Dyadic associations and prediction of maternal and paternal sexual satisfaction in couples-Findings from an 18-year longitudinal study.

Background: : Sexual satisfaction is one of many crucial factors for the long-term success of romantic relationships. Longitudinal studies examining the dyadic associations between maternal and paternal factors in middle adulthood for predicting sexual satisfaction in later adulthood are scarce. Method: The German longitudinal intervention study "Future Family" followed families with at least one child over 18-years (Pre: N = 477, mothers: M = 35.2 years, fathers: M = 38.8 years, children: M = 4.1 years). At the time of the 18-year follow-up, N = 150 mothers (M = 54.1 years) were still living together with the biological fathers (M = 56.1 years; mean relationship duration: 32 years). Dyadic associations between individual and dyadic factors at Pre were analyzed with Actor-Partner Interdependence models to predict sexual satisfaction 18 years later. Results: Higher relationship quality was significantly associated with higher levels of one's own sexual satisfaction 18 years later. Higher levels of maternal and paternal mental health problems were linked to lower levels of sexual satisfaction in both the individual themselves and their partner. General life satisfaction of mothers and fathers only predicted their own sexual satisfaction. The model for dysfunctional parenting yielded no significant effects. Conclusions: The results indicate that relationship quality, mental health problems, and general life satisfaction of both parents could be starting points for preventive and therapeutic interventions to achieve long-term effects in sexual satisfaction in married couples.

Upward Lightning at Wind Turbines: Risk Assessment From Larger-Scale Meteorology.

Upward lightning (UL) has become a major threat to the growing number of wind turbines producing renewable electricity. It can be much more destructive than downward lightning due to the large charge transfer involved in the discharge process. Ground-truth lightning current measurements indicate that less than 50% of UL could be detected by lightning location systems (LLS). UL is expected to be the dominant lightning type during the cold season. However, current standards for assessing the risk of lightning at wind turbines mainly consider summer lightning, which is derived from LLS. This study assesses the risk of LLS-detectable and LLS-undetectable UL at wind turbines using direct UL measurements at instrumented towers. These are linked to meteorological data using random forests. The meteorological drivers for the absence/occurrence of UL are found from these models. In a second step, the results of the tower-trained models are extended to a larger study area (central and northern Germany). The tower-trained models for LLS-detectable lightning are independently verified at wind turbine sites in this area and found to reliably diagnose this type of UL. Risk maps based on cold season case study events show that high probabilities in the study area coincide with actual UL flashes. This lends credibility to the application of the model to all UL types, increasing both risk and affected areas.

Characterization of Native COMPASS Complex in Urothelial Carcinoma Cells by Size Exclusion Chromatography.

The human COMPASS complexes regulate gene expression during development and cell differentiation. Three distinct subunits, KMT2C, KMT2D, and KDM6A (also known as UTX), are frequently mutated in urothelial carcinoma, possibly disrupting the formation of functional COMPASS complexes. Here, we describe methods to evaluate the formation of these large native protein complexes in urothelial carcinoma (UC) cell lines harboring different mutations in KMT2C/D. To this end COMPASS complexes were purified from nuclear extracts by size exclusion chromatography (SEC) using a Sepharose 6 column. SEC fractions were then separated by 3-8% Tris-acetate gradient polyacrylamide gel and the COMPASS complex subunits KMT2C, UTX, WDR5, and RBBP5 were detected by immunoblotting. In this fashion, the formation of a COMPASS complex could be observed in UC cells with wild-type but not in cells with mutant KMT2C and KMTD.

Multi-element isotopic analysis of hot particles from Chornobyl.

