Frequency of Sexual Problems and Related Psychosocial Characteristics in Cancer Patients—Findings From an Epidemiological Multicenter Study in Germany

Background: Multimodal cancer treatments are often associated with sexual problems. Identifying patients with sexual problems could help further elucidate serious issues with their sexuality and thus promote or maintain patients’ sexual health. We aimed to assess the occurrence of sexual problems in patients across different tumor locations and to explore associated sociodemographic, medical and psychosocial factors. Methods: We included 3,677 cancer patients (mean age 58 years, age range 18– 75 years, 51.4% women) from a large epidemiological multicenter study in Germany on average 13.5 months after cancer diagnosis. The occurrence and frequency of sexual problems were assessed via a binary item on the problem checklist of the Distress Thermometer (DT). Controlled associations of these problems with sociodemographic, medical and psychosocial factors including distress (DT), anxiety (GAD-7), depression (PHQ-9), quality of life (EORTC-QLQ-C30), and social support (SSUK-8) are analyzed using logistic regression analysis. Results: We found that 31.8% of patients reported sexual problems, with a significant higher proportion in men (40.5%) compared to women (23.7%), OR 2.35, 95% CI [1.80– 3.07] and a higher proportion in patients with a partner (35.6%) compared to those without a partner (3.5%), OR 2.83, 95% CI [2.17–3.70]. Tumor location was associated with occurrence of sexual problems: patients with cancer, affecting the male genital organs had the highest chance for sexual problems, OR 2.65, 95% CI [1.18–3.95]. There was no significant difference in the occurrence of sexual problems between age groups OR 0.99, 95% CI [2.13–3.53] and type of therapy (e.g., operation OR 0.91, 95% CI [0.72–1.15]). Sexual problems were further associated with elevated levels of anxiety, OR 1.05, 95% CI [1.02–1.10], less social support, OR 0.93, 95% CI [0.90–0.97] and lower quality of life in terms of impaired functioning (e.g., social function, OR 0.99, 95% CI [0.99–1.00]). Conclusions: Sexual problems are commonly reported by patients. Male patients and those living with a partner are more likely to report sexual problems. Sexual problems are associated with different aspects of well-being. The findings imply the practical relevance to screen for sexual problems among patients and identified groups that should be particularly monitored

New functions of the p53 tumor suppressor at mitochondria and in the nucleus

p53 ist der wichtigste humane Tumorsuppressor, der die Tumorbildung hauptsächlich über Wachstumsarrest oder Apoptoseinduktion verhindert. Die proapoptotische Funktion läuft über einen transkriptionsabhängigen Weg im Nukleus oder einen transkriptionsunabhängigen Weg an den Mitochondrien. Die nukleären Aufgaben von p53 als Transkriptionsfaktor können von dominant-inhibitorisch wirkenden Varianten der p53-Genfamilie blockiert werden. Wir konnten Hinweise beibringen, dass diese dominanten Inhibitoren keinen Einfluß auf die extra-nukleären p53-Funktionen an den Mitochondrien aufweisen, weil p53 hier als Monomer vorliegt und nicht wie im Zellkern als Tetramer. Weiterhin fanden wir Evidenzen, dass p53 nach seiner Translation zunächst in den Zellkern transportiert und erst nach Stressstimulus durch Mdm2 aus dem Zellkern exportiert wird, um an die Mitochondrien zu translozieren. Die mitochondriale Biogenese wurde durch p53 nicht nachweislich beeinflusst. Neuere Daten haben gezeigt, dass p53 auch ohne Zellstress an den Promotoren einiger seiner Zielgene gebunden vorliegt, ohne diese zu transaktivieren. Es stellte sich daher die Frage, wie die Regulation des bereits Promotor-gebundenem p53 erfolgt. Mit NIR, einem Inhibitor von Acetyltransferasen, konnte ein neuer negativer Regulator von p53 identifiziert werden, der die Transkription p53-responsiver Gene und die Apoptose in Abhängigkeit von p53 beeinflussen kann.p53 is the most important human tumor suppressor which inhibits tumor formation primarily by growth arrest or apoptosis induction. The proapoptotic function is mediated either by transcription-dependent pathways in the nucleus or by transcription-independent pathways at mitochondria. The nuclear tasks of p53 as transcription factor can be inhibited by dominant-negatively acting variants of the p53 gene family. We found indications that these dominant inhibitors spare the extra-nuclear functions of p53 at mitochondria because mitochondrial p53 is present as a monomer and not as a tetramer as in the nucleus. Furthermore, we found evidence that p53 has to be exported out of the nucleus by Mdm2 after a stress stimulus in order to translocate to mitochondria. Mitochondrial biogenesis was not demonstrably influenced by p53. Recent studies have shown that p53 is bound to a subset of promoters of its target genes without cell stress and without transactivating them. This raises the question how promoter-bound p53 is regulated. A new negative regulator of p53, NIR, an inhibitor of acetyltransferases, was identified which is able to influence transcription of p53 responsive genes and apoptosis in dependence of p53

