[Psychiatry without coercion-Exclude the coercion or the patients?].

Background: With reference to the United Nations Convention on the Rights of Persons with Disabilities (UN CRPD), a fundamental change in psychiatric care in Germany was proposed in 2019 by Zinkler and von Peter, supported by a legal perspective from Kammeier, which has since led to controversial debates. Essentially, the aim is not only to reduce coercion in psychiatry to a minimum, but also to fundamentally exclude it in a psychiatry that only provides care. The function as an agent of social control is to be returned from psychiatry to state institutions.

City 5.0: Citizen involvement in the design of future cities.

A citizen-centric view is key to channeling technological affordances into the development of future cities in which improvements are made with the quality of citizens' life in mind. This paper proposes City 5.0 as a new citizen-centric design paradigm for future cities, in which cities can be seen as markets connecting service providers with citizens as consumers.

Irradiated Triple-Negative Breast Cancer Co-Culture Produces a Less Oncogenic Extracellular Matrix.

Triple-negative breast cancer is the most common and most deadly cancer among women. Radiation is a mainstay of treatment, administered after surgery, and used in the hope that any remaining cancer cells will be destroyed. While the cancer cell response is normally the focus of radiation therapy, little is known about the tumor microenvironment response after irradiation.

Activation of PPARα by Fenofibrate Attenuates the Effect of Local Heart High Dose Irradiation on the Mouse Cardiac Proteome.

Radiation-induced cardiovascular disease is associated with metabolic remodeling in the heart, mainly due to the inactivation of the transcription factor peroxisome proliferator-activated receptor alpha (PPARα), thereby inhibiting lipid metabolic enzymes. The objective of the present study was to investigate the potential protective effect of fenofibrate, a known agonist of PPARα on radiation-induced cardiac toxicity. To this end, we compared, for the first time, the cardiac proteome of fenofibrate- and placebo-treated mice 20 weeks after local heart irradiation (16 Gy) using label-free proteomics.

In vitro cellular and proteome assays identify Wnt pathway and CDKN2A-regulated senescence affected in mesenchymal stem cells from mice after a chronic LD gamma irradiation in utero.

Reliable data on the effects of chronic prenatal exposure to low dose (LD) of ionizing radiation in humans are missing. There are concerns about adverse long-term effects that may persist throughout postnatal life of the offspring. Due to their slow cell cycle kinetics and life-long residence time in the organism, mesenchymal stem cells (MSCs) are more susceptible to low level genotoxic stress caused by extrinsic multiple LD events.

[Community mental health approaches for avoidance of patient placement in closed psychiatric facilities-a positioning].

Background: In many cases the placement of people with mental disorders in closed residential homes is an expression of the lack of alternative care options. In the area of tension between the need for security in the case of chronically self-endangering behavior, recurrent acute psychiatric crisis interventions and a lack of perspective to establish a permanent therapy, in many places a placement in a closed facility approved under care law is carried out.

Objective: What alternatives are there to closed institutional care in the psychiatric care system in Germany?

Methods: A trialogical discussion process was carried out in an expert panel taking the relevant literature into consideration and with the participation of organizations of those affected and their relatives.

A Five-Year report on the conception and establishment of the MSc Radiation Biology at the Technical University of Munich.

Purpose: The MSc Radiation Biology course is a highly interdisciplinary degree program placing radiation biology at the interface between biology, medicine, and physics, as well as their associated technologies. The goal was to establish an internationally acknowledged program with diverse and heterogeneous student cohorts, who benefit from each other academically as well as culturally. We have completed a Five-Year evaluation of the program to assess our qualification profile and the further direction we want to take.

Integrated analysis of single-cell RNA-seq and bulk RNA-seq unravels tumour heterogeneity plus M2-like tumour-associated macrophage infiltration and aggressiveness in TNBC.

Triple-negative breast cancer (TNBC) is characterized by a more aggressive clinical course with extensive inter- and intra-tumour heterogeneity. Combination of single-cell and bulk tissue transcriptome profiling allows the characterization of tumour heterogeneity and identifies the association of the immune landscape with clinical outcomes. We identified inter- and intra-tumour heterogeneity at a single-cell resolution.

Extended in vitro culture of primary human mesenchymal stem cells downregulates Brca1-related genes and impairs DNA double-strand break recognition.

Mesenchymal stem cells (MSCs) are multilineage adult stem cells with considerable potential for cell-based regenerative therapies. In vitro expansion changes their epigenetic and cellular properties, with a poorly understood impact on DNA damage response (DDR) and genome stability. We report here results of a transcriptome-based pathway analysis of in vitro-expanded human bone marrow-derived mesenchymal stem cell (hBM-MSCs), supplemented with cellular assays focusing on DNA double-strand break (DSB) repair.

Oncogenic Linear Collagen VI of Invasive Breast Cancer Is Induced by CCL5.

The triple-negative breast tumor boundary is made of aligned, linear collagen. The pro-oncogenic impact of linear collagen is well established; however, its mechanism of formation is unknown. An in vitro analogue of the tumor border is created by a co-culture of MDA-MB-231 cells, adipose derived stem cells, and dermal fibroblasts.

A novel epigenetic signature for overall survival prediction in patients with breast cancer.

Background: Breast cancer is the most common malignancy in female patients worldwide. Because of its heterogeneity in terms of prognosis and therapeutic response, biomarkers with the potential to predict survival or assist in making treatment decisions in breast cancer patients are essential for an individualised therapy. Epigenetic alterations in the genome of the cancer cells, such as changes in DNA methylation pattern, could be a novel marker with an important role in the initiation and progression of breast cancer.

Long-term culture of mesenchymal stem cells impairs ATM-dependent recognition of DNA breaks and increases genetic instability.

