The Germans vs. Mario Draghi

As the stress in financial markets is bound to return, the ECB and its president may run into a severe reputational crisis in the Eurozone’s biggest country. This column looks at the deeper roots of German anti-ECB sentiment

Perceived Limitations of Telemedicine from a Phenomenological Perspective

In the course of healthcare digitization, the roles of therapists and patients are likely to change. To shape a theoretical based process of technological transformation, a phenomenological perspective on Information and Communication Technology (ICT) is introduced. Therefore, this paper illustrates the benefit of a holistic view on patients and therapists to describe and explain phenomena concerning Human Technology Interaction (HTI). The differentiation between a measurable objective body and a habitual subjective body helps to evaluate and anticipate constituting factors of accepting telemedicine systems. Taking into account findings from a secondary analysis of semi-structured interviews we conducted with primary care physicians, we develop a phenomenological framework for HTI in healthcare. Our aim is to structure future research concerning design implications for ICT and the implementation of telemedicine systems in clinical and primary care

Building Digital Bridges: Exploring the Digitized Collaboration of General Practitioners and Mobile Care in Rural Areas

In the process of digitalization of healthcare, professionals, such as mobile care nurses or general practitioners, are facing both new challenges and opportunities. Digital technologies thereby promise to affect the cooperation of healthcare professionals on various levels, e.g., increasing quality of care, improving interprofessional communication, or optimizing economic aspects of care. Our study examines current issues of healthcare professionals concerning a digital change of care. We conducted qualitative interviews with primary care practitioners and providers of mobile care (nurses and care managers) to understand perceived obstacles in the process of digitalization and to formulate possible implications to encounter those obstacles. Our results suggest that insufficient communication and a lack of mutual trust have to be considered relevant issues. We therefore propose to focus future research on the interchangeability of different communication and documentation systems

Beyond Intuition: Towards a Framework for Empirical-Based Design Theory Building in Design Science Research

Over the past twenty years, Design Science Research (DSR) has received major attention within the IS domain. Besides constructing and evaluating artefacts, researchers put effort into theorizing on IT design and its effects on users. Here, the development and testing of design theories is of major interest. Yet, design theory studies often lack empirical investigations on the identification of appropriate design features. Whereas in general DSR activities incorporate empirical investigations on many levels, the intertwined development of a theoretical model in connection with design features can further profit from empirical investigations by exploring the design realm of a specific context. We therefore propose a qualitative five-step approach suitable for inducing design features and theoretical constructs by engaging experienced stakeholders. We present a case study on the development of a support system for physiotherapeutic treatments, illustrating the proposed approach

Virtual Reality Technologies in Health Care: A Literature Review of Theoretical Foundations

The digitization of health care promises an improvement of medical care through the adoption of virtual reality (VR) related technologies. Although most undergoing mechanisms of clinical effectiveness are yet not defined theoretically, research approaches have already taken place in several empirical settings. To structure current and upcoming scientific work in this field, we conducted a literature review with regard to theoretical implications of both IS-related and healthcare-related research. We found several theoretical bases to build upon in the field of psychology, but expressed a need for enrichment of theoretical foundations in the field of IS research. We therefore plead for a theoretical foundation enriched by synergetic concepts of clinically effective VR related technologies. Finally, we conclude that VR related technologies appear as a promising approach worth further theoretical and empirical research in order to improve medical care

hsa‐miR‐374b‐5p regulates expression of the gene U2AF homology motif (UHM) kinase 1

Objective: We aimed to identify a microRNA (miRNA) that is significantly upregulated in blood and in cells of the oral mucosa upon exposure to the periodontitis main risk factors oral inflammation and tobacco smoke, to subsequently identify its target gene and to describe the molecular mechanism of gene regulation. Background: miRNAs are associated with many disorders. Array-based miRNA expression studies indicated a number of differentially expressed miRNAs in the pathology of oral diseases. However, these miRNAs mostly lacked replication, and their target genes have remained unknown. Methods: 863 miRNAs were analyzed in blood from 18 PD cases and 70 controls (Geniom Biochip). Selected miRNAs were analyzed for upregulation in the inflamed oral mucosa of PD patients using published miRNA expression profiling studies from gingival cells. hsa-miR-374b-5p mimic was overexpressed in primary gingival fibroblasts (pGFs) from 3 donors, and genome-wide mRNA expression was quantified (Clarion Array). Gene-specific regulation was validated by qRT-PCR and Luciferase activity in HeLa cells. Results: hsa-miR-374b-5p showed >twofold change (FC) in 3 independent studies performed in blood, gingival tissues, and cells. After hsa-miR-374b-5p overexpression, genome-wide expression analysis showed UHMK1 as top 1 downregulated gene in pGFs (p = 2.5 × 10-04 , fold change = -1.8). Reporter genes demonstrated that hsa-miR-374b-5p downregulates mRNA levels (p = .02; FC = -1.5), leading to reduction in protein activity (p = .013, FC = -1.3). Conclusions: hsa-miR-374b-5p is upregulated in blood and ginvial cells exposed to oral inflammation and tobacco smoke and regulates UHMK1, which has a role in osteoclast differentiation

A microglial activity state biomarker panel differentiates FTD-granulin and Alzheimer's disease patients from controls

