German Central Institute for Social Issues

Zivilgesellschaftliches Engagement gegen Rechtsextremismus in ländlichen Räumen trifft auf eine provinzielle politische Kultur. Provinzielle politische Kultur ist dadurch charakterisiert, dass „jede:r jede:n kennt“ und ist, daraus folgend, geprägt durch personenzentrierte Politik, Konformitätsdruck, Konsens- und Harmonieorientierung, Misstrauen gegenüber und Ablehnung von Fremden und insgesamt eine reaktionäre lokale Identität. Im Beitrag wird analysiert, wie sie sich auf das Engagement gegen die umtriebigen extrem rechten Akteur:innen in zwei Nachbardörfern auswirkt. Basierend auf qualitativen Interviews und Beobachtungen wird gezeigt, wie die provinzielle politische Kultur das Engagement gegen Rechtsextremismus in einem Dorf behindert, im anderen jedoch befördert.

Following new recommendations from the World Health Organization (WHO) on the treatment of tuberculosis (TB) in 2025, the Tuberculosis Guidelines Group for Germany, Austria and Switzerland has decided to update the guidelines for the treatment of drug-resistant tuberculosis (DR-TB) as well. DR-TB includes resistant forms of Mycobacterium tuberculosis, including isoniazid monoresistance, multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB), pre-extensively drug-resistant TB (pre-XDR-TB) and extensively drug-resistant TB (XDR-TB). For MDR/RR-TB and pre-XDR-TB without additional resistance to bedaquiline and/or linezolid, two 6-month, purely oral short-term regimens are recommended (BPaLM or BDLLfx for MDR/RR-TB and BPaL or BDLC for pre-XDR-TB [*B = bedaquiline, C = clofazimine, D = delamanid, L = linezolid, Lfx = levofloxacin; M = moxifloxacin; Pa = pretomanid]). In cases of severe or extensive disease and immunosuppression, therapy can be extended to 9 months, for example, or carried out as an individualized 18-month regimen. For XDR-TB and intolerance to bedaquiline or linezolid, individualized combination therapies with at least four effective substances are recommended. In addition to pharmacological aspects, this update emphasizes the importance of quality-assured diagnostics, secure drug supply and socio-medical support to prevent treatment discontinuation. Due to the low number of cases, treatment in specialized centers or in cooperation with them is recommended. The aim is to provide effective, tolerable therapy that is adapted to the resistance situation in order to ensure therapeutic success and prevent further development of drug-resistance.

Abstract BACKGROUND Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults, characterized by high invasiveness and aggressive growth, resulting in a poor prognosis with a median overall survival rate of 14 to 17 months. Standard treatment schemes, including surgical resection, temozolomide and radiotherapy, have yielded only modest clinical benefit. While immunotherapeutic approaches have succeeded in various malignancies, their efficacy in GBM has been limited. The PD-1/PD-L1 pathway, crucial in immune regulation, has emerged as a promising therapeutic target. Through the PD-1/PD-L1 interaction, GBM cells evade immune surveillance by activating PD-1 receptors on immune cells, inhibiting T-cell responses and promoting tumor progression. GBM cells upregulate PD-L1 expression through receptors such as EGFR, IFNGR, and c-Met-R. Radiotherapy has also been shown to increase PD-L1 expression. Understanding the mechanisms driving PD-L1 expression is essential for overcoming therapeutic resistance and improving treatment strategies for GBM. This study seeks to identify the signaling pathways responsible for PD-L1 upregulation in GBM after irradiation. MATERIAL AND METHODS We investigated the impact of hypofractionated radiotherapy (2x5Gy) combined with various signaling pathway Inhibitors (Akt-Inhibitor VIII, c-Met-Inhibitor 1, Cobimetinib, Encorafenib, Erlotinib, m-TOR-Inhibitor 3, Vemurafenib and SC79) on the expression profile of the immune checkpoint molecules PD-L1/2 in the murine GBM cell line GL261-luc2 using flow cytometry. Cell viability and toxicity assays identified EC50 values. Combinations of the most effective inhibitors to decrease PD-L1 and PD-L2 expression were subsequently tested on human GBM cell lines (U118, U138, HROG-06). Additionally, RNA-sequencing was performed on irradiated human GBM cell lines. Based on the transcriptomic findings, further flow cytometric analyses were conducted to assess the effects of CXCR2 inhibition with Reparixin on PD-L1 regulation. Supernatants were collected to evaluate neuroinflammatory analytes. RESULTS Our findings indicate that the RAS/ERK and PI3K/Akt/mTOR signaling pathways contribute to the upregulation of irradiation-dependent expression of PD-L1. Inhibitors of these pathways show time- and dose-dependent toxicity and suppress cellular proliferation, requiring dose optimization in future studies. CONCLUSION Modulating these pathways post-irradiation may reduce GBM cell radioresistance, necessitating further investigation into potential molecular targets.

