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Soil organisms and specifically microorganisms are indispensable to life on Earth. They regulate essential ecosystem functions from carbon sequestration to primary production. These organisms often experience stress when the balance of the soil system is disrupted by agricultural practices and environmental disturbances. A new stressor is plastic, which can be found in soils, in and around soil-dwelling organisms, and close to plants. The presence of plastic can affect soil chemistry, plant growth and the survival of higher-order organisms. Microbial organisms respond sensitively to these changes in their surroundings and will thus be (in)directly affected by plastic. Eventually, this results in a different microbial activity, composition and reduced diversity. Plastic might even serve as a specific habitat for microorganisms, generally referred to as the plastisphere. In this review, we make predictions based on the observed effects of (micro)plastics and the potential impact on the plant-soil-microbiome system. We use prior knowledge of other disturbances (e.g. tillage and pesticides) which have been studied for many years in relation to the soil microbial community. Further research is needed to develop standardized methods to study smaller plastic particles (micro- and nanoplastics) as these play the most dominant role in terrestrial ecosystems.

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We report on a patient who presented with refractory subacute cutaneous lupus erythematosus. The scaly annular and polycyclic patches/plaques, and hyperkeratotic lesions on multiple fingers improved rapidly after treatment with baricitinib.

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OBJECTIVES: Controversy exists about the integration of erlotinib in patients with EGFR wildtype, advanced NSCLC. MATERIALS AND METHODS: We included patients with advanced NSCLC receiving at least two lines of palliative systemic treatment between January 2005 and December 2014 and not harbouring targetable driver mutations. Primary study endpoint was overall survival (OS), secondary endpoint progression-free survival (PFS). We used Kaplan-Meier statistics, multivariate Cox regression and Propensity score or Inverse Probability Weights (IPW) matching to compare clinical outcome between patients receiving erlotinib in second or further line and those receiving chemotherapy only. The study had a power of 90% to detect a survival superiority of 30%. RESULTS: From a total of 827 patients, we excluded 171 patients with potentially curative treatment, 189 receiving treatment outside of our institute, 206 receiving no or only one line of systemic treatment, 6 with ALK translocations and 28 with EGFR mutations. From 227 patients in the final efficacy analysis, 125 patients received erlotinib in second (89 patients), third (28) or further-line (8), and 102 patients received chemotherapy only. Women and never smokers were significantly overrepresented in the erlotinib group. Both OS (hazard ratio (HR)=1.14, 95% CI 0.80-1.63, P=0.448) and PFS (HR=1.20, 95% CI 0.95-1.52, P=0.119) were similar in the erlotinib compared to the chemotherapy group using IPW-adjusted Cox regression analysis treating the use of erlotinib as a time-dependent covariate starting from second-line treatment and stratified for ECOG performance status and treatment line. ECOG performance status was the most powerful covariate to select patients for erlotinib treatment. CONCLUSION: The present study suggests erlotinib to have similar clinical efficacy compared to chemotherapy in patients with pretreated advanced NSCLC and no known molecular targetable alterations.

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BACKGROUND: Impulsive decision making is a hallmark of frequently occurring addiction disorders including alcohol dependence (AD). Therefore, ameliorating impulsive decision making is a promising target for the treatment of AD. Previous studies have shown that modafinil enhances cognitive control functions in various psychiatric disorders. However, the effects of modafinil on delay discounting and its underlying neural correlates have not been investigated as yet. The aim of the current study was to investigate the effects of modafinil on neural correlates of impulsive decision making in abstinent AD patients and healthy control (HC) subjects. METHOD: A randomized, double-blind, placebo-controlled, within-subjects cross-over study using functional magnetic resonance imaging (fMRI) was conducted in 14 AD patients and 16 HC subjects. All subjects participated in two fMRI sessions in which they either received a single dose of placebo or 200 mg of modafinil 2 h before the session. During fMRI, subjects completed a delay-discounting task to measure impulsive decision making. RESULTS: Modafinil improved impulsive decision making in AD pateints, which was accompanied by enhanced recruitment of frontoparietal regions and reduced activation of the ventromedial prefrontal cortex. Moreover, modafinil-induced enhancement of functional connectivity between the superior frontal gyrus and ventral striatum was specifically associated with improvement in impulsive decision making. CONCLUSIONS: These findings indicate that modafinil can improve impulsive decision making in AD patients through an enhanced coupling of prefrontal control regions and brain regions coding the subjective value of rewards. Therefore, the current study supports the implementation of modafinil in future clinical trials for AD.

