| 1. |
- Braun, Barbara, et al.
(författare)
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Gamblers seeking treatment : Who does and who doesn't?
- 2014
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Ingår i: Journal of Behavioral Addictions. - 2062-5871 .- 2063-5303. ; 3:3, s. 189-198
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: As only a minority of pathological gamblers (PGr) presents for treatment, further knowledge about help-seeking behavior is required in order to enhance treatment utilization. The present study investigated factors associated with treatment participation in gamblers in Germany. As subclinical pathological gamblers (SPGr, fulfilling one to four DSM-IV-criteria) are target of early intervention due to high risk of transition to pathological gambling, they were subject of special interest. Methods: The study analyzed data from a general population survey (n = 234, SPGr: n = 198, PGr: n = 36) and a treatment study (n = 329, SPGr: n = 22, PGr: n = 307). A two-step weighting procedure was applied to ensure comparability of samples. Investigated factors included socio-demographic variables, gambling behavior, symptoms of pathological gambling and substance use. Results: In PGr, regular employment and non-German nationality were positively associated with being in treatment while gambling on the Internet and gaming machines and fulfilling more DSM-IV-criteria lowered the odds. In SPGr, treatment attendance was negatively associated with married status and alcohol consumption and positively associated with older age, higher stakes, more fulfilled DSM-IV criteria and regular smoking. Conclusions: In accordance to expectations more severe gambling problems and higher problem awareness and/or external pressure might facilitate treatment entry. There are groups with lower chances of being in treatment: women, ethnic minorities, and SPGr. We propose target group specific offers, use of Internet-based methods as possible adaptions and/or extensions of treatment offers that could enhance treatment attendance.
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| 2. |
- Hess, Timo, et al.
(författare)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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| 3. |
- Ludwig, Monika, et al.
(författare)
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Gambling experiences, problems, research and policy : gambling in Germany
- 2013
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Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 108:9, s. 1554-1561
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Tidskriftsartikel (refereegranskat)abstract
- Aims The objective of this paper is to present an overview of gambling in Germany, including historical development, legislative and economic changes as well as treatment options and their effectiveness. Methods The available scientific literature and research reports on gambling in Germany were reviewed to obtain relevant information on history, commercialization, legislation, treatment and research agenda. Results Gambling in Germany is characterized by compromises between protective and economic efforts. At present, gambling is illegal in Germany, and provision is subject to the state monopoly. Mere gaming machines (specific slot machines) are not classified as gambling activity, permitting commercial providers. In recent years, implementing regulations for state gambling and gaming machines have been changed. Concerning the treatment of pathological gambling, various options exist; treatment costs have been covered by health and pension insurance since 2001. Information on the effectiveness of treatment in Germany is limited. Similarly, the number of peer-reviewed publications on gambling is small. Conclusions German gambling legislation was subject to major changes in the past years. Based on the available body of research (longitudinal), studies on risk and protective factors and the aetiology of pathological gambling are needed. The effectiveness of pathological gambling treatment in Germany and the impact of gambling regulations on gambling behaviour also need to be investigated.
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| 4. |
- Ludwig, Monika, et al.
(författare)
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Has gambling changed after major amendments of gambling regulations in Germany? A propensity score analysis
- 2012
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Ingår i: Journal of Behavioral Addictions. - 2062-5871 .- 2063-5303. ; 1:4, s. 151-161
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This study examined changes in general population gambling in the light of two major amendments of the German gambling regulation, the Fifth Amendment of the German Gambling Ordinance (AGO) for commercial amusement machines with prizes (AWP) and the State Treaty on Gambling (STG) for gambling activities subject to the state monopoly. Methods: Applying cross-sectional data from the 2006 and 2009 Epidemiological Survey of Substance Abuse (ESA), propensity-score-matched samples of 7,970 subjects and 3,624 12-month gamblers aged 18-64 years were used for analyses. Logistic regression was employed to examine changes in gambling controlling for possible confounding variables. Results: Overall participation in state gambling activities, participation in lotto as well as TV lottery decreased and gambling on Internet card games increased. No changes were found for any other gambling activity, 12-month prevalence of any gambling and pathological gambling. While weekly gambling declined, overall multiple gambling increased. Effects were similar in the total sample and among current gamblers. Conclusions: Prohibiting specific gambling activities, e. g., Internet gambling, seem to be insufficient approaches to change gambling behavior. Supply reduction might need to be enhanced by changes in game characteristics and implementation of early intervention measures. However, long-term consequences are uncertain and further monitoring is needed.
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| 5. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 6. |
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| 7. |
- Krampert, Monika, et al.
