Hasil untuk "Other systems of medicine"

I. Jammer, Nadine Wickboldt, M. Sander et al.

P. Pound, N. Britten, M. Morgan et al.

Wenchuan Qi, Yida Wang, Sitthichock Vadphimai et al.

Objective:. Pre-mRNA alternative splicing (AS) is an important post-transcriptional regulation mechanism. The abnormal splicing of genes can lead to cardiovascular diseases. Acupuncture has been shown to alleviate myocardial ischemia-reperfusion injury (MIRI), but most studies have focused on the regulation of gene expression by acupuncture. Previously, we reported that electroacupuncture (EA) can relieve angina by regulating the AS of GABARG2; however, the genome-wide regulation of AS by EA remains unknown. Methods:. We explored the protective effects of EA on MIRI. We then studied the AS profiles retrieved from the previously submitted to Gene Expression Omnibus (GEO) database and analyzed the data using the replicate multivariate analysis of transcript splicing (rMATS) tool. Subsequently, we conducted validation experiments on splicing regulatory factors and their target genes modulated by EA, as identified through bioinformatics analysis. Results:. The results showed that EA at PC6 point could effectively alleviate MIRI. More than 200 differential alternative splicing events (ASEs) changed following MIRI. The differential ASEs underwent protein–protein interaction (PPI) network analysis, gene ontology (GO) enrichment, and pathway analysis, and were shown to be involved in distinct biological functions, especially in the maintenance of synaptic structure. Enrichment analysis also identified several pathways that are potentially associated with the progression of MIRI. Importantly, we identified critical ASEs and pathways that could be completely rescued by EA treatment. In the validation experiments, we found that AS of the key gene CAMK2G, associated with synaptic function, is regulated by the expression level of the MBNL1 protein modulated by EA. Conclusions:. Our results indicate that EA is not only an effective procedure to protect against MIRI by rescuing gene expression but also rescues abnormal ASEs. This study is a major contribution to a genome-wide comprehensive analysis of the regulation of AS by EA in MIRI.

Thompson CC, Saracco B, Pruthi A et al.

Carol C Thompson,1 Benjamin Saracco,2,3 Anika Pruthi,3 Elizabeth Cerceo4 1Department of Educational Leadership, Administration, and Research, Rowan University, Glassboro, NJ, USA; 2Rowan University Libraries, Rowan University, Glassboro, NJ, USA; 3Cooper Medical School of Rowan University, Rowan University, Camden, NJ, USA; 4Department of Medicine, Cooper Medical School of Rowan University, Camden, NJ, USACorrespondence: Carol C Thompson, Department of Educational Leadership, Administration, and Research, Rowan University, Glassboro, NJ, 08086, USA, Email thompsonc@rowan.eduAbstract: Alpha-gal syndrome (AGS), a tick-borne allergy, is increasing as its vectors migrate throughout the US and the world. There were an estimated 450,000 cases in the US. AGS reactions to mammalian foods and medical products include delayed anaphylaxis, urticaria, gastrointestinal and cardiac symptoms often difficult to connect to the source. Despite its seriousness, provider knowledge is limited. This rapid review investigated published works on AGS from 2020 to 24; it also sought to determine the breadth of AGs publications across different fields and specialties. We identified 355 studies of AGS diagnosis and management from 2020 to 2024 via Cochrane Central, Medline via the PubMed interface, and Embase (additional grey literature via Web of Science and Google Scholar). Studies were assessed for quality and risk of bias using JBI critical appraisal tools. Two hundred and nineteen studies met the criteria. One hundred and sixty-eight (77%) were full studies; 51 (23%) were conference presentations. Studies remained largely confined to allergy and immunology literature, despite their implications for other organ systems. Although patients present with symptoms to emergency departments and dermatology clinics there is a paucity of literature in those fields and others; several studies document practitioners’ lack of knowledge. Inclusion of content within medical school curricula is needed to establish foundational knowledge on the topic. With the increase in patients presenting with AGS, and with the reach of AGS across multiple fields, physicians and other health care providers need to be able to diagnose and then manage AGS with their patients. This rapid review has documented the problem of silos in disseminating information about AGS widely through the medical field. The remedy for a lack of practitioner knowledge is education.Keywords: tick-borne, allergy, mammalian products, provider knowledge, immunology, red meat

Adil Mardinoglu, Hasan Turkez, Minho Shong et al.

