The disrupted molecular circadian clock of monocytes and macrophages in allergic inflammation.

Introduction: Macrophage dysfunction is a common feature of inflammatory disorders such as asthma, which is characterized by a strong circadian rhythm. Methods and results: We monitored the protein expression pattern of the molecular circadian clock in human peripheral blood monocytes from healthy, allergic, and asthmatic donors during a whole day. Monocytes cultured of these donors allowed us to examine circadian protein expression in human monocyte-derived macrophages, M1- and M2- polarized macrophages. In monocytes, particularly from allergic asthmatics, the oscillating expression of circadian proteins CLOCK, BMAL, REV ERBs, and RORs was significantly altered. Similar changes in BMAL1 were observed in polarized macrophages from allergic donors and in tissue-resident macrophages from activated precision cut lung slices. We confirmed clock modulating, anti-inflammatory, and lung-protective properties of the inverse ROR agonist SR1001 by reduced secretion of macrophage inflammatory protein and increase in phagocytosis. Using a house dust mite model, we verified the therapeutic effect of SR1001 in vivo. Discussion: Overall, our data suggest an interaction between the molecular circadian clock and monocytes/macrophages effector function in inflammatory lung diseases. The use of SR1001 leads to inflammatory resolution in vitro and in vivo and represents a promising clock-based therapeutic approach for chronic pulmonary diseases such as asthma.

Catch Recognition in Automated American Football Training Using Machine Learning.

In order to train receivers in American football in a targeted and individual manner, the strengths and weaknesses of the athletes must be evaluated precisely. As human resources are limited, it is beneficial to do it in an automated way. Automated passing machines are already given, therefore the motivation is to design a computer-based system that records and automatically evaluates the athlete's catch attempts. The most fundamental evaluation would be whether the athlete has caught the pass successfully or not. An experiment was carried out to gain data about catch attempts that potentially contain information about the outcome of such. The experiment used a fully automated passing machine which can release passes on command. After a pass was released, an audio and a video sequence of the specific catch attempt was recorded. For this purpose, an audio-visual recording system was developed which was integrated into the passing machine. This system is used to create an audio and video dataset in the amount of 2276 recorded catch attempts. A Convolutional Neural Network (CNN) is used for feature extraction with downstream Long Short-Term Memory (LSTM) to classify the video data. Classification of the audio data is performed using a one-dimensional CNN. With the chosen neural network architecture, an accuracy of 92.19% was achieved in detecting whether a pass had been caught or not. The feasibility for automatic classification of catch attempts during automated catch training is confirmed with this result.

Monocytes and Macrophages Serve as Potent Prostaglandin D2 Sources during Acute, Non-Allergic Pulmonary Inflammation.

Acute respiratory inflammation, most commonly resulting from bacterial or viral infection, is one of the leading causes of death and disability worldwide. The inflammatory lipid mediator prostaglandin D2 (PGD2) and its rate-limiting enzyme, hematopoietic PGD synthase (hPGDS), are well-known drivers of allergic pulmonary inflammation. Here, we sought to investigate the source and role of hPGDS-derived PGD2 in acute pulmonary inflammation. Murine bronchoalveolar monocytes/macrophages from LPS- but not OVA-induced lung inflammation released significant amounts of PGD2. Accordingly, human monocyte-derived macrophages expressed high basal levels of hPGDS and released significant levels of PGD2 after LPS/IFN-γ, but not IL-4 stimulation. Human peripheral blood monocytes secreted significantly more PGD2 than monocyte-derived macrophages. Using human precision-cut lung slices (PCLS), we observed that LPS/IFN-γ but not IL-4/IL-13 drive PGD2 production in the lung. HPGDS inhibition prevented LPS-induced PGD2 release by human monocyte-derived macrophages and PCLS. As a result of hPGDS inhibition, less TNF-α, IL-6 and IL-10 could be determined in PCLS-conditioned medium. Collectively, this dataset reflects the time-dependent release of PGD2 by human phagocytes, highlights the importance of monocytes and macrophages as PGD2 sources and suggests that hPGDS inhibition might be a potential therapeutic option for acute, non-allergic lung inflammation.

[Treatment of psychosomatic disorders occurring in the vocational context - concept and first findings ]. / Behandlung psychosomatischer Beschwerden im Arbeitskontext - Konzept und erste Daten.

OBJECTIVES: Psychosomatic symptoms often present within the vocational context. The unmet need for easily accessible and early interventions led to the development of a variety of offers in this area. From a scientific point of view, the question of how such a "psychosomatic consultation in the workplace" (PCIW) is best conceptualized remains open. METHODS: We analysed treatment documentation for all patients of two recently established PCIW from January 2011 to January 2012 both descriptively and by qualitative content analysis. RESULTS: A total of 67 patients were seen, 75% of whom were male. For 75% of users PCIW constituted the first contact with psychosomatic-psychotherapeutic-psychiatric services. For about 80%of the patients a work-related aetiology could be considered. 40%of patients were recommended to outpatient psychotherapeutic care. CONCLUSIONS: PCIW represents an easily accessible therapeutic offer in the vocational context. There often is a mix of work-related and personal problems that suggests the cooperation of occupational and psychosomatic physicians.

Patients and staff perceptions of cancer patients' quality of life.

BACKGROUND: Discrepancies exist in estimation of quality of life (QL) by patients and caregivers but underlying factors are incompletely characterised. METHODS: QL of 153 patients was estimated by themselves, by 70 nurses and by 53 physicians in a cross-sectional study. Variables which could influence inter-rater agreement were evaluated. RESULTS: Inter-rater agreement of QL was fair (r = .292) between patients and nurses and between patients and physicians (r = .154). Inter-rater agreement with nurses was significantly lower concerning fatigue and pain for patients with a Karnofsky Index <50 when compared to patients with a KI > 50. Their inter-rater agreement with physicians was significantly lower for fatigue, pain and physical functioning. Agreement on the degree of anxiety was significantly (p = .009) better for female patients. Agreement on the need for social assistance (p = .01) and physical functioning (p = .03) was significantly better for male patients. Agreement with patients on their physical functioning was significantly (p = .03) better for male nurses and male physicians (r = .944) than for female nurses and female physicians (r = .674). CONCLUSIONS: Our study showed that estimation of overall QL of patients by professional caregivers is inaccurate. Inter-rater agreement was influenced by KI of patients, by gender of patients and caregivers and by professional experience of nurses.