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Background: Remission is arguably the ultimate therapeutic goal in rheumatoid arthritis (RA). Applying modern strategies, clinical remission can be achieved in a substantial number of patients with early RA (ERA). Even in those patients, the number and scope of erosions can increase. We, therefore, investigated the value of MRI for the detection of radiological progression in patients with DAS28 improvement and/or clinical remission of the German Remission-plus cohort.Methods: Data-sets of 80 RA patients (according to 2010 ACR/EULAR criteria) from the Remission-plus study cohort, who fulfilled the following criteria, were retrospectively analysed: availability of two consecutive MRI scans (low-field MRI, follow-up interval 1 year) of the clinically dominant hand and wrist, and the presence of DAS28 (CRP) scores at both time points, which was used to assess disease activity.Results: Seventy-one of the 80 investigated patients presented a numerical improvement of the DAS28 (CRP) after 12 months (DAS28(CRP) T0 average (Ø) 4.96, SD 1.2; DAS28 T4 (12 month) Ø 2.6, SD 1.0), 73% of them also improved in the RAMRIS-Score, while 24% demonstrated an increase despite DAS28 improvement and 3% showed equal values. 48% of patients who improved in the DAS28 reached EULAR remission. 41% of these patients had an increase in the RAMRIS Erosion-subscore after 12 months. When considering EULAR response criteria (non-response (n = 7), moderate response (n = 19), good response (n = 45)), an increase of erosions was found in 71.4% of non-responders, 52.6% of moderate responders, and 31.1% of good responders after 12 months, all compared to baseline.Conclusion: Up to 40% of patients in this study demonstrated a progressive erosive disease detected by MRI despite DAS28 improvement or EULAR remission. Future studies are needed to determine the prognostic clinical impact of disease progression in MRI despite clinical remission, and to investigate if DAS28 remission may be an insufficient therapeutic goal and should be accompanied by MRI remission criteria. [ABSTRACT FROM AUTHOR]

Background Alcohol consumption has been suggested to be associated with a dysregulation in habit formation and execution in dependent patients. Although there are established craving questionnaires assessing various components of craving, to our knowledge, no questionnaire exists to assess habitual and automated substance intake. In this study, we present and validate the 'Craving Automated Scale for Alcohol' ( CAS-A), a newly developed questionnaire assessing craving and other components of automated addictive behavior. Methods Forty-three recently detoxified alcohol-dependent patients were examined in an inpatient setting using a cross-sectional design. The CAS-A, a self-report questionnaire, was applied. According to classical test theory, we conducted principal component analyses (PCAs) to identify the components of CAS-A, after which we validated it using established craving questionnaires. Thirty-two healthy participants served as a control group. Results Our first-order PCA identified a 5-factor solution. A second-order analysis then identified 2 general factors. These factors were partially associated with established craving measures and with the severity of dependence. Conclusions Our findings suggest that CAS-A assesses additional components of addictive behavior compared to established measures. We interpret the 5 CAS-A factors as 'only aware in hindsight,' 'no deliberate decision,' 'contrary to intention,' 'no perception,' and 'no control.' We suggest the 2 general factors be interpreted as 'unaware' and 'nonvolitional.' Our results indicate that the CAS-A indeed assesses some components of automated craving and automated drinking behavior in a more sophisticated way than established questionnaires. The CAS-A as a retrospective questionnaire can be considered to be a trait rather than a state measure. [ABSTRACT FROM AUTHOR]

Background Effect sizes of pharmacotherapy in alcoholism are modest. They might improve if subjects could be divided into more homogeneous subgroups and would then be treated targeted to their neurobiological profile. In such an effort, we tested neural cue reactivity as a potential predictor of treatment response to naltrexone. Alcohol-associated cues cause brain activations in mesocorticolimbic networks due to the positive reinforcing properties of alcohol. These activations were reported to be associated with relapse behavior. Naltrexone, an antagonist at the mu-opioid receptor, improves drinking behavior in some but not all patients probably by blocking the positive reinforcement of alcohol. Conversely, acamprosate is proposed to modulate negative reinforcement (withdrawal and cue-induced withdrawal). Identifying subjects with elevated cue reactivity and testing their response to medical treatment could thus improve our understanding of some of the mechanisms underlying pharmacotherapy response. Methods A picture-perception task featuring alcohol-related and neutral stimuli was presented to 64 recently detoxified alcohol-dependent patients. Patients came from 1 center of a larger double-blind randomized multicenter clinical trial (the 'PREDICT Study'). They were scanned prior to being randomized to either naltrexone or acamprosate. We examined the interaction between medication and functional magnetic resonance imaging ( fMRI) cue reactivity, as measured by the percentage of voxels activated, using the time to the first severe relapse as the outcome criterion. Our a priori formulated hypothesis was that naltrexone but not acamprosate should be efficacious in subjects with high cue reactivity. Results We observed an interaction effect between pretreatment brain activation induced by alcohol images and medication (acamprosate/naltrexone) on relapse behavior. In line with our hypothesis, this interaction was driven by treatment response to naltrexone in patients with elevated pretreatment cue reactivity in the ventral striatum. Conclusions fMRI has the potential for predicting treatment response to naltrexone in a subgroup of alcohol-dependent patients. However, this approach will be limited to researching the mechanisms and principles of treatment response. [ABSTRACT FROM AUTHOR]

