["The total time spent by the general practitioner decreases": The referring physician's view of a palliative day care clinic]. / "Der zeitliche Gesamtaufwand für den Hausarzt sinkt": Die Sicht der Zuweisenden auf eine palliativmedizinische Tagesklinik.

BACKGROUND: Palliative day-care clinics (PDCCs) can complement inpatient and outpatient specialized palliative care. Some studies have shown improvements in the patients'́ symptoms, functional level and psychological well-being, while others have not. This study aimed to document the experience of referring physicians with PDCCs. METHOD: A postal questionnaire was sent to referring physicians between 11/2020 and 3/2021. The questionnaire included open and closed questions about professional background, symptom control, medical / psychosocial benefits for patients and challenges in the collaboration. Closed, 5-point scaled questions were analyzed descriptively with IBM SPSS Statistics 25®, open questions with a thematic content analysis using MAXQDA 2020®. RESULTS: Of the 96 referring physicians contacted, 76 questionnaires were returned (79%), 73 of which could be analyzed. Most referring physicians were general practitioners (57%), followed by oncologists (28%). 12% had completed further training in palliative medicine and had been working with patients with palliative care needs for an average of almost 19 years. On average, they had referred 24 patients (range 1-200) to a PDCC. 93% said that inpatient stays were delayed or avoided by PDCCs. 97% were of the opinion that their patients achieved a (great or rather great) benefit from medical treatment, and 96% thought that they benefited (to a great or rather great degree) from psychosocial treatment. 58% said that their own time spent with patients treated at the PDCC had decreased. In addition, a total of 227 open comments on challenges in cooperation, suggestions for optimization, reasons for referring patients and general wishes for PDCCs were analyzed. DISCUSSION: The high response rate to the questionnaires shows that PDCCs are of great importance to referring physicians. They consider the cooperation with PDCCs to be supportive and helpful for both themselves and their patients. CONCLUSION: PDCCs make an important contribution to palliative care. Almost all respondents believe that treatment at a PDCC prevents or delays hospitalization.

"My everyday life has returned to normal"- Experiences of patients and relatives with a palliative day care clinic: a qualitative evaluation study.

PURPOSE: Palliative day care clinics (PDCCs) complement inpatient and home palliative care and provide access to a range of multi-professional services. However, they are not part of standard care in Germany. Yet, international studies show that PDCCs have a positive impact on e.g. quality of life. To evaluate one of the first PDCCs in Germany (Aschaffenburg-Alzenau (PDCC-AA)) by describing the experiences, satisfaction, challenges, wishes of patients and relatives and possible alternatives to treatment in the PDCC. METHODS: Qualitative study using semi-structured telephone interviews. Data was analyzed using qualitative structuring content analysis according to Kuckartz with deductive a priori categories and inductive subcategories. RESULTS: A total of 31 patients and 38 relatives completed telephone interviews. The majority of patients were diagnosed with a cancer or tumor disease. The following four main themes emerged: (1) alternatives to treatment at the PDCC, (2) symptom relief, (3) sense of security, (4) "everyday life framing" (normality of everyday life). Participants valued the medical treatment (especially for pain), psychosocial support given and having direct access to a range of services (e.g., wound care and pleural drainage), while relatives valued being provided respite services. A sense of security, availability of therapies, and devoted time that healthcare providers spent to explain e.g., treatment options were mentioned most positively, as well as confidence in dealing with the illness. As to whether there was an alternative to treatment in the PDCC, some saw further inpatient stays, the emergency room or care by general practitioners as options (although not preferred). Patients expressed concern that they were not treated and informed according to their needs in other care settings. CONCLUSIONS: PDCCs may close a gap between inpatient and home palliative care. Participants mentioned that hospital stays can be delayed or even prevented.

Endothelin-1 driven proliferation of pulmonary arterial smooth muscle cells is c-fos dependent.