Abstract Generating longitudinal and multi-layered big biological data is crucial for effectively implementing artificial intelligence (AI) and systems biology approaches in characterising whole-body biological functions in health and complex disease states. Big biological data consists of multi-omics, clinical, wearable device, and imaging data, and information on diet, drugs, toxins, and other environmental factors. Given the significant advancements in omics technologies, human metabologenomics, and computational capabilities, several multi-omics studies are underway. Here, we first review the recent application of AI and systems biology in integrating and interpreting multi-omics data, highlighting their contributions to the creation of digital twins and the discovery of novel biomarkers and drug targets. Next, we review the multi-omics datasets generated worldwide to reveal interactions across multiple biological layers of information over time, which enhance precision health and medicine. Finally, we address the need to incorporate big biological data into clinical practice, supporting the development of a clinical decision support system essential for AI-driven hospitals and creating the foundation for an AI and systems biology-based healthcare model.

A. Santini, G. Tenore, E. Novellino

Satoru Sekine, Satoru Sekine, Yoshimi Sakurai et al.

IntroductionIn rehabilitation practices, expert therapists are believed to proficiently observe and assist patients. However, limited research has quantified the gaze behaviors of physical therapists during patient support. This study investigated the gaze patterns of expert and novice physical therapists from a first-person perspective during the process of assisting collaborators to stand. The aim was to determine which body parts received prolonged attention and to explore the characteristics of the support provided.MethodsSeven experienced physical therapists were recruited as expert participants, and 17 physical therapy students served as novice participants. We also recruited additional students as collaborators and asked them to behave as if they were patients. Both expert and novice participants wore a wearable eye tracker while assisting the collaborators to stand. We analyzed the gaze focus on specific body parts and the center of mass sway of the collaborators.ResultsExperts spent 10.75% of the total time gazing at the head area, compared to 4.06% for novices, with experts displaying significantly longer gaze durations (p < .05). Furthermore, there was a significant difference in the number of gaze fixations, with experts averaging 25.71 fixations and novices 8.65 (p < .05). Experts also facilitated a slower sway in the collaborator's center of mass (0.44 m/s for experts vs. 0.49 m/s for novices; p < .01) and positioned the collaborator with a more pronounced trunk flexion during sitting and standing transitions (41.0 degrees for experts vs. 37.8 degrees for novices; p < .01).DiscussionThe findings suggest that experts may monitor the collaborator's center of mass position by focusing on the head area. Properly positioning the head forward may allow for optimal forward movement of the center of mass, potentially reducing the effort required by the collaborator to stand. This study is the first to explore differences in support strategies through the measurement of physical therapists’ gaze during assistance.

Wei Liu, Wenyi Ge, Qi Zhao et al.

Abstract Background Dysphagia, a common complication of acute stroke, is associated with increased mortality and morbidity. Acupuncture, a widely used swallowing therapy in China, has been suggested as an effective therapy for treating Post-Stroke Dysphagia (PSD) by recent meta-analyses and guidelines. The use of resting-state functional Magnetic Resonance Imaging (rs-fMRI) and Diffusion Tensor Imaging (DTI) could explore the change of regional spontaneous neural activity, functional relationships between brain regions, and white matter connectivity patterns after acupuncture intervention for PSD. This trial aims to evaluate the efficacy of acupuncture treatment for PSD and explore its central mechanism by neuroimaging. Methods/design This randomized controlled trial will recruit 40 PSD patients. All patients will be randomized to either the Real Acupuncture (RA) or Sham Acupuncture (SA) group by a ratio of 1:1. All patients will receive immediate acupuncture treatment in the MRI scanning room, followed by four weeks of long-term acupuncture treatment. The primary outcomes are the rs-fMRI and DTI indicators, which will be evaluated after the immediate and long-term acupuncture treatment. The secondary outcomes are the scales that assess the efficacy, including the Functional Oral Intake Scale (FOIS), Water Swallowing Test (WST), Swallowing Quality Of Life Questionnaire (SWAL-QOL), and National Institute of Health Stroke Scale (NIHSS). The modified version of the Massachusetts General Hospital Acupuncture Sensation Scale (M-MASS) and fMRI sensation record table will also be evaluated. Discussion This protocol presents the design of a randomized, single-blind trial that will evaluate the efficacy and explore the neural plasticity of acupuncture treatment for PSD. This trial will deepen our insight into the clinical value of acupuncture for PSD and initially probe into the time-dosage-effect mechanism of acupuncture. Trial registration numbers Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2300067480. This study was registered on 9th January 2023.

