A multiplexed bacterial two-hybrid for rapid characterization of protein-protein interactions and iterative protein design.

Protein-protein interactions (PPIs) are crucial for biological functions and have applications ranging from drug design to synthetic cell circuits. Coiled-coils have been used as a model to study the sequence determinants of specificity. However, building well-behaved sets of orthogonal pairs of coiled-coils remains challenging due to inaccurate predictions of orthogonality and difficulties in testing at scale. To address this, we develop the next-generation bacterial two-hybrid (NGB2H) method, which allows for the rapid exploration of interactions of programmed protein libraries in a quantitative and scalable way using next-generation sequencing readout. We design, build, and test large sets of orthogonal synthetic coiled-coils, assayed over 8,000 PPIs, and used the dataset to train a more accurate coiled-coil scoring algorithm (iCipa). After characterizing nearly 18,000 new PPIs, we identify to the best of our knowledge the largest set of orthogonal coiled-coils to date, with fifteen on-target interactions. Our approach provides a powerful tool for the design of orthogonal PPIs.

E-healthcare for Diabetes Mellitus Type 2 Patients - A Randomised Controlled Trial in Slovenia.

BACKGROUND: Telemonitoring and web-based interventions are increasingly used in primary-care practices in many countries for more effective management of patients with diabetes mellitus (DM). A new approach in treating patients with diabetes mellitus in family practices, based on ICT use and nurse practitioners, has been introduced and evaluated in this study. METHOD: Fifteen Slovene family practices enrolled 120 DM patients treated only with a diet regime and/or tablets into the study. 58 of them were included into the interventional group, and the other 62 DM patients into the control group, within one-year-long interventional, randomised controlled trial. Patients in the control group had conventional care for DM according to Slovenian professional guidelines, while the patients in the interventional group were using also the eDiabetes application. Patients were randomised through a balanced randomisation process. RESULTS: Significant reductions of glycated haemoglobin (HbA1c) values were found after 6 and 12 months among patients using this eDiabetes application (p<0.05). Among these patients, a significant correlation was also found between self-monitored blood pressure and the final HbA1c values. Diabetic patients' involvement in web-based intervention had only transient impact on their functional health status. CONCLUSION: This eDiabetes application was confirmed to be an innovative approach for better self-management of DM type 2 patients not using insulin. Both a significant reduction of HbA1c values and a significant correlation between the average self-measured blood pressure and the final HbA1c values in the interventional group were found. Nurse practitioners - as diabetes care coordinators - could contribute to better adherence in diabetes e-care.

Feasibility of an eHealth service to support collaborative depression care: results of a pilot study.

BACKGROUND: Treatments and organizational changes supported by eHealth are beginning to play an important role in improving disease treatment outcome and providing cost-efficient care management. "Improvehealth.eu" is a novel eHealth service to support the treatment of patients with depressive disorder. It offers active patient engagement and collaborative care management by combining Web- and mobile-based information and communication technology systems and access to care managers. OBJECTIVES: Our objective was to assess the feasibility of a novel eHealth service. METHODS: The intervention--the "Improvehealth.eu" service--was explored in the course of a pilot study comparing two groups of patients receiving treatment as usual and treatment as usual with eHealth intervention. We compared patients' medication adherence and outcome measures between both groups and additionally explored usage and overall perceptions of the intervention in intervention group. RESULTS: The intervention was successfully implemented in a pilot with 46 patients, of whom 40 were female. Of the 46 patients, 25 received treatment as usual, and 21 received the intervention in addition to treatment as usual. A total of 55% (12/25) of patients in the former group and 45% (10/21) in the latter group finished the 6-month pilot. Available case analysis indicated an improvement of adherence in the intervention group (odds ratio [OR] = 10.0, P = .03). Intention-to-treat analysis indicated an improvement of outcome in the intervention group (ORs ranging from 0.35 to 18; P values ranging from .003 to .20), but confidence intervals were large due to small sample sizes. Average duration of use of the intervention was 107 days. The intervention was well received by 81% (17/21) of patients who reported feeling actively engaged, in control of their disease, and that they had access to a high level of information. In all, 33% (7/21) of the patients also described drawbacks of the intervention, mostly related to usability issues. CONCLUSIONS: The results of this pilot study indicate that the intervention was well accepted and helped the patients in the course of treatment. The results also suggest the potential of the intervention to improve both medication adherence and outcome measures of treatment, including reduction of depression severity and patients becoming "healthy."