(författare)
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Smad7 Regulates the Adult Neural Stem/Progenitor Cell Pool in a Transforming Growth Factor β- and Bone Morphogenetic Protein-Independent Manner
- 2010
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Ingår i: Molecular and Cellular Biology. - : American Society for Microbiology. - 0270-7306 .- 1098-5549. ; 30:14, s. 3685-3694
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Tidskriftsartikel (refereegranskat)abstract
- Members of the transforming growth factor beta (TGF-beta) family of proteins modulate the proliferation, differentiation, and survival of many different cell types. Neural stem and progenitor cells (NPCs) in the adult brain are inhibited in their proliferation by TGF-beta and by bone morphogenetic proteins (BMPs). Here, we investigated neurogenesis in a hypomorphic mouse model for the TGF-beta and BMP inhibitor Smad7, with the hypothesis that NPC proliferation might be reduced due to increased TGF-beta and BMP signaling. Unexpectedly, we found enhanced NPC proliferation as well as an increased number of label-retaining cells in vivo. The enhanced proliferation potential of mutant cells was retained in vitro in neurosphere cultures. We observed a higher sphere-forming capacity as well as faster growth and cell cycle progression. Use of specific inhibitors revealed that these effects were independent of TGF-beta and BMP signaling. The enhanced proliferation might be at least partially mediated by elevated signaling via epidermal growth factor (EGF) receptor, as mutant cells showed higher expression and activation levels of the EGF receptor. Conversely, an EGF receptor inhibitor reduced the proliferation of these cells. Our data indicate that endogenous Smad7 regulates neural stem/progenitor cell proliferation in a TGF-beta- and BMP-independent manner.
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| 8. |
- Lochbuehler, Kirsten, et al.
(författare)
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Substance use and the usage of social media, computer games, and gambling among apprentices at vocational schools : [Substanzkonsum und nutzung von sozialen medien, computerspielen und glücksspielen unter auszubildenden an beruflichen schulen]
- 2024
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Ingår i: Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz. - 1436-9990. ; 67:4, s. 465-474
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of the current study was to assess the prevalence of the (problematic) consumption of alcohol, tobacco, and cannabis as well as the (problematic) use of social media, e‑products, computer games, and gambling among apprentices. Method: Cross-sectional survey of 4591 apprentices at 17 vocational schools from Bavaria, Schleswig-Holstein, and Hamburg. Data was collected using questionnaires between March 2021 and April 2022. The primary endpoints were the 30-day prevalence and the problematic consumption and usage behavior of the mentioned substances/behaviors using screening instruments. Results: Among the assessed substances/behaviors, social media were used most frequently by the apprentices with a 30-day prevalence of 97.7%, followed by alcohol (64.3%) and computer games (55.8%). Cigarettes were consumed by 35.1%, e‑products by 17.9%, and cannabis by 15.4% of the apprentices. Of the apprentices, 12.2% reported having gambled in the past 30 days. Rates of problematic use were 47.4% for alcohol, 18.0% for tobacco, 6.2% for e‑products, and 1.6% for cannabis. Problematic use of social media was indicated by 45.0% of the apprentices, of gambling by 2.2%, and of computer games by 0.7%. Discussion: These results suggest that apprentices constitute a risk group for problematic substance use, indicating increased need for intervention. In particular, secondary prevention efforts in the areas of alcohol and social media should be taken into consideration due to their widespread prevalence in the vocational school setting.
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| 9. |
- Marschallinger, Julia, et al.
(författare)
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Age-dependent and differential effects of Smad7ΔEx1 on neural progenitor cell proliferation and on neurogenesis
- 2014
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Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 57, s. 149-154
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Tidskriftsartikel (refereegranskat)abstract
- We recently reported that young (3 to 4months old) mice lacking Exon 1 of the Smad7 gene (S7ΔEx1 mice) show enhanced proliferation of neural stem and progenitor cells (NPCs) in the hippocampal dentate gyrus (DG) and in the subventricular zone (SVZ) of the lateral ventricles. It remained unclear, however, whether this phenotype would persist along aging, the latter typically being associated with a profound decrease in neurogenesis. Analysis of NPCs' proliferation based on the cell cycle marker PCNA in 12month-old S7ΔEx1 mice revealed a reversal of the phenotype. Hence, in contrast to their younger counterparts, 12month-old S7ΔEx1 mice had a reduced number of proliferating cells, compared to wildtype (WT) mice. At the same time, the survival of newly generated cells was enhanced in the aged transgenic animals. 12month-old S7ΔEx1 mice further displayed a reduced level of neurogenesis based on the numbers of cells expressing doublecortin (DCX), a marker for newborn neurons. The reduced neurogenesis in aged S7ΔEx1 mice was not due to a stem cell depletion, which might have occurred as a consequence of hyperproliferation in the young mice, since the number of Nestin and Sox2 positive cells was similar in WT and S7ΔEx1 mice. Instead, Nestin positive cells in the DG as well as primary neurosphere cultures derived from 12month-old S7ΔEx1 mice had a reduced capability to proliferate. However, after passaging, when released from their age- and niche-associated proliferative block, neurospheres from aged S7ΔEx1 mice regained the hyperproliferative property. Further, pSmad2 antibody staining intensity was elevated in the DG and SVZ of 12-month old transgenic compared to WT mice, indicating increased intracellular TGF-beta signaling in the aged S7ΔEx1 mice. In summary, this points toward differential effects of S7ΔEx1 on neurogenesis: (i) a hyperproliferation in young animals caused by a cell autonomous mechanism, and (ii) a TGF-beta dependent modulation of neurogenesis in aged S7ΔEx1 animals that abrogates the cell-intrinsic hyperproliferative properties and results in reduced proliferation, increased stem cell quiescence, and enhanced survival of newly generated cells.
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| 10. |
- Muus, Christoph, et al.
(författare)
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Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 546-559
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention. An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.
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