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Rezension zu: Häusermann, Silja und Herbert Kitschelt (Hrsg.). 2024. Beyond Social Democracy. The Transformation of the Left in Emerging Knowledge Societies
No full textFate or Free Will? The Reception of Greek Religion in Jean Cocteau’s La Machine Infernale (1934)
Full text linkIn the present article we propose to analyse the link between Greek religion and philosophical concepts of the human condition as a problem of reconciling determinism and at the same time free will, with its existential and moral implications. This issue has remained a matter of revision and discussion throughout the ages and latitudes within philosophy, but also in the literature, where through myths, these questions reappear, although in very different historical and religious contexts. We propose to approach these themes through the myth of Oedipus, immortalised by Sophocles in his tragedy Oedipus Rex, which Jean Cocteau, in the tragic interwar period, rereads and resemanticises, but without losing the essential question of whether there is an insurmountable destiny that imposes itself on free will
Emetophobia (fear of vomiting): A meta-analysis
No full textEmetophobia refers to a specific fear of vomiting. There are only few original research studies on this condition and no study that has meta-analytically synthesized findings to describe the characteristics of persons with emetophobia. To this end, we extracted data from 31 reports and—as we examined different dependent variables—each meta-analysis was based on five to 21 samples. The pooled mean age of persons with emetophobia was 29 years but was reduced to 21–27 years when adjusting for publication bias. The pooled mean age of disorder onset was 10 years. The pooled proportion of females was 91 %. The pooled proportions of reporting fear of vomiting oneself, fear of seeing others vomit, or both, were 47 %, 11 %, and 39 %. The most common comorbid mental disorders were social anxiety disorder, depression, and generalized anxiety disorder. The pooled point prevalence of emetophobia was 5 %. Higher emetophobic symptomatology moderately related to higher disgust propensity and higher anxiety, and weakly related to higher depressive symptomatology. This meta-analysis is the first to quantify that most adults with emetophobia are in early adulthood but the disorder started in childhood, almost all are women, the primary locus of fear is vomiting oneself, the most common comorbid mental disorders are other anxiety and affective disorders, and higher emetophobic symptomatology relates to a more general tendency to be easily disgusted and to be anxious. Studies based on representative samples to obtain reliable estimates on the prevalence of emetophobia are needed
CRISPR‐Cas9 screen reveals that inhibition of enhancer of zeste homolog 2 sensitizes malignant T cells to dimethyl‐fumarate‐induced cell death
No full textConstitutive activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway is a hallmark of many lymphocyte-associated cancers, including cutaneous T-cell lymphoma (CTCL) and its leukemic variant, the Sézary syndrome. Dimethyl fumarate (DMF) has been identified as a promising NF-κB-targeted therapy and has shown positive outcomes in a phase II clinical trial involving patients with Sézary syndrome. However, limited responsiveness remains a significant challenge. Through a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screen, we identified enhancer of zeste homolog 2 (EZH2; also known as histone-lysine N-methyltransferase) as a critical target for enhancing DMF-induced cell death. EZH2, the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), is responsible for the methylation of histone H3 (H3K27). Combining DMF with the US Food and Drug Administration (FDA)-approved EZH2 inhibitor tazemetostat significantly increases cell death in patient-derived CTCL cells, offering a promising strategy to improve therapeutic outcomes and overcome limited responsiveness to DMF
The burden of back pain on hospital staff in a maximum care facility in Germany – a survey
Full text linkPurpose:
Back pain is a prevalent musculoskeletal condition affecting individuals across various professions. It is a significant cause of disability and reduced quality of life. The aim of this study was to determinate the prevalence of back pain and identify its associated risk factors among clinical staff members.
Methods:
This study examines back pain among hospital-staff at a maximum-care hospital in Germany through a questionnaire distributed to all employees at a University Hospital between September and December 2023.
Results:
A total of 739 employee questionnaires were returned and evaluated, comprising 508 fully completed and 231 partially completed questionnaires. Seventy-seven percent of participants were female, and the average age was 40.5 years. Back pain-related reduced work performance was reported by 57.5 %. Lifetime lower back pain was indicated by 72.1 %. Mean pain ratings on the VAS were 7.5 ± 2.2 for lifetime pain and 6.2 ± 2.2 for the last 12 months. Female gender (OR = 1.5; p = 0.003), living in a partnership (OR = 1.4; p = 0.02), chronic illnesses (OR = 6.4; p = 0.01) and excessive workload (OR = 3.0; p = 0.05) were identified as risk factors, whereas membership in a sports club (OR = 0.55; p = 0.05) was identified as preventive factor. Participants that reported an aggravation of their back pain the COVID-19 pandemic were 6.4 times likely to report back pain during the last 12 months (p = 0.01).
