Physiological intron retaining transcripts in the cytoplasm abound during human motor neurogenesis.

Intron retention (IR) is now recognized as a dominant splicing event during motor neuron (MN) development; however, the role and regulation of intron-retaining transcripts (IRTs) localized to the cytoplasm remain particularly understudied. Here we show that IR is a physiological process that is spatiotemporally regulated during MN lineage restriction and that IRTs in the cytoplasm are detected in as many as 13% (n = 2297) of the genes expressed during this process. We identify a major class of cytoplasmic IRTs that are not associated with reduced expression of their own genes but instead show a high capacity for RNA-binding protein and miRNA occupancy. Finally, we show that ALS-causing VCP mutations lead to a selective increase in cytoplasmic abundance of this particular class of IRTs, which in turn temporally coincides with an increase in the nuclear expression level of predicted miRNA target genes. Altogether, our study identifies a previously unrecognized class of cytoplasmic intronic sequences with potential regulatory function beyond gene expression.

Direct m6A recognition by IMP1 underlays an alternative model of target selection for non-canonical methyl-readers.

m6A methylation provides an essential layer of regulation in organismal development, and is aberrant in a range of cancers and neuro-pathologies. The information encoded by m6A methylation is integrated into existing RNA regulatory networks by RNA binding proteins that recognise methylated sites, the m6A readers. m6A readers include a well-characterised class of dedicated proteins, the YTH proteins, as well as a broader group of multi-functional regulators where recognition of m6A is only partially understood. Molecular insight in this recognition is essential to build a mechanistic understanding of global m6A regulation. In this study, we show that the reader IMP1 recognises the m6A using a dedicated hydrophobic platform that assembles on the methyl moiety, creating a stable high-affinity interaction. This recognition is conserved across evolution and independent from the underlying sequence context but is layered upon the strong sequence specificity of IMP1 for GGAC RNA. This leads us to propose a concept for m6A regulation where methylation plays a context-dependent role in the recognition of selected IMP1 targets that is dependent on the cellular concentration of available IMP1, differing from that observed for the YTH proteins.

The TH1 cell lineage-determining transcription factor T-bet suppresses TH2 gene expression by redistributing GATA3 away from TH2 genes.

Lineage-determining transcription factors (LD-TFs) drive the differentiation of progenitor cells into a specific lineage. In CD4+ T cells, T-bet dictates differentiation of the TH1 lineage, whereas GATA3 drives differentiation of the alternative TH2 lineage. However, LD-TFs, including T-bet and GATA3, are frequently co-expressed but how this affects LD-TF function is not known. By expressing T-bet and GATA3 separately or together in mouse T cells, we show that T-bet sequesters GATA3 at its target sites, thereby removing GATA3 from TH2 genes. This redistribution of GATA3 is independent of GATA3 DNA binding activity and is instead mediated by the T-bet DNA binding domain, which interacts with the GATA3 DNA binding domain and changes GATA3's sequence binding preference. This mechanism allows T-bet to drive the TH1 gene expression program in the presence of GATA3. We propose that redistribution of one LD-TF by another may be a common mechanism that could explain how specific cell fate choices can be made even in the presence of other transcription factors driving alternative differentiation pathways.

Offerings and User Demands of eHealth Services in Spain: National Survey.

