Adipocyte C1QTNF5 expression is BMI-dependently related to early adipose tissue dysfunction and systemic CTRP5 serum levels in obese children.

BACKGROUND/OBJECTIVES: The recently identified adipocytokine C1QTNF5 (encodes for CTRP5) has been demonstrated to inhibit pro-metabolic insulin signaling in adipocytes. We hypothesized that adipocyte C1QTNF5 expression in subcutaneous (sc) adipose tissue (AT) would correlate with the degree of obesity, systemic CTRP5 serum levels, and early AT and metabolic dysfunction in children. SUBJECTS/METHODS: Sc AT samples were obtained from 33 healthy Caucasian lean children aged 10.06±4.84 years and 42 overweight and obese children aged 13.34±3.12 years. C1QTNF5 expression in sc AT as well as in investigated cell lines was assessed by quantitative real-time PCR. Systemic CTRP5 levels were assessed by ELISA. RESULTS: C1QTNF5 expression in sc adipocytes increased with body mass index (BMI) standard deviation score (SDS; R=0.48, P<0.001), body fat percentage (R=0.4, P=0.004), adipocyte number (R=0.69, P<0.001) and systemic CTRP5 serum levels (R=0.28, P=0.025) whereas expression in the stromal vascular fraction (SVF) was inversely correlated with BMI SDS (R=-0.24, P=0.04). Multiple regression analysis confirmed that BMI SDS was the strongest independent predictor for C1QTNF5 expression in sc adipocytes. SVF C1QTNF5 levels strongly correlated with SVF CD31 expression (R=0.54, P<0.001) indicating expression by endothelial cells. Primary human endothelial cells demonstrated stronger expression compared with human Simpson-Golahbi-Behmel syndrome pre-adipocytes and adipocytes. Adipocyte C1QTNF5 expression levels were BMI-dependently related to fasting insulin (R=0.3, P=0.03) and leptin serum levels (R=0.5, P<0.001). Sc AT samples containing crown-like structures (CLS) demonstrated increased adipocyte C1QTNF5 expression compared to CLS-negative samples (P=0.03). Functionally, tumor necrosis factor (TNF)α caused a fourfold induction of C1QTNF5 in human adipocytes (P<0.001) and a 50% reduction in primary human endothelial cells (P<0.001). CONCLUSIONS: In children adipocyte C1QTNF5 expression is already strongly related to the degree of obesity and is associated with obesity-related AT alterations, systemic CTRP5 serum levels as well as circulating markers of metabolic disease and is positively regulated by TNFα in vitro.

METRNL decreases during adipogenesis and inhibits adipocyte differentiation leading to adipocyte hypertrophy in humans.

BACKGROUND: Meteorin-like (METRNL) is a recently described circulating protein shown to be highly expressed in white adipose tissue and to beneficially affect energy metabolism in mice. OBJECTIVE: We systematically evaluated the role of METRNL for human adipogenesis and its association with obesity, browning and hyperinsulinemia in children. In addition, we assessed the functional relevance of METRNL for human adipogenesis. RESULTS: METRNL expression decreased during human adipocyte differentiation in vitro. Coherently, METRNL expression was lower in isolated adipocytes compared with stromal vascular fraction (SVF) cells in human samples. Withdrawal of the peroxisome proliferator-activated receptor-γ (PPARγ) agonist rosiglitazone from adipogenic media partially preserved the METRNL downregulation during adipogenesis. METRNL expression was higher in adipocytes of obese compared with lean children and correlated with adipocyte size, whereas in SVF METRNL expression correlated with proliferation capacity. Concordantly, overexpression of METRNL inhibited human adipocyte differentiation as shown by decreased lipogenesis and lower expression of PPARγ and markers of adipogenesis, whereas experimental downregulation promoted adipogenesis. Proliferation, in contrast, was advanced by METRNL overexpression. These interactions with adipose tissue dynamics may contribute to the clinically observed body mass index-independent association of METRNL expression with hyperinsulinemia and adipose tissue inflammation in human samples. METRNL was not associated with UCP1 expression or induction of browning in white adipocytes. CONCLUSIONS: Taken together, the downregulation of METRNL during adipogenesis and functional induction of increased proliferation in SVF cells with concomitant inhibition of adipocyte differentiation may result in hypertrophic AT accumulation. This may also explain our observations of increased METRNL expression in adipocytes but not SVF cells in obese children compared with lean children and the subsequent hyperinsulinemia.

The lower saxony bank of health. rationale, principles, services, organization and architectural framework.