Pulmonary hypertension (PH) is characterized by enhanced pulmonary artery smooth muscle cell (PASMC) proliferation leading to vascular remodeling. Although, multiple factors have been associated with pathogenesis of PH the underlying mechanisms are not fully understood. Here, we hypothesize that already very short exposure to hypoxia may activate molecular cascades leading to vascular remodeling. Microarray studies from lung homogenates of mice exposed to only 3h of hypoxia revealed endothelin-1 (ET-1) and connective tissue growth factor (CTGF) as the most upregulated genes, and the mitogen-activated protein kinase (MAPK) pathway as the most differentially regulated pathway. Evaluation of these results in vitro showed that ET-1 but not CTGF stimulation of human PASMCs increased DNA synthesis and expression of proliferation markers such as Ki67 and cell cycle regulator, cyclin D1. Moreover, ET-1 treatment elevated extracellular signal-regulated kinase (Erk)-dependent c-fos expression and phosphorylation of c-fos and c-jun transcription factors. Silencing of c-fos with siRNA abrogated the ET-1-induced proliferation of PASMCs. Expression and immunohistochemical analyses revealed higher levels of total and phosphorylated c-fos and c-jun in the vessel wall of lung samples of human idiopathic pulmonary arterial hypertension patents, hypoxia-exposed mice and monocrotaline-treated rats as compared to control subjects. These findings shed the light on the involvement of c-fos/c-jun in the proliferative response of PASMCs to ET-1 indicating that already very short hypoxia exposure leads to the regulation of mediators involved in vascular remodeling underlying PH.

BDNF/TrkB signaling augments smooth muscle cell proliferation in pulmonary hypertension.

Pulmonary hypertension (PH) is a life-threatening disorder that is characterized by pulmonary arterial smooth muscle cell (PASMC) hyperplasia. Until now, little was been known about early changes that underlie the manifestation of PH. To characterize these early changes, we performed whole-genome microarray analysis of lungs from mice exposed to either 24 hours hypoxia or normoxia. TrkB, a member of the tyrosine kinase receptor family, and its ligand, brain-derived neurotrophic factor (BDNF), were strongly up-regulated in hypoxic mouse lungs, as well as in arteries of patients suffering from idiopathic pulmonary arterial hypertension (IPAH). BDNF stimulation of PASMC in vitro resulted in increased proliferation, TrkB and ERK1/2 phosphorylation, and nuclear translocation of the transcription factor early growth response factor 1 (Egr-1). In addition, increased Egr-1 expression was observed in idiopathic PAH lungs. The pro-proliferative effect of BDNF was attenuated by TrkB kinase inhibitor (K252a) or ERK1/2 inhibitor (U0126) pretreatment, and by knocking down Egr-1. Consequently, we have identified the BDNF-TrkB-ERK1/2 pathway as a proproliferative signaling pathway for PASMC in PH. Interference with this pathway may thus serve as an attractive reverse remodeling approach.

Systematic comparison of the T7-IVT and SMART-based RNA preamplification techniques for DNA microarray experiments.

BACKGROUND: Small biological samples obtained from biopsies or laser microdissection often do not yield sufficient RNA for successful microarray hybridization; therefore, RNA amplification is performed before microarray experiments. We compared 2 commonly used techniques for RNA amplification. METHODS: We compared 2 commercially available methods, Arcturus RiboAmp for in vitro transcription (IVT) and Clontech BD SMART for PCR, to preamplify 50 ng of total RNA isolated from mouse livers and kidneys. Amplification factors of 3 sequences were determined by real-time PCR. Differential expression profiles were compared within and between techniques as well as with unamplified samples with 10K 50mer oligomer-spotted microarrays (MWG Biotech). The microarray results were validated on the transcript and protein levels by comparison with public expression databases. RESULTS: Amplification factors for specific sequences were lower after 2 rounds of IVT than after 12 cycles of SMART. Furthermore, IVT showed a clear decrease in amplification with increasing distance of the amplified sequences from the polyA tail, indicating generation of smaller products. In the microarray experiments, reproducibility of the duplicates was highest after SMART. In addition, SMART-processed samples showed higher correlation when compared with unamplified samples as well as with expression databases. CONCLUSIONS: Whenever 1 round of T7-IVT does not yield sufficient product for microarray hybridization, which is usually the case when <200 ng of total RNA is used as starting material, we suggest the use of SMART PCR for preamplification.

Squint-induced Modification of Visual Receptive Fields in the Lateral Suprasylvian Cortex of the Cat: Binocular Interaction, Vertical Effect and Anomalous Correspondence.

In this study, we investigated the receptive field properties of single cells in the lateral suprasylvian area of strabismic cats. More than three times as many cells could be driven by the non-operated than by the operated eye. Many more cells could be activated by the contralateral than by the ipsilateral eye. In both area 17 and the lateral suprasylvian area, more cells preferred horizontal rather than vertical or oblique orientations ('vertical effect'). In addition, a small percentage of cells in the lateral suprasylvian area showed an adaptive shift of spatial coordinates; this shift could provide the neural basis of anomalous retinal correspondence.