Microscopic fuel fragments, so-called "hot particles", were released during the 1986 accident at the Chornobyl nuclear powerplant and continue to contaminate the exclusion zone in northern Ukraine. Isotopic analysis can provide vital information about sample origin, history and contamination of the environment, though it has been underutilized due to the destructive nature of most mass spectrometric techniques, and inability to remove isobaric interference. Recent developments have diversified the range of elements that can be investigated through resonance ionization mass spectrometry (RIMS), notably in the fission products. The purpose of this study is to demonstrate the application of multi-element analysis on hot particles as relates to their burnup, particle formation in the accident, and weathering. The particles were analysed with two RIMS instruments: resonant-laser secondary neutral mass spectrometry (rL-SNMS) at the Institute for Radiation Protection and Radioecology (IRS) in Hannover, Germany, and laser ionization of neutrals (LION) at Lawrence Livermore National Laboratory (LLNL) in Livermore, USA. Comparable results across instruments show a range of burnup dependent isotope ratios for U and Pu and Cs, characteristic of RBMK-type reactors. Results for Rb, Ba and Sr show the influence of the environment, retention of Cs in the particles and time passed since fuel discharge.

Upward Lightning at the Gaisberg Tower: The Larger-Scale Meteorological Influence on the Triggering Mode and Flash Type.

Upward lightning is rarer than downward lightning and requires tall (100+ m) structures to initiate. It may be either self-initiated or triggered by other lightning discharges. While conventional lightning location systems (LLSs) detect most of the upward lightning flashes superimposed by pulses or return strokes, they miss a specific flash type that consists only of a continuous current. Globally, only few specially instrumented towers can record this flash type. The proliferation of wind turbines in combination with damages from upward lightning necessitates an improved understanding under which conditions self-initiated upward lightning and the continuous-current-only subtype occur. This study uses a random forest machine learning model to find the larger-scale meteorological conditions favoring the occurrence of the different phenomena. It combines ground truth lightning current measurements at the specially instrumented tower at Gaisberg mountain in Austria with variables from larger-scale meteorological reanalysis data (ERA5). These variables reliably explain whether upward lightning is self-initiated or triggered by other lightning discharges. The most important variable is the height of the -10°C isotherm above the tall structure: the closer it is, the higher is the probability of self-initiated upward lightning. For the different flash types, this study finds a relationship to the larger-scale electrification conditions and the LLS-detected lightning situation in the vicinity. Lower amounts of supercooled liquid water, solid, and liquid differently sized particles and no LLS-detected lightning events nearby favor the continuous-current-only subtype compared to the other subtypes, which preferentially occur with LLS-detected lightning events within 3 km from the Gaisberg Tower.

Indium tin oxide ultrafast laser lift-off ablation mechanisms and damage minimization.

We draw comparisons between the ablation and damage mechanisms that occur for both film and substrate irradiation using atomic force microscopy, scanning electron microscopy, and pump-probe reflectometry. For substrate irradiation, energy absorbed at the film-substrate interface creates a confined energy situation, resulting in a photomechanical lift-off. A partial ablation at the edges of the ablated zone formed the burr and was reduced in height by minimizing the area subject to the partial ablation threshold fluence. Substrate damage is understood to arise from free electron diffusion from indium tin oxide and subsequent laser heating. We establish a process window for substrate irradiation in a single-pulse ablation regime between approximately two to three times the ablation threshold of 0.18 J/cm2, validating the process window seen in literature and provide a crucial understanding for the ablation mechanisms of transparent conductive films.

Effects of active musical engagement during physical exercise on anxiety, pain and motivation in patients with chronic pain.