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BACKGROUND: Impulsivity is a hallmark of addiction and predicts treatment response and relapse. Impulsivity is, however, a complex construct. Translational cross-species research is needed to give us greater insight into the neurobiology and the role of impulsivity in addiction and to help with the development of new treatment strategies for improving patients' impulse control. AIM: To review recent evidence concerning the concept of impulsivity and the role of impulsivity in addiction. METHOD: The concept and neurobiology of impulsivity are reviewed from a translational perspective. The role of impulsivity in addiction and implications for treatment are discussed. RESULTS: Our recent translational cross-species study indicates that impulsivity is made up of several, separate independent features with partly distinct underlying neurobiological substrates. There are also indications that these features make a unique and independent contribution to separate stages of the addiction cycle. CONCLUSION: In addition, the improvement of impulse control is a promising new target area for treatments that could lead to better results. However, those involved in developing new treatment strategies will have to take into account the complexity and multidimensional character of impulsivity.

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RATIONALE: Impulsivity and craving are both associated with higher relapse rates and a worse prognosis in patients with a substance use disorder, but the relationship between these two phenomena has been largely ignored in the field of alcohol use disorders. OBJECTIVES: The primary aim of this study was to investigate the relationship between different dimensions of impulsivity and different forms of self-reported craving. Additionally, the influence of the severity of alcohol dependence on impulsivity, craving, and on their relationship was exploed. METHODS: Impulsivity and craving levels were investigated in 87 abstinent alcohol-dependent (AD) patients using a broad range of self-report questionnaires and behavioral impulsivity measures. Alcohol use was measured by means of the timeline followback method. RESULTS: Higher scores of emotional craving (Alcohol Urge Questionnaire-AUQ) were significantly related to higher self-reported impulsivity (Barratt Impulsiveness Scale, version 11) and to higher cognitive impulsivity (information sampling task). Additionally, exploratory analyses suggest that these relationships are more pronounced in severe AD patients compared to less severe AD patients. No significant relationships were found between emotional craving (AUQ) and motor impulsivity (stop signal task) or delay discounting and between obsessive-compulsive craving (Obsessive Compulsive Drinking Scale) and measures of impulsivity. CONCLUSIONS: Emotional craving is related to self-reported impulsivity and to cognitive impulsivity. These relationships seem to be more pronounced in AD patients with severe alcohol dependence. Further research is needed to explore the effect of this relationship on treatment outcome and relapse.

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BACKGROUND: In Article 107 of the hospital legislation the Belgian government provides for a possible reorganisation of current mental health care. According to the Article, hospital managers and the medical staff of residential care units in each region are permitted tot re-allocate resources in such a way that their current government allowance is used for the development of an alternative type of health care that is more community-based. AIM: To explore the possible consequences that such a step is likely to have on the current users of long-term residential care. METHOD: We looked critically at the draft text which was circulated in order tot explain the proposed reorganisation. We evaluated the scientific evidence concerning the feasibility of the ideas put forward in the text, focusing particularly on the care of patients with a serious mental illness. RESULTS: The method, which involves the re-allocation of funds in order to stimulate the reorganisation of care, is considered to be self-defeating. On the one hand, it constitutes a threat, leading to possible closure of the least profitable services, including hospital wards for long-stay patients. On the other hand, the proposed health care organisation poses a threat to the very group of patients who reside in such hospitals and it may in fact lower the level of care they receive. CONCLUSION: It will be necessary to check on the effects that this reorganisation will have on patients with a serious mental illness. We therefore propose some ways of monitoring the effects that the planned reorganisation is likely to have on this vulnerable group of patients.

