Вероятностный анализ перетоков по межсистемным связям

В результате проведенного анализа определен характер связей, а также характеристики, определяющие нагрузку ЛЭП, и их динамика. Исследована связь величин активных и реактивных мощностей при согласованных и встречных перетоках. Установлены достаточные статистические выборки, с приемлемой точностью описывающие процесс в целом

To what extent are psychological variables considered in the study of risk and protective factors for suicidal thoughts and behaviours in individuals with cancer? A systematic review of 70 years of research

Psychological variables substantially shape the risk of suicidal thoughts and behaviours (STBs). However, it is unclear to what extent they are considered in individuals with cancer. We synthesized the quantitative research landscape concerning psychological risk/protective factors of STBs in the (psycho-) oncological context. This pre-registered review (PROSPERO-ID CRD42022331484) systematically searched the databases PubMed/Medline, CINAHL, PsycInfo, Cochrane Library, and Web of Science (as well as the grey literature and preprints). Risk of bias (RoB) was estimated using the ROBINS-I tool. Of 11,159 retrieved records, 319 studies were eligible for inclusion. Of those, 163 (51.1%) had investigated psychological factors (affective: n = 155; social: n = 65; cognitive: n = 63; personality/individual differences: n = 37; life events: n = 6), in a combined 3,561,741 participants. The most common STBs were suicidal ideation (n = 107) or death wishes (n = 20) rather than behaviour (suicide deaths: n = 26; attempts: n = 14). Most studies had a serious RoB. Thus, a large body of research investigated STBs in cancer patients/survivors, but it rarely aligned with the theoretical or clinical developments in suicide research. We propose a conceptual model of STBs in cancer delineating moderation and mediation effects to advance the integration of the fields, and to future research and practice

Final Evaluation of a Clinical Phase III Trial Comparing Treosulfan to Busulfan-Based Conditioning Therapy Prior to Allogeneic Hematopoietic Stem Cell Transplantation of Adult Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients Ineligible to Standard Myeloablative Regimens

Background Allogeneic hematopoietic stem cell transplantation (HCT) remains a challenge in elderly and comorbid AML and MDS patients. This patient population is at increased risk for non-relapse mortality (NRM) when treated with standard myeloablative conditioning and was selected to compare a newly developed treosulfan-based with a well-established reduced intensity busulfan-based preparative regimen in a prospective randomized clinical phase III trial. Methods Adult patients with AML in remission or MDS scheduled for HCT from matched related or unrelated donors, aged ≥50 years or with a comorbidity index (HCT-CI) of >2 were enrolled by a central stratified randomization procedure. Treatment arms consisted of intravenous (IV) treosulfan (10 g/m²/day [d-4 to d-2]) or IV busulfan (3.2 mg/kg/day [d-4 to d-3]), both combined with IV fludarabine (30 mg/m²/day [d-6 to d-2]). The primary objective was to compare event-free survival (EFS) at two years with relapse/progression of disease, graft failure, or death reported as events. Secondary endpoints were safety evaluation (according to CTCAE v4.03), engraftment, chimerism, overall survival (OS), relapse/progression incidence (RI), NRM and acute or chronic GvHD. After a previously conducted confirmatory interim analysis (based on 476 patients), which resulted in early termination of patient accrual due to significant non-inferiority of treosulfan treatment with improved EFS, NRM and OS (Beelen et al., ASH 2017), results of the final analysis of all 570 randomized patients including post surveillance data are provided here. Results Median age of the 551 patients (352 AML; 199 MDS) included in the full analysis set (268 treosulfan; 283 busulfan) was 60 years (range: 31, 70). Frequencies of early adverse events (d-6 to d+28) and incidences of acute and chronic GvHD were largely comparable between the two regimens, while extensive chronic GvHD was numerically in favor of treosulfan (19.7% vs. 26.7%; p=0.0750). Primary neutrophil recovery at day +28 was comparable, while the rate of complete donor-type chimerism (day +28) was higher after treosulfan (93.2% vs. 83.3%; p Conclusions Final evaluation of this phase III trial substantiates the previous confirmatory analysis resulting in significantly improved survival after treosulfan-based conditioning. Due to the reduction of NRM a major clinical benefit of the new treosulfan conditioning regimen was demonstrated in the selected AML/MDS patient population