ABSTRACT Trust in the police is essential for democratic legitimacy, yet it is declining across Western Europe. Immigrants and their descendants, who face disproportionate levels of discrimination, report particularly low levels of trust. While previous research has focused primarily on police-specific discrimination, it overlooks three important distinctions: First, between individuals without police contact versus individuals with non-discriminatory encounters; second, between police-specific discrimination and broader forms of everyday racism; and last, potential generational differences. This article addresses these gaps by analysing how reported experiences of police-specific and everyday racist discrimination affect police trust among immigrants and their descendants in Germany. Using data from two waves of the DeZIM.panel (N = 1,001), we find that both forms of discrimination are negatively associated with trust. However, respondents who had non-discriminatory contact with the police report significantly higher trust than those with no contact at all. Importantly, everyday racism reduces trust independently.

Rheumatoid arthritis (RA) and other inflammatory arthritis are systemic diseases that primarily affect the joints, characterized by synovial inflammation and progressive cartilage and bone degradation. The temporomandibular joint (TMJ) is reported to be involved in over 50% of RA cases, often leading to severe jaw pain and compromised oral function. Despite its prevalence, TMJ involvement is often underestimated, and its cellular and molecular mechanisms remain poorly understood. Due to the unique biological and functional properties of the TMJ, inflammatory pathways observed in other joints such as the well-studied ankle joint may not directly apply to the TMJ. This study aimed to establish a reliable inflammatory arthritis model for investigating TMJ-specific pathomechanisms. The human TNF-α transgenic (hTNFtg) mouse model effectively replicated TMJ pathology seen in arthritic patients, including increased synovial inflammation (p=0.0024) and severe bone loss (p=0.009) as compared to control mice assessed by micro-computed tomography and histomorphometry. These changes were driven by increased osteoclast numbers (p=0.0331) and upregulation of genes associated with bone resorption such as Acp5 (p=0.0003) and Ctsk (p=0.0025). Notably, we observed that the TMJ displays a unique pattern of immune cell infiltration and pro-inflammatory cytokine expression compared to the ankle joint, particularly with respect to T cell recruitment. These findings were further supported by bulk RNA sequencing, which revealed overall increased inflammation in both the ankle joint and TMJ of hTNFtg mice compared to the control group. Interestingly, while the expression of immune cell and pro-inflammatory cytokine-related gene sets was higher in the ankle joint, the TMJ showed increased expression of genes associated with energy consumption and bone resorption-related enzymes. These findings highlight the TMJ as a distinct anatomical site with heightened susceptibility to arthritis-related damage and emphasize the need for greater awareness and targeted research to improve disease management for affected individuals.

Background: Gastrointestinal leaks and fistulae are serious conditions with the potential to be life-threatening, and they are of significant relevance for both endoscopists and surgeons. These conditions may present in a wide variety of ways in clinical settings. These defects may arise from malignant or inflammatory conditions, or may be iatrogenic, occurring after surgery, endoscopic, or radiation therapy. The therapeutic approach to these conditions is often complex and is associated with a high incidence of morbidity. Consequently, in recent years, advances in interventional endoscopic techniques have earned a pivotal role in the management of gastrointestinal defects, both as a first-line treatment and as a rescue therapy. The advent of clips and luminal stents marked the advent of gastrointestinal defect therapy. However, the advent of innovative endoscopic closure devices and techniques, such as endoscopic internal drainage, suturing systems, and vacuum therapy, has broadened the indications of endoscopy for the management of gastrointestinal wall defects. This is because surgical therapy still tends to be complex and is plagued by high rates of morbidity. Summary: A successful endoscopic management of gastrointestinal leaks and fistulae necessitates a tailored and multidisciplinary approach, based on the aforementioned factors, in addition to local expertise and the availability of devices. Moreover, a standardized evidence-based algorithm for the management of GI defects is still not available. Endotherapy represents a minimally invasive, effective approach with lower morbidity and mortality compared to surgical techniques.

Abstract Polarised positions over the issue of migration became vocal in the German public sphere as the ‘long summer of migration’ in 2015 unfolded. These positions are mirrored in both ‘solidarity cities’ with inclusive practices of migrant reception and ‘anti-solidarity cities’ with a dominance of anti-migrant sentiment and mobilisation. In this chapter, we unpack these ambivalent dynamics by analysing migration-related protests between 2014 and 2018 in two medium-sized towns in East Germany, Neuruppin and Plauen. Based on a combination of quantitative protest event data and qualitative interviews, we explain why Neuruppin has evolved as a ‘solidarity city’ with high levels of pro-migrant protest, while in Plauen, anti-migrant actors have dominated the streets. Investigating the contentious and contingent nature of migrant solidarity from a comparative perspective and focusing on medium-sized towns, this chapter complements the widespread focus on single case studies of ‘solidarity cities’ in large urban centres.

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Einleitung und historischer HintergrundVon den Gelehrten der Antike ber scholastische Lehrer im Mittelalter und Professoren der Neuzeit bis in die Moderne spiegelt sich die Rolle des Professoriats in der Institution wider, die ihr designierter Ort ist.Die Geschichte des Professoriats ist untrennbar verbunden mit der Entstehung der ersten Universitten im 11.Jahrhundert aus klerikalen Institutionen und von besonderer Relevanz war schon damals die Quelle, aus der die Bezge fr das Lehrpersonal finanziert wurden.Im Mittelalter war diese Finanzierung eine groe Herausforderung.Da es keine staatlichen Haushalte