BACKGROUND: The accelerated development of information and communication technologies has made health care one of the pioneering fields in the incorporation of these tools. As new technologies have been applied, existing technologies have been sophisticated and improved and the concept of eHealth has expanded. However, these advances and expansion of eHealth do not seem to have served to adapt the supply of services to users' demands; rather, supply seems to be governed by other variables. OBJECTIVE: The main objective of this work was to review the existing differences between user demands and the supply of eHealth services in Spain and their causes. The aim is to provide information on the level of use of the services and the causes of the variation in demand for these services, which can be useful in correcting existing differences and adapting them to the needs of users. METHODS: A survey, "Use and Attitudes Toward eHealth in Spain," was applied by telephone to a sample of 1695 people aged 18 years and over, taking into account sociodemographic profile characteristics (sex, age, habitat, educational level). The confidence level was set at 95% and the margin of error was ±2.45 for the whole sample. RESULTS: The survey results showed that the online doctor's appointment service is the most frequently used eHealth service by users: 72.48% of respondents used this service at some point and 21.28% stated that they use it regularly. The other services showed significantly lower percentages of use, including "managing health cards" (28.04%), "consulting medical history" (20.37%), "managing test results" (20.22%), "communicating with health professionals" (17.80%), and "requesting a change of doctor" (13.76%). Despite this low usage, a large majority of respondents (80.00%) attach great importance to all the services offered. Overall, 16.52% of the users surveyed were willing to make new service requests to the regional websites, with 9.33% of them highlighting services such as "the availability of a complaints and claims mailbox," "the possibility of consulting medical records," and "the availability of more detailed information on medical centers (location, medical directory, waiting lists, etc)." Other outstanding requests (8.00%) were to simplify the procedures for using certain existing services. CONCLUSIONS: The data from the survey show that eHealth services are widely known and highly valued by users, but not all services are used with the same frequency or intensity. It appears that users find it difficult to suggest new services that might be useful to them in terms of demand for new services that do not currently exist. It would be useful to use qualitative studies to gain a deeper understanding of currently unmet needs and the possibilities of eHealth. The lack of access to and use of these services and the unmet needs particularly affect more vulnerable populations who have the greatest difficulty in meeting their needs through alternative means to eHealth.

Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery.

Cyclic AMP (cAMP) is an important signalling molecule across evolution, but its role in malaria parasites is poorly understood. We have investigated the role of cAMP in asexual blood stage development of Plasmodium falciparum through conditional disruption of adenylyl cyclase beta (ACß) and its downstream effector, cAMP-dependent protein kinase (PKA). We show that both production of cAMP and activity of PKA are critical for erythrocyte invasion, whilst key developmental steps that precede invasion still take place in the absence of cAMP-dependent signalling. We also show that another parasite protein with putative cyclic nucleotide binding sites, Plasmodium falciparum EPAC (PfEpac), does not play an essential role in blood stages. We identify and quantify numerous sites, phosphorylation of which is dependent on cAMP signalling, and we provide mechanistic insight as to how cAMP-dependent phosphorylation of the cytoplasmic domain of the essential invasion adhesin apical membrane antigen 1 (AMA1) regulates erythrocyte invasion.

Small molecule inhibitor of Igf2bp1 represses Kras and a pro-oncogenic phenotype in cancer cells.

Igf2bp1 is an oncofetal RNA binding protein whose expression in numerous types of cancers is associated with upregulation of key pro-oncogenic RNAs, poor prognosis, and reduced survival. Importantly, Igf2bp1 synergizes with mutations in Kras to enhance signalling and oncogenic activity, suggesting that molecules inhibiting Igf2bp1 could have therapeutic potential. Here, we isolate a small molecule that interacts with a hydrophobic surface at the boundary of Igf2bp1 KH3 and KH4 domains, and inhibits binding to Kras RNA. In cells, the compound reduces the level of Kras and other Igf2bp1 mRNA targets, lowers Kras protein, and inhibits downstream signalling, wound healing, and growth in soft agar, all in the absence of any toxicity. This work presents an avenue for improving the prognosis of Igf2bp1-expressing tumours in lung, and potentially other, cancer(s).

The distinct RNA-interaction modes of a small ZnF domain underlay TUT4(7) diverse action in miRNA regulation.

TUT4 and the closely related TUT7 are non-templated poly(U) polymerases required at different stages of development, and their mis-regulation or mutation has been linked to important cancer pathologies. While TUT4(7) interaction with its pre-miRNA targets has been characterized in detail, the molecular bases of the broader target recognition process are unclear. Here, we examine RNA binding by the ZnF domains of the protein. We show that TUT4(7) ZnF2 contains two distinct RNA binding surfaces that are used in the interaction with different RNA nucleobases in different targets, i.e that this small domain encodes diversity in TUT4(7) selectivity and molecular function. Interestingly and unlike other well-characterized CCHC ZnFs, ZnF2 is not physically coupled to the flanking ZnF3 and acts independently in miRNA recognition, while the remaining CCHC ZnF of TUT4(7), ZnF1, has lost its intrinsic RNA binding capability. Together, our data suggest that the ZnFs of TUT4(7) are independent units for RNA and, possibly, protein-protein interactions that underlay the protein's functional flexibility and are likely to play an important role in building its interaction network.

IMP1 KH1 and KH2 domains create a structural platform with unique RNA recognition and re-modelling properties.