Conclusion:
Back pain is a widespread condition among healthcare workers, leading to reduced performance and significant healthcare utilization. Employers should prioritize preventive measures and workplace ergonomics to mitigate this burden and enhance employee well-being and productivity
Functional analysis of the RNA polymerase I lobe binding subunits in different states of the transcription cycle
No full textDNA-dependent RNA polymerases (Pols) transcribe the genome of all organisms to RNA (transcriptom). Three nuclear Pols are common to all eukaryotic cells, namely Pol I, Pol II and Pol III. These highly specific multi-subunit enzymes transcribe different sets of genes and differ in subunit composition, associated regulatory elements, and accessory factors. In Saccharomyces cerevisiae, Pol I is composed of 14 subunits and transcribes exclusively ribosomal DNA. Despite its evolutionary conserved ten-subunit catalytic core shared with Pol II and Pol III, Pol I additionally contains the Pol-specific subunits A12.2, A34.5 and A49. These subunits are stably associated with its lobe domain and considered as built-in transcription factors due to functional and structural similarities with transcription factors of Pol II. While Pol II and its transcription factors have been intensively studied, less is known about Pol I and the role of its Pol I-specific subunits for different steps of the transcription cycle. Here, we used a new established Pol I in vitro reconstitution system and in vitro transcription assays with specific templates to investigate the function of different subdomains of A12.2, A34.5 and A49 on transcription initiation and transcription elongation to gain detailed insights for the mechanistic roles these subunits especially in Pol I transcription fidelity and processivity. Transcription fidelity relies either on correct nucleotide selection or on proofreading. While nucleotide selectivity seems to be less influenced by A12.2, A34.5 and A49, proofreading is strongly affected by these subunits. Proofreading entails RNA cleavage and backtracking after misincorporation of nucleotides, as well as re-extension of cleaved RNA. For sufficient RNA cleavage, Pol I requires the subunit A12.2, but not A34.5 and A49. More particularly, only full-length A12.2 containing the conserved amino acids D105 and E106 efficiently mediates RNA cleavage. By contrast, the C-terminal domain of A12.2 alone mediates insufficient RNA cleavage. We conclude that the covalent linkage between the C- and N-terminal domains of A12.2 as well as the amino acids D105/E106 are required for the high intrinsic cleavage activity of Pol I. Similar to the function of A12.2, TFIIS stimulates the intrinsic cleavage activity of Pol II thereby promoting proofreading. Domains of A12.2 and TFIIS are only partly exchangeable which gives mechanistic insights in the elongation/cleavage mode of Pol I and Pol II. Further, RNA cleavage activity as well as backtracking of Pol I is strongly stimulated by A34.5 together with A49 or the N-terminal and linker domains of A49 (A49NTL). Re-extension of cleaved RNAs is only promoted by full-length A49 in combination with A34.5. Experiments with different domains of the lobe binding subunits revealed that the cleavage activity in combination with either the heterodimer or A49LCT is required for processivity of Pol I. Summarizing, the interplay of the Pol I-specific subunits positively influence transcription elongation. It seems that domains of the Pol I-specific subunits have either a positive effect on transcription fidelity (A12.2 and A49NTL/A34.5) or on transcription processivity (A49LCT). Furthermore, I could show that the interplay between the Pol I-specific subunits A12.2, A34.5 or A49 Is not only important for efficient transcription elongation, but also for efficient transcription initiation. These results suggest that the interplay between the Pol I-specific subunits A12.2, A49 and A34.5 is not only important for efficient transcription elongation, but also for efficient transcription initiation.
