Innate Type 2 Response to Aspergillus fumigatus in a Murine Model of Atopic Dermatitis–like Skin Inflammation

Background@#Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease mediated by T helper type 2 (Th2) cells in acute phase. Group 2 innate lymphoid cells (ILCs) play a role in the initiation of the Th2 response. Although mold exposure is associated with the development of AD, studies on the underlying mechanisms are lacking. This study investigated whether group 2 ILCs are involved in inflammation in AD-like skin induced by Aspergillus fumigatus (Af). @*Methods@#We investigated changes of group 2 ILCs population in Af-induced AD-like skin lesions. To induce AD-like skin lesions, Af extracts were applied to the dorsal skin of BALB/c and Rag1−/− mice five times per week, with repeat exposures at 2-week intervals. @*Results@#The clinical parameters were higher in the Af-treated group than in the control group. Histologic findings revealed epiderrmal and dermal thickening as well as eosinophil and mast cell infiltration into the skin of Af-treated mice. Populations of group 2 ILCs in the skin were also significantly higher in the Af-treated group. In addition, interleukin-33 mRNA expression was significantly higher in the skin lesions of the Af-treated mice. In the Rag1−/− mice lacking mature lymphocytes, AD-like skin lesions were still induced by Af and ILCs depletion using an anti-CD90.2 mAb lowered the Af-induced inflammatory response. @*Conclusions@#Group 2 ILCs may play a role in a murine model of Af-induced AD-like skin lesions.

Innate Type 2 Response to Aspergillus fumigatus in a Murine Model of Atopic Dermatitis–like Skin Inflammation

Background@#Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease mediated by T helper type 2 (Th2) cells in acute phase. Group 2 innate lymphoid cells (ILCs) play a role in the initiation of the Th2 response. Although mold exposure is associated with the development of AD, studies on the underlying mechanisms are lacking. This study investigated whether group 2 ILCs are involved in inflammation in AD-like skin induced by Aspergillus fumigatus (Af). @*Methods@#We investigated changes of group 2 ILCs population in Af-induced AD-like skin lesions. To induce AD-like skin lesions, Af extracts were applied to the dorsal skin of BALB/c and Rag1−/− mice five times per week, with repeat exposures at 2-week intervals. @*Results@#The clinical parameters were higher in the Af-treated group than in the control group. Histologic findings revealed epiderrmal and dermal thickening as well as eosinophil and mast cell infiltration into the skin of Af-treated mice. Populations of group 2 ILCs in the skin were also significantly higher in the Af-treated group. In addition, interleukin-33 mRNA expression was significantly higher in the skin lesions of the Af-treated mice. In the Rag1−/− mice lacking mature lymphocytes, AD-like skin lesions were still induced by Af and ILCs depletion using an anti-CD90.2 mAb lowered the Af-induced inflammatory response. @*Conclusions@#Group 2 ILCs may play a role in a murine model of Af-induced AD-like skin lesions.

ERRATUM: Correction of Funding Resource: Development of Aspergillus fumigatus-induced chronic atopic dermatitis mouse model

In this article, the funding resource was misprinted unintentionally.

Development of Aspergillus fumigatus-induced chronic atopic dermatitis mouse model

PURPOSE: Atopic dermatitis (AD) is the most common chronic and relapsing inflammatory skin disease with skin barrier defects and altered immune responses. Chronic inflammation leads to irreversible fibrosis in the skin and there is no treatment to completely abolish the inflammation and fibrosis. To prevent or treat the chronic process of AD, it is necessary to develop a murine model of AD that reflects the chronic process to identify the mechanism. The aims of this study were to develop a chronic AD model with a crude extract Aspergillus fumigatus (Af) antigen. METHODS: We applied Af extract (40 µg) epicutaneously to the dorsal skin of BALB/c mice for 5 consecutive days per week during a period of 5 weeks for a chronic AD model, and 5 consecutive days repeatedly with 2 weeks interval for an acute AD model. RESULTS: The clinical score and transepidermal water loss were more increased in the chronic AD model than in the acute AD model. Histologic findings showed that more increased epidermal thickness, neutrophil infiltration and hyperkeratosis in the chronic model than in the acute model. Skin fibrosis was more prominent in the chronic model than in the acute model. The mRNA expression levels of transforming growth factor (TGF)-β, thymic stromal lymphopoietin, and interleukin-33 were increased in the skin of the chronic model compared to the acute model. The levels of total IgE, Af-specific IgE, IgG1, and IgG2a were significantly increased in the chronic model compared to controls. CONCLUSION: The Af-induced chronic AD model showed prominent fibrosis and increased TGF-β expression in the skin, which suggests that these models may be useful in the research for the mechanism of the chronic process in AD.