Nucleolar-nucleoplasmic shuttling of TARG1 and its control by DNA damage-induced poly-ADP-ribosylation and by nucleolar transcription

Macrodomains are conserved protein folds associated with ADP-ribose binding and turnover. ADP-ribosylation is a posttranslational modification catalyzed primarily by ARTD (aka PARP) enzymes in cells. ARTDs transfer either single or multiple ADP-ribose units to substrates, resulting in mono- or poly-ADP-ribosylation. TARG1/C6orf130 is a macrodomain protein that hydrolyzes mono-ADP-ribosylation and interacts with poly-ADP-ribose chains. Interactome analyses revealed that TARG1 binds strongly to ribosomes and proteins associated with rRNA processing and ribosomal assembly factors. TARG1 localized to transcriptionally active nucleoli, which occurred independently of ADP-ribose binding. TARG1 shuttled continuously between nucleoli and nucleoplasm. In response to DNA damage, which activates ARTD1/2 (PARP1/2) and promotes synthesis of poly-ADP-ribose chains, TARG1 re-localized to the nucleoplasm. This was dependent on the ability of TARG1 to bind to poly-ADP-ribose. These findings are consistent with the observed ability of TARG1 to competitively interact with RNA and PAR chains. We propose a nucleolar role of TARG1 in ribosome assembly or quality control that is stalled when TARG1 is re-located to sites of DNA damage

The effects of E2, the ERα -agonist ZK 281471 and the ERß-agonist ZK 281738 on the mammary tissue of the sprague-dawley-rat

Hintergrund: Der Zusammenhang zwischen der Hormonersatztherapie und Brustkrebs, untersucht anhand einer histologischen Tierstudie. Methoden: Nach 30-tägigen subkutanen Injektionen wurden die Einflüsse der Testsubstanzen (ERα-Agonist ZK 281471, ERß-Agonist ZK 281738) in verschiedenen Einzeldosen sowie in Kombination mit dem Antiöstrogen ICI 182,780 auf das Mammagewebe der Sprague-Dawley-Ratte untersucht. Anhand histologischer Schnitte, die mit Hämatoxylin und Eosin gefärbt wurden, erfolgte die Beurteilung der proliferationsaktivierenden Effekte der Testsubstanzen auf die Mammastrukturen Duktus und Lobulus im Vergleich zu einer unbehandelten Kontrollgruppe. Zur Bestätigung der östrogenen Wirkung des ERα-Agonisten ZK 281471 und ERß-Agonisten ZK 281738 diente die Bestimmung des Uterusgwichtes sowie der LH-und Prolaktinserumspiegel. Ergebnisse: Bezüglich des Uterusgewichtes und der LH-und Prolaktinserumspiegel zeigten der ERα-Agonist ZK 281471 und E2 nahezu identische Ergebnisse. Insbesondere in der mittleren und hohen Dosis führten beide Substanzen zur signifikanten Reduktion der LH-Serumspiegel und erhöhten die Prolaktin-Serumspiegel sowie das Uterusgewicht. Kombiniert mit ICI 182,780 ließen sich diese östrogenen Effekte inhibieren die LH-Serumspiegel stiegen an und die Prolaktinspiegel und das Uterusgewicht nahmen ab. Der ERß-Agonist ZK 281738 erzielte nur in hoher Dosis vergleichbare Effekte wie E2 und der ERα-Agonist ZK 281471. Ähnliche Resultate zeigten sich auch im Mammagewebe. Die Einzeldosen der Testsubstanzen übten in unteschiedlicher Ausprägung proliferierenden Einfluss auf die Mammastrukturen Duktus und Lobulus aus. Die Proliferationsraten der Testsubstanzen befanden sich nahezu alle oberhalb der Kontrollguppe, diejenigen der Duktus fast vollständig, die der Lobuli teilweise signifikant. Die ER-Agonisten ZK 281471 (ERα) und ZK 281738 (ERß) führten dabei zu einer fast durchgehend stärkeren Proliferation der Mammastrukturen als E2 in gleicher Dosis. Der ERß-Agonist ZK 281738 bewirkte nur in hoher Dosis ähnlich starke Proliferationen wie der ERα-Agonist ZK 281471. ICI 182,780 inhibierte nur die Proliferationsaktivität des ERα-Agonisten ZK 281471 und von E2. In Kombination mit dem ERß-Agonisten ZK 281738 zeigte es keine proliferationshemmende Wirkung. Zusammenfassung: Die Studie zeigte, dass der ERß-Agonist ZK 281738 am Brustgewebe nur in hoher Dosis eine ähnlich hohe Proliferationsaktivität erzielte wie der ERα-Agonist ZK 281471. Folglich liegt die Vermutung nahe, dass die östrogenen Effekte am Brustgewebe möglicherweise primär über den ERα vermittelt werden. Da die Proliferationsaktivität von E2 und des ERα-Agonisten ZK 281471 in Kombination mit ICI 182,780 inhibiert werden konnte, würde das Brustkrebsrisiko wahrscheinlich nicht erhöht werden. Im Gegensatz dazu liess sich die Proliferationsaktivität des ERß-Agonisten ZK 281738 durch ICI 182,780 nicht inhibieren, wodurch das Brustkrebsrisiko möglicherweise zunimmt

