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Prostate cancer (PCa) shows strong dependence on the androgen receptor (AR) pathway. Here, we show that squalene epoxidase (SQLE), an enzyme of the cholesterol biosynthesis pathway, is overexpressed in advanced PCa and its expression correlates with poor survival. SQLE expression is controlled by micro-RNA 205 (miR-205), which is significantly downregulated in advanced PCa. Restoration of miR-205 expression or competitive inhibition of SQLE led to inhibition of de novo cholesterol biosynthesis. Furthermore, SQLE was essential for proliferation of AR-positive PCa cell lines, including abiraterone or enzalutamide resistant derivatives, and blocked transactivation of the AR pathway. Inhibition of SQLE with the FDA approved antifungal drug terbinafine also efficiently blocked orthotopic tumour growth in mice. Finally, terbinafine reduced levels of prostate specific antigen (PSA) in three out of four late-stage PCa patients. These results highlight SQLE as a therapeutic target for the treatment of advanced PCa. Cholesterol metabolism is involved in the progression of aggressive prostate cancer (PCa). Here the authors show that miR-205 downregulation promotes cholesterol synthesis and androgen receptor signalling in PCa through enhancing the expression of the rate-limiting enzyme of cholesterol synthesis, squalene epoxidase.

IntroductionChildren, who are particularly vulnerable in emergency situations, need tailored mental health strategies.ObjectivesWe investigated the impact of the COVID-19 pandemic on anger and life satisfaction in children.MethodsSeptember 2021, we conducted a cross-sectional study in Preveza, Greece, interviewing 91 students aged 10-12 years from four elementary schools. The survey included socio-demographic questions, the Anger Expression Scale for Children (AESC), and the Satisfaction with Life Scale (SWLS). AESC scores range from 6 to 30 indicating anger severity, while SWLS scores between 5-9 signify extreme dissatisfaction and 31-35 extreme satisfaction.ResultsSignificant correlations were found between the number of siblings (p 0.004), duration of electronic play (p 0.005), and duration of sleep (p 0.014) with life satisfaction. Children without siblings, with limited play consumption, and early bedtimes had lower life satisfaction. The presence of a television in their room (p 0.027) and daily use of television and social media (p 0.007) correlated with anger management and behavior. Social media/TV use was associated with better anger management.ConclusionsDespite the pandemic lasting almost two years, children’s anger levels in Preveza remained stable, possibly due to outdoor activities and online interactions. These findings provide insights for policy makers, healthcare professionals, and parents seeking to improve anger management of children.Disclosure of InterestNone Declared

IntroductionThe global COVID-19 pandemic and subsequent lockdowns have significantly impacted global wellbeing and highlighted the close link between mental and physical health. Social isolation and quarantine have proven to be major stressors, leading to emotional distress and unpredictable psychological consequences.ObjectivesWe explored the pandemic’s impact on individuals’ physical and mental health and social relationships.MethodsWe conducted a cross-sectional study using a questionnaire which included among other socio-democratic questions, the Fear of COVID-19 Scale, the World Health Organization Quality-of-Life Scale (WHOQOL-BREF) and the Toronto Empathy Questionnaire (TEQ).ResultsA total of 511 adults (55.1% males) participated in this study. Participants reported increased social media use (more than 4-5 times/week) during the lockdown, which was associated with increased fear of COVID-19 and negative effects on mental and physical health, and social relationships (p<0.01). Conversely, non-work-related outings (once a week) were associated with lower fear (p<0.01) and better well-being (p<0.05). Higher fear, particularly for loved ones, was associated with negative effects. The level of physical health was moderate to high, with varying levels of satisfaction in different areas. Empathy correlated with increased fear (p<0.01) and reduced mobility (p<0.05).ConclusionsThe COVID-19 pandemic and lockdowns significantly affected physical and mental health, highlighting the importance of tailoring interventions for vulnerable populations and promoting adaptive coping strategies in times of crisis.Disclosure of InterestNone Declared

IntroductionThose who have lost loved ones to COVID-19 may be considered at risk of complicated grief. A 5-item mental health screening tool called the Pandemic Grief Scale (PGS) was developed to find likely instances of dysfunctional grief during the pandemic.ObjectivesTo develop a Greek version of PGS and to explore the validity and reliability among the general population in Greece in order to further use it as clinical mental health screener.MethodsWe conducted a cross-sectional study between January and April 2022, and 342 persons were recruited. The questionnaire included socio-demographic parameters, the PGS, the Brief Resilience Coping Scale to capture tendencies to cope with stress and the Athens Insomnia Scale to assess the insomnia symptoms. Based on experiences over the previous two weeks, each PGS item is scored on a 4-point scale, from 0 (not at all) to 3 (almost every day), with higher rating and a cut-off of 7 indicating dysfunctional grief. Prior to the psychometric validation a linguistic validation and adaptation in Greek was performed.ResultsA total of 342 patients participated in the study, 67.8 % were females and 27.8% were 18-30 years old. Coefficient Validity Ratio (CVR) results showed that 100% (n = 5) of items were acceptable. Value of Cronbach’s alpha was found 0.848. A one-factor model was conducted by Confirmatory Factor Analysis (CFA), giving acceptable global fit indices. The resulting global fit indices [Standardized Root Mean Square Residual (SRMR) = 0.037, Comparative Fit Index (CFI) = 0.952, Tucker–Lewis Index (TLI)= 0.903] showed that the 5 items in one-factor solution proposed by the primary researchers shouldn’t be rejected for the Greek version. The Bartlett Test of Sphericity was 758.08 (p <0.001). The Kaiser-Meyer-Olkin Measure of Sampling Adequacy was 0.826, showing that the data is suitable for factor analysis. The one-factor solution derived in our study consisted of 5 items. The total explained variance was 64.3 %.ConclusionsThe findings of this research support the PGS psychometric validity and reliability. PGS is suitable to be used in healthcare to identify and assist individuals, who are experiencing this type of pandemic-related dysfunctional grief as it is a screening tool that it’s simple to use, access, and understand.Disclosure of InterestNone Declared