How to Sustain Smart Connected Hospital Services: An Experience from a Pilot Project on IoT-Based Healthcare Services / 대한의료정보학회지

OBJECTIVES: This paper describes an experience of implementing seamless service trials online and offline by adopting Internet of Things (IoT) technology based on near-field communication (NFC) tags and Bluetooth low-energy (BLE) beacons. The services were provided for both patients and health professionals. METHODS: The pilot services were implemented to enhance healthcare service quality, improve patient safety, and provide an effective business process to health professionals in a tertiary hospital in Seoul, Korea. The services to enhance healthcare service quality include healing tours, cancer information/education, psychological assessments, indoor navigation, and exercise volume checking. The services to improve patient safety are monitoring of high-risk inpatients and delivery of real-time health information in emergency situations. In addition, the services to provide an effective business process to health professionals include surveys and web services for patient management. RESULTS: Considering the sustainability of the pilot services, we decided to pause navigation and patient monitoring services until the interference problem could be completely resolved because beacon signal interference significantly influences the quality of services. On the other hand, we had to continue to provide new wearable beacons to high-risk patients because of hygiene issues, so the cost increased over time and was much higher than expected. CONCLUSIONS: To make the smart connected hospital services sustainable, technical feasibility (e.g., beacon signal interference), economic feasibility (e.g., continuous provision of new necklace beacons), and organizational commitment and support (e.g., renewal of new alternative medical devices and infrastructure) are required.

Action Research on Development and Application of Internet of Things Services in Hospital / 대한의료정보학회지

OBJECTIVES: Services based on the Internet of Things (IoT) technologies have emerged in various business environments. To enhance health service quality and maximize benefits, this study applied an IoT technology based on NFC and iBeacon as an omni-channel service for patient care in hospitals. METHODS: Application of the IoT technology based on NFC and iBeacon was conducted in a general hospital during August 2015 through June 2016, and the development and evaluation results were aligned to an action research framework. The five phases in the action research included diagnosing, planning action, taking action, evaluating action, and specifying learning phases. RESULTS: During the first two phases, problems of functional operations in a hospital were diagnosed and eight service models were designed by using iBeacon and NFC to solve the problems. Service models were applied to the hospital by installing beacons, wearable beacons, beacon scanners, and NFC tags during the third phase. During the fourth and fifth phases, the roles and benefits of stakeholders participating in the service models were evaluated, and issues and knowledge of the whole application process were derived and summarized from technological, economic, social and legal perspectives, respectively. CONCLUSIONS: From an action research perspective, IoT-based healthcare services were developed and verified. IoT-based services enable the hospital to acquire lifelog data for precision medicine and ultimately be able to go one step closer to precision medical care. The derived service models could provide patients more enhanced healthcare services and improve the work efficiency and effectiveness of the hospital.

Proteomic Analysis of Serum from Patients with Major Depressive Disorder to Compare Their Depressive and Remission Statuses

OBJECTIVE: Currently, there are a few biological markers to aid in the diagnosis and treatment of depression. However, it is not sufficient for diagnosis. We attempted to identify differentially expressed proteins during depressive moods as putative diagnostic biomarkers by using quantitative proteomic analysis of serum. METHODS: Blood samples were collected twice from five patients with major depressive disorder (MDD) at depressive status before treatment and at remission status during treatment. Samples were individually analyzed by liquid chromatography-tandem mass spectrometry for protein profiling. Differentially expressed proteins were analyzed by label-free quantification. Enzyme-linked immunosorbent assay (ELISA) results and receiver-operating characteristic (ROC) curves were used to validate the differentially expressed proteins. For validation, 8 patients with MDD including 3 additional patients and 8 matched normal controls were analyzed. RESULTS: The quantitative proteomic studies identified 10 proteins that were consistently upregulated or downregulated in 5 MDD patients. ELISA yielded results consistent with the proteomic analysis for 3 proteins. Expression levels were significantly different between normal controls and MDD patients. The 3 proteins were ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4 and complement component 1qC, which were upregulated during the depressive status. The depressive status could be distinguished from the euthymic status from the ROC curves for these proteins, and this discrimination was enhanced when all 3 proteins were analyzed together. CONCLUSION: This is the first proteomic study in MDD patients to compare intra-individual differences dependent on mood. This technique could be a useful approach to identify MDD biomarkers, but requires additional proteomic studies for validation.