During the first weeks of abstinence, alcohol craving in patients may increase or "incubate." We hypothesize that Naltrexone (NTX) blocks this incubation effect. Here, we compared NTX effects on neural alcohol cue reactivity (CR) over the first weeks of abstinence and on long-term clinical outcomes to standard treatment. Male alcohol-dependent patients (n = 55) and healthy controls (n = 35) were enrolled. Participants underwent baseline psychometric testing and functional magnetic resonance imaging (fMRI) assessment of mesolimbic alcohol CR. Patients participated in a standard treatment program with the option of adjuvant NTX. They received another scan after 2 weeks of treatment. We found higher CR in several brain regions in patients versus healthy controls. CR significantly increased over 2 weeks in the standard treatment group (n = 13) but not in the NTX group (n = 22). NTX significantly attenuated CR in the left putamen and reduced relapse risk to heavy drinking within 3 months of treatment. Additionally, increased CR in the left putamen and its course over time predicted both NTX response and relapse risk. Carrier status for the functional OPRM1 variant rs1799971:A > G was considered but had no effect on NTX efficacy. In conclusion, NTX was most effective in patients with high CR in the left putamen. While the results from our naturalistic study await further confirmation from prospective randomized trials, they support a potential role of neural CR as a biomarker in the development of precision medicine approaches with NTX. [ABSTRACT FROM AUTHOR]

Using a sample of 714 private family influenced businesses in Germany, we investigate the relationship of goal alignment between owners and managers and the existence of a board of directors. Agency theory and stewardship theory serve as theoretical bases for our study. We find that firms with relatively high levels of goal alignment are less likely to have a board of directors. Our results provide support for the substitution hypothesis of formal by social control mechanisms. Furthermore, the findings show that firms without a board and with relatively low levels of goal alignment have less family members in the top management team. This circumstance might in turn be a trigger for owners to install a board. [ABSTRACT FROM AUTHOR]

Background: Breathing retraining techniques have received increased attention in the management of asthma, because there is growing evidence of the usefulness of such methods in improving quality of life, reducing symptoms and reducing bronchodilator use. Our study investigated the effect of anthroposophic therapeutic speech (ATS), which uses sounds and syllabic rhythm to improve articulation, breathing and cardiorespiratory interaction, in patients with asthma in a real-life outpatient setting.Methods: In a randomised controlled crossover trial, patients with asthma in three centres in Switzerland and Germany were randomised to either receive 11 ATS sessions or to wait. Subsequently, patients changed either to wait or to receive ATS. Primary outcomes were changes from the beginning to the end of each phase in the Asthma Quality of Life Questionnaire (AQLQ) and spirometry parameters. Secondary outcomes were changes in inhaled glucocorticoids, the Asthma Control Test (ACT), peak flow and asthma exacerbations.Results: Altogether, 63 patients were randomised, of which 56 were enrolled and 49 completed the study. Statistically significant differences between the ATS groups and waiting control groups were found for the overall AQLQ score (d = 0.86, p = 0.001) and the domain scores for symptoms, activity limitation and emotional function as well as ACT score (d = 0.53, p = 0.048). No significant differences were observed in spirometry parameters, inhaled glucocorticoids, peak flow and days without asthma exacerbation per week. No serious adverse events occurred during ATS sessions.Conclusions: ATS significantly improves asthma control and quality of life in patients with asthma. Whether ATS may improve lung function remains to be shown.Trial Registration: ClinicalTrials.gov NCT02501824 . Retrospectively registered on 8 July 2015. [ABSTRACT FROM AUTHOR]