INTRODUCTION: This article is part of a Focus Theme of METHODS of Information in Medicine on Health Record Banking. BACKGROUND: Poor communication of health care information between health care providers (HCP) is still a major problem. One recent approach is the concept of Health Record Banking. OBJECTIVES: With this report we want to introduce the Lower Saxony Bank of Health (LSBH) to the international community. The main objective of this paper is to report and explain: 1) why this organization has been founded, 2) which basic principles have been set, 3) which services will be provided, 4) which type of organization has been chosen, and 5) which architectural framework has been selected. METHODS: To report and discuss how we plan to achieve the intended objectives. RESULTS: The LSBH was founded as an entrepreneurial company, regarding itself as a neutral third-party information broker. The bank does not store medical documents on its central servers but offers a document registry with links to documents stored at participating health care providers. Subject to valid patient consent, the LSBH grants access to these documents to authorized health care providers. To implement our services, we chose the established technical frameworks of the Integrating the Healthcare Enterprise (IHE) initiative using cross-enterprise document sharing (XDS). CONCLUSIONS: Different approaches to establish health information exchange (HIE) are in early stages and some have failed in the past. Health Record Banking can address major challenges described in the literature about HIE. The future will show if our provider-sponsored business model is sustainable. After reaching a stable network, we intend to add additional HCPs, e.g., care homes or ambulance services, to the network.

Home-centered health-enabling technologies and regional health information systems. An integration approach based on international standards.

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Using Data from Ambient Assisted Living and Smart Homes in Electronic Health Records". OBJECTIVES: In this paper, we present a prototype of a Home-Centered Health-Enabling Technology (HET-HC), which is able to capture, store, merge and process data from various sensor systems at people's home. In addition, we present an architecture designed to integrate HET-HC into an exemplary regional Health Information System (rHIS). METHODS: rHIS are traditionally document-based to fit to the needs in a clinical context. However, HET-HC are producing continuous data streams for which documents might be an inappropriate representation. Therefore, the HET-HC could register placeholder-documents at rHIS. These placeholder-documents are assembled upon user-authenticated request by the HET-HC and are always up-to-date. Moreover, it is not trivial to find a clinical coding system for continuous sensor data and to make the data machine-readable in order to enhance the interoperability of such systems. Therefore, we propose the use of SNOCAP-HET, which is a nomenclature to describe the context of sensor-based measurements in health-enabling technologies. RESULTS: We present an architectural approach to integrate HET-HC into rHIS. Our solution is the centralized registration of placeholder-documents with rHIS and the decentralized data storage at people's home. CONCLUSIONS: We concluded that the presented architecture of integrating HET-HC into rHIS might fit well to the traditional approach of document-based data storage. Data security and privacy issues are also duly considered.

Authentication systems for securing clinical documentation workflows. A systematic literature review.

CONTEXT: Integration of electronic signatures embedded in health care processes in Germany challenges health care service and supply facilities. The suitability of the signature level of an eligible authentication procedure is confirmed for a large part of documents in clinical practice. However, the concrete design of such a procedure remains unclear. OBJECTIVE: To create a summary of usable user authentication systems suitable for clinical workflows. DATA SOURCE: A Systematic literature review based on nine online bibliographic databases. Search keywords included authentication, access control, information systems, information security and biometrics with terms user authentication, user identification and login in title or abstract. Searches were run between 7 and 12 September 2011. Relevant conference proceedings were searched manually in February 2013. Backward reference search of selected results was done. SELECTION: Only publications fully describing authentication systems used or usable were included. Algorithms or purely theoretical concepts were excluded. Three authors did selection independently. DATA EXTRACTION AND ASSESSMENT: Semi-structured extraction of system characteristics was done by the main author. Identified procedures were assessed for security and fulfillment of relevant laws and guidelines as well as for applicability. Suitability for clinical workflows was derived from the assessments using a weighted sum proposed by Bonneau. RESULTS: Of 7575 citations retrieved, 55 publications meet our inclusion criteria. They describe 48 different authentication systems; 39 were biometric and nine graphical password systems. Assessment of authentication systems showed high error rates above European CENELEC standards and a lack of applicability of biometric systems. Graphical passwords did not add overall value compared to conventional passwords. Continuous authentication can add an additional layer of safety. Only few systems are suitable partially or entirely for use in clinical processes. CONCLUSIONS: Suitability strongly depends on national or institutional requirements. Four authentication systems seem to fulfill requirements of authentication procedures for clinical workflows. Research is needed in the area of continuous authentication with biometric methods. A proper authentication system should combine all factors of authentication implementing and connecting secure individual measures.