Frequency of Sexual Problems and Related Psychosocial Characteristics in Cancer Patients—Findings From an Epidemiological Multicenter Study in Germany

Background: Multimodal cancer treatments are often associated with sexual problems. Identifying patients with sexual problems could help further elucidate serious issues with their sexuality and thus promote or maintain patients’ sexual health. We aimed to assess the occurrence of sexual problems in patients across different tumor locations and to explore associated sociodemographic, medical and psychosocial factors. Methods: We included 3,677 cancer patients (mean age 58 years, age range 18– 75 years, 51.4% women) from a large epidemiological multicenter study in Germany on average 13.5 months after cancer diagnosis. The occurrence and frequency of sexual problems were assessed via a binary item on the problem checklist of the Distress Thermometer (DT). Controlled associations of these problems with sociodemographic, medical and psychosocial factors including distress (DT), anxiety (GAD-7), depression (PHQ-9), quality of life (EORTC-QLQ-C30), and social support (SSUK-8) are analyzed using logistic regression analysis. Results: We found that 31.8% of patients reported sexual problems, with a significant higher proportion in men (40.5%) compared to women (23.7%), OR 2.35, 95% CI [1.80– 3.07] and a higher proportion in patients with a partner (35.6%) compared to those without a partner (3.5%), OR 2.83, 95% CI [2.17–3.70]. Tumor location was associated with occurrence of sexual problems: patients with cancer, affecting the male genital organs had the highest chance for sexual problems, OR 2.65, 95% CI [1.18–3.95]. There was no significant difference in the occurrence of sexual problems between age groups OR 0.99, 95% CI [2.13–3.53] and type of therapy (e.g., operation OR 0.91, 95% CI [0.72–1.15]). Sexual problems were further associated with elevated levels of anxiety, OR 1.05, 95% CI [1.02–1.10], less social support, OR 0.93, 95% CI [0.90–0.97] and lower quality of life in terms of impaired functioning (e.g., social function, OR 0.99, 95% CI [0.99–1.00]). Conclusions: Sexual problems are commonly reported by patients. Male patients and those living with a partner are more likely to report sexual problems. Sexual problems are associated with different aspects of well-being. The findings imply the practical relevance to screen for sexual problems among patients and identified groups that should be particularly monitored

Frequency of Sexual Problems and Related Psychosocial Characteristics in Cancer Patients—Findings From an Epidemiological Multicenter Study in Germany

Background: Multimodal cancer treatments are often associated with sexual problems. Identifying patients with sexual problems could help further elucidate serious issues with their sexuality and thus promote or maintain patients’ sexual health. We aimed to assess the occurrence of sexual problems in patients across different tumor locations and to explore associated sociodemographic, medical and psychosocial factors. Methods: We included 3,677 cancer patients (mean age 58 years, age range 18– 75 years, 51.4% women) from a large epidemiological multicenter study in Germany on average 13.5 months after cancer diagnosis. The occurrence and frequency of sexual problems were assessed via a binary item on the problem checklist of the Distress Thermometer (DT). Controlled associations of these problems with sociodemographic, medical and psychosocial factors including distress (DT), anxiety (GAD-7), depression (PHQ-9), quality of life (EORTC-QLQ-C30), and social support (SSUK-8) are analyzed using logistic regression analysis. Results: We found that 31.8% of patients reported sexual problems, with a significant higher proportion in men (40.5%) compared to women (23.7%), OR 2.35, 95% CI [1.80– 3.07] and a higher proportion in patients with a partner (35.6%) compared to those without a partner (3.5%), OR 2.83, 95% CI [2.17–3.70]. Tumor location was associated with occurrence of sexual problems: patients with cancer, affecting the male genital organs had the highest chance for sexual problems, OR 2.65, 95% CI [1.18–3.95]. There was no significant difference in the occurrence of sexual problems between age groups OR 0.99, 95% CI [2.13–3.53] and type of therapy (e.g., operation OR 0.91, 95% CI [0.72–1.15]). Sexual problems were further associated with elevated levels of anxiety, OR 1.05, 95% CI [1.02–1.10], less social support, OR 0.93, 95% CI [0.90–0.97] and lower quality of life in terms of impaired functioning (e.g., social function, OR 0.99, 95% CI [0.99–1.00]). Conclusions: Sexual problems are commonly reported by patients. Male patients and those living with a partner are more likely to report sexual problems. Sexual problems are associated with different aspects of well-being. The findings imply the practical relevance to screen for sexual problems among patients and identified groups that should be particularly monitored