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions. These goals are achieved by: (A) using innovative mHealth (mobile health) tools to longitudinally monitor the effects of triggers and modifying factors on drug consumption patterns in real life in a cohort of 900 patients with alcohol use disorder. This approach will be complemented by animal models of addiction with 24/7 automated behavioural monitoring across an entire disease trajectory; i.e. from a naïve state to a drug-taking state to an addiction or resilience-like state. (B) The identification and, if applicable, computational modelling of key molecular, neurobiological and psychological mechanisms (e.g., reduced cognitive flexibility) mediating the effects of such triggers and modifying factors on disease trajectories. (C) Developing and testing non-invasive interventions (e.g., Just-In-Time-Adaptive-Interventions (JITAIs), various non-invasive brain stimulations (NIBS), individualized physical activity) that specifically target the underlying mechanisms for regaining control over drug intake. Here, we will report on the most important results of the first funding period and outline our future research strategy., (© 2024 The Author(s). Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

The neuroprotective effects of leptin and its role in addictive disorders has been highlighted by several recent studies. However, its potential effects on morphological alterations in alcohol dependence are yet to be investigated. Associations between leptin and the longitudinal courses of gray matter volume (GMV) and cortical thickness (CT) were investigated in N = 62 alcohol-dependent patients that underwent structural magnetic resonance imaging after a mean abstinence of 12 (baseline) and 27 days (follow-up) respectively. Blood samples were collected at baseline to determine leptin levels. A cohort of N = 74 healthy individuals served as a reference sample. At baseline, alcohol-dependent patients compared to healthy controls displayed smaller GMV in the insula, parts of the superior, middle and inferior frontal gyri and hippocampal regions and thinner CT in the insula, parts of the superior and middle frontal cortices, the lateral orbitofrontal cortex and parts of the occipital and lingual cortices that partially recovered during abstinence (p FWE  < 0.05). In alcohol-dependent patients, leptin was a significant predictor of GMV and CT recovery in the areas that showed the strongest whole-brain effects, specifically GMV in the right insula (R 2  = 0.070, p FDR  = 0.040) and left inferior frontal triangular gyrus (R 2  = 0.076, p FDR  = 0.040), as well as CT in the left insula (R 2  = 0.158, p FDR  = 0.004) and right superior frontal cortex (R 2  = 0.180, p FDR  = 0.004). Present results support the role of leptin in predicting GMV and CT recovery during the first month of abstinence in alcohol-dependent patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Molecular and cellular research modalities for the study of liver pathologies have been tremendously improved over the recent decades. Advanced technologies offer novel opportunities to establish cell isolation techniques with excellent purity, paving the path for 2D and 3D microscopy and high-throughput assays (e.g., bulk or single-cell RNA sequencing). The use of stem cell and organoid research will help to decipher the pathophysiology of liver diseases and the interaction between various parenchymal and non-parenchymal liver cells. Furthermore, sophisticated animal models of liver disease allow for the in vivo assessment of fibrogenesis, portal hypertension and hepatocellular carcinoma (HCC) and for the preclinical testing of therapeutic strategies. The purpose of this review is to portray in detail novel in vitro and in vivo methods for the study of liver cell biology that had been presented at the workshop of the 8th meeting of the European Club for Liver Cell Biology (ECLCB-8) in October of 2018 in Bonn, Germany., Competing Interests: The authors have no conflicts of interest.

One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake., (© 2019 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Given that previous studies demonstrated that smoking-related cues (like cigarette packages) grab the attention of smokers and thereby contribute to craving and tobacco seeking we investigated how pictorial health warnings presented on cigarette packages affect attention allocation towards cigarette packages. The WHO advises the use of pictorial health warnings on cigarette packages. However, at present no experimental studies are available investigating if pictorial warnings modulate incentive properties of cigarette packages. Fifty-nine tobacco smokers and 55 non-smokers performed a visual dot probe task to assess attention allocation towards cigarette packages with and without health warnings. Smokers were divided a priori in a group of light smokers (<20 cigarettes/day; n=39) and heavy smokers (≥20 cigarettes/day; n=20). Psychometric measures on anxiety and nicotine craving were administered. Light smokers showed an attentional bias towards packages without pictorial warnings while no effects were observed in the other groups. In heavy smokers attention allocation towards pictorial health warnings was associated with an increase of craving and anxiety. The results have a potential public health perspective as pictorial health warnings might be an effective strategy to reduce attentional bias towards cigarette packages of light smokers, while counterproductive effects in heavy smokers warrant further investigation., (Copyright © 2011 Elsevier B.V. All rights reserved.)