeks of treatment (171 metformin, 182 placebo).The HOME trial was designed to study the metabolic and cardiovascular effects of metformin during a follow-up of 4 years. Presented here are the results of an interim analysis after 16 weeks of treatment.When compared with placebo, metformin treatment was associated with an increase in urinary albumin excretion of 21% (−1 to +48;P = 0.06); a decrease in plasma von Willebrand factor of 6% (−10 to−2;P = 0.0007); a decrease in soluble vascular cell adhesion molecule-1 of 4% (−7 to−2;P = 0.0002); a decrease in soluble E-selectin of 6% (−10 to−2;P = 0.008); a decrease in tissue-type plasminogen activator of 16% (−20 to−12;P < 0.0001); and a decrease in plasminogen activator inhibitor-1 of 20% (−27 to−10;P = 0.0001). These changes could not be explained by metformin-associated changes in glycaemic control, body weight or insulin dose. Markers of inflammation, i.e. C-reactive protein and soluble intercellular adhesion molecule-1, did not change with metformin treatment.In patients with type 2 diabetes treated with insulin, metformin treatment was associated with improvement of endothelial function, which was largely unrelated to changes in glycaemic control, but not with improvement of chronic, low-grade inflammation. [ABSTRACT FROM AUTHOR]

Copyright of Verhaltenstherapie is the property of Karger AG and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Verhaltenstherapie is the property of Karger AG and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this paper, the authors present a technique aimed at increasing the efficiency of biological waste air treatment. The objective is to modify the existing biological waste air treatment systems (i.e. biofilters) to reduce the emitted substances and their potential environmental impacts. The principle of the ionization system is described, along with the first experiences of applying those methods during the rotting process. The investigated system is evaluated by means of life cycle impact assessment, with a focus on odour. It is demonstrated which of the measured substances (i.e. VOC) can potentially contribute to the odorant concentration. Further, it is shown which odour-intensive substances can be reduced by deploying ionization. Finally, the authors respond to the fact that the cleaning efficiency of ionization strongly depends on the humidity of the treated waste gas stream. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. The accumulation of AGE is thought to play a role in the pathogenesis of chronic complications of diabetes mellitus and renal failure. All current measurements of AGE accumulation require invasive sampling. We exploited the fact that several AGE exhibit autofluorescence to develop a non-invasive tool for measuring skin AGE accumulation, the Autofluorescence Reader (AFR). We validated its use by comparing the values obtained using the AFR with the AGE content measured in extracts from skin biopsies of diabetic and control subjects. Methods. Using the AFR with an excitation light source of 300–420 nm, fluorescence of the skin was measured at the arm and lower leg in 46 patients with diabetes (Type 1 and 2) and in 46 age- and sex-matched control subjects, the majority of whom were Caucasian. Autofluorescence was defined as the average fluorescence per nm over the entire emission spectrum (420–600 nm) as ratio of the average fluorescence per nm over the 300–420-nm range. Skin biopsies were obtained from the same site of the arm, and analysed for collagen-linked fluorescence (CLF) and specific AGE: pentosidine, Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL). Results. Autofluorescence correlated with CLF, pentosidine, CML, and CEL (r=0.47–0.62, p≤0.002). In 32 of 46 diabetic patients (70%), autofluorescence values were above the 95% CI of the mean value in control subjects, and correlated with age, diabetes duration, mean HbA1c of the previous year and creatinine levels. Conclusions/interpretation. The AFR offers a simple alternative to invasive measurement of AGE accumulation and, to date, has been validated in non-pigmented skin. The AFR may prove to be a useful clinical tool for rapid risk assessment of AGE-related long-term complications in diabetes mellitus and in other conditions associated with AGE accumulation. [ABSTRACT FROM AUTHOR]