Resistance of mitochondrial p53 to dominant inhibition

<p>Abstract</p> <p>Background</p> <p>Mutation of a tumor suppressor allele leaves the second as backup. Not necessarily so with p53. This homo-tetrameric transcription factor can become contaminated with mutant p53 through hetero-tetramerization. In addition, it can be out-competed by the binding to p53 DNA recognition motifs of transactivation-incompetent isoforms (ΔN and ΔTA-isoforms) of the p53/p63/p73 family of proteins. Countermeasures against such dominant-negative or dominant-inhibitory action might include the evolutionary gain of novel, transactivation-independent tumor suppressor functions by the wild-type monomer.</p> <p>Results</p> <p>Here we have studied, mostly in human HCT116 colon adenocarcinoma cells with an intact p53 pathway, the effects of dominant-inhibitory p53 mutants and of Δex2/3p73, a tumor-associated ΔTA-competitor of wild-type p53, on the nuclear transactivation-dependent and extra-nuclear transactivation-independent functions of wild-type p53. We report that mutant p53 and Δex2/3p73, expressed from a single gene copy per cell, interfere with the stress-induced expression of p53-responsive genes but leave the extra-nuclear apoptosis by mitochondrial p53 largely unaffected, although both wild-type and mutant p53 associate with the mitochondria. In accord with these observations, we present evidence that in contrast to nuclear p53 the vast majority of mitochondrial p53, be it wild-type or mutant, is consisting of monomeric protein.</p> <p>Conclusion</p> <p>The extra-nuclear p53-dependent apoptosis may constitute a fail-safe mechanism against dominant inhibition.</p

MDM2 binds and inhibits vitamin D receptor

<p>The E3 ubiquitin ligase and transcriptional repressor MDM2 is a potent inhibitor of the p53 family of transcription factors and tumor suppressors. Herein, we report that vitamin D receptor (VDR), another transcriptional regulator and probably, tumor suppressor, is also bound and inhibited by MDM2. This interaction was not affected by vitamin D ligand. VDR was ubiquitylated in the cell and its steady-state level was controlled by the proteasome. Strikingly, overproduced MDM2 reduced the level of VDR whereas knockdown of endogenous MDM2 increased the level of VDR. In addition to ubiquitin-marking proteins for degradation, MDM2, once recruited to promoters by DNA-binding interaction partners, can inhibit the transactivation of genes. Transient transfections with a VDR-responsive <i>luciferase</i> reporter revealed that low levels of MDM2 potently suppress VDR-mediated transactivation. Conversely, knockdown of MDM2 resulted in a significant increase of transcript from the <i>CYP24A1</i> and <i>p21</i> genes, noted cellular targets of transactivation by liganded VDR. Our findings suggest that MDM2 negatively regulates VDR in some analogy to p53.</p

KNOGA. Fossilfri framdrift för tunga långväga godstransporter på väg : kostnadsfördelning och risker för olika aktörer (Executive summary)

Användningen av förnybar energi i transportsektorn behöver öka för att vi ska nå de svenska klimatmålen om minskade växthusgasutsläpp från inrikes transporterna med 70 procent till 2030, och nettonollutsläpp från samtliga sektorer till 2045. Ökningen av förnybara drivmedel behöver ske i alla segment och över hela fordonsflottan. Idag används främst diesel som drivmedel för tunga långväga godstransporter på väg men det finns alternativ för fossilfri framdrift.  Denna studie har kvantifierat kostnadsstrukturer och analyserat riskfördelning mellan olika aktörer för fossilfria framdriftstekniker för tunga långväga godstransporter på väg och jämfört dem med alternativet att fortsätta använda diesel som drivmedel.  Följande tekniker är inkluderade i studien: biobränslen (flytande och gasformiga), batterielektriska fordon (BEV), elvägar (tre olika tekniker), vätgasdrivna bränslecellsfordon (H2-FCEV) samt elektrobränslen. Beräkningar görs för år 2030 och 2045.  Från de fem huvudkategorierna för fossilfri framdrift har ett antal representativa motortekniker, bränsleproduktionstekniker och råvaror valts ut för att analyseras i detalj. Detta har resulterat i ett trettiotal olika fossilfria alternativ till dagens användning av fossil diesel