The experience of anxiety is central to the development of chronic pain. Music listening has been previously shown to exert analgesic effects. Here we tested if an active engagement in music making is more beneficial than music listening in terms of anxiety and pain levels during physical activity that is often avoided in patients with chronic pain. We applied a music feedback paradigm that combines music making and sports exercise, and which has been previously shown to enhance mood. We explored this method as an intervention to potentially reduce anxiety in a group of patients with chronic pain (N = 24, 20 female and 4 men; age range 34-64, M = 51.67, SD = 6.84) and with various anxiety levels. All participants performed two conditions: one condition, Jymmin, where exercise equipment was modified with music feedback so that it could be played like musical instruments by groups of three. Second, a conventional workout condition where groups of three performed exercise on the same devices but where they listened to the same type of music passively. Participants' levels of anxiety, mood, pain and self-efficacy were assessed with standardized psychological questionnaires before the experiment and after each condition. Results demonstrate that exercise with musical feedback reduced anxiety values in patients with chronic pain significantly as compared to conventional workout with passive music listening. There were no significant overall changes in pain, but patients with greater anxiety levels compared to those with moderate anxiety levels were observed to potentially benefit more from the music feedback intervention in terms of alleviation of pain. Furthermore, it was observed that patients during Jymmin more strongly perceived motivation through others. The observed diminishing effects of Jymmin on anxiety have a high clinical relevance, and in a longer term the therapeutic application could help to break the Anxiety Loop of Pain, reducing chronic pain. The intervention method, however, also has immediate benefits to chronic pain rehabilitation, increasing the motivation to work out, and facilitating social bonding.

Mental health, partnerships, and sexual behavior of German university students after the third wave of the COVID-19 pandemic.

Objective: This study examined the state of mental health, partnerships, and sexual activity of German university students after the third wave of the COVID-19 pandemic. Participants and methods: In June and July 2021, 928 students (23.6 years; 63.5% female) from four universities in Germany participated in an online survey that assessed depressive and anxiety symptoms as well as data on partnerships and sexuality. Results: Of the students, 56.4% were above the cutoff for clinically relevant depressive symptoms and 35.7% were above the cutoff for clinically relevant anxiety symptoms. Female gender, higher academic-related stress, lower financial resources, higher strain due to COVID-19, and more loneliness were associated with more severe symptoms. A quarter of the students each reported an improvement or deterioration in their partnerships. Conclusions: Student mental health appears to be worse compared to pre-pandemic and first wave data. It should be examined whether symptoms decrease when universities reopen.

Proteomic and transcriptomic profiles of human urothelial cancer cells with histone deacetylase 5 overexpression.

Urothelial carcinoma (UC) of the urinary bladder is a prevalent cancer worldwide. Because histone deacetylases (HDACs) are important factors in cancer, targeting these epigenetic regulators is considered an attractive strategy to develop novel anticancer drugs. Whereas HDAC1 and HDAC2 promote UC, HDAC5 is often downregulated and only weakly expressed in UC cell lines, suggesting a tumor-suppressive function. We studied the effect of stable lentiviral-mediated HDAC5 overexpression in four UC cell lines with different phenotypes (RT112, VM-Cub-1, SW1710, and UM-UC-3, each with vector controls). In particular, comprehensive proteomics and RNA-seq transcriptomics analyses were performed on the four cell line pairs, which are described here. For comparison, the immortalized benign urothelial cell line HBLAK was included. These datasets will be a useful resource for researchers studying UC, and especially the influence of HDAC5 on epithelial-mesenchymal transition (EMT). Moreover, these data will inform studies on HDAC5 as a less studied member of the HDAC family in other cell types and diseases, especially fibrosis.

Epigenetics in the Diagnosis and Therapy of Malignant Melanoma.

Epigenetic mechanisms are fundamentally important for cancer initiation and development. However, a survey of the literature reveals that, to date, they appear less comprehensively investigated in melanoma than in many other cancers, e.g., prostate, breast, and colon carcinoma. The aim of this review is to provide a short summary of epigenetic aspects of functional relevance for melanoma pathogenesis. In addition, some new perspectives from epigenetic research in other cancers with potential for melanoma diagnosis and therapy are introduced. For example, the PrimeEpiHit hypothesis in urothelial carcinoma, which, similarly to malignant melanoma, can also be triggered by a single exogenous noxa, states that one of the first steps for cancer initiation could be epigenetic changes in key genes of one-carbon metabolism. The application of such insights may contribute to further progress in the diagnosis and therapy of melanoma, a deadly type of cancer.

Alterations of Chromatin Regulators in the Pathogenesis of Urinary Bladder Urothelial Carcinoma.