Consequently, our results significantly contribute to the identification of functional similarities and differences between subdomains of Pol I-specific subunits and subdomains of corresponding transcription factors of Pol II for unravelling features unique to the Pol I machinery. For ongoing and future research, our experimental setup will help to fill the gap in knowledge about the Pol I machinery and its “built-in” factors and about their role in transcription termination including transcription through nucleosomes
Impact of Liver and Kidney Function on Vitamin D3 Metabolism in Female and Male Patients Undergoing Allogeneic Hematopoietic Stem-Cell Transplantation
No full textWe previously described that elevated levels of the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) during the early phase of allogeneic hematopoietic stem-cell transplantation (HSCT) can predict one-year transplant-related mortality (1y-TRM). Given that the liver and kidneys are the primary organs responsible for the effective conversion of vitamin D3, we investigated whether liver and/or kidney function, inflammation, or patient sex might influence vitamin D3 metabolism and, consequently, patient outcomes during transplantation. We found that female patients exhibited higher levels of 1,25(OH)2D3 at the time of transplantation compared with male patients. However, 1,25(OH)2D3 levels were associated with 1y-TRM in both sexes. No correlation was found between liver-associated markers, such as bilirubin, or the inflammation marker C-reactive protein (CRP) and serum levels of vitamin D3 metabolites in either female or male patients. However, serum levels of 1,25(OH)2D3, but not 25(OH)D3 correlated with the creatinine-based estimated glomerular filtration rate (eGFR), indicating that 1,25(OH)2D3 levels are associated with kidney function in HSCT patients. However, a Cox regression analysis, adjusted for baseline risk factors, demonstrated that high peri-transplant levels of 1,25(OH)2D3 (measured from days −2 to 7) remained a significant predictor of patient survival, even when eGFR was taken into account (hazard ratio = 0.99; p = 0.004). These findings suggest that optimal serum levels of 1,25(OH)2D3 may not be achievable in some HSCT patients and that kidney function alone cannot explain why some patients fail to reach the optimal 1,25(OH)2D3 threshold. These data support the potential use of 1,25(OH)2D3 as a prophylactic agent, particularly in patients with pre-existing kidney disease
Dataset to "Crossed Andreev reflection in topological insulator nanowire T junctions"
No full textNumerical data used in the figures of the publicatio
Pnictogenium Ions as a Powerful Tool for the Synthesis of Three‐ and Five‐Membered Interpnictogen Chains
No full textIntensive care needs after hip and knee replacement: understanding risk profiles for severe postoperative complications
No full textBackground
The etiology of serious life-threatening events after total joint arthroplasty (TJA) is poorly elaborated and understood in literature. The purpose of this study was to identify independent predictors of postoperative intensive care following total hip arthroplasty (THA) and total knee arthroplasty (TKA) and to clarify the circumstances leading to these transfers.
Material and methods
A total of 142 patients suffering from postoperative intensive care-dependent serious adverse events (Clavien–Dindo classification Grade IV, CD°IV) after THA or TKA were matched 1:1 with non-CD°IV patients using propensity score matching for age, sex, comorbidity (Charlson Comorbidity Index, CCI), and year of treatment. Possible predictive factors for the need of postoperative intensive care were initially evaluated using univariate tests, followed by multivariate regression analyses to identify independent predictors.
Results
CD°IV transfers correlate with higher Hospitality Frailty Risk Score levels (HFRS) [mean 4.4 (standard deviation, SD 3.8) versus mean 3.0 (SD 3.0); p < 0.001], higher American Society of Anesthesiologists Physical Status Classification System (ASA) Scores [mean 2.5 (SD 0.6) versus mean 2.3 (SD 0.7); p = 0.02], a greater proportion of octogenarians [35.9% (n = 51) versus 23.9% (n = 34); p = 0.028] and a higher incidence of medical complications [97.9% (n = 139) versus 60.6% (n = 86); p < 0.001] compared with an adjusted control group after total joint arthroplasty (TJA).
Multivariate regression analysis confirmed “Frailty” (odds ratio, OR 1.14, 95% confidence intervals, CI 1.05–1.23, p = .002), preexisting cardiological (odds ratio, OR 2.0, 95% confidence intervals, CI 1.004–4.1, p = 0.049) and gastrointestinal secondary diagnoses (OR 3.0, 95% CI 1.3–6.9, p = 0.01), and intake of anticoagulants (OR 2.7, 95% CI 1.6–4.6, p < 0.001) as independent risk factors for CD°IV intensive care unit (ICU) transfers after TJA.
Conclusions
Patients with CD°IV events after THA and TKA represent a complex, vulnerable, and multimorbid patient population. There is a need for a multidisciplinary approach that integrates prehabilitation and perioperative risk assessments to reduce the occurrence of severe, life-threatening events requiring ICU care