BackgroundWith the emergence of microglia-modulating therapies there is an urgent need for reliable biomarkers to evaluate microglial activation states.MethodsUsing mouse models and human induced pluripotent stem cell-derived microglia (hiMGL), genetically modified to yield the most opposite homeostatic (TREM2-knockout) and disease-associated (GRN-knockout) states, we identified microglia activity-dependent markers. Non-targeted mass spectrometry was used to identify proteomic changes in microglia and cerebrospinal fluid (CSF) of Grn- and Trem2-knockout mice. Additionally, we analyzed the proteome of GRN- and TREM2-knockout hiMGL and their conditioned media. Candidate marker proteins were tested in two independent patient cohorts, the ALLFTD cohort (GRN mutation carriers versus non-carriers), as well as the proteomic data set available from the EMIF-AD MBD study.ResultsWe identified proteomic changes between the opposite activation states in mouse microglia and CSF, as well as in hiMGL cell lysates and conditioned media. For further verification, we analyzed the CSF proteome of heterozygous GRN mutation carriers suffering from frontotemporal dementia (FTD). We identified a panel of six proteins (FABP3, MDH1, GDI1, CAPG, CD44, GPNMB) as potential indicators for microglial activation. Moreover, we confirmed three of these proteins (FABP3, GDI1, MDH1) to be significantly elevated in the CSF of Alzheimer's (AD) patients. Remarkably, each of these markers differentiated amyloid-positive cases with mild cognitive impairment (MCI) from amyloid-negative individuals.ConclusionsThe identified candidate proteins reflect microglia activity and may be relevant for monitoring the microglial response in clinical practice and clinical trials modulating microglial activity and amyloid deposition. Moreover, the finding that three of these markers differentiate amyloid-positive from amyloid-negative MCI cases in the AD cohort suggests that these proteins associate with a very early immune response to seeded amyloid. This is consistent with our previous findings in the Dominantly Inherited Alzheimer's Disease Network (DIAN) cohort, where soluble TREM2 increases as early as 21 years before symptom onset. Moreover, in mouse models for amyloidogenesis, seeding of amyloid is limited by physiologically active microglia further supporting their early protective role. The biological functions of some of our main candidates (FABP3, CD44, GPNMB) also further emphasize that lipid dysmetabolism may be a common feature of neurodegenerative disorders

Granulysin-Expressing CD4+ T Cells as Candidate Immune Marker for Tuberculosis during Childhood and Adolescence

BACKGROUND: Granulysin produced by cytolytic T cells directly contributes to immune defense against tuberculosis (TB). We investigated granulysin as a candidate immune marker for childhood and adolescent TB. METHODS: Peripheral blood mononuclear cells (PBMC) from children and adolescents (1-17 years) with active TB, latent TB infection (LTBI), nontuberculous mycobacteria (NTM) infection and from uninfected controls were isolated and restimulated in a 7-day restimulation assay. Intracellular staining was then performed to analyze antigen-specific induction of activation markers and cytotoxic proteins, notably, granulysin in CD4(+) CD45RO(+) memory T cells. RESULTS: CD4(+) CD45RO(+) T cells co-expressing granulysin with specificity for Mycobacterium tuberculosis (Mtb) were present in high frequency in TB-experienced children and adolescents. Proliferating memory T cells (CFSE(low)CD4(+)CD45RO(+)) were identified as main source of granulysin and these cells expressed both central and effector memory phenotype. PBMC from study participants after TB drug therapy revealed that granulysin-expressing CD4(+) T cells are long-lived, and express several activation and cytotoxicity markers with a proportion of cells being interferon-gamma-positive. In addition, granulysin-expressing T cell lines showed cytolytic activity against Mtb-infected target cells. CONCLUSIONS: Our data suggest granulysin expression by CD4(+) memory T cells as candidate immune marker for TB infection, notably, in childhood and adolescence

Removing Biofilms from Microstructured Titanium Ex Vivo: A Novel Approach Using Atmospheric Plasma Technology

The removal of biofilms from microstructured titanium used for dental implants is a still unresolved challenge. This experimental study investigated disinfection and removal of in situ formed biofilms from microstructured titanium using cold atmospheric plasma in combination with air/water spray. Titanium discs (roughness (Ra): 1.96 µm) were exposed to human oral cavities for 24 and 72 hours (n = 149 each) to produce biofilms. Biofilm thickness was determined using confocal laser scanning microscopy (n = 5 each). Plasma treatment of biofilms was carried out ex vivo using a microwave-driven pulsed plasma source working at temperatures from 39 to 43°C. Following plasma treatment, one group was air/water spray treated before re-treatment by second plasma pulses. Vital microorganisms on the titanium surfaces were identified by contact culture (Rodac agar plates). Biofilm presence and bacterial viability were quantified by fluorescence microscopy. Morphology of titanium surfaces and attached biofilms was visualized by scanning electron microscopy (SEM). Total protein amounts of biofilms were colorimetrically quantified. Untreated and air/water treated biofilms served as controls. Cold plasma treatment of native biofilms with a mean thickness of 19 µm (24 h) to 91 µm (72 h) covering the microstructure of the titanium surface caused inactivation of biofilm bacteria and significant reduction of protein amounts. Total removal of biofilms, however, required additional application of air/water spray, and a second series of plasma treatment. Importantly, the microstructure of the titanium discs was not altered by plasma treatment. The combination of atmospheric plasma and non-abrasive air/water spray is applicable for complete elimination of oral biofilms from microstructured titanium used for dental implants and may enable new routes for the therapy of periimplant disease