Urothelial carcinoma (UC) is the most frequent histological type of cancer in the urinary bladder. Genomic changes in UC activate MAPK and PI3K/AKT signal transduction pathways, which increase cell proliferation and survival, interfere with cell cycle and checkpoint control, and prevent senescence. A more recently discovered additional category of genetic changes in UC affects chromatin regulators, including histone-modifying enzymes (KMT2C, KMT2D, KDM6A, EZH2), transcription cofactors (CREBBP, EP300), and components of the chromatin remodeling complex SWI/SNF (ARID1A, SMARCA4). It is not yet well understood how these changes contribute to the development and progression of UC. Therefore, we review here the emerging knowledge on genomic and gene expression alterations of chromatin regulators and their consequences for cell differentiation, cellular plasticity, and clonal expansion during UC pathogenesis. Our analysis identifies additional relevant chromatin regulators and suggests a model for urothelial carcinogenesis as a basis for further mechanistic studies and targeted therapy development.

The Dual Histone Deacetylase-Proteasome Inhibitor RTS-V5 Acts Synergistically With Ritonavir to Induce Endoplasmic Reticulum Stress in Bladder Cancer Cells.

BACKGROUND/AIM: Simultaneous inhibition of histone deacetylase and proteasomes induces endoplasmic reticulum (ER) stress efficiently. RTS-V5 is the first dual histone deacetylase-proteasome inhibitor, and we anticipated that combining it with the cytochrome P450 family 3 subfamily A member 4 inhibitor ritonavir would enhance its activity in bladder cancer cells. MATERIALS AND METHODS: Using bladder cancer cells (human T-24, J-82, murine MBT-2), we evaluated the ability and mechanism by which the combination of RTS-V5 and ritonavir induced ER stress and killed cancer cells. RESULTS: The combination of RTS-V5 and ritonavir triggered robust apoptosis and inhibited bladder cancer growth effectively in vitro and in vivo. It caused ubiquitinated protein accumulation and induced ER stress synergistically. The combination inhibited the mammalian target of rapamycin pathway by increasing the expression of AMP-activated protein kinase. We also found that the combination caused histone and tubulin hyperacetylation. CONCLUSION: Ritonavir enhances the ability of RTS-V5 to cause ER stress in bladder cancer cells.

Time-resolved ultrafast laser ablation dynamics of thin film indium tin oxide.

The interaction of ultrashort laser pulses above the ablation threshold of thin-film indium tin oxide (ITO) is examined with pump-probe microscopy. We are able to observe photomechanical spallation at delay times of hundreds of picoseconds, which plays a stronger role near the ablation threshold of 0.17 J/cm2. A phase explosion may also be observed at tens of picoseconds, playing a stronger role for increasing peak fluences. As one exceeds the material removal efficiency maximum near 0.6 J/cm2, a second spallation is observable in the center of the irradiated spot at a delay time of one nanosecond and corresponds to a crater depth of 50 nanometers. No discernable ridge formation has been observed. We recommend an industrial processing window of at least two pulses per position with a peak fluence between 0.6-1.0 J/cm2.

Feature-based molecular networking for identification of organic micropollutants including metabolites by non-target analysis applied to riverbank filtration.

Due to growing concern about organic micropollutants and their transformation products (TP) in surface and drinking water, reliable identification of unknowns is required. Here, we demonstrate how non-target liquid chromatography (LC)-high-resolution tandem mass spectrometry (MS/MS) and the feature-based molecular networking (FBMN) workflow provide insight into water samples from four riverbank filtration sites with different redox conditions. First, FBMN prioritized and connected drinking water relevant and seasonally dependent compounds based on a modification-aware MS/MS cosine similarity. Within the resulting molecular networks, forty-three compounds were annotated. Here, carbamazepine, sartans, and their respective TP were investigated exemplarily. With chromatographic information and spectral similarity, four additional TP (dealkylated valsartan, dealkylated irbesartan, two oxygenated irbesartan isomers) and olmesartan were identified and partly verified with an authentic standard. In this study, sartans and TP were investigated and grouped regarding their removal behavior under different redox conditions and seasons for the first time. Antihypertensives were grouped into compounds being well removed during riverbank filtration, those primarily removed under anoxic conditions, and rather persistent compounds. Observed seasonal variations were mainly limited to varying river water concentrations. FBMN is a powerful tool for identifying previously unknown or unexpected compounds and their TP in water samples by non-target analysis.