Annamma Spudich

Renewed awareness of the potentials of traditional medical systems and the limits of biomedicine have opened the dialog on making integrative medical therapies more mainstream. The vast resources of traditional medical knowledge from classical medical texts, folk medical practices based on the rich biodiversity available in India, and sophisticated experimental science and biomedical practice, places India in a unique place to lead the effort into integrative medicine to address some of the emerging global health care issues. Frequent use of antibiotics for minor ailments, for example, have been shown to develop adverse consequences for individuals and for public health globally. Here I propose that educating the public with controlled outcome-based studies, on the power of traditional therapies to stimulate the immune system, enhance anti-inflammatory activities and to promote cell growth, are needed to bring back traditional remedies into everyday use for minor illnesses in place of commonly used biomedicines that have long term adverse consequences. For simplicity, such studies should begin with single medicinal plants that derive from folk and Ayurvedic traditions. In addition, fundamental principles underlying the efficacy of traditional therapies and their long-term advantage for wellness, needs to be integral parts of education of biomedical physicians to make integrative medicine a reality.

Matthew B Hoy

M. Sellami, O. Slimeni, A. Pokrywka et al.

The use of herbal medicinal products and supplements has increased during last decades. At present, some herbs are used to enhance muscle strength and body mass. Emergent evidence suggests that the health benefits from plants are attributed to their bioactive compounds such as Polyphenols, Terpenoids, and Alkaloids which have several physiological effects on the human body. At times, manufacturers launch numerous products with banned ingredient inside with inappropriate amounts or fake supplement inducing harmful side effect. Unfortunately up to date, there is no guarantee that herbal supplements are safe for anyone to use and it has not helped to clear the confusion surrounding the herbal use in sport field especially. Hence, the purpose of this review is to provide guidance on the efficacy and side effect of most used plants in sport. We have identified plants according to the following categories: Ginseng, alkaloids, and other purported herbal ergogenics such as Tribulus Terrestris, Cordyceps Sinensis. We found that most herbal supplement effects are likely due to activation of the central nervous system via stimulation of catecholamines. Ginseng was used as an endurance performance enhancer, while alkaloids supplementation resulted in improvements in sprint and cycling intense exercises. Despite it is prohibited, small amount of ephedrine was usually used in combination with caffeine to enhance muscle strength in trained individuals. Some other alkaloids such as green tea extracts have been used to improve body mass and composition in athletes. Other herb (i.e. Rhodiola, Astragalus) help relieve muscle and joint pain, but results about their effects on exercise performance are missing.

K. A. Szychowski, Bartosz Skóra, T. Pomianek et al.

The Inonotus obliquus (I. obliquus) mushroom was traditionally used to treat various gastrointestinal diseases. For many years, mounting evidence has indicated the potential of I. obliquus extracts for treatment of viral and parasitic infections. Furthermore, substances from I. obiquus have been shown to stimulate the immune system. The most promising finding was the demonstration that I. obliquus has hypoglycemic and insulin sensitivity potential. This review summarizes the therapeutic potential of I. obliquus extracts in counteracting the progression of cancers and diabetes mellitus as well as their antiviral and antiparasitic activities and antioxidant role. As shown by literature data, various authors have tried to determine the molecular mechanism of action of I. obliquus extracts. Two mechanisms of action of I. obliquus extracts are currently emerging. The first is associated with the broad-sense impact on antioxidant enzymes and the level of reactive oxygen species (ROS). The other is related to peroxisome proliferator-activated receptor gamma (PPARγ) effects. This receptor may be a key factor in the anti-inflammatory, antioxidant, and anti-cancer activity of I. obliquus extracts. It can be concluded that I. obliquus fits the definition of functional food and has a potentially positive effect on health beyond basic nutrition; however, studies that meet the evidence-based medicine (EBM) criteria are needed.