IGF2 mRNA-binding protein 1 (IMP1) is a key regulator of messenger RNA (mRNA) metabolism and transport in organismal development and, in cancer, its mis-regulation is an important component of tumour metastasis. IMP1 function relies on the recognition of a diverse set of mRNA targets that is mediated by the combinatorial action of multiple RNA-binding domains. Here, we dissect the structure and RNA-binding properties of two key RNA-binding domains of IMP1, KH1 and KH2, and we build a kinetic model for the recognition of RNA targets. Our data and model explain how the two domains are organized as an intermolecular pseudo-dimer and that the important role they play in mRNA target recognition is underpinned by the high RNA-binding affinity and fast kinetics of this KH1KH2-RNA recognition unit. Importantly, the high-affinity RNA-binding by KH1KH2 is achieved by an inter-domain coupling 50-fold stronger than that existing in a second pseudo-dimer in the protein, KH3KH4. The presence of this strong coupling supports a role of RNA re-modelling in IMP1 recognition of known cancer targets.

The structure of the RbBP5 ß-propeller domain reveals a surface with potential nucleic acid binding sites.

The multi-protein complex WRAD, formed by WDR5, RbBP5, Ash2L and Dpy30, binds to the MLL SET domain to stabilize the catalytically active conformation required for histone H3K4 methylation. In addition, the WRAD complex contributes to the targeting of the activated complex to specific sites on chromatin. RbBP5 is central to MLL catalytic activation, by making critical contacts with the other members of the complex. Interestingly its only major structural domain, a canonical WD40 repeat ß-propeller, is not implicated in this function. Here, we present the structure of the RbBP5 ß-propeller domain revealing a distinct, feature rich surface, dominated by clusters of Arginine residues. Our nuclear magnetic resonance binding data supports the hypothesis that in addition to the role of RbBP5 in catalytic activation, its ß-propeller domain is a platform for the recruitment of the MLL complexes to chromatin targets through its direct interaction with nucleic acids.

[Opinion of doctors and users on e-health advances in primary care]. / Opinión de los facultativos y usuarios sobre avances de la e-salud en atención primaria.

OBJECTIVE: To find out the opinions of users and primary care doctors on the progress of e-health in primary care. DESIGN: Focus groups set up between 1st May and 25th September 2018. LOCATION: Primary care level in regional online health services. PARTICIPANTS: A total of 29 users and 33 primary care doctors linked to primary care that were contacted, through user associations and regional public health services, respectively. METHOD: Inductive analysis of transcripts from focus groups about the following issues: accessibility and security; efficiency; information and technical problems; potentialities. RESULTS: Online health services are positively valued in terms of cost savings both by users and doctors of primary care. Nevertheless, face-to-face interaction is still considered a key factor in the quality of service. When it comes to the access and provision of e-health services, there is shared concern for the security of the data and for the training deficiencies of users and doctors. An adequate design of the applications becomes a condition for the acceptance and diffusion of technologies that support online health. CONCLUSIONS: Health authorities should intensify the use of new technologies oriented towards easing the work of doctors, simplifying bureaucratic tasks, providing diagnostic and prescription security, and protecting data. As long as systems generate failures and mistrust, new technologies will remain to be perceived as a complement, but not as an alternative to the traditional care model.

Lin28a uses distinct mechanisms of binding to RNA and affects miRNA levels positively and negatively.

Lin28a inhibits the biogenesis of let-7 miRNAs by triggering the polyuridylation and degradation of their precursors by terminal uridylyltransferases TUT4/7 and 3'-5' exoribonuclease Dis3l2, respectively. Previously, we showed that Lin28a also controls the production of neuro-specific miRNA-9 via a polyuridylation-independent mechanism. Here we reveal that the sequences and structural characteristics of pre-let-7 and pre-miRNA-9 are eliciting two distinct modes of binding to Lin28a. We present evidence that Dis3l2 controls miRNA-9 production. Finally, we show that the constitutive expression of untagged Lin28a during neuronal differentiation in vitro positively and negatively affects numerous other miRNAs. Our findings shed light on the role of Lin28a in differentiating cells and on the ways in which one RNA-binding protein can perform multiple roles in the regulation of RNA processing.

An RRM-ZnF RNA recognition module targets RBM10 to exonic sequences to promote exon exclusion.