Early childhood parenting and adolescent bullying behavior: Evidence from a randomized intervention at ten-year follow-up.

RATIONALE: Bullying in education is a significant public health problem with long-run life cycle consequences, but efforts to reduce bullying were met with mixed results. We ask whether improving early childhood parenting can reduce subsequent bullying behavior by the children. METHOD: We analyze ten-year follow-up of a randomized intervention where the parents of preschool children received a training aimed at improving parenting techniques, such as disciplinary strategies. 280 parents in 17 preschools were cluster-randomized at the preschool level (intervention group, cluster = 11, n = 186 vs. control group, cluster = 6, n = 94). Their children were followed ten years later, at ages between 12 and 16, with overall attrition rate of 12.5%. Ordinary least squares is used to estimate the intent-to-treat effects, controlling for the baseline characteristics of the child and the mother. Multiple imputation and inverse probability weighting are used to account for attrition and wild-cluster bootstrap test is used for statistical inference with few clusters. We estimate treatment-on-the-treated effects using two-stage least squares to account for noncompliance in the intervention group. Finally, we examine the associations between bullying and externalizing behavior. RESULTS: Adolescent children are significantly less likely to bully their peers if their parents received the parenting training when their children were in preschools. The effects are stronger for boys and for aggressive forms of bullying such as 'beating' and 'threatening'. Treatment-on-the-treated effects are greater in magnitude and more significant than intent-to-treat effects, suggesting that the effects are driven by program participants. No effect is found for cyberbullying and for victimization. The results were robust to using multiple imputation and inverse probability weighting. We also find suggestive evidence that the effects on bullying are not explained by changes in externalizing behavior. CONCLUSION: We show that improving early childhood parenting can have important public health benefits through reduction in adolescent bullying behavior.

Ubiquitin-proteasome System Is a Promising Target for Killing Cisplatin-resistant Bladder Cancer Cells.

BACKGROUND/AIM: Activation of the ubiquitin-proteasome system (UPS) has been shown to be associated with drug resistance in cancer. Using bladder cancer cells, we investigated the association between UPS activation and cisplatin resistance and also the efficacy of UPS-targeting drugs. MATERIALS AND METHODS: We established cisplatin-resistant bladder cancer cells (J82-cisR, T24-cisR) and examined the activation status of the UPS and the efficacy of MLN7243, oprozomib, ixazomib, and RTS-V5. RESULTS: The UPS in cisplatin-resistant bladder cancer cells was activated compared to that in their parental controls. All the UPS-targeting drugs induced apoptosis and inhibited growth more effectively in the cisplatin-resistant bladder cancer cells than they did in the parental controls. Furthermore, these UPS-targeting drugs induced endoplasmic reticulum stress by causing unfolded protein accumulation at lower concentrations in the cisplatin-resistant bladder cancer cells. CONCLUSION: Targeting the UPS could be an effective strategy for treating cisplatin-resistant bladder cancer.

Epigenetic Treatment of Urothelial Carcinoma Cells Sensitizes to Cisplatin Chemotherapy and PARP Inhibitor Treatment.