James I. Andorko, C. Jewell

Abstract Recent research in the vaccine and immunotherapy fields has revealed that biomaterials have the ability to activate immune pathways, even in the absence of other immune‐stimulating signals. Intriguingly, new studies reveal these responses are influenced by the physicochemical properties of the material. Nearly all of this work has been done in the vaccine and immunotherapy fields, but there is tremendous opportunity to apply this same knowledge to tissue engineering and regenerative medicine. This review discusses recent findings that reveal how material properties—size, shape, chemical functionality—impact immune response, and links these changes to emerging opportunities in tissue engineering and regenerative medicine. We begin by discussing what has been learned from studies conducted in the contexts of vaccines and immunotherapies. Next, research is highlighted that elucidates the properties of materials that polarize innate immune cells, including macrophages and dendritic cells, toward either inflammatory or wound healing phenotypes. We also discuss recent studies demonstrating that scaffolds used in tissue engineering applications can influence cells of the adaptive immune system—B and T cell lymphocytes—to promote regenerative tissue microenvironments. Through greater study of the intrinsic immunogenic features of implantable materials and scaffolds, new translational opportunities will arise to better control tissue engineering and regenerative medicine applications.

Xiaoli Chu, B. Sun, Qingchun Huang et al.

Modern computer technology sheds light on new ways of innovating Traditional Chinese Medicine (TCM). One method that gets increasing attention is the quantitative research method, which makes use of data mining and artificial intelligence technology as well as the mathematical principles in the research on rationales, academic viewpoints of famous doctors of TCM, dialectical treatment by TCM, clinical technology of TCM, the patterns of TCM prescriptions, clinical curative effects of TCM and other aspects. This paper reviews the methods, means, progress and achievements of quantitative research on TCM. In the core database of the Web of Science, "Traditional Chinese Medicine", "Computational Science" and "Mathematical Computational Biology" are selected as the main retrieval fields, and the retrieval time interval from 1999 to 2019 is used to collect relevant literature. It is found that researchers from China Academy of Chinese Medical Sciences, Zhejiang University, Chinese Academy of Sciences and other institutes have opened up new methods of research on TCM since 2009, with quantitative methods and knowledge presentation models. The adopted tools mainly consist of text mining, knowledge discovery, technologies of the TCM database, data mining and drug discovery through TCM calculation, etc. In the future, research on quantitative models of TCM will focus on solving the heterogeneity and incompleteness of big data of TCM, establishing standardized treatment systems, and promoting the development of modernization and internationalization of TCM.

Gholam-Hassan Danaei, Arian Amali, Mohammad Karami et al.

Abstract Background Diazinon (DZN), a widely used chemical herbicide for controlling agricultural pests, is an important organophosphorus pesticide and an environmental pollutant which induces toxic effects on living organisms during long-term exposure. Thymoquinone (TQ) is a phytochemical bioactive compound with antioxidant and anti-inflammatory properties. We aimed to evaluate the protective effects of TQ against DZN-induced hepatotoxicity through alleviating oxidative stress and enhancing cholinesterase (ChE) enzyme activity. Methods Rats were randomly divided into six groups (n = 8); a negative control group receiving corn oil; a group only receiving DZN (20 mg/kg/day); a group treated with TQ (10 mg/kg/day), and three treatment groups as TQ + DZN, receiving different doses of TQ (2.5, 5, and 10 mg/kg/day). All experimental animals were orally treated for 28 consecutive days. The levels of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactic acid dehydrogenase (LDH) were determined. In addition, ChE activity and histopathological changes were evaluated. Results The results showed that DZN decreased GSH level (p < 0.01) and SOD activity (p < 0.01) in parallel to an increase in MDA level (p < 0.01) and increased the activity of AST, ALT, ALP, and LDH (p < 0.01) in comparison to the negative control group. Our findings demonstrated that TQ administration could diminish hepatotoxicity and reduce oxidative damage in DZN-treated rats, which could be linked to its antioxidant and free radical scavenging properties. It was also observed that TQ 10 mg/kg remarkably increased the activity of acetylcholinesterase, butyrylcholinesterase, and SOD enzymes, elevated GSH, decreased MDA, and reduced pathological alternations of the liver induced by DZN. Conclusion Thymoquinone 10 mg/kg increased the activity of plasma and blood cholinesterases and reduced DZN-induced alternations of the liver. Improvement of butyryl- and acetylcholinesterase activity suggests that maybe TQ supplement could be beneficial as pre-exposure prophylaxis among farm workers spraying pesticides.