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BACKGROUND: For more than two decades psychiatrists have known about and have promoted modafinil, a very promising stimulant that boosts wakefulness in cases of narcolepsy and also enhances cognitive functions. At present, however, we must conclude that modafinil is hardly ever used to treat illness other than narcolepsy. AIM: To review current attitudes and practice with regard to the use and efficacy of modafinil in the treatment of psychiatric disorders. METHOD: Relevant placebo-controlled studies were retrieved via PubMed (Medline) and Web of Science. RESULTS: Modafinil is used experimentally to treat ADHD, mood disorders, schizophrenia and substance-dependence. Compared to placebo, modafinil achieves positive but mainly variable results on different clinical and cognitive measures. It achieves results very rapidly, within a week, but over a period of time the results stabilise. CONCLUSION: Modafinil is particularly successful in the treatment of ADHD, depression and cocaine-dependency on measures of attention and hyperactivity, fatigue and cocaine-use respectively. There is a need for further placebo-controlled trials with longer follow-up periods and larger sample size in order to ensure the safety of the product and to refine its area of efficacy.

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BACKGROUND: Non-specific bronchial hyperresponsiveness (NSBH) is a known predictor of accelerated rate of decline in lung function in smokers. Polymorphisms of the beta(2) adrenergic receptor (ADRB2) have previously been associated with NSBH and bronchodilator response (BDR) in asthmatics. Based on these associations, we hypothesised that ADRB2 polymorphisms would be associated with NSBH and BDR as well as an accelerated rate of decline in lung function among smokers. METHODS: The prevalence of two ADRB2 polymorphisms, Arg16-->Gly and Gln27-->Glu, was examined in 587 smokers chosen from the NHLBI Lung Health Study for having the fastest (n=282) and slowest (n=305) 5 year rate of decline in forced expiratory volume in 1 second (FEV(1); mean DeltaFEV(1) -4.14 and +1.08% predicted/year, respectively). RESULTS: Contrary to our hypothesis, no ADRB2 allele or haplotype was associated with NSBH, BDR, or rate of decline in lung function. However, there was a significant negative association between heterozygosity at position 27 and a fast decline in lung function (adjusted odds ratio 0.56, 95% CI 0.40 to 0.78, p=0.0007). CONCLUSIONS: Heterozygosity at position 27 may be protective against an accelerated rate of decline in lung function. The polymorphism at position 16 does not contribute to the rate of decline in lung function, measures of NSBH, or BDR in smokers.

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Asthma is a complex genetic disease with multiple genes involved in the pathogenesis. Some of these genes have been investigated to determine whether they influence an individual's response to asthma medication. We summarise the recent developments in the genetics of asthma as they pertain to the three main treatments available - inhaled glucocorticoids (GCs), (2)-agonists and leukotriene modulators. It has been shown that polymorphisms in the (2)-adrenergic receptor ((2)AR) gene influence responsiveness to (2)-agonists. Polymorphisms in the 5-lipoxygenase (5-LO) gene and the leukotriene C(4) (LTC4) synthase gene have been associated with response to medications that target the LT pathway. However, no polymorphisms have been identified that influence response to anticholinergics or are involved in steroid resistance. In the future, knowledge of an individual's genotype may help us tailor treatment to make it the most appropriate form for that asthmatic individual.

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BACKGROUND: There is increasing evidence that the cytokine network is central to the immunopathology of inflammatory airway diseases. The interleukin 1 (IL-1) receptor antagonist (IL-1RN) is a naturally occurring anti-inflammatory agent that binds to the IL-1 receptor but does not possess agonist activity. Each of the genes of the IL-1 locus on chromosome 2q14 is polymorphic. The IL1RN gene contains an 86 bp tandem repeat and allele 2 of this polymorphism has been associated with various inflammatory diseases. The IL-1beta (IL1B) gene contains a promoter polymorphism (C-511T) that has been associated with inflammatory diseases and is in linkage disequilibrium with the IL1RN polymorphism. METHODS: We investigated whether polymorphisms in the IL1B and IL1RN genes were associated with rate of decline of lung function. Genotypes were determined in 284 smokers with a rapid decline in lung function and 306 smokers with no decline in lung function. RESULTS: None of the genotypes was associated with the rate of decline of lung function. However, the distribution of IL1B/IL1RN haplotypes was different between smokers with a rapid decline in lung function and those with no decline in lung function (p=0.0005). CONCLUSION: These results suggest that IL1B/IL1RN haplotypes play a role in the rate of decline in lung function in smokers.