Background: Mesenchymal stem cells (MSCs) are attracting increasing interest for cell-based therapies, making use of both their immuno-modulating and regenerative potential. For such therapeutic applications, a massive in vitro expansion of donor cells is usually necessary to furnish sufficient material for transplantation. It is not established to what extent the long-term genomic stability and potency of MSCs can be compromised as a result of this rapid ex vivo expansion.

Factors affecting the performance of public out-patient services.

Objective The delivery of public out-patient services is an essential part of complex healthcare systems, but the contribution of public out-patient services is often ill defined and poorly evaluated. The aim of this study was to identify and better understand those factors that may affect the performance of out-patient services to provide health service managers, clinicians and executives with a conceptual framework for future decision-making processes. Methods The present qualitative research involved five exploratory case studies.

Analytical confirmation of imidacloprid poisoning in granivorous Cape spurfowl (Pternistis capensis).

Reports were received that Cape spurfowl (Pternistis capensis) fell during flight and scrambled uncoordinatedly for cover and some died. Three carcases were submitted for necropsy examination, which revealed mainly congestion of the carcases and haemorrhages. Common causes of acute mortalities in birds were first excluded, but there was a history of possible exposure to imidacloprid-treated barley seeds.

NHEJ Contributes to the Fast Repair of Radiation-induced DNA Double-strand Breaks at Late Prophase I Telomeres.

Exposure of cells to ionizing radiation induces DNA double-strand breaks. To repair double-strand breaks correctly, cells must distinguish between the ends of chromosomes (telomeres) and DNA double-strand breaks within chromosomes. Double-strand breaks in telomeric DNA may lead to telomere shortening and mutagenesis.

Lifetime study in mice after acute low-dose ionizing radiation: a multifactorial study with special focus on cataract risk.

Because of the increasing application of ionizing radiation in medicine, quantitative data on effects of low-dose radiation are needed to optimize radiation protection, particularly with respect to cataract development. Using mice as mammalian animal model, we applied a single dose of 0, 0.063, 0.

Time to wait: a systematic review of strategies that affect out-patient waiting times.

Objective Out-patient waiting times pose a significant challenge for public patients in need of specialist evaluation and intervention. The aim of the present study was to identify and categorise effective strategies to reduce waiting times for specialist out-patient services with a focus on the Australian healthcare system. Methods A systematic review of major health databases was conducted using the key terms 'outpatient*' AND 'waiting time', 'process*' AND 'improvement in outpatient clinics'.

DNA repair kinetics in SCID mice Sertoli cells and DNA-PKcs-deficient mouse embryonic fibroblasts.

Noncycling and terminally differentiated (TD) cells display differences in radiosensitivity and DNA damage response. Unlike other TD cells, Sertoli cells express a mixture of proliferation inducers and inhibitors in vivo and can reenter the cell cycle. Being in a G-like cell cycle stage, TD Sertoli cells are expected to repair DSBs by the error-prone nonhomologous end-joining pathway (NHEJ).

p53-Dependent Senescence in Mesenchymal Stem Cells under Chronic Normoxia Is Potentiated by Low-Dose γ-Irradiation.

Mesenchymal stem cells (MSCs) are a source of adult multipotent cells important in tissue regeneration. Murine MSCs are known to proliferate poorly in vitro under normoxia. The aim of this study is to analyze the interaction of nonphysiological high oxygen and low-dose γ-irradiation onto growth, senescence, and DNA damage.

Three-dimensional microtissues essentially contribute to preclinical validations of therapeutic targets in breast cancer.

A 3D microtissues using T47D and JIMT-1 cells were generated to analyze tissue-like response of breast cancer cells after combined human epidermal growth factor receptor 2 (HER2)-targeted treatment and radiation. Following lentiviral knockdown of HER2, we compared growth rate alterations using 2D monolayers, 3D microtissues, and mouse xenografts. Additionally, to model combined therapeutic strategies, we treated HER2-depleted T47D cells and 3D microtissues using trastuzumab (anti-HER2 antibody) in combination with irradiation.

Short and long-term phototoxicity in cells expressing genetic reporters under nanosecond laser exposure.

Nanosecond-duration laser pulses are exploited in a plethora of therapeutic and diagnostic applications, such as optoacoustic imaging. However, phototoxicity effects of pulsed radiation in living cells, in particular those expressing genetic reporters, are not well understood. We established a three-dimensional fluorescent protein expressing cellular model in order to reliably investigate the extent and major exposure parameters responsible for both photobleaching and phototoxicity under pulsed laser exposure, unveiling a variety of possible effects on living cells, from reversible photobleaching to cytotoxicity and cell death.

Additive impact of HER2-/PTK6-RNAi on interactions with HER3 or IGF-1R leads to reduced breast cancer progression in vivo.

The human epidermal growth factor receptor 2 (HER2) and the protein tyrosine kinase 6 (PTK6) are often co- and over-expressed in invasive breast cancers. At early diagnosis, only distinct groups, such as HER2-or hormone receptor-positive benefit from a targeted therapy. However, a part of these tumours develops resistance within a year of administration of the drug but the majority of the patients depends on general therapies with severe side effects.

A Rb1 promoter variant with reduced activity contributes to osteosarcoma susceptibility in irradiated mice.

Background: Syndromic forms of osteosarcoma (OS) account for less than 10% of all recorded cases of this malignancy. An individual OS predisposition is also possible by the inheritance of low penetrance alleles of tumor susceptibility genes, usually without evidence of a syndromic condition. Genetic variants involved in such a non-syndromic form of tumor predisposition are difficult to identify, given the low incidence of osteosarcoma cases and the genetic heterogeneity of patients.