Zhenghui Pan, Mengqian Li, Zhiyu Jin et al.

Traditional Chinese Medicine (TCM) has some advantages, such as a multi-component, multi-target, and overall action, which makes the research on the compatibility of TCM formula a key and difficult point. On the contrary, network pharmacology (NP) uses high-throughput screening, computer simulation, and network database retrieval to reveal the drug–gene–target–disease interaction network, predict the mechanism of action of drugs through network relationships, and evaluate the efficacy and adverse reactions of drugs, thereby determining drugs with high efficiency and low toxicity. Therefore, the TCM formula has its unique TCM theories, and this paper primarily introduces the status quo of TCM compound prescriptions using TCM theories and NP, namely, the treatment theory of TCM (the core of TCM treatment and the principle of compatibility of TCM), as the theoretical guidance to evaluate drug's properties, efficacy, and toxicity. In addition, this study aims to predict drug's mechanism of action, interaction relationship, and matching selection to provide a high-efficiency and low-toxicity TCM formula and new insights into the follow-up study of TCM formula.

Renju Kunjumon, Anil John Johnson, Sabulal Baby

Background: Phytochemistry of Centella asiatica (CA) gained momentum after the discovery of asiaticoside in the early 1940s. Though there is lot of literature on this precious herb, its chemistry has not been comprehensively reviewed. Moreover, several duplicate names, synonyms and contradictory findings were observed in CA literature. The traditional, food and vegetable, pharmaceutical and cosmetic uses of CA are steadily on the rise, resulting in its ever increasing biomass requirements. Methods: This article is an inclusive review of the last eight decades of chemistry of CA. Its biological activities, food and beverage, cosmetic applications and natural and alternate biomass sources are also assessed. CA literature for this review was gathered from web-based resources such as PubMed, Scopus and Google Scholar, and chemical structures were drawn using ChemDraw software. Results: So far 139 secondary metabolites were isolated from CA, viz., ursane-type triterpenes (11), oleanane-type triterpenes (5), ursane-type triterpene glycosides (30), oleanane-type triterpene glycosides (14), dammarane-type triterpene glycosides (15), steroids (4), steroid glycosides (2), flavonoids (18), polyacetylenes (9), phenolic acids (13) and other miscellaneous compounds (18). Of these 139 compounds, 70 are new entities described for the first time. Most prominent CA metabolites are the four ursane type triterpenes, viz., asiatic acid, madecassic acid, asiaticoside and madecassoside. Naming issues and contradictory findings are resolved in this article. Biological activities of CA and its secondary metabolites are also reviewed. The wide use of CA as a vegetable and food ingredient is justified by the antioxidant activities of its phenolics, flavonoids and other constituents. The traditional uses, geographical sources, conservation status, industrial demand, elite clones, alternative sources, chemical variability, ecological and other allied parameters and quality control requirements of CA are also discussed in the context of its chemistry and secondary metabolites. Conclusion: This review emphasizes the need to study the biology of the least investigated CA metabolites, viz., oleanane-type triterpenoids, caffeoyl quinic acids, polyacetylenes, phenolics, miscellaneous compounds. Moreover, a comprehensive description of the secondary metabolites in CA will aid its future chemistry, biosynthesis, chemical transformation and biological activity studies.

Gistha Nugraha, Rosatyani Puspita Adiati

Tujuan dari penelitian ini adalah untuk mengetahui apakah kecerdasan emosional memiliki hubungan dengan work-life balance pada karyawan startup. Startup memiliki jam kerja yang fleksibel dan fast paced, sehingga waktu karyawan banyak dihabiskan untuk bekerja. Maka dari itu dibutuhkan kecerdasan emosional untuk dapat menentukan peran sesuai dengan situasi yang dibutuhkan. Meskipun begitu, terdapat penelitian lain yang memiliki hasil berlawanan. Metode yang digunakan adalah metode survei dengan teknik non-probability sampling dengan kriteria partisipan Warga Negara Indonesia, berdomisili di Indonesia, rentang usia 18 – 54 tahun serta bekerja di perusahaan startup. Alat ukur yang digunakan adalah The Assessing Emotions Scale (33 item) dan Work-life Balance Scale (17 item). Data dianalisis menggunakan Uji Korelasi Pearson product-moment. Hasil yang didapat adalah tidak terdapat hubungan yang signifikan antara kecerdasan emosional dengan work-life balance pada karyawan startup.