RBM10 is an RNA-binding protein that plays an essential role in development and is frequently mutated in the context of human disease. RBM10 recognizes a diverse set of RNA motifs in introns and exons and regulates alternative splicing. However, the molecular mechanisms underlying this seemingly relaxed sequence specificity are not understood and functional studies have focused on 3΄ intronic sites only. Here, we dissect the RNA code recognized by RBM10 and relate it to the splicing regulatory function of this protein. We show that a two-domain RRM1-ZnF unit recognizes a GGA-centered motif enriched in RBM10 exonic sites with high affinity and specificity and test that the interaction with these exonic sequences promotes exon skipping. Importantly, a second RRM domain (RRM2) of RBM10 recognizes a C-rich sequence, which explains its known interaction with the intronic 3΄ site of NUMB exon 9 contributing to regulation of the Notch pathway in cancer. Together, these findings explain RBM10's broad RNA specificity and suggest that RBM10 functions as a splicing regulator using two RNA-binding units with different specificities to promote exon skipping.

Structure of a Spumaretrovirus Gag Central Domain Reveals an Ancient Retroviral Capsid.

The Spumaretrovirinae, or foamy viruses (FVs) are complex retroviruses that infect many species of monkey and ape. Despite little sequence homology, FV and orthoretroviral Gag proteins perform equivalent functions, including genome packaging, virion assembly, trafficking and membrane targeting. However, there is a paucity of structural information for FVs and it is unclear how disparate FV and orthoretroviral Gag molecules share the same function. To probe the functional overlap of FV and orthoretroviral Gag we have determined the structure of a central region of Gag from the Prototype FV (PFV). The structure comprises two all α-helical domains NtDCEN and CtDCEN that although they have no sequence similarity, we show they share the same core fold as the N- (NtDCA) and C-terminal domains (CtDCA) of archetypal orthoretroviral capsid protein (CA). Moreover, structural comparisons with orthoretroviral CA align PFV NtDCEN and CtDCEN with NtDCA and CtDCA respectively. Further in vitro and functional virological assays reveal that residues making inter-domain NtDCEN-CtDCEN interactions are required for PFV capsid assembly and that intact capsid is required for PFV reverse transcription. These data provide the first information that relates the Gag proteins of Spuma and Orthoretrovirinae and suggests a common ancestor for both lineages containing an ancient CA fold.

High prevalence of diabetes in patients with rheumatoid arthritis: results from a questionnaire survey linked to claims data.

Objectives: To investigate the prevalence of diabetes in patients with RA and the impact of diabetes on self-reported outcomes and health care. Methods: RA patients between the ages of 18 and 79 years were randomly selected from a nationwide statutory health insurance fund and were surveyed about rheumatological care and disease burden. Comorbid diabetes (E10-14) was analysed regarding age, sex, BMI and socioeconomic status. Disease burden, comorbidity and prescriptions were compared in RA patients with and without diabetes. Predictors of rheumatological care were identified by multivariate regression. Results: Of the 2535 RA patients, 498 (20%) had diabetes. Diabetes was more frequent in males, in older patients, in patients with a higher BMI and in those with a lower socioeconomic status. All disease outcomes were poorer in RA-diabetes patients and were mainly attributable to a higher BMI. RA-diabetes patients received less DMARDs (40% vs 48%) and had more hospital stays (41% vs 30%) than patients without diabetes (all P < 0.05). Rates of cardiovascular disease (35% vs 15%), depression (39% vs 26%) and renal failure (23% vs 8%) were higher in RA-diabetes patients (all P < 0.0001). They were less frequently treated by rheumatology specialists: 57% vs 67%; odds ratio = 0.64 (95% CI: 0.45, 0.92), after controlling for confounders. Conclusion: The prevalence of diabetes in patients with RA is high and is associated with known sociodemographic factors. More than 40% of patients with RA and diabetes were not under rheumatological care even though they reported a high disease burden, were frequently hospitalized and often presented with further comorbidities.

Waiting times in primary care depending on insurance scheme in Germany.