Muscle-invasive urothelial carcinoma (UC) is treated with cisplatin-based chemotherapy, which is only moderately efficient, mostly due to development of resistance. New therapy approaches are therefore urgently needed. Epigenetic alterations due to frequent mutations in epigenetic regulators contribute to development of the disease and to treatment resistance, and provide targets for novel drug combination therapies. Here, we determined the cytotoxic impact of the second-generation bromodomain protein inhibitor (BETi) PLX51107 on UC cell lines (UCC) and normal HBLAK control cells. PLX51107 inhibited proliferation, induced apoptosis, and acted synergistically with the histone deacetylase inhibitor romidepsin. While PLX51107 caused significant DNA damage, DNA damage signaling and DNA repair were impeded, a state defined as BRCAness. Accordingly, the drug strongly synergized with cisplatin more efficiently than romidepsin, and with the PARP inhibitor talazoparib to inhibit proliferation and induce cell death in UCC. Thus, a BETi can be used to "episensitize" UC cells to cytotoxic chemotherapy and inhibitors of DNA repair by inducing BRCAness in non BRCA1/2 mutated cancers. In clinical applications, the synergy between PLX51107 and other drugs should permit significant dosage reductions to minimize effects on normal tissues.

[How do Adolescents see their Parents? Prevalences, Predictors and Relationships in Longitudinal and Cross-Section Research]. / Welches Bild haben Jugendliche von ihren Eltern? Prävalenzen, Prädiktoren und Zusammenhänge im Längs- und Querschnitt.

How do Adolescents see their Parents? Prevalences, Predictors and Relationships in Longitudinal and Cross-Section Research The parent-child relationship has a significant influence on the psychological and social development of a young person in adolescence. The parental image from the perspective of the adolescent has rarely been examined. The aim of this study is to examine the parental images of adolescents in terms of family cohesion, conflicts and overprotection for differences between the paternal and the maternal images and between girls and boys. Furthermore, a cross-section examines the relationship between the parental images and psychological disorders, and, in a longitudinal 10-year study, whether the parental images can be predicted through risk factors in childhood. The sample includes 343 young people with an average age of 14 years, 46 % are girls. The parental images were recorded with the "Elternbildfragebogen" (Parental Image Questionnaire; EBF-KJ; Titze u. Lehmkuhl, 2010). Compared to fathers, mothers are assessed more positively in terms of their cohesion, but at the same time they also show more conflictual and higher overprotection behavior. Very few differences were found between girls and boys. There were consistently significant correlations between the parental images and internalizing and externalizing symptomatology, such that cohesion is a protective factor and conflicts and overprotection are risk factors for the development of psychological disorders. Some aspects of the images of the mother and father can be significantly predicted by the parents' education and by psychological disorders in childhood. Future research should examine the influence of possible mediators and moderators.

Downregulation of Cell Cycle and Checkpoint Genes by Class I HDAC Inhibitors Limits Synergism with G2/M Checkpoint Inhibitor MK-1775 in Bladder Cancer Cells.

Since genes encoding epigenetic regulators are often mutated or deregulated in urothelial carcinoma (UC), they represent promising therapeutic targets. Specifically, inhibition of Class-I histone deacetylase (HDAC) isoenzymes induces cell death in UC cell lines (UCC) and, in contrast to other cancer types, cell cycle arrest in G2/M. Here, we investigated whether mutations in cell cycle genes contribute to G2/M rather than G1 arrest, identified the precise point of arrest and clarified the function of individual HDAC Class-I isoenzymes. Database analyses of UC tissues and cell lines revealed mutations in G1/S, but not G2/M checkpoint regulators. Using class I-specific HDAC inhibitors (HDACi) with different isoenzyme specificity (Romidepsin, Entinostat, RGFP966), cell cycle arrest was shown to occur at the G2/M transition and to depend on inhibition of HDAC1/2 rather than HDAC3. Since HDAC1/2 inhibition caused cell-type-specific downregulation of genes encoding G2/M regulators, the WEE1 inhibitor MK-1775 could not overcome G2/M checkpoint arrest and therefore did not synergize with Romidepsin inhibiting HDAC1/2. Instead, since DNA damage was induced by inhibition of HDAC1/2, but not of HDAC3, combinations between inhibitors of HDAC1/2 and of DNA repair should be attempted.