Currently, the mainly used characteristics to predict outcome or treatment response in patients with breast cancer are tumor size, N-status, histological grade and receptor status (ER/PgR). However, these conventional clinico-pathological characteristics are of limited value. More accurate determinators are needed to select patients who are most likely to benefit from treatment in terms of prognosis as well as treatment response. Proliferation and apoptosis are assumed to play a key role in tumor progression as well as response to treatment. Currently, an increasing number of molecular factors controlling apoptosis as well as proliferation is known. The clinical relevance of apoptotic tumor markers in the treatment strategy of patients with breast cancer is the subject of this review. In addition, potential future developments are discussed. [ABSTRACT FROM AUTHOR]

Screening for sexually transmitted diseases (STDs) in early pregnancy is included in routine antenatal care for several infectious agents in many western European countries. Pharmaco-economics of these interventions have been evaluated. Currently, reconsideration of anternatal screening is ongoing, with explicit attention given to extending the STD testing to some other infectious agents, such as HIV and Chlamydia trachomatis (CT). This paper examines the socio-economics of such extensions for the Netherlands and the UK. Based on pharmaco-economic investigations in the UK and the Netherlands, we argue that serious consideration should be given to expanding antenatal STD screening to include universal testing for HIV and CT. Further research should be directed to the economic aspects of paediatric HIV infection and the epidemiology of CT in pregnancy. [ABSTRACT FROM AUTHOR]

This paper compares AIDS hospital care in several European-Union countries. For this purpose hospital-care utilisation studies on inpatient days and outpatient contacts were analysed in a generic approach controlling for severity stages of AIDS. Lifetime hospital-care needs for AIDS are derived, providing useful information for health-care policy makers. In a next step, lifetime estimates are linked to estimated annual new cases of AIDS, resulting from standardised epidemiological modelling. These results on AIDS impact at the population level are reported including statistical confidence limits. Both lifetime hospital- care needs at the patient level and AIDS impact at the population level are compared between countries and related to characteristics of the national AIDS epidemics and health-care systems. A person with AIDS has a contact - either inpatient day or outpatient visit - with the hospital in 14% (UK) to 24% (France) of the days spent in the AIDS stage. Related to the national AIDS epidemics (epidemiological impact), Italy and Greece have high levels of outpatient contacts per million population. Estimated hospital-bed needs for AIDS in 1995 are up to 2.13% (in Spain) of total national acute-care hospital beds available. Estimated per-capita needs for outpatient visits in 1995 are highest in Italy, corresponding to 108 doctor full-time equivalents. In a case-study for Greece and The Netherlands, differences in hospital-care utilisation patterns were assessed to correspond with differences in their health-care systems (number of hospital beds, doctors and nurses per capita and some qualitative characteristics of medical care in both countries). International comparison of AIDS hospital care is possible using standardised analysis of national hospital-care utilisation data and standardised epidemiological modelling. Estimates of lifetime hospital-care needs are an essential input for cost-effectiveness analyses used to aid health-care policy decision-making. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to determine the costs associated with influenza and the cost effectiveness (net costs per life-year gained) of influenza vaccination in The Netherlands.Design and Setting: The economic evaluation comprised a cost-of-illness assessment and a cost-effectiveness analysis, both of which were conducted from the healthcare perspective in The Netherlands. The modelling framework for the economic evaluation linked epidemiological aspects of influenza (e.g. incidence, mortality, years of life lost) to vaccination coverage and healthcare resource use. Healthcare resource use was specified for hospitalisations, general practitioner visits and drugs.Intervention: The intervention assessed in the cost-effectiveness analysis was influenza vaccination.Main Outcome Measures and Results: The costs of influenza were estimated to be 31 million euros (EUR) for the influenza season 1995/96 in The Netherlands (EUR1 approximately $US1.1). For the extended programme in 1997/98, i.e. all elderly people, the cost-effectiveness ratio was estimated at EUR1820 per life-year gained. Sub-group analysis demonstrated that the programme had a more favourable cost effectiveness among the chronically ill elderly population (cost saving) than among the rest of the elderly population (EUR6900 per life-year gained).Conclusion: Influenza vaccination has a cost-effectiveness ratio that is better than or comparable to that of other implemented Dutch programmes in the prevention of infectious diseases. [ABSTRACT FROM AUTHOR]