BACKGROUND: Waiting times for an outpatient appointment in Germany differ between insurants of the statutory and private health insurance schemes, especially for specialised care. The aim of this study was to uncover possible differences in waiting times depending on health insurance scheme and to identify predictors for excessive waiting times in primary care. METHODS: We used data of the Bertelsmann Foundation Healthcare Monitor, which is a repeated cross sectional study dealing with experiences in health care and attitudes towards current health policy themes. We analysed the surveys conducted from 2011 to 2013, with respondents assigned to their health insurance fund, namely AOK, BARMER GEK, BKK, DAK, TK, IKK, other statutory funds and private funds. The mean waiting times for an appointment and spent in a physician's waiting room, and the satisfaction with waiting times were evaluated with respect to different health insurance funds. A logistic regression model was used to calculate the chance of excessive waiting times with respect to health insurance fund, age, sex, health and socioeconomic status. The ninetieth percentile of the waiting time distribution (10 days) was chosen as the cut-off point between average and excessive. RESULTS: A total of 5618 respondents were analysed. Mean waiting times in primary care were low (4.0 days) and homogeneous (SHIs: 3.6-4.9 days), even though privately insured respondents reported shorter waiting times for appointments (3.3 days). They also reported a greater satisfaction with waiting times (77.5%) than SHI insurants (64.5%). However, we identified a group (10.1%), who experienced excessive waiting times in primary care. Compared to privately insured respondents, the chance of excessive waiting times was increased for SHI insurants (highest odds ratio for BKK: 2.17; 95%-CI: 1.38-3.42). Additionally, higher age and residence in East Germany were associated with higher chances of waiting times of 10 days or more. CONCLUSIONS: Primary care in Germany is readily accessible with generally short waiting times. However, barriers in access to the health care system affect a certain part of patients depending on insurance status, age and region of residence. Ways to improve the access need to be studied.

Influenza vaccination rates before and after admission to nursing homes in Germany.

BACKGROUND: Influenza vaccination is highly recommended for nursing home residents. However, it is known that vaccination coverage is low in the general population. AIMS: We aim to find out whether influenza vaccination coverage differs for nursing home residents between the year before and after admission and factors determining the chance to receive vaccination. METHODS: Claims data of the health insurance fund DAK of at least 65-year-olds were used. The proportion of residents with influenza vaccination were compared in the year before and after the admission stratified by several covariates. A multivariate logistic regression analysis was conducted to obtain predictors for influenza vaccination after admission. RESULTS: Vaccination coverage was overall higher in the year after admission (53.0%) than before (38.3%). Differences in vaccination coverage between most covariates evened out after admission. Differences remained for region of residence and number of comorbidities. The strongest predictor for receiving a vaccination after admission was the vaccination status before admission (OR 3.5; 95% CI 3.3-3.6) followed by region and number of comorbidities. DISCUSSION: Overall, vaccination coverage of nursing home residents remains lower than recommended. Doctor-patient contacts whether due to care for comorbidities or as a continuation of the relation over the time of admission to the nursing home seem to assure vaccination for residents. CONCLUSION: Clear and unambiguous evidence of vaccine safety and efficacy for different subgroups within the same age group as well as organizational efforts to increase vaccination within nursing homes would be recommended.

[Prescription frequency of physical therapy and analgesics before total hip and knee arthroplasy : An epidemiological analysis of routine health care data from Germany]. / Verordnungshäufigkeit physikalischer Therapien und Analgetika vor dem Einsatz einer Hüft- bzw. Kniegelenks-Endoprothese : Eine versorgungsepidemiologische Analyse basierend auf GKV-Routinedaten aus Deutschland.

BACKGROUND: Osteoarthritis of the hip or knee joint is a widespread disease with a strong influence on the quality of life. At present, the extent of conservative treatment with physical therapies and analgesics before the use of a total joint arthroplasty (TJA) of the hip or knee is largely unclear in Germany. OBJECTIVES: The aim was to analyze the prescription frequency according to regional and socio-demographic factors. MATERIALS AND METHODS: Based on routine health care data from BARMER insurance, patients who received a TJA of the hip or knee from 2011 to 2013 were analyzed. Included were consistently insured patients with the main discharge diagnosis of osteoarthritis who did not receive any further TJA for eight quarters before and after replacement. The prescription frequency of physical therapies and analgesics, stratified according to age groups, gender, number of comorbidities and federal state was analyzed. RESULTS: 40,242 persons with hip TJA and 35,652 persons with knee TJA were included. In the year prior to surgery, 49.4% of patients (hip TJA: 49.9%; knee TJA: 48.9%) received at least one physical therapy and 81.0% were prescribed analgesics. Regionally, the prescription frequency of physical therapies for hip TJA varied between 35.7% (Bremen) and 70.6% (Saxony) and for knee TJA between 37.6% (Saarland) and 66.9% (Saxony). CONCLUSION: The prescription frequency of physical therapy does not fully correspond to current treatment recommendations. The prescription of physical therapies in the year before the TEP shows regional differences, with fundamentally lower prescription frequencies in the former states of West Germany.