IntroductionThe COVID-19 pandemic has placed extraordinary mental health burdens on healthcare professionals. For women, it is a major challenge to reconcile the diverse roles of a professional, mother, and wife. The COVID-19 pandemic has exacerbated this, increasing their vulnerability to mental health issues.ObjectivesThe aim of the study was to assess COVID-19-related mental health of healthcare professionals and to investigate whether possible gender differences as well as other parameters are associated with mental health disturbances.MethodsWe conducted a nationwide cross-sectional study of healthcare professionals working in hospitals or primary care settings in Greece from April to June 2022. Participants answered a questionnaire that included socio-demographic and other parameters, the Coronavirus Anxiety Scale (CAS), the Coronavirus Reassurance-Seeking Behaviors Scale (CRBS), and the Obsession with COVID-19 scale (OCS).ResultsA total of 464 healthcare professionals participated in the study, 71.2% were females and two-thirds were 31-50 years old. Elevated levels of anxiety, frequent reassurance seeking activities and persistent troubling thoughts related to COVID-19 were found in 5.8%, 3.2% and 6.1%, respectively. However, females reported significant higher mean levels on CAS and CRBS compared to males (2.41 vs 1.60, p=0.015, and 3.36 vs 2.64, p=0.041, respectively). Participants living in smaller areas had increased levels on all three scales (CAS, p < 0.001; CRBS, p = 0.007; OCS, p < 0.001), indicating thus higher coronaphobia, more frequent reassurance-seeking behaviors and disturbed thinking about COVID-19, compared to healthcare workers living in urban regions. Furthermore, lower educational level is also associated with higher values on CAS, CRBS and OCS (p < 0.003; p = 0.017; p < 0.023, respectively). Nurses experience higher anxiety scores (2.96) than physicians (1.92, p=0.013) or other healthcare workers (1.87, p=0.016). No dysfunctional thinking about COVID-19 is observed in medical doctors, whereas nurses and other healthcare workers experience higher levels on OCS.ConclusionsOur study does not show any worrying increased psychological dysfunction related to COVID-19 pandemic among healthcare workers in general. However, females have increased levels than males. Thus, support and mental health protecting strategies should be applied primarily to female healthcare professionals when necessary.Disclosure of InterestNone Declared

Background. Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of renal cell carcinoma, whose clinical behaviour and metastatic potential have not been fully elucidated to date. There are only a few metastatic cases in the literature, which all either featured sarcomatoid differentiation or were synchronously metastasised at diagnosis. Case Presentation. We report a case of a 49-year-old male with end-stage kidney disease on dialysis, presenting with multiple osseous metastases of a mucin-poor variant of MTSCC of the kidney, without sarcomatoid differentiation, two years after bilateral nephrectomy for papillary renal cell carcinoma (RCC) at a curable stage. After retrospectively reexamining the initial nephrectomy specimens, the tumour of the right kidney was also diagnosed as a mucin-poor variant of MTSCC, while the tumour of the left kidney was confirmed as a papillary RCC. Conclusions. It is proposed that MTSCC can be associated with end-stage renal disease and that particularly the mucin-poor variant is easily confused with papillary renal cell carcinoma, as happened in this case. Although it is considered as a relatively indolent malign entity, it can metastasise even years after successful primary surgical treatment. This implies, besides accurate diagnosis, that MTSCC patients should be monitored closely in the follow-up period.

In January 2015, the research group \"bladder cancer research\" was founded as part of the GeSRU Academics research initiative. A general challenge to work successfully in a novel network structure is to identify common scientific topics and technical expertise in the group. Thus, one of the first tasks was to learn about current research projects from members within the group in order to address a project that suits the group's expertise. The following review summarizes three different directions that are key projects in Urologic Departments at German Universities that will be the basis to start fruitful collaborations.

Zusammenfassung Im Januar 2015 wurde im Rahmen der Gründung der GeSRU Academics die Forschergruppe „Blasenkarzinom Experimentell“ initiiert. Eine der grundlegenden Herausforderungen, um in einem Netzwerkverbund produktiv arbeiten zu können, ist das Herausarbeiten thematischer und methodischer Expertise als Voraussetzung für gemeinsame Projekte. Daher war es der Gruppe ein erstes Anliegen, die Forschungsschwerpunkte einzelner Mitglieder zu bündeln und darzustellen, um im Anschluss aktuelle Fragestellungen zu formulieren. Im folgenden Übersichtsbeitrag werden drei Themenkomplexe erläutert, die eine hohe Aufmerksamkeit an verschiedenen Standorten in Deutschland erfahren und daher in Verbundprojekte münden sollen.