Patricia de Moraes Mello Boccolini, Cristiano Siqueira Boccolini

Background The use of medicinal plants or other alternative practices can be the only therapeutic resources for many communities and ethnic groups, especially in developing countries. In Brazil, the Ministry of Health incorporated Complementary and Alternative Medicine (CAM) as a public health policy since 2006. The aim of this study was to evaluate the prevalence of CAM use in Brazil. Methods This was a cross-sectional study performed as an epidemiological survey, with data from the National Health Survey, 2013 that evaluated a sample of adult Brazilians (18+ years old). The outcome was the use of CAM therapies, such as acupuncture, homeopathy, medicinal plants and herbal medicines in the last 12 months. We employed a logistic regression model (CI 95%) to evaluate the chances of CAM use. Results The prevalence of CAM use in Brazil was 4.5%. The subjects with higher chances to use CAM were: women (AOR = 1.42), aged > 40 years (AOR = 1.64), with higher educational levels (AOR = 2.35), and residents at North (AOR = 2.02) and South (AOR = 1.67) regions of Brazil, all with p -value < 0.001. According to the socioeconomic status, subjects from upper classes had higher chances to use acupuncture and homeopathy when compared to the other classes, and individuals from lower classes had higher chances to use medicinal plants and herbal medicines. Almost half of all individuals reporting CAM use did so outside the health care system. The Brazilian Unified Health System (SUS) was the least used funding for CAM when compared to other types of funding. Conclusions We recommend that the Ministry of Health invests in capacity building for health professionals who work with CAM, providing structure for those practices in health services, increasing the access of CAM therapies for SUS users, and improving the registering of information about those therapies, encouraging the use of CAM by the Brazilian population.

H. Prokosch, T. Acker, J. Bernarding et al.

Summary Introduction: This article is part of the Focus Theme of Methods of Information in Medicine on the German Medical Informatics Initiative. Similar to other large international data sharing networks (e.g. OHDSI, PCORnet, eMerge, RD-Connect) MIRACUM is a consortium of academic and hospital partners as well as one industrial partner in eight German cities which have joined forces to create interoperable data integration centres (DIC) and make data within those DIC available for innovative new IT solutions in patient care and medical research. Objectives: Sharing data shall be supported by common interoperable tools and services, in order to leverage the power of such data for biomedical discovery and moving towards a learning health system. This paper aims at illustrating the major building blocks and concepts which MIRACUM will apply to achieve this goal. Governance and Policies: Besides establishing an efficient governance structure within the MIRACUM consortium (based on the steering board, a central administrative office, the general MIRACUM assembly, six working groups and the international scientific advisory board), defining DIC governance rules and data sharing policies, as well as establishing (at each MIRACUM DIC site, but also for MIRACUM in total) use and access committees are major building blocks for the success of such an endeavor. Architectural Framework and Methodology: The MIRACUM DIC architecture builds on a comprehensive ecosystem of reusable open source tools (MIRACOLIX), which are linkable and interoperable amongst each other, but also with the existing software environment of the MIRACUM hospitals. Efficient data protection measures, considering patient consent, data harmonization and a MIRACUM metadata repository as well as a common data model are major pillars of this framework. The methodological approach for shared data usage relies on a federated querying and analysis concept. Use Cases: MIRACUM aims at proving the value of their DIC with three use cases: IT support for patient recruitment into clinical trials, the development and routine care implementation of a clinico-molecular predictive knowledge tool, and molecular-guided therapy recommendations in molecular tumor boards. Results: Based on the MIRACUM DIC release in the nine months conceptual phase first large scale analysis for stroke and colorectal cancer cohorts have been pursued. Discussion: Beyond all technological challenges successfully applying the MIRACUM tools for the enrichment of our knowledge about diagnostic and therapeutic concepts, thus supporting the concept of a Learning Health System will be crucial for the acceptance and sustainability in the medical community and the MIRACUM university hospitals.