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STUDY/PRINCIPLES: Pulmonary rehabilitation programmes are often costly and dependent on the infrastructure of specialised centres. We developed a modular, outpatient-based rehabilitation programme, which is inexpensive and can be implemented in a variety of settings. The aim of this study was to determine the effects and feasibility of this programme. METHODS: Thirteen patients with COPD and 7 patients with asthma were enrolled by their primary care physician because of dyspnoea. Initial assessment included cardiopulmonary exercise testing, six-minute walking distance, lung function testing and multiple questionnaires addressing dyspnoea, depression and quality of life issues. The training consisted of 36 sessions of high intensity training of 2 hours duration to improve exercise tolerance, including 30 minutes of stationary cycling at the anaerobic threshold. Another complete assessment was done on completion of the study at 3 months. RESULTS: The six-minute walking distance improved significantly from 401 to 551 m (p < 0.0001). The maximal exercise capacity increased significantly from 85 W to 99 W (p < 0.001). The anaerobic threshold remained unchanged despite the high intensity training. There was a reduction of dyspnoea and an improvement of quality of life. CONCLUSION: This study shows that our outpatient rehabilitation programme leads to a benefit in exercise tolerance and health related quality of life comparable to other programmes published in the literature. The rehabilitation programme was very well accepted among patients, primary care physicians and health insurers.

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Authors summarise the two-decade experience of their department in severe tissue necrosis of penis and scrotum. Presented cases represent a shared field of urology with dermatology, infectology, nephrology and andrology. Tissue necrosis extended to different depth of the penis, from superficial skin and subcutaneous tissues, fascias to the entire organ. Underlying diseases are acute and chronic inflammations, metabolic diseases, vascular lesions. Diagnostic difficulties and therapeutic choices, both conservative and operative, are discussed.

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The idea that an abnormality in the beta(2)-adrenergic receptor contributes to asthma has been a long-standing hypothesis. Since the discovery of functionally relevant polymorphisms in the beta(2)-adrenergic receptor gene, there has been intensive research on their impact on asthma and related phenotypes, particularly the responsiveness to bronchodilators. It is the aim of this chapter to summarize the latest developments in this interesting field of research.

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We present two cases initially diagnosed as Crohn's disease which were treated with immunosuppressive drugs. In both patients the development of an amoebic liver abscess led to the correct diagnosis of amoebic dysentery. The pitfalls of the diagnosis of amoebic colitis and the possible influence of immunosuppression in the development of extraintestinal amoebiasis are discussed.

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The 57 year old woman presented with diffuse muscle spasms and delirium. Prior to presentation, she complained of progressive muscle pain, weakness and a weight loss of 10 kg over several months. Laboratory investigation showed hypopituitarism and a syndrome of inappropriate antidiuretic hormone secretion. Magnetic resonance imaging revealed an empty sella. The primary and secondary syndromes of empty sella are discussed.

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Salmeterol provides bronchoprotection against a number of constrictor stimuli for more than 12 h after a single dose. This effect could be due either to functional antagonism at the level of airway smooth muscle or to cell-stabilizing effects of the compound. In this study, we attempted to clarify this mechanism by comparing the effects of salmeterol (50 micrograms), salbutamol (200 micrograms) and placebo on the airway responsiveness to histamine (to assess functional antagonism), and to adenosine 5'-monophosphate (AMP) (to assess additional cell-stabilizing effects), 14 h after drug treatment. Thirteen patients with mild allergic asthma were studied in a double-blind, randomized protocol on 6 days, at least 48 h apart. Forced expiratory volume in one second (FEV1) was measured before and 15 min after inhalation of the study medication. Then, 14 h later (8 a.m. the following morning), a bronchoprovocation test with histamine or AMP was performed. We found that 14 h after inhalation, salmeterol still had a significant effect on FEV1 in comparison to placebo and salbutamol. The provocative dose producing a 20% fall in FEV1 (PD20histamine) was significantly increased after salmeterol, whilst the increase in PD20AMP did not reach significance. The shift in PD20 (in doubling dose steps) induced by salmeterol pretreatment was not different between histamine and AMP. We conclude that the prolonged protective effect of salmeterol occurs via an extended bronchodilating and functional antagonistic action and not via a cell-stabilizing effect.

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