Seeing the past in a new light: Change in reports of childhood abuse and neglect before and after inpatient psychotherapy and its relevance for change in depression symptoms (Postprint)

Objective: As changes in mental representations have been discussed as mechanisms of change in psychotherapy, the question arises whether recollections of childhood abuse and neglect are altered as well and how they relate to symptom changes. Method: Individuals in psychosomatic inpatient treatment (N = 488, 60.5% women) filled out the Childhood Trauma Questionnaire (CTQ) and Patient Health Questionnaire (PHQ-9). Changes in both were investigated with correlations and t-tests. Linear regression analysis was used to test whether CTQ changes predicted symptom changes. Network analysis was performed to ascertain structural connections between somatic and emotional-cognitive depression symptoms and CTQ subscales before and after treatment. Results: After treatment (duration in days: M = 52.83, SD = 20.94), patients reported fewer depression symptoms (d = 0.84), while CTQ scores increased slightly (d = 0.11). Changes in the CTQ predicted recovery from depression symptoms in a statistically significant way (β = .133, p = .001). We did not observe changes in the overall network structure between baseline assessment and discharge. Conclusion: The findings suggest that the evaluation of past experiences can change over multiple weeks of psychotherapy. Further, these updated mental representations, indicating a greater recognition of past adversity, may contribute to symptom relief

A systematic review on sex- and gender-sensitive research in public mental health during the first wave of the COVID-19 crisis

Background Sex and gender are important modifiers of mental health and behavior in normal times and during crises. We investigated whether they were addressed by empirical, international research which explored the mental health and health behavior ramifications after the onset of the COVID-19 pandemic. Methods We systematically searched the databases PsyArXiv, PubMed, PsycInfo, Psyndex, PubPsych, Cochrane Library, and Web of Science for studies assessing mental health outcomes (main outcomes) as well as potential risk and protective health behavior (additional outcomes) up to July 2, 2020. Findings Most of the 80 publications fulfilling the selection criteria reflected the static difference perspective treating sex and gender as dichotomous variables. The focus was on internalizing disorders (esp. anxiety and depression) burdening women in particular, while externalizing disorders were neglected. Sex- and gender-specific evaluation of mental health care use has also been lacking. With respect to unfavorable health behavior in terms of adherence to prescribed protective measures, men constitute a risk group. Interpretations Women remain a vulnerable group burdened by multiple stresses and mental health symptoms. The neglect of sex and gender-specific evaluation of aggression-related disorders, substance addiction, and mental health care use in the early stage represents a potentially dangerous oversight

Geschlechterunterschiede bei Gewalterfahrungen und -auswirkungen

Rüweler M, Ernst C, Wattenberg I, Hornberg C. Geschlechterunterschiede bei Gewalterfahrungen und -auswirkungen. In: Hurrelmann K, Kolip P, eds. Handbuch Geschlecht und Gesundheit. Bern: Verlag Hans Huber; 2015