[Outpatient emergency treatment of nursing home residents : Analysis of insurance claims data]. / Ambulante Notfallversorgung von Pflegeheimbewohnern : Auswertung von GKV-Routinedaten.

BACKGROUND: Utilization of outpatient emergency services by nursing home residents is increasing; however, out of hours medical care (OOHC) in Germany has not yet been studied. OBJECTIVE: In Bremen the used billing codes enabled a comparison between the use of outpatient emergency care in the year before and the year after admission to a nursing home stratified by emergency departments and OOHC. MATERIAL AND METHODS: In this retrospective cohort study we used insurance claims data of residents in Bremen, who were insured in a large German statutory health insurance (DAK-Gesundheit). We compared the use of emergency care in hospitals or OOHC practices in the year before and the year after admission to a nursing home. The incidence rates of visits, distribution on weekdays and coded diagnoses were investigated. RESULTS: We included 1175 nursing home residents (77% female) with a mean age of 85 years. After admission to a nursing home the incidence rate of visits in the OOHC practices increased from 30.4 up to 63.7 and in emergency departments (ED) from 27.4 up to 50.7 per 100 person years. A total of 59% of all visits in OOHC practices were on weekends. The most common diagnoses in ED were injuries and poisoning (75%) while a wide range of diagnoses were coded in the OOHC practices. CONCLUSION: There is a significant difference between diagnoses in the ED and OOHC practices. More research is needed to assess the appropriateness of care.

The devil is in the domain: understanding protein recognition of multiple RNA targets.

RNA regulation provides a finely tuned and highly co-ordinated control of gene expression. Regulation is mediated by hundreds to thousands of multi-functional RNA-binding proteins which often interact with large sets of RNAs. In this brief review, we focus on a recent work that highlights how the proteins use multiple RNA-binding domains to interact selectively with the different RNA targets. Deconvoluting the molecular complexity of the RNA regulatory network is essential to understanding cell differentiation and function, and requires accurate models for protein-RNA recognition and protein target selectivity. We discuss that the structural and molecular understanding of the key determinant of recognition, together with the availability of methods to examine protein-RNA interactions at the transcriptome level, may provide an avenue to establish these models.

Pain, depressive symptoms and medication in German patients with rheumatoid arthritis-results from the linking patient-reported outcomes with claims data for health services research in rheumatology (PROCLAIR) study.

PURPOSE: Pain and depressive symptoms are common in patients with rheumatoid arthritis (RA). Information on the prevalence and treatment of both conditions in German RA patients is scarce. METHODS: Using data from a nationwide statutory health insurance fund (BARMER GEK), 6193 RA patients aged 18 to 79 years were provided with a questionnaire covering a variety of items such as demographics, medical condition and quality of life in 2015. Pain caused by the joint disorder (11-point scale) was classified as none existent/mild, moderate or severe. Depressive symptoms were determined using the World Health Organization's five-item Well-being Index and categorized as none existent, mild or moderate/severe. Another item covered additional use of over-the-counter drugs. Data were linked to dispensation records. RESULTS: A total of 3140 RA patients were included. Median age was 66 years (79% female). About 70% of patients were classified as having moderate or severe pain. Depressive symptoms were found in 52% and were far more common among patients with higher pain levels. Analgesic treatment ranged from 45% to 76% (non-opioid analgesics) and from 6% to 33% (opioids) in patients with no/mild pain and those reporting severe pain, respectively. In patients reporting moderate or severe pain, substantially higher prevalences of opioid use were observed among those with depressive symptoms. Depending on depressive symptoms, antidepressant use ranged from 7% to 37%. Overall, over-the-counter drug use varied between 30% and 59%. CONCLUSIONS: Pain and depressive symptoms are highly prevalent in German RA patients, often present together and influence each other's treatment. Copyright © 2017 John Wiley & Sons, Ltd.